Showing papers on "Thiamine published in 2008"

Rapid HPLC Measurement of Thiamine and Its Phosphate Esters in Whole Blood

Abstract: Background: Thiamine (vitamin B1) deficiency is associated with severe diseases such as beriberi and Wernicke encephalopathy. Although most Americans have sufficient dietary intake, thiamine deficiency is observed in the alcohol-dependent and elderly populations. Measurement of thiamine concentration in whole blood provides an assessment of vitamin B1 status in at-risk individuals. Method: We used TCA to precipitate proteins in whole blood. Thiamine and its phosphate esters were derivatized using potassium ferricyanide to thiochromes, which were separated by gradient elution on a reversed-phase HPLC column and detected by fluorescence. The method was validated for linearity, limit of quantification, imprecision, accuracy, and interference. Results obtained with this method were compared with those produced by the method currently used in our clinical laboratory. Reference values of thiamine and its phosphate esters were determined in samples obtained from self-reported healthy adults who were not taking vitamin supplements. To shorten analysis time, our method used whole blood rather than washed erythrocytes, did not require lengthy enzymatic dephosphorylation, and had a simple mobile phase. Results: The method was linear to 4000 nmol/L. The lower limit of quantification was 3 nmol/L. The within-run CV was <3.5% and total CV was <9.4%. This method correlated with our current method ( r = 0.97). Approximately 90% of the total thiamine content in whole blood was present as thiamine diphosphate (TDP). The means (ranges) for an apparently healthy population were 114 (70–179) nmol/L for TDP and 125 (75–194) nmol/L for total thiamine. Results for separation and measurement of free thiamine and thiamine phosphate esters in whole blood were obtained within 5.5 min. Conclusion: We developed an HPLC method that allows separation and measurement of free thiamine and thiamine phosphate esters in whole blood and provides more rapid results than other methods.

Modulation of thiamine metabolism in Zea mays seedlings under conditions of abiotic stress

Abstract: The responses of plants to abiotic stress involve the up-regulation of numerous metabolic pathways, including several major routes that engage thiamine diphosphate (TDP)-dependent enzymes. This suggests that the metabolism of thiamine (vitamin B1) and its phosphate esters in plants may be modulated under various stress conditions. In the present study, Zea mays seedlings were used as a model system to analyse for any relation between the plant response to abiotic stress and the properties of thiamine biosynthesis and activation. Conditions of drought, high salt, and oxidative stress were induced by polyethylene glycol, sodium chloride, and hydrogen peroxide, respectively. The expected increases in the abscisic acid levels and in the activities of antioxidant enzymes including catalase, ascorbate peroxidase, and glutathione reductase were found under each stress condition. The total thiamine compound content in the maize seedling leaves increased under each stress condition applied, with the strongest effects on these levels observed under the oxidative stress treatment. This increase was also found to be associated with changes in the relative distribution of free thiamine, thiamine monophosphate (TMP), and TDP. Surprisingly, the activity of the thiamine synthesizing enzyme, TMP synthase, responded poorly to abiotic stress, in contrast to the significant enhancement found for the activities of the TDP synthesizing enzyme, thiamine pyrophosphokinase, and a number of the TDP/TMP phosphatases. Finally, a moderate increase in the activity of transketolase, one of the major TDP-dependent enzymes, was detectable under conditions of salt and oxidative stress. These findings suggest a role of thiamine metabolism in the plant response to environmental stress.

Effects of thiamine and benfotiamine on intracellular glucose metabolism and relevance in the prevention of diabetic complications

