Showing papers on "Thiamine published in 2016"
TL;DR: Administration of thiamine did not improve lactate levels or other outcomes in the overall group of patients with septic shock and elevated lactate and a statistically significant decrease in mortality over time was not found.
Abstract: Objective:To determine if intravenous thiamine would reduce lactate in patients with septic shock.Design:Randomized, double-blind, placebo-controlled trial.Setting:Two US hospitals.Patients:Adult patients with septic shock and elevated (> 3 mmol/L) lactate between 2010 and 2014.Interventions:Thiamin
220 citations
TL;DR: In this study microwave-assisted hydrothermal method was used to prepare highly luminescent carbon dots within a minute from tender coconut water to test for rapid detection of thiamine (vitamin B1) and the results show they are suitable for this application too.
161 citations
TL;DR: It is shown that in preclinical models, reduced thiamine can drive AD‐like abnormalities, including memory deficits, neuritic plaques, and hyperphosphorylation of tau, and excessThiamine diminishesAD‐like pathologies.
Abstract: The earliest and perhaps best example of an interaction between nutrition and dementia is related to thiamine (vitamin B1). Throughout the last century, research showed that thiamine deficiency is associated with neurological problems, including cognitive deficits and encephalopathy. Multiple similarities exist between classical thiamine deficiency and Alzheimer's disease (AD) in that both are associated with cognitive deficits and reductions in brain glucose metabolism. Thiamine-dependent enzymes are critical components of glucose metabolism that are reduced in the brains of AD patients and by thiamine decline, and a decrease in their levels could account for the reduction in glucose metabolism. In preclinical models, reduced thiamine can drive AD-like abnormalities, including memory deficits, neuritic plaques, and hyperphosphorylation of tau. Furthermore, excess thiamine diminishes AD-like pathologies. In addition to dietary deficits, drugs or other manipulations that interfere with thiamine absorption can cause thiamine deficiency. Elucidating the reasons why the brains of AD patients are functionally thiamine deficient and determining the effects of thiamine restoration may provide critical information to help treat patients with AD.
135 citations
TL;DR: THI1 overexpressors proved to be more sensitive to ABA than the wild type with respect to both the activation of guard cell slow type anion channels and stomatal closure; this effectively reduced the rate of water loss from the plant and thereby enhanced its level of drought tolerance.
Abstract: Thiamine is required for both plant growth and development. Here, the involvement of a thiamine thiazole synthase, THI1, has been demonstrated in both guard cell abscisic acid (ABA) signaling and the drought response in Arabidopsis (Arabidopsis thaliana). THI1 overexpressors proved to be more sensitive to ABA than the wild type with respect to both the activation of guard cell slow type anion channels and stomatal closure; this effectively reduced the rate of water loss from the plant and thereby enhanced its level of drought tolerance. A yeast two-hybrid strategy was used to screen a cDNA library from epidermal strips of leaves for THI1 regulatory factors, and identified CPK33, a Ca(2+)-dependent protein kinase, as interactor with THI1 in a plasma membrane-delimited manner. Loss-of-function cpk33 mutants were hypersensitive to ABA activation of slow type anion channels and ABA-induced stomatal closure, while the CPK33 overexpression lines showed opposite phenotypes. CPK33 kinase activity was essential for ABA-induced stomatal closure. Consistent with their contrasting regulatory role over stomatal closure, THI1 suppressed CPK33 kinase activity in vitro. Together, our data reveal a novel regulatory role of thiamine thiazole synthase to kinase activity in guard cell signaling.
62 citations
TL;DR: It is demonstrated that C. sorokiniana can exude sufficient tryptophan and thiamine to allow IAA production by a PGPB during their interaction, as part of a communication between the two microorganisms.
58 citations
TL;DR: In this article, a retrospective study of patients admitted to a cancer hospital and diagnosed with Wernicke-Korsakoff syndrome (WKS) during routine care on a psychiatric consultation service was conducted.
54 citations
TL;DR: Thiamine supplementation led to clinical improvement in patients early treated and restored thiamine values in fibroblasts and cerebrospinal fluid and a profound deficiency of free-thiamine was found in the CSF and fibro Blasts of patients with thienine transporter-2 deficiency.
