101. Metab Brain Dis. 1998 Mar;13(1):43-53.
Plasma thiamine deficiency associated with Alzheimer's disease but not Parkinson's disease.
Gold M, Hauser RA, Chen MF.
University of South Florida College of Medicine, Department of Neurology, Tampa 33612, USA. firstname.lastname@example.org
In this study we compared plasma and erythrocyte thiamine levels in a group of patients with idiopathic Parkinson's Disease (iPD) to a group of patients with probable Alzheimer's Disease (pAD). pAD patients had significantly lower plasma thiamine levels (raw and z-score) than iPD patients. A significantly higher number of pAD patients had plasma thiamine deficiencies than iPD patients. The demographics of our patient groups were similar to those reported by other investigators, making age, sex and nutritional status unlikely explanations for our findings. These results suggest that plasma thiamine deficiency is associated with pAD but not with iPD.
102. Anticancer Res. 1998 Jan-Feb;18(1B):595-602.
Thiamine supplementation to cancer patients: a double edged sword.
Boros LG, Brandes JL, Lee WN, Cascante M, Puigjaner J, Revesz E, Bray TM, Schirmer WJ, Melvin WS.
Ohio State University College of Medicine, Department of Surgery, Columbus 43210, USA. Iboros@magnus.acs.ohio-state.edu
The objectives of this review are to (a) explain the mechanism by which thiamine (vitamin B1) promotes nucleic acid ribose synthesis and tumor cell proliferation via the nonoxidative transketolase (TK) pathway; (b) estimate the thiamine intake of cancer patients and (c) provide background information and to develop guidelines for alternative treatments with antithiamine transketolase inhibitors in the clinical setting. Clinical and experimental data demonstrate increased thiamine utilization of human tumors and its interference with experimental chemotherapy. Analysis of RNA ribose indicates that glucose carbons contribute to over 90% of ribose synthesis in cultured cervix und pancreatic carcinoma cells and that ribose is synthesized primarily through the thiamine dependent TK pathway (> 70%). Antithiamine compounds significantly inhibit nucleic acid synthesis and tumor cell proliferation in vitro and in vivo in several tumor models. The medical literature reveals little information regarding the role of the thiamine dependent TK reaction in tumor cell ribose production which is a central process in de novo nucleic acid synthesis and the salvage pathways for purines. Consequently, current thiamine administration protocols oversupply thiamine by 200% to 20,000% of the recommended dietary allowance, because it is considered harmless and needed by cancer patients. The thiamine dependent TK pathway is the central avenue which supplies ribose phosphate for nucleic acids in tumors and excessive thiamine supplementation maybe responsible for failed therapeutic attempts to terminate cancer cell proliferation. Limited administration of thiamine and concomitant treatment with transketolase inhibitors is a more rational approach to treat cancer.
103. East Afr Med J. 1997 Dec;74(12):803-8.
Evaluation of the efficacy of thiamine and pyridoxine in the treatment of symptomatic diabetic peripheral neuropathy.
Abbas ZG, Swai AB.
Muhimbili University College of Health Sciences, University of Dar es Salaam, Tanzania.
The clinical response to therapeutic doses of two vitamins were determined in diabetic patients with symptomatic peripheral neuropathy. Of 200 consecutive patients, 100 were randomly allocated to treatment with both thiamine (25 mg/day) and pyridoxine (50 mg/day) group A and the rest group B to treatment with an identical tablet containing 1 mg/day each of thiamine and pyridoxine. Pain, numbness, paraesthesia and impairment of sensation and ankle in the legs were graded into none, mild, moderate or severe. Blood thiamine levels were measured using HPLC fluorimetry. Four weeks after starting treatment the grade was less than on the first visit in 88.9%, 82.5% and 89.7% of those whose worst symptoms were pain, numbness and paraesthesia respectively for group A compared with 11.1%, 40.5% and 39.4% respectively for group B. The severity of signs of peripheral neuropathy decreased in 48.9% of patients in group A compared with 11.4% in group B. The mean (s.e.) pre-treatment whole blood thiamine levels decreased with increasing severity of symptoms: 64.2 (2.81), 57.7 (3.25) and 52.2 (2.14) micrograms/l for those with mild, moderate and severe symptoms respectively (analysis of variance, p = 0.03). Diabetic peripheral neuropathy in Dar es Salaam is associated with thiamine deficiency. Dietary guidelines for diabetic patients should emphasize a balanced diet.
104. Diabetes Care. 1998 Jan;21(1):38-41.
Long-term follow-up of diabetes in two patients with thiamine-responsive megaloblastic anemia syndrome.
Valerio G, Franzese A, Poggi V, Tenore A.
Department of Pediatrics, School of Medicine, University of Udine, Italy.
OBJECTIVE: To describe a 15-year follow-up of diabetes and to present data regarding pancreatic beta-cell function in two adolescents affected by the thiamine-responsive megaloblastic anemia (TRMA) syndrome. CASE REPORTS: The first patient (PMR) is a 17.5-year-old Italian girl who presented megaloblastic anemia at 7.5 months of age. At age 2.5 years, because of the presence of diabetes and sensorineural deafness, she was diagnosed with TRMA syndrome and started treatment with thiamine-HCl, followed very early by benzoyloxymethyl-thiamine (BOM-T). The second patient (PF) is a 16.8-year-old Italian boy born to consanguineous parents. Sensorineural deafness was diagnosed at age 1.5 years, while diabetes with ketoacidosis and megaloblastic anemia were diagnosed at age 3 years. Treatment with thiamine HCl was started immediately after diagnosis and changed to BOM-T 2 months later. Subsequent to the initiation of the vitamin, the two patients did not require insulin for approximately 7 and 10 years, respectively. Puberty was determinant in deteriorating the metabolic control in these patients, leading to treatment with an oral hypoglycemic agent and finally to a reinstitution of insulin therapy. CONCLUSIONS: The hormonal assessment in our patients (normal insulin response to oral glucose in childhood, preserved C-peptide secretion in case 2) and the good response to an oral hypoglycemic agent would indicate that the pancreatic disease may initiate as type 2 diabetes and may progress after several years to an insulin-requiring diabetes, as indicated by the exhaustion of the insulin secretory capacity.
105. Med Hypotheses. 1997 Dec;49(6):487-95.
Concept of the noncoenzymatic thiamine effect.
Vinogradov VV, Vodoyevich VP, Rozhko AV, Vinogradov SV.
Institute of Biochemistry, Academy of Sciences of Belarus, Grodno.
The experimental and clinical data on different aspects of vitamin and hormone relationships have been summarized in the form of a general concept of the noncoenzymatic thiamine effect, on the basis of a number of premises: (1) discovery of tissue factors limiting the manifestation of the specific activity of administered thiamine (the presence of a tissue buffer depot of easily accessible coenzymes, and lack of free apoenzymes); (2) evidence of a thiamine effect on the pancreatic insulin-synthesizing function; (3) stimulation of metabolic thiamine effects, including the effects of insulin administration on thiamine-dependent enzymes; (4) determination of the features of hormonal control of thiamine metabolism in the body; (5) confirmation of the predictive force of the concept by clinical trials of the new strategy of thiamine therapy.
106. J Neurochem. 1997 Nov;69(5):2005-10.
Low thiamine diphosphate levels in brains of patients with frontal lobe degeneration of the non-Alzheimer's type.
Bettendorff L, Mastrogiacomo F, Wins P, Kish SJ, Grisar T, Ball MJ.
Laboratory of Neurochemistry, University of Liege, Belgium.
We compared the thiamine and thiamine phosphate contents in the frontal, temporal, parietal, and occipital cortex of six patients with frontal lobe degeneration of the non-Alzheimer's type (FNAD) or frontotemporal dementia with five age-, postmortem delay-, and agonal status-matched control subjects. Our results reveal a 40-50% decrease in thiamine diphosphate (TDP) in the cortex of FNAD patients, whereas thiamine monophosphate was increased 49-119%. TDP synthesizing and hydrolyzing enzymes were unaffected. The activity of citrate synthase, a mitochondrial marker enzyme, was decreased in the frontal cortex of patients with FNAD, but no correlation with TDP content was found. These results suggest that decreased contents of TDP, which is essentially mitochondrial, is a specific feature of FNAD. As TDP is an essential cofactor for oxidative metabolism and neurotransmitter synthesis, and because low thiamine status (compared with other species) is a constant feature in humans, a nearly 50% decrease in cortical TDP content may contribute significantly to the clinical symptoms observed in FNAD. This study also provides a basis for a trial of thiamine, to improve the cognitive status of the patients.
107. J Intern Med. 1997 Dec;242(6):491-5.
No difference in blood thiamine diphosphate levels between Swedish Caucasian patients with congestive heart failure treated with furosemide and patients without heart failure.
Yue QY, Beermann B, Lindstrom B, Nyquist O.
Department of Clinical Pharmacology, Huddinge University Hospital, Sweden.
OBJECTIVES: To determine whether furosemide treatment in congestive heart failure (CHF) patients is associated with thiamine deficiency. DESIGN: Patients without heart failure and without diuretic treatment were included to compare with patients with CHF belonging to New York Heart Association (NYHA) functional class II and III-IV, respectively, and receiving furosemide therapy. SETTING: All patients were recruited from the emergency ward of the cardiology section. Huddinge University Hospital, where they were admitted due to CHF or acute myocardial infarction. SUBJECTS: Ninety-nine patients were included from whom a blood sample was taken, as well as routine admission blood samples for the analysis of thiamine diphosphate (TPP) concentrations. Patients taking vitamin preparations were excluded. MAIN OUTCOME MEASURES: Blood TPP concentrations were measured by high performance liquid chromatography (HPLC) and compared between the patient groups by the use of ANOVA. RESULTS: No significant difference was found between the groups in blood TPP concentrations. CONCLUSIONS: Thiamine deficiency may not be a complication of furosemide treatment in the studied Swedish patient population.
108. Vopr Pitan. 1997;(4):6-8.
[ Indicators of thiamine content and energy homeostasis in alcoholic psychosis]
[Article in Russian]
Bolko EP, Sidorov PI, Solov'ev AG, Kirpich IA.
In dynamics of acute alcoholic psychoses--delirium and hallucinosis-- considerable deficit of thiamine in the organisms of ill people that can not be compensated while desintoxicative treatment and signs of energy homeostasis changes and of deterioration of tissues reserves depending on the type of psychoses were determined. Pathogenic peculiarities of the revealed disorders were analysed, possible compensative mechanisms connected in particular with the rise of pyruvate utilization speed and activation of glyconeogenesis while leaving the psychotic state were considered.
109. Miner Electrolyte Metab. 1997;23(3-6):277-82.
Comparison of the thiamine level in blood and erythrocyte transketolase activity in hemodialyzed and nondialyzed patients during recombinant human erythropoietin therapy.
Pietrzak I, Baczyk K.
Department of Nephrology, University of Medical Sciences, Poznan, Poland.
Thiamine and erythrocyte transketolase activity (ETKA) disturbances in end-stage renal disease are caused mainly by uremia and dialysis treatment. We examined whether recombinant human erythropoietin (rhEPO) can correct these abnormalities in uremic patients. Thirteen hemodialysis (HD) and 12 nondialyzed (ND) anemic patients showed decreased free and total thiamine levels in plasma and in erythrocytes and decreased ETKA when compared to 20 healthy subjects. Thiamine blood levels (mumol/l) were determined using a fluorimetric technique, and ETKA (mumol/l per minute) was assessed with a photocolorimetric method. Over 20 weeks of study, rhEPO was given intravenously for 8 weeks at 50 Ul/kg body weight (BW) three times a week, and subcutaneously for 4 weeks at 25 Ul/kg BW, twice a week, and for the last 8 weeks at 25 Ul/kg BW once a week. The correction of anemia was associated with an increase in plasma thiamine and erythrocyte total thiamine as well as ETKA in HD patients and with an increase in erythrocyte total thiamine in ND patients only during the period of intravenous infusions.
110. Ann N Y Acad Sci. 1997 Sep 26;826:516-9.
Importance of vascular changes in selective neurodegeneration with thiamine deficiency.
Gibson GE, Calingasan NY, Baker H, Gandy S, Sheu KF.
Cornell University Medical College, Burke Medical Research Institute, White Plains, New York 10605, USA.
These results demonstrate that early alterations in the BBB may underlie selective vulnerability in this model of chronic reduced oxidative metabolism. Changes in the BBB (IgG extravasation) precede alterations in APP processing and cell death. Since thiamine-dependent enzymes are also reduced in the brain in Alzheimer's disease, similar processes may be important in the pathophysiology of the disease.
111. Am J Clin Nutr. 1997 Oct;66(4):925-8.
The response to treatment of subclinical thiamine deficiency in the elderly.
Wilkinson TJ, Hanger HC, Elmslie J, George PM, Sainsbury R.
Department of Health Care of the Elderly, Princess Margaret Hospital, Christchurch, New Zealand.
The significance of subclinical thiamine deficiency in the elderly was determined by assessing response to thiamine supplementation in a randomized double-blind, placebo-controlled trial. Thirty-five of 222 people aged > or = 65 y had two concentrations of erythrocyte thiamine pyrophosphate (TPP) < 140 nmol/L 3 mo apart and 41 other people had the first, but not the second, TPP concentration below this value. Both groups were randomly assigned in a double-blind trial to oral thiamine (10 mg/d) or a placebo. All subjects randomly assigned to receive thiamine showed increases in TPP concentrations compared with control subjects. Only the subjects with persistently low TPP concentrations showed subjective benefits from treatment with improvements in quality of life (measured on a visual analogue scale; P = 0.02) and decreases in systolic blood pressure (P = 0.05) and weight (P < 0.01) when compared with subjects given placebo. There was a trend toward benefits in sleep and energy (P = 0.07). We conclude that a low TPP concentration on two occasions is a better predictor of response to treatment than an isolated measurement. Quality of life was enhanced by providing thiamine supplements. Blood pressure and weight were lower after thiamine supplementation.
112. Mol Cell Biochem. 1997 Sep;174(1-2):121-4.
Reversibility of thiamine deficiency-induced partial necrosis and mitochondrial uncoupling by addition of thiamine to neuroblastoma cell suspensions.
Bettendorff L, Goessens G, Sluse FE.
Laboratory of Neurochemistry, University of Liege, Belgium.
Culture of neuroblastoma cells in the presence of low thiamine concentration (16 nM) and of the transport inhibitor amprolium leads to the appearance of signs of necrosis: the chromatin condenses, the oxygen consumption decreases and is uncoupled, the mitochondrial cristae are disorganized, the thiamine diphosphate-dependent dehydrogenase activities are impaired. When 10 microM thiamine are added to these cells, the basal respiration increases, the coupled respiration is restored and mitochondrial morphology is recovered within 1 h. Addition of succinate, which is oxidized via a thiamine diphosphate-independent dehydrogenase, to digitonin-permeabilized cells immediately restores a coupled respiration. Our results suggest that the slowing of the citric acid cycle is the cause of the biochemical lesion induced by severe thiamine deficiency and that part of the mitochondria remain functional.
113. J Intern Med. 1997 Aug;242(2):179-83.
Protection against cardiovascular collapse in an alcoholic patient with thiamine deficiency by concomitant alcoholic ketoacidosis.
Bakker SJ, ter Maaten JC, Hoorntje SJ, Gans RO.
Department of Medicine, University Hospital Vrije Universiteit, Amsterdam, The Netherlands.
Hyperlactataemia due to thiamine deficiency has so far only been reported in the setting of full-blown cardiovascular beriberi with congestive heart failure and systemic vasodilatation. Poor tissue oxygenation and impaired lactate clearance by the liver are generally accepted as underlying causes of the elevated lactate levels. We present an alcoholic patient with thiamine deficiency-induced hyperlactataemia and accompanying alcoholic ketoacidosis, who did not display the circulatory disturbances that are characteristic of cardiovascular beriberi. The hypothesis will be presented that the concomitant presence of alcoholic ketoacidosis has prevented haemodynamic deterioration. Putative mechanisms that could explain such an effect are discussed in detail, with special reference to the role of acetyl-CoA and adenosine.