Abstract: Thiamine (vitamin B1) is an essential cofactor in most organisms and is required at several stages of anabolic and catabolic intermediary metabolism, such as intracellular glucose metabolism, and is also a modulator of neuronal and neuro-muscular transmission. Lack of thiamine or defects in its intracellular transport can cause a number of severe disorders. Thiamine acts as a coenzyme for transketolase (TK) and for the pyruvate dehydrogenase and α-ketoglutarate dehydrogenase complexes, enzymes which play a fundamental role for intracellular glucose metabolism. In particular, TK is able to shift excess fructose-6-phosphate and glycerhaldeyde-3-phosphate from glycolysis into the pentose-phosphate shunt, thus eliminating these potentially damaging metabolites from the cytosol. Diabetes might be considered a thiamine-deficient state, if not in absolute terms at least relative to the increased requirements deriving from accelerated and amplified glucose metabolism in non-insulin dependent tissues that, like the vessel wall, are prone to complications. A thiamine/TK activity deficiency has been described in diabetic patients, the correction of which by thiamine and/or its lipophilic derivative, benfotiamine, has been demonstrated in vitro to counteract the damaging effects of hyperglycaemia on vascular cells. Little is known, however, on the positive effects of thiamine/benfotiamine administration in diabetic patients, apart from the possible amelioration of neuropathic symptoms. Clinical trials on diabetic patients would be necessary to test this vitamin as a potential and inexpensive approach to the prevention and/or treatment of diabetic vascular complications.

Metabolic and Structural Role of Thiamine in Nervous Tissues

Abstract: In the literature, previous descriptions of the role of thiamine (B1 vitamin) focused mostly on its biochemical functions as a coenzyme precursor of some key enzymes of the carbohydrate metabolism. This report reviews recent developments on the metabolic and structural role of thiamine, e.g., the coenzyme and noncoenzyme functions of the vitamin. Taking into account analysis of our experimental data relating to the effects of thiamine deficiency on developing central nervous system (CNS) and data available in literature, we seek to establish a clear difference between the metabolic and structural role of thiamine. Our experimental data indicate that the specific and nonspecific effects express two diametrically diverse functions of thiamine in development: the nonspecific effects show up the metabolic consequences of thiamine deficiency resulting in apoptosis and severe cellular deficit; inversely, the specific effects announced the structural consequences of thiamine deficiency, described as cellular membrane damage, irregular and ectopic cells. The review highlights the existence of noncoenzyme functions of this vitamin through its interactions with biological membranes.

Benfotiamine exhibits direct antioxidative capacity and prevents induction of DNA damage in vitro

Abstract: Background Complications in diabetes mellitus are partially mediated by enhanced formation of reactive oxygen species. Among the factors involved in reactive oxygen species formation, advanced glycation end products play a key role. Owing to a reduced activity of the enzyme transketolase, which requires diphosphorylated thiamine (vitamin B1) as cofactor, an accumulation of those deleterious glucose metabolites especially in diabetic patients can be observed. Benfotiamine, a lipophilic thiamine diphosphate prodrug, prevented early renal and retinal changes in animal studies, and reduced neuropathic pain in clinical studies. Several mechanisms for these activities have been described. We investigated for the first time direct antioxidant abilities of benfotiamine. Additionally, a potential DNA protective effect of benfotiamine was analysed. Methods Oxidative stress was detected by flow cytometry, antioxidative capacity was measured with the ferric reducing ability of plasma (FRAP) assay, two endpoints for genomic damage were assessed: the comet assay and the micronucleus test, and the expression and activity of transketolase was quantified. Results Benfotiamine prevented oxidative stress induced by the mutagen 4-nitroquinoline-1-oxide (NQO), the uremic toxin indoxyl sulfate, and the peptide hormone angiotensin II in three different kidney cell lines. Cell-free experiments showed a direct antioxidant effect of benfotiamine, which might account for the protective effect. Oxidative DNA damage, induced by angiotensin II, was completely prevented by benfotiamine. Incubation with benfotiamine increased transketolase expression and activity in the cells. Conclusions Benfotiamine shows a direct antioxidant action. This effect of benfotiamine may be involved in the improvement of diabetic late complications, including peripheral neuropathy. Copyright © 2008 John Wiley & Sons, Ltd.

Benfotiamine, a synthetic S-acyl thiamine derivative, has different mechanisms of action and a different pharmacological profile than lipid-soluble thiamine disulfide derivatives.