Abstract: Thiamine transporter-2 deficiency is caused by mutations in the SLC19A3 gene. As opposed to other causes of Leigh syndrome, early administration of thiamine and biotin has a dramatic and immediate clinical effect. New biochemical markers are needed to aid in early diagnosis and timely therapeutic intervention. Thiamine derivatives were analysed by high performance liquid chromatography in 106 whole blood and 38 cerebrospinal fluid samples from paediatric controls, 16 cerebrospinal fluid samples from patients with Leigh syndrome, six of whom harboured mutations in the SLC19A3 gene, and 49 patients with other neurological disorders. Free-thiamine was remarkably reduced in the cerebrospinal fluid of five SLC19A3 patients before treatment. In contrast, free-thiamine was slightly decreased in 15.2% of patients with other neurological conditions, and above the reference range in one SLC19A3 patient on thiamine supplementation. We also observed a severe deficiency of free-thiamine and low levels of thiamine diphosphate in fibroblasts from SLC19A3 patients. Surprisingly, pyruvate dehydrogenase activity and mitochondrial substrate oxidation rates were within the control range. Thiamine derivatives normalized after the addition of thiamine to the culture medium. In conclusion, we found a profound deficiency of free-thiamine in the CSF and fibroblasts of patients with thiamine transporter-2 deficiency. Thiamine supplementation led to clinical improvement in patients early treated and restored thiamine values in fibroblasts and cerebrospinal fluid.
54 citations
TL;DR: This narrative review provides evidence for thiamine as treatment in critical conditions requiring metabolic resuscitation, and gives rationale to the consideration of increasedThiamine supplementation in therapeutic foods for malnourished children.
Abstract: In humans, thiamine is a micronutrient prone to depletion that may result in severe clinical abnormalities. This narrative review summarizes current knowledge on thiamine deficiency (TD) and bridges the gap between pathophysiology and clinical presentation by integrating thiamine metabolism at subcellular level with its function to vital organs. The broad clinical spectrum of TD is outlined, with emphasis on conditions encountered in tropical pediatric practice. In particular, TD is associated with type B lactic acidosis and classic forms of beriberi in children, but it is often unrecognized. Other severe acute conditions are associated with hypermetabolism, inducing a functional TD. The crucial role of thiamine in infant cognitive development is also highlighted in this review, along with analysis of the potential impact of TD in refeeding syndrome during severe acute malnutrition (SAM). This review aims to increase clinical awareness of TD in tropical settings where access to diagnostic tests is poor, and advocates for an early therapeutic thiamine challenge in resource-limited settings. Moreover, it provides evidence for thiamine as treatment in critical conditions requiring metabolic resuscitation, and gives rationale to the consideration of increased thiamine supplementation in therapeutic foods for malnourished children.
53 citations
Stockholm University1, University of Vigo2, United States Geological Survey3, University of Massachusetts Dartmouth4, Swedish University of Agricultural Sciences5, Karlstad University6, Karolinska Institutet7, Utrecht University8, Medical Products Agency9, University of Iceland10, National Marine Fisheries Service11, National Veterinary Institute12
TL;DR: The problem of thiamine deficiency is considerably more widespread and severe than previously reported and linked to secondary effects on growth, condition, liver size, blood chemistry and composition, histopathology, swimming behaviour and endurance, parasite infestation, and reproduction.
Abstract: Many wildlife populations are declining at rates higher than can be explained by known threats to biodiversity. Recently, thiamine (vitamin B1) deficiency has emerged as a possible contributing cause. Here, thiamine status was systematically investigated in three animal classes: bivalves, ray-finned fishes, and birds. Thiamine diphosphate is required as a cofactor in at least five life-sustaining enzymes that are required for basic cellular metabolism. Analysis of different phosphorylated forms of thiamine, as well as of activities and amount of holoenzyme and apoenzyme forms of thiamine-dependent enzymes, revealed episodically occurring thiamine deficiency in all three animal classes. These biochemical effects were also linked to secondary effects on growth, condition, liver size, blood chemistry and composition, histopathology, swimming behaviour and endurance, parasite infestation, and reproduction. It is unlikely that the thiamine deficiency is caused by impaired phosphorylation within the cells. Rather, the results point towards insufficient amounts of thiamine in the food. By investigating a large geographic area, by extending the focus from lethal to sublethal thiamine deficiency, and by linking biochemical alterations to secondary effects, we demonstrate that the problem of thiamine deficiency is considerably more widespread and severe than previously reported.
