2017 |
Li, C; Miao, X; Li, F; Wang, S; Liu, Q; wang, Y; Sun, J Oxidative Stress-Related Mechanisms and Antioxidant Therapy in Diabetic Retinopathy. Journal Article Oxidative Medicine and Cellular Longevity, 2017 , pp. 1-15, 2017. @article{Perraudinb, title = {Oxidative Stress-Related Mechanisms and Antioxidant Therapy in Diabetic Retinopathy.}, author = {C Li and X Miao and F Li and S Wang and Q Liu and Y wang and J Sun}, doi = {10.1155/2017/9702820}, year = {2017}, date = {2017-02-06}, journal = {Oxidative Medicine and Cellular Longevity}, volume = {2017}, pages = {1-15}, abstract = {Diabetic retinopathy (DR) is one of the most common microvascular complications of diabetes and is the leading cause of blindness in young adults. Oxidative stress has been implicated as a critical cause of DR. Metabolic abnormalities induced by high-glucose levels are involved in the development of DR and appear to be influenced by oxidative stress. The imbalance between reactive oxygen species (ROS) production and the antioxidant defense system activates several oxidative stress-related mechanisms that promote the pathogenesis of DR. The damage caused by oxidative stress persists for a considerable time, even after the blood glucose concentration has returned to a normal level. Animal experiments have proved that the use of antioxidants is a beneficial therapeutic strategy for the treatment of DR, but more data are required from clinical trials. The aims of this review are to highlight the improvements to our understanding of the oxidative stress-related mechanisms underlying the development of DR and provide a summary of the main antioxidant therapy strategies used to treat the disease.}, keywords = {}, pubstate = {published}, tppubtype = {article} } Diabetic retinopathy (DR) is one of the most common microvascular complications of diabetes and is the leading cause of blindness in young adults. Oxidative stress has been implicated as a critical cause of DR. Metabolic abnormalities induced by high-glucose levels are involved in the development of DR and appear to be influenced by oxidative stress. The imbalance between reactive oxygen species (ROS) production and the antioxidant defense system activates several oxidative stress-related mechanisms that promote the pathogenesis of DR. The damage caused by oxidative stress persists for a considerable time, even after the blood glucose concentration has returned to a normal level. Animal experiments have proved that the use of antioxidants is a beneficial therapeutic strategy for the treatment of DR, but more data are required from clinical trials. The aims of this review are to highlight the improvements to our understanding of the oxidative stress-related mechanisms underlying the development of DR and provide a summary of the main antioxidant therapy strategies used to treat the disease. |
2016 |
Rahimi-Madiseh, M; Malekpour-Tehrani, A; Bahmani, M; Rafieian-Kopaei, M The research and development on the antioxidants in prevention of diabetic complications Journal Article Asian Pacific Journal of Tropical Medicine, 9 (9), pp. 825-831, 2016. @article{Perraudinbc, title = {The research and development on the antioxidants in prevention of diabetic complications}, author = {M Rahimi-Madiseh and A Malekpour-Tehrani and M Bahmani and M Rafieian-Kopaei}, doi = {10.1016/j.apjtm.2016.07.001}, year = {2016}, date = {2016-05-01}, journal = {Asian Pacific Journal of Tropical Medicine}, volume = {9}, number = {9}, pages = {825-831}, abstract = {Diabetes mellitus can damage the eyes, kidneys, nerves and heart. Microvascular and macrovascular disorders are the leading causes of morbidity and mortality in diabetic patients. Hyperglycemia can increase the indicators of lipid peroxidation and oxidative stress in which free radicals have the main role in the pathogenesis of these complications. Therefore, antioxidants which combat oxidative stress should be able to prevent and repair free radicals induced damages. Although free radicals contribute to kidney damage, atherosclerosis, diabetes, heart disease, nephrotoxicity and hepatotoxicity; however, clinical trials do not uniquely confirm a substantial impact on diabetic damage. It seems that antioxidants in vegetables, fruits and grains help preventing diabetes complications; however, there is little evidence that taking single antioxidants such as vitamin E or vitamin C protect these complications. The findings about combination antioxidants are also complicated and not entirely clear. In this review paper we tried to present the role of oxidative stress on micro-vascular complications of type 2 diabetes mellitus. Other objective of this paper is to review the new findings about the role of various antioxidants on prevention and treatment of diabetes mellitus as well as its complications including retinopathy, nephropathy and neuropathy}, keywords = {}, pubstate = {published}, tppubtype = {article} } Diabetes mellitus can damage the eyes, kidneys, nerves and heart. Microvascular and macrovascular disorders are the leading causes of morbidity and mortality in diabetic patients. Hyperglycemia can increase the indicators of lipid peroxidation and oxidative stress in which free radicals have the main role in the pathogenesis of these complications. Therefore, antioxidants which combat oxidative stress should be able to prevent and repair free radicals induced damages. Although free radicals contribute to kidney damage, atherosclerosis, diabetes, heart disease, nephrotoxicity and hepatotoxicity; however, clinical trials do not uniquely confirm a substantial impact on diabetic damage. It seems that antioxidants in vegetables, fruits and grains help preventing diabetes complications; however, there is little evidence that taking single antioxidants such as vitamin E or vitamin C protect these complications. The findings about combination antioxidants are also complicated and not entirely clear. In this review paper we tried to present the role of oxidative stress on micro-vascular complications of type 2 diabetes mellitus. Other objective of this paper is to review the new findings about the role of various antioxidants on prevention and treatment of diabetes mellitus as well as its complications including retinopathy, nephropathy and neuropathy |
Kay, AM; Simpson, CL; Jr, JA Steward The Role of AGE/RAGE Signaling in Diabetes-Mediated Vascular Calcification. Journal Article Journal of Diabetes Reasearch, 2016 , pp. 1 - 8, 2016. @article{Perraudinbb, title = {The Role of AGE/RAGE Signaling in Diabetes-Mediated Vascular Calcification.}, author = {AM Kay and CL Simpson and JA Steward Jr}, doi = {10.1155/2016/6809703}, year = {2016}, date = {2016-05-19}, journal = {Journal of Diabetes Reasearch}, volume = {2016}, pages = {1 - 8}, abstract = {AGE/RAGE signaling has been a well-studied cascade in many different disease states, particularly diabetes. Due to the complex nature of the receptor and multiple intersecting pathways, the AGE/RAGE signaling mechanism is still not well understood. The purpose of this review is to highlight key areas of AGE/RAGE mediated vascular calcification as a complication of diabetes. AGE/RAGE signaling heavily influences both cellular and systemic responses to increase bone matrix proteins through PKC, p38 MAPK, fetuin-A, TGF-β, NFκB, and ERK1/2 signaling pathways in both hyperglycemic and calcification conditions. AGE/RAGE signaling has been shown to increase oxidative stress to promote diabetes-mediated vascular calcification through activation of Nox-1 and decreased expression of SOD-1. AGE/RAGE signaling in diabetes-mediated vascular calcification was also attributed to increased oxidative stress resulting in the phenotypic switch of VSMCs to osteoblast-like cells in AGEs-induced calcification. Researchers found that pharmacological agents and certain antioxidants decreased the level of calcium deposition in AGEs-induced diabetes-mediated vascular calcification. By understanding the role the AGE/RAGE signaling cascade plays diabetes-mediated vascular calcification will allow for pharmacological intervention to decrease the severity of this diabetic complication.}, keywords = {}, pubstate = {published}, tppubtype = {article} } AGE/RAGE signaling has been a well-studied cascade in many different disease states, particularly diabetes. Due to the complex nature of the receptor and multiple intersecting pathways, the AGE/RAGE signaling mechanism is still not well understood. The purpose of this review is to highlight key areas of AGE/RAGE mediated vascular calcification as a complication of diabetes. AGE/RAGE signaling heavily influences both cellular and systemic responses to increase bone matrix proteins through PKC, p38 MAPK, fetuin-A, TGF-β, NFκB, and ERK1/2 signaling pathways in both hyperglycemic and calcification conditions. AGE/RAGE signaling has been shown to increase oxidative stress to promote diabetes-mediated vascular calcification through activation of Nox-1 and decreased expression of SOD-1. AGE/RAGE signaling in diabetes-mediated vascular calcification was also attributed to increased oxidative stress resulting in the phenotypic switch of VSMCs to osteoblast-like cells in AGEs-induced calcification. Researchers found that pharmacological agents and certain antioxidants decreased the level of calcium deposition in AGEs-induced diabetes-mediated vascular calcification. By understanding the role the AGE/RAGE signaling cascade plays diabetes-mediated vascular calcification will allow for pharmacological intervention to decrease the severity of this diabetic complication. |
2015 |
Jhajharia, K; Parolia, A; Shetty, KV; Mehta, LK Biofilm in endodontics: A review. Journal Article J Int Soc Prev Community Dent, 5 (1), pp. 1 - 12, 2015. @article{Perraudinbj, title = {Biofilm in endodontics: A review.}, author = {K Jhajharia and A Parolia and KV Shetty and LK Mehta}, doi = {10.4103/2231-0762.151956.}, year = {2015}, date = {2015-01-01}, journal = {J Int Soc Prev Community Dent}, volume = {5}, number = {1}, pages = {1 - 12}, abstract = {Endodontic disease is a biofilm-mediated infection, and primary aim in the management of endodontic disease is the elimination of bacterial biofilm from the root canal system. The most common endodontic infection is caused by the surface-associated growth of microorganisms. It is important to apply the biofilm concept to endodontic microbiology to understand the pathogenic potential of the root canal microbiota as well as to form the basis for new approaches for disinfection. It is foremost to understand how the biofilm formed by root canal bacteria resists endodontic treatment measures. Bacterial etiology has been confirmed for common oral diseases such as caries and periodontal and endodontic infections. Bacteria causing these diseases are organized in biofilm structures, which are complex microbial communities composed of a great variety of bacteria with different ecological requirements and pathogenic potential. The biofilm community not only gives bacteria effective protection against the host's defense system but also makes them more resistant to a variety of disinfecting agents used as oral hygiene products or in the treatment of infections. Successful treatment of these diseases depends on biofilm removal as well as effective killing of biofilm bacteria. So, the fundamental to maintain oral health and prevent dental caries, gingivitis, and periodontitis is to control the oral biofilms. From these aspects, the formation of biofilms carries particular clinical significance because not only host defense mechanisms but also therapeutic efforts including chemical and mechanical antimicrobial treatment measures have the most difficult task of dealing with organisms that are gathered in a biofilm. The aim of this article was to review the mechanisms of biofilms' formation, their roles in pulpal and periapical pathosis, the different types of biofilms, the factors influencing biofilm formation, the mechanisms of their antimicrobial resistance, techniques to identify biofilms.}, keywords = {}, pubstate = {published}, tppubtype = {article} } Endodontic disease is a biofilm-mediated infection, and primary aim in the management of endodontic disease is the elimination of bacterial biofilm from the root canal system. The most common endodontic infection is caused by the surface-associated growth of microorganisms. It is important to apply the biofilm concept to endodontic microbiology to understand the pathogenic potential of the root canal microbiota as well as to form the basis for new approaches for disinfection. It is foremost to understand how the biofilm formed by root canal bacteria resists endodontic treatment measures. Bacterial etiology has been confirmed for common oral diseases such as caries and periodontal and endodontic infections. Bacteria causing these diseases are organized in biofilm structures, which are complex microbial communities composed of a great variety of bacteria with different ecological requirements and pathogenic potential. The biofilm community not only gives bacteria effective protection against the host's defense system but also makes them more resistant to a variety of disinfecting agents used as oral hygiene products or in the treatment of infections. Successful treatment of these diseases depends on biofilm removal as well as effective killing of biofilm bacteria. So, the fundamental to maintain oral health and prevent dental caries, gingivitis, and periodontitis is to control the oral biofilms. From these aspects, the formation of biofilms carries particular clinical significance because not only host defense mechanisms but also therapeutic efforts including chemical and mechanical antimicrobial treatment measures have the most difficult task of dealing with organisms that are gathered in a biofilm. The aim of this article was to review the mechanisms of biofilms' formation, their roles in pulpal and periapical pathosis, the different types of biofilms, the factors influencing biofilm formation, the mechanisms of their antimicrobial resistance, techniques to identify biofilms. |
Li, W; Zhu, S; Hu, J Bone Regeneration Is Promoted by Orally Administered Bovine Lactoferrin in a Rabbit Tibial Distraction Osteogenesis Model. Journal Article Clin Orthop Relat Res, 473 (7), pp. 2383 - 2393, 2015. @article{Perraudinbh, title = {Bone Regeneration Is Promoted by Orally Administered Bovine Lactoferrin in a Rabbit Tibial Distraction Osteogenesis Model.}, author = {W Li and S Zhu and J Hu}, doi = {10.1007/s11999-015-4270-5}, year = {2015}, date = {2015-01-02}, journal = {Clin Orthop Relat Res}, volume = {473}, number = {7}, pages = {2383 - 2393}, abstract = {BACKGROUND: Lactoferrin, an iron-binding glycoprotein which belongs to the transferrin family, has been shown to promote bone growth. However, reports regarding effects of lactoferrin on bone regeneration during distraction osteogenesis are limited. Our study was designed to investigate the effect of bovine lactoferrin treatment on bone formation of the distracted callus. QUESTIONS/PURPOSES: We asked whether bovine lactoferrin enhances bone formation of the distraction callus as determined by (1) radiographic and histologic appearances; (2) dual-energy x-ray absorptiometry (DXA) analysis of bone mineral composition and bone mineral density; (3) micro-CT measures of trabecular architecture; and (4) biomechanical strength of the healing bone. Additionally, serology, reverse transcription (RT)-PCR, and immunohistochemistry were used to explore the possible mechanisms of bovine lactoferrin use on bone formation during distraction osteogenesis. METHODS: Unilateral tibial osteodistraction was performed on 80 New Zealand White rabbits with a distraction rate of 1 mm per day for 10 days. Animals then were divided randomly into two groups: (1) vehicle and (2) bovine lactoferrin. At 4 and 8 weeks after completion of distraction, the animals were sacrificed. Lengthened tibias and serum samples were obtained and subjected to radiologic, DXA, micro-CT, histologic, and biomechanical examinations, and serum, RT-PCR and immunohistochemical analyses. RESULTS: Radiologic, DXA, micro-CT, histologic, and biomechanical examinations indicated that bovine lactoferrin treatment not only accelerated bone formation at early stages of distraction osteogenesis but also promoted bone consolidation at late stages. The ultimate force of the distracted calluses was increased by 37% (118.8 ± 6.65 N in the lactoferrin group and 86.5 ± 5.47 N in the vehicle group; p < 0.001) and 84% (384.8 ± 18.4 N in the lactoferrin group and 209.0 ± 15.2 N in the vehicle group; p < 0.001) at 4 and 8 weeks, respectively. Moreover, serum analysis showed that bovine lactoferrin treatment significantly increased serum levels of bone alkaline phosphatase and decreased serum levels of tartrate resistant acid phosphatase 5b. In addition, RT-PCR and immunohistochemical analyses suggested that bovine lactoferrin treatment induced a lower receptor activator of nuclear factor-kappaB (RANK) ligand/osteoprotegerin (RANKL/OPG) ratio in the distracted callus. CONCLUSIONS: The results of our study suggest that bovine lactoferrin treatment could promote bone regeneration during distraction osteogenesis in the rabbit. The results indicate that the OPG/RANKL/RANK system might be a major mechanism for increased bone formation and decreased bone resorption in distraction osteogenesis with bovine lactoferrin treatment. CLINICAL RELEVANCE: Oral administration of bovine lactoferrin may provide a feasible approach for promoting osteogenesis during distraction osteogenesis}, keywords = {}, pubstate = {published}, tppubtype = {article} } BACKGROUND: Lactoferrin, an iron-binding glycoprotein which belongs to the transferrin family, has been shown to promote bone growth. However, reports regarding effects of lactoferrin on bone regeneration during distraction osteogenesis are limited. Our study was designed to investigate the effect of bovine lactoferrin treatment on bone formation of the distracted callus. QUESTIONS/PURPOSES: We asked whether bovine lactoferrin enhances bone formation of the distraction callus as determined by (1) radiographic and histologic appearances; (2) dual-energy x-ray absorptiometry (DXA) analysis of bone mineral composition and bone mineral density; (3) micro-CT measures of trabecular architecture; and (4) biomechanical strength of the healing bone. Additionally, serology, reverse transcription (RT)-PCR, and immunohistochemistry were used to explore the possible mechanisms of bovine lactoferrin use on bone formation during distraction osteogenesis. METHODS: Unilateral tibial osteodistraction was performed on 80 New Zealand White rabbits with a distraction rate of 1 mm per day for 10 days. Animals then were divided randomly into two groups: (1) vehicle and (2) bovine lactoferrin. At 4 and 8 weeks after completion of distraction, the animals were sacrificed. Lengthened tibias and serum samples were obtained and subjected to radiologic, DXA, micro-CT, histologic, and biomechanical examinations, and serum, RT-PCR and immunohistochemical analyses. RESULTS: Radiologic, DXA, micro-CT, histologic, and biomechanical examinations indicated that bovine lactoferrin treatment not only accelerated bone formation at early stages of distraction osteogenesis but also promoted bone consolidation at late stages. The ultimate force of the distracted calluses was increased by 37% (118.8 ± 6.65 N in the lactoferrin group and 86.5 ± 5.47 N in the vehicle group; p < 0.001) and 84% (384.8 ± 18.4 N in the lactoferrin group and 209.0 ± 15.2 N in the vehicle group; p < 0.001) at 4 and 8 weeks, respectively. Moreover, serum analysis showed that bovine lactoferrin treatment significantly increased serum levels of bone alkaline phosphatase and decreased serum levels of tartrate resistant acid phosphatase 5b. In addition, RT-PCR and immunohistochemical analyses suggested that bovine lactoferrin treatment induced a lower receptor activator of nuclear factor-kappaB (RANK) ligand/osteoprotegerin (RANKL/OPG) ratio in the distracted callus. CONCLUSIONS: The results of our study suggest that bovine lactoferrin treatment could promote bone regeneration during distraction osteogenesis in the rabbit. The results indicate that the OPG/RANKL/RANK system might be a major mechanism for increased bone formation and decreased bone resorption in distraction osteogenesis with bovine lactoferrin treatment. CLINICAL RELEVANCE: Oral administration of bovine lactoferrin may provide a feasible approach for promoting osteogenesis during distraction osteogenesis |
Bascones-Martínez, A; Muñoz-Corcuera, M; Bascones-Ilundain, J Diabetes and periodontitis: A bidirectional relationship Journal Article Med Clin (Barc), 145 (1), pp. 31 - 35, 2015. @article{Perraudinbi, title = {Diabetes and periodontitis: A bidirectional relationship}, author = {A Bascones-Martínez and M Muñoz-Corcuera and J Bascones-Ilundain}, doi = {10.1016/j.medcli.2014.07.019.}, year = {2015}, date = {2015-01-02}, journal = {Med Clin (Barc)}, volume = {145}, number = {1}, pages = {31 - 35}, abstract = {Diabetes mellitus is a group of metabolic diseases characterized by hyperglycemia resulting from defects in insulin secretion, a defect in insulin action or a combination of both. Periodontitis is now considered a chronic localized infection of the oral cavity that can trigger inflammatory host immune responses at local and systemic levels, and can also be a source of bacteremia. It is now known that periodontitis has an influence on the pathogenesis of certain systemic diseases. The biological relationship between diabetes and periodontal disease is well documented. In the mid-90s sufficient scientific support for the association between diabetes and periodontitis was published, and periodontitis was designated as the sixth complication of diabetes. There have been studies that show an improvement in both clinical and immunological parameters of periodontitis and glycemic control in long-term diabetes after treatment of periodontal disease. In addition, scientific evidence confirms that poorer glycemic control contributes to a worse periodontal condition. The interplay between the 2 conditions highlights the importance of the need for a good communication between the internist and dentist about diabetic patients, considering always the possibility that the 2 diseases may be occurring simultaneously in order to ensure an early diagnosis of both.}, keywords = {}, pubstate = {published}, tppubtype = {article} } Diabetes mellitus is a group of metabolic diseases characterized by hyperglycemia resulting from defects in insulin secretion, a defect in insulin action or a combination of both. Periodontitis is now considered a chronic localized infection of the oral cavity that can trigger inflammatory host immune responses at local and systemic levels, and can also be a source of bacteremia. It is now known that periodontitis has an influence on the pathogenesis of certain systemic diseases. The biological relationship between diabetes and periodontal disease is well documented. In the mid-90s sufficient scientific support for the association between diabetes and periodontitis was published, and periodontitis was designated as the sixth complication of diabetes. There have been studies that show an improvement in both clinical and immunological parameters of periodontitis and glycemic control in long-term diabetes after treatment of periodontal disease. In addition, scientific evidence confirms that poorer glycemic control contributes to a worse periodontal condition. The interplay between the 2 conditions highlights the importance of the need for a good communication between the internist and dentist about diabetic patients, considering always the possibility that the 2 diseases may be occurring simultaneously in order to ensure an early diagnosis of both. |
Llambés, F; Arias-Herrera, S; Caffesse, R Relationship between diabetes and periodontal infection. Journal Article World J Diabetes, 6 (7), pp. 927 - 935, 2015. @article{Perraudinbg, title = {Relationship between diabetes and periodontal infection.}, author = {F Llambés and S Arias-Herrera and R Caffesse}, doi = {10.4239/wjd.v6.i7.927}, year = {2015}, date = {2015-02-02}, journal = {World J Diabetes}, volume = {6}, number = {7}, pages = {927 - 935}, abstract = {Periodontal disease is a high prevalent disease. In the United States 47.2% of adults ≥ 30 years old have been diagnosed with some type of periodontitis. Longitudinal studies have demonstrated a two-way relationship between diabetes and periodontitis, with more severe periodontal tissue destruction in diabetic patients and poorer glycemic control in diabetic subjects with periodontal disease. Periodontal treatment can be successful in diabetic patients. Short term effects of periodontal treatment are similar in diabetic patients and healthy population but, more recurrence of periodontal disease can be expected in no well controlled diabetic individuals. However, effects of periodontitis and its treatment on diabetes metabolic control are not clearly defined and results of the studies remain controversial.}, keywords = {}, pubstate = {published}, tppubtype = {article} } Periodontal disease is a high prevalent disease. In the United States 47.2% of adults ≥ 30 years old have been diagnosed with some type of periodontitis. Longitudinal studies have demonstrated a two-way relationship between diabetes and periodontitis, with more severe periodontal tissue destruction in diabetic patients and poorer glycemic control in diabetic subjects with periodontal disease. Periodontal treatment can be successful in diabetic patients. Short term effects of periodontal treatment are similar in diabetic patients and healthy population but, more recurrence of periodontal disease can be expected in no well controlled diabetic individuals. However, effects of periodontitis and its treatment on diabetes metabolic control are not clearly defined and results of the studies remain controversial. |
