Showing papers on "Thiamine published in 2010"

EFNS guidelines for diagnosis, therapy and prevention of Wernicke encephalopathy.

Abstract: Background: Although Wernicke encephalopathy (WE) is a preventable and treatable disease it still often remains undiagnosed during life. Objectives: To create practical guidelines for diagnosis, management and prevention of the disease. Methods: We searched MEDLINE, EMBASE, LILACS, Cochrane Library. Conclusions and recommendations: 1 The clinical diagnosis of WE should take into account the different presentations of clinical signs between alcoholics and non alcoholics (Recommendation Level C); although prevalence is higher in alcoholics, WE should be suspected in all clinical conditions which could lead to thiamine deficiency (good practice point – GPP). 2 The clinical diagnosis of WE in alcoholics requires two of the following four signs; (i) dietary deficiencies (ii) eye signs, (iii) cerebellar dysfunction, and (iv) either an altered mental state or mild memory impairment (Level B). 3 Total thiamine in blood sample should be measured immediately before its administration (GPP). 4 MRI should be used to support the diagnosis of acute WE both in alcoholics and non alcoholics (Level B). 5 Thiamine is indicated for the treatment of suspected or manifest WE. It should be given, before any carbohydrate, 200 mg thrice daily, preferably intravenously (Level C). 6 The overall safety of thiamine is very good (Level B). 7 After bariatric surgery we recommend follow-up of thiamine status for at least 6 months (Level B) and parenteral thiamine supplementation (GPP). 8 Parenteral thiamine should be given to all at-risk subjects admitted to the Emergency Room (GPP). 9 Patients dying from symptoms suggesting WE should have an autopsy (GPP).

Thiamine Status in Humans and Content of Phosphorylated Thiamine Derivatives in Biopsies and Cultured Cells

Abstract: Background Thiamine (vitamin B1) is an essential molecule for all life forms because thiamine diphosphate (ThDP) is an indispensable cofactor for oxidative energy metabolism. The less abundant thiamine monophosphate (ThMP), thiamine triphosphate (ThTP) and adenosine thiamine triphosphate (AThTP), present in many organisms, may have still unidentified physiological functions. Diseases linked to thiamine deficiency (polyneuritis, Wernicke-Korsakoff syndrome) remain frequent among alcohol abusers and other risk populations. This is the first comprehensive study on the distribution of thiamine derivatives in human biopsies, body fluids and cell lines. Methodology and Principal Findings Thiamine derivatives were determined by HPLC. In human tissues, the total thiamine content is lower than in other animal species. ThDP is the major thiamine compound and tissue levels decrease at high age. In semen, ThDP content correlates with the concentration of spermatozoa but not with their motility. The proportion of ThTP is higher in humans than in rodents, probably because of a lower 25-kDa ThTPase activity. The expression and activity of this enzyme seems to correlate with the degree of cell differentiation. ThTP was present in nearly all brain and muscle samples and in ∼60% of other tissue samples, in particular fetal tissue and cultured cells. A low ([ThTP]+[ThMP])/([Thiamine]+[ThMP]) ratio was found in cardiovascular tissues of patients with cardiac insufficiency. AThTP was detected only sporadically in adult tissues but was found more consistently in fetal tissues and cell lines. Conclusions and Significance The high sensitivity of humans to thiamine deficiency is probably linked to low circulating thiamine concentrations and low ThDP tissue contents. ThTP levels are relatively high in many human tissues, as a result of low expression of the 25-kDa ThTPase. Another novel finding is the presence of ThTP and AThTP in poorly differentiated fast-growing cells, suggesting a hitherto unsuspected link between these compounds and cell division or differentiation.

Saccharomyces cerevisiae THI4p is a suicide thiamine thiazole synthase

Abstract: Vitamin B1 (thiamin) was the first vitamin to be discovered more than a century ago, but some of the details of its biosynthesis remain unclear because of the complexity and novelty of this process. In yeast, the protein THI4p catalyses the assembly of the thiazole moiety of vitamin B1 in a complex reaction involving the conversion of NAD, glycine and sulphide to an adenylated carboxythiazole phosphate. The source of the sulphide and the mechanism by which it is incorporated into the thiazole is not known. Chatterjee et al. now report the first full reconstitution of THI4p-catalysed thiamin thiazole biosynthesis. They show that a conserved cysteine residue of THI4p acts as the source of sulphur, meaning that this protein is in fact a co-substrate of the biosynthetic pathway. THI4p can do this only once, so that it is a cofactor or 'suicide enzyme' rather that a true multi-turnover enzyme. Thiamine pyrophosphate 1 is an essential cofactor in all living systems1. Its biosynthesis involves the separate syntheses of the pyrimidine 2 and thiazole 3 precursors, which are then coupled2. Two biosynthetic routes to the thiamine thiazole have been identified. In prokaryotes, five enzymes act on three substrates to produce the thiazole via a complex oxidative condensation reaction, the mechanistic details of which are now well established2,3,4,5,6. In contrast, only one gene product is involved in thiazole biosynthesis in eukaryotes (THI4p in Saccharomyces cerevisiae)7. Here we report the preparation of fully active recombinant wild-type THI4p, the identification of an iron-dependent sulphide transfer reaction from a conserved cysteine residue of the protein to a reaction intermediate and the demonstration that THI4p is a suicide enzyme undergoing only a single turnover.

