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Vine J, Lee JH, Balaji L, Grossestreuer AV, Morton A, Peradze N, Antony N, Berlin N, Kravitz MS, Leland SB, Berg K, Moskowitz A, Donnino MW, Liu X. Cellular oxygen consumption in patients with diabetic ketoacidosis. Intensive Care Med Exp 2024; 12:97. [PMID: 39497011 PMCID: PMC11535118 DOI: 10.1186/s40635-024-00673-0] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/04/2024] [Accepted: 09/11/2024] [Indexed: 11/06/2024] Open
Abstract
BACKGROUND Diabetic ketoacidosis (DKA) is a potentially life-threatening disorder associated with severe alterations in metabolism and acid-base status. Mitochondrial dysfunction is associated with diabetes and its complications. Thiamine and coenzyme Q10 (CoQ10) are important factors in aerobic metabolism. In this study, we measured cellular oxygen consumption rates (OCRs) and the effects of in vitro administration of thiamine and CoQ10 on OCRs in patients with DKA versus healthy controls. METHODS Blood samples were collected from a prospective cohort of patients with DKA and from controls. Cellular OCRs were measured in peripheral blood mononuclear cells (PBMC) without treatment and after treatment with thiamine, CoQ10, or both. The mitochondrial profile was measured using an XFe96 Extracellular Flux Analyzer and XF Cell Mito Stress Test Kit (Seahorse Bioscience). A linear quantile mixed model was used to compare OCRs and estimate treatment effects. RESULTS A total of 62 patients with DKA and 48 controls were included in the study. The median basal and maximal OCRs were lower in the DKA group than in the control group (basal: 4.7 [IQR: 3.3, 7.9] vs. 7.9 [5.0, 9.5], p = 0.036; maximal: 16.4 [9.5, 28.1] vs. 31.5 [20.6, 46.0] pmol/min/µg protein, p < 0.001). In DKA samples, basal and maximal OCRs were significantly increased when treated with thiamine, CoQ10, or both. In controls, basal and maximal OCR were significantly increased only with thiamine treatment. CONCLUSION Mitochondrial metabolic profiles of patients with DKA demonstrated lower cellular oxygen consumption when compared to healthy controls. Oxygen consumption increased significantly in cells of patients with DKA treated with thiamine or CoQ10. These results suggest that thiamine and CoQ10 could potentially have therapeutic benefits in DKA via their metabolic effects on mitochondrial cellular respiration.
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Affiliation(s)
- Jacob Vine
- Center for Resuscitation Science, Beth Israel Deaconess Medical Center, 330 Brookline Ave, Boston, MA, 02215, USA
| | - John H Lee
- Center for Resuscitation Science, Beth Israel Deaconess Medical Center, 330 Brookline Ave, Boston, MA, 02215, USA
- Department of Emergency Medicine, Beth Israel Deaconess Medical Center, 330 Brookline Ave, Boston, MA, 02215, USA
| | - Lakshman Balaji
- Center for Resuscitation Science, Beth Israel Deaconess Medical Center, 330 Brookline Ave, Boston, MA, 02215, USA
- Department of Emergency Medicine, Beth Israel Deaconess Medical Center, 330 Brookline Ave, Boston, MA, 02215, USA
| | - Anne V Grossestreuer
- Center for Resuscitation Science, Beth Israel Deaconess Medical Center, 330 Brookline Ave, Boston, MA, 02215, USA
- Department of Emergency Medicine, Beth Israel Deaconess Medical Center, 330 Brookline Ave, Boston, MA, 02215, USA
| | - Andrea Morton
- Center for Resuscitation Science, Beth Israel Deaconess Medical Center, 330 Brookline Ave, Boston, MA, 02215, USA
- Department of Microbiology and Pathology at Brigham Women's Hospital, Boston, MA, USA
| | - Natia Peradze
- Center for Resuscitation Science, Beth Israel Deaconess Medical Center, 330 Brookline Ave, Boston, MA, 02215, USA
- Invicro, Needham, MA, USA
| | - Nivedha Antony
- Center for Resuscitation Science, Beth Israel Deaconess Medical Center, 330 Brookline Ave, Boston, MA, 02215, USA
- Department of Emergency Medicine, Beth Israel Deaconess Medical Center, 330 Brookline Ave, Boston, MA, 02215, USA
| | - Noa Berlin
- Center for Resuscitation Science, Beth Israel Deaconess Medical Center, 330 Brookline Ave, Boston, MA, 02215, USA
- Department of Clinical Sciences, Cummings School of Veterinary Medicine at Tufts University, North Grafton, MA, USA
| | - Max S Kravitz
- Center for Resuscitation Science, Beth Israel Deaconess Medical Center, 330 Brookline Ave, Boston, MA, 02215, USA
- Department of Emergency Medicine, Beth Israel Deaconess Medical Center, 330 Brookline Ave, Boston, MA, 02215, USA
| | - Shannon B Leland
- Center for Resuscitation Science, Beth Israel Deaconess Medical Center, 330 Brookline Ave, Boston, MA, 02215, USA
- Department of Anesthesiology, Critical Care and Pain Medicine, Boston Children's Hospital, Boston, MA, USA
| | - Katherine Berg
- Center for Resuscitation Science, Beth Israel Deaconess Medical Center, 330 Brookline Ave, Boston, MA, 02215, USA
- Division of Pulmonary, Critical Care, and Sleep Medicine, Beth Israel Deaconess Medical Center, 330 Brookline Ave, Boston, MA, 02215, USA
| | - Ari Moskowitz
- Center for Resuscitation Science, Beth Israel Deaconess Medical Center, 330 Brookline Ave, Boston, MA, 02215, USA
- Division of Critical Care Medicine, Montefiore Medical Center, The Bronx, NY, USA
- Bronx Center for Critical Care Outcomes and Resuscitation Research, The Bronx, NY, USA
| | - Michael W Donnino
- Center for Resuscitation Science, Beth Israel Deaconess Medical Center, 330 Brookline Ave, Boston, MA, 02215, USA
- Department of Emergency Medicine, Beth Israel Deaconess Medical Center, 330 Brookline Ave, Boston, MA, 02215, USA
- Division of Pulmonary, Critical Care, and Sleep Medicine, Beth Israel Deaconess Medical Center, 330 Brookline Ave, Boston, MA, 02215, USA
| | - Xiaowen Liu
- Center for Resuscitation Science, Beth Israel Deaconess Medical Center, 330 Brookline Ave, Boston, MA, 02215, USA.
- Department of Emergency Medicine, Beth Israel Deaconess Medical Center, 330 Brookline Ave, Boston, MA, 02215, USA.
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Abdelmonem M, Ali SO, Al-Mokaddem AK, Ghaiad HR. Ameliorating diabetes-induced testicular dysfunction by modulating PKC/Nrf2/Bcl-2 signaling: Protective role of sulbutiamine. Biofactors 2024; 50:845-862. [PMID: 38344831 DOI: 10.1002/biof.2046] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/25/2023] [Accepted: 01/23/2024] [Indexed: 08/09/2024]
Abstract
The prevalence of testicular dysfunction is increasing as it is a common diabetes mellites (DM) complication. The objective of this study is to explore the potential protective effect of sulbutiamine against testicular hypofunction associated with streptozotocin (STZ)-induced DM in rats. Sulbutiamine was administered orally (60 mg/kg) to male Wistar rats for 8 weeks starting 72 h after a single injection of STZ (45 mg/kg, i.p.). Blood glucose level (BGL), serum testosterone level, sperm number, and motility were determined. Testicular tissue was examined histopathologically, and the Johnson score was evaluated. Levels of malondialdehyde (MDA), protein kinase C (PKC), nuclear factor erythroid-derived 2-like 2 (Nrf2), and proliferating cell nuclear antigen (PCNA) were measured. Apoptosis was evaluated by immunohistochemical determination of B-cell lymphoma protein 2 (Bcl-2), Bcl-2 associated X-protein (Bax), and caspase-3. Sulbutiamine administration managed to reduce BGL and boost testicular function as manifested by increased testicular weight, testosterone level, sperm number, and motility compared to the STZ group. Additionally, histopathological examination revealed an improved histological picture and Johnson score of testicular tissue after sulbutiamine treatment. Sulbutiamine administration reduced testicular PKC, MDA, and PCNA levels and increased Nrf2 compared to the untreated group. Moreover, sulbutiamine treatment suppressed apoptosis triggered by STZ as evidenced by elevated Bcl-2, decreased Bax and reduced caspase-3. The present work revealed for the first time a promising protective role of sulbutiamine against STZ-induced testicular dysfunction which may add to the clinical utility of sulbutiamine. The underlying mechanisms involve reducing BGL and PKC, activating Nrf2 and inhibiting apoptosis.
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Affiliation(s)
- Maha Abdelmonem
- Biochemistry Department, Faculty of Pharmacy, Cairo University, Cairo, Egypt
| | - Shimaa O Ali
- Biochemistry Department, Faculty of Pharmacy, Cairo University, Cairo, Egypt
| | - Asmaa K Al-Mokaddem
- Pathology Department, Faculty of Veterinary Medicine, Cairo University, Cairo, Egypt
| | - Heba R Ghaiad
- Biochemistry Department, Faculty of Pharmacy, Cairo University, Cairo, Egypt
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Cheng Y, Chen Y, Li K, Liu S, Pang C, Gao L, Xie J, Wenjing LV, Yu H, Deng B. How inflammation dictates diabetic peripheral neuropathy: An enlightening review. CNS Neurosci Ther 2024; 30:e14477. [PMID: 37795833 PMCID: PMC11017439 DOI: 10.1111/cns.14477] [Citation(s) in RCA: 27] [Impact Index Per Article: 27.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/17/2023] [Revised: 08/28/2023] [Accepted: 09/08/2023] [Indexed: 10/06/2023] Open
Abstract
BACKGROUND Diabetic peripheral neuropathy (DPN) constitutes a debilitating complication associated with diabetes. Although, the past decade has seen rapid developments in understanding the complex etiology of DPN, there are no approved therapies that can halt the development of DPN, or target the damaged nerve. Therefore, clarifying the pathogenesis of DPN and finding effective treatment are the crucial issues for the clinical management of DPN. AIMS This review is aiming to summary the current knowledge on the pathogenesis of DPN, especially the mechanism and application of inflammatory response. METHODS We systematically summarized the latest studies on the pathogenesis and therapeutic strategies of diabetic neuropathy in PubMed. RESULTS In this seminal review, the underappreciated role of immune activation in the progression of DPN is scrutinized. Novel insights into the inflammatory regulatory mechanisms of DPN have been unearthed, illuminating potential therapeutic strategies of notable clinical significance. Additionally, a nuanced examination of DPN's complex etiology, including aberrations in glycemic control and insulin signaling pathways, is presented. Crucially, an emphasis has been placed on translating these novel understandings into tangible clinical interventions to ameliorate patient outcomes. CONCLUSIONS This review is distinguished by synthesizing cutting-edge mechanisms linking inflammation to DPN and identifying innovative, inflammation-targeted therapeutic approaches.
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Affiliation(s)
- Yifan Cheng
- Center for Rehabilitation Medicine, Department of Neurology, Zhejiang Provincial People's HospitalAffiliated People's Hospital, Hangzhou Medical CollegeHangzhouChina
| | - Yinuo Chen
- Department of NeurologyFirst Affiliated Hospital of Wenzhou Medical UniversityWenzhouZhejiang ProvinceChina
- First School of Clinical MedicineWenzhou Medical UniversityWenzhouZhejiang ProvinceChina
| | - Kezheng Li
- Department of NeurologyFirst Affiliated Hospital of Wenzhou Medical UniversityWenzhouZhejiang ProvinceChina
- First School of Clinical MedicineWenzhou Medical UniversityWenzhouZhejiang ProvinceChina
| | - Shuwei Liu
- First School of Clinical MedicineWenzhou Medical UniversityWenzhouZhejiang ProvinceChina
| | - Chunyang Pang
- Department of NeurologyFirst Affiliated Hospital of Wenzhou Medical UniversityWenzhouZhejiang ProvinceChina
| | - Lingfei Gao
- Department of NeurologyFirst Affiliated Hospital of Wenzhou Medical UniversityWenzhouZhejiang ProvinceChina
| | - Jiali Xie
- Department of Neurology, Shanghai East HospitalTongji UniversityShanghaiP.R. China
| | - L. V. Wenjing
- Department of GeriatricsThe Affiliated Hospital of Qingdao UniversityQingdaoShandong ProvinceChina
| | - Huan Yu
- Department of PediatricsSecond Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical UniversityWenzhouChina
| | - Binbin Deng
- Department of NeurologyFirst Affiliated Hospital of Wenzhou Medical UniversityWenzhouZhejiang ProvinceChina
- First School of Clinical MedicineWenzhou Medical UniversityWenzhouZhejiang ProvinceChina
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Zhu J, Hu Z, Luo Y, Liu Y, Luo W, Du X, Luo Z, Hu J, Peng S. Diabetic peripheral neuropathy: pathogenetic mechanisms and treatment. Front Endocrinol (Lausanne) 2024; 14:1265372. [PMID: 38264279 PMCID: PMC10803883 DOI: 10.3389/fendo.2023.1265372] [Citation(s) in RCA: 52] [Impact Index Per Article: 52.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/22/2023] [Accepted: 12/14/2023] [Indexed: 01/25/2024] Open
Abstract
Diabetic peripheral neuropathy (DPN) refers to the development of peripheral nerve dysfunction in patients with diabetes when other causes are excluded. Diabetic distal symmetric polyneuropathy (DSPN) is the most representative form of DPN. As one of the most common complications of diabetes, its prevalence increases with the duration of diabetes. 10-15% of newly diagnosed T2DM patients have DSPN, and the prevalence can exceed 50% in patients with diabetes for more than 10 years. Bilateral limb pain, numbness, and paresthesia are the most common clinical manifestations in patients with DPN, and in severe cases, foot ulcers can occur, even leading to amputation. The etiology and pathogenesis of diabetic neuropathy are not yet completely clarified, but hyperglycemia, disorders of lipid metabolism, and abnormalities in insulin signaling pathways are currently considered to be the initiating factors for a range of pathophysiological changes in DPN. In the presence of abnormal metabolic factors, the normal structure and function of the entire peripheral nervous system are disrupted, including myelinated and unmyelinated nerve axons, perikaryon, neurovascular, and glial cells. In addition, abnormalities in the insulin signaling pathway will inhibit neural axon repair and promote apoptosis of damaged cells. Here, we will discuss recent advances in the study of DPN mechanisms, including oxidative stress pathways, mechanisms of microvascular damage, mechanisms of damage to insulin receptor signaling pathways, and other potential mechanisms associated with neuroinflammation, mitochondrial dysfunction, and cellular oxidative damage. Identifying the contributions from each pathway to neuropathy and the associations between them may help us to further explore more targeted screening and treatment interventions.
