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Benfotiamine supplementation prevents oxidative stress in anterior tibialis muscle and heart

Journal of Integrative Medicine 2019年第6期17卷 423-429页

作者： Alisson de Carvalho Goncalves Einy Jéssika Siqueira Moreira Guilherme Vannucchi Portari Laboratory of Experimental Nutrition Health Sciences InstituteFederal University of Triangulo MineiroUberabaMG 38025-440Brazil Department of Nutrition Health Sciences InstituteFederal University of Triangulo MineiroUberabaMG 38025-440Brazil

Objective: This study aimed to evaluate the influence of oral supplementation with benfotiamine on oxidative stress in the liver, heart and muscles of endurance-trained mice.Methods: Twenty-five male BALB/c mice were allocated to the following treatment groups: standard diet and sedentary activity(Sta–Sed), benfotiamine–supplemented diet and sedentary activity(Ben–Sed),standard diet and training activity(Sta–Tr) and benfotiamine–supplemented diet and training activity(Ben–Tr). The training comprised 6 weeks of endurance swimming training. The concentration of thiobarbituric acid reactive substances(TBARS), carbonylated proteins, total thiols and non-protein thiols was analyzed in the liver, heart and tibialis anterior muscle.Results: In the muscle, TBARS concentration in the Sta–Sed group was higher than that in other groups;in the heart, TBARS concentration in the Sta–Sed and Ben–Tr groups was higher than that in the Ben–Sed group. The carbonyl content of the muscle tissues was higher in the Sta–Sed group than in both supplemented groups. In liver, the carbonyl content was lower in the Ben–Sed group than in the Sta–Sed group.The level of total thiols was lower in the Ben–Sed group than in the Sta–Tr group. In the heart, the level of total thiols was higher in the Ben–Sed group than in the Ben–Tr group. The concentration of non-protein thiols in the muscle was higher in the Ben–Sed group than in the Ben–Tr group, whereas in the heart, concentration of non-protein thiols of Sta–Tr group was lower than that of Sta–Sed group.Conclusion: The results show that benfotiamine is an efficient antioxidant for the anterior tibialis muscle and heart;however, swimming training did not alter redox status.

关键词： Benfotiamine thiamine Endurance exercise Oxidative stress Vitamins

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Case Report:Wernicke encephalopathy following splenectomy in a patient with liver cirrhosis:a case report and review of the literature

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Journal of Zhejiang University-Science B(Biomedicine & Biotechnology) 2010年第6期11卷 433-436页

作者： Xia-ping ZHANG Yuan-qiang LU Wei-dong HUANG Department of Emergency the First Affiliated HospitalSchool of MedicineZhejiang UniversityHangzhou 310003China

Objective:To report a case of Wernicke encephalopathy in the early stage after surgery.Methods:A nonalcoholic female patient with hepatitis B-related cirrhosis and hypersplenism underwent splenectomy in a local hospital.No surgical complications occurred and the patient recovered well.However,on the eighth postoperative day she developed psychiatric and neurological disturbance without an obvious cause.She was then admitted to our hospital.Brain magnetic resonance imaging(MRI) with FLAIR T2 showed symmetric high-signal intensities in the periaqueductal area of the midbrain,which were consistent with Wernicke encephalopathy.She was thus given in-tramuscular thiamine immediately.Results:After the administration of thiamine,the patient's confused mental state resolved within 3 d,and her dystaxia gradually improved over the next 5 d.The brain MRI with FLAIR T2 was re-examined one month after the episode,and showed nearly complete resolution of the previously abnormal signal intensities in the periaqueductal area of the midbrain.Conclusion:Physicians should be aware of the possibility of acute Wernicke encephalopathy,especially in patients with liver dysfunction.

关键词：关键词 Wernicke encephalopathy 肝肝硬化 thiamine 脾切除术

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Wernicke encephalopathy in children and adolescents

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World Journal of Pediatrics 2014年第4期10卷 293-298页

作者： Matt Lallas Jay Desai Division of Neurology Children's Hospital Los AngelesCaliforniaUSA Keck School of Medicine of University of Southern California CaliforniaUSA