114. Am J Clin Nutr. 1997 Aug;66(2):320-6.
Thiamine uptake in human intestinal biopsy specimens, including observations from a patient with acute thiamine deficiency.
Laforenza U, Patrini C, Alvisi C, Faelli A, Licandro A, Rindi G.
Institute of Human Physiology, University of Pavia, Italy.
Mucosal biopsy specimens obtained by routine endoscopy from 108 human subjects, including one patient with thiamine deficiency, were incubated at 37 degrees C in oxygenated calcium-free Krebs-Ringer solution (pH 7.5) containing tritiated thiamine and [14C]dextran as a marker of adherent mucosal water. The amount of labeled thiamine taken up was measured radiometrically. In subjects with no clinical evidence of thiamine deficiency, 1) thiamine uptake by duodenal mucosa had a hyperbolic time course, reaching equilibrium at 10 min; 2) thiamine concentrations < 2.5 mumol/L were taken up predominantly by a saturable mechanism displaying Michaelis-Menten kinetics (K(m) 4.4 mumol/L and Jmax 2.3 pmol.mg wet tissue-1.6 min-1), whereas higher concentrations were taken up by passive diffusion; 3) thiamine transport had different capacities along the gastrointestinal tract (duodenum >> colon > stomach); and 4) thiamine uptake was competitively inhibited in the duodenum by thiamine analogs, albeit with a different order of potency compared with rats, and was blocked by 2,4-dinitrophenol. In the thiamine-deficient patient, the duodenal saturable uptake was increased, with higher K(m) and Jmax values. In conclusion, physiologic concentrations of thiamine were transported in human small intestine by a specific mechanism dependent on cellular metabolism, whose transporters appear to be down-regulated.
115. Alcohol Alcohol. 1997 Jul-Aug;32(4):493-500.
Thiamine deficiency in head injury: a missed insult?
Ferguson RK, Soryal IN, Pentland B.
Scottish Brain Injury Rehabilitation Service, Astley Ainslie Hospital, Grange Loan, Edinburgh, UK.
Practice regarding the use of thiamine in head-injured patients at risk of Wernicke-Korsakoff syndrome in Scottish neurosurgical units was surveyed by questionnaire and revealed no clear policy. A 2 year retrospective study of 218 admissions to one of these units of patients who had taken alcohol shortly before sustaining head injury is also described. The minority (20.6%) of the total had been given thiamine, with just over half (56.1%) of those categorized as alcoholic receiving this treatment. Additional carbohydrate loads, in the form of i.v. dextrose or parenteral nutrition, had been given to 44.5% of patients and only 28.9% of this group had also been given thiamine. The dose and duration of thiamine given was inadequate in most cases. It is suggested that failure to ensure that head injury patients at risk of Wernicke-Korsakoff syndrome receive appropriate thiamine prophylaxis represents a missed and treatable additional insult to the damaged brain.
116. Cleft Palate Craniofac J. 1997 Jul;34(4):318-24.
Application of thiamine in preventing malformations, specifically cleft alveolus and palate, during the intrauterine development of rats.
Bienengraber V, Fanghanel J, Malek FA, Kundt G.
Division of Experimental Dentistry, University of Rostock, Federal Republic of Germany.
OBJECTIVE: Animal experiments were conducted to test the reproducibility of previously documented antiteratogenic effects of thiamine on cleft formation in the craniofacial system. DESIGN: Thirteen gravid Wistar rats carrying 98 fetuses were given the hydrazine derivative procarbacine (200 mg/kg BW) on the fourteenth day postconception (PC) to induce malformations, chiefly cleft alveolus and palate (day of determining presence of sperm was called the first day PC). Seven of the treated gravid rats carrying 48 fetuses were additionally given a daily dose of 200 mg/kg thiamine from the thirteenth to the nineteenth day PC. OUTCOME MEASURES: A comparative analysis of the fetuses in both experimental groups was conducted externally and, for the skeleton, macroscopically using special staining techniques; the heads were analyzed using successional histologic sections; bodies were examined stereomicroscopically using the razor-blade sectioning technique. RESULTS: In 12 of the 16 parameters evaluated, no statistically significant differences were found between experimental groups. In some cases, we even observed an amplifying effect of thiamine on the development of malformations in the rat strain used in our study. CONCLUSIONS: Because several previous authors have repeatedly described treatment with thiamine as one of the sufficient prophylactic measures in slowing the development of viscerocranial malformations, especially cleft alveolus and palate, it is of utmost importance that the timing of treatment and dosage of thiamine be taken into consideration not only in animal experiments but also when applying results to humans.
117. MMWR Morb Mortal Wkly Rep. 1997 Jun 13;46(23):523-8.
Lactic acidosis traced to thiamine deficiency related to nationwide shortage of multivitamins for total parenteral nutrition -- United States, 1997.
[No authors listed]
Since November 1996, there has been a nationwide shortage of intravenous (IV) multivitamins (MVIs) used in U.S. hospitals and home-health-care agencies for total parenteral nutrition (TPN). Patients receiving TPN without MVI supplementation are at risk for thiamine deficiency and life-threatening complications associated with severe deficiency of thiamine, a coenzyme necessary for oxidation of keto acids (Figure 1). This report describes three patients receiving TPN who had thiamine deficiency-related lactic acidosis in 1997 and presents recommendations for alternatives to parenteral MVI during the shortage.
118. Nutrition. 1997 Jun;13(6):547-53.
Comment in: Nutrition. 1997 Jun;13(6):571-2.
Stability of ranitidine and thiamine in parenteral nutrition solutions.
Baumgartner TG, Henderson GN, Fox J, Gondi U.
Shands Hospital, University of Florida, Gainesville 32610-0316, USA.
Our objectives were to ascertain the stability of thiamine HCl (3 mg/L) and ranitidine HCl (150 mg/L) at room and refrigeration temperatures in a central vein formula of parenteral nutrition (PN) solution (containing 6% amino acid, 25% carbohydrate, macro- and microminerals, and multivitamins) and to determine the effect of ranitidine on the stability of thiamine. Stability of thiamine and ranitidine in PN solutions was also compared with PN-salt solutions, which contained no amino acids or carbohydrates, to indirectly ascertain the impact of these macronutrients on the stability of these moieties. High-pressure liquid chromatography (HPLC) methods were developed to measure thiamine and ranitidine in the PN mixture. Stability studies were conducted in triplicate and each sample was assayed in duplicate using newly developed HPLC methods. Refrigeration provided stability for both ranitidine and thiamine for extended periods of time. At room temperature, ranitidine was also shown to be stable for about 188 h; there was, however, significant degradation of thiamine at 24 h with, and without, addition of ranitidine. The time required for 10% of thiamine to degrade was calculated to be 12.9 h for the PN mixture containing multivitamins and ranitidine; 11.1 h for the PN mixture containing multivitamins alone; and 33.4 h for the PN mixture containing only thiamine HCl. This work suggests that the concentration of thiamine in this central vein PN formula, with or without ranitidine, falls below the 90% acceptable stability within 24 h.
119. Psychiatry Res. 1997 May 30;70(3):165-74.
Beneficial effects of thiamine on recognition memory and P300 in abstinent cocaine-dependent patients.
Easton CJ, Bauer LO.
Department of Psychiatry, University of Connecticut Health Center, Farmington 06030-2103, USA.
The present study evaluated the effects of thiamine vs. placebo on memory task performance and event-related electroencephalographic potentials in eight abstinent cocaine-dependent patients. Patients orally ingested 5 g of thiamine and 5 g of a lactose placebo on two separate days scheduled approximately 1 week apart. The order of administration was randomized. Double-blind procedures were followed. Approximately 3 h after ingesting the capsules, patients completed Sternberg's (1975) memory scanning task during which performance and event-related potentials (P300) were recorded simultaneously. Thiamine was found to significantly improve recognition accuracy and P300 amplitude, at the midline parietal (Pz) electrode. The improvement was most reliable under conditions of increased memory load. These preliminary findings justify a further examination of the relation between thiamine's hypothesized effects on central nervous system cholinergic function, and the direct and indirect effects of cocaine abuse.
120. Alcohol Alcohol. 1997 May-Jun;32(3):207-9.
Comment in: Alcohol Alcohol. 1998 Sep-Oct;33(5):549-51.
Parenteral thiamine and Wernicke's encephalopathy: the balance of risks and perception of concern.
Thomson AD, Cook CC.
Greenwich District Hospital, Vanbrugh Hill, London, UK.
Wernicke's encephalopathy, a disorder with significant mortality and high morbidity, is common amongst alcohol-dependent patients. Thiamine deficiency appears to play a key role in its aetiology, and parenteral high-dose thiamine is effective in prophylaxis and treatment. Unfortunately, reports of rare anaphylactoid reactions have led to a dramatic reduction in the use of parenteral thiamine, and it is possible that this change in treatment has led, or will lead, to an increase in morbidity and mortality. There is a need for education of doctors who treat alcohol-dependent patients, in order to ensure appropriate use of parenteral thiamine in prophylaxis and treatment of this disorder.
121. Nutrition. 1997 Feb;13(2):110-7.
Clinical and biochemical aspects of thiamine treatment for metabolic acidosis during total parenteral nutrition.
Nakasaki H, Ohta M, Soeda J, Makuuchi H, Tsuda M, Tajima T, Mitomi T, Fujii K.
Department of Surgery, Tokai University Oiso Hospital, Kanagawa, Japan.
We encountered six cases of total parenteral nutrition (TPN)-associated lactic acidosis during the 6-y period of 1988-1993. The patients were characterized by severe disease of the digestive organs, minimal food intake before surgery, and postoperative TPN with no food intake and with no vitamin supplements. Within 4 wk of TPN, they developed hypotension (< or = 80/60 mmHg), Kussmaul's respiration, and clouding of consciousness, as well as abdominal pain not directly related to the underlying disease. Routine laboratory examinations revealed no acute aggravation in hepatic, renal, or pancreatic functions. Arterial blood gas analysis showed pH < or = 7.134 and base excess < or = -17.5 mmol/L. Additional laboratory examinations revealed serum lactate > or = 10.9 mmol/L, serum pyruvate > or = 159 mumol/L, and lactate/pyruvate ratio > or = 0.029. None of the patients responded to sodium bicarbonate or other conventional emergency treatments for shock and lactic acidosis. After the first case, we suspected that thiamine deficiency might be responsible for this pathologic condition, Serum thiamine was proved to be < or = 196 nmol/L in 5 patients. Thiamine replenishment at intravenous doses of 100 mg every 12 h resolved lactic acidosis and improved the clinical condition in 3 patients. This article includes a review of 11 relevant reports published from 1982-1992 and a discussion of the biochemical mechanism of onset of thiamine deficiency-associated lactic acidosis. We emphasize the needs (1) to supplement TPN with thiamine-containing vitamins for the patients whose food intake does not meet nutritional requirements; (2) to monitor the patients routinely measuring serum thiamine concentration and erythrocyte transketolase activity during TPN; and (3) to intravenously replenish using high-dose thiamine simultaneously with the manifestation of signs and symptoms of lactic acidosis.
122. Psychopharmacology (Berl). 1997 Jan;129(1):66-71.
Thiamine supplementation mood and cognitive functioning.
Benton D, Griffiths R, Haller J.
Department of Psychology, University of Wales Swansea, UK.
One hundred and twenty young adult females took either a placebo or 50 mg thiamine, each day for 2 months. Before and after taking the tablets, mood, memory and reaction times were monitored. An improvement in thiamine status was associated with reports of being more clearheaded, composed and energetic. The taking of thiamine had no influence on memory but reaction times were faster following supplementation. These influences took place in subjects whose thiamine status, according to the traditional criterion, was adequate.
123. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 1996 Dec;82(6):634-6.
Recurrent aphthous stomatitis and thiamine deficiency.
Haisraeli-Shalish M, Livneh A, Katz J, Doolman R, Sela BA.
Department of Orthodontics, Tel Aviv University, Israel.
Recurrent aphthous stomatitis is a disease of unknown cause. To examine whether thiamine (vitamin B1) deficiency is associated with recurrent aphthous stomatitis, we studied vitamin B1 levels in 70 patients with recurrent aphthous stomatitis and in 50 members of a control group. The vitamin B1 level was determined as thiamine pyrophosphate effect on transketolase activity in red blood cell lysates. Low levels of vitamin B1 were detected in 49 patients but in only two members of the control group (p < 0.0001). These low levels were not associated with patient age, sex, or underlying disease causing recurrent aphthous stomatitis. Our finding suggests an association between thiamine deficiency and recurrent aphthous stomatitis.
124. Am J Gastroenterol. 1996 Dec;91(12):2555-9.
Thiamine status in patients receiving long-term home parenteral nutrition.
Schiano TD, Klang MG, Quesada E, Scott F, Tao Y, Shike M.
Department of Medicine, The University of Chicago Medical Center, Illinois 60637, USA.
OBJECTIVES: Clinical thiamine deficiency can occur in patients receiving total parenteral nutrition (TPN) without thiamine supplementation. Because considerable breakdown of thiamine may occur in the presence of bisulfite-containing amino acid solutions, subclinical thiamine deficiency may develop with the use of these solutions, even with appropriate thiamine supplementation. The current American Medical Association-Food and Drug Administration approved injectable multivitamin formula contains 3 mg of thiamine. This study was undertaken to determine whether this quantity of thiamine is sufficient to avoid clinical thiamine deficiency in long-term home TPN patients with negligible oral thiamine absorption and in the presence of bisulfite-containing amino acid solutions. METHODS: Twenty-four long-term home TPN patients with oral caloric intakes below the norm were evaluated. Seventeen patients suffered from short bowel syndrome or radiation enteritis, and another three had draining gastrostomies that precluded all intestinal absorption. The duration of TPN therapy ranged between 1 and 164 months. Thiamine status was assessed by assaying thiamine pyrophosphate, transketolase activity, and blood thiamine levels. RESULTS: All thiamine pyrophosphate and erythrocyte transketolase activity levels were within the normal range. CONCLUSIONS: This study demonstrates that the currently recommended 3 mg of thiamine hydrochloride added to TPN solutions is adequate to maintain normal thiamine status. This should prevent the development of thiamine deficiency even in patients with compromised intestinal thiamine absorption, and in the presence of bisulfite-containing amino acid solutions.
125. Biochim Biophys Acta. 1996 Nov 15;1317(2):101-4.
Thiamine (vitamin B1) supplementation does not reduce fasting blood homocysteine concentration in most homozygotes for homocystinuria.
Franken DG, Blom HJ, Boers GH, Tangerman A, Thomas CM, Trijbels FJ.
Department of Radiology, University Hospital Nijmegen, The Netherlands.
Homozygotes for homocystinuria due to cystathionine synthase (CS) deficiency accumulate homocysteine and methionine in their blood and tissues. High-dose pyridoxin, folic acid, vitamin B12, or betaine are therapeutical options to lower the elevated homocysteine concentration. These compounds stimulate the transsulfuration or remethylation of homocysteine. Despite such treatment, elevated blood homocysteine concentrations may persist in many homocystinurics. Therefore, it is warranted to study alternative regimen to reduce the blood homocysteine concentration in homocystinurics. Apart from entering the transsulfuration pathway, methionine can be catabolized via the transamination pathway, by conversion into 4-methylthio-2-oxobutyrate (MTOB), followed by oxidative decarboxylation of MTOB to 3-methylthiopropionate. Thiamine pyrophosphate, the active form of thiamine, is a cofactor of the supposed rate-limiting oxidative decarboxylation in the transamination of methionine. The effect of thiamine administered in 2 or 3 daily doses of 25 mg orally, was studied in nine homozygote CS deficient patients. Methionine levels decreased in 6 out of 9 patients. In 8 out of 9 patients, however, the levels of plasma homocysteine remained virtually unchanged, as did the serum transamination metabolites in all patients. We conclude that vitamin B1 cannot be used as an additional homocysteine-lowering treatment in most homozygotes for homocystinuria.