52 citations
TL;DR: The measurement of blood thiamine metabolites by HPLC is an ideal diagnostic test for AD with inexpensive, easy to perform, noninvasive merits.
49 citations
TL;DR: Results did not indicate any need to add thiamine above levels recommended for fish in general, and recommended B-vitamin supplementation in plant based diets for Atlantic salmon should be adjusted.
Abstract: Aiming to re-evaluate current recommendations for nutrient supplementations when Atlantic salmon are fed diets based on plant ingredients, two regression experiments, with parr and post-smolt, were conducted. A control diet was included to evaluate if ingredients supplied sufficient nutrients without any added nutrient package (NP). The nutrient package consisted of vitamins B, C, E, minerals, cholesterol, methionine, taurine and histidine. This paper focus on B-vitamins. In parr, growth, health and welfare parameters responded on NP additions, but this was not observed in the seawater stage. During three months of feeding, parr tripled their weight. Parr given diets added the NP above NRC (2011) showed improved protein retention, and reduced liver and viscera indices. Post-smolt fed the same diets during five months showed a doubling of weight, but did not respond to the variation in NP to the same extent as parr. Significant regressions were obtained in body compartments for several of the B-vitamins in the premix. Whole body biotin concentration was unaffected by micronutrient premix level, and mRNA expression of the enzymes dependent of biotin showed only weak increases with increased biotin. Muscle thiamine plateaued at a diet level similar to NRC (2011) recommendation in freshwater, and showed stable values independent on premix addition in seawater. The mRNA expression of the enzyme G6PDH (glucose-6-phosphate dehydrogenase) is sensitive to thiamine availability; results did not indicate any need to add thiamine above levels recommended for fish in general. Niacin showed a steady increase in whole body concentrations as feed niacin increased. Muscle riboflavin peaked at a diet level of 12.4 mg kg-1. Sufficient riboflavin is important to avoid e.g., development of cataract. Cataract was not registered to be any problem, neither in fresh- nor in seawater. Cobalamin (B 12) in muscle and liver was saturated at 0.17 mg kg-1 diet. Muscle pyridoxine showed a dose-dependent level in muscle, and peaked around 10 mg kg -1 diet. White muscle ASAT (asparagine amino transferase) activity steadily increased, with indications of stable values when dietary pyridoxine was around 10-16 mg kg -1 diet. Pantothenic acid increased in gill tissue up to a level of 5.5 mg kg -1 soft gill tissue; at a dietary level of 22 mg kg-1. Improved performance, and coverage of metabolic need for niacin was at a dietary level of 66 mg kg -1, riboflavin 10-12 mg kg-1, pyridoxine 10 mg kg-1 and panthotenic acid 22 mg kg-1. Based on these results, recommended B-vitamin supplementation in plant based diets for Atlantic salmon should be adjusted.
TL;DR: In this article, the effect of thiamine on rice root-knot nematode infection was evaluated. But no direct toxic effects of VB1 on nematore viability and infectivity were observed.
Abstract: Thiamine (vitamin B1, VB1) can act as a plant defence trigger, or priming agent, leading to a rapid counterattack on pathogen invasion. In this study, the priming effect of thiamine on rice (Oryza sativa cv. Nipponbare) and its activity against root-knot nematode (Meloidogyne graminicola) infection were evaluated. Thiamine treatment and subsequent nematode inoculation activated hydrogen peroxide (H2O2) accumulation and lignin deposition in plant roots, and this correlated with enhanced transcription of OsPAL1 and OsC4H, two genes involved in the phenylpropanoid pathway. The number of nematodes in rice roots was slightly but significantly reduced, and the development of the nematodes was delayed, whereas no direct toxic effects of VB1 on nematode viability and infectivity were observed. The combined application of thiamine with l-2-aminooxy-3-phenylpropionic acid (AOPP), an inhibitor of phenylalanine ammonia-lyase (PAL), significantly hampered the VB1-priming capacity. These findings indicate that thiamine-induced priming in rice involves H2O2 and phenylpropanoid-mediated lignin production, which hampers nematode infection. Further cellular and molecular studies on the mechanism of thiamine-induced defence will be useful for the development of novel nematode control strategies.