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Affiliation(s)
- Jinxi Zhu
- Department of Anesthesiology, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China
- The Second Clinical Medical College of Nanchang University, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China
| | - Ziyan Hu
- Department of Anesthesiology, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China
- The Second Clinical Medical College of Nanchang University, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China
| | - Yifan Luo
- Department of Anesthesiology, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China
| | - Yinuo Liu
- Department of Anesthesiology, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China
| | - Wei Luo
- Department of Sports Medicine, Huashan Hospital, Fudan University, Shanghai, China
| | - Xiaohong Du
- Department of Anesthesiology, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China
| | - Zhenzhong Luo
- Department of Anesthesiology, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China
| | - Jialing Hu
- Department of Emergency Medicine, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China
| | - Shengliang Peng
- Department of Anesthesiology, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, China
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Zakarneh S, Khial Y, Tayyem R. Dietary Factors Associated with Glycemic Control in Children and Adolescents with Type 1 Diabetes. Curr Pediatr Rev 2024; 21:29-39. [PMID: 37608667 DOI: 10.2174/1573396320666230822095948] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/01/2023] [Revised: 05/26/2023] [Accepted: 06/21/2023] [Indexed: 08/24/2023]
Abstract
Type 1 diabetes mellitus (T1DM) is a chronic metabolic disease that results from the autoimmune destruction of pancreatic β-cells, leading to insulin deficiency and hyperglycemia. It is a common chronic disease in childhood, with a prevalence of 1 in 300 children in the United States and an increasing incidence of 2-5% annually, worldwide. Managing T1DM requires regular insulin administration, adjustment of food intake and exercise, and a comprehensive understanding of nutrition. This review aims to explore the relationship between dietary factors, physical activity, obesity, genetics, and glycemic control in children and adolescents with T1DM. To conduct this review, we conducted a thorough search of publications from December 2004 through April 2022 using PubMed, ScienceDirect, and Embase databases. Key topics included obesity, children, adolescents, nutrients, carbohydrates, proteins, fat, water-soluble vitamins, fat-soluble vitamins, dietary patterns, fruits and vegetables, physical activity, genetics, food habits, carbohydrate count and environmental factors.
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Affiliation(s)
- Sara Zakarneh
- Department of Nutrition & Food Technology, Faculty of Agriculture, The University of Jordan, Amman, 11942, Jordan
| | - Yasmin Khial
- Department of Human Nutrition, College of Health Science, Qatar University, Doha, Qatar
| | - Reema Tayyem
- Department of Human Nutrition, College of Health Science, Qatar University, Doha, Qatar
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Biswas A, Choudhury AD, Agrawal S, Bisen AC, Sanap SN, Verma SK, Kumar M, Mishra A, Kumar S, Chauhan M, Bhatta RS. Recent Insights into the Etiopathogenesis of Diabetic Retinopathy and Its Management. J Ocul Pharmacol Ther 2024; 40:13-33. [PMID: 37733327 DOI: 10.1089/jop.2023.0068] [Citation(s) in RCA: 15] [Impact Index Per Article: 15.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 09/22/2023] Open
Abstract
Purpose: Diabetic retinopathy (DR) is a microvascular retinal disease associated with chronic diabetes mellitus, characterized by the damage of blood vessels in the eye. It is projected to become the leading cause of blindness, given the increasing burden of the diabetic population worldwide. The diagnosis and management of DR pose significant challenges for physicians because of the involvement of multiple biochemical pathways and the complexity of ocular tissues. This review aims to provide a comprehensive understanding of the molecular pathways implicated in the pathogenesis of DR, including the polyo pathway, hexosamine pathway, protein kinase C (PKC), JAK/STAT signaling pathways, and the renin-angiotensin system (RAS). Methods: Academic databases such as PubMed, Scopus, Google Scholar and Web of Science was systematically searched using a carefully constructed search strategy incorporating keywords like "Diabetic Retinopathy," "Molecular Pathways," "Pharmacological Treatments," and "Clinical Trials" to identify relevant literature for the comprehensive review. Results: In addition to activating other inflammatory cascades, these pathways contribute to the generation of oxidative stress within the retina. Furthermore, it aims to explore the existing pharmacotherapy options available for the treatment of DR. In addition to conventional pharmacological therapies such as corticosteroids, antivascular endothelial growth factors, and nonsteroidal anti-inflammatory drugs (NSAIDs), this review highlights the potential of repurposed drugs, phyto-pharmaceuticals, and novel pipeline drugs currently undergoing various stages of clinical trials. Conclusion: Overall, this review serves as a technical exploration of the complex nature of DR, highlighting both established and emerging molecular pathways implicated in its pathogenesis. Furthermore, it delves into the available pharmacological treatments, as well as the promising repurposed drugs, phyto-pharmaceuticals, and novel drugs currently being evaluated in clinical trials, with a focus on their specific mechanisms of action.
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Affiliation(s)
- Arpon Biswas
- Pharmaceutics and Pharmacokinetic Division, CSIR-Central Drug Research Institute, Lucknow, India
- Jawaharlal Nehru University, New Delhi, India
| | - Abhijit Deb Choudhury
- Pharmaceutics and Pharmacokinetic Division, CSIR-Central Drug Research Institute, Lucknow, India
- Jawaharlal Nehru University, New Delhi, India
| | - Sristi Agrawal
- Pharmaceutics and Pharmacokinetic Division, CSIR-Central Drug Research Institute, Lucknow, India
- Academy of Scientific and Innovative Research, New Delhi, India
| | - Amol Chhatrapati Bisen
- Pharmaceutics and Pharmacokinetic Division, CSIR-Central Drug Research Institute, Lucknow, India
- Academy of Scientific and Innovative Research, New Delhi, India
| | - Sachin Nashik Sanap
- Pharmaceutics and Pharmacokinetic Division, CSIR-Central Drug Research Institute, Lucknow, India
- Academy of Scientific and Innovative Research, New Delhi, India
| | - Sarvesh Kumar Verma
- Pharmaceutics and Pharmacokinetic Division, CSIR-Central Drug Research Institute, Lucknow, India
- Jawaharlal Nehru University, New Delhi, India
| | - Mukesh Kumar
- Pharmaceutics and Pharmacokinetic Division, CSIR-Central Drug Research Institute, Lucknow, India
- Jawaharlal Nehru University, New Delhi, India
| | - Anjali Mishra
- Pharmaceutics and Pharmacokinetic Division, CSIR-Central Drug Research Institute, Lucknow, India
- Academy of Scientific and Innovative Research, New Delhi, India
| | - Shivansh Kumar
- Pharmaceutics and Pharmacokinetic Division, CSIR-Central Drug Research Institute, Lucknow, India
| | - Mridula Chauhan
- Pharmaceutics and Pharmacokinetic Division, CSIR-Central Drug Research Institute, Lucknow, India
| | - Rabi Sankar Bhatta
- Pharmaceutics and Pharmacokinetic Division, CSIR-Central Drug Research Institute, Lucknow, India
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Li K, Chen Y, Xie J, Cai W, Pang C, Cui C, Huan Y, Deng B. How vitamins act as novel agents for ameliorating diabetic peripheral neuropathy: A comprehensive overview. Ageing Res Rev 2023; 91:102064. [PMID: 37689144 DOI: 10.1016/j.arr.2023.102064] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/19/2023] [Revised: 08/10/2023] [Accepted: 09/01/2023] [Indexed: 09/11/2023]
Abstract
Diabetic peripheral neuropathy (DPN) is a pervasive and incapacitating sequela of diabetes, affecting a significant proportion of those diagnosed with the disease, yet an effective treatment remains elusive. Vitamins have been extensively studied, emerging as a promising target for diagnosing and treating various systemic diseases, but their role in DPN is not known. This review collates and synthesizes knowledge regarding the interplay between vitamins and DPN, drawing on bibliographies from prior studies and relevant articles, and stratifying the therapeutic strategies from prophylactic to interventional. In addition, the clinical evidence supporting the use of vitamins to ameliorate DPN is also evaluated, underscoring the potential of vitamins as putative therapeutic agents. We anticipate that this review will offer novel insights for developing and applying vitamin-based therapies for DPN.
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Affiliation(s)
- Kezheng Li
- Department of Neurology, First Affiliated Hospital of Wenzhou Medical University, Wenzhou, PR China; First School of Clinical Medicine, Wenzhou Medical University, Wenzhou, PR China
| | - Yinuo Chen
- Department of Neurology, First Affiliated Hospital of Wenzhou Medical University, Wenzhou, PR China; First School of Clinical Medicine, Wenzhou Medical University, Wenzhou, PR China
| | - Jiali Xie
- Department of Neurology, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, PR China
| | - Weiwei Cai
- Department of Rheumatology and Immunology, Beijing Hospital, Beijing, PR China
| | - Chunyang Pang
- Department of Neurology, First Affiliated Hospital of Wenzhou Medical University, Wenzhou, PR China
| | - Can Cui
- Department of Clinical Sciences Malmö, Lund University, Skåne, Sweden
| | - Yu Huan
- Department of Pediatrics, Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, PR China
| | - Binbin Deng
- Department of Neurology, First Affiliated Hospital of Wenzhou Medical University, Wenzhou, PR China; First School of Clinical Medicine, Wenzhou Medical University, Wenzhou, PR China.
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Fang F, Xia J, Quan S, Chen S, Deng GJ. Metal- and Solvent-Free Synthesis of Substituted Pyrimidines via an NH 4I-Promoted Three-Component Tandem Reaction. J Org Chem 2023; 88:14697-14707. [PMID: 37773063 DOI: 10.1021/acs.joc.3c01700] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 09/30/2023]
Abstract
A facile and practical approach for the preparation of substituted pyrimidines from ketones, NH4OAc, and N,N-dimethylformamide dimethyl acetal has been described. This NH4I-promoted three-component tandem reaction affords a broad range of substituted pyrimidines in acceptable yields under metal- and solvent-free conditions. The present methodology features the advantages of simple and easily available starting materials, metal- and solvent-free conditions, a broad substrate scope with good functional group tolerance, and gram-scale synthesis.
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Affiliation(s)
- Fang Fang
- Key Laboratory of Environmentally Friendly Chemistry and Application of Ministry of Education Hunan Province, Key Laboratory of Green Organic Synthesis and Application, College of Chemistry, Xiangtan University, Xiangtan 411105, P. R. China
- College of Materials and Chemical Engineering, Hunan City University, Yiyang 413000, P. R. China
| | - Jie Xia
- Key Laboratory of Environmentally Friendly Chemistry and Application of Ministry of Education Hunan Province, Key Laboratory of Green Organic Synthesis and Application, College of Chemistry, Xiangtan University, Xiangtan 411105, P. R. China
| | - Siying Quan
- Key Laboratory of Environmentally Friendly Chemistry and Application of Ministry of Education Hunan Province, Key Laboratory of Green Organic Synthesis and Application, College of Chemistry, Xiangtan University, Xiangtan 411105, P. R. China
| | - Shanping Chen
- Key Laboratory of Environmentally Friendly Chemistry and Application of Ministry of Education Hunan Province, Key Laboratory of Green Organic Synthesis and Application, College of Chemistry, Xiangtan University, Xiangtan 411105, P. R. China
| | - Guo-Jun Deng
- Key Laboratory of Environmentally Friendly Chemistry and Application of Ministry of Education Hunan Province, Key Laboratory of Green Organic Synthesis and Application, College of Chemistry, Xiangtan University, Xiangtan 411105, P. R. China
- School of Chemistry and Chemical Engineering, Henan Normal University, Xinxiang 453007, P. R. China
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Ziad E, Sadat S, Farzadfar F, Malekpour MR. Prescription pattern analysis of Type 2 Diabetes Mellitus: a cross-sectional study in Isfahan, Iran. BioData Min 2023; 16:29. [PMID: 37864248 PMCID: PMC10588025 DOI: 10.1186/s13040-023-00344-y] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/27/2023] [Accepted: 09/20/2023] [Indexed: 10/22/2023] Open
Abstract
BACKGROUND Patients with Type 2 Diabetes Mellitus (T2DM) are at a higher risk of polypharmacy and more susceptible to irrational prescriptions; therefore, pharmacological therapy patterns are important to be monitored. The primary objective of this study was to highlight current prescription patterns in T2DM patients and compare them with existing Standards of Medical Care in Diabetes. The second objective was to analyze whether age and gender affect prescription patterns. METHOD This cross-sectional study was conducted using the Iran Health Insurance Organization (IHIO) prescription database. It was mined by an Association Rule Mining (ARM) technique, FP-Growth, in order to find co-prescribed drugs with anti-diabetic medications. The algorithm was implemented at different levels of the Anatomical Therapeutic Chemical (ATC) classification system, which assigns different codes to drugs based on their anatomy, pharmacological, therapeutic, and chemical properties to provide an in-depth analysis of co-prescription patterns. RESULTS Altogether, the prescriptions of 914,652 patients were analyzed, of whom 91,505 were found to have diabetes. According to our results, prescribing Lipid Modifying Agents (C10) (56.3%), Agents Acting on The Renin-Angiotensin System (C09) (48.9%), Antithrombotic Agents (B01) (35.7%), and Beta Blocking Agents (C07) (30.1%) were meaningfully associated with the prescription of Drugs Used in Diabetes. Our study also revealed that female diabetic patients have a higher lift for taking Thyroid Preparations, and the older the patients were, the more they were prone to take neuropathy-related medications. Additionally, the results suggest that there are gender differences in the association between aspirin and diabetes drugs, with the differences becoming less pronounced in old age. CONCLUSIONS Almost all of the association rules found in this research were clinically meaningful, proving the potential of ARM for co-prescription pattern discovery. Moreover, implementing level-based ARM was effective in detecting difficult-to-spot rules. Additionally, the majority of drugs prescribed by physicians were consistent with the Standards of Medical Care in Diabetes.