126. Diabetologia. 1996 Nov;39(11):1263-8.
Comment in: Diabetologia. 1997 Jun;40(6):741-2.
Thiamine corrects delayed replication and decreases production of lactate and advanced glycation end-products in bovine retinal and human umbilical vein endothelial cells cultured under high glucose conditions.
La Selva M, Beltramo E, Pagnozzi F, Bena E, Molinatti PA, Molinatti GM, Porta M.
Department of Internal Medicine, University of Turin, Italy.
This study aimed at verifying whether thiamine, a co-enzyme which decreases intracellular glycolysis metabolites by allowing pyruvate and glyceraldheyde 3-phosphate to enter the Krebs cycle and the pentose-phosphate shunt, respectively, corrects delayed replication caused by high glucose concentrations in cultured human umbilical vein (HUVEC) and bovine retinal endothelial cells (BREC). After incubation in physiological (5.6 mmol/l) or high (28.0 mmol/l) glucose with or without 150 mumol/l thiamine, cells were counted and proliferation assessed by mitochondrial dehydrogenase activity. Lactate was measured in both cell types as an index of glycolytic activity and fluorescent advanced glycosylation end-products (AGE) concentration was determined in the HUVEC lysate. Both cell counts and proliferation assays in either of the cell types confirmed the impairment to cell replication induced by high glucose. When thiamine was added to cells kept under high glucose conditions, the number of surviving cells was significantly increased and the reduced cell proliferation appeared to be corrected. Lactate assays confirmed the increased production of this metabolite by BREC and HUVEC in high glucose, which was reduced by thiamine. Fluorescent AGE determination showed that thiamine may prevent non-enzymatic glycation in HUVEC. Thiamine restores cell replication, decreases the glycolytic flux and prevents fluorescent AGE formation in endothelial cells cultured in high glucose, suggesting that abnormal levels of glycolytic metabolite(s) may damage cells.
127. J Pediatr. 1996 Nov;129(5):758-60.
Primary treatment of propionic acidemia complicated by acute thiamine deficiency.
Matern D, Seydewitz HH, Lehnert W, Niederhoff H, Leititis JU, Brandis M.
Department of Pediatrics, Albert-Ludwigs-University, Freiburg, Germany.
Propionic acidemia is often manifested during the neonatal period with vomiting, failure to thrive, lethargy, and hyperammonemic coma when catabolism is prolonged. Mild lactic acidosis frequently accompanies metabolic decompensation. We present two patients with propionic acidemia whose initial manifestation was complicated by severe lactic acidosis caused by thiamine deficiency, which resulted from an inadequate supply of, and an increased need for, thiamine during metabolic stress. To prevent acute thiamine deficiency, we propose early vitamin supplementation during treatment of any severe metabolic decompensation accompanied by insufficient food intake.
128. J Stud Alcohol. 1996 Nov;57(6):581-4.
Thiamine absorption in alcoholic delirium patients.
Department of Psychiatry, St. Josef-Hospital, Oberhausen, Germany.
OBJECTIVE: The role of a deficiency of vitamin B1 in the development of alcoholic complaints is confined to the case of the Wernicke-Korsakov syndrome. Findings concerning a deficiency of thiamine in alcoholics in comparison with normal persons are contradictory and there are no differentiated tests in the case of delirium tremens. In this study the vitamin B1 absorption in patients with delirium tremens was of interest in connection with the presence or absence of hallucinations and autonomic symptoms. METHOD: Male patients (N = 70) with delirium tremens were compared with a group of 13 controls. The controls and patients were hospitalized in order to ensure abstinence from alcohol. The examination of the delirium patients was carried out with their consent after termination of the delirium tremens and again on discontinuance of drug therapy. In the case of 33 delirium patients the absorption of thiamine was tested again 4 weeks after the first examination. RESULTS: The absorption of vitamin B1 was in general only minimally lower in the case of the delirium patients in comparison with the nonalcoholics. The results showed, however, a considerably greater range of scattering of vitamin B1 absorption in the delirium patients. The absorption conditions showed marked improvement in the 4 weeks after delirium. The extent of absorption of vitamin B1 showed no influence on the duration of delirium. The patients with visual hallucinations, however, showed lower thiamine absorption than patients without such symptoms, whereas no dependence of autonomic symptoms on vitamin B1 absorption was seen. CONCLUSIONS: The disturbed absorption conditions in the delirium patients were obvious at the time of the examination as demonstrated by the wide range of absorption values. Improvement or near normal conditions were registered 4 weeks after the delirium. The absorption conditions had possibly already improved during the few days of alcohol abstinence in the course of the delirium treatment. The reduced vitamin B1 absorption of patients suffering from visual hallucination corresponds to observations of alcoholic hallucinosis.
129. Cardiologia. 1996 Sep;41(9):883-6.
[Thiamine-deficiency cardiopathy: a rare cause of cardiac failure in childhood]
[Article in Italian]
Minneci C, De Simone L, Repetto T, Manetti A.
UO Cardiologia Pediatrica, Azienda Ospedaliera A Meyer, Firenze.
Cardiac beriberi is a rare cause of heart failure in infancy and the diagnosis is often very difficult. We describe the case of a 4-year-old girl admitted to our Hospital with symptoms of heart failure and diagnosis of myocarditis. In children with acute cardiac failure and suggestive history and signs of peripheral neuropathy, thiamine deficiency should be suspected.
130. Alcohol Alcohol. 1996 Sep;31(5):493-501.
Thiamine pyrophosphate effect and normalized erythrocyte transketolase activity ratio in Wernicke-Korsakoff patients and acute alcoholics undergoing detoxification.
Rooprai HK, Pratt OE, Shaw GK, Thomson AD.
Department of Neuropathology, Institute of Psychiatry, London, UK.
Thiamine deficiency may be assessed clinically by an abnormally low specific erythrocyte transketolase activity and/or by abnormally large activation by thiamine diphosphate in vitro (or 'TPP effect'). In the present investigation, we report erythrocyte transketolase activation by TPP in acute alcoholics and Wernicke-Korsakoff patients undergoing detoxification. A new age-dependent parameter was used to improve the reliability of transketolase activity as an indicator of marginal thiamine deficiency. Thus normalized transketolase activity ratio (NTKZ), primary activation ratio (PAR) and further activation ratio (FAR) were measured in 29 acute alcoholics and 12 Wernicke-Korsakoff patients upon admission, and also on 47 control subjects. It was possible to follow up 14 of the 29 acute alcoholics after 7 days of treatment. Twenty-one per cent of the acute alcoholics and 33% of the Wernicke-Korsakoff patients, on admission to the detoxification Unit, had NTKZ values beyond the defined critical conditions for thiamine deficiency, whereas 7% of the former and 25% of the latter had PAR values beyond these critical conditions. Furthermore, all three parameters were significantly different in the Wernicke-Korsakoff patients compared to the other groups. The pattern of improvement of the different parameters on follow-up varied considerably and is difficult to explain, as only the NTKZ was statistically significant. Hence, only eight out of 14 acute alcoholics showed improvement in NTKZ, seven showed improvement of PAR and six showed improvement of FAR after treatment. Five patients showed improvement of both NTKZ and PAR and none of the patients showed improvement of all three parameters. We conclude that our findings confirm previous reports and that this modified transketolase activation test improves its reliability as an indicator of marginal thiamine deficiency.
131. Am J Pathol. 1996 Sep;149(3):1063-71.
Novel neuritic clusters with accumulations of amyloid precursor protein and amyloid precursor-like protein 2 immunoreactivity in brain regions damaged by thiamine deficiency.
Calingasan NY, Gandy SE, Baker H, Sheu KF, Smith JD, Lamb BT, Gearhart JD, Buxbaum JD, Harper C, Selkoe DJ, Price DL, Sisodia SS, Gibson GE.
Cornell University Medical College, Burke Medical Research Institute, White Plains, New York 10605, USA.
Experimental thiamine deficiency (TD) is a classical model of a nutritional deficit associated with a generalized impairment of oxidative metabolism and selective cell loss in the brain. In rats, TD-induced cell degeneration is accompanied by an accumulation of amyloid precursor protein (APP)/amyloid precursor-like protein 2 (APLP2) immunoreactivity in abnormal neurites and perikarya along the periphery of, or scattered within, the lesion. Prompted by these data and our previous findings of a genetic variation in the development of TD symptoms, we extended our studies to mice. C57BL/6, ApoE knockout, and APP YAC transgenic mice received thiamine-deficient diet and pyrithiamine injections. Unlike rats, APP/APLP2-immunoreactive neurites in all strains of mice were sparsely scattered within damaged areas and did not delimit the thalamic lesion. In addition, abnormal clusters of intensely immunoreactive neurites occurred only in areas of damage including the thalamus, mammillary body, and inferior colliculus. The clusters appeared as either irregular clumps or round or oval rosettes that strikingly resembled the neuritic component of Alzheimer amyloid plaques. However, immunostaining using various antisera to synthetic amyloid beta-protein (A beta 1-40) and thioflavine S histochemistry failed to show evidence of a component of A beta Neither APP/APLP2-immunoreactive clusters nor amyloid plaques were observed in the brain from patients with Wernicke-Korsakoff syndrome, the clinical manifestation of TD in man. Our results demonstrate species (i.e., genetic) differences in the response to TD-induced damage and support a role for APP and APLP2 in the response to brain injury. This is the first report that chronic oxidative deficits can lead to this novel pathology.
132. Am J Clin Nutr. 1996 Sep;64(3):347-53.
Comment in: Am J Clin Nutr. 1996 Sep;64(3):383-4. Am J Clin Nutr. 1997 Apr;65(4):1090-2. Am J Clin Nutr. 1997 Apr;65(4):1092-3.
Biochemical evidence of thiamine depletion during the Cuban neuropathy epidemic, 1992-1993.
Macias-Matos C, Rodriguez-Ojea A, Chi N, Jimenez S, Zulueta D, Bates CJ.
Institute of Nutrition and Food Hygiene, Havana.
During an epidemic outbreak of neuropathy in Cuba during 1992-1993, blood and urine samples were collected from 107 persons with confirmed neuropathy, from 106 control subjects without clinical abnormality who were broadly matched with the affected persons by age and domicile, and from 537 unmatched subjects, also free from clinical abnormality. The unmatched subjects lived in two locations in Cuba; at each location they were drawn from two age ranges: 11-15-y-old secondary school students and 16-64-y-old adults. Measurements of urinary thiamine and blood transketolase and its activation with thiamine pyrophosphate were made. For the neuropathy subjects, these measurements were repeated after 3 wk of rehabilitation. All groups showed biochemical evidence of thiamine depletion affecting 30-70% of their members, which is a high prevalence. Severity of biochemical depletion was, however, no greater in the neuropathy subjects than in the control subjects (P > 0.05). However, it was greater in Pinar del Rio, where the incidence of disease was higher, than in the city of Havana, where less disease was seen. Although the majority of the affected subjects responded biochemically to a daily oral multivitamin supplement containing thiamine (P < 0.001), in some cases normal biochemical status was not achieved even after 3 wk of intensive treatment. In the affected group, thiamine status was inversely correlated with the amount of alcohol consumed (P = 0.007). Thiamine status at the outset was correlated with clinical outcome after treatment. Although neither thiamine depletion nor alcohol abuse were likely to have been the sole cause of the neuropathy epidemic, they may have been contributory factors. Thiamine supplementation or food fortification may therefore be necessary in Cuba.
133. Mov Disord. 1996 Jul;11(4):437-9.
Brain levels of thiamine and its phosphate esters in Friedreich's ataxia and spinocerebellar ataxia type 1.
Bettendorff L, Mastrogiacomo F, LaMarche J, Dozic S, Kish SJ.
Laboratory of Neurochemistry, University of Liege, Belgium.
Decreased blood and cerebrospinal fluid levels of thiamine have been reported in patients with spinocerebellar ataxia disorders. To determine whether a thiamine deficiency is present in the brain, we measured levels of thiamine and its phosphate esters thiamine monophosphate (TMP) and thiamine diphosphate (TDP), in postmortem cerebellar and cerebral cortices of patients with Friedreich's ataxia (FA) and spinocerebellar ataxia type 1 (SCA1). Brain levels of free (nonphosphorylated) thiamine, TMP, TDP, and total thiamine in FA and SCA1 were, on average, not significantly different from control values. However, a nonsignificant trend was observed for slightly reduced levels of TDP and total thiamine in cerebellar cortex of the SCA1 patients, a finding that might be related to the severe neuronal damage in this brain area. We conclude that in FA, brain thiamine concentrations are normal, whereas in SCA1 the levels are, at most, only slightly reduced.
134. J Nutr. 1996 Jul;126(7):1791-8.
Thiamine pyrophosphate-requiring enzymes are altered during pyrithiamine-induced thiamine deficiency in cultured human lymphoblasts.
Pekovich SR, Martin PR, Singleton CK.
Department of Molecular Biology, Vanderbilt University, Nashville, TN 37325, USA.
The most common of the severe complications of thiamine deficiency are beriberi and Wernicke-Korsakoff syndrome. To help clarify the biochemical basis for these disorders, a cell culture system has been established in which pyrithiamine, a potent thiamine transport inhibitor, was used to mimic different degrees of thiamine deficiency within human lymphoblasts. Activities of both transketolase and alpha-ketoglutarate dehydrogenase (alpha-KGDH) decreased at the same rate and to roughly the same levels in response to thiamine deficiency within a given cell line. However, variation in sensitivity to thiamine deficiency, as judged by the relative percentage of loss of enzymatic activities, was found when different cell lines were compared. When exogenous thiamine pyrophosphate was added to the activity assays, differences between transketolase and alpha-KGDH became readily apparent. Only 25% of the lost transketolase activity was present as apo-enzyme, whereas 70% of the lost alpha-KGDH activity was present in the apo-enzyme form. For transketolase, the non-recoverable activity was due mainly to a decrease in the synthesis rate of the protein during thiamine deficiency, suggesting that thiamine has a direct effect on the expression of the transketolase gene and/or protein. PMID: 8683340
135. Tijdschr Gerontol Geriatr. 1996 Jun;27(3):97-101.
[Failure in self care and heart failure, thiamine deficiency in geriatric patients]
[Article in Dutch]
te Water W, Jellesma-Eggenkamp MJ, Bruijns E.
Ziekenhuis Rijnstate, afdeling klinische geriatrie, Arnhem.
In two patients admitted to a geriatric ward cardiac failure was based on a thiamine deficiency (wet beri-beri). After supplementation with thiamine they recovered completely. The first patient had a insufficient diet of only canned food, whereas the second patient suffered from both alcoholism and insufficient nutrients. These geriatric patients suffered from a serious illness due to a combination of somatic, psychological, functional en social factors. Thiamine is a co-enzyme in many metabolic processes. A thiamine deficiency is defined as a serum concentration below 95 nmol/1. Other diseases associated with thiamine deficiency are the Wernicke-Korsakoff syndrome and peripheral polyneuropathy (dry beri-beri). Not only alcoholics but also elderly patients with malnutrition are at risk of thiamine deficiency and associated diseases. Do not hesitate to supplement thiamine in case of cardiac failure because of possible thiamine deficiency. PMID: 8701451
136. Acta Paediatr. 1996 May;85(5):625-8.
Pyruvate dehydrogenase deficiency in a child responsive to thiamine treatment.
Pastoris O, Savasta S, Foppa P, Catapano M, Dossena M.
Institute of Pharmacology, Science Faculty, University of Pavia, Italy.
We report the clinical features in a 4-year-old child who was investigated for a suspected metabolic disorder but was subsequently diagnosed as having a pyruvate dehydrogenase deficiency. A muscle biopsy was performed and the data obtained suggested thiamine treatment which resulted in a regression of the clinical findings and a return to normal values of blood lactic and pyruvic acids. The interruption of thiamine supplementation after 1 year of treatment led to a prompt recurrence of the previous clinical and biochemical symptoms. PMID: 8827113
137. Ann Neurol. 1996 May;39(5):585-91.
Brain thiamine, its phosphate esters, and its metabolizing enzymes in Alzheimer's disease.
