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OBJECTIVE: To develop a predictive model for thiamine responsive disorders (TRDs) among infants and young children hospitalized with signs or symptoms suggestive of thiamine deficiency disorders (TDDs) based on response to therapeutic thiamine in a high-risk setting. STUDY DESIGN: Children aged 21 days to <18 months hospitalized with signs or symptoms suggestive of TDD in northern Lao People's Democratic Republic were treated with parenteral thiamine (100 mg daily) for ≥3 days in addition to routine care. Physical examinations and recovery assessments were conducted frequently for 72 hours after thiamine was initiated. Individual case reports were independently reviewed by three pediatricians who assigned a TRD status (TRD or non-TRD), which served as the dependent variable in logistic regression models to identify predictors of TRD. Model performance was quantified by empirical area under the receiver operating characteristic curve. RESULTS: A total of 449 children (median [Q1, Q3] 2.9 [1.7, 5.7] months old; 70.3% exclusively/predominantly breastfed) were enrolled; 60.8% had a TRD. Among 52 candidate variables, those most predictive of TRD were exclusive/predominant breastfeeding, hoarse voice/loss of voice, cyanosis, no eye contact, and no diarrhea in the previous 2 weeks. The area under the receiver operating characteristic curve (95% CI) was 0.82 (0.78, 0.86). CONCLUSIONS: In this study, the majority of children with signs or symptoms of TDD responded favorably to thiamine. While five specific features were predictive of TRD, the high prevalence of TRD suggests that thiamine should be administered to all infants and children presenting with any signs or symptoms consistent with TDD in similar high-risk settings. The usefulness of the predictive model in other contexts warrants further exploration and refinement. TRIAL REGISTRATION: Clinicaltrials.gov NCT03626337.
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População do Sudeste Asiático , Deficiência de Tiamina , Tiamina , Humanos , Laos/epidemiologia , Lactente , Masculino , Feminino , Deficiência de Tiamina/diagnóstico , Deficiência de Tiamina/epidemiologia , Deficiência de Tiamina/tratamento farmacológico , Estudos Prospectivos , Tiamina/uso terapêutico , Tiamina/administração & dosagem , Recém-Nascido , Complexo Vitamínico B/uso terapêutico , Complexo Vitamínico B/administração & dosagemRESUMO
We report a case of cardiac beriberi in a 76-year-old man who was hospitalized with a congestive condition of subacute onset, diagnosed as high-output heart failure associated with severe tricuspid regurgitation and indication for caval valve implantation, which, after thiamine replacement, resulted in improvement of all conditions. (Level of Difficulty: Beginner.).
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Resumo O beribéri é a manifestação clínica da deficiência grave e prolongada de tiamina (vitamina B1). Doença negligenciada que acomete a população de baixa renda, em situação de insegurança alimentar e nutricional. O objetivo do estudo foi comparar casos de beribéri em indígenas com casos em não indígenas no Brasil. Trata-se de estudo transversal de casos notificados de beribéri no período de 2013 a 2018, no formulário do SUS (FormSUS) do Ministério da Saúde. Foram comparados os casos em indígenas e em não indígenas pelo teste qui-quadrado ou teste exato de Fisher com nível de significância de p < 0,05. No período estudado foram notificados no país 414 casos de beribéri, sendo 210 (50,7%) indígenas. Referiram consumo de bebidas alcoólicas 58,1% dos indígenas e 71,6% dos não-indígenas (p = 0,004); adicionalmente, 71,0% dos indígenas consumiam caxiri (bebida alcoólica tradicional fermentada). Relataram fazer esforço físico diário 76,1% dos indígenas e 40,2% dos não-indígenas (p <0 ,001). Conclui-se que o beribéri no país acomete mais indígenas e está relacionado ao consumo de álcool e ao esforço físico.