Asmat, U; K, Abad; Ismail, K Diabetes mellitus and oxidative stress-A concise review. Journal Article Saudi Pharmaceutical Journal, 24 , pp. 547-553, 2015. @article{Perraudinbf, title = {Diabetes mellitus and oxidative stress-A concise review.}, author = {U Asmat and Abad K and K Ismail}, doi = {10.1016/j.jsps.2015.03.013}, year = {2015}, date = {2015-03-16}, journal = {Saudi Pharmaceutical Journal}, volume = {24}, pages = {547-553}, abstract = {Human body is continuously exposed to different types of agents that results in the production of reactive species called as free radicals (ROS/RNS) which by the transfer of their free unpaired electron causes the oxidation of cellular machinery. In order to encounter the deleterious effects of such species, body has got endogenous antioxidant systems or it obtains exogenous antioxidants from diet that neutralizes such species and keeps the homeostasis of body. Any imbalance between the RS and antioxidants leads to produce a condition known as "oxidative stress" that results in the development of pathological condition among which one is diabetes. Most of the studies reveal the inference of oxidative stress in diabetes pathogenesis by the alteration in enzymatic systems, lipid peroxidation, impaired Glutathione metabolism and decreased Vitamin C levels. Lipids, proteins, DNA damage, Glutathione, catalane and superoxide dismutase are various biomarkers of oxidative stress in diabetes mellitus. Oxidative stress induced complications of diabetes may include stroke, neuropathy, retinopathy and nephropathy. The basic aim of this review was to summarize the basics of oxidative stress in diabetes mellitus}, keywords = {}, pubstate = {published}, tppubtype = {article} } Human body is continuously exposed to different types of agents that results in the production of reactive species called as free radicals (ROS/RNS) which by the transfer of their free unpaired electron causes the oxidation of cellular machinery. In order to encounter the deleterious effects of such species, body has got endogenous antioxidant systems or it obtains exogenous antioxidants from diet that neutralizes such species and keeps the homeostasis of body. Any imbalance between the RS and antioxidants leads to produce a condition known as "oxidative stress" that results in the development of pathological condition among which one is diabetes. Most of the studies reveal the inference of oxidative stress in diabetes pathogenesis by the alteration in enzymatic systems, lipid peroxidation, impaired Glutathione metabolism and decreased Vitamin C levels. Lipids, proteins, DNA damage, Glutathione, catalane and superoxide dismutase are various biomarkers of oxidative stress in diabetes mellitus. Oxidative stress induced complications of diabetes may include stroke, neuropathy, retinopathy and nephropathy. The basic aim of this review was to summarize the basics of oxidative stress in diabetes mellitus |
Pisoschi, AM; Pop, A The role of antioxidants in the chemistry of oxidative stress: A review. Journal Article Eur J Med Chem, 95 , pp. 55-74, 2015. @article{Perraudinbe, title = {The role of antioxidants in the chemistry of oxidative stress: A review.}, author = {AM Pisoschi and A Pop}, doi = {10.1016/j.ejmech.2015.04.040}, year = {2015}, date = {2015-06-01}, journal = {Eur J Med Chem}, volume = {95}, pages = {55-74}, abstract = {This Review Article is focused on the action of the reactive oxygenated species in inducing oxidative injury of the lipid membrane components, as well as on the ability of antioxidants (of different structures and sources, and following different mechanisms of action) in fighting against oxidative stress. Oxidative stress is defined as an excessive production of reactive oxygenated species that cannot be counteracted by the action of antioxidants, but also as a perturbation of cell redox balance. Reactive oxygenated/nitrogenated species are represented by superoxide anion radical, hydroxyl, alkoxyl and lipid peroxyl radicals, nitric oxide and peroxynitrite. Oxidative stress determines structure modifications and function modulation in nucleic acids, lipids and proteins. Oxidative degradation of lipids yields malondialdehyde and 4-hydroxynonenal, but also isoprostanes, from unsaturated fatty acids. Protein damage may occur with thiol oxidation, carbonylation, side-chain oxidation, fragmentation, unfolding and misfolding, resulting activity loss. 8-hydroxydeoxyguanosine is an index of DNA damage. The involvement of the reactive oxygenated/nitrogenated species in disease occurrence is described. The unbalance between the oxidant species and the antioxidant defense system may trigger specific factors responsible for oxidative damage in the cell: over-expression of oncogene genes, generation of mutagen compounds, promotion of atherogenic activity, senile plaque occurrence or inflammation. This leads to cancer, neurodegeneration, cardiovascular diseases, diabetes, kidney diseases. The concept of antioxidant is defined, along with a discussion of the existent classification criteria: enzymatic and non-enzymatic, preventative or repair-systems, endogenous and exogenous, primary and secondary, hydrosoluble and liposoluble, natural or synthetic. Primary antioxidants are mainly chain breakers, able to scavenge radical species by hydrogen donation. Secondary antioxidants are singlet oxygen quenchers, peroxide decomposers, metal chelators, oxidative enzyme inhibitors or UV radiation absorbers. The specific mechanism of action of the most important representatives of each antioxidant class (endogenous and exogenous) in preventing or inhibiting particular factors leading to oxidative injury in the cell, is then reviewed. Mutual influences, including synergistic effects are presented and discussed. Prooxidative influences likely to occur, as for instance in the presence of transition metal ions, are also reminded.}, keywords = {}, pubstate = {published}, tppubtype = {article} } This Review Article is focused on the action of the reactive oxygenated species in inducing oxidative injury of the lipid membrane components, as well as on the ability of antioxidants (of different structures and sources, and following different mechanisms of action) in fighting against oxidative stress. Oxidative stress is defined as an excessive production of reactive oxygenated species that cannot be counteracted by the action of antioxidants, but also as a perturbation of cell redox balance. Reactive oxygenated/nitrogenated species are represented by superoxide anion radical, hydroxyl, alkoxyl and lipid peroxyl radicals, nitric oxide and peroxynitrite. Oxidative stress determines structure modifications and function modulation in nucleic acids, lipids and proteins. Oxidative degradation of lipids yields malondialdehyde and 4-hydroxynonenal, but also isoprostanes, from unsaturated fatty acids. Protein damage may occur with thiol oxidation, carbonylation, side-chain oxidation, fragmentation, unfolding and misfolding, resulting activity loss. 8-hydroxydeoxyguanosine is an index of DNA damage. The involvement of the reactive oxygenated/nitrogenated species in disease occurrence is described. The unbalance between the oxidant species and the antioxidant defense system may trigger specific factors responsible for oxidative damage in the cell: over-expression of oncogene genes, generation of mutagen compounds, promotion of atherogenic activity, senile plaque occurrence or inflammation. This leads to cancer, neurodegeneration, cardiovascular diseases, diabetes, kidney diseases. The concept of antioxidant is defined, along with a discussion of the existent classification criteria: enzymatic and non-enzymatic, preventative or repair-systems, endogenous and exogenous, primary and secondary, hydrosoluble and liposoluble, natural or synthetic. Primary antioxidants are mainly chain breakers, able to scavenge radical species by hydrogen donation. Secondary antioxidants are singlet oxygen quenchers, peroxide decomposers, metal chelators, oxidative enzyme inhibitors or UV radiation absorbers. The specific mechanism of action of the most important representatives of each antioxidant class (endogenous and exogenous) in preventing or inhibiting particular factors leading to oxidative injury in the cell, is then reviewed. Mutual influences, including synergistic effects are presented and discussed. Prooxidative influences likely to occur, as for instance in the presence of transition metal ions, are also reminded. |
Marco, Di E; Sharma, CJha; Wilkinson-Berka, JL; Jandeleit-Dahm, KA; de Haan, JB Are reactive oxygen species still the basis for diabetic complications? Journal Article Clin Sci (Lond)., 129 (2), pp. 199-216, 2015. @article{Perraudinbd, title = {Are reactive oxygen species still the basis for diabetic complications?}, author = {Di E Marco and CJha Sharma and JL Wilkinson-Berka and KA Jandeleit-Dahm and JB de Haan}, doi = {10.1042/CS20150093}, year = {2015}, date = {2015-07-01}, journal = {Clin Sci (Lond).}, volume = {129}, number = {2}, pages = {199-216}, abstract = {Despite the wealth of pre-clinical support for a role for reactive oxygen and nitrogen species (ROS/RNS) in the aetiology of diabetic complications, enthusiasm for antioxidant therapeutic approaches has been dampened by less favourable outcomes in large clinical trials. This has necessitated a re-evaluation of pre-clinical evidence and a more rational approach to antioxidant therapy. The present review considers current evidence, from both pre-clinical and clinical studies, to address the benefits of antioxidant therapy. The main focus of the present review is on the effects of direct targeting of ROS-producing enzymes, the bolstering of antioxidant defences and mechanisms to improve nitric oxide availability. Current evidence suggests that a more nuanced approach to antioxidant therapy is more likely to yield positive reductions in end-organ injury, with considerations required for the types of ROS/RNS involved, the timing and dosage of antioxidant therapy, and the selective targeting of cell populations. This is likely to influence future strategies to lessen the burden of diabetic complications such as diabetes-associated atherosclerosis, diabetic nephropathy and diabetic retinopathy.}, keywords = {}, pubstate = {published}, tppubtype = {article} } Despite the wealth of pre-clinical support for a role for reactive oxygen and nitrogen species (ROS/RNS) in the aetiology of diabetic complications, enthusiasm for antioxidant therapeutic approaches has been dampened by less favourable outcomes in large clinical trials. This has necessitated a re-evaluation of pre-clinical evidence and a more rational approach to antioxidant therapy. The present review considers current evidence, from both pre-clinical and clinical studies, to address the benefits of antioxidant therapy. The main focus of the present review is on the effects of direct targeting of ROS-producing enzymes, the bolstering of antioxidant defences and mechanisms to improve nitric oxide availability. Current evidence suggests that a more nuanced approach to antioxidant therapy is more likely to yield positive reductions in end-organ injury, with considerations required for the types of ROS/RNS involved, the timing and dosage of antioxidant therapy, and the selective targeting of cell populations. This is likely to influence future strategies to lessen the burden of diabetic complications such as diabetes-associated atherosclerosis, diabetic nephropathy and diabetic retinopathy. |
Balan, P; Gogineni, S B; Kumari, S N; Shetty, V; Rangare, A L; Castelino, R L; Areekat, F K Candida Carriage Rate and Growth Characteristics of Saliva in Diabetes Mellitus Patients: A Case-Control Study. Journal Article Journal of Dental Research, Dental Clinics, Dental Prospects, 9 (4), pp. 274–279, 2015. @article{DentProspects2015, title = {Candida Carriage Rate and Growth Characteristics of Saliva in Diabetes Mellitus Patients: A Case-Control Study.}, author = {P Balan and S B Gogineni and S N Kumari and V Shetty and A L Rangare and R L Castelino and F K Areekat}, doi = {10.15171/joddd.2015.048}, year = {2015}, date = {2015-12-30}, journal = {Journal of Dental Research, Dental Clinics, Dental Prospects}, volume = {9}, number = {4}, pages = {274–279}, abstract = {Background and aims. The aim of this study was to establish a relationship between salivary glucose levels and Candida carriage rate in type 2 diabetes mellitus patients and assess the growth characteristics and acid production of Candida in glucose-supplemented saliva. Materials and methods. A total of 90 subjects, 30 with controlled type 2 diabetes, 30 with uncontrolled type 2 diabetes and 30 without diabetes (control subjects), aged 30‒60 years, participated in the study. Unstimulated saliva was collected and investigated for glucose levels (GOD-POD method), colony-forming units (CFU) of Candida and salivary pH, using Indikrom paper strips). Analysis of statistical significance of salivary glucose and PH levels was carried out using post hoc Tukey HSD test. Correlation of Candida carriage rate with salivary glucose and salivary PH in the study groups and control group was made using Pearson’s correlation. Results. Candida CFUs were significantly higher in diabetic subjects, with a significant and positive correlation with salivary glucose levels. There was a negative correlation between salivary PH levels and Candida carriage rate. Conclusion. Increased salivary glucose was associated with increased prevalence of oral Candida in diabetic subjects. The growth of Candida in saliva was accompanied by a rapid decline in PH, which in turn favored their growth.}, keywords = {}, pubstate = {published}, tppubtype = {article} } Background and aims. The aim of this study was to establish a relationship between salivary glucose levels and Candida carriage rate in type 2 diabetes mellitus patients and assess the growth characteristics and acid production of Candida in glucose-supplemented saliva. Materials and methods. A total of 90 subjects, 30 with controlled type 2 diabetes, 30 with uncontrolled type 2 diabetes and 30 without diabetes (control subjects), aged 30‒60 years, participated in the study. Unstimulated saliva was collected and investigated for glucose levels (GOD-POD method), colony-forming units (CFU) of Candida and salivary pH, using Indikrom paper strips). Analysis of statistical significance of salivary glucose and PH levels was carried out using post hoc Tukey HSD test. Correlation of Candida carriage rate with salivary glucose and salivary PH in the study groups and control group was made using Pearson’s correlation. Results. Candida CFUs were significantly higher in diabetic subjects, with a significant and positive correlation with salivary glucose levels. There was a negative correlation between salivary PH levels and Candida carriage rate. Conclusion. Increased salivary glucose was associated with increased prevalence of oral Candida in diabetic subjects. The growth of Candida in saliva was accompanied by a rapid decline in PH, which in turn favored their growth. |
2014 |
Wu, Y; Tang, L; Chen, B Oxidative Stress: Implications for the Development of Diabetic Retinopathy and Antioxidant Therapeutic Perspectives Journal Article Oxidative Medicine and Cellular Longevity, 2014 , pp. 1 - 12, 2014. @article{Perraudinbp, title = {Oxidative Stress: Implications for the Development of Diabetic Retinopathy and Antioxidant Therapeutic Perspectives}, author = {Y Wu and L Tang and B Chen}, doi = {10.1155/2014/752387}, year = {2014}, date = {2014-01-01}, journal = {Oxidative Medicine and Cellular Longevity}, volume = {2014}, pages = {1 - 12}, abstract = {In recent decades, localized tissue oxidative stress has been implicated as a key component in the development of diabetic retinopathy (DR). Increasing evidence shows that oxidative stress caused by diabetes-induced metabolic abnormalities is the most common mechanism associated with the pathogenesis of DR for both type 1 and type 2 diabetes. Increase in intracellular reactive oxygen species (ROS) concentrations results in the activation of several mechanisms involved in the pathogenesis of DR. In particular, damage or dysfunction caused by oxidative stress still persists even after glycemia has been normalized. Despite considerable evidence showing the beneficial effects of antioxidants in preventing the development of retinopathy, results from large-scale clinical trials on classic antioxidants are somewhat ambiguous. Scavenging reactive radicals may not be the most ideal antioxidant strategy in DR. Advances in understanding the function of ROS in the development of DR can lead to the development of new therapeutic strategies based on the mechanisms of ROS generation and scavenging. Increasing amounts of data have demonstrated the promising prospect of antioxidant therapy and its beneficial effects in vision protection. Therefore, new strategies that utilize antioxidants as additive therapy should be implemented in the treatment of DR.}, keywords = {}, pubstate = {published}, tppubtype = {article} } In recent decades, localized tissue oxidative stress has been implicated as a key component in the development of diabetic retinopathy (DR). Increasing evidence shows that oxidative stress caused by diabetes-induced metabolic abnormalities is the most common mechanism associated with the pathogenesis of DR for both type 1 and type 2 diabetes. Increase in intracellular reactive oxygen species (ROS) concentrations results in the activation of several mechanisms involved in the pathogenesis of DR. In particular, damage or dysfunction caused by oxidative stress still persists even after glycemia has been normalized. Despite considerable evidence showing the beneficial effects of antioxidants in preventing the development of retinopathy, results from large-scale clinical trials on classic antioxidants are somewhat ambiguous. Scavenging reactive radicals may not be the most ideal antioxidant strategy in DR. Advances in understanding the function of ROS in the development of DR can lead to the development of new therapeutic strategies based on the mechanisms of ROS generation and scavenging. Increasing amounts of data have demonstrated the promising prospect of antioxidant therapy and its beneficial effects in vision protection. Therefore, new strategies that utilize antioxidants as additive therapy should be implemented in the treatment of DR. |
Inubushi, T; Kawazoe, A; Miyauchi, M; Yanagisawa, S; Subarnbhesaj, A; Chanbora, C; Ayuningtyas, NF; Ishikado, A; Tanaka, ES; Takata, T Lactoferrin inhibits infection-related osteoclastogenesis without interrupting compressive force-related osteoclastogenesis. Journal Article Arch Oral Biol., 59 (2), pp. 226 - 232, 2014. @article{Perraudinbn, title = {Lactoferrin inhibits infection-related osteoclastogenesis without interrupting compressive force-related osteoclastogenesis.}, author = {T Inubushi and A Kawazoe and M Miyauchi and S Yanagisawa and A Subarnbhesaj and C Chanbora and NF Ayuningtyas and A Ishikado and ES Tanaka and T Takata}, doi = {10.1016/j.archoralbio.2013.11.002}, year = {2014}, date = {2014-01-02}, journal = {Arch Oral Biol.}, volume = {59}, number = {2}, pages = {226 - 232}, abstract = {BACKGROUND: Control of periodontal tissue inflammation during orthodontic treatment is very important in achieving a favourable therapeutic goal. We previously demonstrated that orally applied bovine lactoferrin (bLF) inhibited LPS-induced bone resorption but not orthodontic force-induced tooth movement in vivo. This study is designed to examine the underlying mechanism of it. METHODS: We examined the inhibitory effects of bLF on the expression of RANKL, OPG, TNF-α and COX-2 in osteoblasts loaded with compressive stress (CS) in comparison with LPS stimulated osteoblasts. Formation of osteoclasts was evaluated by co-culture system. RESULTS: Both CS- and LPS-applications upregulated COX-2 and RANKL but downregulated OPG. TNF-α was upregulated in LPS-stimulated osteoblasts but downregulated in CS-loaded osteoblasts. NS398 (a specific inhibitor of COX-2) significantly inhibited CS-induced RANKL-upregulation but not LPS-induced RANKL upregulation, indicating a critical role of COX-2/PGE2 pathway in CS-induced osteoclastogenesis. bLF significantly downregulated LPS-induced upregulation of RANKL and eliminated OPG suppression but not affected in CS-induced changes. Moreover, bLF significantly decreased LPS-induced osteoclast formation, whereas bLF had no effect on PGE2-induced osteoclast formation. CONCLUSIONS: bLF can effectively suppress harmful bone destruction associated with periodontitis without inhibiting bone remodelling by CS-loading. Therefore, oral administration of bLF may be highly beneficial for control of periodontitis in orthodontic patients.}, keywords = {}, pubstate = {published}, tppubtype = {article} } BACKGROUND: Control of periodontal tissue inflammation during orthodontic treatment is very important in achieving a favourable therapeutic goal. We previously demonstrated that orally applied bovine lactoferrin (bLF) inhibited LPS-induced bone resorption but not orthodontic force-induced tooth movement in vivo. This study is designed to examine the underlying mechanism of it. METHODS: We examined the inhibitory effects of bLF on the expression of RANKL, OPG, TNF-α and COX-2 in osteoblasts loaded with compressive stress (CS) in comparison with LPS stimulated osteoblasts. Formation of osteoclasts was evaluated by co-culture system. RESULTS: Both CS- and LPS-applications upregulated COX-2 and RANKL but downregulated OPG. TNF-α was upregulated in LPS-stimulated osteoblasts but downregulated in CS-loaded osteoblasts. NS398 (a specific inhibitor of COX-2) significantly inhibited CS-induced RANKL-upregulation but not LPS-induced RANKL upregulation, indicating a critical role of COX-2/PGE2 pathway in CS-induced osteoclastogenesis. bLF significantly downregulated LPS-induced upregulation of RANKL and eliminated OPG suppression but not affected in CS-induced changes. Moreover, bLF significantly decreased LPS-induced osteoclast formation, whereas bLF had no effect on PGE2-induced osteoclast formation. CONCLUSIONS: bLF can effectively suppress harmful bone destruction associated with periodontitis without inhibiting bone remodelling by CS-loading. Therefore, oral administration of bLF may be highly beneficial for control of periodontitis in orthodontic patients. |
Hou, JM; Chen, EY; Wei, SC; Lin, F; Lin, QM; Lan, XH; Xue, Y; Wu, M Lactoferrin inhibits apoptosis through insulin-like growth factor I in primary rat osteoblasts. Journal Article Acta Pharmacol Sin, 35 (4), pp. 523 - 530, 2014. @article{Perraudinbo, title = {Lactoferrin inhibits apoptosis through insulin-like growth factor I in primary rat osteoblasts.}, author = {JM Hou and EY Chen and SC Wei and F Lin and QM Lin and XH Lan and Y Xue and M Wu}, doi = {: 10.1038/aps.2013.173}, year = {2014}, date = {2014-01-02}, journal = {Acta Pharmacol Sin}, volume = {35}, number = {4}, pages = {523 - 530}, abstract = {Excessive apoptosis of osteoblasts is the major cause of low bone mass, and bovine lactoferrin (bLF), an iron-binding glycoprotein, might protect osteoblastic cells from apoptosis induced by serum withdrawal. The aim of this study was to elucidate the mechanisms underlying the anti-apoptotic action of bLF in rat osteoblasts in vitro. METHODS: Primary rat osteoblasts were incubated in the presence of varying concentrations of bLF for 24 h. The expression of insulin-like growth factor I (IGF-I) and IGF-I receptor (IGF-IR) was measured uisng RT-PCR and Western blotting. Cell apoptosis was examined with flow cytometry. siRNAs targeting IGF-I was used in this study. RESULTS: Treatment of bLF (0.1-1000 μg/mL) dose-dependently increased the expression of IGF-I and IGF-IR in the osteoblasts. Treatment with bLF (10, 100 μg/mL) markedly inhibited the osteoblast apoptosis (with the rate of total apoptosis of 70% at 10 μg/mL), but the high concentration of bLF (1000 μg/mL) significantly promoted the osteoblast apoptosis. Knockdown of the IGF-I gene in osteoblasts with siRNA markedly increased the osteoblast apoptosis. CONCLUSION: Lactoferrin (10 and 100 μg/mL) effectively inhibits apoptosis of primary rat osteoblasts by upregulating IGF-I expression.}, keywords = {}, pubstate = {published}, tppubtype = {article} } Excessive apoptosis of osteoblasts is the major cause of low bone mass, and bovine lactoferrin (bLF), an iron-binding glycoprotein, might protect osteoblastic cells from apoptosis induced by serum withdrawal. The aim of this study was to elucidate the mechanisms underlying the anti-apoptotic action of bLF in rat osteoblasts in vitro. METHODS: Primary rat osteoblasts were incubated in the presence of varying concentrations of bLF for 24 h. The expression of insulin-like growth factor I (IGF-I) and IGF-I receptor (IGF-IR) was measured uisng RT-PCR and Western blotting. Cell apoptosis was examined with flow cytometry. siRNAs targeting IGF-I was used in this study. RESULTS: Treatment of bLF (0.1-1000 μg/mL) dose-dependently increased the expression of IGF-I and IGF-IR in the osteoblasts. Treatment with bLF (10, 100 μg/mL) markedly inhibited the osteoblast apoptosis (with the rate of total apoptosis of 70% at 10 μg/mL), but the high concentration of bLF (1000 μg/mL) significantly promoted the osteoblast apoptosis. Knockdown of the IGF-I gene in osteoblasts with siRNA markedly increased the osteoblast apoptosis. CONCLUSION: Lactoferrin (10 and 100 μg/mL) effectively inhibits apoptosis of primary rat osteoblasts by upregulating IGF-I expression. |