Mastrogiacoma F, Bettendorff L, Grisar T, Kish SJ.
Human Neurochemical Pathology Laboratory, Clarke Institute of Psychiatry, Toronto, Canada.
Clinical data suggest that high-dose thiamine (vitamin B1) may have a mild beneficial effect in some patients with Alzheimer's disease (AD). Since this action could be related to a brain thiamine deficiency, we measured directly levels of free (nonphosphorylated) thiamine and its phosphate esters, thiamine monophosphate and thiamine diphosphate (TDP), and activities of three TDP-metabolizing enzymes (thiamine pyrophosphokinase, thiamine diphosphatase, and thiamine triphosphatase) in autopsied cerebral cortex of 18 patients with AD and 20 matched controls. In the AD group, mean levels of free thiamine and its monophosphate ester were normal, whereas levels of TDP were significantly reduced by 18 to 21% in all three cortical brain areas examined. Activities of the TDP-metabolizing enzymes were normal in the AD group, suggesting that decreased TDP is not due to altered levels of these enzymes. The TDP decrease could be explained by a cerebral cortical deficiency in AD of ATP, which is needed for TDP synthesis. Although the magnitude of the TDP reduction is slight, a chronic subclinical TDP deficiency could contribute to impaired brain function in AD and might provide the basis for the modest improvement by thiamine in cognitive status of some patients with AD. PMID: 8619543
138. J Pediatr Gastroenterol Nutr. 1996 Apr;22(3):289-95.
Thiamine, riboflavin, folate, and vitamin B12 status of infants with low birth Weights receiving enteral nutrition.
Friel JK, Andrews WL, Long DR, Herzberg G, Levy R.
Department of Biochemistry, Memorial University, St. John's, Newfoundland, Canada.
The purpose of the present study was to monitor the vitamin status of 14 low-birth-weight (LBW) infants (< 1,750 g birth weight) at 2 weeks and an additional four infants at 3 weeks who were receiving an enteral formula providing 247 micrograms/100 kcal thiamine, 617 micrograms/100 kcal riboflavin, 37 micrograms/100 kcal folate, and 0.55 micrograms/100 kcal vitamin B12. The mean birth weight of the 18 infants was 1,100 +/- 259 g, and mean gestational age was 29 +/- 2 weeks. Weekly blood, 24-h urine collections, and dietary intake data were obtained. For thiamine, red blood cell (RBC) transketolase activity was within the normal range for all infants. For riboflavin, RBC glutathione reductase activity was normal for all infants except one. We calculated from intake and urinary excretion data that these infants require 225 micrograms/100 kcal thiamine and 370 micrograms/100 kcal riboflavin, respectively. Mean plasma folate levels were 21 +/- 11 ng/ml at 2 weeks and 18 +/- 5 ng/ml at 3 weeks. RBC folate levels were 455 +/- 280 ng/ml at 2 weeks and 391 +/- 168 ng/ml at 3 weeks. All folate blood values were normal, except for one subject with an elevated level (59 ng/ml). Vitamin B12 plasma values were 737 +/- 394 pg/ml at 2 weeks and 768 +/- 350 pg/ml at 3 weeks, and all values were normal except for three infants with elevated values. In conclusion, appropriate vitamin status was maintained during this short observational period, during administration of this enteral formula; however, riboflavin concentrations in the enteral feed may be excessive. PMID: 8708883
139. Biochem Biophys Res Commun. 1996 Mar 7;220(1):113-9.
Thiamine pyrophosphate and pyridoxamine inhibit the formation of antigenic advanced glycation end-products: comparison with aminoguanidine.
Booth AA, Khalifah RG, Hudson BG.
Department of Biochemistry and Molecular Biology, University of Kansas Medical Center, Kansas City 66160-7421, USA.
Nonenzymatic glycation of proteins by glucose leading to the formation of toxic and immunogenic advanced glycation end products (AGEs) may be a major contributor to the pathological manifestations of diabetes mellitus, aging, and, possibly, neurodegenerative diseases such as Alzheimer's. We tested the in vitro inhibition of antigenic AGE formation on bovine serum albumin, ribonuclease A, and human hemoglobin by various vitamin B1 and B6 derivatives. Among the inhibitors, pyridoxamine and thiamine pyrophosphate potently inhibited AGE formation and were more effective than aminoguanidine, suggesting that these two compounds may have novel therapeutic potential in preventing vascular complications of diabetes. An unexpected finding was that aminoguanidine inhibited the late kinetic stages of glycation much more weakly than the early phase. PMID: 8602828
140. Ukr Biokhim Zh. 1996 Mar-Apr;68(2):3-14.
[The neural activity of thiamine: facts and hypotheses]
[Article in Russian]
Parkhomenko IuM, Donchenko GV, Protasova ZS.
A review of some experimental results as to identification of the specific role of thiamine in functioning of nerve cells is presented. Failure to attribute high neuroactivity of thiamine considering only its known biochemical function as a coenzyme precursor of some key Enzymes of the carbohydrate metabolism has formed conceptions existence of non-coenzyme functions in this vitamin which are realized in nerve cells. The Investigation of this thiamine function has been developing mainly in two principal directions the study of participation of biologically active thiamine derivatives is functioning of the excited membrane ion channels and the study of their role in the synthesis and metabolism of acetylcholine. Taking into account analysis of their own data and those available in literature, the authors formulate a hypothesis which attributes high neuroactivity of thiamine not to the existence of a certain function in the nerve cells new for this vitamin but only to the peculiarities of the structure-functional organization of the cells the existence of excited membrane, and interdependence between the cellular metabolism and transport of loss via the membrane, which underlies regulation of the synthesis, release, capture and catabolism of neurotransmitters. PMID: 9005657
141. Metab Brain Dis. 1996 Mar;11(1):95-106.
Effects of thiamine supplementation on exercise-induced fatigue.
Suzuki M, Itokawa Y.
Institute of Health & Sports Sciences, University of Tsukuba, Japan.
High-dose thiamine (vitamin B1) supplementation (100 mg/day) may be helpful in preventing or accelerating recovery from exercise-induced fatigue. Sixteen volunteer male athletes volunteer, 8 with a blood thiamine level of 40 ng/ml or more (normal thiamine group) and 8 with levels below that level (low thiamine group) were selected as subjects. They exercised on a bicycle ergometer and the effects of thiamine supplementation were compared with placebo. Blood thiamine level markedly increased following supplementation of thiamine for 3 days before exercise. Exercise-induced changes in hemodynamic parameters and cardiopulmonary function indicated the onset of fatigue. Thiamine supplementation significantly suppressed the increase in blood glucose in the normal thiamine group and significantly decreased the number of complaints shortly after exercise in the subjective fatigue assessment of 30 items. PMID: 8815395
142. Metab Brain Dis. 1996 Mar;11(1):9-17.
Neuropathology of thiamine deficiency disorders.
Department of Pathology, University of Sydney, Australia.
The Wernicke-Korsakoff syndrome (WKS) is the most frequently encountered manifestation of thiamine deficiency in Western society. It is commonly seen in alcoholic patients, but may also occur in patients with impaired nutrition from other causes, such as those with gastrointestinal disease or AIDS. The pathology is restricted to the central nervous system and is characterised by neuronal loss, gliosis and vascular damage in regions surrounding the third and fourth ventricles and the cerebral aqueduct. In addition to WKS, thiamine deficiency may also result in beriberi, a cardiac and peripheral nervous system disease, and it has been implicated in the pathogenesis of cerebellar degeneration and peripheral neuropathy. Thus thiamine deficiency results in significant nervous system pathology and vigilance should be maintained in the diagnosis and treatment of this readily preventable cause of disease. PMID: 8815394
143. Metab Brain Dis. 1996 Mar;11(1):89-94.
Thiamine therapy in Alzheimer's disease.
Mimori Y, Katsuoka H, Nakamura S.
Third Department of Internal Medicine, Hiroshima University School of Medicine, Japan.
Fursultiamine (TTFD), a derivative of thiamine, at an oral dose of 100 mg/day had a mild beneficial effect in patients with Alzheimer's disease in a 12-week open trial. The improvement could be observed not only in their emotional or other mental symptoms but also in intellectual function. Only mildly impaired subjects showed cognitive improvement. Alzheimer patients' blood levels of thiamine before the trial were within the normal range. No adverse reactions were observed and all patients tolerated the trial well. TTFD could afford an alternate treatment to large doses of thiamine hydrochloride in Alzheimer patients. However, further investigations of the therapeutic implications of thiamine and its possible etiologic clues to Alzheimer's disease are necessary. PMID: 8815393
144. Metab Brain Dis. 1996 Mar;11(1):81-8.
Alterations of thiamine phosphorylation and of thiamine-dependent enzymes in Alzheimer's disease.
Heroux M, Raghavendra Rao VL, Lavoie J, Richardson JS, Butterworth RF.
Neuroscience Research Unit, Hopital Saint-Luc (University of Montreal), Que., Canada.
There is a growing body of evidence to suggest that thiamine neurochemistry is disrupted in Alzheimer's Disease (AD). Studies in autopsied brain tissue from neuropathologically proven AD patients reveal significantly reduced activities of the thiamine phosphate dephosphorylating enzymes thiamine diphosphatase (TDPase) and thiamine monophosphatase (TMPase) as well as the thiamine diphosphate-dependent enzymes, pyruvate dehydrogenase complex, alpha-ketoglutarate dehydrogenase (alpha KGDH) and transketolase. Reductions in enzyme activities are present both in affected areas of AD brain as well as in relatively well conserved tissue. Decreased TDP concentrations and concomitantly increased TMP in autopsied brain tissue from AD patients and in CSF from patients with Dementia of the Alzheimer Type suggests that CNS thiamine phosphorylation-dephosphorylation mechanisms are disrupted in AD. alpha KGDH is a rate-limiting enzyme for cerebral glucose utilization and decreases in its activity are associated with lactic acidosis, cerebral energy failure and neuronal cell loss. Deficiencies of TDP-related metabolic processes could therefore participate in neuronal cell death mechanisms in AD. PMID: 8815392
145. Metab Brain Dis. 1996 Mar;11(1):55-69.
Erratum in: Metab Brain Dis 1996 Sep;11(3):281.
The blood-brain barrier and selective vulnerability in experimental thiamine-deficiency encephalopathy in the mouse.
Harata N, Iwasaki Y.
Department of Physiology, Kyushu University, Faculty of Medicine, Fukuoka, Japan.
The integrity of the blood-brain barrier (BBB) is an important aspect of normal central nervous system (CNS) function. Recently, it was shown that the BBB breakdown is one of the predisposing factors in the pathogenesis of thiamine-deficiency encephalopathy. The result is discussed along with some reviews on previous research of BBB integrity in thiamine deficiency. PMID: 8815390
146. Metab Brain Dis. 1996 Mar;11(1):19-37.
Neuropathology of thiamine deficiency: an update on the comparative analysis of human disorders and experimental models.
Langlais PJ, Zhang SX, Savage LM.
Dept. of Psychology, San Diego State University, CA, USA.
This paper provides a re-examination of the neuroanatomical consequences of thiamine deficiency in light of more recent studies of human disorders and models of experimental thiamine deficiency. A major goal is to elucidate the relative roles of thiamine deficiency and chronic alcohol consumption in the pathogenesis of Wernicke-Korsakoff syndrome (WKS). Particular emphasis is placed on the role of thiamine deficiency in lesions to basal forebrain, raphe, locus coeruleus, white matter and cortex and their role in the cognitive and memory disturbances of human WKS and experimental models of thiamine deficiency. PMID: 8815388
147. Int J Clin Pharmacol Ther. 1996 Feb;34(2):47-50.
Pharmacokinetics of thiamine derivatives especially of benfotiamine.
Pharmacokinetic data of orally administered lipid-soluble thiamine analogues like benfotiamine are reviewed and assessed. It is quite clear that benfotiamine is absorbed much more better than water-soluble thiamine salts: maximum plasma levels of thiamine are about 5 times higher after benfotiamine, the bioavailability is at maximum about 3.6 times as high as that of thiamine hydrochloride and better than other lipophilic thiamine derivates. The physiological activity (alphaETK) increased only after benfotiamine was given. Due to its excellent pharmacokinetic profile benfotiamine should be preferred in treatment of relevant indications. PMID: 8929745
148. Brain Dev. 1996 Jan-Feb;18(1):68-70.
Long-term therapy with cytochrome c, flavin mononucleotide and thiamine diphosphate for a patient with Kearns-Sayre syndrome.
Nakagawa E, Osari S, Yamanouchi H, Matsuda H, Goto Y, Nonaka I.
Department of Child Neurology, National Center Hospital for Mental, Nervous and Muscular Disorders, National Institute of Neuroscience, National Center of Neurology and Psychiatry (NCNP), Kodaira, Tokyo, Japan.
Cardiocrome, containing cytochrome c, flavin mononucleotide and thiamine diphosphate, was administered intravenously for 22 months to a patient with Kearns-Sayre syndrome. This combined therapy alleviated the patient's easy fatigability, motor disability, corneal edema and chilblains, but was not effective for his ophthalmoplegia, blepharoptosis or hearing loss. Truncal ataxia, dysphagia and an atrioventricular block appeared even with this therapy. Although the abnormal distribution of cerebral blood flow demonstrated by single photon emission computed tomography was improved, serial cranial magnetic resonance imaging and electrophysiological examination revealed progressive changes. In conclusion, this therapy was favorably effective for impaired skeletal muscle function and corneal edema, but not for ocular movements, central nervous system symptoms or cardiac conduction abnormalities, because irreversible degeneration had probably occurred in these organs. PMID: 8907347
149. Mycoses. 1996 Jan-Feb;39(1-2):61-6.
Effect of glucose and thiamine concentrations on the formation of macroconidia in dermatophytes. Occurrence of dysgonic Microsporum canis strains in Athens, Greece.
Mavroudeas D, Velegraki A, Leonardopoulos J, Marcelou U.
National Oncology Hospital Agios Savas, Athens, Greece.
Data collected from multiple trials with 110 fresh and preserved clinical isolates of Trichophyton mentagrophytes var. mentagrophytes, T. violaceum, T. rubrum, T. verrucosum, Microsporum canis and Epidermophyton floccosum revealed that production of macroconidia depends on glucose and thiamine concentrations in the medium. Optimal macroconidia production was obtained at the critical concentrations of 5 g l-1 glucose and 0.6 g l-1 thiamine when the two compounds were used in combination. The same conditions also encouraged macroconidia production in aconidial strains of T. verrucosum. Cutaneous inoculation in immunocompetent laboratory rabbits further enhanced the macroconidia producing capacity of the tested strains. Emphasis was placed on the occurrence of dysgonic/atypical strains of M. canis, which readily reverted to their typical phenotypes after growth on medium supplemented with 0.6 g l-1 thiamine, a process greatly augmented after cutaneous animal inoculation. It was verified that selective exogenous factors affect macroconidial production and that the dysgonic group of M. canis constitutes an epidemiologically significant group in the Greater Athens area. This is the first report of the occurrence of such M. canis strains from Greece. PMID: 8786761
150. J Neurochem. 1996 Jan;66(1):250-8.
Thiamine, thiamine phosphates, and their metabolizing enzymes in human brain.
Bettendorff L, Mastrogiacomo F, Kish SJ, Grisar T.
Laboratory of Neurochemistry, University of Liege, Belgium.
Total thiamine (the sum of thiamine and its phosphate esters) concentrations are two- to fourfold lower in human brain than in the brain of other mammals. There were no differences in the total thiamine content between biopsied and autopsied human brain, except that in the latter, thiamine triphosphate was undetectable. The main thiamine phosphate-metabolizing enzymes could be detected in autopsied brain, and the kinetic parameters were comparable to those reported in other species. Thiamine diphosphate levels were lowest in hippocampus (15 +/- 4 pmol/mg of protein) and highest in mammillary bodies (24 +/- 4 pmol/mg of protein). Maximal levels of thiamine and its phosphate ester were found to be present at birth. In parietal cortex and globus pallidus, mean levels of total thiamine in the oldest age group (77-103 years) were, respectively, 21 and 26% lower than those in the middle age group (40-55 years). Unlike cerebral cortex, the globus pallidus showed a sharp drop in thiamine diphosphate levels during infancy, with concentrations in the oldest group being only approximately 50% of the levels present during the first 4 months of life. These data, consistent with previous observations conducted in blood, suggest a tendency toward decreased thiamine status in older people. PMID: 8522961
151. Med J Aust. 1995 Nov 20;163(10):531-4.
Wernicke-Korsakoff syndrome in Sydney hospitals: before and after thiamine enrichment of flour.