Increased protein damage in renal glomeruli, retina, nerve, plasma and urine and its prevention by thiamine and benfotiamine therapy in a rat model of diabetes

Abstract: Aims/hypothesis The aim of this study was to quantify protein damage by glycation, oxidation and nitration in a rat model of diabetes at the sites of development of microvascular complications, including the effects of thiamine and benfotiamine therapy.

Powerful beneficial effects of benfotiamine on cognitive impairment and beta-amyloid deposition in amyloid precursor protein/presenilin-1 transgenic mice.

Abstract: Reduction of glucose metabolism in brain is one of the main features of Alzheimer’s disease. Thiamine (vitamin B1)-dependent processes are critical in glucose metabolism and have been found to be impaired in brains from patients with Alzheimer’s disease. However, thiamine treatment exerts little beneficial effect in these patients. Here, we tested the effect of benfotiamine, a thiamine derivative with better bioavailability than thiamine, on cognitive impairment and pathology alterations in a mouse model of Alzheimer’s disease, the amyloid precursor protein/presenilin-1 transgenic mouse. We show that after a chronic 8 week treatment, benfotiamine dose-dependently enhanced the spatial memory of amyloid precursor protein/presenilin-1 mice in the Morris water maze test. Furthermore, benfotiamine effectively reduced both amyloid plaque numbers and phosphorylated tau levels in cortical areas of the transgenic mice brains. Unexpectedly, these effects were not mimicked by another lipophilic thiamine derivative, fursultiamine, although both benfotiamine and fursultiamine were effective in increasing the levels of free thiamine in the brain. Most notably, benfotiamine, but not fursultiamine, significantly elevated the phosphorylation level of glycogen synthase kinase-3α and -3β, and reduced their enzymatic activities in the amyloid precursor protein/presenilin-1 transgenic brain. Therefore, in the animal Alzheimer’s disease model, benfotiamine appears to improve the cognitive function and reduce amyloid deposition via thiamine-independent mechanisms, which are likely to include the suppression of glycogen synthase kinase-3 activities. These results suggest that, unlike many other thiamine-related drugs, benfotiamine may be beneficial for clinical Alzheimer’s disease treatment.

Screening of a thiamine‐auxotrophic yeast for α‐ketoglutaric acid overproduction

Abstract: Aims To obtain a thiamine-auxotrophic yeast strain that overproduces alpha-ketoglutaric acid (alpha-KG) from glycerol and to investigate nutrient effects on alpha-KG production. Methods and results Yeast strain WSH-Z06, a thiamine auxotroph that gave high yields of alpha-KG from glycerol, was obtained by screening for ampicillin/kanamycin resistance and thiamine auxotrophy. The strain was identified as Yarrowia lipolytica based on physiological, chemical, and phylogenetic analysis. The ability of the strain to convert glycerol to alpha-KG was analysed by investigating the effects of nutritional factors, including thiamine, riboflavin, nitrogen sources, and calcium ion. Conclusions Thiamine and calcium ion concentration had the greatest effect on alpha-KG accumulation. Under optimal conditions, a yield of 39.2 g l(-1)alpha-KG was obtained from 100 g l(-1) glycerol, with 16.84 g l(-1) pyruvate as a by-product. Significance and impact of the study The current work provides a method for screening for an alpha-KG overproducer. Nutrients have a significant impact on alpha-KG production in the yeast strain presented here. The alpha-KG-overproducing yeast strain Y. lipolytica WSH-Z06 is a promising parent strain for further metabolic engineering to lower by-product accumulation and accelerate glycerol utilization.