Background:Wernicke encephalopathy is caused by thiamine(vitamin B1)defi ciency.It is generally considered to be a disease of adult alcoholics.However,it is known to occur in the pediatric population and in non-alcoholic conditions.Data sources:We searched PubMed with the key words Wernicke,thiamine,pediatric,children and adolescents and selected publications that were deemed appropriate.Results:The global prevalence rates of hunger,poverty and resultant nutrient deprivation have decreased in the 21st century.However,several scenarios which may predispose to Wernicke encephalopathy may be increasingly prevalent in children and adolescents such as malignancies,intensive care unit stays and surgical procedures for the treatment of obesity.Other predisposing conditions include magnesium defi ciency and defects in the SLC19A3 gene causing thiamine transporter-2 deficiency.The classic triad consists of encephalopathy,oculomotor dysfunction and gait ataxia but is not seen in a majority of patients.Treatment should be instituted immediately when the diagnosis is suspected clinically without waiting for laboratory confi rmation.Common magnetic resonance findings include symmetric T2 hyperintensities in dorsal medial thalamus,mammillary bodies,periaqueductal gray matter,and tectal plate.Conclusions:Wernicke encephalopathy is a medical emergency.Delay in its recognition and treatment may lead to significant morbidity,irreversible neurological damage or even death.This article aims to raise the awareness of this condition among pediatricians.

关键词： ataxia ophthalmoplegia thiamine vitamin B1 Wernicke encephalopathy

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Amprolium exposure alters mice behavior and metabolism in vivo

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Animal Models and Experimental Medicine 2018年第4期1卷 272-281页

作者： Juliana Oliveira Moraes Samara Dias Cardoso Rodrigues Leidiano Martins Pereira Rita de Cássia Noronha Medeiros Clarissa Amorim Silva de Cordova Fabiano Mendes de Cordova Programa de Pós-Gradua??o em Sanidade Animal e Saúde Pública nos Trópicos Universidade Federal do Tocantins Curso de Medicina Veterinária Universidade Federal do Tocantins Curso de Medicina Universidade Federal do Tocantins

Background: thiamine deficiency(TD) models have been developed, mainly using the thiamine analog pyrithiamine. Other analogs have not been used in rodents. We aimed to evaluate the effects and mechanisms of intraperitoneal(ip) amprolium-induced TD in mice. We also evaluated the associated pathogenesis using antioxidant and anti-inflammatory compounds(Trolox, dimethyl sulfoxide).Methods: Male mice were separated into two groups, one receiving a standard diet(control animals), and the other a TD diet(deficient groups) for 20 days. Control mice were further subdivided into three groups receiving daily ip injections of saline(NaCl0.9%; Cont group), Tolox(Tr group) or dimethyl sulfoxide(DMSO; Dmso group). The three TD groups received amprolium(Amp group), amprolium and Trolox(Amp+Tr group), or amprolium and DMSO(Amp+Dmso group). The animals were subjected to behavioral tests and then euthanized. The brain and viscera were analyzed.Results: Amprolium exposure induced weight loss with hyporexia, reduced the behavioral parameters(locomotion, exploratory activity, and motor coordination), and induced changes in the brain(lower cortical cell viability) and liver(steatosis). Trolox co-treatment partially improved these conditions, but to a lesser extent than DMSO.Conclusions: Amprolium-induced TD may be an interesting model, allowing the deficiency to develop more slowly and to a lesser extent. Amprolium exposure also seems to involve oxidative stress and inflammation, suggested as the main mechanisms of cell dysfunction in TD.

关键词： brain dimethyl sulfoxide thiamine deficiency Trolox

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Evidence for altered thiamine metabolism in diabetes: Is there a potential to oppose gluco- and lipotoxicity by rational supplementation?

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World Journal of Diabetes 2014年第3期5卷 288-295页

作者： Luká? Pácal Katarína Kuricová Katerina Kaňková Department of Pathophysiology Faculty of MedicineMasaryk University