Ma JJ, Truswell AS.
Human Nutrition Unit, University of Sydney, NSW.
OBJECTIVE: To estimate the incidence of Wernicke-Korsakoff syndrome (WKS) before and after the introduction of thiamine enrichment of bread flour in 1991. DESIGN: Retrospective survey of hospital records. Patient records with the diagnostic codes for Wernicke's encephalopathy (WE) or Korsakoff's psychosis (KP) were reviewed and details of acceptable cases were entered onto a data form. SETTING: All 17 major public general hospitals in the Sydney area (New South Wales), between 1978 and 1993. OUTCOME MEASURES: Numbers of confirmed or probable diagnoses of WE, KP or WKS and associated deaths, patient demographic and social characteristics and alcohol intake. RESULTS: 1,267 patients with WKS were found, with 1,012 acute cases. Although numbers of acute cases may have started to fall before 1991, numbers for the last two years were the lowest of all the 16 years (P = 0.004). Cases of KP outnumbered those of WE by about 3:1 and men outnumbered women 4:1. The peak age was 60-64 years (17%) and beer was the most commonly cited alcoholic drink (71%). The red-cell transketolase test was seldom used for diagnosis (3% of acute cases). CONCLUSIONS: The lower number of "acute" cases in 1992 and 1993 is consistent with a preventive effect of mandatory enrichment of bread with thiamine, but is not conclusive evidence. Longer follow-up of Sydney hospitals, results of postmortem examinations and follow-up in other areas of Australia are required. PMID: 8538524
152. Arch Neurol. 1995 Nov;52(11):1081-6.
Plasma and red blood cell thiamine deficiency in patients with dementia of the Alzheimer's type.
Gold M, Chen MF, Johnson K.
Department of Neurology, University of South Florida College of Medicine, Tampa, USA.
OBJECTIVES: To determine the prevalence of plasma thiamine deficiency in patients referred to a memory disorder clinic and to compare plasma thiamine levels with red blood cell (RBC) thiamine levels. To determine if patients with senile dementia of the Alzheimer's type (SDAT) differ from those without SDAT in either plasma or RBC thiamine levels. DESIGN: Case-control study. SETTING: Ambulatory care referral center. PATIENTS: Consecutive sample of 34 patients; 17 patients who met the National Institute of Neurological and Communicative Disorders and Stroke-Alzheimer's Disease and Related Disorders Association criteria for probable Alzheimer's disease and 17 patients with other forms of dementia. METHODS: Plasma and RBC thiamine levels were determined in all patients with the use of a microbiologic assay known for its specificity to biological forms of thiamine. Vitamin supplementation was determined by chart review. OUTCOME MEASURES: Plasma and RBC thiamine levels. RESULTS: Patients with SDAT were found to have significantly lower plasma thiamine levels than patients without SDAT. Low plasma thiamine levels were detected in a significantly larger proportion of patients with SDAT than in patients without SDAT. Red blood cell thiamine levels did not correlate with the clinical diagnosis of SDAT. Vitamin supplementation did not correlate with diagnosis and plasma or RBC thiamine levels. CONCLUSIONS: A significant proportion of patients with SDAT may have a thiamine deficiency, which may have an impact on cognitive function. Currently used assays may not be adequate to assess thiamine status. PMID: 7487560
153. Alcohol Clin Exp Res. 1995 Aug;19(4):1073-7.
Reduced activities of thiamine-dependent enzymes in brains of alcoholics in the absence of Wernicke's encephalopathy.
Lavoie J, Butterworth RF.
Neuroscience Research Unit, Hopital Saint-Luc (University of Montreal), Quebec, Canada.
The relative roles of alcohol per se, thiamine deficiency, and liver disease in the pathogenesis of alcohol-related brain damage have not been fully elucidated. In particular, the extent to which alterations of brain thiamine metabolism contribute to cognitive dysfunction in alcoholism in the absence of Wernicke's encephalopathy has not been established. In the present study, thiamine diphosphate-dependent enzymes were measured using standard spectrophotometric techniques in homogenates of brain tissue obtained at autopsy from eight alcoholic patients, all of whom died in hepatic coma without clinical or neuropathological evidence of Wernicke's encephalopathy and six nonalcoholic, age-matched controls, matched for autopsy delay time and free, at the time of death, from gross malnutrition or other neurological or psychiatric disorders. Transketolase activities were reduced in cerebellum (by 35%, p < 0.01), thalamus (by 35%, p < 0.01), frontal cortex (by 22%, p < 0.01), temporal cortex (by 20%, p < 0.01), and prefrontal cortex (by 19%, p < 0.01). Activities of the pyruvate dehydrogenase complex were selectively reduced in prefrontal cortex by 25% (p < 0.01). Activities of alpha-ketoglutarate dehydrogenase were within normal limits in all brain regions of alcoholic patients. The generalized reductions of transketolase activity undoubtedly result from thiamine deficiency. Previous studies suggest that the presence of liver disease may exacerbate thiamine deficiency in alcoholics. A sustained loss of transketolase activity in brain could result in disruption of pentose shunt activity and concomitant reductions in reducing equivalents and lipid metabolism within the cell. The selective loss of pyruvate dehydrogenase activity in prefrontal cortex of alcoholic cirrhotics could relate to the phenomenon of hepatic coma.(ABSTRACT TRUNCATED AT 250 WORDS) PMID: 7485819
154. Intern Med. 1995 Jul;34(7):674-5.
Thiamine deficiency and pulmonary hypertension in Crow-Fukase syndrome.
Okura H, Gohma I, Hatta K, Imanaka T.
Department of Internal Medicine, Tenri Hospital.
A 57-year-old woman with Crow-Fukase syndrome presented thiamine deficiency and pulmonary hypertension of unknown etiology. After oral administration of prednisolone and thiamine, echocardiogram showed marked improvement of the pulmonary hypertension. To our knowledge, this is the first case of this syndrome associated with thiamine deficiency and precapillary pulmonary hypertension, which may play a role in the pathogenesis of polyneuropathy and heart failure of this syndrome. PMID: 7496083
155. Am J Med. 1995 May;98(5):485-90.
Improved left ventricular function after thiamine supplementation in patients with congestive heart failure receiving long-term furosemide therapy.
Shimon I, Almog S, Vered Z, Seligmann H, Shefi M, Peleg E, Rosenthal T, Motro M, Halkin H, Ezra D.
Division of Clinical Pharmacology, Sheba Medical Center, Tel-Hashomer, Israel.
PURPOSE: We have previously found thiamine (vitamin B1) deficiency in patients with congestive heart failure (CHF) who had received long-term furosemide therapy. In the present study, we assessed the effect of thiamine repletion on thiamine status, functional capacity, and left ventricular ejection fraction (LVEF) in patients with moderate to severe CHF who had received furosemide in doses of 80 mg/d or more for at least 3 months. PATIENTS AND METHODS: Thirty patients were randomized to 1 week of double-blind inpatient therapy with either i.v. thiamine 200 mg/d or placebo (n = 15 each). All previous drugs were continued. Following discharge, all 30 patients received oral thiamine 200 mg/d as outpatients for 6 weeks. Thiamine status was determined by the erythrocyte thiamine-pyrophosphate effect (TPPE). LVEF was determined by echocardiography. RESULTS: TPPE, diuresis, and LVEF were unchanged with i.v. placebo. After i.v. thiamine, TPPE decreased (11.7% +/- 6.5% to 5.4% +/- 3.2%; P < 0.01). LVEF increased (0.28 +/- 0.11 to 0.32 +/- 0.09; P < 0.05), as did diuresis (1,731 +/- 800 mL/d to 2,389 +/- 752 mL/d; P < 0.02), and sodium excretion (84 +/- 52 mEq/d to 116 +/- 83 mEq/d, P < 0.05). In the 27 patients completing the full 7-week intervention, LVEF rose by 22% (0.27 +/- 0.10 to 0.33 +/- 0.11, P < 0.01). CONCLUSIONS: Thiamine repletion can improve left ventricular function and biochemical evidence of thiamine deficiency in some patients with moderate-to-severe CHF who are receiving longterm furosemide therapy. PMID: 7733128
156. Alcohol Clin Exp Res. 1995 Apr;19(2):523-6.
Thiamine phosphatases in human brain: regional alterations in patients with alcoholic cirrhosis.
Rao VL, Butterworth RF.
Neuroscience Research Unit, Hopital Saint-Luc (University of Montreal), Quebec, Canada.
Activities of thiamine monophosphatase (TMPase) and thiamine diphosphatase (TDPase) were measured in homogenates of brain tissue obtained at autopsy from eight alcoholic cirrhotic patients who died in hepatic coma and nine controls matched for age and for postmortem delay interval and free from neurological or psychiatric disorders, hepatic disease, or other conditions of grossly impaired nutritional status. Enzyme activities were measured by standard spectrophotometric techniques. Both TMPase and TDPase were distributed unevenly in brain with highest activities being recorded in temporal cortex. Regional correlations between TMPase and TDPase, however, were poor. TDPase activities in brain tissue from alcoholic cirrhotic patients were significantly increased in 5 of 6 brain regions, by 26 to 153% (p < 0.05). TMPase activities in alcoholic cirrhotics, on the other hand, were unchanged in all brain regions, with the exception of caudate nucleus where they were increased by 70% (p < 0.05). These findings add to the substantial body of evidence suggesting that alcoholic liver disease is associated with abnormal thiamine status and with altered thiamine neurochemistry. Increased TDP degradation resulting from increased activities of TDPase could contribute to the pathophysiological mechanisms involved in alcohol-related brain dysfunction. PMID: 7625592
157. Med J Malaysia. 1995 Mar;50(1):17-20.
Thiamine responsive ankle oedema in detention centre inmates.
Medical Unit, District Hospital, Teluk Intan, Perak.
Twenty-seven inmates from a detention centre in Perak were evaluated for possible causes of their ankle oedema. Physical examination and biochemical evaluation did not show any evidence of renal or hepatic dysfunction. The cardiac origin of their problem was suggested by the presence of other signs of heart failure in three of them and by radiological evidence of cardiomegaly in 40% of them. All the patients who returned for review demonstrated a prompt clinical response to thiamine replacement therapy. PMID: 7752970
158. Metab Brain Dis. 1995 Mar;10(1):9-16.
The contribution of alcohol, thiamine deficiency and cirrhosis of the liver to cerebral cortical damage in alcoholics.
Department of Anatomical Pathology, Royal Prince Alfred Hospital, Camperdown, Australia.
The relative roles of alcohol toxicity, thiamine deficiency and cirrhosis of the liver in the pathogenesis of alcohol-related brain damage are unclear. Brain shrinkage and neuronal loss from four regions of the cortex was determined in 22 alcoholics with the Wernicke-Korsakoff Syndrome (WKS), cirrhosis of the liver or neither of these complications and compared to 22 age-matched non-alcoholic controls. Brain shrinkage was most marked in those alcoholics with WKS. Neuronal loss occurred only from the superior cortex and was of equal magnitude in all alcoholic subgroups. In an animal model of alcohol abuse and thiamine deficiency, neuronal loss from the cerebral cortex occurred in a time-dependent manner. Furthermore, those cells which contained the calcium-binding protein parvalbumin appeared to be preferentially damaged in this model. PMID: 7596332
159. Metab Brain Dis. 1995 Mar;10(1):57-72.
Presentation of acute Wernicke's encephalopathy and treatment with thiamine.
Wood B, Currie J.
University of Melbourne, Department of Community Medicine and Public Health, Parkville, Victoria, Australia.
Thirty two cases of acute Wernicke's encephalopathy were observed in a period of 33 months, and prior to the mandatory thiamine enrichment of Australian bread-making flour in 1991. These cases were carefully assessed by multiple tests at specified intervals prior to, and following thiamine administration until discharge from hospital. Structured scoring of neurological signs and symptoms, CT scans, psychometry, nutritional measurements, and liver biopsies were performed. There was variation in the presentation and severity of clinical signs and symptoms and in response to treatment. All patients had alcohol-related liver disease, and the results indicated that fatty liver was important in presentation and in response to treatment with thiamine. Other forms of alcohol related brain damage were present in these patients, most of whom were in the 4th or 5th decade of life and had been drinking beer to excess for more than 20 years. PMID: 7596329
160. Metab Brain Dis. 1995 Mar;10(1):1-8.
Pathophysiology of alcoholic brain damage: synergistic effects of ethanol, thiamine deficiency and alcoholic liver disease.
Neuroscience Research Unit, Hopital Saint-Luc (University of Montreal), Quebec, H2X 3J4 Canada.
Chronic alcoholism results in brain damage and dysfunction leading to a constellation of neuropsychiatric symptoms including cognitive dysfunction, the Wernicke-Korsakoff Syndrome, alcoholic cerebellar degeneration and alcoholic dementia. That these clinically-defined entities result from independent pathophysiologic mechanisms is unlikely. Alcohol and its metabolite acetaldehyde are directly neurotoxic. Alcoholics are thiamine deficient as a result of poor diet, gastrointestinal disorders and liver disease. In addition, both alcohol and acetaldehyde have direct toxic effects on thiamine-related enzymes in liver and brain. Alcoholics frequently develop severe liver disease and liver disease per se results in altered thiamine homeostasis, in cognitive dysfunction and in neuropathologic damage to astrocytes. The latter may result in the loss of neuron-astrocytic trafficking of neuroactive amino acids and thiamine esters, essential to CNS function. The present review article proposes mechanisms whereby the effects of alcohol, thiamine deficiency and liver disease combine synergistically to contribute to the phenomena of cognitive dysfunction and "alcoholic brain damage". PMID: 7596324
161. J Nutr. 1995 Feb;125(2):189-94.
The thiamine-dependent hysteretic behavior of human transketolase: implications for thiamine deficiency.
Singleton CK, Pekovich SR, McCool BA, Martin PR.
Department of Molecular Biology, Vanderbilt University, Nashville, TN 37235.
We have investigated the hysteretic properties of human transketolase with emphasis on its dependency on thiamine pyrophosphate concentration. As demonstrated previously, the reaction progress curves revealed a slow transition from an initial low velocity to a faster final steady-state velocity, characterized by the rate constant tau-1. The rate of the transition was dependent on the concentration of the thiamine pyrophosphate cofactor, with progressively longer transition times found as the concentration of thiamine pyrophosphate was decreased. At physiological thiamine pyrophosphate concentrations, the inverse rate constant was in the range of 10 to 20 min for fibroblast-derived transketolase and increased dramatically with only small decreases from these levels of thiamine pyrophosphate. Variation in the lag was found when transketolase from different individuals was examined. Moreover, at low levels of thiamine, the rate of the transition was different between fibroblast- and lymphoblast-derived transketolase. The substantial lag in formation of active holoenzyme and the findings of interindividual variation and cell type variation in the lag period suggest mechanisms for the loss of transketolase activity during thiamine deficiency and may explain, at least in part, the differential sensitivity to deficiency demonstrated by tissues and individuals. PMID: 7861245
162. Clin Chim Acta. 1995 Jan 31;234(1-2):91-100.
Comparison of erythrocyte transketolase activity with thiamine and thiamine phosphate ester levels in chronic alcoholic patients.
Herve C, Beyne P, Letteron P, Delacoux E.
Service de Biochimie, Hopital Beaujon, Clichy, France.