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Affiliation(s)
- Elnaz Ziad
- School of Industrial and Systems Engineering, Tarbiat Modares University, Tehran, Islamic Republic of Iran
| | - Somayeh Sadat
- Centre for Analytics and Artificial Intelligence Engineering, University of Toronto, Toronto, Canada.
| | - Farshad Farzadfar
- Non-Communicable Diseases Research Center, Endocrinology and Metabolism Population Sciences Institute, Tehran University of Medical Sciences, Tehran, Islamic Republic of Iran
| | - Mohammad-Reza Malekpour
- Non-Communicable Diseases Research Center, Endocrinology and Metabolism Population Sciences Institute, Tehran University of Medical Sciences, Tehran, Islamic Republic of Iran
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Bansal S, Burman A, Tripathi AK. Advanced glycation end products: Key mediator and therapeutic target of cardiovascular complications in diabetes. World J Diabetes 2023; 14:1146-1162. [PMID: 37664478 PMCID: PMC10473940 DOI: 10.4239/wjd.v14.i8.1146] [Citation(s) in RCA: 17] [Impact Index Per Article: 8.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/29/2023] [Revised: 03/21/2023] [Accepted: 05/22/2023] [Indexed: 08/11/2023] Open
Abstract
The incidence of type 2 diabetes mellitus is growing in epidemic proportions and has become one of the most critical public health concerns. Cardiovascular complications associated with diabetes are the leading cause of morbidity and mortality. The cardiovascular diseases that accompany diabetes include angina, myocardial infarction, stroke, peripheral artery disease, and congestive heart failure. Among the various risk factors generated secondary to hyperglycemic situations, advanced glycation end products (AGEs) are one of the important targets for future diagnosis and prevention of diabetes. In the last decade, AGEs have drawn a lot of attention due to their involvement in diabetic patho-physiology. AGEs can be derived exogenously and endogenously through various pathways. These are a non-homogeneous, chemically diverse group of compounds formed non-enzymatically by condensation between carbonyl groups of reducing sugars and free amino groups of protein, lipids, and nucleic acid. AGEs mediate their pathological effects at the cellular and extracellular levels by multiple pathways. At the cellular level, they activate signaling cascades via the receptor for AGEs and initiate a complex series of intracellular signaling resulting in reactive oxygen species generation, inflammation, cellular proliferation, and fibrosis that may possibly exacerbate the damaging effects on cardiac functions in diabetics. AGEs also cause covalent modifications and cross-linking of serum and extracellular matrix proteins; altering their structure, stability, and functions. Early diagnosis of diabetes may prevent its progression to complications and decrease its associated comorbidities. In the present review, we recapitulate the role of AGEs as a crucial mediator of hyperglycemia-mediated detrimental effects in diabetes-associated complications. Furthermore, this review presents an overview of future perspectives for new therapeutic interventions to ameliorate cardiovascular complications in diabetes.
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Affiliation(s)
- Savita Bansal
- Department of Biochemistry, Institute of Home Sciences, University of Delhi, New Delhi 110016, India
| | - Archana Burman
- Department of Biochemistry, Institute of Home Economics, University of Delhi, New Delhi 110016, India
| | - Asok Kumar Tripathi
- Department of Biochemistry, University College of Medical Sciences, University of Delhi, New Delhi 110095, India
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11
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Li X, Wang Z, Wang J, Lu J, Mao J, Han D, Li K. Measurement and Correlation of Solubility of Thiamine Nitrate in Three Binary Solvents and Thermodynamic Properties for the Solutions in Different Binary Mixtures at (278.15-313.15) K. Molecules 2023; 28:5012. [PMID: 37446674 DOI: 10.3390/molecules28135012] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/29/2023] [Revised: 06/14/2023] [Accepted: 06/20/2023] [Indexed: 07/15/2023] Open
Abstract
The solubility of thiamine nitrate in {(methanol, acetone, isopropanol) + water} solvents will provide essential support for crystallization design and further theoretical studies. In this study, the solubility was experimentally measured over temperatures ranging from 278.15 to 313.15 K under atmospheric pressure using a dynamic method. The solubility increased with increasing temperature at a constant solvent composition. The dissolving capacity of thiamine nitrate in the three binary solvent mixtures at constant temperature in the low ratio of water ranked as water + methanol > water + acetone > water + isopropanol generally. Interestingly, in the high ratio of water systems, especially when the molar concentration of water was greater than 0.6, the dissolving capacity ranked as water + acetone > water + methanol > water + isopropanol. Additionally, the modified Apelblat equation, λh equation, van't Hoff equation and NRTL model were used to correlate the solubility data in binary mixtures. It turned out that all the selected thermodynamic models could give satisfactory results. Furthermore, the thermodynamic properties of the dissolution process of thiamine nitrate were also calculated based on the modified van't Hoff equation. The results indicate that the dissolution process of the thiamine nitrate in the selected solvents is all endothermic.
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Affiliation(s)
- Xinda Li
- State Key Laboratory of Chemical Engineering, School of Chemical Engineering and Technology, Tianjin University, Tianjin 300072, China
| | - Zhengjiang Wang
- Xi'an TPRI Water-Management & Environmental Protection Co., Ltd., Xi'an 710054, China
| | - Jing Wang
- Xi'an TPRI Water-Management & Environmental Protection Co., Ltd., Xi'an 710054, China
| | - Jiaqi Lu
- Xi'an TPRI Water-Management & Environmental Protection Co., Ltd., Xi'an 710054, China
| | - Jin Mao
- Xi'an TPRI Water-Management & Environmental Protection Co., Ltd., Xi'an 710054, China
| | - Dandan Han
- State Key Laboratory of Chemical Engineering, School of Chemical Engineering and Technology, Tianjin University, Tianjin 300072, China
| | - Kangli Li
- Institute of Shaoxing, Tianjin University, Shaoxing 312300, China
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12
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Mann RH. Impaired Thiamine Metabolism in Amyotrophic Lateral Sclerosis and Its Potential Treatment With Benfotiamine: A Case Report and a Review of the Literature. Cureus 2023; 15:e40511. [PMID: 37333039 PMCID: PMC10274516 DOI: 10.7759/cureus.40511] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 06/15/2023] [Indexed: 06/20/2023] Open
Abstract
Homogenates of brain tissue from the frontal cortex at autopsy in patients with amyotrophic lateral sclerosis (ALS) showed dramatically reduced levels of the enzyme thiamine pyrophosphatase (TPPase), the enzyme responsible for the conversion of thiamine pyrophosphate (TPP) to thiamine monophosphate (TMP). Additionally, free thiamine (vitamin B1) and TMP levels have been shown to be significantly reduced in the plasma and cerebral spinal fluid (CSF) of patients with ALS. These findings suggest that there is impaired thiamine metabolism in patients with ALS. Impaired thiamine metabolism decreases adenosine triphosphate (ATP) production and is a well-established cause of neurodegeneration. Decreased levels of TPPase, resulting in decreased levels of TMP in the cells of the frontal cortex, might account for the focal neurodegenerative changes observed in motor neurons in ALS. Benfotiamine, a safe, lipid-soluble, highly absorbable thiamine analogue, significantly raises free thiamine, TMP, and TPP levels in the blood. A case in which benfotiamine may have positively impacted the symptoms of a patient with ALS is presented. The use of benfotiamine in patients with ALS appears to be a promising therapeutic option. Considering the severity and the lack of satisfactory treatment options associated with this disease, more research on the effects of benfotiamine on the course of ALS is urgently needed.
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13
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Wu HHL, McDonnell T, Chinnadurai R. Physiological Associations between Vitamin B Deficiency and Diabetic Kidney Disease. Biomedicines 2023; 11:biomedicines11041153. [PMID: 37189771 DOI: 10.3390/biomedicines11041153] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/02/2023] [Revised: 03/24/2023] [Accepted: 04/10/2023] [Indexed: 05/17/2023] Open
Abstract
The number of people living with chronic kidney disease (CKD) is growing as our global population continues to expand. With aging, diabetes, and cardiovascular disease being major harbingers of kidney disease, the number of people diagnosed with diabetic kidney disease (DKD) has grown concurrently. Poor clinical outcomes in DKD could be influenced by an array of factors-inadequate glycemic control, obesity, metabolic acidosis, anemia, cellular senescence, infection and inflammation, cognitive impairment, reduced physical exercise threshold, and, importantly, malnutrition contributing to protein-energy wasting, sarcopenia, and frailty. Amongst the various causes of malnutrition in DKD, the metabolic mechanisms of vitamin B (B1 (Thiamine), B2 (Riboflavin), B3 (Niacin/Nicotinamide), B5 (Pantothenic Acid), B6 (Pyridoxine), B8 (Biotin), B9 (Folate), and B12 (Cobalamin)) deficiency and its clinical impact has garnered greater scientific interest over the past decade. There remains extensive debate on the biochemical intricacies of vitamin B metabolic pathways and how their deficiencies may affect the development of CKD, diabetes, and subsequently DKD, and vice-versa. Our article provides a review of updated evidence on the biochemical and physiological properties of the vitamin B sub-forms in normal states, and how vitamin B deficiency and defects in their metabolic pathways may influence CKD/DKD pathophysiology, and in reverse how CKD/DKD progression may affect vitamin B metabolism. We hope our article increases awareness of vitamin B deficiency in DKD and the complex physiological associations that exist between vitamin B deficiency, diabetes, and CKD. Further research efforts are needed going forward to address the knowledge gaps on this topic.
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Affiliation(s)
- Henry H L Wu
- Renal Research Laboratory, Kolling Institute of Medical Research, Royal North Shore Hospital, The University of Sydney, Sydney, NSW 2065, Australia
| | - Thomas McDonnell
- Department of Renal Medicine, Northern Care Alliance NHS Foundation Trust, Salford M6 8HD, UK
| | - Rajkumar Chinnadurai
- Department of Renal Medicine, Northern Care Alliance NHS Foundation Trust, Salford M6 8HD, UK
- Faculty of Biology, Medicine & Health, The University of Manchester, Manchester M1 7HR, UK
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14
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Chehayeb RJ, Ilagan-Ying YC, Sankey C. Addressing Cognitive Biases in Interpreting an Elevated Lactate in a Patient with Type 1 Diabetes and Thiamine Deficiency. J Gen Intern Med 2023; 38:1547-1551. [PMID: 36814053 PMCID: PMC9946700 DOI: 10.1007/s11606-023-08091-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Grants] [Track Full Text] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/24/2022] [Accepted: 02/08/2023] [Indexed: 02/24/2023]
Abstract
We present the case of a young woman admitted for diabetic ketoacidosis with persistent, asymptomatic lactic acid (LA) elevation during the evolving COVID-19 pandemic. Cognitive biases in interpreting an elevated LA in this patient's care resulted in an extensive infectious workup instead of the low-cost and potentially diagnostic provision of empiric thiamine. We discuss clinical patterns and etiologies of LA elevation and the role of thiamine deficiency. We also address cognitive biases potentially affecting the interpretation of elevated lactate levels and provide guidance for clinicians to determine appropriate patients for empiric thiamine administration.
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Affiliation(s)
| | | | - Christopher Sankey
- General Internal Medicine, Yale School of Medicine, New Haven, CT, USA.
- Yale New Haven Hospital, New Haven, CT, USA.
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15
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Al-Kharashi L, Attia H, Alsaffi A, Almasri T, Arafa M, Hasan I, Alajami H, Ali R, Badr A. Pentoxifylline and thiamine ameliorate rhabdomyolysis-induced acute kidney injury in rats via suppressing TLR4/NF-κB and NLRP-3/caspase-1/gasdermin mediated-pyroptosis. Toxicol Appl Pharmacol 2023; 461:116387. [PMID: 36690085 DOI: 10.1016/j.taap.2023.116387] [Citation(s) in RCA: 11] [Impact Index Per Article: 5.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/17/2022] [Revised: 01/12/2023] [Accepted: 01/16/2023] [Indexed: 01/21/2023]
Abstract
Acute kidney injury (AKI) is a common complication of rhabdomyolysis (RM), a syndrome characterized by skeletal muscle damage resulting in renal tubular oxidative stress, inflammation, and activated toll like receptor-4 (TLR-4) and NOD-like receptor protein-3 (NLRP-3) inflammasome. Pyroptosis is a programmed cell death mediated by NLRP-3 leading to the activation of caspase-1 and gasdermin D (GSDMD), the hallmark of pyroptosis. This study aims to investigate the renoprotective effects of two antioxidants; pentoxifylline (PTX) and thiamine (TM) via targeting the aforementioned pathways. RM-AKI was induced in male Albino Wistar rats by intramuscular injection of glycerol (50% v/v, 10 ml/kg). PTX (100 mg/kg, oral) and TM (25 mg/kg, i.p) were administered for 12 days prior glycerol injection and continued for 3 days following induction of RM-AKI. Serum creatinine, blood urea nitrogen (BUN), creatin kinase, lipid peroxides, total antioxidant activity, inflammatory markers (tumor necrosis factor-α, interleukin-1β, and nuclear factor kappa B), TLR4, NLRP-3, caspase-1, GSDMD and c-myc (an apoptotic marker) were estimated. Compared to AKI model, co-administered drugs revealed a significant improvement in renal function and pathology as indicated by the reduction in serum creatinine, BUN and protein cast accumulation. The elevations of oxidative stress, and inflammatory markers as well as the over-expression of c-myc were alleviated. Protein levels of TLR4, NLRP3, cleaved caspase-1, and GSDMD were significantly elevated in RM-AKI model, and this elevation was attenuated by the tested drugs. In conclusion, PTX and TM could be a potential renoprotective approach for patients with RM through targeting TLR4/NF-κB and NLRP-3/caspase-1/gasdermin mediated-pyroptosis pathways.
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Affiliation(s)
- Layla Al-Kharashi
- Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, Riyadh 11495, Saudi Arabia
| | - Hala Attia
- Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, Riyadh 11495, Saudi Arabia; Department of Biochemistry, College of Pharmacy, Mansoura University, Mansoura 35516, Egypt.
| | - Aljazzy Alsaffi
- College of Pharmacy, King Saud University, Riyadh 11495, Saudi Arabia
| | - Toka Almasri
- College of Pharmacy, King Saud University, Riyadh 11495, Saudi Arabia
| | - Maha Arafa
- Pathology Department, College of Medicine, King Saud University, Riyadh 11495, Saudi Arabia
| | - Iman Hasan
- Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, Riyadh 11495, Saudi Arabia
| | - Hanaa Alajami
- Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, Riyadh 11495, Saudi Arabia
| | - Rehab Ali
- Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, Riyadh 11495, Saudi Arabia
| | - Amira Badr
- Department of Pharmacology and Toxicology, College of Pharmacy, King Saud University, Riyadh 11495, Saudi Arabia; Department of Pharmacology and Toxicology, College of Pharmacy, Ain Shams, University, Heliopolis, Cairo, Egypt
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16
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Pathak R, Sachan N, Chandra P. Mechanistic approach towards diabetic neuropathy screening techniques and future challenges: A review. Biomed Pharmacother 2022; 150:113025. [PMID: 35658222 DOI: 10.1016/j.biopha.2022.113025] [Citation(s) in RCA: 10] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/23/2022] [Revised: 04/16/2022] [Accepted: 04/20/2022] [Indexed: 11/24/2022] Open
Abstract
Diabetic neuropathy, also called peripheral diabetic neuropathy (PDN), is among the most significant diabetes health consequences, alongside diabetic nephropathy, diabetic cardiomyopathy and diabetic retinopathy. Diabetic neuropathy is the existence of signs and indications of peripheral nerve damage in patients with diabetes after other causes have been governed out. Diabetic neuropathy is a painful and severe complication of diabetes that affects roughly 20% of people. The development of diabetic neuropathy is regulated by blood arteries that nourish the peripheral nerves and metabolic problems such as increased stimulation of polyol pathway, loss of myo-inositol and enhanced non-enzymatic glycation. It's divided into four types based on where neurons are most affected: autonomic, peripheral, proximal, and focal, with each kind presenting different symptoms like numbing, gastrointestinal disorders, and heart concerns. Pharmacotherapy for neuropathic pain is complex and for many patients, effective treatment is lacking; as a result, scientific proof recommendations are crucial. As a result, the current demand is to give the most vital medications or combinations of drugs that work directly on the nerves to help diabetic neuropathy patients feel less pain without causing any adverse effects. In diabetic neuropathy research, animal models are ubiquitous, with rats and mice being the most typically chosen for various reasons. This review covers the epidemiology, clinical features, pathology, clinical symptom, mechanism of diabetic neuropathy development, diagnosis, screening models of animals, diabetic neuropathy pharmacotherapy.