Growing prevalence of diabetes(type 2 as well as type 1) and its related morbidity due to vascular complications creates a large burden on medical care worldwide. Understanding the molecular pathogenesis of chronic micro-, macro- and avascular complications mediated by hyperglycemia is of crucial importance since novel therapeutic targets can be identified and tested. thiamine(vitamin B1) is an essential cofactor of several enzymes involved in carbohydrate metabolism and published data suggest that thiamine metabolism in diabetes is deficient. This review aims to point out the physiological role of thiamine in metabolism of glucose and amino acids, to present overview of thiamine metabolism and to describe the consequences of thiamine deficiency(either clinically manifest or latent). Furthermore, we want to explain why thiamine demands are increased in diabetes and to summarise data indicating thiamine mishandling in diabetics(by review of the studies mapping the prevalence and the degree ofthiamine deficiency in diabetics). Finally, we would like to summarise the evidence for the beneficial effect of thiamine supplementation in progression of hyperglycemia-related pathology and, therefore, to justify its importance in determining the harmful impact of hyperglycemia in diabetes. Based on the data presented it could be concluded that although experimental studies mostly resulted in beneficial effects, clinical studies of appropriate size and duration focusing on the effect of thiamine supplementation/therapy on hard endpoints are missing at present. Moreover, it is not currently clear which mechanisms contribute to the deficient action of thiamine in diabetes most. Experimental studies on the molecular mechanisms of thiamine deficiency in diabetes are critically needed before clear answer to diabetes community could be given.

关键词： Diabetes thiamine Vitamin B1 Transketolase Benfotiamine Hyperglycemia Nephropathy Metabolic syndrome Cardiovascular disease Chronic kidney disease

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Shoshin syndrome: report of a treatable disaster

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Journal of Acute Disease 2019年第2期8卷 78-81页

作者： Tommaso Valobra Umberto Ceratti Alessandra Cernuschi Medical High Dependency Unit Department of MedicineOspedale Niguarda Ca'GrandaMilanoItaly

Shoshin syndrome is a rare fulminating heart failure caused by thiamine deficiency. In Japanese 'sho' means acute damage and 'shin' means heart. It consists of a rare and hyperacute manifestation of beriberi that was first described in polished white rice-eating communities in various locations across Asia including China, Japan and Indonesia. In a totally different context, ‘Shoshin’ is a word from Zen Buddhism meaning 'beginner's mind', which is considered the necessary attitude to approach the Zen practice. This case report is a prime example of clinical manifestations of thiamine deficiency for the presence of both cardiological and neurological disorders, for hyperacute onset of cardiac failure (shoshin syndrome), for the simultaneous involvement of peripheral and central nervous system, and for the dramatic global recovery after thiamine replacement therapy. We therefore explain why the physician should adopt a beginner’s mind in clinical practice.

关键词： thiamine Shoshin Beriberi Wernike Alcoholic

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Impact of Low Back Pain on Quality of Life: Assessment by Patient Functionality Questionnaire and Treatment Results Using a Combination of Diclofenac plus B Vitamins or Diclofenac Monotherapy

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International Journal of Clinical Medicine 2016年第2期7卷 113-119页

作者： Mauro Geller Marco Antonio Mibielli Carlos Pereira Nunes Adenilson de Souza da Fonseca Stephanie Wrobel Goldberg Lisa Oliveira Teresópolis Medical School UNIFESO Rio de Janeiro Brazil Washington University School of Medicine St. Louis MO USA

Objective: To analyze the Patient Functionality Questionnaire (PFQ) scores of the patients treated with either Diclofenac + B vitamins (Group DB) or Diclofenac monotherapy (Group D) in order to better understand the impact of the combination of diclofenac with vitamins B1, B6, and B12 on quality of life. Research Design/Methods: We performed a post-hoc analysis of tabulated data generated during the DOLOR study (Diclofenac plus B vitamins versus diclofenac monotherapy in lumbago: the DOLOR study), using the software GraphPad Prism 5 for Windows, v5.04. The absolute number or percentage of “True”/“False” respondents for each questionnaire item at each study visit, together with the absolute number and percentage of subjects with no change, improvement, or worsening of each PFQ item at each study visit, within and between treatment groups were arranged on contingency tables and analyzed with the Chi-squared or Fisher’s Exact test. Results: At pretreatment there were no statistically significant differences between treatment groups (p > 0.05 for all items). At Visit 2 in both treatment groups, there were statistically significant improvements in individual question responses in each of the 12 items of the questionnaire (p < 0.05 for all items). At Visit 2, comparing the distribution of patients in each treatment group with “improvement”, “no change”, or “worsening”, there was a statistically significant superiority among subjects of group DB in response to items 1, 6, 8, and 10. At Visit 3, both groups had statistically significant (p < 0.001) improvements in each individual item of the PFQ in relation to pretreatment values. The distribution of subjects in each treatment group presenting with “improvement”, “no change”, or “worsening” at Visit 3 varied significantly in favor of group DB in the responses to item 4. At Visit 4, the subjects remaining in treatment in both groups showed statistically significant improvement in PFQ responses in relation to pretreatment values (p < 0.05).