Thiamine Biosynthesis in Saccharomyces cerevisiae Is Regulated by the NAD+-Dependent Histone Deacetylase Hst1

Abstract: Genes encoding thiamine biosynthesis enzymes in microorganisms are tightly regulated such that low environmental thiamine concentrations activate transcription and high concentrations are repressive. We have determined that multiple thiamine (THI) genes in Saccharomyces cerevisiae are also regulated by the intracellular NAD+ concentration via the NAD+-dependent histone deacetylase (HDAC) Hst1 and, to a lesser extent, Sir2. Both of these HDACs associate with a distal region of the affected THI gene promoters that does not overlap with a previously defined enhancer region bound by the thiamine-responsive Thi2/Thi3/Pdc2 transcriptional activators. The specificity of histone H3 and/or H4 deacetylation carried out by Hst1 and Sir2 at the distal promoter region depends on the THI gene being tested. Hst1/Sir2-mediated repression of the THI genes occurs at the level of basal expression, thus representing the first set of transcription factors shown to actively repress this gene class. Importantly, lowering the NAD+ concentration and inhibiting the Hst1/Sum1 HDAC complex elevated the intracellular thiamine concentration due to increased thiamine biosynthesis and transport, implicating NAD+ in the control of thiamine homeostasis.

Loss of astrocytic glutamate transporters in Wernicke encephalopathy

Abstract: Wernicke encephalopathy (WE), a neurological disorder caused by thiamine deficiency (TD), is characterized by structural damage in brain regions that include the thalamus and cerebral cortex. The basis for these lesions is unclear, but may involve a disturbance of glutamatergic neurotransmission. We have therefore investigated levels of the astrocytic glutamate transporters EAAT1 and EAAT2 in order to evaluate their role in the pathophysiology of this disorder. Histological assessment of the frontal cortex revealed a significant loss of neurons in neuropathologically confirmed cases of WE compared with age-matched controls, concomitant with decreases in alpha-internexin and synaptophysin protein content of 67 and 52% by immunoblotting. EAAT2 levels were diminished by 71% in WE, with levels of EAAT1 also reduced by 62%. Loss of both transporter sites was confirmed by immunohistochemical methods. Development of TD in rats caused a profound loss of EAAT1 and EAAT2 in the thalamus accompanied by decreases in other astrocyte-specific proteins. Treatment of TD rats with N-acetylcysteine prevented the downregulation of EAAT2 in the medial thalamus, and ameliorated the loss of several other astrocyte proteins, concomitant with increased neuronal survival. Our results suggest that (1) loss of EAAT1 and EAAT2 glutamate transporters is associated with structural damage to the frontal cortex in patients with WE, (2) oxidative stress plays an important role in this process, and (3) TD has a profound effect on the functional integrity of astrocytes. Based on these findings, we recommend that early treatment using a combination of thiamine AND antioxidant approaches should be an important consideration in cases of WE.

Cardiac oxidative stress is involved in heart failure induced by thiamine deprivation in rats

Abstract: Thiamine is an important cofactor of metabolic enzymes, and its deficiency leads to cardiovascular dysfunction. First, we characterized the metabolic status measuring resting oxygen consumption rate and lactate blood concentration after 35 days of thiamine deficiency (TD). The results pointed to a decrease in resting oxygen consumption and a twofold increase in blood lactate. Confocal microscopy showed that intracellular superoxide (approximately 40%) and H(2)O(2) (2.5 times) contents had been increased. In addition, biochemical activities and protein expression of SOD, glutathione peroxidase, and catalase were evaluated in hearts isolated from rats submitted to thiamine deprivation. No difference in SOD activity was detected, but protein levels were found to be increased. Catalase activity increased 2.1 times in TD hearts. The observed gain in activity was attended by an increased catalase protein level. However, a marked decrease in glutathione peroxidase activity (control 435.3 + or - 28.6 vs. TD 199.4 + or - 30.2 nmol NADPH x min(-1) x ml(-1)) was paralleled by a diminution in the protein levels. Compared with control hearts, we did observe a greater proportion of apoptotic myocytes by TdT-mediated dUTP nick end labeling (TUNEL) and caspase-3 reactivity techniques. These results indicate that during TD, reactive oxygen species (ROS) production may be enhanced as a consequence of the installed acidosis. The perturbation in the cardiac myocytes redox balance was responsible for the increase in apoptosis.