Włodarski, KH; Galus, R; Brodzikowska, A; Włodarski, PK; Wojtowicz, A The importance of lactoferrin in bone regeneration] Journal Article Pol Merkur Lekarski, 37 (217), pp. 65-67, 2014. @article{Perraudinbm, title = {The importance of lactoferrin in bone regeneration]}, author = {KH Włodarski and R Galus and A Brodzikowska and PK Włodarski and A Wojtowicz}, doi = {PMID: 25154204}, year = {2014}, date = {2014-01-04}, journal = {Pol Merkur Lekarski}, volume = {37}, number = {217}, pages = {65-67}, abstract = {Lactoferrin is an iron-binding protein secreted by mammary gland, thus present in milk and in colostrum, which are a cheap and easy to obtain sources of this protein. Lactoferrin is also present in specific granules of neutrophils. Lactoferrin is a multifunctional agent involved, among others in the immune response and in the regulation of bone metabolism. Lactoferrin actives of osteoblast proliferation and bone matrix secretion, and inhibits apoptosis of osteoblast and osteoclastogenesis. Lactoferrin administered to rodents accelerates bone healing and prevents bone loss induced by ovariectomy. Therefore the use of lactoferrin or milk whey in osteoporosis treatment and prevention is postulated.}, keywords = {}, pubstate = {published}, tppubtype = {article} } Lactoferrin is an iron-binding protein secreted by mammary gland, thus present in milk and in colostrum, which are a cheap and easy to obtain sources of this protein. Lactoferrin is also present in specific granules of neutrophils. Lactoferrin is a multifunctional agent involved, among others in the immune response and in the regulation of bone metabolism. Lactoferrin actives of osteoblast proliferation and bone matrix secretion, and inhibits apoptosis of osteoblast and osteoclastogenesis. Lactoferrin administered to rodents accelerates bone healing and prevents bone loss induced by ovariectomy. Therefore the use of lactoferrin or milk whey in osteoporosis treatment and prevention is postulated. |
Rajendran, P; Nandakumar, N; Rengarajan, T; Palaniswami, R; Gnanadhas, EN; Lakshminarasaiah, US; Gopas, J; Nishigaki, I Antioxidants and human diseases. Journal Article Clin Chim Acta, 436 , pp. 332-347, 2014. @article{Perraudinbl, title = {Antioxidants and human diseases.}, author = {P Rajendran and N Nandakumar and T Rengarajan and R Palaniswami and EN Gnanadhas and US Lakshminarasaiah and J Gopas and I Nishigaki}, doi = {10.1016/j.cca.2014.06.004}, year = {2014}, date = {2014-03-01}, journal = {Clin Chim Acta}, volume = {436}, pages = {332-347}, abstract = {Oxidative stress plays a pivotal role in the development of human diseases. Reactive oxygen species (ROS) that includes hydrogen peroxide, hyphochlorus acid, superoxide anion, singlet oxygen, lipid peroxides, hypochlorite and hydroxyl radical are involved in growth, differentiation, progression and death of the cell. They can react with membrane lipids, nucleic acids, proteins, enzymes and other small molecules. Low concentrations of ROS has an indispensable role in intracellular signalling and defence against pathogens, while, higher amounts of ROS play a role in number of human diseases, including arthritis, cancer, diabetes, atherosclerosis, ischemia, failures in immunity and endocrine functions. Antioxidants presumably act as safeguard against the accumulation of ROS and their elimination from the system. The aim of this review is to highlight advances in understanding of the ROS and also to summarize the detailed impact and involvement of antioxidants in selected human diseases.}, keywords = {}, pubstate = {published}, tppubtype = {article} } Oxidative stress plays a pivotal role in the development of human diseases. Reactive oxygen species (ROS) that includes hydrogen peroxide, hyphochlorus acid, superoxide anion, singlet oxygen, lipid peroxides, hypochlorite and hydroxyl radical are involved in growth, differentiation, progression and death of the cell. They can react with membrane lipids, nucleic acids, proteins, enzymes and other small molecules. Low concentrations of ROS has an indispensable role in intracellular signalling and defence against pathogens, while, higher amounts of ROS play a role in number of human diseases, including arthritis, cancer, diabetes, atherosclerosis, ischemia, failures in immunity and endocrine functions. Antioxidants presumably act as safeguard against the accumulation of ROS and their elimination from the system. The aim of this review is to highlight advances in understanding of the ROS and also to summarize the detailed impact and involvement of antioxidants in selected human diseases. |
Wu, Y; Tang, L; Chen, B Oxidative stress: implications for the development of diabetic retinopathy and antioxidant therapeutic perspectives. Journal Article Oxidative Medicine and Cellular Longevity, 2014 , pp. 1 - 12, 2014. @article{Perraudinbk, title = {Oxidative stress: implications for the development of diabetic retinopathy and antioxidant therapeutic perspectives.}, author = {Y Wu and L Tang and B Chen}, doi = {10.1155/2014/752387.}, year = {2014}, date = {2014-07-01}, journal = {Oxidative Medicine and Cellular Longevity}, volume = {2014}, pages = {1 - 12}, abstract = {In recent decades, localized tissue oxidative stress has been implicated as a key component in the development of diabetic retinopathy (DR). Increasing evidence shows that oxidative stress caused by diabetes-induced metabolic abnormalities is the most common mechanism associated with the pathogenesis of DR for both type 1 and type 2 diabetes. Increase in intracellular reactive oxygen species (ROS) concentrations results in the activation of several mechanisms involved in the pathogenesis of DR. In particular, damage or dysfunction caused by oxidative stress still persists even after glycemia has been normalized. Despite considerable evidence showing the beneficial effects of antioxidants in preventing the development of retinopathy, results from large-scale clinical trials on classic antioxidants are somewhat ambiguous. Scavenging reactive radicals may not be the most ideal antioxidant strategy in DR. Advances in understanding the function of ROS in the development of DR can lead to the development of new therapeutic strategies based on the mechanisms of ROS generation and scavenging. Increasing amounts of data have demonstrated the promising prospect of antioxidant therapy and its beneficial effects in vision protection. Therefore, new strategies that utilize antioxidants as additive therapy should be implemented in the treatment of DR.}, keywords = {}, pubstate = {published}, tppubtype = {article} } In recent decades, localized tissue oxidative stress has been implicated as a key component in the development of diabetic retinopathy (DR). Increasing evidence shows that oxidative stress caused by diabetes-induced metabolic abnormalities is the most common mechanism associated with the pathogenesis of DR for both type 1 and type 2 diabetes. Increase in intracellular reactive oxygen species (ROS) concentrations results in the activation of several mechanisms involved in the pathogenesis of DR. In particular, damage or dysfunction caused by oxidative stress still persists even after glycemia has been normalized. Despite considerable evidence showing the beneficial effects of antioxidants in preventing the development of retinopathy, results from large-scale clinical trials on classic antioxidants are somewhat ambiguous. Scavenging reactive radicals may not be the most ideal antioxidant strategy in DR. Advances in understanding the function of ROS in the development of DR can lead to the development of new therapeutic strategies based on the mechanisms of ROS generation and scavenging. Increasing amounts of data have demonstrated the promising prospect of antioxidant therapy and its beneficial effects in vision protection. Therefore, new strategies that utilize antioxidants as additive therapy should be implemented in the treatment of DR. |
2013 |
Taylor, JJ; Preshaw, PM; Lalla, E A review of the evidence for pathogenic mechanisms that may link periodontitis and diabetes Journal Article J Periodontol, 84 (4), pp. 113-134, 2013. @article{Perraudinbq, title = {A review of the evidence for pathogenic mechanisms that may link periodontitis and diabetes}, author = {JJ Taylor and PM Preshaw and E Lalla}, doi = {10.1902/jop.2013.134005}, year = {2013}, date = {2013-01-01}, journal = {J Periodontol}, volume = {84}, number = {4}, pages = {113-134}, abstract = {AIMS: To review the evidence for the molecular and cellular processes that may potentially link periodontal disease and diabetes. The pathogenic roles of cytokines and metabolic molecules (e.g. glucose, lipids) are explored and the role of periodontal bacteria is also addressed. Paradigms for bidirectional relationships between periodontitis and diabetes are discussed and opportunities for elaborating these models are considered. METHODS: Database searches were performed using MeSH terms, keywords, and title words. Studies were evaluated and summarized in a narrative review. RESULTS: Periodontal microbiota appears unaltered by diabetes and there is little evidence that it may influence glycaemic control. Small-scale clinical studies and experiments in animal models suggest that IL-1b, TNF-a, IL-6, OPG and RANKL may mediate periodontitis in diabetes. The AGE-RAGE axis is likely an important pathway of tissue destruction and impaired repair in diabetes-associated periodontitis. A role for locally activated pro-inflammatory factors in the periodontium, which subsequently impact on diabetes, remains speculative. CONCLUSION: There is substantial information on potential mechanistic pathways which support a close association between diabetes and periodontitis, but there is a real need for longitudinal clinical studies using larger patient groups, integrated with studies of animal models and cells/tissues in vitro.}, keywords = {}, pubstate = {published}, tppubtype = {article} } AIMS: To review the evidence for the molecular and cellular processes that may potentially link periodontal disease and diabetes. The pathogenic roles of cytokines and metabolic molecules (e.g. glucose, lipids) are explored and the role of periodontal bacteria is also addressed. Paradigms for bidirectional relationships between periodontitis and diabetes are discussed and opportunities for elaborating these models are considered. METHODS: Database searches were performed using MeSH terms, keywords, and title words. Studies were evaluated and summarized in a narrative review. RESULTS: Periodontal microbiota appears unaltered by diabetes and there is little evidence that it may influence glycaemic control. Small-scale clinical studies and experiments in animal models suggest that IL-1b, TNF-a, IL-6, OPG and RANKL may mediate periodontitis in diabetes. The AGE-RAGE axis is likely an important pathway of tissue destruction and impaired repair in diabetes-associated periodontitis. A role for locally activated pro-inflammatory factors in the periodontium, which subsequently impact on diabetes, remains speculative. CONCLUSION: There is substantial information on potential mechanistic pathways which support a close association between diabetes and periodontitis, but there is a real need for longitudinal clinical studies using larger patient groups, integrated with studies of animal models and cells/tissues in vitro. |
Maritim, AC; Sanders, RA; III, JB Watkins Diabetes, Oxidative Stress, and Antioxidants: A review Journal Article J Biochem Molecular Toxicologt, 17 (1), pp. 24-38, 2013. @article{Perraudinbr, title = {Diabetes, Oxidative Stress, and Antioxidants: A review}, author = {AC Maritim and RA Sanders and JB Watkins III}, doi = {10.1002/jbt.10058}, year = {2013}, date = {2013-01-01}, journal = {J Biochem Molecular Toxicologt}, volume = {17}, number = {1}, pages = {24-38}, abstract = {Increasing evidence in both experimental and clinical studies suggests that oxidative stress plays a major role in the pathogenesis of both types of diabetes mellitus. Free radicals are formed disproportionately in diabetes by glucose oxidation, nonenzymatic glycation of proteins, and the subsequent oxidative degradation of glycated proteins. Abnormally high levels of free radicals and the simultaneous decline of antioxidant defense mechanisms can lead to damage of cellular organelles and enzymes, increased lipid peroxidation, and development of insulin resistance. These consequences of oxidative stress can promote the development of complications of diabetes mellitus. Changes in oxidative stress biomarkers, including superoxide dismutase, catalase, glutathione reductase, glutathione peroxidase, glutathione levels, vitamins, lipid peroxidation, nitrite concentration, nonenzymatic glycosylated proteins, and hyperglycemia in diabetes, and their consequences, are discussed in this review. In vivo studies of the effects of various conventional and alternative drugs on these biomarkers are surveyed. There is a need to continue to explore the relationship between free radicals, diabetes, and its complications, and to elucidate the mechanisms by which increased oxidative stress accelerates the development of diabetic complications, in an effort to expand treatment options}, keywords = {}, pubstate = {published}, tppubtype = {article} } Increasing evidence in both experimental and clinical studies suggests that oxidative stress plays a major role in the pathogenesis of both types of diabetes mellitus. Free radicals are formed disproportionately in diabetes by glucose oxidation, nonenzymatic glycation of proteins, and the subsequent oxidative degradation of glycated proteins. Abnormally high levels of free radicals and the simultaneous decline of antioxidant defense mechanisms can lead to damage of cellular organelles and enzymes, increased lipid peroxidation, and development of insulin resistance. These consequences of oxidative stress can promote the development of complications of diabetes mellitus. Changes in oxidative stress biomarkers, including superoxide dismutase, catalase, glutathione reductase, glutathione peroxidase, glutathione levels, vitamins, lipid peroxidation, nitrite concentration, nonenzymatic glycosylated proteins, and hyperglycemia in diabetes, and their consequences, are discussed in this review. In vivo studies of the effects of various conventional and alternative drugs on these biomarkers are surveyed. There is a need to continue to explore the relationship between free radicals, diabetes, and its complications, and to elucidate the mechanisms by which increased oxidative stress accelerates the development of diabetic complications, in an effort to expand treatment options |
Cueno, ME; Imai, K; Matsukawa, N; Tsukahara, T; Kurita-Ochiai, T; Ochiai, K Butyric acid retention in gingival tissue induces oxidative stress in jugular blood mitochondria. Journal Article Cell Stress and Chaperones, 18 , pp. 661-665, 2013. @article{Perraudinbs, title = {Butyric acid retention in gingival tissue induces oxidative stress in jugular blood mitochondria.}, author = {ME Cueno and K Imai and N Matsukawa and T Tsukahara and T Kurita-Ochiai and K Ochiai}, doi = {10.1007/s12192-013-0409-z}, year = {2013}, date = {2013-01-01}, journal = {Cell Stress and Chaperones}, volume = {18}, pages = {661-665}, abstract = {Butyric acid (BA) is a major extracellular metabolite produced by anaerobic periodontopathic bacteria and is commonly deposited in the gingival tissue. BA induces mitochondrial oxidative stress in vitro; however, its effects in vivo were never elucidated. Here, we determined the effects of butyric acid retention in the gingival tissues on oxidative stress induction in the jugular blood mitochondria. We established that BA injected in the rat gingival tissue has prolonged retention in gingival tissues. Blood taken at 0, 60, and 180 min after BA injection was used for further analysis. We isolated blood mitochondria, verified its purity, and measured hydrogen peroxide (H2O2), heme, superoxide (SOD), and catalase (CAT) to determine BA effects. We found that H2O2, heme, SOD, and CAT levels all increased after BA injection. This would insinuate that mitochondrial oxidative stress was induced ascribable to BA.}, keywords = {}, pubstate = {published}, tppubtype = {article} } Butyric acid (BA) is a major extracellular metabolite produced by anaerobic periodontopathic bacteria and is commonly deposited in the gingival tissue. BA induces mitochondrial oxidative stress in vitro; however, its effects in vivo were never elucidated. Here, we determined the effects of butyric acid retention in the gingival tissues on oxidative stress induction in the jugular blood mitochondria. We established that BA injected in the rat gingival tissue has prolonged retention in gingival tissues. Blood taken at 0, 60, and 180 min after BA injection was used for further analysis. We isolated blood mitochondria, verified its purity, and measured hydrogen peroxide (H2O2), heme, superoxide (SOD), and catalase (CAT) to determine BA effects. We found that H2O2, heme, SOD, and CAT levels all increased after BA injection. This would insinuate that mitochondrial oxidative stress was induced ascribable to BA. |
2012 |
Zhu, L; Jens, K The role of hydrogen peroxide in environmental adaptation of oral microbial communities. Journal Article Oxidative Medicine and Cellular longevity, 2012 , pp. 1 - 10, 2012. @article{Perraudinbu, title = {The role of hydrogen peroxide in environmental adaptation of oral microbial communities.}, author = {L Zhu and K Jens}, doi = {10.1155/2012/717843}, year = {2012}, date = {2012-01-01}, journal = {Oxidative Medicine and Cellular longevity}, volume = {2012}, pages = {1 - 10}, abstract = {Oral streptococci are able to produce growth-inhibiting amounts of hydrogen peroxide (H(2)O(2)) as byproduct of aerobic metabolism. Several recent studies showed that the produced H(2)O(2) is not a simple byproduct of metabolism but functions in several aspects of oral bacterial biofilm ecology. First, the release of DNA from cells is closely associated to the production of H(2)O(2) in Streptococcus sanguinis and Streptococcus gordonii. Extracellular DNA is crucial for biofilm development and stabilization and can also serve as source for horizontal gene transfer between oral streptococci. Second, due to the growth inhibiting nature of H(2)O(2), H(2)O(2) compatible species associate with the producers. H(2)O(2) production therefore might help in structuring the initial biofilm development. On the other hand, the oral environment harbors salivary peroxidases that are potent in H(2)O(2) scavenging. Therefore, the effects of biofilm intrinsic H(2)O(2) production might be locally confined. However, taking into account that 80% of initial oral biofilm constituents are streptococci, the influence of H(2)O(2) on biofilm development and environmental adaptation might be under appreciated in current research}, keywords = {}, pubstate = {published}, tppubtype = {article} } Oral streptococci are able to produce growth-inhibiting amounts of hydrogen peroxide (H(2)O(2)) as byproduct of aerobic metabolism. Several recent studies showed that the produced H(2)O(2) is not a simple byproduct of metabolism but functions in several aspects of oral bacterial biofilm ecology. First, the release of DNA from cells is closely associated to the production of H(2)O(2) in Streptococcus sanguinis and Streptococcus gordonii. Extracellular DNA is crucial for biofilm development and stabilization and can also serve as source for horizontal gene transfer between oral streptococci. Second, due to the growth inhibiting nature of H(2)O(2), H(2)O(2) compatible species associate with the producers. H(2)O(2) production therefore might help in structuring the initial biofilm development. On the other hand, the oral environment harbors salivary peroxidases that are potent in H(2)O(2) scavenging. Therefore, the effects of biofilm intrinsic H(2)O(2) production might be locally confined. However, taking into account that 80% of initial oral biofilm constituents are streptococci, the influence of H(2)O(2) on biofilm development and environmental adaptation might be under appreciated in current research |
Bharateesh, J; Ahmed, M; Kokila, G Diabetes and Oral Health: A Case-control Study. Journal Article Int J Prev Med, 3 (11), pp. 806 - 809, 2012. @article{Perraudinbv, title = {Diabetes and Oral Health: A Case-control Study.}, author = {J Bharateesh and M Ahmed and G Kokila}, doi = {PMC3506093}, year = {2012}, date = {2012-01-01}, journal = {Int J Prev Med}, volume = {3}, number = {11}, pages = {806 - 809}, abstract = {BACKGROUND: Diabetes mellitus, according to World Health Organization (WHO) is a silent epidemic which affects large number of people around the world and is directly related to the oral health status of the patients. OBJECTIVES: To know the prevalence of common dental diseases such as dental caries, periodontal diseases (pyorrhea), and treatment needs in a group of adult diabetic patients in private medical establishments of Tumkur city, south India, in comparison with non-diabetic patients. To create awareness among general medical practitioners about the common oral manifestations of diabetes and the importance of periodical dental check up for diabetics. METHODS: A group of 300 diabetic patients (males = 186}, keywords = {}, pubstate = {published}, tppubtype = {article} } BACKGROUND: Diabetes mellitus, according to World Health Organization (WHO) is a silent epidemic which affects large number of people around the world and is directly related to the oral health status of the patients. OBJECTIVES: To know the prevalence of common dental diseases such as dental caries, periodontal diseases (pyorrhea), and treatment needs in a group of adult diabetic patients in private medical establishments of Tumkur city, south India, in comparison with non-diabetic patients. To create awareness among general medical practitioners about the common oral manifestations of diabetes and the importance of periodical dental check up for diabetics. METHODS: A group of 300 diabetic patients (males = 186 |
Po-Chang, Lum Peng Lim Interrelationships of periodontitis and diabetes: A review of the current literature Journal Article Journal of Dental Sciences, 7 , pp. 272-282, 2012. @article{Article, title = {Interrelationships of periodontitis and diabetes: A review of the current literature}, author = {Lum Peng Lim Po-Chang}, doi = {http://dx.doi.org/10.1016/j.jds.2012.02.002}, year = {2012}, date = {2012-01-01}, journal = {Journal of Dental Sciences}, volume = {7}, pages = {272-282}, abstract = {Abstract Diabetes and periodontitis are common chronic diseases in the world, and abundant epidemiological evidence implies a bidirectional relationship between the two diseases. It appears that diabetes is a risk factor for greater periodontal destruction, whereas managing periodontitis can also contribute to better glycemic control. The underlying regulatory mechanisms are also bidirectional. The hyperglycemic status may directly alter subgingival microbial compositions, impair cellular function, and change collagen metabolism. The formation of advanced glycation end-products (AGEs) can further modify the extracellular matrix, and establishment of cellular receptor binding can amplify inflammation. Moreover, periodontitis also induces hyperlipidemia and insulin resistance. This cyclical relationship converges via overproduction of proinflammatory cytokines, such as tumor necrosis factor-a and interleukin-1b. Thus, this article highlights the importance of maintaining periodontal health to eliminate systemic complications and meticulous metabolic control to prevent further periodontal destruction. From a systemic aspect, targeting proinflammatory cytokines or receptors of AGEs could be a potential modality for treating periodontitis. Copyright ª 2012, Association for Dental Sciences of the Republic of China. Published by Elsevier Taiwan LLC. All rights reserved.}, keywords = {}, pubstate = {published}, tppubtype = {article} } Abstract Diabetes and periodontitis are common chronic diseases in the world, and abundant epidemiological evidence implies a bidirectional relationship between the two diseases. It appears that diabetes is a risk factor for greater periodontal destruction, whereas managing periodontitis can also contribute to better glycemic control. The underlying regulatory mechanisms are also bidirectional. The hyperglycemic status may directly alter subgingival microbial compositions, impair cellular function, and change collagen metabolism. The formation of advanced glycation end-products (AGEs) can further modify the extracellular matrix, and establishment of cellular receptor binding can amplify inflammation. Moreover, periodontitis also induces hyperlipidemia and insulin resistance. This cyclical relationship converges via overproduction of proinflammatory cytokines, such as tumor necrosis factor-a and interleukin-1b. Thus, this article highlights the importance of maintaining periodontal health to eliminate systemic complications and meticulous metabolic control to prevent further periodontal destruction. From a systemic aspect, targeting proinflammatory cytokines or receptors of AGEs could be a potential modality for treating periodontitis. Copyright ª 2012, Association for Dental Sciences of the Republic of China. Published by Elsevier Taiwan LLC. All rights reserved. |
Po-Chang, Lum Peng Lim Interrelationships of periodontitis and diabetes: A review of the current literature Journal Article Journal of Dental Sciences, 7 , pp. 272-282, 2012. @article{Perraudinbw, title = {Interrelationships of periodontitis and diabetes: A review of the current literature}, author = {Lum Peng Lim Po-Chang}, doi = {http://dx.doi.org/10.1016/j.jds.2012.02.002}, year = {2012}, date = {2012-01-01}, journal = {Journal of Dental Sciences}, volume = {7}, pages = {272-282}, abstract = {Abstract Diabetes and periodontitis are common chronic diseases in the world, and abundant epidemiological evidence implies a bidirectional relationship between the two diseases. It appears that diabetes is a risk factor for greater periodontal destruction, whereas managing periodontitis can also contribute to better glycemic control. The underlying regulatory mechanisms are also bidirectional. The hyperglycemic status may directly alter subgingival microbial compositions, impair cellular function, and change collagen metabolism. The formation of advanced glycation end-products (AGEs) can further modify the extracellular matrix, and establishment of cellular receptor binding can amplify inflammation. Moreover, periodontitis also induces hyperlipidemia and insulin resistance. This cyclical relationship converges via overproduction of proinflammatory cytokines, such as tumor necrosis factor-a and interleukin-1b. Thus, this article highlights the importance of maintaining periodontal health to eliminate systemic complications and meticulous metabolic control to prevent further periodontal destruction. From a systemic aspect, targeting proinflammatory cytokines or receptors of AGEs could be a potential modality for treating periodontitis. Copyright ª 2012, Association for Dental Sciences of the Republic of China. Published by Elsevier Taiwan LLC. All rights reserved}, keywords = {}, pubstate = {published}, tppubtype = {article} } Abstract Diabetes and periodontitis are common chronic diseases in the world, and abundant epidemiological evidence implies a bidirectional relationship between the two diseases. It appears that diabetes is a risk factor for greater periodontal destruction, whereas managing periodontitis can also contribute to better glycemic control. The underlying regulatory mechanisms are also bidirectional. The hyperglycemic status may directly alter subgingival microbial compositions, impair cellular function, and change collagen metabolism. The formation of advanced glycation end-products (AGEs) can further modify the extracellular matrix, and establishment of cellular receptor binding can amplify inflammation. Moreover, periodontitis also induces hyperlipidemia and insulin resistance. This cyclical relationship converges via overproduction of proinflammatory cytokines, such as tumor necrosis factor-a and interleukin-1b. Thus, this article highlights the importance of maintaining periodontal health to eliminate systemic complications and meticulous metabolic control to prevent further periodontal destruction. From a systemic aspect, targeting proinflammatory cytokines or receptors of AGEs could be a potential modality for treating periodontitis. Copyright ª 2012, Association for Dental Sciences of the Republic of China. Published by Elsevier Taiwan LLC. All rights reserved |