Abstract: Background Lipid-soluble thiamine precursors have a much higher bioavailability than genuine thiamine and therefore are more suitable for therapeutic purposes. Benfotiamine (S-benzoylthiamine O-monophosphate), an amphiphilic S-acyl thiamine derivative, prevents the progression of diabetic complications, probably by increasing tissue levels of thiamine diphosphate and so enhancing transketolase activity. As the brain is particularly sensitive to thiamine deficiency, we wanted to test whether intracellular thiamine and thiamine phosphate levels are increased in the brain after oral benfotiamine administration.

Identification of Genes Encoding the Folate- and Thiamine-Binding Membrane Proteins in Firmicutes

Abstract: Genes encoding high-affinity folate- and thiamine-binding proteins (FolT, ThiT) were identified in the Lactobacillus casei genome, expressed in Lactococcus lactis, and functionally characterized. Similar genes occur in many Firmicutes, sometimes next to folate or thiamine salvage genes. Most thiT genes are preceded by a thiamine riboswitch.

AtTHIC, a gene involved in thiamine biosynthesis in Arabidopsis thaliana.

Abstract: Thiamine (vitamin B(1)) is an essential compound for organisms. It contains a pyrimidine ring structure and a thiazole ring structure. These two moieties of thiamine are synthesized independently and then coupled together. Here we report the molecular characterization of AtTHIC, which is involved in thiamine biosynthesis in Arabidopsis. AtTHIC is similar to Escherichia coli ThiC, which is involved in pyrimidine biosynthesis in prokaryotes. Heterologous expression of AtTHIC could functionally complement the thiC knock-out mutant of E. coli. Downregulation of AtTHIC expression by T-DNA insertion at its promoter region resulted in a drastic reduction of thiamine content in plants and the knock-down mutant thic1 showed albino (white leaves) and lethal phenotypes under the normal culture conditions. The thic1 mutant could be rescued by supplementation of thiamine and its defect functions could be complemented by expression of AtTHIC cDNA. Transient expression analysis revealed that the AtTHIC protein targets plastids and chloroplasts. AtTHIC was strongly expressed in leaves, flowers and siliques and the transcription of AtTHIC was downregulated by extrinsic thiamine. In conclusion, AtTHIC is a gene involved in pyrimidine synthesis in the thiamine biosynthesis pathway of Arabidopsis, and our results provide some new clues for elucidating the pathway of thiamine biosynthesis in plants.

Prevention of incipient diabetic cardiomyopathy by high-dose thiamine.

Abstract: Diabetic cardiomyopathy can progress toward overt heart failure with increased mortality. The hexosamine biosynthesis pathway has been implicated in signaling for fibrosis by the kidney. Thiamine (vitamin B1) is an indispensable coenzyme and required at intracellular glucose metabolism. In this study, we assessed if decrease of flux through the hexosamine biosynthesis pathway induced by high-dose thiamine therapy counteracts diabetes-induced cardiac fibrosis. The diabetes model used was the streptozotocin-induced diabetic rat. Normal control and diabetic rats were studied for 2 weeks with and without thiamine, and followings were analyzed; plasma biochemicals (total cholesterol and triglycerides), morphological changes, mRNA abundance relevant to cardiac failure (brain natriuretic peptide) and fibrosis (transforming growth factor-s1, thrombospondine, fibronectin, plasminogen activator-I and connective tissue growth factor) as well as and matrix metalloproteinase activity were investigated. Thiamine repletion prevented diabetes-induced cardiac fibrosis without changes in plasma glucose concentration. This was achieved by prevention of thiamine depletion, increased pro-fibrotic mRNA abundance and decreased metalloproteinase activity in the heart of diabetic rats. O-glycosylated protein was significantly higher in the left ventricular of diabetic rats compared to control rats, which was decreased by thiamine administration. Thiamine repletion prevented diabetes-induced cardiac fibrosis in experimental diabetes, probably by suppression of hexosamine biosynthesis pathway.

Antioxidant effect of thiamine on acutely alcoholized rats and lack of efficacy using thiamine or glucose to reduce blood alcohol content.