Measurement of Serum, Liver, and Brain Cytokine Induction, Thiamine Levels, and Hepatopathology in Rats Exposed to a 4-Day Alcohol Binge Protocol

Abstract: IN HUMAN AND rodent studies, recent high-level ethanol (EtOH) exposure is associated with elevated brain levels of the magnetic resonance spectroscopy (MRS) signal representing choline-containing compounds (Cho). Studies using in vivo MRS have reported that Cho levels are higher in the parietal gray matter of alcohol-dependent individuals compared with controls (Meyerhoff et al., 2004), and high Cho levels in the frontal cortex correlate with the amount of alcohol consumed by social drinkers (Ende et al., 2006). Similarly, wild-type rats exposed to EtOH as their sole fluid source for 16 weeks (Lee et al., 2001), to escalating doses of EtOH via vapor inhalation (Zahr et al., 2009), and to 4 days of binge EtOH via oral gavage (Zahr et al., 2010) demonstrate significant elevations in brain Cho. As elevated brain Cho is observed in animal models of acute experimental allergic encephalomyelitis (Brenner et al., 1993) and in the acute inflammatory stage of multiple sclerosis (De Stefano et al., 2005; Tartaglia et al., 2002; Van Au Duong et al., 2007), a posited interpretation for elevated brain Cho in response to EtOH is neuroinflammation. The hallmark of neuroinflammation is the activation of microglial cells, which may then release pro-inflammatory factors, including cytokines such as tumor necrosis factor (TNF-α) (Kreutzberg, 1996). Cytokines are polypeptides and glycoproteins that form a key part of a complex network that regulate immune and inflammatory responses (Gallin and Snyderman, 1999). Cytokines including TNF-α, interferons (IFN), interleukins (IL), and growth-regulated oncogenes (GRO, also known as chemokine C-X-C motif ligand 1: CXCL1) are mediators that are induced during an immune response. Although alcohol exposure can modulate the human immune system (e.g., McClain and Cohen, 1989; Szabo et al., 1996), it is not obvious that cytokine induction occurs in the absence of alcoholic liver disease (e.g., Jarvelainen et al., 1999; McClain et al., 2004; Tilg et al., 2003) or thiamine deficiency (Hazell and Butterworth, 2009), known concomitants of severe and chronic alcoholism. Brain tissue recovered from chronic alcoholics compared with tissue from healthy donors was found to express higher levels of the cytokine monocyte chemoattractant protein-1 (MCP-1, also known as chemokine C-C motif ligand 2: CCL2) in the ventral tegmental area (VTA), substantia nigra, hippocampus, and amygdala and to have higher microglial activation in the cingulate cortex, VTA, and midbrain (He and Crews, 2008); in 4 of the 8 alcoholic brains analyzed, however, cause of death involved complications related to liver disease (He and Crews, 2008). The potential relevance of liver pathology to human alcohol studies requires acknowledgment because nearly every stage in the transition from steatosis to cirrhosis is associated with an inflammatory component and cytokine response (e.g., Bode and Bode, 2005; McMullen et al., 2005; Valles et al., 2003). Confirming this relation, knock-out mice lacking the TNF-α receptor are resistant to the effects of chronic EtOH in that they fail to develop steatosis, inflammation, or necrosis of the liver (Yin et al., 1999). Thiamine deficiency is another potential attendant of chronic alcoholism (Harper, 2006) and may also contribute to neuroinflammation (Hazell and Butterworth, 2009). The levels of thiamine and its phosphate derivatives, thiamine monophosphate (TMP) and thiamine diphosphate (TDP), can be low in human alcoholics, even without a history of Wernicke’s Encephalopathy (Mancinelli et al., 2003; Tallaksen et al., 1992a,b). Animal models of thiamine deficiency have revealed reactive gliosis (Karuppagounder et al., 2007; Todd and Butterworth, 1999) and increases in the levels of pro-inflammatory markers such as TNF-α (Karuppagounder et al., 2007; Vemuganti et al., 2006). Thus, experimental EtOH models seeking evidence of inflammatory processes should also assess thiamine status. While in vitro studies indicate that EtOH can modify microglial function (e.g., Choi et al., 2005; Fernandez-Lizarbe et al., 2009; Lee et al., 2004), there is a scarcity of data regarding the in vivo effects of EtOH, especially on the brain’s immune response. In in vivo animal models of EtOH intoxication, challenge with the bacterial toll-like receptor ligand endotoxin lipopolysaccharide (LPS) is often necessary to achieve a robust immune response (e.g., Jarvelainen et al., 1999; Qin et al., 2008). Alternatively, intermittent EtOH exposure may be necessary to observe neuroinflammation. For example, intermittent compared with continuous EtOH exposure increased the number of microglia in the cerebellar vermis of wild-type male Wistar rats (Riikonen et al., 2002), and intermittent compared with no EtOH exposure increased microglial activation as indicated by elevated OX-6 staining in the dentate gyrus of the wild-type female adolescent Wistar rat hippocampus (Ward et al., 2009). Cyclooxygenase-2 (COX-2), another inflammatory mediator, is upregulated in the wild-type male adolescent Wistar rat neocortex, hippocampus, and cerebellum following exposure to 3 cycles of 2 days with EtOH (3 g/kg) followed by 2 days without EtOH administration (Pascual et al., 2007). This pattern of findings suggests a significant role of repeated EtOH withdrawals in promoting inflammation. Exceptions to such examples include the reporting of elevations in COX-2 in various brain regions of the adult male Sprague–Dawley rat following a 4-day binge EtOH exposure as used herein (but see Knapp and Crews, 1999; Valles et al., 2004). To provide evidence that elevations in brain Cho are associated with EtOH-induced brain cytokine induction independent of repeated bouts of withdrawal, biochemical signs of liver pathology, or thiamine deficiency, the levels of TNF-α, IFN-γ, IL-1β, IL-4, IL-5, IL-13, and GRO/CXCL1 were determined in serum, liver, and brain samples from adult wild-type Wistar rats exposed to the same 4 days of binge EtOH treatment via oral gavage used for the MRS studies. Of these 7 cytokines, 4 (i.e., TNF-α, IFN-γ, IL-1β, IL-4) have previously been explored in the alcohol literature. Liver pathology and thiamine deficiency were investigated contemporaneously for potential discounting of these factors as contributors to any alcohol-exposure effect detected.