Inubushi, T; Kawazoe, A; Miyauchi, M; Kudo, Y; Ao, M; Ishikado, A; andT Takata, Makino T Molecular mechanisms of the inhibitory effects of bovine lactoferrin on lipopolysaccharide-mediated osteoclastogenesis. Journal Article J Biol Chem, 287 (28), pp. 23527 - 23536, 2012. @article{Perraudinbt, title = {Molecular mechanisms of the inhibitory effects of bovine lactoferrin on lipopolysaccharide-mediated osteoclastogenesis.}, author = {T Inubushi and A Kawazoe and M Miyauchi and Y Kudo and M Ao and A Ishikado and Makino T andT Takata}, doi = {10.1074/jbc.M111.324673}, year = {2012}, date = {2012-01-03}, journal = {J Biol Chem}, volume = {287}, number = {28}, pages = {23527 - 23536}, abstract = {Lactoferrin (LF) is an important modulator of the immune response and inflammation. It has also been implicated in the regulation of bone tissue. In our previous study we demonstrated that bovine LF (bLF) reduces LPS-induced bone resorption through a reduction of TNF-α production in vivo. However, it was not known how bLF inhibits LPS-mediated TNF-α and RANKL (receptor activator of nuclear factor κB ligand) production in osteoblasts. In this study we show that bLF impairs LPS-mediated TNF-α and RANKL production. bLF inhibited LPS-mediated osteoclastogenesis via osteoblasts in a co-culture system. Furthermore, bLF pretreatment inhibited LPS-induced NFκB DNA binding activity as well as IκBα and IKKβ (IκB kinase β) phosphorylation. MAP kinase activation was also inhibited by bLF pretreatment. However, bLF pretreatment failed to block the degradation of IRAK1 (interleukin-1 receptor-associated kinase 1), which is an essential event after its activation. Remarkably, we found that bLF pretreatment inhibited LPS-mediated Lys-63-linked polyubiquitination of TNF receptor-associated factor 6 (TRAF6). We also found that bLF is mainly endocytosed through LRP1 (lipoprotein receptor-related protein-1) and intracellular distributed bLF binds to endogenous TRAF6. In addition, bLF inhibited IL-1β- and flagellin-induced TRAF6-dependent activation of the NFκB signaling pathway. Collectively, our findings demonstrate that bLF inhibits NFκB and MAP kinase activation, which play critical roles in chronic inflammatory disease by interfering with the TRAF6 polyubiquitination process. Thus, bLF could be a potent therapeutic agent for inflammatory diseases associated with bone destruction, such as periodontitis and rheumatoid arthritis.}, keywords = {}, pubstate = {published}, tppubtype = {article} } Lactoferrin (LF) is an important modulator of the immune response and inflammation. It has also been implicated in the regulation of bone tissue. In our previous study we demonstrated that bovine LF (bLF) reduces LPS-induced bone resorption through a reduction of TNF-α production in vivo. However, it was not known how bLF inhibits LPS-mediated TNF-α and RANKL (receptor activator of nuclear factor κB ligand) production in osteoblasts. In this study we show that bLF impairs LPS-mediated TNF-α and RANKL production. bLF inhibited LPS-mediated osteoclastogenesis via osteoblasts in a co-culture system. Furthermore, bLF pretreatment inhibited LPS-induced NFκB DNA binding activity as well as IκBα and IKKβ (IκB kinase β) phosphorylation. MAP kinase activation was also inhibited by bLF pretreatment. However, bLF pretreatment failed to block the degradation of IRAK1 (interleukin-1 receptor-associated kinase 1), which is an essential event after its activation. Remarkably, we found that bLF pretreatment inhibited LPS-mediated Lys-63-linked polyubiquitination of TNF receptor-associated factor 6 (TRAF6). We also found that bLF is mainly endocytosed through LRP1 (lipoprotein receptor-related protein-1) and intracellular distributed bLF binds to endogenous TRAF6. In addition, bLF inhibited IL-1β- and flagellin-induced TRAF6-dependent activation of the NFκB signaling pathway. Collectively, our findings demonstrate that bLF inhibits NFκB and MAP kinase activation, which play critical roles in chronic inflammatory disease by interfering with the TRAF6 polyubiquitination process. Thus, bLF could be a potent therapeutic agent for inflammatory diseases associated with bone destruction, such as periodontitis and rheumatoid arthritis. |
Preshaw, P M; Alba, A L; Herrera, D; Jepsen, S; Konstantinidis, A; Makrilakis, K; Taylor, R Periodontitis and diabetes: a two-way relationship Journal Article Diabetologia, 55 , pp. 21-31, 2012. @article{Diabetologia2012, title = {Periodontitis and diabetes: a two-way relationship}, author = {P M Preshaw and A L Alba and D Herrera and S Jepsen and A Konstantinidis and K Makrilakis and R Taylor}, doi = {10.1007/s00125-011-2342-y}, year = {2012}, date = {2012-11-06}, journal = {Diabetologia}, volume = {55}, pages = {21-31}, abstract = {Periodontitis is a common chronic inflammatory disease characterised by destruction of the supporting structures of the teeth (the periodontal ligament and alveolar bone). It is highly prevalent (severe periodontitis affects 10–15% of adults) and has multiple negative impacts on quality of life. Epidemiological data confirm that diabetes is a major risk factor for periodontitis; susceptibility to periodontitis is increased by approximately threefold in people with diabetes. There is a clear relationship between degree of hyperglycaemia and severity of periodontitis. The mechanisms that underpin the links between these two conditions are not completely understood, but involve aspects of immune functioning, neutrophil activity, and cytokine biology. There is emerging evidence to support the existence of a two-way relationship between diabetes and periodontitis, with diabetes increasing the risk for periodontitis, and periodontal inflammation negatively affecting glycaemic control. Incidences of macroalbuminuria and end-stage renal disease are increased twofold and threefold, respectively, in diabetic individuals who also have severe periodontitis compared to diabetic individuals without severe periodontitis. Furthermore, the risk of cardiorenal mortality (ischaemic heart disease and diabetic nephropathy combined) is three times higher in diabetic people with severe periodontitis than in diabetic people without severe periodontitis. Treatment of periodontitis is associated with HbA1c reductions of approximately 0.4%. Oral and periodontal health should be promoted as integral components of diabetes management.}, keywords = {}, pubstate = {published}, tppubtype = {article} } Periodontitis is a common chronic inflammatory disease characterised by destruction of the supporting structures of the teeth (the periodontal ligament and alveolar bone). It is highly prevalent (severe periodontitis affects 10–15% of adults) and has multiple negative impacts on quality of life. Epidemiological data confirm that diabetes is a major risk factor for periodontitis; susceptibility to periodontitis is increased by approximately threefold in people with diabetes. There is a clear relationship between degree of hyperglycaemia and severity of periodontitis. The mechanisms that underpin the links between these two conditions are not completely understood, but involve aspects of immune functioning, neutrophil activity, and cytokine biology. There is emerging evidence to support the existence of a two-way relationship between diabetes and periodontitis, with diabetes increasing the risk for periodontitis, and periodontal inflammation negatively affecting glycaemic control. Incidences of macroalbuminuria and end-stage renal disease are increased twofold and threefold, respectively, in diabetic individuals who also have severe periodontitis compared to diabetic individuals without severe periodontitis. Furthermore, the risk of cardiorenal mortality (ischaemic heart disease and diabetic nephropathy combined) is three times higher in diabetic people with severe periodontitis than in diabetic people without severe periodontitis. Treatment of periodontitis is associated with HbA1c reductions of approximately 0.4%. Oral and periodontal health should be promoted as integral components of diabetes management. |
2011 |
Al-Rawi, NH Oxidative stress, antioxidant status and lipid profile in the saliva of type 2 diabetics. Journal Article Diabetes & Vascular Disease Research, 8 (1), pp. 22-28, 2011. @article{Perraudinby, title = {Oxidative stress, antioxidant status and lipid profile in the saliva of type 2 diabetics.}, author = {NH Al-Rawi}, doi = {10.1177/1479164110390243.}, year = {2011}, date = {2011-01-01}, journal = {Diabetes & Vascular Disease Research}, volume = {8}, number = {1}, pages = {22-28}, abstract = {BACKGROUND: The aim of this study was to assess the salivary content of lipid peroxidation and antioxidants in patients with type 2 diabetes. METHOD: We studied 25 patients with type 2 diabetes and other 25 age- and sex-matched health control. To evaluate the oxidative status we measured the levels of malondialdehyde (MDA) in the saliva and serum of all participants. Lipid profile was also estimated through measuring total cholesterol, triglycerides, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C) and very low-density lipoprotein cholesterol (VLDL-C) levels. Antioxidant levels were also assessed through measuring the salivary and serum concentration of uric acid, superoxide dismutase and reduced glutathione (GSH). RESULTS: The high concentration of lipid fractions in saliva usually follows that recorded in serum. Salivary MDA levels, a product of lipid peroxidation, were significantly increased among diabetics together with uric acid. However, GSH levels were similar to those of the control group. CONCLUSION: Lipid peroxidation and antioxidant parameters assessed in saliva of diabetic patients may be of great importance in evaluating the disease activity and severity. The increase in lipid peroxidation and the tendency of antioxidants to rise in diabetes is probably due to an adaptive response to the pro-oxidant status of diabetes}, keywords = {}, pubstate = {published}, tppubtype = {article} } BACKGROUND: The aim of this study was to assess the salivary content of lipid peroxidation and antioxidants in patients with type 2 diabetes. METHOD: We studied 25 patients with type 2 diabetes and other 25 age- and sex-matched health control. To evaluate the oxidative status we measured the levels of malondialdehyde (MDA) in the saliva and serum of all participants. Lipid profile was also estimated through measuring total cholesterol, triglycerides, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C) and very low-density lipoprotein cholesterol (VLDL-C) levels. Antioxidant levels were also assessed through measuring the salivary and serum concentration of uric acid, superoxide dismutase and reduced glutathione (GSH). RESULTS: The high concentration of lipid fractions in saliva usually follows that recorded in serum. Salivary MDA levels, a product of lipid peroxidation, were significantly increased among diabetics together with uric acid. However, GSH levels were similar to those of the control group. CONCLUSION: Lipid peroxidation and antioxidant parameters assessed in saliva of diabetic patients may be of great importance in evaluating the disease activity and severity. The increase in lipid peroxidation and the tendency of antioxidants to rise in diabetes is probably due to an adaptive response to the pro-oxidant status of diabetes |
Naot, D; Chhana, A; Matthews, BG; Callon, KE; Tong, PC; Lin, JM; Costa, JL; Watson, M; Grey, AB; J., Cornish J Molecular mechanisms involved in the mitogenic effect of lactoferrin in osteoblasts. Journal Article Bone, 49 (2), pp. 217 - 224, 2011. @article{Perraudinbx, title = {Molecular mechanisms involved in the mitogenic effect of lactoferrin in osteoblasts.}, author = {D Naot and A Chhana and BG Matthews and KE Callon and PC Tong and JM Lin and JL Costa and M Watson and AB Grey and Cornish J J.}, doi = {10.1016/j.bone.2011.04.002}, year = {2011}, date = {2011-01-02}, journal = {Bone}, volume = {49}, number = {2}, pages = {217 - 224}, abstract = {Lactoferrin, an iron-binding glycoprotein present in milk and other exocrine secretions in mammals, is anabolic to bone at physiological concentrations. Lactoferrin stimulates the proliferation, differentiation and survival of osteoblasts, as well as potently inhibiting osteoclastogenesis in bone marrow cultures. In the current study we further investigated the mechanism of action of lactoferrin in osteoblasts. We used low-density arrays to measure the level of expression of 45 genes in MC3T3-E1 osteoblast-like cells treated with lactoferrin, and identified transient, dose-dependent increases in the transcription levels of interleukin-6, of the pro-inflammatory factor prostaglandin-endoperoxide synthase 2 (Ptgs2), and of the transcription factor nuclear factor of activated T cells (Nfatc1). We demonstrated similar changes in primary osteoblast cultures from human and rat. Levels of prostaglandin E2 were increased in conditioned media collected from osteoblasts treated with lactoferrin, indicating that the activity of the enzyme cyclooxygenase 2 (COX2), which is encoded by Ptgs2, was also up-regulated. Using a luciferase reporter construct we showed that lactoferrin induced transcription from the NFAT consensus sequence. We found that inhibiting either COX2 or NFATc1 activity blocked the mitogenic effect of lactoferrin in osteoblasts and that inhibition of NFATc1 activity partially blocked the transcriptional activation of Ptgs2. Our study has provided the first evidence that COX2 and NFATc1 activities are increased by lactoferrin, and demonstrated a role for each of these molecules as mediators of the mitogenic effects of lactoferrin in osteoblasts.}, keywords = {}, pubstate = {published}, tppubtype = {article} } Lactoferrin, an iron-binding glycoprotein present in milk and other exocrine secretions in mammals, is anabolic to bone at physiological concentrations. Lactoferrin stimulates the proliferation, differentiation and survival of osteoblasts, as well as potently inhibiting osteoclastogenesis in bone marrow cultures. In the current study we further investigated the mechanism of action of lactoferrin in osteoblasts. We used low-density arrays to measure the level of expression of 45 genes in MC3T3-E1 osteoblast-like cells treated with lactoferrin, and identified transient, dose-dependent increases in the transcription levels of interleukin-6, of the pro-inflammatory factor prostaglandin-endoperoxide synthase 2 (Ptgs2), and of the transcription factor nuclear factor of activated T cells (Nfatc1). We demonstrated similar changes in primary osteoblast cultures from human and rat. Levels of prostaglandin E2 were increased in conditioned media collected from osteoblasts treated with lactoferrin, indicating that the activity of the enzyme cyclooxygenase 2 (COX2), which is encoded by Ptgs2, was also up-regulated. Using a luciferase reporter construct we showed that lactoferrin induced transcription from the NFAT consensus sequence. We found that inhibiting either COX2 or NFATc1 activity blocked the mitogenic effect of lactoferrin in osteoblasts and that inhibition of NFATc1 activity partially blocked the transcriptional activation of Ptgs2. Our study has provided the first evidence that COX2 and NFATc1 activities are increased by lactoferrin, and demonstrated a role for each of these molecules as mediators of the mitogenic effects of lactoferrin in osteoblasts. |
Valerio, M A; Kanjirath, P P; Klausner, C P; Peters, M C A qualitative examination of patient awareness and understanding of type 2 diabetes and oral health needs Journal Article Diabetes Research and Clinical Practice. Elesevier Ireland, 93 (2), pp. 159-165, 2011. @article{DiabetesResearch2011, title = {A qualitative examination of patient awareness and understanding of type 2 diabetes and oral health needs}, author = {M A Valerio and P P Kanjirath and C P Klausner and M C Peters}, doi = {10.1016/j.diabres.2011.03.034}, year = {2011}, date = {2011-08-01}, journal = {Diabetes Research and Clinical Practice. Elesevier Ireland}, volume = {93}, number = {2}, pages = {159-165}, abstract = {The study examined awareness and understanding of the bidirectional relationship between type 2 diabetes and oral health care in adult patients with type 2 diabetes. Methods: Focus groups were held with 30 participants with type 2 diabetes. Groups were comprised of African Americans (n = 16), Hispanics (n = 6), and Caucasians (n = 8). A grounded theory approach was used to analyse and interpret findings. Results: Participants were unaware of the relationship between type 2 diabetes and oral health but were concerned about the influence of poor oral health on quality of life. Having diabetes was reported as a potential challenge for the coordination and receipt of dental care. Patient-provider communication of diabetes and oral health needs were perceived to be inadequate. Conclusions: Patients with type 2 diabetes are at-risk for poor oral health, yet have limited awareness and understanding of the specific oral health care needs and risks associated with type 2 diabetes. This lack of awareness and understanding of the relationship between diabetes and oral health may be an indicator of inadequate oral health literacy. Addressing the relationship between diabetes and oral health with patients may improve dental outcomes, increase quality of life, and promote oral health literacy in at-risk populations.}, keywords = {}, pubstate = {published}, tppubtype = {article} } The study examined awareness and understanding of the bidirectional relationship between type 2 diabetes and oral health care in adult patients with type 2 diabetes. Methods: Focus groups were held with 30 participants with type 2 diabetes. Groups were comprised of African Americans (n = 16), Hispanics (n = 6), and Caucasians (n = 8). A grounded theory approach was used to analyse and interpret findings. Results: Participants were unaware of the relationship between type 2 diabetes and oral health but were concerned about the influence of poor oral health on quality of life. Having diabetes was reported as a potential challenge for the coordination and receipt of dental care. Patient-provider communication of diabetes and oral health needs were perceived to be inadequate. Conclusions: Patients with type 2 diabetes are at-risk for poor oral health, yet have limited awareness and understanding of the specific oral health care needs and risks associated with type 2 diabetes. This lack of awareness and understanding of the relationship between diabetes and oral health may be an indicator of inadequate oral health literacy. Addressing the relationship between diabetes and oral health with patients may improve dental outcomes, increase quality of life, and promote oral health literacy in at-risk populations. |
2010 |
Cornish, J; Naot, D Lactoferrin as an effector molecule in the skeleton. Journal Article Biometals, 23 (3), pp. 425-430, 2010. @article{Perraudinbz, title = {Lactoferrin as an effector molecule in the skeleton.}, author = {J Cornish and D Naot}, doi = {10.1007/s10534-010-9320-6}, year = {2010}, date = {2010-01-02}, journal = {Biometals}, volume = {23}, number = {3}, pages = {425-430}, abstract = {Lactoferrin is a pleiotropic factor with potent antimicrobial and immunomodulatory activities. In recent years, studies have shown that lactoferrin also acts on the skeleton to promote bone growth. Lactoferrin stimulates the proliferation and differentiation of the bone forming cells, the osteoblasts, and acts as a survival factor for these cells. Lactoferrin also inhibits osteoclastogenesis, reducing the number of cells that can actively resorb bone, thus producing a greater overall increase in bone volume. In vivo, local injection of lactoferrin results in substantial increases in bone area, establishing lactoferrin as an effector molecule in the skeleton. Investigations of the mechanism of action of lactoferrin in bone cells showed that the mitogenic effect of lactoferrin in osteoblasts is mediated mainly through LRP1, a member of the low density lipoprotein receptor-related proteins. Lactoferrin induces activation of p42/44 MAPK signaling as well as PI3-kinase-dependent phosphorylation of Akt in osteoblasts. Differential gene expression studies indicated a possible role for the activation of IGF1, Ptgs2 and Nfatc1 in mediating the mitogenic activity of lactoferrin in osteoblasts. Lactoferrin is a positive regulator of bone with a possible physiological role in bone growth and healing. There is a growing interest in the potential use of lactoferrin for the improvement of bone health, and in a number of recent studies dietary lactoferrin supplementation improved bone mineral density and bone strength. Lactoferrin appears to be a promising candidate for the development of an anabolic therapeutic factor for osteoporosis.}, keywords = {}, pubstate = {published}, tppubtype = {article} } Lactoferrin is a pleiotropic factor with potent antimicrobial and immunomodulatory activities. In recent years, studies have shown that lactoferrin also acts on the skeleton to promote bone growth. Lactoferrin stimulates the proliferation and differentiation of the bone forming cells, the osteoblasts, and acts as a survival factor for these cells. Lactoferrin also inhibits osteoclastogenesis, reducing the number of cells that can actively resorb bone, thus producing a greater overall increase in bone volume. In vivo, local injection of lactoferrin results in substantial increases in bone area, establishing lactoferrin as an effector molecule in the skeleton. Investigations of the mechanism of action of lactoferrin in bone cells showed that the mitogenic effect of lactoferrin in osteoblasts is mediated mainly through LRP1, a member of the low density lipoprotein receptor-related proteins. Lactoferrin induces activation of p42/44 MAPK signaling as well as PI3-kinase-dependent phosphorylation of Akt in osteoblasts. Differential gene expression studies indicated a possible role for the activation of IGF1, Ptgs2 and Nfatc1 in mediating the mitogenic activity of lactoferrin in osteoblasts. Lactoferrin is a positive regulator of bone with a possible physiological role in bone growth and healing. There is a growing interest in the potential use of lactoferrin for the improvement of bone health, and in a number of recent studies dietary lactoferrin supplementation improved bone mineral density and bone strength. Lactoferrin appears to be a promising candidate for the development of an anabolic therapeutic factor for osteoporosis. |
2009 |
Webb, CB; Falkowski, L Oxidative stress and innate immunity in feline patients with diabetes mellitus: the role of nutrition. Journal Article J Feline Med Surg, 11 (4), pp. 271-276, 2009. @article{Perraudinb_28, title = {Oxidative stress and innate immunity in feline patients with diabetes mellitus: the role of nutrition.}, author = {CB Webb and L Falkowski}, doi = {10.1016/j.jfms.2008.07.004}, year = {2009}, date = {2009-01-01}, journal = {J Feline Med Surg}, volume = {11}, number = {4}, pages = {271-276}, abstract = {This study was undertaken to test the hypothesis that oxidative stress is increased and neutrophil function is decreased in cats with diabetes mellitus (DM). Measures of oxidative stress and neutrophil function were evaluated in 20 control and 15 diabetic cats. Cats were then fed a diet designed specifically for feline diabetics (Purina DM Dietetic Management Feline Formula) for 8 weeks, after which all assays were repeated. Cats with DM had significantly less plasma superoxide dismutase (SOD) than control cats, consistent with a greater degree of oxidative stress in the DM group. Following 8 weeks of consuming a diabetes-specific diet glutathione peroxidase, an antioxidant enzyme increased significantly in both groups. Other parameters of oxidative stress, as well as neutrophil function, were similar between groups and did not change following dietary intervention. The DM cats were significantly older and heavier than the control cats, which may have contributed to differences in parameters of oxidative stress and levels of antioxidant enzymes between these groups, but the decreased level of SOD enzyme in the diabetic group would appear to support the continued development of targeted antioxidant supplementation for this cats with this disease.}, keywords = {}, pubstate = {published}, tppubtype = {article} } This study was undertaken to test the hypothesis that oxidative stress is increased and neutrophil function is decreased in cats with diabetes mellitus (DM). Measures of oxidative stress and neutrophil function were evaluated in 20 control and 15 diabetic cats. Cats were then fed a diet designed specifically for feline diabetics (Purina DM Dietetic Management Feline Formula) for 8 weeks, after which all assays were repeated. Cats with DM had significantly less plasma superoxide dismutase (SOD) than control cats, consistent with a greater degree of oxidative stress in the DM group. Following 8 weeks of consuming a diabetes-specific diet glutathione peroxidase, an antioxidant enzyme increased significantly in both groups. Other parameters of oxidative stress, as well as neutrophil function, were similar between groups and did not change following dietary intervention. The DM cats were significantly older and heavier than the control cats, which may have contributed to differences in parameters of oxidative stress and levels of antioxidant enzymes between these groups, but the decreased level of SOD enzyme in the diabetic group would appear to support the continued development of targeted antioxidant supplementation for this cats with this disease. |