Abstract Beriberi is the clinical manifestation of severe and prolonged thiamine (vitamin B1) deficiency. It is a neglected disease that affects low-income populations facing food and nutrition insecurity. The aim of this study was to compare cases of beriberi among indigenous and non-indigenous people in Brazil. We conducted a cross-sectional study using data on cases of beriberi during the period July 2013-September 2018 derived from beriberi notification forms available on the FormSUS platform. Cases in indigenous and non-indigenous patients were compared using the chi-squared test or Fisher's exact test, adopting a significance level of 0.05. A total of 414 cases of beriberi were reported in the country during the study period, 210 of which (50.7%) were among indigenous people. Alcohol consumption was reported by 58.1% of the indigenous patients and 71.6% of the non-indigenous patients (p = 0.004); 71.0% of the indigenous patients reported that they consumed caxiri, a traditional alcoholic drink. Daily physical exertion was reported by 76.1% of the indigenous patients and 40.2% of the non-indigenous patients (p < 0.001). It is concluded that beriberi disproportionately affects indigenous people and is associated with alcohol consumption and physical exertion.
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Abstract Objective: In this study, we created an animal model to demonstrate the effects of thiamine on the hearing pathways of new-borns during pregnancy and lactation by inducing a dietary thiamine deficiency in the mother. Methods: The study included 16 female Wistar albino rats. The animals were separated into four groups and provided the appropriate amounts of dietary thiamine according to their groups during pre-pregnancy, pregnancy, and lactation periods. Three pups from each mother were included in the study, and 12 pups were selected from each group. On the fortieth day after birth, the auditory pathways of 48 pups in the 4 groups were examined electro physiologically and ultra-structurally. Results: In Group N-N, morphology of hair cells stereocilia degeneration was not obtained in all turns of cochlea. In Group N-T, Inner Hair Cells (IHCs) and Outher Hair Cells (OHCs) stereocilia didn't show degeneration in all turns of cochlea but had rupture inrows of HCs stereocilia. In group T-N IHCs stereocilia less degeneration was observed in all turns of cochlea. OHC stereocilia partial loss was observed only in basal turn of cochlea. In Group T-T IHCs stereocilia was observed less degeneration and rupture in all turns of cochlea. Conclusion: Thiamine is vital for the development of cochlear hair cells during both prenatal and postnatal periods. Even partial deficiency of thiamine causes significant degeneration to the auditory pathway. Level of evidence: The level of evidence of this article is 5. This article is an experimental animal and laboratory study.
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OBJECTIVE: In this study, we created an animal model to demonstrate the effects of thiamine on the hearing pathways of new-borns during pregnancy and lactation by inducing a dietary thiamine deficiency in the mother. METHODS: The study included 16 female Wistar albino rats. The animals were separated into four groups and provided the appropriate amounts of dietary thiamine according to their groups during pre-pregnancy, pregnancy, and lactation periods. Three pups from each mother were included in the study, and 12 pups were selected from each group. On the fortieth day after birth, the auditory pathways of 48 pups in the 4 groups were examined electro physiologically and ultra-structurally. RESULTS: In Group N-N, morphology of hair cells stereocilia degeneration was not obtained in all turns of cochlea. In Group N-T, Inner Hair Cells (IHCs) and Outher Hair Cells (OHCs) stereocilia didn't show degeneration in all turns of cochlea but had rupture inrows of HCs stereocilia. In group T-N IHCs stereocilia less degeneration was observed in all turns of cochlea. OHC stereocilia partial loss was observed only in basal turn of cochlea. In Group T-T IHCs stereocilia was observed less degeneration and rupture in all turns of cochlea. CONCLUSION: Thiamine is vital for the development of cochlear hair cells during both prenatal and postnatal periods. Even partial deficiency of thiamine causes significant degeneration to the auditory pathway. LEVEL OF EVIDENCE: The level of evidence of this article is 5. This article is an experimental animal and laboratory study.