A maize thiamine auxotroph is defective in shoot meristem maintenance.

Abstract: Plant shoots undergo organogenesis throughout their life cycle via the perpetuation of stem cell pools called shoot apical meristems (SAMs). SAM maintenance requires the coordinated equilibrium between stem cell division and differentiation and is regulated by integrated networks of gene expression, hormonal signaling, and metabolite sensing. Here, we show that the maize (Zea mays) mutant bladekiller1-R (blk1-R) is defective in leaf blade development and meristem maintenance and exhibits a progressive reduction in SAM size that results in premature shoot abortion. Molecular markers for stem cell maintenance and organ initiation reveal that both of these meristematic functions are progressively compromised in blk1-R mutants, especially in the inflorescence and floral meristems. Positional cloning of blk1-R identified a predicted missense mutation in a highly conserved amino acid encoded by thiamine biosynthesis2 (thi2). Consistent with chromosome dosage studies suggesting that blk1-R is a null mutation, biochemical analyses confirm that the wild-type THI2 enzyme copurifies with a thiazole precursor to thiamine, whereas the mutant enzyme does not. Heterologous expression studies confirm that THI2 is targeted to chloroplasts. All blk1-R mutant phenotypes are rescued by exogenous thiamine supplementation, suggesting that blk1-R is a thiamine auxotroph. These results provide insight into the role of metabolic cofactors, such as thiamine, during the proliferation of stem and initial cell populations.

Anorexia nervosa and Wernicke-Korsakoff syndrome: a case report

Abstract: Wernicke's encephalopathy is an acute, potentially fatal, neuropsychiatric syndrome resulting from thiamine deficiency. The disorder is still greatly under-diagnosed, and failure to promptly identify and adequately treat the condition can lead to death or to the chronic form of the encephalopathy - Korsakoff's syndrome. Wernicke's encephalopathy has traditionally been associated with alcoholism but, in recent years, there has been an increase in the number of clinical settings in which the disorder is observed. We report the case of a 45-year-old Caucasian woman who arrived at the emergency room presenting signs of marked malnutrition and mental confusion, ataxic gait and ophthalmoplegia. Main laboratory test findings included low serum magnesium and megaloblastic anemia. Brain magnetic resonance imaging revealed increased T2 signal in the supratentorial paraventricular region, the medial regions of the thalamus and the central and periaqueductal midbrain. The diagnosis of Wernicke's encephalopathy was made at once and immediate reposition of thiamine and magnesium was started. The patient had a long history of recurrent thoughts of being overweight, severe self-imposed diet restrictions and self-induced vomiting. She had also been drinking gin on a daily basis for the last eight years. One day after admittance the acute global confusional state resolved, but she presented severe memory deficits and confabulation. After six months of outpatient follow-up, memory deficits remained unaltered. In this case, self-imposed long-lasting nutritional deprivation is thought to be the main cause of thiamine deficiency and subsequent encephalopathy, but adjunct factors, such as magnesium depletion and chronic alcohol misuse, might have played an important role, especially in the development of Korsakoff's syndrome. The co-morbidity between eating disorders and substance abuse disorders has emerged as a significant health issue for women, and the subgroup of patients with anorexia nervosa who also misuse alcohol is probably at a particular risk of developing Wernicke-Korsakoff syndrome. The present case report highlights this relevant issue.