Jenssen, H; Hancock, RE Antimicrobial properties of lactoferrin Journal Article Biochimie, 91 (1), pp. 19-29, 2009. @article{Perraudinb_27, title = {Antimicrobial properties of lactoferrin}, author = {H Jenssen and RE Hancock}, doi = {10.1016/j.biochi.2008.05.015}, year = {2009}, date = {2009-01-15}, journal = {Biochimie}, volume = {91}, number = {1}, pages = {19-29}, abstract = {Milk is a vital nutritional source for the offspring of all mammals, including humans. In addition to its nutritional value, it is a rich source of proteins including lactoferrin. Lactoferrin is a truly multifunctional protein that has been studied extensively over the past decades. It is best known for its ability to bind iron, which eventually led to the discovery of its antibacterial activity. In addition, lactoferrin has demonstrated potent antiviral, antifungal and antiparasitic activity, towards a broad spectrum of species. It is also considered to be an important host defense molecule during infant development. In this review, we focus on the antimicrobial activities of lactoferrin with particular emphasis on antibacterial and antiviral activities, although its antifungal and -parasitic activity are also discussed.}, keywords = {}, pubstate = {published}, tppubtype = {article} } Milk is a vital nutritional source for the offspring of all mammals, including humans. In addition to its nutritional value, it is a rich source of proteins including lactoferrin. Lactoferrin is a truly multifunctional protein that has been studied extensively over the past decades. It is best known for its ability to bind iron, which eventually led to the discovery of its antibacterial activity. In addition, lactoferrin has demonstrated potent antiviral, antifungal and antiparasitic activity, towards a broad spectrum of species. It is also considered to be an important host defense molecule during infant development. In this review, we focus on the antimicrobial activities of lactoferrin with particular emphasis on antibacterial and antiviral activities, although its antifungal and -parasitic activity are also discussed. |
Pierce, A; Legrand, D; Mazurier, J La lactoferrine : une protéine multifonctionnelle Lactoferrin: a multifunctional protein Journal Article Med Sci (Paris, 25 , pp. 361-369, 2009. @article{perraudinb_26, title = {La lactoferrine : une protéine multifonctionnelle Lactoferrin: a multifunctional protein}, author = {A Pierce and D Legrand and J Mazurier}, doi = {10.1051/medsci/2009254361}, year = {2009}, date = {2009-04-15}, journal = {Med Sci (Paris}, volume = {25}, pages = {361-369}, abstract = {La lactoferrine est une molécule énigmatique et fascinante apparue avec les mammifères ; elle appartient à la famille des transferrines, mais contrairement à la transferrine, qui a un rôle clé de transporteur du fer, la lactoferrine n’est pas impliquée dans l’homéostasie martiale. Les recherches entreprises depuis son isolement en 1960 n’ont pas réussi à complètement élucider sa fonction. Elle a longtemps été considérée comme un simple chélateur de fer protégeant contre les infections bactériennes par sa capacité à priver les bactéries du fer nécessaire à leur croissance. Depuis ces dix dernières années, de nouvelles fonctions orchestrées par la lactoferrine ont été découvertes : immunomodulation, protection contre le cancer et régulation de la croissance osseuse. L’objectif de cet article est de faire connaître les multiples facettes de cette molécule et d’en souligner l’implication dans de nombreux mécanismes de défense de l’organisme. Abstract Lactoferrin (Lf) is an iron-binding glycoprotein of the transferrin family that is expressed and secreted by glandular cells and found in the secondary granules of neutrophils from which it is released in infected tissues and blood during the inflammatory process. Initially described as an iron-binding molecule with bacteriostatic properties, Lf is now known to be a multifunctional or multi-tasking protein. It is a major component of the innate immune system of mammals. Its protective effects range from direct anti-microbial activities against a large panel of microorganisms including bacteria, viruses, fungi, and parasites, to anti-inflammatory and anti-cancer activities. While iron chelation is central to some of the biological functions of Lf, other activities involve interactions of Lf with molecular and cellular components of both hosts and pathogens. Its powerful antimicrobial activities, immunomodulatory properties and prevention of septic shock, anti-carcinogenic functions and its growing importance in iron delivery and bone growth, combined with the data obtained either by in vivo studies or clinical trials, make this molecule and its derivatives very promising tools for health or nutritional applications.}, keywords = {}, pubstate = {published}, tppubtype = {article} } La lactoferrine est une molécule énigmatique et fascinante apparue avec les mammifères ; elle appartient à la famille des transferrines, mais contrairement à la transferrine, qui a un rôle clé de transporteur du fer, la lactoferrine n’est pas impliquée dans l’homéostasie martiale. Les recherches entreprises depuis son isolement en 1960 n’ont pas réussi à complètement élucider sa fonction. Elle a longtemps été considérée comme un simple chélateur de fer protégeant contre les infections bactériennes par sa capacité à priver les bactéries du fer nécessaire à leur croissance. Depuis ces dix dernières années, de nouvelles fonctions orchestrées par la lactoferrine ont été découvertes : immunomodulation, protection contre le cancer et régulation de la croissance osseuse. L’objectif de cet article est de faire connaître les multiples facettes de cette molécule et d’en souligner l’implication dans de nombreux mécanismes de défense de l’organisme. Abstract Lactoferrin (Lf) is an iron-binding glycoprotein of the transferrin family that is expressed and secreted by glandular cells and found in the secondary granules of neutrophils from which it is released in infected tissues and blood during the inflammatory process. Initially described as an iron-binding molecule with bacteriostatic properties, Lf is now known to be a multifunctional or multi-tasking protein. It is a major component of the innate immune system of mammals. Its protective effects range from direct anti-microbial activities against a large panel of microorganisms including bacteria, viruses, fungi, and parasites, to anti-inflammatory and anti-cancer activities. While iron chelation is central to some of the biological functions of Lf, other activities involve interactions of Lf with molecular and cellular components of both hosts and pathogens. Its powerful antimicrobial activities, immunomodulatory properties and prevention of septic shock, anti-carcinogenic functions and its growing importance in iron delivery and bone growth, combined with the data obtained either by in vivo studies or clinical trials, make this molecule and its derivatives very promising tools for health or nutritional applications. |
2008 |
Abbeele, Vanden A; de Meel, H; Ahariz, M; Perraudin, JP; Beyer, I; Courtois, P Denture contamination by yeasts in the elderly Journal Article Gerodontology, 25 (4), pp. 222-228, 2008. @article{Perraudinb_29, title = {Denture contamination by yeasts in the elderly}, author = {Vanden A Abbeele and H de Meel and M Ahariz and JP Perraudin and I Beyer and P Courtois}, doi = {10.1111/j.1741-2358.2007.00247.x}, year = {2008}, date = {2008-01-02}, journal = {Gerodontology}, volume = {25}, number = {4}, pages = {222-228}, abstract = {OBJECTIVES: The aim of this study was to investigate yeast carriage in healthy denture wearers by swabbing and to evaluate the effect of denture hygiene habits. MATERIALS AND METHODS: Denture wearers (n = 87) without evidence of denture stomatitis or any other oral disease were investigated by separately swabbing the fitting surface of the upper denture and the corresponding palatal mucosa in contact with the appliance. In a group of volunteers, a gel without any active compound was spread on the palatal side of the denture once in every morning for 2 weeks. RESULTS: Screening showed Candida colonisation of upper prosthesis in 75.9% of individuals. The most frequent species isolated were Candida albicans (77.9% of the positive cultures), Candida glabrata (44.1%) and Candida tropicalis (19.1%). Carriage of more than one yeast species was found in 48.5% of the contaminated dentures. There was a statistically significant association between denture contamination and palatal mucosa colonisation (chi-squared test: p < 0.0001). Repeated swabbings after 1 week as well as during a weekly follow-up for 1 month confirmed the denture contamination and its degree of severity. A daily gel application produced a yeast-count decrease to 10% of the initial value after 2 weeks (chi-squared test: p = 0.0134 and p = 0.2841 for prosthesis and palatal mucosa, respectively). CONCLUSION: This study documented the reliability of oral swabbing when investigating yeast carriage in healthy denture wearers. Moreover, just a diagnostic tool, sampling upper dentures for Candida could be the opportunity to verify the patient's compliance to hygiene advice.}, keywords = {}, pubstate = {published}, tppubtype = {article} } OBJECTIVES: The aim of this study was to investigate yeast carriage in healthy denture wearers by swabbing and to evaluate the effect of denture hygiene habits. MATERIALS AND METHODS: Denture wearers (n = 87) without evidence of denture stomatitis or any other oral disease were investigated by separately swabbing the fitting surface of the upper denture and the corresponding palatal mucosa in contact with the appliance. In a group of volunteers, a gel without any active compound was spread on the palatal side of the denture once in every morning for 2 weeks. RESULTS: Screening showed Candida colonisation of upper prosthesis in 75.9% of individuals. The most frequent species isolated were Candida albicans (77.9% of the positive cultures), Candida glabrata (44.1%) and Candida tropicalis (19.1%). Carriage of more than one yeast species was found in 48.5% of the contaminated dentures. There was a statistically significant association between denture contamination and palatal mucosa colonisation (chi-squared test: p < 0.0001). Repeated swabbings after 1 week as well as during a weekly follow-up for 1 month confirmed the denture contamination and its degree of severity. A daily gel application produced a yeast-count decrease to 10% of the initial value after 2 weeks (chi-squared test: p = 0.0134 and p = 0.2841 for prosthesis and palatal mucosa, respectively). CONCLUSION: This study documented the reliability of oral swabbing when investigating yeast carriage in healthy denture wearers. Moreover, just a diagnostic tool, sampling upper dentures for Candida could be the opportunity to verify the patient's compliance to hygiene advice. |
Taylor, G W; Borgnakke, W S Periodontal diseases: association with diabetes, glycemic control and complications Journal Article Oral Diseases, 14 (3), pp. 191-203, 2008. @article{OralDiseases, title = {Periodontal diseases: association with diabetes, glycemic control and complications}, author = {G W Taylor and W S Borgnakke}, doi = {10.1111/j.1601-0825.2008.01442.x}, year = {2008}, date = {2008-04-11}, journal = {Oral Diseases}, volume = {14}, number = {3}, pages = {191-203}, abstract = {Objective: This report reviews the evidence for adverse effects of diabetes on periodontal health and periodontal disease on glycemic control and complications of diabetes. Design: MEDLINE search of the English language literature identified primary research reports published on (a) relationships between diabetes and periodontal diseases since 2000 and (b) effects of periodontal infection on glycemic control and diabetes complications since 1960. Results: Observational studies provided consistent evidence of greater prevalence, severity, extent, or progression of at least one manifestation of periodontal disease in 13/17 reports reviewed. Treatment and longitudinal observational studies provided evidence to support periodontal infection having an adverse effect on glycemic control, although not all investigations reported an improvement in glycemic control after periodontal treatment. Additionally, evidence from three observational studies supported periodontal disease increasing the risk for diabetes complications and no published reports refuted the findings. Conclusion: The evidence reviewed supports diabetes having an adverse effect on periodontal health and periodontal infection having an adverse effect on glycemic control and incidence of diabetes complications. Further rigorous study is necessary to establish unequivocally that treating periodontal infections can contribute to glycemic control management and to the reduction of the burden of diabetes complications.}, keywords = {}, pubstate = {published}, tppubtype = {article} } Objective: This report reviews the evidence for adverse effects of diabetes on periodontal health and periodontal disease on glycemic control and complications of diabetes. Design: MEDLINE search of the English language literature identified primary research reports published on (a) relationships between diabetes and periodontal diseases since 2000 and (b) effects of periodontal infection on glycemic control and diabetes complications since 1960. Results: Observational studies provided consistent evidence of greater prevalence, severity, extent, or progression of at least one manifestation of periodontal disease in 13/17 reports reviewed. Treatment and longitudinal observational studies provided evidence to support periodontal infection having an adverse effect on glycemic control, although not all investigations reported an improvement in glycemic control after periodontal treatment. Additionally, evidence from three observational studies supported periodontal disease increasing the risk for diabetes complications and no published reports refuted the findings. Conclusion: The evidence reviewed supports diabetes having an adverse effect on periodontal health and periodontal infection having an adverse effect on glycemic control and incidence of diabetes complications. Further rigorous study is necessary to establish unequivocally that treating periodontal infections can contribute to glycemic control management and to the reduction of the burden of diabetes complications. |
2006 |
Cornish, J; Palmano, K; Callon, KE; Watson, M; Lin, JM; Valenti, P; ana Grey, Naot AB D; Reid, IR Lactoferrin and bone; structure-activity relationships. Journal Article Biochem Cell Biol, 84 (3), pp. 297 - 302, 2006. @article{Perraudinb_30, title = {Lactoferrin and bone; structure-activity relationships.}, author = {J Cornish and K Palmano and KE Callon and M Watson and JM Lin and P Valenti and Naot AB D ana Grey and IR Reid}, doi = {10.1139/o06-057}, year = {2006}, date = {2006-01-02}, journal = {Biochem Cell Biol}, volume = {84}, number = {3}, pages = {297 - 302}, abstract = {The maintenance of the mechanical integrity of the skeleton depends on bone remodeling, the well-coordinated balance between bone formation by osteoblasts and bone resorption by osteoclasts. The coupled action of osteoblasts and osteoclasts is regulated by the action of many local and circulating hormones and factors as well as central regulation by a neurological mechanism. We have previously shown that lactoferrin can promote bone growth. At physiological concentrations, lactoferrin potently stimulates the proliferation and differentiation of primary osteoblasts and acts as a survival factor. Lactoferrin also affects osteoclasts, potently inhibiting their formation. In vivo, local injection of lactoferrin results in substantial increases in bone formation and bone area. In a critical bone-defect model in vivo, lactoferrin was also seen to promote bone growth. The mitogenic effect of lactoferrin in osteoblast-like cells is mediated mainly through low-density lipoprotein-receptor protein-1 (LRP1), a member of the low-density lipoprotein-receptor-related proteins that are primarily known as endocytic receptors; however, LRP1 is not necessary for the anti-apoptotic actions of lactoferrin. Lactoferrin also induces the activation of p42/44 mitogen-activated protein kinase (MAPK) signalling and the PI3-kinase-dependent phosphorylation of Akt in osteoblasts. In this study, we examined other properties of lactoferrin and the way they affect osteogenic activity. The degree of glycosylation, iron-binding, and the structure-activity relationships indicate that lactoferrin maintains osteogenic activity in deglycosylated, holo, and apo forms, and in with various small fragments of the molecule. These data suggest that lactoferrin signals through more than 1 membrane-bound receptor to produce its anabolic skeletal effects, and that it signals through diverse pathways. We conclude that lactoferrin might have a physiological role in bone growth and healing and a potential therapeutic role as an anabolic factor in osteoporosis.}, keywords = {}, pubstate = {published}, tppubtype = {article} } The maintenance of the mechanical integrity of the skeleton depends on bone remodeling, the well-coordinated balance between bone formation by osteoblasts and bone resorption by osteoclasts. The coupled action of osteoblasts and osteoclasts is regulated by the action of many local and circulating hormones and factors as well as central regulation by a neurological mechanism. We have previously shown that lactoferrin can promote bone growth. At physiological concentrations, lactoferrin potently stimulates the proliferation and differentiation of primary osteoblasts and acts as a survival factor. Lactoferrin also affects osteoclasts, potently inhibiting their formation. In vivo, local injection of lactoferrin results in substantial increases in bone formation and bone area. In a critical bone-defect model in vivo, lactoferrin was also seen to promote bone growth. The mitogenic effect of lactoferrin in osteoblast-like cells is mediated mainly through low-density lipoprotein-receptor protein-1 (LRP1), a member of the low-density lipoprotein-receptor-related proteins that are primarily known as endocytic receptors; however, LRP1 is not necessary for the anti-apoptotic actions of lactoferrin. Lactoferrin also induces the activation of p42/44 mitogen-activated protein kinase (MAPK) signalling and the PI3-kinase-dependent phosphorylation of Akt in osteoblasts. In this study, we examined other properties of lactoferrin and the way they affect osteogenic activity. The degree of glycosylation, iron-binding, and the structure-activity relationships indicate that lactoferrin maintains osteogenic activity in deglycosylated, holo, and apo forms, and in with various small fragments of the molecule. These data suggest that lactoferrin signals through more than 1 membrane-bound receptor to produce its anabolic skeletal effects, and that it signals through diverse pathways. We conclude that lactoferrin might have a physiological role in bone growth and healing and a potential therapeutic role as an anabolic factor in osteoporosis. |
Mealey, B L; Oates, T W Diabetes Mellitus and Periodontal Diseases Journal Article Journal of Periodontology, 77 (8), pp. 1289-1303, 2006. @article{Periodontol2006, title = {Diabetes Mellitus and Periodontal Diseases}, author = {B L Mealey and T W Oates}, doi = {10.1902/jop.2006.050459}, year = {2006}, date = {2006-02-01}, journal = {Journal of Periodontology}, volume = {77}, number = {8}, pages = {1289-1303}, edition = {2006}, abstract = {Background: The purpose of this review is to provide the reader with practical knowledge concerning the relationship between diabetes mellitus and periodontal diseases. Over 200 articles have been published in the English literature over the past 50 years examining the relationship between these two chronic diseases. Data interpretation is often confounded by varying definitions of diabetes and periodontitis and different clinical criteria applied to prevalence, extent, and severity of periodontal diseases, levels of glycemic control, and complications associated with diabetes. Methods: This article provides a broad overview of the predominant findings from research published in English over the past 20 years, with reference to certain “classic” articles published prior to that time. Results: This article describes current diagnostic and classification criteria for diabetes and answers the following questions: 1) Does diabetes affect the risk of periodontitis, and does the level of metabolic control of diabetes have an impact on this relationship? 2) Do periodontal diseases affect the pathophysiology of diabetes mellitus or the metabolic control of diabetes? 3) What are the mechanisms by which these two diseases interrelate? and 4) How do people with diabetes and periodontal disease respond to periodontal treatment? Conclusions: Diabetes increases the risk of periodontal diseases, and biologically plausible mechanisms have been demonstrated in abundance. Less clear is the impact of periodontal diseases on glycemic control of diabetes and the mechanisms through which this occurs. Inflammatory periodontal diseases may increase insulin resistance in a way similar to obesity, thereby aggravating glycemic control. Further research is needed to clarify this aspect of the relationship between periodontal diseases and diabetes. Periodically, the Board of Trustees of the American Academy of Periodontology identifies the need for review of the literature on a specific topic and requests the Editor-in-Chief of the Journal of Periodontology to commission such a review. The selected author is solely responsible for the content, and the manuscript is peer reviewed, like all other Journal articles. The Academy's Board of Trustees does not review or approve the manuscript prior to publication, and the content of the review should not be construed as Academy policy.}, keywords = {}, pubstate = {published}, tppubtype = {article} } Background: The purpose of this review is to provide the reader with practical knowledge concerning the relationship between diabetes mellitus and periodontal diseases. Over 200 articles have been published in the English literature over the past 50 years examining the relationship between these two chronic diseases. Data interpretation is often confounded by varying definitions of diabetes and periodontitis and different clinical criteria applied to prevalence, extent, and severity of periodontal diseases, levels of glycemic control, and complications associated with diabetes. Methods: This article provides a broad overview of the predominant findings from research published in English over the past 20 years, with reference to certain “classic” articles published prior to that time. Results: This article describes current diagnostic and classification criteria for diabetes and answers the following questions: 1) Does diabetes affect the risk of periodontitis, and does the level of metabolic control of diabetes have an impact on this relationship? 2) Do periodontal diseases affect the pathophysiology of diabetes mellitus or the metabolic control of diabetes? 3) What are the mechanisms by which these two diseases interrelate? and 4) How do people with diabetes and periodontal disease respond to periodontal treatment? Conclusions: Diabetes increases the risk of periodontal diseases, and biologically plausible mechanisms have been demonstrated in abundance. Less clear is the impact of periodontal diseases on glycemic control of diabetes and the mechanisms through which this occurs. Inflammatory periodontal diseases may increase insulin resistance in a way similar to obesity, thereby aggravating glycemic control. Further research is needed to clarify this aspect of the relationship between periodontal diseases and diabetes. Periodically, the Board of Trustees of the American Academy of Periodontology identifies the need for review of the literature on a specific topic and requests the Editor-in-Chief of the Journal of Periodontology to commission such a review. The selected author is solely responsible for the content, and the manuscript is peer reviewed, like all other Journal articles. The Academy's Board of Trustees does not review or approve the manuscript prior to publication, and the content of the review should not be construed as Academy policy. |
2005 |