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Affiliation(s)
- Rashmi Pathak
- School of Pharmaceutical Sciences, IFTM University, Lodhipur Rajput Delhi Road (NH-24), Moradabad, UP 244102, India
| | - Neetu Sachan
- School of Pharmaceutical Sciences, IFTM University, Lodhipur Rajput Delhi Road (NH-24), Moradabad, UP 244102, India
| | - Phool Chandra
- School of Pharmaceutical Sciences, IFTM University, Lodhipur Rajput Delhi Road (NH-24), Moradabad, UP 244102, India.
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17
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Subramani PA, Shaik FB, Michael RD, Panati K, Narala VR. Thiamine Is a Natural Peroxisome Proliferator–Activated Receptor Gamma (PPAR-γ) Activator. LETT DRUG DES DISCOV 2022. [DOI: 10.2174/1570180819666220127121403] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022]
Abstract
Background:
There has been increasing evidence for the correlation between thiamine deficiency and type 2 diabetes (T2D). T2D is a condition in which an individual’s insulin sensitivity is highly compromised. Peroxisome proliferator–activated receptor gamma (PPAR-γ) is a ligand-activated transcription factor etiologically relevant to T2D. We hypothesized that thiamine could be a PPAR-γ ligand and thus activate PPAR-γ and ameliorate T2D.
Objective:
This study aims to establish thiamine as a PPAR-γ ligand via molecular docking and dynamics simulations (MDS) and thiamine’s ability to induce adipogenesis, upregulating PPAR-γ and AP-2 genes using in vitro assays.
Methods:
Thiamine/PPAR-γ binding was studied using Schrödinger’s Glide. The bound complex was simulated in the OPLS 2005 force field using Desmond. 3T3-L1 preadipocyte cells were differentiated in the presence of thiamine and rosiglitazone and stained with Oil Red O. Nuclear protein from the differentiated cells was used to study the binding of the PPAR-γ response element (PPRE) using an ELISA-based assay. mRNA from differentiated cells was used to study the expression of genes using quantitative RT-PCR.
Results:
In silico docking shows that thiamine binds with PPAR-γ. MDS indicate that the interactions between thiamine and PPAR-γ are stable over a significant period. Thiamine induces the differentiation of 3T3-L1 preadipocytes in a dose-dependent manner and enhances the PPRE-binding activity of PPAR-γ. Thiamine treatment significantly increases the mRNA levels of PPAR-γ and AP-2 genes.
Conclusion:
Our results show that thiamine is a PPAR-γ ligand. Animal studies and clinical trials are required to corroborate the results obtained.
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Affiliation(s)
- Parasuraman Aiya Subramani
- Department of Zoology, Yogi Vemana University, Kadapa, A.P., 516 005, India
- Centre for Fish Immunology, School of Life Sciences, Vels University, Pallavaram, Chennai-600117, India
| | | | - R. Dinakaran Michael
- Centre for Fish Immunology, School of Life Sciences, Vels University, Pallavaram, Chennai-600117, India
| | - Kalpana Panati
- Department of Biotechnology, Government College for Men, Kadapa -516 004, India
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18
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Tanaka H, Anno T, Takenouchi H, Iwamoto H, Kaneto H, Okimoto N, Tomoda K. Case Report: Severe Edema and Marked Weight Gain Induced by Marginal Thiamine Deficiency in a Patient With Alcohol Dependency and Type 2 Diabetes Mellitus. Front Nutr 2021; 8:675992. [PMID: 34977103 PMCID: PMC8714915 DOI: 10.3389/fnut.2021.675992] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/04/2021] [Accepted: 11/18/2021] [Indexed: 11/13/2022] Open
Abstract
Background: Patients with alcohol use disorder (AUD) may develop peripheral edema due to alcohol-related liver, renal, or heart disease. Thiamine deficiency is reported to occur in AUD and type 2 diabetes mellitus (T2DM). Thiamine deficiency may also cause peripheral edema. Thiamine is essential for optimal glucose metabolism through its role as an essential co-factor for key enzymes in intermediary metabolism. Since glucose metabolism worsens under diabetic conditions, it seems that a relative shortage of thiamine may occur more easily in patients with diabetes mellitus. Case Presentation: A 59-year-old Japanese man was admitted to the hospital with severe peripheral edema. His background history included alcohol liver disease (ALD), chronic renal failure (CRF), and T2DM. His body mass index (BMI) at admission was 37.7 kg/m2 and this represented a 30 kg increase in body weight over 2 months. Laboratory investigations showed anemia, liver and renal injury, hyperglycemia, and marginal hypothyroidism. The plasma thiamine diphosphate concentration was 20 ng/mL (reference range: 24–66 ng/mL). Diet therapy of 1,600 kcal/day and intravenous fursultiamine hydrochloride therapy (50 mg/once a day, seven days) was commenced in combination with intravenous diuretics. After one week, the plasma thiamine concentration was 853 ng/mL, and the patient's body weight had reduced by 18 kg. Conclusions: Patients with T2DM and AUD may develop severe peripheral edema in the context of marginal thiamine deficiency. Fursultiamine hydrochloride (50 mg/once a day, seven days) restored normal plasma thiamine concentrations and may have contributed to the rapid resolution of severe peripheral edema in this case. Empirical treatment with thiamine should be considered in patients with severe peripheral edema in the context of AUD and T2DM.
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Affiliation(s)
- Hitomi Tanaka
- Department of General Internal Medicine, Kawasaki Medical School, Okayama, Japan
| | - Takatoshi Anno
- Department of General Internal Medicine, Kawasaki Medical School, Okayama, Japan
- *Correspondence: Takatoshi Anno
| | - Haruka Takenouchi
- Department of General Internal Medicine, Kawasaki Medical School, Okayama, Japan
| | - Hideyuki Iwamoto
- Department of General Internal Medicine, Kawasaki Medical School, Okayama, Japan
| | - Hideaki Kaneto
- Department of Diabetes, Endocrinology and Metabolism, Kawasaki Medical School, Kurashiki, Japan
| | - Niro Okimoto
- Department of General Internal Medicine, Kawasaki Medical School, Okayama, Japan
| | - Koichi Tomoda
- Department of General Internal Medicine, Kawasaki Medical School, Okayama, Japan
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19
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Kale MB, Bajaj K, Umare M, Wankhede NL, Taksande BG, Umekar MJ, Upaganlawar A. Exercise and Nutraceuticals: Eminent approach for Diabetic Neuropathy. Curr Mol Pharmacol 2021; 15:108-128. [PMID: 34191703 DOI: 10.2174/1874467214666210629123010] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/15/2020] [Revised: 02/28/2021] [Accepted: 03/05/2021] [Indexed: 11/22/2022]
Abstract
Diabetic neuropathy is an incapacitating chronic pathological condition that encompasses a large group of diseases and manifestations of nerve damage. It affects approximately 50% of patients with diabetes mellitus. Autonomic, sensory, and motor neurons are affected. Disabilities are severe, along with poor recovery and diverse pathophysiology. Physical exercise and herbal-based therapies have the potential to decrease the disabilities associated with diabetic neuropathy. Aerobic exercises like walking, weight lifting, the use of nutraceuticals and herbal extracts are found to be effective. Literature from the public domain was studied emphasizing various beneficial effects of different exercises, use of herbal and nutraceuticals for their therapeutic action in diabetic neuropathy. Routine exercises and administration of herbal and nutraceuticals, either the extract of plant material containing the active phytoconstituent or isolated phytoconstituent at safe concentration, have been shown to have promising positive action in the treatment of diabetic neuropathy. Exercise has shown promising effects on vascular and neuronal health and has proven to be well effective in the treatment as well as prevention of diabetic neuropathy by various novel mechanisms, including herbal and nutraceuticals therapy is also beneficial for the condition. They primarily show the anti-oxidant effect, secretagogue, anti-inflammatory, analgesic, and neuroprotective action. Severe adverse events are rare with these therapies. The current review investigates the benefits of exercise and nutraceutical therapies in the treatment of diabetic neuropathy.
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Affiliation(s)
- Mayur Bhimrao Kale
- Shrimati Kishoritai Bhoyar College of Pharmacy, New Kamptee, Nagpur 441002, Maharashtra, India
| | - Komal Bajaj
- Shrimati Kishoritai Bhoyar College of Pharmacy, New Kamptee, Nagpur 441002, Maharashtra, India
| | - Mohit Umare
- Shrimati Kishoritai Bhoyar College of Pharmacy, New Kamptee, Nagpur 441002, Maharashtra, India
| | - Nitu L Wankhede
- Shrimati Kishoritai Bhoyar College of Pharmacy, New Kamptee, Nagpur 441002, Maharashtra, India
| | | | - Milind Janrao Umekar
- Shrimati Kishoritai Bhoyar College of Pharmacy, New Kamptee, Nagpur 441002, Maharashtra, India
| | - Aman Upaganlawar
- SNJB's Shriman Sureshdada Jain College of Pharmacy, Neminagar, Chandwad-42310, Nasik, Maharashtra, India
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20
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Sambon M, Wins P, Bettendorff L. Neuroprotective Effects of Thiamine and Precursors with Higher Bioavailability: Focus on Benfotiamine and Dibenzoylthiamine. Int J Mol Sci 2021; 22:ijms22115418. [PMID: 34063830 PMCID: PMC8196556 DOI: 10.3390/ijms22115418] [Citation(s) in RCA: 18] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/30/2021] [Revised: 05/10/2021] [Accepted: 05/18/2021] [Indexed: 11/25/2022] Open
Abstract
Thiamine (vitamin B1) is essential for brain function because of the coenzyme role of thiamine diphosphate (ThDP) in glucose and energy metabolism. In order to compensate thiamine deficiency, several thiamine precursors with higher bioavailability were developed since the 1950s. Among these, the thioester benfotiamine (BFT) has been extensively studied and has beneficial effects both in rodent models of neurodegeneration and in human clinical studies. BFT has antioxidant and anti-inflammatory properties that seem to be mediated by a mechanism independent of the coenzyme function of ThDP. BFT has no adverse effects and improves cognitive outcome in patients with mild Alzheimer’s disease (AD). Recent in vitro studies show that another thiamine thioester, dibenzoylthiamine (DBT) is even more efficient that BFT, especially with respect to its anti-inflammatory potency. Thiamine thioesters have pleiotropic properties linked to an increase in circulating thiamine concentrations and possibly in hitherto unidentified metabolites in particular open thiazole ring derivatives. The identification of the active neuroprotective derivatives and the clarification of their mechanism of action open extremely promising perspectives in the field of neurodegenerative, neurodevelopmental and psychiatric conditions.
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21
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Watanabe Y, Mawatari A, Aita K, Sato Y, Wada Y, Nakaoka T, Onoe K, Yamano E, Akamatsu G, Ohnishi A, Shimizu K, Sasaki M, Doi H, Senda M. PET imaging of 11C-labeled thiamine tetrahydrofurfuryl disulfide, vitamin B 1 derivative: First-in-human study. Biochem Biophys Res Commun 2021; 555:7-12. [PMID: 33812058 DOI: 10.1016/j.bbrc.2021.03.119] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/16/2021] [Accepted: 03/21/2021] [Indexed: 11/29/2022]
Abstract
Vitamine B1 thiamine is an essential component for glucose metabolism and energy production. The disulfide derivative, thiamine tetrahydrofurfuryl disulfide (TTFD), is more absorbent compared to readily-available water-soluble thiamine salts since it does not require the rate-limiting transport system required for thiamine absorption. However, the detailed pharmacokinetics of thiamine and TTFD under normal and pathological conditions were not clarified yet. Recently, 11C-labeled thiamine and TTFD were synthesized by our group, and their pharmacokinetics were investigated by PET imaging in normal rats. In this study, to clarify the whole body pharmacokinetics of [11C]TTFD in human healthy volunteers, we performed first-in-human PET imaging study with [11C]TTFD, along with radiation dosimetry of [11C]TTFD in humans. METHODS Synthesis of [11C]TTFD was improved for clinical study. Dynamic whole-body PET images were acquired on three young male normal subjects after intravenous injection of [11C]TTFD. VOIs were defined for source organs on the PET images to measure time-course of [11C]TTFD uptake as percentage injected dose and the number of disintegrations for each organ. Radiation dosimetry was calculated with OLINDA/EXM. RESULTS We succeeded in developing the improved synthetic method of [11C]TTFD for the first-in-human PET study. In the whole body imaging, uptake of [11C]TTFD by various tissues was almost plateaued at 10 min after intravenous injection, afterward gradually increased for the brain and urinary bladder (urine). %Injected dose was high in the liver, kidney, urinary bladder, heart, spine, brain, spleen, pancreas, stomach, and salivary glands, in this order. %Injected dose per gram of tissue was high also in the pituitary. By dosimetry, the effective radiation dose of [11C]TTFD calculated was 5.5 μSv/MBq (range 5.2-5.7). CONCLUSION Novel synthetic method enabled clinical PET study with [11C]TTFD, which is a safe PET tracer with a dosimetry profile comparable to other common 11C-PET tracers. Pharmacokinetics of TTFD in the pharmacological dose and at different nutritional states could be further investigated by future quantitative PET studies. Noninvasive in vivo PET imaging for pathophysiology of thiamine-related function may provide diagnostic evidence of novel information about vitamin B1 deficiency in human tissues.