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Vias Auditivas , Deficiência de Tiamina , Gravidez , Animais , Ratos , Feminino , Ratos Wistar , Células Ciliadas Auditivas , Cóclea , Tiamina/farmacologia , Células Ciliadas Auditivas ExternasRESUMO
BACKGROUND: Thiamine (vitamin B1) is a cofactor for enzymes of central energy metabolism and its deficiency (TD) impairs oxidative phosphorylation, increases oxidative stress, and activates inflammatory processes that can lead to neurodegeneration. Wernicke-Korsakoff syndrome (WKS) is a consequence of chronic TD, which leads to extensive neuronal death, and is associated with neuropathological disorders, including cognitive deficits and amnesia. The hippocampus is one of the brain areas most affected by WKS. B1 replacement may not be enough to prevent the irreversible cognitive deficit associated with WKS. MATERIALS AND METHODS: An organotypic hippocampal slice culture (OHC) model was developed to investigate, using immunofluorescence and confocal microscopy and transcriptome analysis, the molecular mechanisms underlying the neurodegeneration associated with TD. The effect of anti-inflammatory pharmacological intervention with resveratrol (RSV) was also assessed in B1-deprived OHCs. RESULTS: In OHCs cultured without B1, neuronal density decayed after 5 days and, on the 7th day, the epigenetic markings H3K4me3 and H3K9me3 were altered in mature neurons likely favoring gene transcription. Between the 7th and the 14th day, a pulse of neurogenesis was observed followed by a further massive neuron loss. Transcriptome analysis at day nine disclosed 89 differentially expressed genes in response to B1 deprivation. Genes involved in tryptophan metabolism and lysine degradation KEGG pathways, and those with Gene Ontology (GO) annotations related to the organization of the extracellular matrix, cell adhesion, and positive regulation of synaptic transmission were upregulated. Several genes of the TNF and FoxO signaling pathways and with GO terms related to inflammation were inhibited in response to B1 deprivation. Nsd1, whose product methylates histone H3 lysine 36, was upregulated and the epigenetic marking H3K36me3, associated with negative regulation of neurogenesis, was increased in neurons. Treating B1-deprived OHCs with RSV promoted an earlier neurogenesis pulse. CONCLUSION: Neuroregeneration occurs in B1-deficient hippocampal tissue during a time window. This phenomenon depends on reducing neuroinflammation and, likely, on metabolic changes, allowing acetyl-CoA synthesis from amino acids to ensure energy supply via oxidative phosphorylation. Thus, neuroinflammation is implicated as a major regulator of hippocampal neurogenesis in TD opening a new search space for treating WKS.
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Doenças Neuroinflamatórias , Deficiência de Tiamina , Humanos , Lisina/metabolismo , Deficiência de Tiamina/complicações , Deficiência de Tiamina/metabolismo , Deficiência de Tiamina/patologia , Neurogênese/fisiologia , Hipocampo/metabolismo , Tiamina/metabolismo , Neurônios/metabolismoRESUMO
Background: Polioencephalomalacia (PEM) is a neurological disease in ruminants, which is characterized by malacia of brain gray matter. Thiamine deficiency and sulfur intoxication are the most common causes of PEM in sheep. Affected animals present signs of cerebrocortical syndrome, including amaurosis, ataxia, head pressing, mental depression, seizures, and opisthotonus. The neurological examination aims to determine the neurolocalization of the lesions and advanced imaging techniques are useful for confirming the affected area(s) in the central nervous system. The aim of this study is to describe clinical features and ante-mortem diagnosis using magnetic resonance imaging (MRI) in a sheep with PEM. Case: A 18-month-old male Dorper sheep from a flock started receiving concentrate 7 days before. According to the owner, no clinical signs of abnormality were observed on the previous morning. However, in the afternoon, the animal became selfisolated and did not follow the flock to the sheepfold. The following day, he was found in recumbency. Physical examination revealed lateral recumbency, rectal temperature 39.5ºC, 52 bpm, 120 bpm, congested mucous membranes, capillary refill time 1 s, ruminal (4/5 min) and intestinal hypomotility. The assessment of the central nervous system revealed a decreased level of consciousness, focal seizures, opisthotonus, and absence of menace response. The following differential diagnoses were listed: PEM, head trauma, focal symmetrical encephalomalacia, bacterial encephalitis, and rabies. Treatment was composed of dexamethasone [0.2 mg/kg - i.v., SID (1st-3rd day), 0.1 mg/kg, i.v., SID (4th-6th day), and 0.05 mg/kg, i.v., SID (7th-9th day)]; mannitol [1 g/kg - i.v. and diazepam 0.4 mg/kg, i.v. single dose at admission]; vitamin B1 [10 mg/kg - i.m., SID], furosemide [1 mg/kg - i.v., SID for 3 days] and sulfadoxine/trimethoprim [30 mg/kg - i.m., SID for 10 days]. After the initial treatment, the patient showed mild clinical improvement; however, the amaurosis was still present. Magnetic resonance imaging of the brain was performed on the 2nd day of hospitalization, showing a symmetrical hypersignal in the parietal and occipital cortices, in the axial and sagittal sequences weighted in T2 and FLAIR. Discussion: This study aimed to describe the clinical signs and MRI findings in a sheep with PEM. In this case, the sudden change to the feed composition probably led to ruminal dysbiosis, inhibition of thiamine-producing microorganisms and proliferation of bacteria that synthesize thiaminase. Thiamine therapy proved to be effective and capable of reverting the clinical signs. The decrease in the level of consciousness, cortical blindness, and opisthotonus are due to alterations in the parietal cortex, in the occipital cortex, and in the cerebellum, respectively, which were demonstrated by hypersignal areas in the MRI. Therefore, the neurolocalization of the lesion based on neurologic examination and the MRI findings were related. The physicochemical and cytological evaluations of the cerebrospinal fluid, and dosage of thiamine and the concentration of hydrogen sulphide in the rumen were not performed. However, the response to thiamine treatment associated with the neurologic examination and MRI findings helped in determining the diagnosis. Additionally, MRI can be used as a useful tool for the ante mortem diagnosis of PEM.