Abstract: Although there is no consensus about the use of glucose and thiamine for the treatment of acute ethanol intoxication, this is a routine practice in many countries. Our objective was to determine the efficacy of this treatment and the changes it causes in the antioxidant status of the liver. Male Wistar rats were intoxicated with an ethanol dose of 5 g/kg and divided into three groups: ethanol (EtOH; untreated), EtOH+G (treated with glucose), and EtOH+B1 (treated with thiamine). Blood and urinary ethanol as well as hepatic malondialdehyde, reduced glutathione and vitamin E were determined in all animals. Blood alcohol levels did not differ between groups, although urinary excretion was about four times higher in the group treated with thiamine (EtOH+B1). The malondialdehyde, reduced glutathione and vitamin E values used here as parameters of the antioxidant system of the liver showed improvement for the thiamine-treated group (EtOH+B1). Treatment with glucose or thiamine was ineffective in reducing blood alcohol levels in rats with acute ethanol intoxication. However, the beneficial effect of thiamine as an antioxidant for ethanol metabolism was demonstrated. Further investigations are necessary to clarify the urinary excretion of ethanol reported here for the first time and the possibility of using thiamine as an antioxidant in situations of chronic alcohol use.

Thiamine responsive pyruvate dehydrogenase deficiency in an adult with peripheral neuropathy and optic neuropathy

Abstract: Pyruvate dehydrogenase complex (PDHc) is a thiamine dependent key enzyme for energy production which catalyses decarboxylation of pyruvate into acetyl CoA for the Krebs cycle.1 PDHc deficiency is generally (80%) caused by mutations in the E1α subunit gene, PDHA1 , located on chromosome Xp22.1, but other genes have been reported to be mutated (eg, PDHX , encoding the E3 binding protein, DLAT , encoding the E2 subunit PDHX, and PDHB , encoding the E1 beta subunit). The disease usually presents with lactic acidosis, psychomotor retardation and Leigh syndrome leading to death or severe handicap in infancy or childhood.1 Mild forms, compatible with surviving into adulthood, have rarely been reported. A 26-year-old man was born at 8 months’ gestation, following maternal eclampsia. His psychomotor development was normal. From the age of 2 years he suffered from paroxysmal walking difficulties that appeared exclusively during fever episodes. These “crises” lasted from several hours to days during which he experienced limb weakness and ataxia. One episode was remarkable for blurring of consciousness and another for external ophthalmoplegia. Episodes persisted until adulthood at a frequency of approximately 1 per year. In between crises, the patient had kyphoscoliosis, absent tendon reflexes, pes cavus and mild …

Synthesis and biological evaluation of pyrophosphate mimics of thiamine pyrophosphate based on a triazole scaffold.

Abstract: Novel triazole-based pyrophosphate analogues of thiamine pyrophosphate (TPP) have been synthesised and tested for inhibition of pyruvate decarboxylase (PDC) from Zymomonas mobilis The thiazolium ring of thiamine was replaced by a triazole in an efficient two-step procedure Pyrophosphorylation then gave extremely potent triazole inhibitors with KI values down to 20 pM, compared to a KD value of 035 μM for TPP This triazole scaffold was used for further investigation and six analogues containing mimics of the pyrophosphate group were synthesised and tested for inhibition of PDC Several effective analogues were found with KI values down to around 1 nM

Pyruvate Dehydrogenase Deficiency Presenting as Intermittent Isolated Acute Ataxia