Johansen, JS; Harris, AK; Rychly, DJ; Ergul, A Oxidative stress and the use of antioxidants in diabetes: linking basic science to clinical practice. Journal Article Cardiovascular Diabetology, 1 , pp. 1 - 11, 2005. @article{Perraudinb_32, title = {Oxidative stress and the use of antioxidants in diabetes: linking basic science to clinical practice.}, author = {JS Johansen and AK Harris and DJ Rychly and A Ergul}, doi = {10.1186/1475-2840-4-5}, year = {2005}, date = {2005-01-01}, journal = {Cardiovascular Diabetology}, volume = {1}, pages = {1 - 11}, abstract = {Cardiovascular complications, characterized by endothelial dysfunction and accelerated atherosclerosis, are the leading cause of morbidity and mortality associated with diabetes. There is growing evidence that excess generation of highly reactive free radicals, largely due to hyperglycemia, causes oxidative stress, which further exacerbates the development and progression of diabetes and its complications. Overproduction and/or insufficient removal of these free radicals result in vascular dysfunction, damage to cellular proteins, membrane lipids and nucleic acids. Despite overwhelming evidence on the damaging consequences of oxidative stress and its role in experimental diabetes, large scale clinical trials with classic antioxidants failed to demonstrate any benefit for diabetic patients. As our understanding of the mechanisms of free radical generation evolves, it is becoming clear that rather than merely scavenging reactive radicals, a more comprehensive approach aimed at preventing the generation of these reactive species as well as scavenging may prove more beneficial. Therefore, new strategies with classic as well as new antioxidants should be implemented in the treatment of diabetes.}, keywords = {}, pubstate = {published}, tppubtype = {article} } Cardiovascular complications, characterized by endothelial dysfunction and accelerated atherosclerosis, are the leading cause of morbidity and mortality associated with diabetes. There is growing evidence that excess generation of highly reactive free radicals, largely due to hyperglycemia, causes oxidative stress, which further exacerbates the development and progression of diabetes and its complications. Overproduction and/or insufficient removal of these free radicals result in vascular dysfunction, damage to cellular proteins, membrane lipids and nucleic acids. Despite overwhelming evidence on the damaging consequences of oxidative stress and its role in experimental diabetes, large scale clinical trials with classic antioxidants failed to demonstrate any benefit for diabetic patients. As our understanding of the mechanisms of free radical generation evolves, it is becoming clear that rather than merely scavenging reactive radicals, a more comprehensive approach aimed at preventing the generation of these reactive species as well as scavenging may prove more beneficial. Therefore, new strategies with classic as well as new antioxidants should be implemented in the treatment of diabetes. |
Naot, D; Grey, A; Reid, IR; Cornish, J Lactoferrin - A Novel Bone Growth Factor Journal Article Clinical Medicine & Research, 3 (2), pp. 93-101, 2005. @article{Perraudinb_31, title = {Lactoferrin - A Novel Bone Growth Factor}, author = {D Naot and A Grey and IR Reid and J Cornish}, doi = {PMID: 16012127}, year = {2005}, date = {2005-01-02}, journal = {Clinical Medicine & Research}, volume = {3}, number = {2}, pages = {93-101}, abstract = {Lactoferrin is an iron-binding glycoprotein that belongs to the transferrin family. It is present in breast milk, in epithelial secretions, and in the secondary granules of neutrophils. In healthy subjects lactoferrin circulates at concentrations of 2-7 x 10(-6) g/ml. Lactoferrin is a pleiotropic factor with potent antimicrobial and immunomodulatory activities. Recently, we have shown that lactoferrin can also promote bone growth. At physiological concentrations, lactoferrin potently stimulates the proliferation and differentiation of primary osteoblasts and also acts as a survival factor inhibiting apoptosis induced by serum withdrawal. Lactoferrin also affects osteoclast formation and, in murine bone marrow culture, lactoferrin potently inhibits osteoclastogenesis. In vivo, local injection of lactoferrin above the hemicalvaria of adult mice results in substantial increases in the dynamic histomorphometric indices of bone formation and bone area. The mitogenic effect of lactoferrin in osteoblast-like cells is mediated mainly through LRP1, a member of the family of low-density lipoprotein receptor-related proteins that are primarily known as endocytic receptors. Using confocal laser scanning microscopy, we demonstrated that fluorescently labeled lactoferrin is endocytosed and can be visualized in the cytoplasm of primary osteoblastic cells. Lactoferrin also induces activation of p42/44 MAPK signaling in primary osteoblasts, but the two pathways seem to operate independently as activation of MAPK signaling, but not endocytosis, is necessary for the mitogenic effect of lactoferrin. We conclude that lactoferrin may have a physiological role in bone growth and healing, and a potential therapeutic role as an anabolic factor in osteoporosis.}, keywords = {}, pubstate = {published}, tppubtype = {article} } Lactoferrin is an iron-binding glycoprotein that belongs to the transferrin family. It is present in breast milk, in epithelial secretions, and in the secondary granules of neutrophils. In healthy subjects lactoferrin circulates at concentrations of 2-7 x 10(-6) g/ml. Lactoferrin is a pleiotropic factor with potent antimicrobial and immunomodulatory activities. Recently, we have shown that lactoferrin can also promote bone growth. At physiological concentrations, lactoferrin potently stimulates the proliferation and differentiation of primary osteoblasts and also acts as a survival factor inhibiting apoptosis induced by serum withdrawal. Lactoferrin also affects osteoclast formation and, in murine bone marrow culture, lactoferrin potently inhibits osteoclastogenesis. In vivo, local injection of lactoferrin above the hemicalvaria of adult mice results in substantial increases in the dynamic histomorphometric indices of bone formation and bone area. The mitogenic effect of lactoferrin in osteoblast-like cells is mediated mainly through LRP1, a member of the family of low-density lipoprotein receptor-related proteins that are primarily known as endocytic receptors. Using confocal laser scanning microscopy, we demonstrated that fluorescently labeled lactoferrin is endocytosed and can be visualized in the cytoplasm of primary osteoblastic cells. Lactoferrin also induces activation of p42/44 MAPK signaling in primary osteoblasts, but the two pathways seem to operate independently as activation of MAPK signaling, but not endocytosis, is necessary for the mitogenic effect of lactoferrin. We conclude that lactoferrin may have a physiological role in bone growth and healing, and a potential therapeutic role as an anabolic factor in osteoporosis. |
2004 |
Bonnefont-Rousselot, D The role of antioxidant micronutrients in the prevention of diabetic complications Journal Article Treat Endocrinology, 3 (1), pp. 41-52, 2004. @article{Perraudinb_34, title = {The role of antioxidant micronutrients in the prevention of diabetic complications}, author = {D Bonnefont-Rousselot}, doi = {10/PMID: 15743112}, year = {2004}, date = {2004-01-01}, journal = {Treat Endocrinology}, volume = {3}, number = {1}, pages = {41-52}, abstract = {Diabetes mellitus is associated with an increased production of reactive oxygen species and a reduction in antioxidant defenses. This leads to oxidative stress, which is partly responsible for diabetic complications. Tight glycemic control is the most effective way of preventing or decreasing these complications. Nevertheless, antioxidant micronutrients can be proposed as adjunctive therapy in patients with diabetes. Indeed, some minerals and vitamins are able to indirectly participate in the reduction of oxidative stress in diabetic patients by improving glycemic control and/or are able to exert antioxidant activity. This article reviews the use of minerals (vanadium, chromium, magnesium, zinc, selenium, copper) and vitamins or cofactors (tocopherol [vitamin E], ascorbic acid [vitamin C], ubidecarenone [ubiquinone; coenzyme Q], nicotinamide, riboflavin, thioctic acid [lipoic acid], flavonoids) in diabetes, with a particular focus on the prevention of diabetic complications. Results show that dietary supplementation with micronutrients may be a complement to classical therapies for preventing and treating diabetic complications. Supplementation is expected to be more effective when a deficiency in these micronutrients exists. Nevertheless, many clinical studies have reported beneficial effects in individuals without deficiencies, although several of these studies were short term and had small sample sizes. However, a randomized, double-blind, placebo-controlled, multicenter trial showed that thioctic acid at an oral dosage of 800 mg/day for 4 months significantly improved cardiac autonomic neuropathy in type 2 diabetic patients. Above all, individuals with diabetes should be educated about the importance of consuming adequate amounts of vitamins and minerals from natural food sources, within the constraints of recommended sugar and carbohydrate intake.}, keywords = {}, pubstate = {published}, tppubtype = {article} } Diabetes mellitus is associated with an increased production of reactive oxygen species and a reduction in antioxidant defenses. This leads to oxidative stress, which is partly responsible for diabetic complications. Tight glycemic control is the most effective way of preventing or decreasing these complications. Nevertheless, antioxidant micronutrients can be proposed as adjunctive therapy in patients with diabetes. Indeed, some minerals and vitamins are able to indirectly participate in the reduction of oxidative stress in diabetic patients by improving glycemic control and/or are able to exert antioxidant activity. This article reviews the use of minerals (vanadium, chromium, magnesium, zinc, selenium, copper) and vitamins or cofactors (tocopherol [vitamin E], ascorbic acid [vitamin C], ubidecarenone [ubiquinone; coenzyme Q], nicotinamide, riboflavin, thioctic acid [lipoic acid], flavonoids) in diabetes, with a particular focus on the prevention of diabetic complications. Results show that dietary supplementation with micronutrients may be a complement to classical therapies for preventing and treating diabetic complications. Supplementation is expected to be more effective when a deficiency in these micronutrients exists. Nevertheless, many clinical studies have reported beneficial effects in individuals without deficiencies, although several of these studies were short term and had small sample sizes. However, a randomized, double-blind, placebo-controlled, multicenter trial showed that thioctic acid at an oral dosage of 800 mg/day for 4 months significantly improved cardiac autonomic neuropathy in type 2 diabetic patients. Above all, individuals with diabetes should be educated about the importance of consuming adequate amounts of vitamins and minerals from natural food sources, within the constraints of recommended sugar and carbohydrate intake. |
Vincent, AM; Russell, JW; Low, P; Feldman, EL Oxidative stress in the pathogenesis of diabetic neuropathy. Journal Article Endocrine Reviews, 25 (4), pp. 612-628, 2004. @article{Perraudinb_35, title = {Oxidative stress in the pathogenesis of diabetic neuropathy.}, author = {AM Vincent and JW Russell and P Low and EL Feldman}, doi = {10.1210/er.2003-0019}, year = {2004}, date = {2004-01-01}, journal = {Endocrine Reviews}, volume = {25}, number = {4}, pages = {612-628}, abstract = {Oxidative stress results from a cell or tissue failing to detoxify the free radicals that are produced during metabolic activity. Diabetes is characterized by chronic hyperglycemia that produces dysregulation of cellular metabolism. This review explores the concept that diabetes overloads glucose metabolic pathways, resulting in excess free radical production and oxidative stress. Evidence is presented to support the idea that both chronic and acute hyperglycemia cause oxidative stress in the peripheral nervous system that can promote the development of diabetic neuropathy. Proteins that are damaged by oxidative stress have decreased biological activity leading to loss of energy metabolism, cell signaling, transport, and, ultimately, to cell death. Examination of the data from animal and cell culture models of diabetes, as well as clinical trials of antioxidants, strongly implicates hyperglycemia-induced oxidative stress in diabetic neuropathy. We conclude that striving for superior antioxidative therapies remains essential for the prevention of neuropathy in diabetic patients.}, keywords = {}, pubstate = {published}, tppubtype = {article} } Oxidative stress results from a cell or tissue failing to detoxify the free radicals that are produced during metabolic activity. Diabetes is characterized by chronic hyperglycemia that produces dysregulation of cellular metabolism. This review explores the concept that diabetes overloads glucose metabolic pathways, resulting in excess free radical production and oxidative stress. Evidence is presented to support the idea that both chronic and acute hyperglycemia cause oxidative stress in the peripheral nervous system that can promote the development of diabetic neuropathy. Proteins that are damaged by oxidative stress have decreased biological activity leading to loss of energy metabolism, cell signaling, transport, and, ultimately, to cell death. Examination of the data from animal and cell culture models of diabetes, as well as clinical trials of antioxidants, strongly implicates hyperglycemia-induced oxidative stress in diabetic neuropathy. We conclude that striving for superior antioxidative therapies remains essential for the prevention of neuropathy in diabetic patients. |
Cornish, J; Callon, KE; Naot, D; Palmano, KP; Banovic, T; Bava, U; Watson, M; Lin, JM; Tong, PC; Chen, Q; Chan, VA; Reid, HE; Fazzalari, N; Baker, HM; Baker, EN; Haggarty, NW; Grey, AB; Reid., IR Lactoferrin is a potent regulator of bone cell activity and increases bone formation in vivo Journal Article bstractSend to Endocrinology, 145 (9), pp. 4366 - 4374, 2004. @article{Perraudinb_33, title = {Lactoferrin is a potent regulator of bone cell activity and increases bone formation in vivo}, author = {J Cornish and KE Callon and D Naot and KP Palmano and T Banovic and U Bava and M Watson and JM Lin and PC Tong and Q Chen and VA Chan and HE Reid and N Fazzalari and HM Baker and EN Baker and NW Haggarty and AB Grey and IR Reid.}, doi = {10.1210/en.2003-1307}, year = {2004}, date = {2004-01-02}, journal = {bstractSend to Endocrinology}, volume = {145}, number = {9}, pages = {4366 - 4374}, abstract = {Lactoferrin is an iron-binding glycoprotein present in epithelial secretions, such as milk, and in the secondary granules of neutrophils. We found it to be present in fractions of milk protein that stimulated osteoblast growth, so we assessed its effects on bone cell function. Lactoferrin produced large, dose-related increases in thymidine incorporation in primary or cell line cultures of human or rat osteoblast-like cells, at physiological concentrations (1-100 microg/ml). Maximal stimulation was 5-fold above control. Lactoferrin also increased osteoblast differentiation and reduced osteoblast apoptosis by up to 50-70%. Similarly, lactoferrin stimulated proliferation of primary chondrocytes. Purified, recombinant, human, or bovine lactoferrins had similar potencies. In mouse bone marrow cultures, osteoclastogenesis was dose-dependently decreased and was completely arrested by lactoferrin, 100 microg/ml, associated with decreased expression of receptor activator of nuclear factor-kappaB ligand. In contrast, lactoferrin had no effect on bone resorption by isolated mature osteoclasts. Lactoferrin was administered over calvariae of adult mice for 5 d. New bone formation, assessed using fluorochrome labels, was increased 4-fold by a 4-mg dose of lactoferrin. Thus, lactoferrin has powerful anabolic, differentiating, and antiapoptotic effects on osteoblasts and inhibits osteoclastogenesis. Lactoferrin is a potential therapeutic target in bone disorders such as osteoporosis and is possibly an important physiological regulator of bone growth.}, keywords = {}, pubstate = {published}, tppubtype = {article} } Lactoferrin is an iron-binding glycoprotein present in epithelial secretions, such as milk, and in the secondary granules of neutrophils. We found it to be present in fractions of milk protein that stimulated osteoblast growth, so we assessed its effects on bone cell function. Lactoferrin produced large, dose-related increases in thymidine incorporation in primary or cell line cultures of human or rat osteoblast-like cells, at physiological concentrations (1-100 microg/ml). Maximal stimulation was 5-fold above control. Lactoferrin also increased osteoblast differentiation and reduced osteoblast apoptosis by up to 50-70%. Similarly, lactoferrin stimulated proliferation of primary chondrocytes. Purified, recombinant, human, or bovine lactoferrins had similar potencies. In mouse bone marrow cultures, osteoclastogenesis was dose-dependently decreased and was completely arrested by lactoferrin, 100 microg/ml, associated with decreased expression of receptor activator of nuclear factor-kappaB ligand. In contrast, lactoferrin had no effect on bone resorption by isolated mature osteoclasts. Lactoferrin was administered over calvariae of adult mice for 5 d. New bone formation, assessed using fluorochrome labels, was increased 4-fold by a 4-mg dose of lactoferrin. Thus, lactoferrin has powerful anabolic, differentiating, and antiapoptotic effects on osteoblasts and inhibits osteoclastogenesis. Lactoferrin is a potential therapeutic target in bone disorders such as osteoporosis and is possibly an important physiological regulator of bone growth. |
2003 |
Maritim, AC; Sanders, RA; 3rd, JB Watkins Diabetes, oxidative stress, and antioxidants: a review Journal Article Journal Biochemistry Molecular Toxicology, 17 (1), 2003. @article{Perraudinb_37, title = {Diabetes, oxidative stress, and antioxidants: a review}, author = {AC Maritim and RA Sanders and JB Watkins 3rd}, doi = {10.1002/jbt.10058}, year = {2003}, date = {2003-01-01}, journal = {Journal Biochemistry Molecular Toxicology}, volume = {17}, number = {1}, abstract = {Increasing evidence in both experimental and clinical studies suggests that oxidative stress plays a major role in the pathogenesis of both types of diabetes mellitus. Free radicals are formed disproportionately in diabetes by glucose oxidation, nonenzymatic glycation of proteins, and the subsequent oxidative degradation of glycated proteins. Abnormally high levels of free radicals and the simultaneous decline of antioxidant defense mechanisms can lead to damage of cellular organelles and enzymes, increased lipid peroxidation, and development of insulin resistance. These consequences of oxidative stress can promote the development of complications of diabetes mellitus. Changes in oxidative stress biomarkers, including superoxide dismutase, catalase, glutathione reductase, glutathione peroxidase, glutathione levels, vitamins, lipid peroxidation, nitrite concentration, nonenzymatic glycosylated proteins, and hyperglycemia in diabetes, and their consequences, are discussed in this review. In vivo studies of the effects of various conventional and alternative drugs on these biomarkers are surveyed. There is a need to continue to explore the relationship between free radicals, diabetes, and its complications, and to elucidate the mechanisms by which increased oxidative stress accelerates the development of diabetic complications, in an effort to expand treatment options}, keywords = {}, pubstate = {published}, tppubtype = {article} } Increasing evidence in both experimental and clinical studies suggests that oxidative stress plays a major role in the pathogenesis of both types of diabetes mellitus. Free radicals are formed disproportionately in diabetes by glucose oxidation, nonenzymatic glycation of proteins, and the subsequent oxidative degradation of glycated proteins. Abnormally high levels of free radicals and the simultaneous decline of antioxidant defense mechanisms can lead to damage of cellular organelles and enzymes, increased lipid peroxidation, and development of insulin resistance. These consequences of oxidative stress can promote the development of complications of diabetes mellitus. Changes in oxidative stress biomarkers, including superoxide dismutase, catalase, glutathione reductase, glutathione peroxidase, glutathione levels, vitamins, lipid peroxidation, nitrite concentration, nonenzymatic glycosylated proteins, and hyperglycemia in diabetes, and their consequences, are discussed in this review. In vivo studies of the effects of various conventional and alternative drugs on these biomarkers are surveyed. There is a need to continue to explore the relationship between free radicals, diabetes, and its complications, and to elucidate the mechanisms by which increased oxidative stress accelerates the development of diabetic complications, in an effort to expand treatment options |
Bell, NH RANK Ligand and the regulation of skeletal remodeling Journal Article Journal Clinical Investigation, 111 (8), pp. 1120 - 1122, 2003. @article{Perraudinb_36, title = {RANK Ligand and the regulation of skeletal remodeling}, author = {NH Bell}, doi = {10.1172/JCI200318358}, year = {2003}, date = {2003-04-15}, journal = {Journal Clinical Investigation}, volume = {111}, number = {8}, pages = {1120 - 1122}, abstract = {No}, keywords = {}, pubstate = {published}, tppubtype = {article} } No |
2002 |
Qian, ZM Nitric oxide and changes of iron metabolism in exercise. Journal Article Biol. Rev, 77 , pp. 529-536, 2002. @article{Perraudinb_39, title = {Nitric oxide and changes of iron metabolism in exercise.}, author = {ZM Qian}, doi = {10.1017/S1464793102005997}, year = {2002}, date = {2002-01-01}, journal = {Biol. Rev}, volume = {77}, pages = {529-536}, abstract = {Accumulated data imply that exercise itself might not lead to a true iron deficiency or 'sport anaemia' in a healthy athlete who has adequate iron intake. The higher prevalence of iron deficiency anaemia in younger female athletes might be not due to exercise itself, but probably results from dietary choices, inadequate iron intake and menstruation. These factors can also induce iron deficiency or anaemia in the general population. However, exercise does affect iron metabolism, leading to low or sub-optimal iron status. The underlying mechanism is unknown. In this review, recent advances in the study of the effect of exercise on iron metabolism and nitric oxide, and the relationship between nitric oxide and iron status in exercise are discussed. A hypothesis that increased production of nitric oxide might contribute to sub-optimal iron status in exercise is proposed.}, keywords = {}, pubstate = {published}, tppubtype = {article} } Accumulated data imply that exercise itself might not lead to a true iron deficiency or 'sport anaemia' in a healthy athlete who has adequate iron intake. The higher prevalence of iron deficiency anaemia in younger female athletes might be not due to exercise itself, but probably results from dietary choices, inadequate iron intake and menstruation. These factors can also induce iron deficiency or anaemia in the general population. However, exercise does affect iron metabolism, leading to low or sub-optimal iron status. The underlying mechanism is unknown. In this review, recent advances in the study of the effect of exercise on iron metabolism and nitric oxide, and the relationship between nitric oxide and iron status in exercise are discussed. A hypothesis that increased production of nitric oxide might contribute to sub-optimal iron status in exercise is proposed. |
Akpan, A; Morgan, R Oral candidosis Journal Article Postgrad Med J, 78 (922), pp. 455-459, 2002. @article{Perraudinb_40, title = {Oral candidosis}, author = {A Akpan and R Morgan}, doi = {10.1136/pmj.78.922.455}, year = {2002}, date = {2002-01-01}, journal = {Postgrad Med J}, volume = {78}, number = {922}, pages = {455-459}, abstract = {Oral candidiasis is a common opportunistic infection of the oral cavity caused by an overgrowth of Candida species, the commonest being Candida albicans. The incidence varies depending on age and certain predisposing factors. There are three broad groupings consisting of acute candidiasis, chronic candidiasis, and angular cheilitis. Risk factors include impaired salivary gland function, drugs, dentures, high carbohydrate diet, and extremes of life, smoking, diabetes mellitus, Cushing's syndrome, malignancies, and immunosuppressive conditions. Management involves taking a history, an examination, and appropriate antifungal treatment with a few requiring samples to be taken for laboratory analysis. In certain high risk groups antifungal prophylaxis reduces the incidence and severity of infections. The prognosis is good in the great majority of cases.}, keywords = {}, pubstate = {published}, tppubtype = {article} } Oral candidiasis is a common opportunistic infection of the oral cavity caused by an overgrowth of Candida species, the commonest being Candida albicans. The incidence varies depending on age and certain predisposing factors. There are three broad groupings consisting of acute candidiasis, chronic candidiasis, and angular cheilitis. Risk factors include impaired salivary gland function, drugs, dentures, high carbohydrate diet, and extremes of life, smoking, diabetes mellitus, Cushing's syndrome, malignancies, and immunosuppressive conditions. Management involves taking a history, an examination, and appropriate antifungal treatment with a few requiring samples to be taken for laboratory analysis. In certain high risk groups antifungal prophylaxis reduces the incidence and severity of infections. The prognosis is good in the great majority of cases. |