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Animais , Masculino , Deficiência de Tiamina/veterinária , Ovinos , Encefalomalacia/veterinária , Encefalomalacia/diagnóstico por imagem , Espectroscopia de Ressonância Magnética , Necrose/veterinária , Doenças do Sistema Nervoso/veterináriaRESUMO
BACKGROUND: Beriberi is the clinical manifestation of thiamine deficiency. It is multicausal and typically associated with poverty and food insecurity among vulnerable populations, such as indigenous people. OBJECTIVE: The objective of this study was to carry out a spatial analysis of reported cases of beriberi among indigenous people in Brazil. METHODS: Cross-sectional study using time series data on suspected cases of beriberi reported to the Ministry of Health via the FormSUS between July 2013 and September 2018. Indigenous villages were georeferenced, and Kernel density estimation was used to identify patterns of the spatial distribution of beriberi cases. RESULTS: A total of 414 cases of beriberi were reported in the country of which 210 (50.7%) were indigenous people. All the cases in indigenous people occurred in states located in the Legal Amazon (Maranhão, Roraima, and Tocantins). Kernel density estimation showed high-density areas in Tocantins and Roraima. CONCLUSIONS: This is the first nationwide study of reported cases of beriberi. The findings can be used to guide actions that contribute to the monitoring and prevention of beriberi among indigenous people.
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Beriberi , Beriberi/epidemiologia , Brasil/epidemiologia , Estudos Transversais , Humanos , Povos Indígenas , Pobreza , TiaminaRESUMO
ABSTRACT The Paraguayan War ended 150 years ago. Back then, there were outbreaks of combatants' limb weakness and tingling related to "palustrian cachexia", not clearly funded at the time on nutritional deficiency, the use of native flora to feed troops, and alcoholism. We report a case of a soldier with ascending paralysis, mental confusion and finally tetraplegia with preserved oculomotricity. This would probably be a case of locked-in syndrome (LIS) due to Gayet-Wernicke's encephalopathy consequent to thiamine deficiency. The role of thiamine in the peripheral or central nervous system expression was shown decades later to be related to poor diet, or use of foods containing thiaminase or thiamine antagonists, worsened by the fact that the bodily stores of thiamine are restricted, and deficits may grow fast.
RESUMO A Guerra do Paraguai terminou há 150 anos. Houve surtos de fraqueza dos membros dos combatentes e parestesias relacionadas à "caquexia palustre", não claramente fundamentados na época sobre deficiência nutricional, o uso da flora nativa para alimentar as tropas e o alcoolismo. Referimo-nos a um caso de um militar com paralisia ascendente, confusão mental e finalmente tetraplegia com oculomotricidade preservada. Esse relato seria provavelmente devido a um caso de "síndrome do encarceramento" secundário à encefalopatia de Gayet-Wernicke consequente à deficiência de tiamina. O papel da tiamina na expressão periférica ou do SNC foi previsto décadas mais tarde em relação a uma dieta pobre, ou ao uso de alimentos contendo tiamina ou antagonistas da tiamina, agravado pelo fato de que as reservas corporais de tiamina são restritas, e os déficits podem se manifestar rapidamente.