TL;DR: TheThiamine status was affected by SARA in dairy cows and ruminal infusion of thiamine could help attenuate SARA by improving theportions of ruminal volatile fatty acids and reducing lactate contents in rumen fluid and blood.
TL;DR: It is concluded that the riboflavin and thiamine conjugated MWCNTs shown great promising potential in the treatment of cancer, but more exhaustive data is needed in future.
Abstract: In the present investigation, we prepared and evaluated the paclitaxel loaded riboflavin and thiamine conjugated multi walled carbon nanotubes (PTX-Rf-MWCNTs and PTX-Tm-MWCNTs) for targeted delivery to cancer employing MCF-7 cancer cell lines. The developed conjugates were characterized using FTIR, NMR spectroscopy, electron microscopy drug loading, release, stability, hemolytic, ex vivo and in vivo studies etc.
The percent entrapment efficiency was found to be 87.92 ± 0.48 and 82.75 ± 0.47% of PTX-Tm-MWCNTs, PTX-Rf-MWCNTs, respectively. The percent hemolysis of purified MWCNTs, PTX-MWCNTs, PTX-Tm-MWCNTs and PTX-Rf-MWCNTs was found to be 20.49 ± 0.97, 37.39 ± 0.78, 14.61 ± 0.84 and 11.17 ± 0.77% respectively. The PTX-Tm-MWCNTs and PTX-Rf-MWCNTs showed more cytotoxic effect as compared to PTX and PTX-MWCNTs with PTX-Rf-MWCNTs exhibiting the maximum cytotoxic potential. Thus in final outcome, we concluded that the riboflavin and thiamine conjugated MWCNTs shown great promising potential in the treatment of cancer, but more exhaustive data is needed in future.
TL;DR: Thiamine was the first B vitamin to be identified and is also referred to as vitamin B 1 .
Abstract: Thiamine was the first B vitamin to be identified and is also referred to as vitamin B 1 . It is a water-soluble vitamin that is an indispensable constituent of cellular metabolism (1). A lack of this vitamin can, therefore, be potentially life-threatening (2).
TL;DR: A combination of biochemical, physiological, and genetic approaches permitted it to be shown that PUT3 mediates phloem transport of both thiamine and polyamines, and the tissue distribution of these metabolites is altered with growth and developmental consequences.
Abstract: Thiamine (vitamin B1) is ubiquitous and essential for cell energy supply in all organisms as a vital metabolic cofactor, known for over a century. In plants, it is established that biosynthesis de novo is taking place predominantly in green tissues and is furthermore limited to plastids. Therefore, transport mechanisms are required to mediate the movement of this polar metabolite from source to sink tissue to activate key enzymes in cellular energy generating pathways but are currently unknown. Similar to thiamine, polyamines are an essential set of charged molecules required for diverse aspects of growth and development, the homeostasis of which necessitates long-distance transport processes that have remained elusive. Here, a yeast-based screen allowed us to identify Arabidopsis (Arabidopsis thaliana) PUT3 as a thiamine transporter. A combination of biochemical, physiological, and genetic approaches permitted us to show that PUT3 mediates phloem transport of both thiamine and polyamines. Loss of function of PUT3 demonstrated that the tissue distribution of these metabolites is altered with growth and developmental consequences. The pivotal role of PUT3 mediated thiamine and polyamine homeostasis in plants, and its importance for plant fitness is revealed through these findings.
TL;DR: The provision of thiamine after cardiac arrest improved neurological outcome and 10-day survival in mice and PDH activity was markedly depressed in post-cardiac arrest patients suggesting that this pathway may represent a therapeutic target.