Prevention and Treatment of Peripheral Neuropathy after Bariatric Surgery

Abstract: Given the ever-increasing problem of obesity, it is not surprising that the number of patients who undergo bariatric surgery continues to rise. For patients who have gastric banding, the amount of food they can consume is limited, and nausea and vomiting may further limit nutritional intake early on. More extensive procedures, such as the Roux-en-Y or biliopancreatic diversion with or without a duodenal switch, not only restrict intake but also limit absorption in the small intestine. As a result, deficiencies in vitamins, minerals, and trace elements may develop, leading to a variety of neurologic complications. The peripheral neuropathies best described with a clear-cut cause are an acute, frequently painful neuropathy or polyradiculoneuropathy associated with thiamine deficiency, and an isolated neuropathy or myeloneuropathy associated with deficiencies of either vitamin B12 or copper. Thiamine deficiency tends to occur in the first weeks or months after surgery, vitamin B12 deficiency may develop at any time from a few years to many years after surgery, and copper deficiency tends to be a fairly late complication, developing several years to many years following surgery. Patients who have undergone bariatric surgery may also have an increased risk of developing focal neuropathies, though these are less clearly related to specific nutritional deficiencies.Ideally, one would like to prevent these neuropathies, but there is no consensus of opinion as to what vitamins and micronutrients need to be taken following bariatric surgery. In addition, many patients who take supplements early on fail to maintain the regimen even though some of the neuropathies can occur fairly late. Supplements frequently recommended include a multivitamin, iron, vitamin D, folic acid, calcium citrate, and vitamin B12. Although thiamine is typically included in a multivitamin, the amount is fairly small, so I recommend adding 100 mg daily for at least the first year. Some have suggested zinc supplementation, but this is potentially problematic because exogenous zinc may interfere with copper absorption. Obtaining blood work every 6 months after surgery will help to identify and treat nutritional deficiencies early.For those patients who have had a bariatric procedure and then develop a neuropathy, evaluating levels of thiamine, copper, vitamin B12, methylmalonic acid, and homocystine is indicated. In addition, since one deficiency is frequently associated with others, obtaining levels of vitamin A, C, D, K, and E, as well as iron, zinc, selenium, and magnesium is worthwhile. Checking total protein, albumin, and cholesterol also gives a sense of general nutritional status. Occasionally, no clear-cut deficiency of a vitamin, mineral, or trace element can be identified in patients with various peripheral nervous system manifestations. Nevertheless, these patients may have at least some recovery with improving nutritional intake and vitamin supplementation, suggesting that we still do not fully understand how nutritional status affects the peripheral nervous system.

Subacute sensory ataxia and optic neuropathy with thiamine deficiency.

Abstract: Spinazzi et al. describe a case of subacute sensory ataxia and bilateral optic neuropathy associated with thiamine deficiency in a patient with a history of partial gastrectomy. The patient responded well to supplementation with thiamine, showing rapid improvements in ability to walk and normalization of visual field perimetry 2 years after presentation. Background. A 71 year-old man with a history of partial gastrectomy presented to the emergency department with subacute gait instability associated with painful dysesthesias and clumsiness in both hands. 10 years before presentation he had received a diagnosis of megaloblastic anemia, with no neurological involvement, as a result of vitamin B12 and folate deficiency, for which he was receiving regular supplements. Investigations. Neurological examination; routine laboratory testing; MRI of the spine and brain; lumbar puncture; electromyography; sensory, motor and visual evoked potentials, optic nerve optical coherence tomography; immunoelectrophoresis; cryoglobulins; immunological and infection tests; screening for onconeural antibodies; measurement of serum metabolic values, including vitamins B12 and E, folates, homocysteine, copper, zinc and pyruvic acid; transketolase activity; gastrointestinal endoscopies; and the glucose breath test. Diagnosis. Subacute sensory ataxia with bilateral optic neuropathy related to thiamine deficiency resulting from remote partial gastrectomy. Management. Parenteral thiamine supplementation followed by chronic oral thiamine and short-term, low-dose multivitamins.

Cardiac beriberi: often a missed diagnosis.

Abstract: Thiamine deficiency leads to various manifestations due to dysfunction of nervous or cardiovascular system, commonly known as dry and wet beriberi, respectively. The latter, also known as cardiac beriberi is usually missed in clinical practice because of the absence of classically described symptoms such as pedal edema/anasarca. We investigated 55 such infants and prospectively followed their clinical course. All the babies were exclusively breast-fed and their mothers belonged to low socio-economic status with their staple diet consisting of non-parboiled polished rice. Majority presented with tachypnea, chest indrawing and tachycardia and cardiomegaly with dilatation of right heart and pulmonary hypertension on 2D-echocardiography. Low levels of erythrocyte transketolase activity suggested thiamine deficiency that was confirmed by reversion of several clinical features including cardiologic abnormalities to normalcy on thiamine supplementation. We recommend thiamine therapy for infants with unexplained congestive cardiac failure or acute respiratory failure from precarious socio-economic background since it is life-saving in many instances.