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Affiliation(s)
- Yasuyoshi Watanabe
- RIKEN Center for Biosystems Dynamics Research, Kobe, Hyogo, Japan; RIKEN Compass to Healthy Life Research Complex Program, Kobe, Hyogo, Japan.
| | - Aya Mawatari
- RIKEN Center for Biosystems Dynamics Research, Kobe, Hyogo, Japan
| | - Kazuki Aita
- Division of Molecular Imaging, Kobe City Medical Center General Hospital, Kobe, Hyogo, Japan
| | - Yuzuru Sato
- RIKEN Center for Biosystems Dynamics Research, Kobe, Hyogo, Japan
| | - Yasuhiro Wada
- RIKEN Center for Biosystems Dynamics Research, Kobe, Hyogo, Japan
| | | | - Kayo Onoe
- RIKEN Center for Biosystems Dynamics Research, Kobe, Hyogo, Japan
| | - Emi Yamano
- RIKEN Center for Biosystems Dynamics Research, Kobe, Hyogo, Japan; RIKEN Compass to Healthy Life Research Complex Program, Kobe, Hyogo, Japan
| | - Go Akamatsu
- Division of Molecular Imaging, Kobe City Medical Center General Hospital, Kobe, Hyogo, Japan
| | - Akihito Ohnishi
- Division of Molecular Imaging, Kobe City Medical Center General Hospital, Kobe, Hyogo, Japan
| | - Keiji Shimizu
- Division of Molecular Imaging, Kobe City Medical Center General Hospital, Kobe, Hyogo, Japan
| | - Masahiro Sasaki
- Division of Molecular Imaging, Kobe City Medical Center General Hospital, Kobe, Hyogo, Japan
| | - Hisashi Doi
- RIKEN Center for Biosystems Dynamics Research, Kobe, Hyogo, Japan
| | - Michio Senda
- Division of Molecular Imaging, Kobe City Medical Center General Hospital, Kobe, Hyogo, Japan
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Vatsalya V, Li F, Frimodig J, Gala KS, Srivastava S, Kong M, Ramchandani VA, Feng W, Zhang X, McClain CJ. Repurposing Treatment of Wernicke-Korsakoff Syndrome for Th-17 Cell Immune Storm Syndrome and Neurological Symptoms in COVID-19: Thiamine Efficacy and Safety, In-Vitro Evidence and Pharmacokinetic Profile. Front Pharmacol 2021; 11:598128. [PMID: 33737877 PMCID: PMC7960760 DOI: 10.3389/fphar.2020.598128] [Citation(s) in RCA: 9] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/23/2020] [Accepted: 12/10/2020] [Indexed: 12/19/2022] Open
Abstract
Coronavirus disease identified in 2019 (COVID-19) can be complicated by the Th17 cell-mediated IL-17 proinflammatory response. We tested if thiamine can effectively lower the Th17 response in a clinical study [Proinflammatory state in alcohol use disorder patients termed as disease controls (DC)] and corroborated the results using an in vitro study. We developed an effective dose range and model for key pharmacokinetic measures with the potential of targeting the cytokine storm and neurological symptoms of COVID-19. Three-week 200 mg dose of thiamine was administered to sixteen DC patients. Eight healthy volunteers (HV) were also included in this investigation. A subsequent in vitro study was performed to validate the effectiveness of thiamine [100 mg/day equivalent (0.01 μg/ml)] treatment in lowering the Th17 proinflammatory response in a mouse macrophage cell line (RAW264.7) treated with ethanol. Based on recent publications, we compared the results of the IL-17 response from our clinical and in vitro study to those found in other proinflammatory disease conditions (metabolic conditions, septic shock, viral infections and COVID-19) and effective and safe dose ranges of thiamine. We developed a pharmacokinetic profile for thiamine dose range as a novel intervention strategy in COVID-19. DC group showed significantly elevated proinflammatory cytokines compared to HV. Thiamine-treated DC patients showed significant lowering in IL-17 and increase in the IL-22 levels. In humans, a range of 79-474 mg daily of thiamine was estimated to be effective and safe as an intervention for the COVID-19 cytokine storm. A literature review showed that several neurological symptoms of COVID-19 (∼45.5% of the severe cases) occur in other viral infections and neuroinflammatory states that may also respond to thiamine treatment. Thiamine, a very safe drug even at very high doses, could be repurposed for treating the Th17 mediated IL-17 immune storm, and the subsequent neurological symptoms observed in COVID-19. Further studies using thiamine as an intervention/prevention strategy in COVID-19 patients could identify its precise anti-inflammatory role.
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Affiliation(s)
- Vatsalya Vatsalya
- Department of Medicine, University of Louisville, Louisville, KY, United States
- Robley Rex VA Medical Center, Louisville, KY, United States
| | - Fengyuan Li
- Department of Medicine, University of Louisville, Louisville, KY, United States
- University of Louisville Alcohol Research Center, Louisville, KY, United States
| | - Jane Frimodig
- Department of Medicine, University of Louisville, Louisville, KY, United States
- Robley Rex VA Medical Center, Louisville, KY, United States
| | - Khushboo S. Gala
- Department of Medicine, University of Louisville, Louisville, KY, United States
| | - Shweta Srivastava
- Department of Medicine, University of Louisville, Louisville, KY, United States
- Envirome Institute, University of Louisville, Louisville, KY, United States
| | - Maiying Kong
- Robley Rex VA Medical Center, Louisville, KY, United States
- Department of Bioinformatics and Biostatistics, University of Louisville, Louisville, KY, United States
| | - Vijay A. Ramchandani
- National Institute on Alcohol Abuse and Alcoholism, NIH, Bethesda, MD, United States
| | - Wenke Feng
- Department of Medicine, University of Louisville, Louisville, KY, United States
- University of Louisville Alcohol Research Center, Louisville, KY, United States
- Department of Pharmacology and Toxicology, University of Louisville, Louisville, KY, United States
- University of Louisville Hepatobiology and Toxicology COBRE, Louisville, KY, United States
| | - Xiang Zhang
- University of Louisville Alcohol Research Center, Louisville, KY, United States
- Department of Pharmacology and Toxicology, University of Louisville, Louisville, KY, United States
- University of Louisville Hepatobiology and Toxicology COBRE, Louisville, KY, United States
- Department of Chemistry, University of Louisville, Louisville, KY, United States
- Center for Regulatory and Environmental Analytical Metabolomics, University of Louisville, Louisville, KY, United States
| | - Craig J. McClain
- Department of Medicine, University of Louisville, Louisville, KY, United States
- Robley Rex VA Medical Center, Louisville, KY, United States
- University of Louisville Alcohol Research Center, Louisville, KY, United States
- Department of Pharmacology and Toxicology, University of Louisville, Louisville, KY, United States
- University of Louisville Hepatobiology and Toxicology COBRE, Louisville, KY, United States
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Zhang S, Zeng B, Chen Y, Yang M, Kong F, Wei L, Li F, Zhao J, Li Y. Gut microbiota in healthy and unhealthy long-living people. Gene 2021; 779:145510. [PMID: 33600956 DOI: 10.1016/j.gene.2021.145510] [Citation(s) in RCA: 21] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/07/2020] [Revised: 01/26/2021] [Accepted: 02/05/2021] [Indexed: 01/01/2023]
Abstract
The human gut microbiota in long-living people has been characterized, however, its metabolic potential is still largely unknown in this group. In this study, the gut microbiota was assessed in 37 Chinese long-living participants (aged 90 + years) by metagenomic sequencing of stool samples. Participants were categorized into two groups, healthy long-living (n = 28) and unhealthy long-living (n = 9). Gut microbiota composition and function were compared among these two groups. We found that the gut microbiota in the healthy long-living group was significantly separated from the unhealthy group. The healthy long-living group contained a higher abundance of Bacteroidetes and more functional pathways in energy metabolism, glycan biosynthesis and metabolism, metabolism of cofactors and vitamins, and biosynthesis of other secondary metabolites. The unhealthy group contained a higher abundance of Streptococcus and other pathogenic bacteria, and also contained more functional pathways for xenobiotics biodegradation and metabolism than the healthy group. Additionally, the unhealthy group had decreased levels of carbohydrate-active enzymes, including host-glycan and fiber degrading enzymes, and an increase in starch-degrading enzymes. In conclusion, the gut microbiota of unhealthy long-living people contains more pathogenic bacteria, and the overall gut microbiota may be in an unhealthy state, "dysbiosis", which leads to a decrease in carbohydrate digestion, glycan and thiamine (B1) metabolites, and fatty acid biosynthesis.
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Affiliation(s)
- Siyuan Zhang
- Guangdong Provincial Key Laboratory of Animal Molecular Design and Precise Breeding, College of Life Science and Engineering, Foshan University, Foshan, China; School of Laboratory Medicine/Sichuan Provincial Engineering Laboratory for Prevention and Control Technology of Veterinary Drug Residue in Animal-origin Food, Chengdu Medical College, Chengdu 610500, China; Farm Animal Genetic Resources Exploration and Innovation Key Laboratory of Sichuan Province, Sichuan Agricultural University, Chengdu, China
| | - Bo Zeng
- Farm Animal Genetic Resources Exploration and Innovation Key Laboratory of Sichuan Province, Sichuan Agricultural University, Chengdu, China
| | - Yinfeng Chen
- Farm Animal Genetic Resources Exploration and Innovation Key Laboratory of Sichuan Province, Sichuan Agricultural University, Chengdu, China
| | - Mingyao Yang
- Farm Animal Genetic Resources Exploration and Innovation Key Laboratory of Sichuan Province, Sichuan Agricultural University, Chengdu, China
| | - Fanli Kong
- College of Life Science, Sichuan Agricultural University, Ya'an, China
| | - Limin Wei
- Farm Animal Genetic Resources Exploration and Innovation Key Laboratory of Sichuan Province, Sichuan Agricultural University, Chengdu, China
| | - Feng Li
- Farm Animal Genetic Resources Exploration and Innovation Key Laboratory of Sichuan Province, Sichuan Agricultural University, Chengdu, China
| | - Jiangchao Zhao
- Department of Animal Science, Division of Agriculture, University of Arkansas, Fayetteville, State of AR, United States.
| | - Ying Li
- Guangdong Provincial Key Laboratory of Animal Molecular Design and Precise Breeding, College of Life Science and Engineering, Foshan University, Foshan, China.
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Gonçalves SEAB, Gonçalves TJM, Guarnieri A, Risegato RC, Guimarães MP, de Freitas DC. Association between thiamine deficiency and hyperlactatemia among critically ill patients with diabetes infected by SARS-CoV-2. J Diabetes 2021; 13:413-419. [PMID: 33448683 PMCID: PMC8014215 DOI: 10.1111/1753-0407.13156] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/07/2020] [Revised: 01/07/2021] [Accepted: 01/10/2021] [Indexed: 01/09/2023] Open
Abstract
BACKGROUND The present study aims to verify the association between diabetes and thiamine deficiency in critically ill patients infected by severe acute respiratory syndrome coronavirus 2. METHODS This is a descriptive cross-sectional study, whose demographic, anthropometric, and laboratory data (arterial lactate, bicarbonate, and plasma thiamine) were obtained in the first hours of admission to the intensive care unit. Patients with diabetes were compared with individuals without diabetes, and the correlation was performed between thiamine and lactate levels. Thiamine levels <28 μg/L were considered as thiamine deficiency. RESULTS Overall, 270 patients met the inclusion criteria; 51.1% were men, and the median age was 74 years (66.8-81). The median value of thiamine was 54.0 μg/L (38-72.3), and 15.6% had thiamine deficiency. Among patients with diabetes, 26.3% had thiamine deficiency, and 69.3% had hyperlactatemia. There was an association between thiamine deficiency and diabetes (odds ratio 4.28; 95% CI, 2.08-8.81; P < .001). There was a strong negative correlation between thiamine and arterial lactate in patients with diabetes (r = -0.711, P < .001) and a moderate negative correlation in critically ill patients without diabetes (r = -0.489, P < .001). CONCLUSIONS The prevalence of thiamine deficiency in critically ill patients due to coronavirus disease 2019 is higher in patients with diabetes. There is a negative correlation between thiamine and arterial lactate levels, which is higher in people with diabetes.
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Affiliation(s)
| | | | - Andreia Guarnieri
- Sancta Maggiore Hospital, Prevent Senior Private Health OperatorSão PauloBrazil
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25
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Tiwari R, Wal P, Singh P, Tiwari G, Rai A. A Review on Mechanistic and Pharmacological Findings of Diabetic Peripheral Neuropathy including Pharmacotherapy. Curr Diabetes Rev 2021; 17:247-258. [PMID: 32928092 DOI: 10.2174/1573399816666200914141558] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/07/2020] [Revised: 08/01/2020] [Accepted: 08/18/2020] [Indexed: 11/22/2022]
Abstract
BACKGROUND Chronic hyperglycemia and related complications involving peripheral nerves in diabetes are one of the most severe microvascular complications with an average prevalence of 50-60%. Diabetic neuropathy is among the vascular disorders of diabetes, the most debilitating and crippled, lethal condition impacting patients's quality of life. METHODS In the present review article, several hypotheses associated with the pathogenesis of Diabetic Peripheral Neuropathy (DPN) have been introduced, among them metabolic pathways associated with polyol pathway, oxidative stress, production of reactive oxygen species (ROS) amplified under chronic hyperglycemic conditions and activation of transcription factor Nuclear factor-κB (NF- κB). The review article also possesses pathogenetic and pharmacologic treatments along with others, including acupressure, lidocaine, and capsaicin for DPN. CONCLUSION It may be concluded that we can combat the pathogenesis of DPN with different suggested treatments.