TL;DR: The THI11 promoter is a versatile and easy to control regulatory sequence which enables the realization of novel protein production strategies and is compared with the commonly used GAP promoter.
Abstract: The methylotrophic yeast Pichia pastoris is widely used for production of recombinant proteins. Here we characterize a vitamin-sensitive regulatory sequence, which can be controlled independently of the main culture medium compounds such as carbon, nitrogen, or phosphor source. The THI11 promoter (PTHI11 ) sequence derives from a gene involved in biosynthesis of thiamine. For characterization, a P. pastoris strain expressing recombinant human serum albumin under control of PTHI11 was grown in the controlled environment of a bioreactor. The thiamine sensitivity of PTHI11 was proven and specified in batch cultures containing different amounts of extracellular thiamine. Under non-repressing conditions PTHI11 offers a constitutive expression pattern with growth rate dependent product formation. Furthermore, promoter activity and thus product formation can be repressed for a desired period of time by supplementing the culture with a pre-defined amount of exogenous thiamine. Once a threshold of biomass is reached, PTHI11 driven expression starts autonomously without external intervention. Based on these findings a tailor-made process strategy was developed and experimentally verified. Additionally, we compared the THI11 promoter with the commonly used GAP promoter. In conclusion, the THI11 promoter is a versatile and easy to control regulatory sequence which enables the realization of novel protein production strategies. Biotechnol. Bioeng. 2016;113: 2633-2643. © 2016 Wiley Periodicals, Inc.
TL;DR: Limited data suggest that thiamine supplementation is capable of increasingleft ventricular ejection fraction and improving functional capacity in patients with heart failure and a reduced left ventricular ejectedion fraction who were treated with diuretics (predominantly furosemide).
TL;DR: Vitamin B1 and its phosphate derivatives, thiamine monophosphate andThiamine pyrophosphate, are shown to form stable 1:1 host-guest complexes with cucurbit[7]uril (CB[7]) in aqueous solution.
Abstract: Vitamin B1 (1) and its phosphate derivatives, thiamine monophosphate (2) and thiamine pyrophosphate (3), are shown to form stable 1:1 host-guest complexes with cucurbit[7]uril (CB[7]) in aqueous solution. The binding sites of CB[7] on these guests shift from the ethylthiazolium region of 1 to the pyrimidine moiety of 2 and 3 due to the presence of phosphate groups, leading to variations of binding affinities as well as C(2)-H/D exchange rate constants and C(2)-H pKa values with these guest molecules.
TL;DR: Women who consumed thiamine-fortified fish sauce through pregnancy and early lactation had higher eTDP and breast milkThiamine concentrations and their infants had higher ETDP, which was more pronounced in the high group.
Abstract: Importance Infantile beriberi, a potentially fatal disease caused by thiamine deficiency, remains a public health concern in Cambodia and regions where thiamine-poor white rice is a staple food. Low maternal thiamine intake reduces breast milk thiamine concentrations, placing breastfed infants at risk of beriberi. Objective To determine if consumption of thiamine-fortified fish sauce yields higher erythrocyte thiamine diphosphate concentrations (eTDP) among lactating women and newborn infants and higher breast milk thiamine concentrations compared with a control sauce. Design, Setting, and Participants In this double-blind randomized clinical trial, 90 pregnant women were recruited in the Prey Veng province, Cambodia. The study took place between October 2014 and April 2015. Interventions Women were randomized to 1 of 3 groups (n = 30) for ad libitum fish sauce consumption for 6 months: control (no thiamine), low-concentration (2 g/L), or high-concentration (8 g/L) fish sauce. Main Outcomes and Measures Maternal eTDP was assessed at baseline (October 2014) and endline (April 2015). Secondary outcomes, breast milk thiamine concentration and infant eTDP, were measured at endline. Results Women's mean (SD) age and gestational stage were 26 (5) years and 23 (7) weeks, respectively. April 2015 eTDP was measured among 28 women (93%), 29 women (97%), and 23 women (77%) in the control, low-concentration, and high-concentration groups, respectively. In