The effect of chronic alcoholism on biochemical evaluation of thiamine status was studied by the concomitant determination of erythrocyte transketolase (ETK) activity, its relative increase by in vitro addition of thiamine diphosphate (TDP effect) and the direct measurement of thiamine and its phosphate esters by high performance liquid chromatography. Thirty-eight percent of alcoholic subjects showed a thiamine deficiency with decreased thiamine diphosphate concentrations compared with healthy subjects (90.8 +/- 25.7 nmol/l vs. 176 +/- 28.0 nmol/l, respectively, mean +/- S.D., P < 0.001). Thiamine diphosphate concentrations were highly correlated with total thiamine concentrations and TDP effect (respectively r = 0.99 and 0.79, n = 85, P < 0.001). No abnormality in thiamine phosphorylation related to chronic alcoholism was noted. Finally, 47% of these deficient alcoholic patients had normal ETK activity. We concluded that, if indirect evaluation of thiamine status is to be chosen, the determination of ETK activity should be associated with TDP effect since the latter has been shown to be highly linked to total thiamine and thiamine diphosphate in erythrocytes. Furthermore, the direct measurement of thiamine and its phosphate esters was a more sensitive and specific index of thiamine nutrition. PMID: 7758226
163. Biochem Biophys Res Commun. 1994 Nov 30;205(1):967-75.
Thiamine disulfide as a potent inhibitor of human immunodeficiency virus (type-1) production.
Shoji S, Furuishi K, Misumi S, Miyazaki T, Kino M, Yamataka K.
Department of Biochemistry, Faculty of Pharmaceutical Sciences, Kumamoto University, Japan.
Thiol and disulfide compounds were tested as an anti-HIV drug against transactivator (Tat)-mediated transactivation of HIV-1. Of all the compounds tested, thiamine disulfide, alpha-lipoic acid, and N-acetycysteine significantly depressed HIV-1 Tat activity. Thiamine disulfide alone in these compounds possessing anti-HIV-Tat activity markedly inhibited production of progeny HIV-1 in acute and chronic HIV-1-infected CEM at nontoxic concentrations of 500-1000 microM. Thiamine disulfide (500 microM) blocked 99.7% of HIV-1 production after 96 hr culture in acute HIV-1 (LAV-1) infection (m.o.i. = 0.002), whereas it inhibited 90-98% of HIV-1 production in chronic-infected cells (CEM/LAV-1, H9/MN, and Molt-4/IIIB). The results suggest that thiamine disulfide may be important for AIDS chemotherapy. PMID: 7999140
164. Palliat Med. 1994 Oct;8(4):320-4.
Thiamine deficiency in patients admitted to a palliative care unit.
Barbato M, Rodriguez PJ.
Palliative Care Unit, St Joseph's Hospital, Auburn, NSW.
This study looks at the clinical and thiamine status of 50 terminally ill patients who were admitted to a palliative care unit. Thiamine levels were found to be abnormally low in 28% of the patients and borderline in a further 36%. Cognitive impairment, as measured by the mini-metal state examination (MMSE) of Folstein, Folstein and McHugh, was present in 68% of those tested and a significant correlation was found between the MMSE status and thiamine levels. PMID: 7529104
165. Fetal Diagn Ther. 1994 Sep-Oct;9(5):337-40.
Sickle cell and thiamine deficiency: case report of a fetal death.
Multon O, Sibony O, Carbillon L, Guerin JM, Nessman C, Blot P.
Department of Perinatology, Robert Debre Hospital, Paris, France.
The heterozygous state of the sickle cell trait is not known to be a cause of fetal death. This is a report of disseminated placental infarcts associated with thiamine deficiency in a patient with the sickle cell trait. This pathological association suggests an original physiopathological process. PMID: 7818783
166. Pediatr Res. 1994 Sep;36(3):340-6.
Molecular analysis of abnormal pyruvate dehydrogenase in a patient with thiamine-responsive congenital lactic acidemia.
Naito E, Ito M, Takeda E, Yokota I, Yoshijima S, Kuroda Y.
Department of Pediatrics, School of Medicine, University of Tokushima, Japan.
A patient who responded to thiamine therapy with reduction of lactate in the blood and cerebrospinal fluid and clinical improvement was studied. Cultured lymphoblastoid cells of this patient were found to show reduced activities of pyruvate dehydrogenase complex (PDHC) and pyruvate dehydrogenase, decreased affinity of PDHC for thiamine pyrophosphate, and defective activation of PDHC by pyruvate dehydrogenase phosphatase. PDHC deficiency in fibroblasts and biopsied muscle of this patient was also due to the decreased affinity of PDHC for thiamine pyrophosphate. A mutation in the E1 alpha subunit containing the thiamine binding site and serine phosphorylation site regulating the activation/inactivation of PDHC was characterized by the polymerase chain reaction and DNA sequencing. A single A-->G transition was identified at position 131, resulting in the substitution of Arg-44 for His-44. This mutation must be a de novo mutation because it was not found in either parent's genomic DNA. In this study, we have obtained the first evidence at the molecular level for a mutation of thiamine-responsive PDHC deficiency. PMID: 7808831
167. Emerg Med Clin North Am. 1994 May;12(2):301-16.
Reappraisal of the "coma cocktail". Dextrose, flumazenil, naloxone, and thiamine.
Doyon S, Roberts JR.
Department of Emergency Medicine, Mercy Catholic Medical Center, Philadelphia, Pennsylvania.
Flumazenil is an important adjunct to the diagnosis and treatment of benzodiazepine toxicity. It must be used cautiously with attention to a number of clinical caveats. Currently it is advised that flumazenil should not be used routinely in all patients with altered mental status, but when used selectively, it is a very safe and extremely useful antidote. PMID: 8187685
168. J Chromatogr B Biomed Appl. 1994 Mar 4;653(2):217-20.
Determination of thiamine and its phosphate esters in human erythrocytes by high-performance liquid chromatography with isocratic elution.
Herve C, Beyne P, Delacoux E.
Service de Biochimie, Hopital Beaujon, Clichy, France.
A high-performance liquid chromatographic method for the simultaneous determination of thiamine and its phosphate esters in human erythrocytes, using postcolumn derivatization, is presented. The sample preparation and the choice of the analytical column avoid the use of an elution gradient. The four thiamine compounds (thiamine and thiamine monophosphate, diphosphate and triphosphate) are eluted within less than 15 min with a detection limit of ca. 20 fmol. The reproducibility and accuracy of the assay are satisfactory. Normal physiological red blood cell concentrations of the four thiamine compounds are included. PMID: 8205249
169. Neurology. 1994 Mar;44(3 Pt 1):549-51.
A double-blind, placebo-controlled study of the efficacy of thiamine hydrochloride in a seasonal ataxia in Nigerians.
Adamolekun B, Adamolekun WE, Sonibare AD, Sofowora G.
Department of Medicine, Obafemi Awolowo University, Ile-Ife, Nigeria.
We report the results of the first double-blind, placebo-controlled trial of the efficacy of thiamine hydrochloride in a seasonal ataxic syndrome of unknown etiology, endemic to the southwestern part of Nigeria. Thiamine produced a clinically impressive and statistically significant improvement in clinical severity grading in patients with the seasonal ataxia compared with placebo (MANOVA, df = 1, F = 35.087, p < 0.0001), with a significant time-treatment interaction (MANOVA, df = 3, F = 32.36, p < 0.0001). These results provide confirmation for the role of thiamine deficiency in the etiology of the seasonal ataxic syndrome and represent the first advance in the elucidation of the etiology of this syndrome. PMID: 8145931
170. J Biochem Biophys Methods. 1994 Mar;28(2):147-54.
Competitive protein-binding radioassay of thiamine in selected biological materials.
Jagiellonian University, Institute of Molecular Biology, Krakow, Poland.
A principle of competitive protein-binding radioassay is developed for thiamine determination in some biological samples. Thiamine in an assay sample competes with radiolabelled thiamine for Sepharose-immobilized buckwheat-seed thiamine-binding protein. A blank sample is prepared by destruction of thiamine in hot alkaline solution. Model studies show that the radioassay works in thiamine concentration range of 1-10 microM, in samples of moderate ionic strength (up to 0.25 M NaCl) and is specific for thiamine in the presence of up to 5-fold molar excess of thiamine phosphates. Thiamine phosphates can also be determined but after hydrolysis with a suitable phosphatase enzyme (Taka-Diastase). Using this method, thiamine contents are successfully determined: (i) in spinach juice, directly, (ii) in cow's milk, after deproteinization, and (iii) in human urine, after desalting. Both the precision (C.V. less than 15%) and the recovery of thiamine supplements (82-100%, depending on thiamine pre-extraction method) are reasonable. Results of thiamine radioassay show a good correlation with control determinations by the standard thiochrome method. PMID: 8040564
171. Nutr Hosp. 1994 Mar-Apr;9(2):110-3.
[Thiamine deficiency associated with parenteral nutrition: apropos of a new case]
[Article in Spanish]
Sanz Paris A, Albero Gamoa R, Acha Perez FJ, Playan Uson J, Casamayor Peris L, Celaya Perez S.
Servicio de Endocrinologia y Nutricion, Hospital Miguel Servet, Espana.
In thiamine deficiency, the Krebs cycle slows large quantities of pyruvate are diverted to lactate production and anaerobic metabolism begins. The most frequent cause of this syndrome is a dietary deficiency associated to a greater or lesser degree with alcoholism. Other less frequent causes are the ingestion of raw fish contaminated with microbial thiaminases, inborn errors of metabolism and total parenteral nutrition. We present the clinical case of a patient with an acute thiamine deficiency after 15 days of total parenteral nutrition, which improved with intravenous administration of thiamine. The incidence of beriberi among patients undergoing total parenteral nutrition is very low because of the almost systematic addition of vitamin complexes. Our patient's clinical picture was sudden, corresponding to the dry form, with typical neurological symptoms and signs, major metabolic acidosis, hyperglycemia and hyponatremia. The clinical response to the administration of thiamine confirmed the diagnosis. PMID: 8031948
172. Alcohol Alcohol Suppl. 1994;2:273-9.
Thiamine utilization in the pathogenesis of alcohol-induced brain damage.
Martin PR, Pekovich SR, McCool BA, Whetsell WO, Singleton CK.
Department of Psychiatry, Vanderbilt University School of Medicine, Nashville, TN 37240, USA.
There is increasing evidence for the role of thiamine deficiency in ethanol neurotoxicity and in development of alcoholic organic brain disorders other than Wernicke-Korsakoff syndrome [WKS] and cerebellar degeneration. Investigations in humans and in animal models have implicated a reduction in the activities of thiamine-utilizing enzymes as the metabolic basis of tissue injury due to thiamine deficiency. We have investigated the interactions of the thiamine-utilizing enzyme transketolase [Tk], derived from human fibroblasts, lymphoblasts, and various brain regions, with its cofactor, thiamine pyrophosphate [TPP], in an attempt to elucidate the molecular basis of selective brain damage in alcoholism-associated thiamine deficiency. There were no significant differences in the isoelectric pattern of Tk among the nine brain regions (white matter and grey matter) examined. However, Tk activity/mg protein, increase in Tk activity with addition of excess TPP (TPP effect), and TPP-dependent rate of formation of active Tk holoenzyme (tau) varied 2.5-, 6-, and 4-fold, respectively, among these brain regions. These differences in tissue requirements for TPP may contribute to the selective vulnerability of certain brain regions to alcoholism-associated thiamine deficiency, and may influence the pattern of clinical impairment in the individual patient. PMID: 8974347
173. Ann Univ Mariae Curie Sklodowska [Med]. 1994;48 Suppl 3:29-37.
Recombinant human erythropoietin administration improves thiamine content in blood and erythrocytes transketolase activity in pre-dialyzed patients.
Pietrzak I, Baczyk K, Kubiak W.
Klinika Nefrologii, Instytut Chorob Wewnetrznych, Akademia Medyczna im. K. Marcinkowskiego, Poznaniu.
Recombinant human erythropoietin (r-Hu EPO) has proved to be effective in correcting anemia of dialyzed patients. Since 1987 reports have been published announcing the introduction of this hormone to the treatment of anemia in pre-dialyzed patients, too. Besides successful correction of anemia no evidence of acceleration of the progression of renal failure has been noted. The question of whether r-Hu EPO can also correct metabolic disturbances in predialyzed patients is to be answered. These metabolic disturbances comprises, among others, the decrease in thiamine content in blood and the deterioration of erythrocytes transketolase activity (ETKA) we described in another paper. However, as to the present we did not notice any publication concerning the impact, of r-Hu EPO administration on thiamine content in blood and on the ETKA. The purpose of our study was therefore to determine the influence of r-Hu EPO therapy in pre-dialyzed patients on thiamine level in plasma and erythrocytes and on the ETKA. Additionally, we wanted to answer the question if there was any parallel change in hematocrit index, thiamine level in blood and the ETKA in patients we observed during r-Hu EPO therapy. PMID: 8192530
174. Br Med Bull. 1994 Jan;50(1):99-114.
Aetiology of alcoholic brain damage: alcoholic neurotoxicity or thiamine malnutrition?
Academic Department of Psychiatry, Charing Cross and Westminster Medical School, University of London, UK.
The clinical presentation of brain damaged alcoholics is heterogenous and includes minimal cognitive impairment, amnesia and dementia. Whichever neurobiological technique is used, eg neuropathology, structural and functional neuroimaging, the clinico-pathological evidence suggests that thiamine malnutrition, affecting the diencephalon, can account for all clinical forms. Alcohol neurotoxicity can cause neuronal damage in cerebral cortex and can contribute to cognitive impairment but there is little direct evidence to support the need for a distinct clinical category of alcoholic dementia. Most organic brain syndromes in alcoholics therefore can be considered as variants of the Wernicke-Korsakoff syndrome and rigorous attention should be paid to the nutritional status of all alcoholics. PMID: 8149203
175. Gerontology. 1994;40(1):18-24.
Thiamine deficiency in hospitalized elderly patients.
O'Keeffe ST, Tormey WP, Glasgow R, Lavan JN.
Department of Geriatric Medicine, Beaumont Hospital, Dublin, Republic of Ireland.
Necropsy studies suggest that thiamine deficiency is underdiagnosed in life, in part because the classical clinical presentations are uncommon. Anecdotal reports suggest that thiamine deficiency may contribute to the development of delirium, heart failure and peripheral neuropathy in elderly patients, but little systematic research has been reported. We examined thiamine levels in 36 consecutive non-demented, community-dwelling patients admitted to an acute geriatric unit. Marginal thiamine deficiency [thiamine pyrophosphate effect (TPPE) 15-24%] was present in 11 (31%) and definite thiamine deficiency (TPPE > 25%) in 6 (17%) patients. Delirium occurred in 6/19 (32%) patients with normal thiamine status and 13/17 (76%) thiamine-deficient patients (p < 0.025, chi 2 test). One or more other possible causes for delirium were present in all cases. One patient had ocular signs and a dramatic clinical response to vitamin B complex therapy. Absent ankle jerks were noted in 2/19 (10%) patients with normal thiamine status and 7/17 (41%) patients with thiamine deficiency (p = 0.06). There was no difference in anthropometric indices or in the prevalence of other nutrient deficiencies between the two groups. Thiamine deficiency is common in elderly patients admitted to hospital and may contribute to the development of delirium. PMID: 8034199
176. Int J Vitam Nutr Res. 1994;64(2):113-8.
Thiamine status of elderly patients with cardiac failure including the effects of supplementation.
Pfitzenmeyer P, Guilland JC, d'Athis P, Petit-Marnier C, Gaudet M.
Service de Medecine-Geriatrie, Dijon, France.