Abstract: Objective: The aim of this study is to report and emphasize unusual presentations of pyruvate dehydrogenase (PDH) deficiency (OMIM 312170). Methods: PDH activity and PDHA1 gene were studied in two siblings presenting with intermittent ataxia in childhood. Similar presentations in reported PDH-deficient patients were searched for using the Medline database. Results: Both patients had PDH deficiency caused by a new mutation (G585C) in the PDHA1 gene, which is predicted to replace a highly conserved glycine at codon 195 by alanine. Although this mutation lies within the thiamine pyrophosphate binding domain, there was no thiamine responsiveness in vivo. The patients presented recurrent episodes of acute isolated ataxia in infancy. Both had normal blood and CSF lactate levels. Although symptoms initially resolved between episodes during the first decade, both patients subsequently worsened and developed progressive and severe encephalopathy, leading to death in their twenties. The spectrum of intermittent presentations in PDH deficiency includes episodic ataxia, intermittent peripheral weakness, recurrent dystonia and extrapyramidal movement disorders. Conclusions: PDH deficiency should be considered in patients with unexplained intermittent and recurrent acute neurological symptoms. Long-term prognosis and outcome remain uncertain. PDH deficiency can occur even with normal CSF lactate concentration.

Vitamin deficiencies in acutely intoxicated patients in the ED.

Abstract: Objective Physicians often administer intravenous multivitamins to intoxicated patients in the emergency department (ED); however, this practice is not supported by evidence from any prior study. We determined the prevalences of vitamin deficiencies in patients presenting to our ED with alcohol intoxication. Methods This study was a prospective, cross-section, observational study of a convenience sample of ED patients presenting with acute alcohol intoxication. Patients were tested for B12, folate, and thiamine levels as add-ons to their blood samples. Results Seventy-seven patients were included in the final analysis. The mean age was 46 years, and 19% were female; the mean blood alcohol level was 280 mg/dL. Of 75 patients, no one (0%) had low B12 or folate levels (95% confidence interval, 0-0.05); 6 (15%) of 39 patients had low thiamine levels (95% confidence interval, 0.06-0.31). Of these 6 patients, none exhibited clinical signs of thiamine deficiency. Conclusions In our ED, patients with acute ethanol intoxication do not have B12 or folate deficiencies. A significant minority (15%) of patients have thiamine deficiency; its clinical significance is unclear. Widespread administration of multivitamins is unwarranted by these findings, but thiamine may be considered.

A study of acute and chronic anti-nociceptive and anti-inflammatory effects of thiamine in mice.

Abstract: Background: Thiamine (VitB1) is a vitamin with various important physiological functions and postulated therapeutic effects. Its use as an analgesic in neuropathic pain has been undergoing in clinical settings. However, there has been little experimental investigation on this effect. In this study, anti-nociceptive and anti-inflammatory effects of thiamine were investigated in mice. Methods: Three doses of thiamine (50, 100 and 125 mg/kg) were used by intraperitoneal injection in this study. Acute and chronic anti-nociceptive effects were examined using hot plate test alone and after sciatic nerve ligation, respectively. Imipramine (40 mg/kg) was used as positive control. Anti-inflammatory effects of thiamine on acute and chronic inflammation were assessed using xylene-induced edema in ears and granuloma caused by compressed cotton implantation, respectively. Sodium diclofenac (15 mg/kg) was used as positive control. Open field test was performed to differentiate the mice responses in the acute anti-nociceptive tests. Results: All three doses of thiamine showed significant analgesic effects in non-ligated mice and also in neuropathic pain in ligated animals. Increasing the dose of thiamine correlated with a more pronounced and sustained effect. Acute antiinflammatory investigation showed that thiamine injected 30 or 60 minutes before xylene application reduced the weight of edematic ears. However, the effect of thiamine was less pronounced than diclofenac. Furthermore, when injected once daily for 7 days, all doses of thiamine significantly reduced the weight of the cotton disks, showing suppression of granuloma formation. Conclusion: Taken together, it has been shown that thiamine possesses remarkable analgesic activities and also has significant anti-inflammatory effects, confirming its clinical use in controlling pain and less in inflammation. Iran. Biomed. J. 12 (3): 173-178, 2008

Twenty-four-hour urinary thiamine as a biomarker for the assessment of thiamine intake.