modified intent-to-treat analysis, mean baseline-adjusted endline eTDP was higher among women in the low-concentration (282nM; 95% CI, 235nM to 310nM) and high-concentration (254nM; 95% CI, 225nM to 284nM) groups compared with the control group (193nM; 95% CI, 164nM to 222M; P P = .19). Breast milk total thiamine concentrations were 14.4 μg/dL for the control group (95% CI, 12.3 μg/dL to 16.5 μg/dL) (to convert to nanomoles per liter, multiply by 29.6); 20.7 μg/dL for the low-concentration group (95% CI, 18.6 μg/dL to 22.7 μg/dL ); and 17.7 μg/dL for the high-concentration group (95% CI, 15.6 μg/dL to 19.9 μg/dL). Mean (SD) infant age at endline was 16 (8) weeks for the control group, 17 (7) weeks for the low-concentration group, and 14 (8) for the high-concentration group. Infant eTDP was higher among those in the high-concentration group (257nM; 95% CI, 222nM to 291nM; P Conclusions and Relevance Compared with women in the control group, women who consumed thiamine-fortified fish sauce through pregnancy and early lactation had higher eTDP and breast milk thiamine concentrations and their infants had higher eTDP, which was more pronounced in the high group. Thiamine-fortified fish sauce has the potential to prevent infantile beriberi in this population. Trial Registration Clinicaltrials.gov Identifier:NCT02221063
TL;DR: Results suggest that among younger patients with MDD adjuvant thiamine alleviated symptoms of depression faster compared to placebo, and th Liamine might have the potential to counteract the time lag in the antidepressant effects of ADs.
Abstract: Given that antidepressants (ADs) work slowly, there is interest in means to accelerate their therapeutic effect and to reduce side effects. In this regard, thiamine (vitamin B1) is attracting growing interest. Thiamine is an essential nutrient, while thiamine deficiency leads to a broad variety of disorders including irritability and symptoms of depression. Here, we tested the hypothesis that adjuvant thiamine would reduce depression, compared to placebo. A total of 51 inpatients (mean age: 35.2 years; 53 % females) with MDD (Hamilton Depression Rating Scale score (HDRS) at baseline: >24) took part in the study. A standardized treatment with SSRI was introduced and kept at therapeutic levels throughout the study. Patients were randomly assigned either to the thiamine or the placebo condition. Experts rated (HDRS) symptoms of depression at baseline, and after 3, 6, and 12 weeks (end of the study). Between baseline and the end of the study, depression had reduced in both groups. Compared to placebo, adjuvant thiamine improved symptoms of depression after 6 week of treatment, and improvements remained fairly stable until the end of the study, though mean differences at week 12 were not statistically significant anymore. No adverse side effects were reported in either group. Results suggest that among younger patients with MDD adjuvant thiamine alleviated symptoms of depression faster compared to placebo. Importantly, improvements were observed within 6 weeks of initiation of treatment. Thus, thiamine might have the potential to counteract the time lag in the antidepressant effects of ADs.
TL;DR: Evidence collected so far suggests that the administration of thiamine improves outcome in SLC 19A-2, SLC19A3- and TPK1-mutated patients, so most efforts should be aimed at early diagnosis of these disorders.
Abstract: Introduction: Thiamine is a key cofactor for energy metabolism in brain tissue. There are four major genetic defects (SLC19A2, SLC19A3, SLC25A19 and TPK1) involved in the metabolism and transport of thiamine through cellular and mitochondrial membranes. Neurological involvement predominates in three of them (SLC19A3, SCL25A19 and TPK1), whereas patients with SLC19A2 mutations mainly present extra-neurological features (e.g. diabetes mellitus, megaloblastic anaemia and sensori-neural hearing loss). These genetic defects may be amenable to therapeutic intervention with vitamins supplementation and hence, constitutes a main area of research.Areas covered: We conducted a literature review of all reported cases with these genetic defects, and focused our paper on treatment efficacy and safety, adverse effects, dosing and treatment monitoring.Expert commentary: Doses of thiamine vary according to the genetic defect: for SLC19A2, the usual dose is 25–200 mg/day (1–4 mg/kg per day), for SLC19A3, 10–40 mg/...