This study compared the thiamine status of 35 elderly hospital inpatients with cardiac failure (CF) with that of 35 elderly inpatients with other diagnoses (Non-CF). The CF group was then randomly allocated to CF1 group (thiamine treatment, 200 mg per day for 7 days), and CF2 group (non supplemented). The effect of the thiamine treatment on the cardiac failure course was examined. Although there was no significant difference in thiamine status between CF and Non-CF groups, 11.5% of the first group against only 6.0% of the second was deficient with the thiamine pyrophosphate stimulation effect (TPPE) test. The same trend was observed, if NYHA functional assessment was taken into account, thiamine deficiency was more frequent in class 4 than in class 3. No significant difference for thiamin status was observed in patients receiving furosemide treatment and those without furosemide treatment. Although vitamin treatment permitted a significant improvement in thiamine status, the course of the cardiopathy was not significantly different in CF1 (supplemented) and CF2 (non supplemented) groups. Whether systematic thiamine supplementation is indicated in CF patients requires further investigation. PMID: 7960489
177. Pol Arch Med Wewn. 1994;92 Spec No:31-6.
[The influence of intermittent peritoneal dialysis on free and total thiamine concentration in plasma and erythrocytes of patients with end stage renal disease]
[Article in Polish]
Pietrzak I, Baczyk K, Mlynarczyk M.
Kliniki Nefrologii Instytutu Chorob Wewnetrznych AM w Poznaniu.
The concentration of free and total thiamine in plasma (PFTh and PTTh) and in erythrocytes (EFTh and ETTh) was determined in 20 healthy volunteers and in 8 patients suffering from ESRD treated (60 hrs/week) with IPD. Venous blood for determinations was taken immediately before and at the end of the subsequent 20-hrs PD as well as, after 12 and 48 hrs elapsed from the completion of this procedure. Thiamine was determined using fluorimetric method. Mean concentration of PFTH and PTTh as well as ETTh of patients before dialysis was found to be low, but did not differ significantly from those found in the group of healthy volunteers. Mean value of EFTh before PD was statistically lower than in normals (p < 0.05). After dialysis lasting 20 hrs a significant lowering of the concentration of PFTH (p < 0.001) and PTTh (p < 0.01) has been observed, whereas the concentration of EFTh and ETTh significantly increased (p < 0.05). After 12 and 48 hrs elapsed from the completion of dialysis a statistically significant increase in PFTh and PTTh concentration has been noted contrasting with those in EFTh and ETTh, where it felt down. Nevertheless these values in plasma and erythrocytes after 48 hrs from the completion of dialysis did not differ significantly from those found at the beginning of the determination. We conclude that IPD is a procedure exerting short-term lowering of the plasma thiamine concentration with simultaneous increase in those in erythrocytes concentration. Further studies are indispensable to clarify the problem of thiamine supplementation in patients treated with PD. PMID: 7731897
178. Brain Res. 1993 Dec 24;631(2):334-6.
Decreased activities of thiamine diphosphatase in frontal and temporal cortex in Alzheimer's disease.
Rao VL, Richardson JS, Butterworth RF.
Neuroscience Research Unit, Hospital St. Luc (University of Montreal), Ont., Canada.
Thiamine diphosphatase (TDPase) activity was measured using a colorimetric assay in frontal and temporal cortex obtained at autopsy from eight patients with neuropathologically confirmed Alzheimer's disease (AD) and from an equal number of control patients matched for age and autopsy delay interval, free from neurological or psychiatric disorders. TDPase activities were significantly reduced in frontal cortex (by 28%, P < 0.05) and temporal cortex (by 62%, P < 0.01) of AD patients. These findings add to a growing body of evidence of altered thiamine neurochemistry in AD. Given the previous reports of an association of TDPase with cholinergic nerve terminals, loss of TDPase activities could reflect loss of cholinergic neurons in frontal and temporal cortex in AD. PMID: 8131063
179. Ann Neurol. 1993 Nov;34(5):724-6.
Evidence for a central cholinergic effect of high-dose thiamine.
Meador KJ, Nichols ME, Franke P, Durkin MW, Oberzan RL, Moore EE, Loring DW.
Department of Neurology, Medical College of Georgia, Augusta 30912-3280.
In vitro animal studies have suggested that thiamine is involved in the presynaptic release of acetylcholine. Total thiamine content in cholinergic nerve terminals is comparable with that of acetylcholine, and the phosphorylation state of thiamine changes with release of acetylcholine. Thiamine binds to nicotinic receptors and may exhibit anticholinesterase activity. Based on these observations, we investigated the effects of pharmacological doses of thiamine on the cognitive deficits induced by the anticholinergic scopolamine in healthy young adults using a randomized, double-blind, placebo-controlled, double-crossover design. Drug effects were assessed by P3 event-related potential, quantitated electroencephalography, and free recall memory. Conditions included (1) baseline, (2) thiamine 5 gm p.o. and scopolamine 0.007 mg/kg IM, and (3) lactose PO and scopolamine 0.007 mg/kg IM. Thiamine significantly reduced adverse effects of scopolamine on P3 latency, spectral components of electroencephalography, and memory recall. The results are consistent with a cholinomimetic effect of thiamine in the central nervous system. Additional studies are needed to delineate the basic mechanisms and possible therapeutic efficacy of thiamine at pharmacological dosages. PMID: 8239567
180. Br J Clin Pract. 1993 Nov-Dec;47(6):343-4.
Acute encephalopathy due to coexistent nicotinic acid and thiamine deficiency.
Teare JP, Hyams G, Pollock S.
Department of Neurology, Kent & Canterbury Hospital.
We report the case of an alcoholic woman with confusion, catatonia and extrapyramidal signs, who developed features of the Wernicke-Korsakoff syndrome after treatment with intravenous high potency vitamins. We emphasise that this should arouse the suspicion of nicotinic acid deficiency even in the absence of gastrointestinal symptoms or skin lesions. PMID: 8117565
181. Alcohol Clin Exp Res. 1993 Oct;17(5):1084-8.
Thiamine-dependent enzyme changes in the brains of alcoholics: relationship to the Wernicke-Korsakoff syndrome.
Butterworth RF, Kril JJ, Harper CG.
Neuroscience Research Unit, Hopital Saint-Luc (University of Montreal), Quebec, Canada.
Chronic alcoholism results in thiamine deficiency as a consequence of poor nutrition, impaired absorption, and decreased phosphorylation to the enzyme cofactor form of the vitamin, thiamine pyrophosphate (TPP). Results of this study demonstrate significant reductions of TPP-dependent enzymes [pyruvate dehydrogenase complex, alpha-ketoglutarate dehydrogenase (alpha KGDH), and transketolase] in autopsied cerebellar vermis samples from alcoholic patients with the clinical and neuropathologically confirmed diagnosis of Wernicke-Korsakoff Syndrome (WKS). Enzyme activities in brain samples from alcoholics without WKS were within normal limits and activities of a nonthiamine-dependent enzyme, glutamate dehydrogenase, were not significantly different from control values in brain samples from alcoholics with or without WKS. These findings provide evidence, for the first time, of a direct implication of TPP-related metabolic processes in the pathogenesis of WKS. Decreased activities of alpha KGDH could be the trigger for a sequence of metabolic events resulting in energy compromise, and ultimately neuronal death in this syndrome. PMID: 8279670
182. Epilepsy Res. 1993 Oct;16(2):157-63.
Thiamine and folate treatment of chronic epileptic patients: a controlled study with the Wechsler IQ scale.
Botez MI, Botez T, Ross-Chouinard A, Lalonde R.
Hotel-Dieu Hospital, Neurology Service, Montreal, Que., Canada.
Seventy-two epileptic patients receiving phenytoin (PHT) alone or in combination with phenobarbital for more than 4 years were divided into four groups, the first taking two placebo tablets per day; the second folate (5 mg/day) and placebo; the third placebo and thiamine (50 mg/day); and the fourth both vitamins. The clinical trial lasted 6 months. At baseline assessment, 31% of the patients had subnormal blood thiamine levels and 30% had low folate. The vitamin deficiencies were independent phenomena. It was found that thiamine improved neuropsychological functions in both verbal and non-verbal IQ testing. In particular, higher scores were recorded on the block design, digit symbol, similarities and digit span subtests. Folate treatment was ineffective. These results indicate that, in epileptics chronically treated with PHT, thiamine improves neuropsychological functions, such as visuo-spatial analysis, visuo-motor speed and verbal abstracting ability. PMID: 8269914
183. J Geriatr Psychiatry Neurol. 1993 Oct-Dec;6(4):222-9.
Preliminary findings of high-dose thiamine in dementia of Alzheimer's type.
Meador K, Loring D, Nichols M, Zamrini E, Rivner M, Posas H, Thompson E, Moore E.
Department of Neurology, Medical College of Georgia, Augusta 30912-3200.
Thiamine is important not only in the metabolism of acetylcholine but also in its release from the presynaptic neuron. Pathologic, clinical, and biochemical data suggest that thiamine deficiency is detrimental to the cholinergic system and that thiamine-dependent enzymes may be altered in Alzheimer's disease. Two previous studies reported contradictory results in patients with dementia of Alzheimer's type treated with 3 g/day of thiamine. In the present study, we examined the effects of 3 to 8 g/day thiamine administered orally. Our results suggest that thiamine at these pharmacologic dosages may have a mild beneficial effect in dementia of Alzheimer's type. The mechanism of the observed effect is unknown, but the findings warrant further investigation, not only for their therapeutic implications but for their possible etiologic clues. In addition, the results suggest long-term carry-over effects that should be considered in the design of future studies. PMID: 8251051
184. Tohoku J Exp Med. 1993 Oct;171(2):129-33.
Two cases of thiamine deficiency-induced lactic acidosis during total parenteral nutrition.
Kitamura K, Takahashi T, Tanaka H, Shimotsuma M, Hagiwara A, Yamaguchi T, Hashimoto S.
First Department of Surgery, Kyoto Prefectural University of Medicine, Japan.
Two cases of severe lactic acidosis induced by total parenteral nutrition (TPN) are reported. Both cases were admitted to our department for the surgical treatment of advanced gastric cancer, and subsequently underwent TPN because of poor nutritional status. Following the initiation of TPN, both patients went into an unstable circulatory state following shock. Both cases showed signs of peritonitis, suggestive of an intraabdominal abscess, and subsequently underwent an emergency laparotomy to explore the origin of the lactic acidosis. There was, however, no apparent infectious focus which would lead to severe metabolic acidosis in the abdominal cavity. One case died of irreversible shock. The other case similarly exhibited a deteriorated cardiovascular state but promptly responded to the administration of thiamine and was resuscitated. The blood thiamine level was low in both individuals, and the two patients were subsequently diagnosed as having thiamine deficiency-induced lactic acidosis. PMID: 8128481
185. Acta Psychiatr Scand. 1993 Aug;88(2):80-4.
Thiamine pyrophosphate effect and erythrocyte transketolase activity during severe alcohol withdrawal syndrome.
Nordentoft M, Timm S, Hasselbalch E, Roesen A, Gammeltoft S, Hemmingsen R.
Department of Psychiatry, Bispebjerg Hospital, Copenhagen, Denmark.
The thiamine pyrophosphate (TPP) effect and erythrocyte transketolase activity (ETKA) in a group of 28 patients admitted to a psychiatric emergency ward because of severe alcohol withdrawal syndrome were compared with the TPP effect and ETKA in a control group of 20 healthy nonalcoholic volunteers. The patients were treated with 300 mg thiamine 3 times daily as intramuscular injections, and the TPP effect and ETKA were measured after 1 and 4 days of treatment. No difference was found between the patient group and the control group with regard to the TPP effect and ETKA and no decline in the TPP effect was found in the patient group after 4 days of intensive treatment with thiamine. ETKA increased with intensive thiamine treatment, which suggests that ETKA is a sensitive indicator of thiamine deficiency. Serum magnesium, which is a cofactor for thiamine pyrophosphate, decreased significantly with the disappearance of alcohol from the blood in patients with high initial blood alcohol levels, but this shift did not interfere with biological thiamine activity. PMID: 8213210
186. Clin Neuropathol. 1993 Jul-Aug;12(4):184-90.
Hypoxia-ischemia and thiamine deficiency.
Vortmeyer AO, Hagel C, Laas R.
Department of Neuropathology, University of Hamburg, Germany.
In order to test the hypothesis that Wernicke's encephalopathy is of topographic rather than of pathogenetic specificity we examined the brains of 49 patients without any evidence of chronic alcoholism. They had died at least four days after an event of severe hypoxia-ischemia. They all showed extensive lesions in the cortex, in the thalamus and in other regions. In 19 of them there was additional necrosis in the mamillary bodies which apparently was of the same age as the associated cortical and thalamic lesions and which could not be distinguished from Wernicke's encephalopathy. In three of the 19 cases there was a total necrosis within the mamillary bodies. By re-examining the mamillary bodies of 12 known alcoholics without any evidence for an ischemic impact we could affirm that total necrosis may fit into the spectrum of Wernicke's encephalopathy. Our findings demonstrate that the morphological changes in the mamillary bodies due to thiamine deficiency and those due to hypoxia-ischemia may be identical. PMID: 8403626
187. Acta Paediatr Jpn. 1993 Jun;35(3):262-6.
Thiamine-responsive megaloblastic anemia with diabetes mellitus and sensorineural deafness.
Akinci A, Tezic T, Erturk G, Tarim O, Dalva K.
Pediatric Endocrinology Unit, Dr Sami Ulus Children's Hospital, Ankara, Turkey.
This study introduces a patient who has thiamine and thiamine pyrophosphokinase (TPKase) enzyme deficiency associated with diabetes mellitus, sensorineural deafness and thiamine-responsive megaloblastic anemia. Diabetes mellitus was diagnosed when she was 20 months old. After 1 year, macrocytic anemia developed and the thiamine therapy was started at 75 mg/day. During the follow-up, the insulin requirement decreased and even ceased, and macrocytic anemia improved with thiamine treatment. After thiamine therapy was ceased an increase in insulin requirement was observed and macrocytic anemia developed again. PMID: 8394635
188. Vopr Med Khim. 1993 May-Jun;39(3):50-3.
[A comparative assessment of the biochemical criteria of provision of the body with thiamine]
[Article in Russian]
Sokol'nikov AA, Kodentsova VM, Isaeva VA.
Activity of transketolase in erythrocyte hemolysates, estimated by means of measurement of sedoheptulose-7-phosphate content without preinactivation of transaldolase, proved to be 3-4-fold lower as compared with the values observed after preinactivation of transaldolase. The values of thiamine diphosphate (TDP) effect did not depend on conditions of the transketolase reaction, as well as on the colorimetric procedure used for determination of sedoheptulose-7-phosphate. A high inverse correlation was found between the value of TDP effect and an excretion of thiamine with urine in adult patients and in children of 9-13 years old. Normal excretion of thiamine with urine constituted 11-12 micrograms/h in the children of this age as judged from the TDP effect-thiamine excretion in children of this age. PMID: 8333192
189. Neurosurgery. 1993 Apr;32(4):671-4.
Thiamine-deficient encephalopathy in association with aneurysmal subarachnoid hemorrhage: a case report.
Valdueza JM, Puchner MJ, Herrmann HD.
Department of Neurosurgery, University Hospital Hamburg-Eppendorf, Germany.
An alcoholic man who was admitted with an acute onset of neck pain and confusion was diagnosed as suffering from a subarachnoid hemorrhage after rupture of an anterior communicating artery aneurysm. Additionally, he showed a bilateral 6th nerve palsy of variable extent. The postoperative course was complicated by pulmonary edema and adult respiratory distress syndrome. He died on Day 28 after admission. At autopsy, surprisingly, the concomitant diagnosis of acute thiamine-deficient encephalopathy was made. Thiamine had been given only in minimal amounts during hospitalization. We describe the striking clinicopathological features of this previously undocumented case and consider the relationship between the two central nervous diseases. PMID: 8474660
190. Schweiz Med Wochenschr. 1993 Mar 13;123(10):428-31.
[Threatening thiamine deficiency in severe hyperemesis gravidarum]
[Article in German]
Fischer J, Muller A, Pohl C, Jens H.
Universitatsfrauenklinik, Abteilung Innere Medizin I, Tubingen, BRD.
We report the case of a patient with severe hyperemesis gravidarum. During parenteral nutrition the patient developed threatening thiamine deficiency. Wernicke's encephalopathy and tachycardia were predominant in the clinical course. Severe lactic acidosis and prolonged prothrombin time were the leading laboratory features. Thiamine deficiency as a cause of severe metabolic acidosis or coma can be easily ruled out or validated by intravenous thiamine administration. PMID: 8456262
191. Cent Afr J Med. 1993 Feb;39(2):40-1.
Comment in: Cent Afr J Med. 1993 Oct;39(10):216.