Abstract: To investigate 24-h urinary thiamine as a potential biomarker for thiamine intake for use in validation studies to assess the validity of dietary intake data collected by self-reporting dietary methods. Seven male and six female healthy participants living for 30 days in a metabolic suite under strictly controlled conditions consuming their usual diet as assessed beforehand from four consecutive 7-day food diaries kept at home. During the 30-day study, all 24-h urine specimens were collected, validated for their completeness and analysed for thiamine. Thirty-day mean (±s.d.) calculated thiamine intake was 2.22±0.55 mg/day. Thirty-day mean (±s.d.) urinary excretion of thiamine was 526.5±193.0 μg/day (24.7±8.10% of intake). There was a highly significant correlation between individuals' 30-day means of thiamine intake and their mean excretion level (r=0.720; P=0.006), where 1 mg of thiamine intake predicted 268.2 μg of thiamine in urine. The correlations between intake and excretion remained significant when measurement from a single 24-h urine collection was used (r=0.56). Twenty-four-hour urinary thiamine can be used as a concentration biomarker for thiamine intake in dietary validation studies.

Off-pathway, oxygen-dependent thiamine radical in the Krebs cycle.

Abstract: The catalytic cofactor thiamine diphosphate is found in many enzymes of central metabolism and is essential in all extant forms of life. We demonstrate the presence of an oxygen-dependent free radical in the thiamine diphosphate-dependent Escherichia coli 2-oxoglutarate dehydrogenase, which is a key component of the tricarboxylic acid (Krebs) cycle. The radical was sufficiently long-lived to be trapped by freezing in liquid nitrogen, and its electronic structure was investigated by electron paramagnetic resonance (EPR) and electron-nuclear double resonance (ENDOR). Taken together, the spectroscopic results revealed a delocalized pi radical on the enamine-thiazolium intermediate within the enzyme active site. The radical is generated as an intermediate during substrate turnover by a side reaction with molecular oxygen, resulting in the continuous production of reactive oxygen species under aerobic conditions. This off-pathway reaction may account for metabolic dysfunction associated with several neurodegenerative diseases. The possibility that the on-pathway reaction may proceed via a radical mechanism is discussed.

High prevalence of infantile encephalitic beriberi with overlapping features of Leigh's disease.

Abstract: Infantile encephalitic beriberi (IEBB) is a rare form of thiamine deficiency and is poorly described. A proportion of Leigh's disease (LD) patients have similar clinical picture and response to thiamine as beriberi, leading to confusion in diagnosis and management. Data on IEBB and LD is scarce and status of thiamine deficiency in India is controversial. We report several infants with life-threatening respiratory and central nervous system symptoms that overlap between IEBB and LD. Majority had low erythrocyte transketolase levels and responded dramatically to thiamine supplementation suggesting a diagnosis of IEBB. However, presence of characteristic lesions on brain imaging and residual damage in several patients on follow-up does not rule out LD completely. Our study highlights the importance of thiamine deficiency in India, especially in the breast-feds and its overlapping features with LD. Awareness of this common mode of presentation may save patients' lives by early diagnosis and timely thiamine supplementation.

Severe Thiamine Deficiency in Sheep with Acute Ruminal Lactic Acidosis

Abstract: Background: Thiamine status of ruminants is adversely affected in acidic rumen conditions. However, there have been limited published case study data related to thiamine deficiency of ruminants with acute ruminal lactic acidosis (ARLA). Hypothesis: Thiamine deficiency would occur in sheep with ARLA. Animals: Thirteen Ak-Karaman (white Karaman) sheep with ARLA, aged 1 year (ARLA group) and 10 healthy Ak-Karaman sheep, aged 1 year (control group) were used. Methods: After clinical examination, rumen fluid samples of all sheep were obtained with a stomach tube and examined immediately. Blood samples were taken from a jugular vein of the sheep. Erythrocytic transketolase enzyme activity and hence thiamine pyrophosphate (TPP) effect were determined according to Clausen's method. Results: History revealed that all sheep in the ARLA group had accidentally consumed excessive amounts of cracked barley. During clinical examination of the ARLA group, disturbed general condition, engorged scleral vessels, moderate to severe dehydration, and ruminal atony were recorded in the sheep. The results of the ruminal fluid analyses of the ARLA group demonstrated characteristics of ARLA. The results of clinical and ruminal fluid examination of control group were normal. The mean TPP effect (%) in the ARLA group (109 ± 28) was significantly higher than in the control group (22.2 ± 3.7) (P < .001). Conclusions and Clinical Importance: The present study revealed that severe thiamine deficiency occurred in sheep with ARLA. This result indicates that thiamine administration to sheep suffering from acute ruminal acidosis caused by overconsumption of readily fermentable carbohydrates could be beneficial in alleviating thiamine deficiency caused by ruminal acidosis.