关键词： Low Back Pain Quality Of Life Diclofenac thiamine Pyridoxine Cyanocobalamin

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Activation of PKR by Mild Impairment of Oxidative Metabolism in Neurons

Activation of PKR by Mild Impairment of Oxidative Metabolism...

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中国神经科学学会第四次会员代表大会暨第七届全国学术会议

作者： Xin WANG,Zhiqin FAN,Bingwei WANG,Jia LUO,Zun-Ji KE Institute for Nutritional Sciences,Shanghai Institute of Biological Sciences,Chinese Academy of Sciences,Shanghai 200031,China

＜正＞thiamine（vitamin B1） deficiency（TD） causes mild and chronic impairment of oxidative metabolism and induces neuronal death in specific brain regions.The mechanisms underlying TD-induced cell death,however,remain unclear. The double-stranded RNA（dsRNA）-activated protein kinase（PKR） has been well known for its anti-viral function.Upon activation by viral infection or dsRNA,PKR phosphorylates its substrate,theα-subunit of eukaryotic translation factor- 2（eIF2α）,leading to inhibition of translation.In response to various cellular stresses,PKR can also be stimulated by its protein activators,PACT,or its mouse homologue RAX.We demonstrated that TD in mice induced phosphorylation of PKR at Thr446 and Thr451 and phosphorylation of eIF2αat Ser51 in the cerebellum and the thalamus.TD caused phosphorylation of PKR and eIF2αas well as nuclear translocation of PKR in primary cultures of cerebellar granule neurons（CGNs）.PKR phosphorylation is necessary for its nuclear translocation because TD failed to induce nuclear translocation of a T446A/T451A PKR mutant.Both PKR inhibitor and dominant-negative PKR mutant protected CGNs against TD-induced cell death.TD promoted the association between RAX and PKR.Antioxidant vitamin E dramatically decreased the RAX/PKR association and ameliorated TD-induced cell death.Our results indicate that TD-induced neuronal death is at least partially mediated by the activation of PKR.

关键词： oxidative metabolism neurodegeneration PKR neuron thiamine

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Studies on synthesis and metabolic kinetics of a novel PET tracer [18F]-fluorothiamine

Studies on synthesis and metabolic kinetics of a novel PET t...

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中国神经科学学会第十二届全国学术会议

作者： Changpeng Wang Xiaoli Pan Shaoming Sang Chunjiu Zhong Department of Neurology Zhongshan Hospital

Objective: To date, we still lack of effective diagnostic biomarkers or tools for reflecting the progression and prognosis of Alzheimer’s disease(AD). However, one of the invariant pathophysiological characteristics of AD is the decrease of cerebral glucose metabolism, which employ the active form of thiamine—thiamine diphosphate—as the common coenzyme for three key enzymes. Based on large samples research, we established a novel diagnostic method for AD by means of measuring thiamine levels in periphery whole blood, with sensitivity and specificity high up to 80.2% and 87.2%, respectively. Further, we hypothesize that measuring directly thiamine metabolism within brain may possess huger diagnostic value than measuring cerebral glucose metabolism or thiamine metabolism in periphery blood. In this study, we synthesized a novel PET radiotracer——F labeled thiamine(F-thiamine), and shed light on its preliminary pharmacokinetics characteristics. Methods: Tow-step synthesis method was employed to synthesize F-thiamine. After two SN2 type reactions and the subsequent prep-HPLC separation, we synthesized final product successfully and established automated synthesis. Then, 5 ICR male mice were applied on micro PET/CT for 60 min taking F-thiamine as a radiotracer. The uptake value(ID%/g) of left ventricle(LV) ROI was employed to depict basic parameters of pharmacokinetics. The TAC of the same ROI of LV was used as input function of Patlak and Logan plots to study transfer constant(Ki) of whole brain and distribution volume(VD) of liver and kidney. We also analyzed the correlation between AUC(area under curve) values of mice brain and levels of thiamine as well as its phosphate esters in whole blood. After scanning completed and mice awaked from anesthesia, we acquired their urine to analyze the stabilization of F-thiamine and took the result as an indicator to determine whether thiamine had other metabolic pathways in vivo other than phosphorylation. We observed the brain uptake differences of F-thiamine between thiamine

关键词： Alzheimer’s disease thiamine thiamine diphosphate 18F-thiamine Pharmacokinetics

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