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Affiliation(s)
- Ruchi Tiwari
- Department of Pharmacy, Pranveer Singh Institute Of Technology, Kanpur - Agra - Delhi National Highway - 2 , Bhauti - Kanpur - 209305, India
| | - Pranay Wal
- Department of Pharmacy, Pranveer Singh Institute Of Technology, Kanpur - Agra - Delhi National Highway - 2 , Bhauti - Kanpur - 209305, India
| | - Priya Singh
- Department of Pharmacy, Pranveer Singh Institute Of Technology, Kanpur - Agra - Delhi National Highway - 2 , Bhauti - Kanpur - 209305, India
| | - Gaurav Tiwari
- Department of Pharmacy, Pranveer Singh Institute Of Technology, Kanpur - Agra - Delhi National Highway - 2 , Bhauti - Kanpur - 209305, India
| | - Awani Rai
- Department of Pharmacy, Pranveer Singh Institute Of Technology, Kanpur - Agra - Delhi National Highway - 2 , Bhauti - Kanpur - 209305, India
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Therapeutic Prospects for Th-17 Cell Immune Storm Syndrome and Neurological Symptoms in COVID-19: Thiamine Efficacy and Safety, In-vitro Evidence and Pharmacokinetic Profile. MEDRXIV : THE PREPRINT SERVER FOR HEALTH SCIENCES 2020. [PMID: 32869036 DOI: 10.1101/2020.08.23.20177501] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/29/2022]
Abstract
Introduction Emerging infectious diseases, especially the coronavirus disease identified in 2019 (COVID-19), can be complicated by a severe exacerbation in the Th17 cell-mediated IL-17 proinflammatory immune storm. This enhanced immune response plays a major role in mortality and morbidity, including neurological symptoms. We hypothesized that countering the cytokine storm with thiamine may have therapeutic efficacy in lowering the Th17 cell proinflammatory response. We used an in vitro study and corroborated those results in disease controls (DC). We developed an effective dose range and model for key pharmacokinetic measures with the potential of targeting the cytokine storm and neurological symptoms of COVID-19. Study Participants and Methods We investigated the effect of a three-week 200 mg dose of thiamine in lowering the Th17 response in sixteen DC (proinflammatory origin due to heavy alcohol drinking) patients; and eight healthy control/volunteers (HV) as a pilot clinical-translational investigation. To further investigate, we performed an in vitro study evaluating the effectiveness of thiamine treatment in lowering the Th17 proinflammatory response in a mouse macrophage cell line (RAW264.7) treated with ethanol. In this in vitro study, 100 mg/day equivalent (0.01 ug/ml) thiamine was used. Based on recent publications, we compared the results of the IL-17 response from our clinical and in vitro study to those found in other proinflammatory disease conditions (metabolic conditions, septic shock, viral infections and COVID-19), including symptoms, and dose ranges of effective and safe administration of thiamine. We developed a dose range and pharmacokinetic profile for thiamine as a novel intervention strategy in COVID-19 to alleviate the effects of the cytokine storm and neurological symptoms. Results The DC group showed significantly elevated proinflammatory cytokines compared to HV. Three-week of 200 mg daily thiamine treatment significantly lowered the baseline IL-17 levels while increased IL-22 levels (anti-inflammatory response). This was validated by an in vitro macrophage response using a lower thiamine dose equivalent (100 mg), which resulted in attenuation of IL-17 and elevation of IL-22 at the mRNA level compared to the ethanol-only treated group. In humans, a range of 79-474 mg daily of thiamine was estimated to be effective and safe as an intervention for the COVID-19 cytokine storm. A literature review showed that several neurological symptoms of COVID-19 (which exist in 45.5% of the severe cases) occur in other viral infections and neuroinflammatory states that may also respond to thiamine treatment. Discussion The Th17 mediated IL-17 proinflammatory response can potentially be attenuated by thiamine. Thiamine, a very safe drug even at very high doses, could be repurposed for treating the cytokine/immune storm of COVID-19 and the subsequent neurological symptoms observed in COVID-19 patients. Further studies using thiamine as an interventional/prevention strategy in severe COVID-19 patients could identify its precise anti-inflammatory role.
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Blood thiamine pyrophosphate concentration and its correlation with the stage of diabetic retinopathy. Int Ophthalmol 2020; 40:3279-3284. [PMID: 32715366 DOI: 10.1007/s10792-020-01513-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/14/2020] [Accepted: 07/17/2020] [Indexed: 10/23/2022]
Abstract
PURPOSE To assess the possible relationship between blood thiamine pyrophosphate (TPP) concentration and stage of diabetic retinopathy (DR). METHODS This comparative cross-sectional study included 80 patients with type 2 diabetes mellitus (T2DM) and 20 age- and gender-matched healthy controls. Diabetic patients were subclassified into four groups each consisting of 20 subjects: no DR, mild-moderate non-proliferative DR (mild-moderate NPDR), severe NPDR, and proliferative DR (PDR). Blood TPP concentration was assessed with high-performance liquid chromatography (HPLC) assay and was correlated with the stage of DR. RESULTS Mean blood TPP concentration was 80.2 ± 14.8 nmol/L in control group. It was, respectively, 69.85 ± 18.1, 64.95 ± 13.4, 61.9 ± 13.4 and 60.75 ± 14.3 nmol/L in no DR, mild-moderate NPDR, severe NPDR and PDR groups. For mild-moderate NPDR, severe NPDR and PDR groups, TPP concentrations were significantly lower compared with controls (p: 0.014, 0.002, 0.001, respectively). Mean TPP concentration for NPDR patients was higher than for PDR patients, but the difference was not significant (p: 0.478). ANOVA revealed a significant difference between TPP concentrations of groups (p: 0.001). Mean TPP concentration decreased with the stage of DR, and number of patients with thiamine deficiency increased gradually with the stage of DR. A negative correlation was found between the TPP level and occurrence of DR (p: 0.000). CONCLUSION The results suggest that lower blood TPP concentrations were associated with higher risk of DR. Thiamine might play an important role in the pathophysiology and progression of DR. Thiamine and its derivatives might represent an approach to the prevention and/or treatment of early DR.
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Brás IC, König A, Outeiro TF. Glycation in Huntington's Disease: A Possible Modifier and Target for Intervention. J Huntingtons Dis 2020; 8:245-256. [PMID: 31322580 PMCID: PMC6839463 DOI: 10.3233/jhd-190366] [Citation(s) in RCA: 20] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/26/2022]
Abstract
Glycation is the non-enzymatic reaction between reactive dicarbonyls and amino groups, and gives rise to a variety of different reaction products known as advanced glycation end products (AGEs). Accumulation of AGEs on proteins is inevitable, and is associated with the aging process. Importantly, glycation is highly relevant in diabetic patients that experience periods of hyperglycemia. AGEs also play an important role in neurodegenerative diseases including Alzheimer’s (AD) and Parkinson’s disease (PD). Huntington’s disease (HD) is a hereditary neurodegenerative disease caused by an expansion of a CAG repeat in the huntingtin gene. The resulting expanded polyglutamine stretch in the huntingtin (HTT) protein induces its misfolding and aggregation, leading to neuronal dysfunction and death. HD patients exhibit chorea and psychiatric disturbances, along with abnormalities in glucose and energy homeostasis. Interestingly, an increased prevalence of diabetes mellitus has been reported in HD and in other CAG triplet repeat disorders. However, the mechanisms underlying the connection between glycation and HD progression remain unclear. In this review, we explore the possible connection between glycation and proteostasis imbalances in HD, and posit that it may contribute to disease progression, possibly by accelerating protein aggregation and deposition. Finally, we review therapeutic interventions that might be able to alleviate the negative impact of glycation in HD.
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Affiliation(s)
- Inês Caldeira Brás
- Department of Experimental Neurodegeneration, Center for Biostructural Imaging of Neurodegeneration, University Medical Center Göttingen, Göttingen, Germany
| | - Annekatrin König
- Department of Experimental Neurodegeneration, Center for Biostructural Imaging of Neurodegeneration, University Medical Center Göttingen, Göttingen, Germany
| | - Tiago Fleming Outeiro
- Department of Experimental Neurodegeneration, Center for Biostructural Imaging of Neurodegeneration, University Medical Center Göttingen, Göttingen, Germany.,Max Planck Institute for Experimental Medicine, Göttingen, Germany.,Institute of Neuroscience, The Medical School, Newcastle University, Newcastle upon Tyne, United Kingdom
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29
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Singh R, Rao HK, Singh TG. Neuropathic pain in diabetes mellitus: Challenges and future trends. ACTA ACUST UNITED AC 2020. [DOI: 10.1016/j.obmed.2020.100215] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
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Use of Aloe Vera Gel-Based Edible Coating with Natural Anti-Browning and Anti-Oxidant Additives to Improve Post-Harvest Quality of Fresh-Cut ‘Fuji’ Apple. AGRONOMY-BASEL 2020. [DOI: 10.3390/agronomy10040515] [Citation(s) in RCA: 26] [Impact Index Per Article: 5.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/16/2022]
Abstract
Recently, there is increasing use of edible and biodegradable films and packaging that are both environmentally friendly and functional for storage and market distribution. Fresh-cut ‘Fuji’ apples, harvested in an organic farm, were treated, using a spraying technique, with three new edible coatings based on Aloe vera gel (AVG—40% v/w) and in combination with natural additives: lemon essential oil (LEO—1% v/w) and hydroxypropyl methylcellulose (HPMC—0.1% v/w) and compared with untreated sample (CTR), the physicochemical and sensory characteristics and the proximate compounds were evaluated. During cold storage, weight loss, soluble solids content, and color of uncoated slices were reduced, while softening, ripening, browning, and acidity were accelerated. In contrast, the AVG/HPMC treatment significantly delayed the above parameters related to post-harvest quality loss, while the AVG/LEO treatment delayed the browning processes, maintaining an excellent color during cold storage. Concerning proximate compounds, the treatments did not alter their concentration in the fruit tissues. Sensory analyses revealed no detrimental effect on taste, aroma, or flavor. Our data evidenced the positive effect of Aloe vera gel in combination with LEO and HPMC on fresh-cut apple quality as an innovative and sustainable technique to maintain fresh-cut apple quality.
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Transketolase and vitamin B1 influence on ROS-dependent neutrophil extracellular traps (NETs) formation. PLoS One 2019; 14:e0221016. [PMID: 31415630 PMCID: PMC6695114 DOI: 10.1371/journal.pone.0221016] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/11/2018] [Accepted: 07/30/2019] [Indexed: 12/23/2022] Open
Abstract
Neutrophil extracellular traps (NETs) are a recently identified, web-like, extracellular structure composed of decondensed nuclear DNA and associated antimicrobial granules. NETs are extruded into the extracellular environment via the reactive oxygen species (ROS)-dependent cell death pathway participating in inflammation and autoimmune diseases. Transketolase (TKT) is a thiamine pyrophosphate (vitamin B1)-dependent enzyme that links the pentose phosphate pathway with the glycolytic pathway by feeding excess sugar phosphates into the main carbohydrate metabolic pathways to generate biosynthetic reducing capacity in the form of NADPH as a substrate for ROS generation. In this work, TKT was selected as a lead candidate from 24 NET-associated proteins obtained by literature screening and knowledge gap assessment. Consequently, we determined whether TKT influenced NET formation in vitro. We firstly established that the release of ROS-dependent NETs was significantly decreased after purified human PMNs were pretreated with oxythiamine, a TKT inhibitor, and in a concentration dependent manner. As a cofactor for TKT reaction, we evaluated the release of NET formation either in vitamin B1 treatment or in combined use of oxythiamine and vitamin B1, and found that those treatments also exerted a significant suppressive effect on the amount of NET-DNA and ROS production. The regulation of TKT by oxythiamine and/or vitamin B1 may therefore be associated with response to the modulation of NET formation by preventing generation of excessive NETs in inflammatory diseases.
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[Increasing lactate levels during treatment of diabetic ketoacidosis]. Med Klin Intensivmed Notfmed 2019; 115:417-419. [PMID: 30918984 DOI: 10.1007/s00063-019-0562-y] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/07/2018] [Revised: 02/14/2019] [Accepted: 03/18/2019] [Indexed: 10/27/2022]
Abstract
A young woman with type 1 diabetes mellitus and severe diabetic ketoacidosis was treated in an intensive care unit according to the guidelines. Only a few hours after starting the therapy, rising lactate values were diagnosed in the arterial blood gas analysis. Since there were no indications for other reasons of lactatemia, an acute refeeding syndrome caused by the insulin therapy was suspected. Thiamine and phosphate were thus replaced. With this treatment, lactate values fell, supporting the hypothesis of lactatemia due to substrate deficiency.
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Cinici E, Mammadov R, Findik H, Suleyman B, Cetin N, Calik I, Balta H, Hakki Tas I, Sener E, Altuner D. The Protective Effect of Thiamine Pryophosphate Against Sugar-Induced Retinal Neovascularisation in Rats. INT J VITAM NUTR RES 2019; 88:137-143. [PMID: 31165688 DOI: 10.1024/0300-9831/a000248] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/17/2023]
Abstract
The aim of this study was to investigate the effect of thiamine pyrophosphate (TPP), administered via sugar water, on retinal neovascularisation in rats. Animals were assigned to three groups, namely the TPP sugar-water group (TPSWG, n = 12), the control group (CG, n = 12) and the healthy group (HG, n = 12). The TPSWG was injected intraperitoneally with TPP once a day for 6 months. CG and HG rats were given distilled water in the same way. TPSWG and CG rats were left free to access an additional 0.292 mmol /ml of sugar water for 6 months. The fasting blood glucose (FBG) levels of the animals were measured monthly. After 6 months, biochemical, gene expression and histopathologic analyses were carried out in the retinal tissues removed from the animals after they were killed. The measured FBG levels were 6.96 ± 0.09 mmol/ml (p < 0.0001 vs. HG), 6.95 ± 0.06 mmol/ml (p < 0.0001 vs. HG) and 3.94 ± 0.10 mmol/ml in the CG, TPSWG and HG groups, respectively. The malondialdehyde (MDA) levels were found to be 2.82 ± 0.23 (p < 0.0001 vs. HG), 1.40 ± 0.32 (p < 0.0001 vs. HG) and 1.66 ± 0.17 in the CG, TPSWG and HG, respectively. Interleukin 1 beta (IL-1β) gene expression was increased (3.78 ± 0.29, p < 0.0001) and total glutathione (tGSH) was decreased (1.32 ± 0.25, p < 0.0001) in the retinal tissue of CG compared with TPSWG (1.92 ± 0.29 and 3.18 ± 0.46, respectively). Increased vascularisation and oedema were observed in the retinal tissue of CG, while the retinal tissues of TPSWG and HG rats had a normal histopathological appearance. A carbohydrate-rich diet may lead to pathological changes in the retina even in nondiabetics, but this may be overcome by TPP administration.