Lorget, F; Clough, J; Oliveira, M; Daury, MC; Sabokbar, A; Offord, E Lactoferrin reduces in vitro osteoclast differentiation and resorbing activity. Journal Article Biochem Biophys Res Commun, 296 (2), pp. 261 - 266, 2002. @article{Perraudinb_38, title = {Lactoferrin reduces in vitro osteoclast differentiation and resorbing activity.}, author = {F Lorget and J Clough and M Oliveira and MC Daury and A Sabokbar and E Offord}, doi = {PMID: 12163011}, year = {2002}, date = {2002-01-02}, journal = {Biochem Biophys Res Commun}, volume = {296}, number = {2}, pages = {261 - 266}, abstract = {Lactoferrin (LF) is a key modulator of inflammatory response. Since bone and immune systems are genetically and functionally linked, we were interested to know if LF could influence bone remodeling. Bovine LF (bLF) inhibited in vitro bone resorbing activity (IC50, 200 microg/ml) in a rabbit mixed bone cell culture, consisting of authentic osteoclasts in an environment of osteoblast and stromal cells. Using human CD14 selected cells committed toward osteoclasts, bLF (10 microg/ml) stimulated cell proliferation, however, led to an inhibition of calcitonin receptor mRNA expression, a main marker of osteoclast phenotype, and decreased the global resorbing activity. No modulation of RANK mRNA expression was observed and mRNA for RANKL and OPG were not detected in this culture system, suggesting that bLF inhibits osteoclastogenesis and reduces bone resorption through a mechanism independent of OPG/RANKL/RANK. In conclusion, bLF appears to modulate bone remodeling. Its mechanism of action remains to be elucidated.}, keywords = {}, pubstate = {published}, tppubtype = {article} } Lactoferrin (LF) is a key modulator of inflammatory response. Since bone and immune systems are genetically and functionally linked, we were interested to know if LF could influence bone remodeling. Bovine LF (bLF) inhibited in vitro bone resorbing activity (IC50, 200 microg/ml) in a rabbit mixed bone cell culture, consisting of authentic osteoclasts in an environment of osteoblast and stromal cells. Using human CD14 selected cells committed toward osteoclasts, bLF (10 microg/ml) stimulated cell proliferation, however, led to an inhibition of calcitonin receptor mRNA expression, a main marker of osteoclast phenotype, and decreased the global resorbing activity. No modulation of RANK mRNA expression was observed and mRNA for RANKL and OPG were not detected in this culture system, suggesting that bLF inhibits osteoclastogenesis and reduces bone resorption through a mechanism independent of OPG/RANKL/RANK. In conclusion, bLF appears to modulate bone remodeling. Its mechanism of action remains to be elucidated. |
2000 |
Ceriello, A Oxidative stress and glycemic regulation Journal Article Metabolism, 49 (2 Suppl 1), pp. 27-29, 2000. @article{Perraudinb_41, title = {Oxidative stress and glycemic regulation}, author = {A Ceriello}, year = {2000}, date = {2000-01-08}, journal = {Metabolism}, volume = {49}, number = {2 Suppl 1}, pages = {27-29}, abstract = {Oxidative stress is an acknowledged pathogenetic mechanism in diabetic complications. Hyperglycemia is a widely known cause of enhanced free radical concentration, whereas oxidative stress involvement in glycemic regulation is still debated. Glucose transport is a cascade of events starting from the interaction of insulin with its own receptor at the plasma membrane and ending with intracellular glucose metabolism. In this complex series of events, each step plays an important role and can be inhibited by a negative effect of oxidative stress. Several studies show that an acute increase in the blood glucose level may impair the physiological homeostasis of many systems in living organisms. The mechanisms through which acute hyperglycemia exerts these effects may be identified in the production of free radicals. It has been suggested that insulin resistance may be accompanied by intracellular production of free radicals. In adipocytes cultured in vitro, insulin increases the production of hydrogen peroxide, which has been shown to mimic the action of insulin. These data allow us to hypothesize that a vicious circle between hyperinsulinemia and free radicals could be operating: insulin resistance might cause elevated plasma free radical concentrations, which, in turn, might be responsible for a deterioration of insulin action, with hyperglycemia being a contributory factor. Data supporting this hypothesis are available. Vitamin E improves insulin action in healthy, elderly, and non-insulin-dependent diabetic subjects. Similar results can be obtained by vitamin C administration.}, keywords = {}, pubstate = {published}, tppubtype = {article} } Oxidative stress is an acknowledged pathogenetic mechanism in diabetic complications. Hyperglycemia is a widely known cause of enhanced free radical concentration, whereas oxidative stress involvement in glycemic regulation is still debated. Glucose transport is a cascade of events starting from the interaction of insulin with its own receptor at the plasma membrane and ending with intracellular glucose metabolism. In this complex series of events, each step plays an important role and can be inhibited by a negative effect of oxidative stress. Several studies show that an acute increase in the blood glucose level may impair the physiological homeostasis of many systems in living organisms. The mechanisms through which acute hyperglycemia exerts these effects may be identified in the production of free radicals. It has been suggested that insulin resistance may be accompanied by intracellular production of free radicals. In adipocytes cultured in vitro, insulin increases the production of hydrogen peroxide, which has been shown to mimic the action of insulin. These data allow us to hypothesize that a vicious circle between hyperinsulinemia and free radicals could be operating: insulin resistance might cause elevated plasma free radical concentrations, which, in turn, might be responsible for a deterioration of insulin action, with hyperglycemia being a contributory factor. Data supporting this hypothesis are available. Vitamin E improves insulin action in healthy, elderly, and non-insulin-dependent diabetic subjects. Similar results can be obtained by vitamin C administration. |
1999 |
Baynes, JW; Thorpe, SR Role of oxidative stress in diabetic complications: a new perspective on an old paradigm Journal Article Diabetes, 48 (1), pp. 1-9, 1999. @article{Perraudinb_43, title = {Role of oxidative stress in diabetic complications: a new perspective on an old paradigm}, author = {JW Baynes and SR Thorpe}, year = {1999}, date = {1999-01-01}, journal = {Diabetes}, volume = {48}, number = {1}, pages = {1-9}, abstract = {Oxidative stress and oxidative damage to tissues are common end points of chronic diseases, such as atherosclerosis, diabetes, and rheumatoid arthritis. The question addressed in this review is whether increased oxidative stress has a primary role in the pathogenesis of diabetic complications or whether it is a secondary indicator of end-stage tissue damage in diabetes. The increase in glycoxidation and lipoxidation products in plasma and tissue proteins suggests that oxidative stress is increased in diabetes. However, some of these products, such as 3-deoxyglucosone adducts to lysine and arginine residues, are formed independent of oxidation chemistry. Elevated levels of oxidizable substrates may also explain the increase in glycoxidation and lipoxidation products in tissue proteins, without the necessity of invoking an increase in oxidative stress. Further, age-adjusted levels of oxidized amino acids, a more direct indicator of oxidative stress, are not increased in skin collagen in diabetes. We propose that the increased chemical modification of proteins by carbohydrates and lipids in diabetes is the result of overload on metabolic pathways involved in detoxification of reactive carbonyl species, leading to a general increase in steady-state levels of reactive carbonyl compounds formed by both oxidative and nonoxidative reactions. The increase in glycoxidation and lipoxidation of tissue proteins in diabetes may therefore be viewed as the result of increased carbonyl stress. The distinction between oxidative and carbonyl stress is discussed along with the therapeutic implications of this difference}, keywords = {}, pubstate = {published}, tppubtype = {article} } Oxidative stress and oxidative damage to tissues are common end points of chronic diseases, such as atherosclerosis, diabetes, and rheumatoid arthritis. The question addressed in this review is whether increased oxidative stress has a primary role in the pathogenesis of diabetic complications or whether it is a secondary indicator of end-stage tissue damage in diabetes. The increase in glycoxidation and lipoxidation products in plasma and tissue proteins suggests that oxidative stress is increased in diabetes. However, some of these products, such as 3-deoxyglucosone adducts to lysine and arginine residues, are formed independent of oxidation chemistry. Elevated levels of oxidizable substrates may also explain the increase in glycoxidation and lipoxidation products in tissue proteins, without the necessity of invoking an increase in oxidative stress. Further, age-adjusted levels of oxidized amino acids, a more direct indicator of oxidative stress, are not increased in skin collagen in diabetes. We propose that the increased chemical modification of proteins by carbohydrates and lipids in diabetes is the result of overload on metabolic pathways involved in detoxification of reactive carbonyl species, leading to a general increase in steady-state levels of reactive carbonyl compounds formed by both oxidative and nonoxidative reactions. The increase in glycoxidation and lipoxidation of tissue proteins in diabetes may therefore be viewed as the result of increased carbonyl stress. The distinction between oxidative and carbonyl stress is discussed along with the therapeutic implications of this difference |
Tessier, D; Khalil, A; Fülöp, T Effects of an oral glucose challenge on free radicals/antioxidants balance in an older population with type II diabetes. Journal Article Journal of Gerontology, 54A (11), pp. M541 - M545, 1999. @article{Perraudinb_44, title = {Effects of an oral glucose challenge on free radicals/antioxidants balance in an older population with type II diabetes.}, author = {D Tessier and A Khalil and T Fülöp}, doi = {http://biomedgerodontology.oxfordjournals.org}, year = {1999}, date = {1999-01-01}, journal = {Journal of Gerontology}, volume = {54A}, number = {11}, pages = {M541 - M545}, abstract = {BACKGROUND: Our goal was to assess the effect of chronic vs acute hyperglycemia on free radicals (FR)/antioxidants balance in serum and leukocytes in an older (>65 years old) population with type II diabetes mellitus (DM). METHODS: Case-control study comparing older male patients with type II DM with normal controls. FRs and antioxidants were measured at baseline and 120 min after an oral 100-g glucose load. RESULTS: Baseline measurements showed an increased level of oxidized glutathione (GSSG) (p = .01) in the serum of diabetic subjects. Similar findings were observed at the intracellular level in the same group for GSSG (p = .0004), total glutathione (GSH + GSSG) (p = .0001) (GSH is reduced glutathione), decreased GSH/GSSG ratio (p = .0001), and ascorbic acid (p = .008). Monocytes from diabetic subjects produced larger amounts of nitric oxide (NO) in vitro (p = .03). After the oral glucose challenge, between-group comparisons demonstrated similar findings at the intracellular level for increased oxidized glutathione (p = .0004), GSH + GSSG (p = .0001), decreased GSH/GSSG (p = .0001), ascorbic acid (p = .02), and increased NO (p = .02) for the diabetic subjects. Within-group comparisons showed a significant drop of ascorbic acid in the control and the diabetic groups (p < .01), an increased level of GSSG in the diabetic group (p < .01), a decreased GSH/GSSG ratio (p < .05), and decreased production of NO by monocytes after in vitro stimulation in the control group (p < .05). CONCLUSIONS: Our results suggest that type II diabetes in an older population is associated with increased basal oxidative stress. Hyperglycemic challenge is associated with an accentuation of this phenomenon as measured in the leukocytes.}, keywords = {}, pubstate = {published}, tppubtype = {article} } BACKGROUND: Our goal was to assess the effect of chronic vs acute hyperglycemia on free radicals (FR)/antioxidants balance in serum and leukocytes in an older (>65 years old) population with type II diabetes mellitus (DM). METHODS: Case-control study comparing older male patients with type II DM with normal controls. FRs and antioxidants were measured at baseline and 120 min after an oral 100-g glucose load. RESULTS: Baseline measurements showed an increased level of oxidized glutathione (GSSG) (p = .01) in the serum of diabetic subjects. Similar findings were observed at the intracellular level in the same group for GSSG (p = .0004), total glutathione (GSH + GSSG) (p = .0001) (GSH is reduced glutathione), decreased GSH/GSSG ratio (p = .0001), and ascorbic acid (p = .008). Monocytes from diabetic subjects produced larger amounts of nitric oxide (NO) in vitro (p = .03). After the oral glucose challenge, between-group comparisons demonstrated similar findings at the intracellular level for increased oxidized glutathione (p = .0004), GSH + GSSG (p = .0001), decreased GSH/GSSG (p = .0001), ascorbic acid (p = .02), and increased NO (p = .02) for the diabetic subjects. Within-group comparisons showed a significant drop of ascorbic acid in the control and the diabetic groups (p < .01), an increased level of GSSG in the diabetic group (p < .01), a decreased GSH/GSSG ratio (p < .05), and decreased production of NO by monocytes after in vitro stimulation in the control group (p < .05). CONCLUSIONS: Our results suggest that type II diabetes in an older population is associated with increased basal oxidative stress. Hyperglycemic challenge is associated with an accentuation of this phenomenon as measured in the leukocytes. |
Ceriello, Bortolotti N A; and Motz, E; Pieri, C; Marra, M; Tonutti, L; Lizzio, S; Feletto, F; Catone, B; Taboga, C Meal-induced oxidative stress and low-density lipoprotein oxidation in diabetes: the possible role of hyperglycemia Journal Article Metabolism, 48 (12), pp. 1503-1508, 1999. @article{Perraudinb_45, title = {Meal-induced oxidative stress and low-density lipoprotein oxidation in diabetes: the possible role of hyperglycemia}, author = {Bortolotti N A Ceriello and and E Motz and C Pieri and M Marra and L Tonutti and S Lizzio and F Feletto and B Catone and C Taboga}, year = {1999}, date = {1999-01-01}, journal = {Metabolism}, volume = {48}, number = {12}, pages = {1503-1508}, abstract = {Oxidative stress and its contribution to low-density lipoprotein (LDL) oxidation have been implicated in the pathogenesis of vascular diabetic complications. However, the relationship between hyperglycemia, hyperinsulinemia, hyperlipidemia, and oxidative stress is still debated. If plasma glucose and/or insulin and/or lipid are some of the most important determinants of oxidative stress in diabetes, then their typical postprandial elevations in diabetes would be expected to favor oxidative stress and LDL oxidation. To test this hypothesis, in type 2 diabetic patients, we evaluated the effects of two different standard meals designed to produce different levels of postprandial hyperglycemia on the plasma oxidative status and LDL oxidation. The meals were administered in randomized order to each of 10 type 2 diabetic patients. Blood samples were collected at baseline and 60 and 120 minutes after the meals. In every sample, plasma levels of glucose, insulin, cholesterol, triglycerides, nonesterified fatty acids (NEFAs), malondialdehyde (MDA), and the total radical-trapping antioxidant parameter (TRAP) were measured. LDL susceptibility to oxidation was evaluated at baseline and after 120 minutes. Plasma glucose, insulin, triglycerides, and MDA increased and NEFAs and TRAP significantly decreased after either meal. The variations in plasma glucose, MDA, and TRAP were significantly greater and LDL was more susceptible to oxidation after the meal that produced a significantly higher degree of hyperglycemia. These results suggest that postprandial hyperglycemia may contribute to oxidative stress in diabetic patients, providing a mechanistic link between hyperglycemia and diabetic vascular disease}, keywords = {}, pubstate = {published}, tppubtype = {article} } Oxidative stress and its contribution to low-density lipoprotein (LDL) oxidation have been implicated in the pathogenesis of vascular diabetic complications. However, the relationship between hyperglycemia, hyperinsulinemia, hyperlipidemia, and oxidative stress is still debated. If plasma glucose and/or insulin and/or lipid are some of the most important determinants of oxidative stress in diabetes, then their typical postprandial elevations in diabetes would be expected to favor oxidative stress and LDL oxidation. To test this hypothesis, in type 2 diabetic patients, we evaluated the effects of two different standard meals designed to produce different levels of postprandial hyperglycemia on the plasma oxidative status and LDL oxidation. The meals were administered in randomized order to each of 10 type 2 diabetic patients. Blood samples were collected at baseline and 60 and 120 minutes after the meals. In every sample, plasma levels of glucose, insulin, cholesterol, triglycerides, nonesterified fatty acids (NEFAs), malondialdehyde (MDA), and the total radical-trapping antioxidant parameter (TRAP) were measured. LDL susceptibility to oxidation was evaluated at baseline and after 120 minutes. Plasma glucose, insulin, triglycerides, and MDA increased and NEFAs and TRAP significantly decreased after either meal. The variations in plasma glucose, MDA, and TRAP were significantly greater and LDL was more susceptible to oxidation after the meal that produced a significantly higher degree of hyperglycemia. These results suggest that postprandial hyperglycemia may contribute to oxidative stress in diabetic patients, providing a mechanistic link between hyperglycemia and diabetic vascular disease |
Chapple, IL Reactive oxygen species and antioxidants in inflammatory diseases Journal Article J Clin Periodontol, 24 (5), pp. 287-296, 1999. @article{Perraudinb_42, title = {Reactive oxygen species and antioxidants in inflammatory diseases}, author = {IL Chapple}, year = {1999}, date = {1999-05-01}, journal = {J Clin Periodontol}, volume = {24}, number = {5}, pages = {287-296}, abstract = {This paper aims to review the rôle of free radical-induced tissue damage and antioxidant defence mechanisms in inflammatory diseases that involve pathogenic processes similar to the periodontal diseases. There is a clearly defined and substantial role for free radicals or reactive oxygen species (ROS) in periodontitis, but little research has been performed in this area. This paper reviews the considerable data available relating ROS activity and antioxidant defence to inflammatory diseases and attempts to draw parallels with periodontitis, in an effort to stimulate more periodontal research in this important area. The recent discovery of the transcription factor nuclear factor kappa B (NF-kappa B) is reviewed and several potential pathways for cytokine-induced periodontal tissue damage, mediated by NF-kappa B1 are discussed. Emphasis is placed on cytokines that have been studied in periodontitis, principally TNF-alpha, IL-1, IL-6, IL-8 and beta-interferon. The link between cellular production of such important mediators of inflammation and the antioxidant (AO) thiols, cysteine and reduced glutathione (GSH), is discussed and it is hypothesised that NF-kappa B antagonists may offer important therapeutic benefits.}, keywords = {}, pubstate = {published}, tppubtype = {article} } This paper aims to review the rôle of free radical-induced tissue damage and antioxidant defence mechanisms in inflammatory diseases that involve pathogenic processes similar to the periodontal diseases. There is a clearly defined and substantial role for free radicals or reactive oxygen species (ROS) in periodontitis, but little research has been performed in this area. This paper reviews the considerable data available relating ROS activity and antioxidant defence to inflammatory diseases and attempts to draw parallels with periodontitis, in an effort to stimulate more periodontal research in this important area. The recent discovery of the transcription factor nuclear factor kappa B (NF-kappa B) is reviewed and several potential pathways for cytokine-induced periodontal tissue damage, mediated by NF-kappa B1 are discussed. Emphasis is placed on cytokines that have been studied in periodontitis, principally TNF-alpha, IL-1, IL-6, IL-8 and beta-interferon. The link between cellular production of such important mediators of inflammation and the antioxidant (AO) thiols, cysteine and reduced glutathione (GSH), is discussed and it is hypothesised that NF-kappa B antagonists may offer important therapeutic benefits. |
1998 |
Webb, - B C; Thomas, C J; Willcox, M D; Harty, D W; Knox, K W Candida-associated denture stomatitis: aetiology and management: a review. Part 3. Treatment of oral candidosis Journal Article Australian Dental Journal, 43 (4), pp. 244-249, 1998. @article{Webb1998, title = {Candida-associated denture stomatitis: aetiology and management: a review. Part 3. Treatment of oral candidosis}, author = {- B C Webb and C J Thomas and M D Willcox and D W Harty and K W Knox}, editor = {Wiley Online Library}, doi = {10.1111/j.1834-7819.1998.tb00172.x}, year = {1998}, date = {1998-08-30}, journal = {Australian Dental Journal}, volume = {43}, number = {4}, pages = {244-249}, abstract = {Treatment of oral candidosis with topical antifungal agents such as nystatin and amphotericin B is effective initially. However, medication can produce side effects in some patients and when therapy is stopped the condition can recur. Alternative treatment involving the use of antiseptics and disinfecting agents has been shown to play an important role in the control of dental plaque. The use of sodium hypochlorite as an overnight denture soak has been shown to eliminate denture plaque and recent investigations have demonstrated that microwave irradiation of dentures at a specified setting and exposure time is bactericidal and candidacidal.}, keywords = {}, pubstate = {published}, tppubtype = {article} } Treatment of oral candidosis with topical antifungal agents such as nystatin and amphotericin B is effective initially. However, medication can produce side effects in some patients and when therapy is stopped the condition can recur. Alternative treatment involving the use of antiseptics and disinfecting agents has been shown to play an important role in the control of dental plaque. The use of sodium hypochlorite as an overnight denture soak has been shown to eliminate denture plaque and recent investigations have demonstrated that microwave irradiation of dentures at a specified setting and exposure time is bactericidal and candidacidal. |
1995 |
Morris, CJ; Earl, JR; Trenam, CW; Blake, DR Reactive oxygen species and iron--a dangerous partnership in inflammation. Journal Article Int. J. Biochem. Cell. Biol, 27 (2), pp. 109-122, 1995. @article{Perraudinb_46, title = {Reactive oxygen species and iron--a dangerous partnership in inflammation.}, author = {CJ Morris and JR Earl and CW Trenam and DR Blake}, year = {1995}, date = {1995-01-01}, journal = {Int. J. Biochem. Cell. Biol}, volume = {27}, number = {2}, pages = {109-122}, abstract = {Cells of nearly all forms of life require well-defined amounts of iron for survival, replication and expression of differentiated processes. It has a central role in erythropoiesis but is also involved in many other intracellular processes in the tissues of the body. It is the fourth most abundant element in the Earth's crust and the most abundant transition metal in living organisms for which its characteristic chemistry endows it with a series of properties enabling it to fulfil certain biological reactions especially those involving redox mechanisms. It is involved in the transport of oxygen, in electron transfer, in the synthesis of DNA, in oxidations by oxygen (O2) and hydrogen peroxide (H2O2) and in many other processes maintaining normal structure and function of virtually all mammalian cells. Because an iron atom can exist in two valency states, ferrous and ferric, iron became the primordial partner of oxygen in evolution. However, as de Sousa et al. (1989) state, such long standing partnerships have to use protective devices to ensure that the toxicity of neither partner is expressed in the presence of the other. Here, we discuss this dangerous partnership and its relevance to inflammation. The main themes of this review are the known roles of iron in the generation of reactive oxygen intermediates and new developments, including iron and transcription and the reaction of iron with nitric oxide. We also consider the widening recognition of the importance of oxygen metabolites in hypoxia-reperfusion injury and disease of the skin and joint.}, keywords = {}, pubstate = {published}, tppubtype = {article} } Cells of nearly all forms of life require well-defined amounts of iron for survival, replication and expression of differentiated processes. It has a central role in erythropoiesis but is also involved in many other intracellular processes in the tissues of the body. It is the fourth most abundant element in the Earth's crust and the most abundant transition metal in living organisms for which its characteristic chemistry endows it with a series of properties enabling it to fulfil certain biological reactions especially those involving redox mechanisms. It is involved in the transport of oxygen, in electron transfer, in the synthesis of DNA, in oxidations by oxygen (O2) and hydrogen peroxide (H2O2) and in many other processes maintaining normal structure and function of virtually all mammalian cells. Because an iron atom can exist in two valency states, ferrous and ferric, iron became the primordial partner of oxygen in evolution. However, as de Sousa et al. (1989) state, such long standing partnerships have to use protective devices to ensure that the toxicity of neither partner is expressed in the presence of the other. Here, we discuss this dangerous partnership and its relevance to inflammation. The main themes of this review are the known roles of iron in the generation of reactive oxygen intermediates and new developments, including iron and transcription and the reaction of iron with nitric oxide. We also consider the widening recognition of the importance of oxygen metabolites in hypoxia-reperfusion injury and disease of the skin and joint. |