Effect of thiamine concentration on animal health, feedlot performance, carcass characteristics, and ruminal hydrogen sulfide concentrations in lambs fed diets based on 60% distillers dried grains plus solubles.

Abstract: Limited data are available regarding the influence of thiamine supplementation on the incidence of polioencephalomalacia (PEM) in lambs fed diets containing increased concentrations of S in the diet (>0.7%). Therefore, our objective was to evaluate the influence of thiamine supplementation on feedlot performance, carcass quality, ruminal hydrogen sulfide gas concentrations, and incidence of PEM in lambs fed a finishing diet containing 60% distillers dried grains with solubles (DDGS; DM basis). Two studies were conducted using completely randomized designs to evaluate the influence of concentration of thiamine supplementation. Study 1 used 240 lambs fed in 16 pens, whereas study 2 used 55 individually fed lambs. Lamb finishing diets contained 60% DDGS, which resulted in a dietary S concentration of 0.73% (DM basis). Treatments diets were based on the amount of supplemental thiamine provided: 1) no supplemental thiamine (CON), 2) 50 mg/animal per day (LO), 3) 100 mg/animal per day (MED), or 4) 150 mg/animal per day (HI). Additionally, in study 2, a fifth treatment was included, which contained 0.87% S (DM basis; increased S provided by addition of dilute sulfuric acid) and provided 150 mg of thiamine/animal per day (HI+S). In study 1, ADG decreased quadratically (P = 0.04), with lambs fed the CON, LO, and MED diets gaining BW at a greater rate than lambs fed the HI diet. In study 1, DMI responded quadratically (P or = 0.17) in lamb performance were observed in study 2. In both studies, most carcass characteristics were unaffected, with the exception of a tendency for decreased carcass conformation (study 1; P = 0.09) and greater flank streaking (study 2; P = 0.03). No differences in ruminal hydrogen sulfide concentration (P > 0.05) among treatments were apparent until d 10, at which point lambs fed the LO diet had less hydrogen sulfide concentrations than all other treatments. Lambs fed HI had the greatest concentrations of hydrogen sulfide on d 31 (1.07 g of hydrogen sulfide /m(3); P < 0.009). Ruminal pH did not differ (P = 0.13) and averaged 5.6 +/- 0.06. No clinical cases of PEM were observed during the course of either study. The use of thiamine as a dietary additive to aid in the prevention of PEM in finishing lambs does not appear to be necessary under the conditions of this study.

Response of vegetative growth and chemical constituents of Thuja orientalis L. plant to foliar application of different amino acids at Nubaria.

Abstract: A pot experiment was carried out during 2008 and 2009 seasons at Research and production Station, Nubaria of National of Research Centre, Dokki, Egypt to study the response of Thuja orientalis plants to foliar application of tyrosine, thiamine and tryptophan each at (0, 25, 50, and 100 ppm) on vegetative growth expressed as stem length, stem diameter, root length, fresh and dry weight of root and shoot and chemical constituents significantly were affected by the application of almost all of the three amino acids which were used in this study. Tyrosine, Thiamine and Tryptophan promoted all morphological characters. The comparison between the effect of tyrosine, thiamine and tryptophan revealed that the influence of tyrosine on increasing the growth parameters (especially at the rate of 10 ppm, which can be described as the most effective treatment) was superior to other amino acids (thiamine and tryptophan). The three amino acids increased total soluble sugar %, total free amino acid mg/g as well as essential oil %, essential oil yield / plant and N, P, K % and protein. Therefore, amino acid (Tyrosine, Thiamine and Tryptophan) at 100 ppm maybe recommended for promoted growth parameters and the best oil percentage in Thuja orientalis L. seedling. (Journal of American Science 2010;6(8):295-301). (ISSN: 1545- 1003).