Thiamine-responsive acute cerebellar ataxia following febrile illness.
Adamolekun B, Eniola A.
Department of Medicine, Obafemi Awolowo University Teaching Hospital, Ile-Ife, Nigeria.
A case of post-pyrexial acute cerebellar ataxia in a 14 year old girl is presented and the available literature is reviewed. The therapeutic efficacy of thiamine hydrochloride observed in this patient lends some support to the view that acute thiamine depletion may be the pathogenetic mechanism for post-pyrexial acute cerebellar ataxia. PMID: 8261503
192. J Pharm Sci. 1993 Jan;82(1):56-9.
High-performance liquid chromatographic determination of total thiamine in human plasma for oral bioavailability studies.
Mascher H, Kikuta C.
Pharm-Analyt Labor GmbH, Traiskirchen, Austria.
A high-performance liquid chromatographic method for the determination of total thiamine in plasma was developed for a relative bioavailability comparison of two oral thiamine preparations. After separation of thiamine mono- and diphosphates with the phosphatase enzyme, the total thiamine was subjected to reversed-phase high-performance liquid chromatography, postcolumn oxidized to thiochrome with K3[Fe(CN)6], and detected by fluorescence. In the bioavailability study, 16 human subjects were put on a low-thiamine diet for 3 days. On the 2nd and 3rd days, 14 blood samples per subject and day were taken at the same times each day. Drug administration did not take place until the 3rd day. After deduction of the native concentrations of total thiamine detected on the 2nd day (mean value of approximately 7 ng/mL), the post-treatment pharmacokinetic parameters were determined (two different preparations, each with 200 mg of thiamine.HCl). PMID: 8429493
193. Can J Psychiatry. 1992 Nov;37(9):661-2.
Pyridoxine, ascorbic acid and thiamine in Alzheimer and comparison subjects.
Agbayewa MO, Bruce VM, Siemens V.
Department of Psychiatry, University Hospital, University of British Columbia, Vancouver.
We compared the intake and functional levels of vitamins B6, C and B1 in 15 pairs of Alzheimer's disease and normal subjects. These were similar in both groups, except that B1 had lower functional values for the subjects with Alzheimer's disease. This suggests that it is unlikely that B6 or C could be used in the treatment of Alzheimer's disease. The role of B1 needs further exploration. PMID: 1477827
194. Fortschr Med. 1992 Oct 20;110(29):544-8.
[Therapy of neuropathies with a vitamin B combination. Symptomatic treatment of painful diseases of the peripheral nervous system with a combination preparation of thiamine, pyridoxine and cyanocobalamin]
[Article in German]
Eckert M, Schejbal P.
St. Marienhospital, Lunen.
STUDY DESIGN: In an open, multicentric observational study involving 234 doctors in private practice, the evolution of symptoms and the tolerability of a vitamin B preparation (Neurotrat forte) used as treatment in 1,149 patients with polyneuropathy, neuralgia, radiculopathy and neuritis associated with pain and paresthesias, were observed. The form of administration (ampoules, dragees), dosage and duration of treatment were left to the individual care-providing physician. The target symptoms evaluated were intensity of pain, muscle weakness affecting the legs, and paresthesia. RESULTS: Under treatment, there was a clear improvement in these symptoms. At a second examination approximately three weeks after initiation of treatment, a positive effect on pain in particular was observed in 69% of the cases. Similar observations were also made for paresthesias and muscular weakness in the legs. PMID: 1330858
195. J Pediatr. 1992 Oct;121(4):533-8.
Thiamine, riboflavin, and pyridoxine deficiencies in a population of critically ill children.
Seear M, Lockitch G, Jacobson B, Quigley G, MacNab A.
Department of Pediatrics, University of British Columbia, Vancouver, Canada.
The unexpected autopsy finding of Wernicke encephalopathy in three children who died after prolonged enteral feeding prompted us to examine the incidence of thiamine deficiency in three high-risk pediatric populations. We also measured riboflavin and pyridoxine activity in the same groups. We used activated enzyme assays (erythrocyte transketolase, glutathione reductase, aspartate aminotransferase) to assess tissue stores of the dependent vitamin cofactors (thiamine (vitamin B1), riboflavin (vitamin B2), and pyridoxine (vitamin B6), respectively). Using our own reference ranges based on data from 80 healthy adults and children, we prospectively investigated the B vitamin status of three groups of children: (1) 27 patients who were fed solely by nasogastric tube for more than 6 months, (2) 80 children admitted to a pediatric intensive care unit for more than 2 weeks, and (3) 6 children receiving intensive chemotherapy. The upper limits for stimulated enzyme activity in control subjects were unaffected by age or gender (16% for transketolase, 63% for glutathione reductase, 123% for aspartate aminotransferase). Using these limits, 10 (12.5%) of 80 patients receiving intensive care and 4 of 6 patients receiving chemotherapy were thiamine deficient. Elevated levels returned to normal after thiamine supplementation. No patients were pyridoxine deficient, but 3 (3.8%) of the 80 patients receiving intensive care and 1 of the 6 patients receiving chemotherapy were also riboflavin deficient. We conclude that unrecognized thiamine deficiency is common in our pediatric intensive care and oncology groups. This potentially fatal but treatable disease can occur in malnourished patients of any age and is probably underdiagnosed among chronically ill children. Our findings may be applicable to other high-risk pediatric groups. PMID: 1403385
196. Acta Paediatr. 1992 Sep;81(9):723-4.
Shoshin beriberi in an infant of a thiamine-deficient mother.
Paediatric Intensive Care Unit, Royal Children's Hospital, Brisbane, Australia.
The classical form of thiamine deficiency in children is comprised of peripheral neuropathy, encephalopathy and high-output cardiac failure, predominantly right-sided. "Shoshin beriberi" cardiac failure has a different presentation, with vasoconstriction, hypotension and severe metabolic acidosis. A three-month breast-fed infant developed these features (biochemical tests confirmed the diagnosis). His mother, although non-symptomatic, had biochemical evidence of thiamine deficiency. PMID: 1421919
197. J Neurol Neurosurg Psychiatry. 1992 Sep;55(9):826-9.
Haemorrhagic thiamine deficient encephalopathy following prolonged parenteral nutrition.
Vortmeyer AO, Hagel C, Laas R.
Department of Neuropathology, University of Hamburg, Germany.
Neuropathological examination of three patients who were maintained on parenteral nutrition without substitution of thiamine demonstrated an acute haemorrhagic encephalopathy. The lesions differed substantially from the classic features of thiamine deficient encephalopathy regarding the histopathological alterations and the topographical distribution. The extreme rapidity of thiamine deprivation may have been responsible for the abrupt clinical onset of the disease and the intensity of the morphological alterations. PMID: 1402975
198. Eur J Pediatr Surg. 1992 Aug;2(4):241-4.
Lactic acidosis from thiamine deficiency during parenteral nutrition in a two-year-old boy.
Lange R, Erhard J, Eigler FW, Roll C.
General Surgery Department, Essen University Clinic, Germany.
This is a case report of a two-year-old boy who was operated electively for a blind-loop syndrome of the proximal jejunum. Because of the appearance of chylous ascites, parenteral nutrition was carried out postoperatively. The boy developed a severe uncompensated acidosis and paralytic ileus. Relaparotomy on suspicion of ischemic bowel did not explain the cause of the acidosis and ileus. Postoperatively, the child's condition worsened, requiring intensive care. The drastically elevated lactate levels corroborated the eventually suspected diagnosis of a vitamin B1 deficiency syndrome. The administration of thiamine within two hours produced correction of the acidosis without further bicarbonate therapy. In 24 hours circulation was stabilized. Two months post-operatively the boy had completely recovered from the sequelae of his shock event. PMID: 1390556
199. JPEN J Parenter Enteral Nutr. 1992 May-Jun;16(3):241-7.
Thiamine, riboflavin, folate, and vitamin B12 status of low birth weight infants receiving parenteral and enteral nutrition.
Levy R, Herzberg GR, Andrews WL, Sutradhar B, Friel JK.
Department of Biochemistry, Memorial University of Newfoundland, St John's, Canada.
Thirty infants were randomly assigned to receive either 3 mL of MVI-Pediatric supplement (PAR3 group, parenterally fed) or 2 mL (PAR2 group, parenterally fed). For the first week, 100% received total parenteral nutrition (TPN), 50% by the second, and less than 33% by the third. Eighteen control infants received enteral feeds of infant formula. Baseline (before TPN) and subsequent weekly blood samples, dietary data, and 24-hour urine collections were obtained. The adequacies of thiamine and riboflavin were assessed by the thiamine pyrophosphate effect and erythrocyte glutathione reductase activity, respectively. Urinary thiamine and riboflavin levels were measured by fluorometry. Plasma folate, red blood cell folate, urinary folate, and plasma vitamin B12 concentrations were determined by radioassay. No differences between groups were observed in thiamine pyrophosphate effect, erythrocyte glutathione reductase activity, urinary B1 or B2, or red blood cell folate levels at any time. Plasma folate differed (p less than .05) among the PAR3 group (24 +/- 7 ng/mL), and both the PAR2 (13 +/- 5 ng/mL) and enterally fed (ENT) groups (16 +/- 3 ng/mL) before the initiation of feeds, at week 1 (PAR3 = 32 +/- 15 ng/mL; PAR2 = 18 +/- 4 ng/mL; ENT = 19 +/- 9, ng/mL) and between the PAR3 (30 +/- 16 ng/mL) and PAR2 (16 +/- 4 ng/mL) infants at week 2. Plasma vitamin B12 levels differed among the ENT groups (551 +/- 287 pg/mL) and both the parenteral groups (PAR2 = 841 +/- 405 pg/mL; PAR3 = 924 +/- 424 pg/mL) at week 1 and between the ENT (530 +/- 238 pg/mL) and PAR3 (999 +/- 425 pg/mL) groups at week 2.(ABSTRACT TRUNCATED AT 250 WORDS) PMID: 1501354
200. Cancer. 1992 Apr 1;69(7):1710-3.
Thiamine deficiency in hematologic malignant tumors.
van Zaanen HC, van der Lelie J.
Department of Internal Medicine, Academic Medical Centre, Amsterdam, The Netherlands.
The case is reported of a patient with acute myeloid leukemia with severe right-sided congestive heart failure that responded to treatment with thiamine. Leukocytes cells contain relatively high concentrations of thiamine-dependent enzymes compared with erythrocytes. Because no other cause could be found, it was postulated that consumption of thiamine by blast cells was responsible for the deficiency. After studying this patient, the thiamine pyrophosphate (TPP) effect was measured in five other consecutive patients with fast-growing hematologic malignant tumors. In two patients, the TPP effect was elevated slightly, but another patient had a definite thiamine deficiency with severe cardiac failure. It is suggested that the clinician be alert for this underdiagnosed potentially fatal but easily treatable deficiency in nonalcoholic patients with fast-growing hematologic cancers. PMID: 1551055
201. J Neurol Neurosurg Psychiatry. 1992 Feb;55(2):136-7.
Thiamine status in inherited degenerative ataxias.
Pedraza OL, Botez MI.
Neurology Service, Hotel-Dieu de Montreal, Quebec, Canada.
Blood thiamine levels in ataxia patients were studied. No significant differences were found between 30 patients with Friedreich's ataxia and 29 patients with olivopontocerebellar atrophy (OPCA) compared with control subjects. Both OPCA and Friedreich's ataxia patients presented significantly lower cerebrospinal fluid thiamine levels than their controls (p less than 0.001 and p less than 0.04 respectively). These results, discussed in terms of the high degree of cerebellar atrophy on CT scans in OPCA v Friedreich's ataxia patients, seem to correlate with cerebellar thiamine turnover and content. PMID: 1538220
202. Am J Emerg Med. 1992 Jan;10(1):61-3.
Anaphylaxis from administration of intravenous thiamine.
Stephen JM, Grant R, Yeh CS.
Division of Emergency Medicine, Tufts/New England Medical Center, Boston, MA 02111.
The routine administration of intravenous thiamine in the emergency department has become widespread. Although anaphylaxis from intravenous thiamine is felt to be uncommon, it can be life threatening. The authors present such a case and review the literature regarding this clinical entity. This case of anaphylactic reaction appears to be the first instance reported since 1946 in the US literature. However a review revealed that cases of anaphylaxis from thiamine have been reported with some regularity in the non-US literature. Given the large number of patients treated without side effects, it seems that thiamine is relatively safe. However, this case illustrates that the assumption that thiamine is a drug with a completely innocuous nature is not totally accurate. PMID: 1736919
203. Eur J Clin Pharmacol. 1992;42(2):219-22.
Plasma thiamine concentrations after intramuscular and oral multiple dosage regimens in healthy men.
Royer-Morrot MJ, Zhiri A, Paille F, Royer RJ.
Departement de Pharmacologie Clinique, CHRU, France.
A novel liquid chromatographic method for the determination of thiamine in plasma has been developed and has been used to study plasma thiamine concentrations after multiple dosage regimens for 11 days. The method involves purification, concentration and analytical separation of thiochrome on-line, using a switching column system. Ten healthy men were given 500 mg thiamine i.m. once a day (Group 1) and ten were given 250 mg p.o. every 12 h (Group 2). The times to reach steady state (7 and 5.6 days for Groups 1 and 2, respectively) were not different (P greater than 0.05). The mean elimination half-life was 1.8 days. The mean minimum steady-state concentration after the oral regimen (23 micrograms.l-1) was 78% of that after the intramuscular regime (29 micrograms.l-1). PMID: 1618256
204. Age Ageing. 1992 Jan;21(1):67-71.
Thiamine status of elderly patients with cardiac failure.
Kwok T, Falconer-Smith JF, Potter JF, Ives DR.
Department of Medicine for the Elderly, Leicester General Hospital.
This study compared the thiamine status of 37 elderly patients admitted with cardiac failure (CF) with that of 35 unselected elderly patients with other diagnoses (Non-CF), and with that of 41 apparently healthy elderly people. The thiamine pyrophosphate effect (TPPE) on erythrocyte transketolase activity was used to estimate thiamine status. The prevalence of thiamine deficiency (TPPE greater than 19%) on admission in the CF and Non-CF groups was 13% and 29%, respectively. The TPPE of the CF group was significantly lower than that of the Non-CF group, and was not significantly different from that of the elderly control group. The results indicate that thiamine deficiency is not common in an unselected group of elderly inpatients with cardiac failure, but a potential benefit of thiamine supplementation in such patients cannot be ruled out. PMID: 1553864
205. Int J Vitam Nutr Res. 1992;62(2):165-72.
The transport of thiamine, riboflavin and pyridoxal 5'-phosphate by human placenta.
Zempleni J, Link G, Kubler W.
Inst. f. Ernahrungswissenschaft, Justus Liebig-Universitat Giessen, FRG.
In the present examination the concentrations of thiamine, riboflavin and pyridoxal 5'-phosphate in blood plasma of pregnant women and venous and arterial cord plasma were determined. In maternal plasma the concentration was 4.5 nmol/l (thiamine), 22.2 nmol/l (PLP), 8.7 nmol/l (free riboflavin) and 84.5 nmol/l (FAD + FMN). In venous cord plasma the concentration was 45.9 nmol/l (thiamine), 112.1 nmol/l (PLP), 40.6 nmol/l (free riboflavin) and 49.1 nmol/l (FAD + FMN). Therefore the gradients of concentration between maternal plasma and venous cord plasma were 1:10 for thiamine, 1:4.7 for free riboflavin and 1:5 for PLP. For the coenzyme forms of vitamin B2 the maternal circulation showed the higher concentration (1.7:1). Therefore an active transplacentar transport mechanism was assumed. The vitamin concentrations in cord arteria were significantly lower than that in cord vene, indicating a massive retention by the fetus. PMID: 1517040