Kontoghiorghes, GJ; Weinberg, ED Iron: mammalian defense systems, mechanisms of disease, and chelation therapy approaches. Journal Article Blod Rev, 9 (1), pp. 33-45, 1995, ISBN: 7795423. @article{Perraudinb_47, title = {Iron: mammalian defense systems, mechanisms of disease, and chelation therapy approaches.}, author = {GJ Kontoghiorghes and ED Weinberg}, isbn = {7795423}, year = {1995}, date = {1995-01-01}, journal = {Blod Rev}, volume = {9}, number = {1}, pages = {33-45}, abstract = {During the past 6 decades, much attention has been devoted to understanding the uses, metabolism and hazards of iron in living systems. A great variety of heme and non-heme iron-containing enzymes have been characterized in nearly all forms of life. The existence of both ferrous and ferric ions in low- and high-spin configuration, as well as the ability of the metal to function over a wide range of redox potentials, contributes to its unique versatility. Not surprisingly, the singular attributes of iron that permit it to be so useful to life likewise render the metal dangerous to manipulate and to sequester. All vertebrate animals are prone to tissue damage from exposure to excess iron. In order to protect them from this threat, a complex system has evolved to contain and detoxify this metal. This is known as the iron withholding defense system, which mainly serves to scavenge toxic quantities of iron and also for depriving microbial and neoplastic invaders of iron essential for their growth. Since 1970, medical scientists have become increasingly aware of the problems involved in cellular iron homeostasis and of the disease states related to its malfunctioning. Scores of studies have reported that excessive iron in specific tissue sites is associated with development of infection, neoplasia, cardiomyopathy, arthropathy and a variety of endocrine and neurologic deficits. Accordingly, several research groups have attempted to develop chemical agents that might prevent and even eliminate deposits of excess iron. A few of these drugs now are in clinical use, e.g. deferiprone (L1). In the present review, we focus on recent developments in (i) selected aspects of the iron withholding defense system, and (ii) pharmacologic methods that can assist the iron-burdened patient.}, keywords = {}, pubstate = {published}, tppubtype = {article} } During the past 6 decades, much attention has been devoted to understanding the uses, metabolism and hazards of iron in living systems. A great variety of heme and non-heme iron-containing enzymes have been characterized in nearly all forms of life. The existence of both ferrous and ferric ions in low- and high-spin configuration, as well as the ability of the metal to function over a wide range of redox potentials, contributes to its unique versatility. Not surprisingly, the singular attributes of iron that permit it to be so useful to life likewise render the metal dangerous to manipulate and to sequester. All vertebrate animals are prone to tissue damage from exposure to excess iron. In order to protect them from this threat, a complex system has evolved to contain and detoxify this metal. This is known as the iron withholding defense system, which mainly serves to scavenge toxic quantities of iron and also for depriving microbial and neoplastic invaders of iron essential for their growth. Since 1970, medical scientists have become increasingly aware of the problems involved in cellular iron homeostasis and of the disease states related to its malfunctioning. Scores of studies have reported that excessive iron in specific tissue sites is associated with development of infection, neoplasia, cardiomyopathy, arthropathy and a variety of endocrine and neurologic deficits. Accordingly, several research groups have attempted to develop chemical agents that might prevent and even eliminate deposits of excess iron. A few of these drugs now are in clinical use, e.g. deferiprone (L1). In the present review, we focus on recent developments in (i) selected aspects of the iron withholding defense system, and (ii) pharmacologic methods that can assist the iron-burdened patient. |
1991 |
Holt, SC.; Bramanti, TE Factors in virulence expression and their role in periodontal disease pathogenesis Journal Article Criricak Reviews in Oral Biology and medecine, 2 (2), pp. 177-281, 1991, ISBN: 1912148. @article{Perraudinb_49, title = {Factors in virulence expression and their role in periodontal disease pathogenesis}, author = {SC. Holt and TE Bramanti}, isbn = {1912148}, year = {1991}, date = {1991-01-01}, journal = {Criricak Reviews in Oral Biology and medecine}, volume = {2}, number = {2}, pages = {177-281}, abstract = {The classic progression of the development of periodontitis with its associated formation of an inflammatory lesion is characterized by a highly reproducible microbiological progression of a Gram-positive microbiota to a highly pathogenic Gram-negative one. While this Gram-negative microbiota is estimated to consist of at least 300 different microbial species, it appears to consist of a very limited number of microbial species that are involved in the destruction of periodontal diseases. Among these "putative periodontopathic species" are members of the genera Porphyromonas, Bacteroides, Fusobacterium, Wolinella, Actinobacillus, Capnocytophaga, and Eikenella. While members of the genera Actinomyces and Streptococcus may not be directly involved in the microbial progression, these species do appear to be essential to the construction of the network of microbial species that comprise both the subgingival plaque matrix. The temporal fluctuation (emergence/disappearance) of members of this microbiota from the developing lesion appears to depend upon the physical interaction of the periodontal pocket inhabitants, as well as the utilization of the metabolic end-products of the respective species intimately involved in the disease progression. A concerted action of the end-products of prokaryotic metabolism and the destruction of host tissues through the action of a large number of excreted proteolytic enzymes from several of these periodontopathogens contribute directly to the periodontal disease process.}, keywords = {}, pubstate = {published}, tppubtype = {article} } The classic progression of the development of periodontitis with its associated formation of an inflammatory lesion is characterized by a highly reproducible microbiological progression of a Gram-positive microbiota to a highly pathogenic Gram-negative one. While this Gram-negative microbiota is estimated to consist of at least 300 different microbial species, it appears to consist of a very limited number of microbial species that are involved in the destruction of periodontal diseases. Among these "putative periodontopathic species" are members of the genera Porphyromonas, Bacteroides, Fusobacterium, Wolinella, Actinobacillus, Capnocytophaga, and Eikenella. While members of the genera Actinomyces and Streptococcus may not be directly involved in the microbial progression, these species do appear to be essential to the construction of the network of microbial species that comprise both the subgingival plaque matrix. The temporal fluctuation (emergence/disappearance) of members of this microbiota from the developing lesion appears to depend upon the physical interaction of the periodontal pocket inhabitants, as well as the utilization of the metabolic end-products of the respective species intimately involved in the disease progression. A concerted action of the end-products of prokaryotic metabolism and the destruction of host tissues through the action of a large number of excreted proteolytic enzymes from several of these periodontopathogens contribute directly to the periodontal disease process. |
Emrich, LJ; Schlossman, M; Genco, RJ Periodontal disease in non-insulin-dependant diabetes mellitus Journal Article Journal Periodontology, 62 (2), pp. 123-131, 1991. @article{perraudinb_48, title = {Periodontal disease in non-insulin-dependant diabetes mellitus}, author = {LJ Emrich and M Schlossman and RJ Genco}, doi = {10.1902/jop.1991.62.2.123}, year = {1991}, date = {1991-02-01}, journal = {Journal Periodontology}, volume = {62}, number = {2}, pages = {123-131}, abstract = {The relationship between diabetes mellitus and oral health status was determined in Pima Indians from the Gila River Indian Community in Arizona. This tribe of native Americans has the world's highest reported incidence and prevalence of non-insulin-dependent (type 2) diabetes mellitus. The probing attachment level, alveolar bone loss, age, sex, Calculus Index, Plaque Index, Gingival Index, fluorosis, and DMFT as well as the diabetic status was assessed in 1,342 Pima Indians who were at least partially dentate. The prevalence and severity of destructive periodontal disease was determined by measuring probing attachment loss and radiographically apparent interproximal crestal alveolar bone loss, two independent but correlated indicators of periodontal destruction. Only diabetic status, age, and the presence of subgingival calculus were significantly associated with both increased prevalence and greater severity of destructive periodontal disease in this population. Diabetic status was significantly and strongly related to both the prevalence and severity of disease after adjusting for the effects of demographic variables and several indices of oral health including the Plaque Index. Subjects with type 2 diabetes have an increased risk of destructive periodontitis with an odds ratio of 2.81 (95% confidence interval 1.91 to 4.13) when attachment loss is used to measure the disease. The odds ratio for diabetic subjects was 3.43 (95% confidence interval 2.28 to 5.16) where bone loss was used to measure periodontal destruction. These findings demonstrate tht diabetes increases the risk of developing destructive periodontal disease about threefold. Furthermore, diabetes increases the risk of developing periodontal disease in a manner which cannot be explained on the basis of age, sex, and hygiene or other dental measures.}, keywords = {}, pubstate = {published}, tppubtype = {article} } The relationship between diabetes mellitus and oral health status was determined in Pima Indians from the Gila River Indian Community in Arizona. This tribe of native Americans has the world's highest reported incidence and prevalence of non-insulin-dependent (type 2) diabetes mellitus. The probing attachment level, alveolar bone loss, age, sex, Calculus Index, Plaque Index, Gingival Index, fluorosis, and DMFT as well as the diabetic status was assessed in 1,342 Pima Indians who were at least partially dentate. The prevalence and severity of destructive periodontal disease was determined by measuring probing attachment loss and radiographically apparent interproximal crestal alveolar bone loss, two independent but correlated indicators of periodontal destruction. Only diabetic status, age, and the presence of subgingival calculus were significantly associated with both increased prevalence and greater severity of destructive periodontal disease in this population. Diabetic status was significantly and strongly related to both the prevalence and severity of disease after adjusting for the effects of demographic variables and several indices of oral health including the Plaque Index. Subjects with type 2 diabetes have an increased risk of destructive periodontitis with an odds ratio of 2.81 (95% confidence interval 1.91 to 4.13) when attachment loss is used to measure the disease. The odds ratio for diabetic subjects was 3.43 (95% confidence interval 2.28 to 5.16) where bone loss was used to measure periodontal destruction. These findings demonstrate tht diabetes increases the risk of developing destructive periodontal disease about threefold. Furthermore, diabetes increases the risk of developing periodontal disease in a manner which cannot be explained on the basis of age, sex, and hygiene or other dental measures. |
1988 |
Ellison, R T; Giehl, T J; Force, La F M Damage of the outer membrane of enteric gram-negative bacteria by lactoferrin and transferrin Journal Article Infect Immunology, 56 (11), pp. 2774 - 2781, 1988. @article{Perraudin_50, title = {Damage of the outer membrane of enteric gram-negative bacteria by lactoferrin and transferrin}, author = {R T Ellison and T J Giehl and La F M Force}, year = {1988}, date = {1988-11-01}, journal = {Infect Immunology}, volume = {56}, number = {11}, pages = {2774 - 2781}, abstract = {Many studies have shown that lactoferrin and transferrin have antimicrobial activity against gram-negative bacteria, but a mechanism of action has not been defined. We hypothesized that the iron-binding proteins could affect the gram-negative outer membrane in a manner similar to that of the chelator EDTA. The ability of lactoferrin and transferrin to release radiolabeled lipopolysaccharide (LPS) from a UDP-galactose epimerase-deficient Escherichia coli mutant and from wild-type Salmonella typhimurium strains was tested. Initial studies in barbital-acetate buffer showed that EDTA and lactoferrin cause significant release of LPS from all three strains. Further studies found that LPS release was blocked by iron saturation of lactoferrin, occurred between pH 6 and 7.5, was comparable for bacterial concentrations from 10(4) to 10(7) CFU/ml, and increased with increasing lactoferrin concentrations. Studies using Hanks balanced salt solution lacking calcium and magnesium showed that transferrin also could cause LPS release. Additionally, both lactoferrin and transferrin increased the antibacterial effect of a subinhibitory concentration of rifampin, a drug excluded by the bacterial outer membrane. This work demonstrates that these iron-binding proteins damage the gram-negative outer membrane and alter bacterial outer membrane permeability.}, keywords = {}, pubstate = {published}, tppubtype = {article} } Many studies have shown that lactoferrin and transferrin have antimicrobial activity against gram-negative bacteria, but a mechanism of action has not been defined. We hypothesized that the iron-binding proteins could affect the gram-negative outer membrane in a manner similar to that of the chelator EDTA. The ability of lactoferrin and transferrin to release radiolabeled lipopolysaccharide (LPS) from a UDP-galactose epimerase-deficient Escherichia coli mutant and from wild-type Salmonella typhimurium strains was tested. Initial studies in barbital-acetate buffer showed that EDTA and lactoferrin cause significant release of LPS from all three strains. Further studies found that LPS release was blocked by iron saturation of lactoferrin, occurred between pH 6 and 7.5, was comparable for bacterial concentrations from 10(4) to 10(7) CFU/ml, and increased with increasing lactoferrin concentrations. Studies using Hanks balanced salt solution lacking calcium and magnesium showed that transferrin also could cause LPS release. Additionally, both lactoferrin and transferrin increased the antibacterial effect of a subinhibitory concentration of rifampin, a drug excluded by the bacterial outer membrane. This work demonstrates that these iron-binding proteins damage the gram-negative outer membrane and alter bacterial outer membrane permeability. |
1987 |
Carlsson, J Salivary peroxidase: an important part of our defense against oxygen toxicity. Journal Article J Oral Pathol, 16 (8), pp. 412-416, 1987. @article{Perraudinb_50, title = {Salivary peroxidase: an important part of our defense against oxygen toxicity.}, author = {J Carlsson}, year = {1987}, date = {1987-01-01}, journal = {J Oral Pathol}, volume = {16}, number = {8}, pages = {412-416}, abstract = {All living cells convert dioxygen (O2) into the toxic intermediates of oxygen reduction: superoxide radicals, hydrogen peroxide and hydroxyl radicals. The defense against these intermediates works on three levels: 1) the formation of the intermediates is prevented; 2) the intermediates are scavenged; 3) the damaged sites are repaired. Various parts of this defense are found intracellularly, in tissue fluid, in blood plasma and in the external secretions. In the mouth there is a special need for defense against hydrogen peroxide, because hydrogen peroxide is not only formed by bacteria colonizing the mucous membranes but also by the cells of the salivary glands. In saliva the most important part of this defense is salivary peroxidase, which detoxifies hydrogen peroxide in the presence of thiocyanate by converting it into hypothiocyanite, dioxygen and water. In addition, hypothiocyanite stops hydrogen peroxide production by the oral bacteria.}, keywords = {}, pubstate = {published}, tppubtype = {article} } All living cells convert dioxygen (O2) into the toxic intermediates of oxygen reduction: superoxide radicals, hydrogen peroxide and hydroxyl radicals. The defense against these intermediates works on three levels: 1) the formation of the intermediates is prevented; 2) the intermediates are scavenged; 3) the damaged sites are repaired. Various parts of this defense are found intracellularly, in tissue fluid, in blood plasma and in the external secretions. In the mouth there is a special need for defense against hydrogen peroxide, because hydrogen peroxide is not only formed by bacteria colonizing the mucous membranes but also by the cells of the salivary glands. In saliva the most important part of this defense is salivary peroxidase, which detoxifies hydrogen peroxide in the presence of thiocyanate by converting it into hypothiocyanite, dioxygen and water. In addition, hypothiocyanite stops hydrogen peroxide production by the oral bacteria. |
Bibliographydperraudin2018-11-16T05:34:46+00:00
2017 |
Oxidative Stress-Related Mechanisms and Antioxidant Therapy in Diabetic Retinopathy. Journal Article Oxidative Medicine and Cellular Longevity, 2017 , pp. 1-15, 2017. |
2016 |
The research and development on the antioxidants in prevention of diabetic complications Journal Article Asian Pacific Journal of Tropical Medicine, 9 (9), pp. 825-831, 2016. |
The Role of AGE/RAGE Signaling in Diabetes-Mediated Vascular Calcification. Journal Article Journal of Diabetes Reasearch, 2016 , pp. 1 - 8, 2016. |
2015 |
Biofilm in endodontics: A review. Journal Article J Int Soc Prev Community Dent, 5 (1), pp. 1 - 12, 2015. |
Bone Regeneration Is Promoted by Orally Administered Bovine Lactoferrin in a Rabbit Tibial Distraction Osteogenesis Model. Journal Article Clin Orthop Relat Res, 473 (7), pp. 2383 - 2393, 2015. |
Diabetes and periodontitis: A bidirectional relationship Journal Article Med Clin (Barc), 145 (1), pp. 31 - 35, 2015. |
Relationship between diabetes and periodontal infection. Journal Article World J Diabetes, 6 (7), pp. 927 - 935, 2015. |
Diabetes mellitus and oxidative stress-A concise review. Journal Article Saudi Pharmaceutical Journal, 24 , pp. 547-553, 2015. |
The role of antioxidants in the chemistry of oxidative stress: A review. Journal Article Eur J Med Chem, 95 , pp. 55-74, 2015. |
Are reactive oxygen species still the basis for diabetic complications? Journal Article Clin Sci (Lond)., 129 (2), pp. 199-216, 2015. |
Candida Carriage Rate and Growth Characteristics of Saliva in Diabetes Mellitus Patients: A Case-Control Study. Journal Article Journal of Dental Research, Dental Clinics, Dental Prospects, 9 (4), pp. 274–279, 2015. |
2014 |
Oxidative Stress: Implications for the Development of Diabetic Retinopathy and Antioxidant Therapeutic Perspectives Journal Article Oxidative Medicine and Cellular Longevity, 2014 , pp. 1 - 12, 2014. |
Lactoferrin inhibits infection-related osteoclastogenesis without interrupting compressive force-related osteoclastogenesis. Journal Article Arch Oral Biol., 59 (2), pp. 226 - 232, 2014. |
Lactoferrin inhibits apoptosis through insulin-like growth factor I in primary rat osteoblasts. Journal Article Acta Pharmacol Sin, 35 (4), pp. 523 - 530, 2014. |
The importance of lactoferrin in bone regeneration] Journal Article Pol Merkur Lekarski, 37 (217), pp. 65-67, 2014. |
Antioxidants and human diseases. Journal Article Clin Chim Acta, 436 , pp. 332-347, 2014. |
Oxidative stress: implications for the development of diabetic retinopathy and antioxidant therapeutic perspectives. Journal Article Oxidative Medicine and Cellular Longevity, 2014 , pp. 1 - 12, 2014. |
2013 |
A review of the evidence for pathogenic mechanisms that may link periodontitis and diabetes Journal Article J Periodontol, 84 (4), pp. 113-134, 2013. |
Diabetes, Oxidative Stress, and Antioxidants: A review Journal Article J Biochem Molecular Toxicologt, 17 (1), pp. 24-38, 2013. |
Butyric acid retention in gingival tissue induces oxidative stress in jugular blood mitochondria. Journal Article Cell Stress and Chaperones, 18 , pp. 661-665, 2013. |
2012 |
The role of hydrogen peroxide in environmental adaptation of oral microbial communities. Journal Article Oxidative Medicine and Cellular longevity, 2012 , pp. 1 - 10, 2012. |
Diabetes and Oral Health: A Case-control Study. Journal Article Int J Prev Med, 3 (11), pp. 806 - 809, 2012. |
Interrelationships of periodontitis and diabetes: A review of the current literature Journal Article Journal of Dental Sciences, 7 , pp. 272-282, 2012. |
Interrelationships of periodontitis and diabetes: A review of the current literature Journal Article Journal of Dental Sciences, 7 , pp. 272-282, 2012. |
Molecular mechanisms of the inhibitory effects of bovine lactoferrin on lipopolysaccharide-mediated osteoclastogenesis. Journal Article J Biol Chem, 287 (28), pp. 23527 - 23536, 2012. |
Periodontitis and diabetes: a two-way relationship Journal Article Diabetologia, 55 , pp. 21-31, 2012. |
2011 |
Oxidative stress, antioxidant status and lipid profile in the saliva of type 2 diabetics. Journal Article Diabetes & Vascular Disease Research, 8 (1), pp. 22-28, 2011. |
Molecular mechanisms involved in the mitogenic effect of lactoferrin in osteoblasts. Journal Article Bone, 49 (2), pp. 217 - 224, 2011. |
A qualitative examination of patient awareness and understanding of type 2 diabetes and oral health needs Journal Article Diabetes Research and Clinical Practice. Elesevier Ireland, 93 (2), pp. 159-165, 2011. |
2010 |
Lactoferrin as an effector molecule in the skeleton. Journal Article Biometals, 23 (3), pp. 425-430, 2010. |
2009 |
Oxidative stress and innate immunity in feline patients with diabetes mellitus: the role of nutrition. Journal Article J Feline Med Surg, 11 (4), pp. 271-276, 2009. |
Antimicrobial properties of lactoferrin Journal Article Biochimie, 91 (1), pp. 19-29, 2009. |
La lactoferrine : une protéine multifonctionnelle Lactoferrin: a multifunctional protein Journal Article Med Sci (Paris, 25 , pp. 361-369, 2009. |
2008 |
Denture contamination by yeasts in the elderly Journal Article Gerodontology, 25 (4), pp. 222-228, 2008. |
Periodontal diseases: association with diabetes, glycemic control and complications Journal Article Oral Diseases, 14 (3), pp. 191-203, 2008. |
2006 |
Lactoferrin and bone; structure-activity relationships. Journal Article Biochem Cell Biol, 84 (3), pp. 297 - 302, 2006. |
Diabetes Mellitus and Periodontal Diseases Journal Article Journal of Periodontology, 77 (8), pp. 1289-1303, 2006. |
2005 |
Oxidative stress and the use of antioxidants in diabetes: linking basic science to clinical practice. Journal Article Cardiovascular Diabetology, 1 , pp. 1 - 11, 2005. |
Lactoferrin - A Novel Bone Growth Factor Journal Article Clinical Medicine & Research, 3 (2), pp. 93-101, 2005. |
2004 |
The role of antioxidant micronutrients in the prevention of diabetic complications Journal Article Treat Endocrinology, 3 (1), pp. 41-52, 2004. |
Oxidative stress in the pathogenesis of diabetic neuropathy. Journal Article Endocrine Reviews, 25 (4), pp. 612-628, 2004. |
Lactoferrin is a potent regulator of bone cell activity and increases bone formation in vivo Journal Article bstractSend to Endocrinology, 145 (9), pp. 4366 - 4374, 2004. |
2003 |
Diabetes, oxidative stress, and antioxidants: a review Journal Article Journal Biochemistry Molecular Toxicology, 17 (1), 2003. |
RANK Ligand and the regulation of skeletal remodeling Journal Article Journal Clinical Investigation, 111 (8), pp. 1120 - 1122, 2003. |
2002 |
Nitric oxide and changes of iron metabolism in exercise. Journal Article Biol. Rev, 77 , pp. 529-536, 2002. |
Oral candidosis Journal Article Postgrad Med J, 78 (922), pp. 455-459, 2002. |
Lactoferrin reduces in vitro osteoclast differentiation and resorbing activity. Journal Article Biochem Biophys Res Commun, 296 (2), pp. 261 - 266, 2002. |
2000 |
Oxidative stress and glycemic regulation Journal Article Metabolism, 49 (2 Suppl 1), pp. 27-29, 2000. |
1999 |
Role of oxidative stress in diabetic complications: a new perspective on an old paradigm Journal Article Diabetes, 48 (1), pp. 1-9, 1999. |
Effects of an oral glucose challenge on free radicals/antioxidants balance in an older population with type II diabetes. Journal Article Journal of Gerontology, 54A (11), pp. M541 - M545, 1999. |
Meal-induced oxidative stress and low-density lipoprotein oxidation in diabetes: the possible role of hyperglycemia Journal Article Metabolism, 48 (12), pp. 1503-1508, 1999. |
Reactive oxygen species and antioxidants in inflammatory diseases Journal Article J Clin Periodontol, 24 (5), pp. 287-296, 1999. |
1998 |
Candida-associated denture stomatitis: aetiology and management: a review. Part 3. Treatment of oral candidosis Journal Article Australian Dental Journal, 43 (4), pp. 244-249, 1998. |
1995 |
Reactive oxygen species and iron--a dangerous partnership in inflammation. Journal Article Int. J. Biochem. Cell. Biol, 27 (2), pp. 109-122, 1995. |
Iron: mammalian defense systems, mechanisms of disease, and chelation therapy approaches. Journal Article Blod Rev, 9 (1), pp. 33-45, 1995, ISBN: 7795423. |
1991 |
Factors in virulence expression and their role in periodontal disease pathogenesis Journal Article Criricak Reviews in Oral Biology and medecine, 2 (2), pp. 177-281, 1991, ISBN: 1912148. |
Periodontal disease in non-insulin-dependant diabetes mellitus Journal Article Journal Periodontology, 62 (2), pp. 123-131, 1991. |
1988 |
Damage of the outer membrane of enteric gram-negative bacteria by lactoferrin and transferrin Journal Article Infect Immunology, 56 (11), pp. 2774 - 2781, 1988. |
1987 |
Salivary peroxidase: an important part of our defense against oxygen toxicity. Journal Article J Oral Pathol, 16 (8), pp. 412-416, 1987. |