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Affiliation(s)
- Emine Cinici
- 1 Department of Ophthalmology, Erzurum Region Education and Research Hospital, Erzurum, Turkey
| | - Renad Mammadov
- 2 Department of Pharmacology, Faculty of Medicine, Pharmacology Research Laboratory, Erzincan University, Erzincan, Turkey
| | - Huseyin Findik
- 3 Department of Ophthalmology, Faculty of Medicine, Recep Tayyip Erdogan University, Rize, Turkey
| | - Bahadir Suleyman
- 2 Department of Pharmacology, Faculty of Medicine, Pharmacology Research Laboratory, Erzincan University, Erzincan, Turkey
| | - Nihal Cetin
- 2 Department of Pharmacology, Faculty of Medicine, Pharmacology Research Laboratory, Erzincan University, Erzincan, Turkey
| | - Ilknur Calik
- 4 Department of Pathology, Erzurum Region Education and Research Hospital, Pathology Laboratory, Erzurum, Turkey
| | - Hilal Balta
- 4 Department of Pathology, Erzurum Region Education and Research Hospital, Pathology Laboratory, Erzurum, Turkey
| | - Ismail Hakki Tas
- 5 Department of Parasitology, Veterinary Faculty, Ataturk University, Erzurum, Turkey
| | - Ebru Sener
- 4 Department of Pathology, Erzurum Region Education and Research Hospital, Pathology Laboratory, Erzurum, Turkey
| | - Durdu Altuner
- 2 Department of Pharmacology, Faculty of Medicine, Pharmacology Research Laboratory, Erzincan University, Erzincan, Turkey
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Pham VM, Matsumura S, Katano T, Funatsu N, Ito S. Diabetic neuropathy research: from mouse models to targets for treatment. Neural Regen Res 2019; 14:1870-1879. [PMID: 31290436 PMCID: PMC6676867 DOI: 10.4103/1673-5374.259603] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/11/2023] Open
Abstract
Diabetic neuropathy is one of the most serious complications of diabetes, and its increase shows no sign of stopping. Furthermore, current clinical treatments do not yet approach the best effectiveness. Thus, the development of better strategies for treating diabetic neuropathy is an urgent matter. In this review, we first discuss the advantages and disadvantages of some major mouse models of diabetic neuropathy and then address the targets for mechanism-based treatment that have been studied. We also introduce our studies on each part. Using stem cells as a source of neurotrophic factors to target extrinsic factors of diabetic neuropathy, we found that they present a promising treatment.
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Affiliation(s)
- Vuong M Pham
- Department of Medical Chemistry, Kansai Medical University, Hirakata, Osaka, Japan; Singapore Institute for Neurotechnology (SINAPSE), National University of Singapore, Singapore
| | - Shinji Matsumura
- Department of Medical Chemistry, Kansai Medical University, Hirakata, Osaka, Japan
| | - Tayo Katano
- Department of Medical Chemistry, Kansai Medical University, Hirakata, Osaka, Japan
| | - Nobuo Funatsu
- Department of Medical Chemistry, Kansai Medical University, Hirakata, Osaka, Japan
| | - Seiji Ito
- Department of Medical Chemistry, Kansai Medical University, Hirakata; Department of Anesthesiology, Osaka Medical College, Takatsuki, Osaka, Japan
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Karkabounas S, Papadopoulos N, Anastasiadou C, Gubili C, Peschos D, Daskalou T, Fikioris N, Simos YV, Kontargiris E, Gianakopoulos X, Ragos V, Chatzidimitriou M. Effects of α-Lipoic Acid, Carnosine, and Thiamine Supplementation in Obese Patients with Type 2 Diabetes Mellitus: A Randomized, Double-Blind Study. J Med Food 2018; 21:1197-1203. [PMID: 30311825 DOI: 10.1089/jmf.2018.0007] [Citation(s) in RCA: 27] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/03/2023] Open
Abstract
Type 2 diabetes mellitus (T2DM) is evolving to an epidemic of the modern world. T2DM is associated with a number of pathological complications, including cardiovascular disease that is mostly promoted by the increased oxidative stress in type 2 diabetic patients. We performed a randomized double-blind placebo-controlled trial to investigate the effectiveness of an individualized oral supplementation with α-lipoic acid (ALA), carnosine, and thiamine. For that purpose, 82 obese type 2 diabetic patients were randomly assigned to 2 groups, and were either supplemented daily with 7 mg ALA/kg body weight, 6 mg carnosine/kg body weight, and 1 mg thiamine/kg body weight or placebo for 8 weeks. An array of biochemical tests including the estimation of oxidative stress and platelet aggregation were performed at baseline and at follow-up. Moreover, the antiplatelet activity of each of the supplement's components was determined ex vivo at human and washed rabbit platelets. Glucose and HbA1c levels were significantly reduced after supplementation (135.7 ± 19.5 mg/dL vs. 126.5 ± 16.8 mg/dL and 8.3% ± 0.3% vs. 6.03% ± 0.58%, respectively, P < .05); however, insulin was significantly increased (3.6 ± 0.7 μIU/mL vs. 6.8 ± 0.2 μIU/mL, P < .05). The patients treated with the supplement recorded higher follow-up values for HOMA-IR and HOMA-β, and a significant drop in serum hydroperoxide level. Only ALA inhibited platelets aggregation ex vivo through ADP, platelet activating factor, arachidonic acid, epinephrine, collagen, and thrombin pathways. Daily supplementation with an individualized ALA, carnosine, and thiamine supplement effectively reduced glucose concentration in type 2 diabetic patients, probably by increasing insulin production from the pancreas. In addition to that, the reduction of oxidative stress and inhibition of platelet aggregation could potentially provide greater cardiovascular protection. Further studies are needed to fine-tune the supplementation dose-response effects in T2DM patients.
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Affiliation(s)
- Spyridon Karkabounas
- 1 Department of Physiology, Faculty of Medicine, School of Health Sciences; Medical Department; University of Ioannina , Ioannina, Greece
| | - Nikolaos Papadopoulos
- 1 Department of Physiology, Faculty of Medicine, School of Health Sciences; Medical Department; University of Ioannina , Ioannina, Greece
| | - Chryssa Anastasiadou
- 2 Hellenic Agricultural Organization, Fisheries Research Institute , Kavala, Greece
| | - Chrysoula Gubili
- 2 Hellenic Agricultural Organization, Fisheries Research Institute , Kavala, Greece
| | - Dimitrios Peschos
- 1 Department of Physiology, Faculty of Medicine, School of Health Sciences; Medical Department; University of Ioannina , Ioannina, Greece
| | | | - Nikolaos Fikioris
- 1 Department of Physiology, Faculty of Medicine, School of Health Sciences; Medical Department; University of Ioannina , Ioannina, Greece
| | - Yannis V Simos
- 1 Department of Physiology, Faculty of Medicine, School of Health Sciences; Medical Department; University of Ioannina , Ioannina, Greece
| | - Evangelos Kontargiris
- 1 Department of Physiology, Faculty of Medicine, School of Health Sciences; Medical Department; University of Ioannina , Ioannina, Greece .,4 Department of Nursing, Epirus Institute of Technology (T.E.I. of Epirus) , Ioannina, Greece
| | | | - Vasilios Ragos
- 6 Clinic of Maxillofacial Surgery, Medical Department; University of Ioannina , Ioannina, Greece
| | - Maria Chatzidimitriou
- 7 Medical Laboratories, Alexander Technological Institute of Thessaloniki , Thessaloniki, Greece
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Chen JH, Lin X, Bu C, Zhang X. Role of advanced glycation end products in mobility and considerations in possible dietary and nutritional intervention strategies. Nutr Metab (Lond) 2018; 15:72. [PMID: 30337945 PMCID: PMC6180645 DOI: 10.1186/s12986-018-0306-7] [Citation(s) in RCA: 119] [Impact Index Per Article: 17.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/22/2018] [Accepted: 09/21/2018] [Indexed: 02/08/2023] Open
Abstract
Advanced glycation end products (AGEs), a group of compounds that are formed by non-enzymatic reactions between carbonyl groups of reducing sugars and free amino groups of proteins, lipids or nucleic acids, can be obtained exogenously from diet or formed endogenously within the body. AGEs accumulate intracellularly and extracellularly in all tissues and body fluids and can cross-link with other proteins and thus affect their normal functions. Furthermore, AGEs can interact with specific cell surface receptors and hence alter cell intracellular signaling, gene expression, the production of reactive oxygen species and the activation of several inflammatory pathways. High levels of AGEs in diet as well as in tissues and the circulation are pathogenic to a wide range of diseases. With respect to mobility, AGEs accumulate in bones, joints and skeletal muscles, playing important roles in the development of osteoporosis, osteoarthritis, and sarcopenia with aging. This report covered the related pathological mechanisms and the potential pharmaceutical and dietary intervention strategies in reducing systemic AGEs. More prospective studies are needed to determine whether elevated serum AGEs and/or skin autofluorescence predict a decline in measures of mobility. In addition, human intervention studies are required to investigate the beneficial effects of exogenous AGEs inhibitors on mobility outcomes.
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Affiliation(s)
- Jie-Hua Chen
- Science and Technology Centre, By-Health Co. Ltd, No. 3 Kehui 3rd Street, No. 99 Kexue Avenue Central, Science City, Luogang District, Guangzhou, 510000 China
| | - Xu Lin
- CAS Key Laboratory of Nutrition, Metabolism and Food Safety, Shanghai Institute of Nutrition and Health, Shanghai Institutes for Biological Sciences, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, 200031 China
| | - Cuihong Bu
- Science and Technology Centre, By-Health Co. Ltd, No. 3 Kehui 3rd Street, No. 99 Kexue Avenue Central, Science City, Luogang District, Guangzhou, 510000 China
| | - Xuguang Zhang
- Science and Technology Centre, By-Health Co. Ltd, No. 3 Kehui 3rd Street, No. 99 Kexue Avenue Central, Science City, Luogang District, Guangzhou, 510000 China
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Dewanjee S, Das S, Das AK, Bhattacharjee N, Dihingia A, Dua TK, Kalita J, Manna P. Molecular mechanism of diabetic neuropathy and its pharmacotherapeutic targets. Eur J Pharmacol 2018; 833:472-523. [DOI: 10.1016/j.ejphar.2018.06.034] [Citation(s) in RCA: 175] [Impact Index Per Article: 25.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/27/2017] [Revised: 06/15/2018] [Accepted: 06/26/2018] [Indexed: 02/07/2023]
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PET Imaging Analysis of Vitamin B1 Kinetics with [11C]Thiamine and its Derivative [11C]Thiamine Tetrahydrofurfuryl Disulfide in Rats. Mol Imaging Biol 2018; 20:1001-1007. [DOI: 10.1007/s11307-018-1186-y] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/17/2022]
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Gao Y, Wei Y, Wang Y, Gao F, Chen Z. Lycium Barbarum: A Traditional Chinese Herb and A Promising Anti-Aging Agent. Aging Dis 2017; 8:778-791. [PMID: 29344416 PMCID: PMC5758351 DOI: 10.14336/ad.2017.0725] [Citation(s) in RCA: 130] [Impact Index Per Article: 16.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/17/2016] [Accepted: 07/25/2017] [Indexed: 12/16/2022] Open
Abstract
Lycium barbarum has been used in China for more than 2,000 years as a traditional medicinal herb and food supplement. Lycium barbarum contains abundant Lycium barbarum polysaccharides (LBPs), betaine, phenolics, carotenoids (zeaxanthin and β-carotene), cerebroside, 2-O-β-d-glucopyranosyl-l-ascorbic acid (AA-2βG), β-sitosterol, flavonoids and vitamins (in particular, riboflavin, thiamine, and ascorbic acid). LBPs are the primary active components of Lycium barbarum. In this review, we discuss the pharmacological activities of LBPs and other major components. They have been reported to mediate significant anti-aging effects, through antioxidant, immunoregulative, anti-apoptotic activities and reducing DNA damage. Thus, the basic scientific evidence for anti-aging effects of LBPs is already available. However, additional studies are needed to understand mechanisms by which LBPs mediate anti-aging properties. Novel findings from such studies would likely pave the way for the clinical application of traditional chinese medicine Lycium barbarum in modern evidence-based medicine.
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Affiliation(s)
- Yanjie Gao
- Dongfang Hospital, Beijing University of Chinese Medicine, Beijing. China. 100078
| | - Yifo Wei
- Dongfang Hospital, Beijing University of Chinese Medicine, Beijing. China. 100078
| | - Yuqing Wang
- Dongfang Hospital, Beijing University of Chinese Medicine, Beijing. China. 100078
| | - Fang Gao
- Dongfang Hospital, Beijing University of Chinese Medicine, Beijing. China. 100078
| | - Zhigang Chen
- Dongfang Hospital, Beijing University of Chinese Medicine, Beijing. China. 100078
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Solvation behavior and sweetness response of carbohydrates, their derivatives and sugar alcohols in thiamine HCl (vitamin B1) and pyridoxine HCl (vitamin B6) at different temperatures. Food Chem 2017; 237:181-190. [DOI: 10.1016/j.foodchem.2017.05.078] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/04/2017] [Revised: 05/16/2017] [Accepted: 05/16/2017] [Indexed: 02/04/2023]
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41
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Sadowska-Bartosz I, Bartosz G. Effect of glycation inhibitors on aging and age-related diseases. Mech Ageing Dev 2016; 160:1-18. [PMID: 27671971 DOI: 10.1016/j.mad.2016.09.006] [Citation(s) in RCA: 30] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/21/2016] [Revised: 06/30/2016] [Accepted: 09/21/2016] [Indexed: 02/07/2023]
Abstract
Vast evidence supports the view that glycation of proteins is one of the main factors contributing to aging and is an important element of etiopathology of age-related diseases, especially type 2 diabetes mellitus, cataract and neurodegenerative diseases. Counteracting glycation can therefore be a means of increasing both the lifespan and healthspan. In this review, accumulation of glycation products during aging is presented, pathophysiological effects of glycation are discussed and ways of attenuation of the effects of glycation are described, concentrating on prevention of glycation. The effects of glycation and glycation inhibitors on the course of selected age-related diseases, such as Alzheimer's disease, Parkinson's disease and cataract are also reviewed.