TL;DR: There were no differences in post-operative lactate levels or clinical outcomes between patients receiving thiamine or placebo, and Post-operative oxygen consumption was significantly increased among patients receivingThiamine.
Abstract: Thiamine is a vitamin that is essential for adequate aerobic metabolism. The objective of this study was to determine if thiamine administration prior to coronary artery bypass grafting would decrease post-operative lactate levels as a measure of increased aerobic metabolism. We performed a randomized, double-blind, placebo-controlled trial of patients undergoing coronary artery bypass grafting. Patients were randomized to receive either intravenous thiamine (200 mg) or placebo both immediately before and again after the surgery. Our primary endpoint was post-operative lactate levels. Additional endpoints included pyruvate dehydrogenase activity, global and cellular oxygen consumption, post-operative complications, and hospital and intensive care unit length of stay. Sixty-four patients were included. Thiamine levels were significantly higher in the thiamine group as compared to the placebo group immediately after surgery (1200 [683, 1200] nmol/L vs. 9 [8, 13] nmol/L, p < 0.001). There was no difference between the groups in the primary endpoint of lactate levels immediately after the surgery (2.0 [1.5, 2.6] mmol/L vs. 2.0 [1.7, 2.4], p = 0.75). Relative pyruvate dehydrogenase activity was lower immediately after the surgery in the thiamine group as compared to the placebo group (15 % [11, 37] vs. 28 % [15, 84], p = 0.02). Patients receiving thiamine had higher post-operative global oxygen consumption 1 hour after the surgery (difference: 0.37 mL/min/kg [95 % CI: 0.03, 0.71], p = 0.03) as well as cellular oxygen consumption. We found no differences in clinical outcomes. There were no differences in post-operative lactate levels or clinical outcomes between patients receiving thiamine or placebo. Post-operative oxygen consumption was significantly increased among patients receiving thiamine. clinicaltrials.gov NCT02322892
, December 14, 2014
TL;DR: Monitoring of the plasma oxythiamine concentration in renal failure and implementation of high-dose thiamine supplements to counter it may help improve the clinical outcome of patients with renal failure.
TL;DR: Autistic children had normal plasma and urinary thiamine levels whereas plasma TPP concentration was decreased, and the latter may be linked to abnormal tissue handling and/or absorption from gut microbiota of TPP which warrants further investigation.
Abstract: Aims/hypothesis: To assess thiamine and related metabolite status by analysis of plasma and urine in autistic children and healthy controls, correlations to clinical characteristics and link to plasma protein markers of oxidative damage.Methods: 27 children with autism (21 males and 6 females) and 21 (15 males and 6 females) age-matched healthy control children were recruited. The concentration of thiamine and related phosphorylated metabolites in plasma and urine and plasma protein content of dityrosine, N-formylkynurenine and 3-nitrotyrosine was determined.Results: Plasma thiamine and thiamine monophosphate concentrations were similar in both study groups (median [lower–upper quartile]): autistic children – 6.60 nM (4.48–8.91) and 7.00 nM (5.51–8.55), and healthy controls – 6.82 nM (4.47–7.02) and 6.82 nM (5.84–8.91), respectively. Thiamine pyrophosphate (TPP) was decreased 24% in autistic children compared to healthy controls: 6.82 nM (5.81–8.52) versus 9.00 nM (8.41–10.71), p < .01. Urinary ex...
GMC1
TL;DR: If treated early, metabolic acidosis due to thiamine deficiency is associated with good immediate and long term prognosis even if pH is less than 7 at presentation.
TL;DR: The method was validated over the range from 1.0-4000 nM for both cells and the media where complete recovery of the analytes was also achieved and the linearity, sensitivity, specificity, accuracy and precision of the method were evaluated.