Region‐selective alterations of glucose oxidation and amino acid synthesis in the thiamine‐deficient rat brain: a re‐evaluation using 1H/13C nuclear magnetic resonance spectroscopy

Abstract: Thiamine deficiency provides an effective model of selective neuronal cell death. (1)H and (13)C-NMR was used to investigate the effects of thiamine deficiency on the synthesis of amino acids derived from [1-(13)C]glucose in vulnerable (medial thalamus; MT) compared to non-vulnerable (frontal cortex; FC) brain regions. Following 11 days of thiamine deficiency, a time-point associated with the absence of significant neuronal cell death, regional concentrations of glutamate, glutamine and GABA remained unaffected in FC and MT; however, decreased levels of aspartate in MT at this time-point were a predictor of regional vulnerability. De novo synthesis of glutamate and GABA were unaffected at 11 days of thiamine deficiency, while synthesis of [2-(13)C]aspartate was significantly impaired. Glucose loading, which has been shown to exacerbate symptoms in patients with thiamine deficiency, resulted in further decreases of TCA cycle flux and reduced de novo synthesis of glutamate, aspartate and GABA in thiamine-deficient (TD) rats. Isotopomer analysis revealed that impaired TCA cycle flux and decreased aspartate synthesis due to thiamine deficiency occurred principally in neurons. Glucose loading deteriorated TD-related decreases in TCA cycle flux, and concomitantly reduced synthesis of aspartate and glutamate in MT.

Effectiveness and retention of thiamine and its analogs administered to steelhead and landlocked Atlantic salmon.

Abstract: We investigated the feasibility of enhancing the reproduction of steelhead Oncorhynchus mykiss and landlocked Atlantic salmon Salmo salar in lakes where the consumption of alewives Alosa pseudoharengus and other forage fishes containing thiaminase can cause them to become thiamine deficient and thereby reduce the survival of their fry. We evaluated feeding fingerling steelhead excess thiamine hydrochloride (THCl) for 1 or 2 weeks or equimolar amounts of thiamine mononitrate, thiamine-tetrahydro-furfuryl-disulfide, benfotiamine, or dibenzoyl thiamine (DBT). We found minimal internal reserves of thiamine after 6 months. We also compared the ability of injections of thiamine and its analogs to prevent mortality in thiamine-deficient steelhead and Atlantic salmon sac fry and found all forms to be effective, although benfotiamine was the least effective on an equimolar basis. Further, we injected yearling steelhead and found that DBT was tolerated at approximately 11,200 nmol/g of body weight, about 1...

Thiamine withdrawal can lead to diabetic ketoacidosis in thiamine responsive megaloblastic anemia: report of two siblings.

Abstract: Thiamine responsive megaloblastic anemia syndrome (TRMA), an autosomal recessive disorder caused by the deficiency of thiamine transporter protein, is the association of diabetes mellitus, anemia and deafness. Pharmacological dose thiamine normalizes hematological abnormalities and their effects on the course of diabetes mellitus. We report on 8 years follow up of two siblings with TRMA. They presented in the prepubertal period with diabetic ketoacidosis due to lack of thiamine supplementation for 2 months. Their insulin requirements fell rapidly and disappeared with thiamine therapy. Hematological parameters normalized within 30 days. The diabetic picture is responsive to thiamine treatment in patients with TRMA. Insulin dependent diabetes may occur throughout the pubertal period. If thiamine supplementation is not sufficient, ketoacidosis may develop in patients during the prepubertal period.