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Affiliation(s)
- Izabela Sadowska-Bartosz
- Department of Biochemistry and Cell Biology, Faculty of Biology and Agriculture, University of Rzeszow, Zelwerowicza St. 4, 35-604 Rzeszów, Poland.
| | - Grzegorz Bartosz
- Department of Biochemistry and Cell Biology, Faculty of Biology and Agriculture, University of Rzeszow, Zelwerowicza St. 4, 35-604 Rzeszów, Poland; Department of Molecular Biophysics, Faculty of Biology and Environmental Protection, University of Lodz, 90-236 Lodz, Poland
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42
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The uremic toxin oxythiamine causes functional thiamine deficiency in end-stage renal disease by inhibiting transketolase activity. Kidney Int 2016; 90:396-403. [DOI: 10.1016/j.kint.2016.03.010] [Citation(s) in RCA: 35] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/13/2015] [Revised: 02/18/2016] [Accepted: 03/03/2016] [Indexed: 11/21/2022]
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43
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Khalil H, Chambers H, Khalil V, Ang CD. Vitamin B for treating diabetic peripheral neuropathy. Hippokratia 2016. [DOI: 10.1002/14651858.cd012237] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/11/2022]
Affiliation(s)
- Hanan Khalil
- School of Rural Health; Faculty of Medicine, Nursing and Health Sciences; PO Box 973 Moe Victoria Australia 3825
| | - Helen Chambers
- School of Rural Health; Faculty of Medicine, Nursing and Health Sciences; PO Box 973 Moe Victoria Australia 3825
| | - Viviane Khalil
- Peninsula Health; Pharmacy Department; 2 Hastings Rd Frankston Victoria Australia 3199
| | - Cynthia D Ang
- University of the Philippines - College of Medicine and Philippine General Hospital; Department of Rehabilitation Medicine; Taft Avenue Ermita Manila Philippines 1000
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Kuricova K, Pleskacova A, Pacal L, Kankova K. 1,25-Dihydroxyvitamin D increases the gene expression of enzymes protecting from glucolipotoxicity in peripheral blood mononuclear cells and human primary endothelial cells. Food Funct 2016; 7:2537-43. [PMID: 26952188 DOI: 10.1039/c5fo01560j] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/22/2022]
Abstract
Besides its classical function as an orchestrator of calcium and phosphorus homeostasis, vitamin D also affects insulin secretion and tissue efficiency. A number of studies have consistently reported the inverse relationship between vitamin D deficiency and type 2 diabetes. Activation of certain metabolic pathways and down-stream transcription factors may protect from glucolipotoxicity and their targeted activation -e.g. by vitamin D - might explain the detrimental role of vitamin D deficiency in diabetes. The aim of the study was to quantify gene and protein expression of selected enzymes involved in the protection from glucolipotoxicity, specifically glyoxalase 1 (GLO1), and other enzymes with antioxidant activity - hemoxygenase (HMOX), thiamin pyrophosphokinase (TPK1) and transketolase (TKT), under normo- and hyperglycemic conditions and upon addition of vitamin D in peripheral blood mononuclear cells (PBMCs) and human umbilical vein endothelial cells (HUVEC). The results of our study indicate that the active form of vitamin D regulates gene expression of enzymes opposing the harmful effect of glucolipotoxicity whose activities appear to be suppressed by hyperglycemia. However, we were unable to confirm this effect on protein expression. While we cannot speculate on the effect of vitamin D on diabetes itself our results support its role in the protection against existing glucolipotoxicity therefore possibly translating into the prevention of development of diabetic complications.
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Affiliation(s)
- Katarina Kuricova
- Department of Pathophysiology, Faculty of Medicine, Masaryk University, Brno, Czech Republic.
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Lipids and bariatric procedures Part 2 of 2: scientific statement from the American Society for Metabolic and Bariatric Surgery (ASMBS), the National Lipid Association (NLA), and Obesity Medicine Association (OMA) 1. Surg Obes Relat Dis 2016; 12:468-495. [DOI: 10.1016/j.soard.2016.01.007] [Citation(s) in RCA: 37] [Impact Index Per Article: 4.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/07/2016] [Accepted: 01/08/2016] [Indexed: 12/17/2022]
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46
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Harper RM, Kumar R, Macey PM, Harper RK, Ogren JA. Impaired neural structure and function contributing to autonomic symptoms in congenital central hypoventilation syndrome. Front Neurosci 2015; 9:415. [PMID: 26578872 PMCID: PMC4626648 DOI: 10.3389/fnins.2015.00415] [Citation(s) in RCA: 28] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/30/2015] [Accepted: 10/15/2015] [Indexed: 12/30/2022] Open
Abstract
Congenital central hypoventilation syndrome (CCHS) patients show major autonomic alterations in addition to their better-known breathing deficiencies. The processes underlying CCHS, mutations in the PHOX2B gene, target autonomic neuronal development, with frame shift extent contributing to symptom severity. Many autonomic characteristics, such as impaired pupillary constriction and poor temperature regulation, reflect parasympathetic alterations, and can include disturbed alimentary processes, with malabsorption and intestinal motility dyscontrol. The sympathetic nervous system changes can exert life-threatening outcomes, with dysregulation of sympathetic outflow leading to high blood pressure, time-altered and dampened heart rate and breathing responses to challenges, cardiac arrhythmia, profuse sweating, and poor fluid regulation. The central mechanisms contributing to failed autonomic processes are readily apparent from structural and functional magnetic resonance imaging studies, which reveal substantial cortical thinning, tissue injury, and disrupted functional responses in hypothalamic, hippocampal, posterior thalamic, and basal ganglia sites and their descending projections, as well as insular, cingulate, and medial frontal cortices, which influence subcortical autonomic structures. Midbrain structures are also compromised, including the raphe system and its projections to cerebellar and medullary sites, the locus coeruleus, and medullary reflex integrating sites, including the dorsal and ventrolateral medullary nuclei. The damage to rostral autonomic sites overlaps metabolic, affective and cognitive regulatory regions, leading to hormonal disruption, anxiety, depression, behavioral control, and sudden death concerns. The injuries suggest that interventions for mitigating hypoxic exposure and nutrient loss may provide cellular protection, in the same fashion as interventions in other conditions with similar malabsorption, fluid turnover, or hypoxic exposure.
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Affiliation(s)
- Ronald M Harper
- Brain Research Institute, University of California, Los Angeles Los Angeles, CA, USA ; Department of Neurobiology, David Geffen School of Medicine, University of California, Los Angeles Los Angeles, CA, USA
| | - Rajesh Kumar
- Brain Research Institute, University of California, Los Angeles Los Angeles, CA, USA ; Department of Anesthesiology, David Geffen School of Medicine, University of California, Los Angeles Los Angeles, CA, USA ; Department of Radiological Sciences, David Geffen School of Medicine, University of California, Los Angeles Los Angeles, CA, USA ; Department of Bioengineering, University of California, Los Angeles Los Angeles, CA, USA
| | - Paul M Macey
- Brain Research Institute, University of California, Los Angeles Los Angeles, CA, USA ; UCLA School of Nursing, University of California, Los Angeles Los Angeles, CA, USA
| | - Rebecca K Harper
- Department of Neurobiology, David Geffen School of Medicine, University of California, Los Angeles Los Angeles, CA, USA
| | - Jennifer A Ogren
- Department of Neurobiology, David Geffen School of Medicine, University of California, Los Angeles Los Angeles, CA, USA
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Alaei-Shahmiri F, Soares MJ, Zhao Y, Sherriff J. The impact of thiamine supplementation on blood pressure, serum lipids and C-reactive protein in individuals with hyperglycemia: a randomised, double-blind cross-over trial. Diabetes Metab Syndr 2015; 9:213-217. [PMID: 25982678 DOI: 10.1016/j.dsx.2015.04.014] [Citation(s) in RCA: 21] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/30/2023]
Abstract
BACKGROUND The adverse effects of hyperglycemia may be potentiated when it is accompanied with hypertension and dyslipidemia. This study assessed the effects of high dose thiamine on blood pressure, serum lipids and C-reactive protein (hs-CRP) in individuals with impaired glucose metabolism. METHODS This was a double-blind, randomised trial, where 12 hyperglycemic subjects (10 cases of impaired glucose tolerance and 2 new cases of type 2 diabetes mellitus) received both placebo and thiamine capsules (3 × 100 mg/day) for six weeks in a cross-over manner. Anthropometric measurements, systolic and diastolic blood pressure (SBP & DBP), serum cholesterol, triglyceride, HDL-cholesterol, LDL-cholesterol, hs-CRP and thiamine status were evaluated at the start, after three weeks and on the completion of each arm. RESULTS DBP was significantly decreased in participants consuming thiamine supplements for six weeks (67.9 ± 5.8 mm Hg) relative to baseline (71.4 ± 7.4 mm Hg, p=0.005) and week 3 (70.9. ± 5.8 mm Hg, p=0.02). This was accompanied with a tendency toward a lower SBP at week six relative to baseline (116.5 ± 11.0 vs. 120.7 ± 15.3 mm Hg, p=0.06). Also, mean arterial pressure (MAP) determined in the supplement arm after six weeks was significantly lower than baseline (84.1 ± 6.5 vs. 87.8 ± 9.0, p=0.005). These variables did not change in the placebo arm. No significant change was detected in the supplement or placebo arms when lipid profile and hs-CRP were assessed. CONCLUSION/INTERPRETATION High dose thiamine supplementation may have beneficial effects on the blood pressure of individuals with hyperglycemia at early stages, and may have a role in the prevention of further vascular complications. TRIAL REGISTRATION Australian New Zealand Clinical Trials Registry ACTRN12611000051943.
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Affiliation(s)
- F Alaei-Shahmiri
- Department of Nutrition, Dietetics and Food Technology, School of Public Health, Curtin University, Perth, Western Australia 6102.
| | - M J Soares
- Department of Nutrition, Dietetics and Food Technology, School of Public Health, Curtin University, Kent Street, Bentley, Perth, Western Australia, 6102, Australia
| | - Y Zhao
- Department of Nutrition, Dietetics and Food Technology, School of Public Health, Curtin University, Kent Street, Bentley, Perth, Western Australia, 6102, Australia
| | - J Sherriff
- Department of Nutrition, Dietetics and Food Technology, School of Public Health, Curtin University, Kent Street, Bentley, Perth, Western Australia, 6102, Australia
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Puts J, de Groot M, Haex M, Jakobs B. Simultaneous Determination of Underivatized Vitamin B1 and B6 in Whole Blood by Reversed Phase Ultra High Performance Liquid Chromatography Tandem Mass Spectrometry. PLoS One 2015; 10:e0132018. [PMID: 26134844 PMCID: PMC4489891 DOI: 10.1371/journal.pone.0132018] [Citation(s) in RCA: 32] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/06/2015] [Accepted: 06/09/2015] [Indexed: 11/18/2022] Open
Abstract
Background Vitamin B1 (thiamine-diphosphate) and B6 (pyridoxal-5’phosphate) are micronutrients. Analysis of these micronutrients is important to diagnose potential deficiency which often occurs in elderly people due to malnutrition, in severe alcoholism and in gastrointestinal compromise due to bypass surgery or disease. Existing High Performance Liquid Chromatography (HPLC) based methods include the need for derivatization and long analysis time. We developed an Ultra High Performance Liquid Chromatography Tandem Mass spectrometry (UHPLC-MS/MS) assay with internal standards for simultaneous measurement of underivatized thiamine-diphosphate and pyridoxal-5’phosphate without use of ion pairing reagent. Methods Whole blood, deproteinized with perchloric acid, containing deuterium labelled internal standards thiamine-diphosphate(thiazole-methyl-D3) and pyridoxal-5’phosphate(methyl-D3), was analyzed by UHPLC-MS/MS. The method was validated for imprecision, linearity, recovery and limit of quantification. Alternate (quantitative) method comparisons of the new versus currently used routine HPLC methods were established with Deming regression. Results Thiamine-diphosphate and pyridoxal-5’phosphate were measured within 2.5 minutes instrumental run time. Limits of detection were 2.8 nmol/L and 7.8 nmol/L for thiamine-diphosphate and pyridoxal-5’phosphate respectively. Limit of quantification was 9.4 nmol/L for thiamine-diphosphate and 25.9 nmol/L for pyridoxal-5’phosphate. The total imprecision ranged from 3.5–7.7% for thiamine-diphosphate (44–157 nmol/L) and 6.0–10.4% for pyridoxal-5’phosphate (30–130 nmol/L). Extraction recoveries were 101–102% ± 2.5% (thiamine-diphosphate) and 98–100% ± 5% (pyridoxal-5’phosphate). Deming regression yielded slopes of 0.926 and 0.990 in patient samples (n = 282) and national proficiency testing samples (n = 12) respectively, intercepts of +3.5 and +3 for thiamine-diphosphate (n = 282 and n = 12) and slopes of 1.04 and 0.84, intercepts of -2.9 and +20 for pyridoxal-5’phosphate (n = 376 and n = 12). Conclusion The described UHPLC-MS/MS method allows simultaneous determination of underivatized thiamine-diphosphate and pyridoxal-5’phosphate in whole blood without intensive sample preparation.
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Affiliation(s)
- Johan Puts
- Department of Clinical Chemistry and Haematology, Elisabeth-TweeSteden Hospital, Tilburg, The Netherlands
| | - Monique de Groot
- Department of Clinical Chemistry and Haematology, Elisabeth-TweeSteden Hospital, Tilburg, The Netherlands
| | - Martin Haex
- Life Science group, Agilent Technologies, Amstelveen, The Netherlands
| | - Bernadette Jakobs
- Department of Clinical Chemistry and Haematology, Elisabeth-TweeSteden Hospital, Tilburg, The Netherlands
- * E-mail:
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Abstract
Patients suffering from DN (diabetic neuropathy) suffer from the coexistence of positive (i.e. pain, hypersensitivity, tingling, cramps, cold feet, etc.) and negative (i.e. loss of sensory perception, delayed wound healing, etc.) symptoms. Elevated blood glucose alone cannot explain the development and progression of DN. Recently it has been shown that the endogenous reactive metabolite MG (methylglyoxal), elevated as a consequence of reduced Glo1 (glyoxalase I), can contribute to the gain of function via post-translational modification of neuronal ion channels involved in chemosensing and action potential generation in nociceptive nerve endings. The effects of dicarbonyls on the neuronal compartment provides a unifying mechanism for the development of DN. Targeting the accumulation and effects of MG may therefore provide new, more effective, therapeutic approaches for the treatment of DN.
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50
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Abstract
OBJECTIVE Thiamine deficiency has been documented in adults with diabetes and in a single report of reversible encephalopathy in a child with diabetic ketoacidosis. In children who present with severe diabetic ketoacidosis, one of the most serious complications is cerebral edema of which the primary symptom may be encephalopathy. Thiamine deficiency in other disease states has been clearly linked with acute encephalopathy, but there are no data on thiamine status in children with diabetic ketoacidosis. This study describes the prevalence of thiamine deficiency in children with type 1 diabetes mellitus who present with diabetic ketoacidosis and are admitted to the ICU. DESIGN A prospective observational pilot study. SETTING PICU in a tertiary care children's hospital. PATIENTS Children 2-18 years admitted to the ICU for treatment of diabetic ketoacidosis. INTERVENTIONS Treatment of diabetic ketoacidosis. MEASUREMENTS AND MAIN RESULTS Twenty-two patients were enrolled. The mean age was 13.7 ± 3.6 years. Five of 21 patients (23.8%) had thiamine deficiency prior to insulin administration. After 8 hours of insulin therapy, seven of 20 patients (35%) had thiamine deficiency, and four of these seven patients also had thiamine deficiency at presentation. Sixty-eight percent of patients had a decrease in thiamine levels after 8 hours of insulin therapy, with a mean fall of 20 ± 31.4 nmol/L. CONCLUSIONS Thiamine deficiency is common in children with diabetic ketoacidosis, and this deficiency may be worsened by treatment. When metabolic acidosis persists despite appropriate treatment of diabetic ketoacidosis, other factors such as thiamine deficiency should be considered.
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