Adenosine thiamine triphosphate accumulates in Escherichia coli cells in response to specific conditions of metabolic stress

Abstract: E. coli cells are rich in thiamine, most of it in the form of the cofactor thiamine diphosphate (ThDP). Free ThDP is the precursor for two triphosphorylated derivatives, thiamine triphosphate (ThTP) and the newly discovered adenosine thiamine triphosphate (AThTP). While, ThTP accumulation requires oxidation of a carbon source, AThTP slowly accumulates in response to carbon starvation, reaching ~15% of total thiamine. Here, we address the question whether AThTP accumulation in E. coli is triggered by the absence of a carbon source in the medium, the resulting drop in energy charge or other forms of metabolic stress. In minimal M9 medium, E. coli cells produce AThTP not only when energy substrates are lacking but also when their metabolization is inhibited. Thus AThTP accumulates in the presence of glucose, when glycolysis is blocked by iodoacetate, or in the presence lactate, when respiration is blocked by cyanide or anoxia. In both cases, ATP synthesis is impaired, but AThTP accumulation does not appear to be a direct consequence of reduced ATP levels. Indeed, in the CV2 E. coli strain (containing a thermolabile adenylate kinase), the ATP content is very low at 37°C, even in the presence of metabolizable substrates (glucose or lactate) and under these conditions, the cells produce ThTP but not AThTP. Furthermore, we show that ThTP inhibits AThTP accumulation. Therefore, we conclude that a low energy charge is not sufficient to trigger AThTP accumulation and the latter can only accumulate under conditions where no ThTP is synthesized. We further show that AThTP production can also be induced by the uncoupler CCCP but, unexpectedly, this requires the presence of pyruvate or a substrate yielding pyruvate (such a D-glucose or L-lactate). Under the conditions described, AThTP production is not different when RelA or SpoT mutants are used. In E. coli, AThTP accumulates in response to two different conditions of metabolic stress: lack of energy substrates (or inhibition of their metabolization) and uncoupled pyruvate oxidation. Both conditions prevent bacterial growth. There is no obvious link with the stringent response or catabolite repression.

Rapid communication Coronary artery bypass graft surgery depletes plasma thiamine levels

Abstract: Objective: Thiamine is an essential component of cellular metabolism, and lack of this vitamin results in a potentially life-threatening biochemical lesion. The stress of surgery and critical disease depletes electrolytes, minerals, and essential biochemical substrates. We hypothesized that critical illness (represented by major surgery) would result in decreased thiamine levels over time. Methods: We performed a prospective, observational study of serial thiamine levels of 15 patients who underwent non-emergent coronary artery bypass graft surgery. The primary endpoint was change in thiamine levels from before to immediately after surgery. Secondary endpoints included change in thiamine levels from presurgical to 6- and 24-h time points. Results: Of the 15 study patients, 1 did not have a plasma thiamine measurement at time 0 because of laboratory error and could not be accounted for in paired comparisons over time. Plasma thiamine levels decreased significantly from before to after coronary artery bypass grafting (P ¼0.0004). In addition, there was a statistically significant decrease in thiamine levels from before surgery to 24 h (P ¼ 0.003). Conclusion: Our data suggest that major surgery (as a surrogate for the stress of critical illness) depletes thiamine levels; further study is needed to determine whether routine replacement of thiamine in the critically ill is warranted. 2010 Elsevier Inc. All rights reserved.

Thiamine prevents obesity and obesity-associated metabolic disorders in OLETF rats.

Abstract: We previously found that thiamine mitigates metabolic disorders in spontaneously hypertensive rats, harboring defects in glucose and fatty acid metabolism. Mutation of thiamine transporter gene SLC19A2 is linked to type 2 diabetes mellitus. The current study extends our hypothesis that thiamine intervention may impact metabolic abnormalities in Otsuka Long-Evans Tokushima Fatty (OLETF) rats, exhibiting obesity and metabolic disorders similar to human metabolic syndrome. Male OLETF rats (4 wk old) were given free access to water containing either 0.2% or 0% of thiamine for 21 and 51 wk. At the end of treatment, blood parameters and cardiac functions were analyzed. After sacrifice, organs weights, histological findings, and hepatic pyruvate dehydrogenase (PDH) activity in the liver were evaluated. Thiamine intervention averted obesity and prevented metabolic disorders in OLETF rats which accompanied mitigation of reduced lipid oxidation and increased hepatic PDH activity. Histological evaluation revealed that thiamine alleviated adipocyte hypertrophy, steatosis in the liver, heart, and skeletal muscle, sinusoidal fibrosis with formation of basement membranes (called pseudocapillarization) which accompanied significantly reduced expression of laminin β1 and nidogen-1 mRNA, interstitial fibrosis in the heart and kidney, fatty degeneration in the pancreas, thickening of the basement membrane of the vasculature, and glomerulopathy and mononuclear cell infiltration in the kidney. Cardiac and renal functions were preserved in thiamine treatment. Thiamine has a potential to prevent obesity and metabolic disorders in OLETF rats.