Abstract: A new method for reversed phase HPLC determination of thiamine and its major in vivo phosphorylation products, thiamine monophosphate (TMP) and thiamine pyrophosphate (TPP), was developed using tetrabutylammonium hydroxide as the ion-pairing agent. The separation was performed on a Phenomenex Kinetex EVO C18 column with a gradient of a phosphate-buffered aqueous solution of the ion-pair reagent and methanol. The duty cycle for the assay was 13 min and pyrithiamine was successfully used as the internal standard for the first time in a thiamine HPLC measurement protocol. Detection of the fluorescence derivatives of the analytes as well as the IS allowed for lower detection limits in order to support biological applications in cell culture models. The linearity, sensitivity, specificity, accuracy and precision of the method were evaluated and met the requirements specified by the US Food and Drug Administration. The calibration curves proved to be linear and the method was validated over the range from 1.0–4000 nm for both cells and the media where complete recovery of the analytes was also achieved. Copyright © 2015 John Wiley & Sons, Ltd.
TL;DR: The kinetic properties of human GLUD1 and GLUD2 isoenzymes are shown to be similar to those published for GDH1 and GDH2 from bovine brain, and increased functional diversity and specific regulation of GDH isoforms due to alternative splicing and post-translational modifications are considered.
Abstract: Glutamate dehydrogenase (GDH) of animal cells is usually considered to be a mitochondrial enzyme. However, this enzyme has recently been reported to be also present in nucleus, endoplasmic reticulum and lysosomes. These extramitochondrial localizations are associated with moonlighting functions of GDH, which include acting as a serine protease or an ATP-dependent tubulin-binding protein. Here, we review the published data on kinetics and localization of multiple forms of animal GDH taking into account the splice variants, post-translational modifications and GDH isoenzymes, found in humans and apes. The kinetic properties of human GLUD1 and GLUD2 isoenzymes are shown to be similar to those published for GDH1 and GDH2 from bovine brain. Increased functional diversity and specific regulation of GDH isoforms due to alternative splicing and post-translational modifications are also considered. In particular, these structural differences may affect the well-known regulation of GDH by nucleotides which is related to recent identification of thiamine derivatives as novel GDH modulators. The thiamine-dependent regulation of GDH is in good agreement with the fact that the non-coenzyme forms of thiamine, i.e., thiamine triphosphate and its adenylated form are generated in response to amino acid and carbon starvation.
TL;DR: It is shown that thiamine deficiency substantially reduced the energy state in the liver and activated the energy sensor AMP-activated kinase, indicating a severe change in the energy status of the whole organism.
Abstract: Thiamine is one of several essential cofactors for ATP generation. Its deficiency, like in beriberi and in the Wernicke-Korsakoff syndrome, has been studied for many decades. However, its mechanism of action is still not completely understood at the cellular and molecular levels. Since it acts as a coenzyme for dehydrogenases of pyruvate, branched-chain keto acids, and ketoglutarate, its nutritional privation is partly a phenocopy of inborn errors of metabolism, among them maple syrup urine disease. In the present paper, we report metabolic and genomic findings in mice deprived of thiamine. They are similar to the ones we have previously found in biotin deficiency, another ATP generation cofactor. Here we show that thiamine deficiency substantially reduced the energy state in the liver and activated the energy sensor AMP-activated kinase. With this vitamin deficiency, several metabolic parameters changed: blood glucose was diminished and serum lactate was increased, but insulin, triglycerides, and cholesterol, as well as liver glycogen, were reduced. These results indicate a severe change in the energy status of the whole organism. Our findings were associated with modified hepatic levels of the mRNAs of several carbon metabolism genes: a reduction of transcripts for liver glucokinase and fatty acid synthase and augmentation of those for carnitine palmitoyl transferase 1 and phosphoenolpyruvate carboxykinase as markers for glycolysis, fatty acid synthesis, beta-oxidation, and gluconeogenesis, respectively. Glucose tolerance was initially increased, suggesting augmented insulin sensitivity, as we had found in biotin deficiency; however, in the case of thiamine, it was diminished from the 3rd week on, when the deficient animals became undernourished, and paralleled the changes in AKT and mTOR, 2 main proteins in the insulin signaling pathway. Since many of the metabolic and gene expression effects on mice deprived of thiamine are similar to those in biotin deficiency, it may be that they result from a more general impairment of oxidative phosphorylation due to a shortage of ATP generation cofactors. These findings may be relevant to energy-related disorders, among them several inborn errors of metabolism, as well as common energy disorders like obesity, diabetes, and neurodegenerative illnesses.