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Septic shock is associated with unacceptably high mortality rates, mainly in developing countries. New adjunctive therapies have been explored to reduce global mortality related to sepsis. Considering that metabolic changes, mitochondrial dysfunction and increased oxidative stress are specific disorders within the path of septic shock, several micronutrients that could act in cellular homeostasis have been studied in recent decades. Thiamine, also known as vitamin B1, plays critical roles in several biological processes, including the metabolism of glucose, synthesis of nucleic acids and reduction of oxidative stress. Thiamine deficiency could affect up to 70% of critically ill patients, and thiamine supplementation appears to increase lactate clearance and decrease the vasopressor dose. However, there is no evident improvement in the survival of septic patients. Other micronutrients such as vitamin C and D, selenium and zinc have been tested in the same context but have not been shown to improve the outcomes of these patients. Some problems related to the neutrality of these clinical trials are the study design, doses, route, timing, length of intervention and the choice of endpoints. Recently, the concept that multi-micronutrient administration may be better than single-micronutrient administration has gained strength. In general, clinical trials consider the administration of a single micronutrient as a drug. However, the antioxidant defense is a complex system of endogenous agents in which micronutrients act as cofactors, and the physiological interactions between micronutrients are little discussed. In this context, the association of thiamine, vitamin C and corticoids was tested as an adjunctive therapy in septic shock resulting in a significant decrease in mortality. However, after these initial results, no other study conducted with this combination could reproduce those benefits. In addition, the use of low-dose corticosteroids is recommended in patients with septic shock who do not respond to vasopressors, which can affect the action of thiamine. Therefore, given the excellent safety profile, good biologic rationale and promising clinical studies, this review aims to discuss the mechanisms behind and the evidence for single or combined thiamine supplementation improving the prognosis of patients with septic shock.
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A síndrome de Wernicke-Korsakoff é uma rara encefalopatia desencadeada pela deficiência de tiamina, uma vitamina do complexo B, que atua como importante cofator de enzimas responsáveis pela manutenção da homeostase da energia cerebral. Apresentamos o caso de uma paciente de 18 anos, gestante, com diagnóstico prévio de pancreatite aguda biliar, que evoluiu à hiperêmese gravídica e à Wernicke-Korsakoff. Objetivamos, com este trabalho, chamar a atenção para a importância do diagnóstico imediato dessa síndrome diante de seu potencial em causar danos cerebrais irreversíveis, caso não tratada precocemente.
Wernicke-Korsakoff syndrome is a rare encephalopathy triggered by deficiency of thiamine, a B-complex vitamin, which acts as an important cofactor of enzymes responsible for maintaining brain energy homeostasis. We present the case of an 18-year-old pregnant woman with previous diagnosis of acute biliary pancreatitis, who developed hyperemesis gravidarum and Wernicke-Korsakoff. With this work, we aim to draw attention to the importance of the immediate diagnosis of this syndrome in view of its potential to cause irreversible brain damage if not treated early.
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Humanos , Feminino , Gravidez , Adolescente , Deficiência de Tiamina , Encefalopatia de Wernicke/diagnóstico , Síndrome de Korsakoff/diagnóstico , Hiperêmese Gravídica , Relatos de Casos , Doenças do Sistema NervosoRESUMO
The evaluation of thiamine and its derivative phosphate esters levels in pregnant women in rural communities can contribute not only for understanding the specific characteristics of this population regarding nutritional aspects, but also for clarifying the relations of psychiatric manifestations and a vitamin deficit. In the present work we assessed sociodemographic variables, psychiatric parameters and thiamine and its derivative in the whole blood of women in a rural, low-income community in Brazil. A case-control study was done. 94 women were divided in groups using the trimesters of pregnancy as a criterion: each trimester, 1st, 2nd and 3rd had 17, 37 and 38 women, respectively. A control group of non-pregnant women (n-39) was also included. Symptoms of anxiety and depression were assessed using the HAMA Scale and Beck Inventory, respectively. The thiamine and its phosphorylated derivatives concentrations were determined in whole blood samples using the HPLC method. The results suggest that physiological mechanisms linked to the metabolic pathways of thiamine may play a role in some neurobiological substrate involved in the regulation of emotional state. Thus, social vulnerability is identified as an important factor to be considered in the evaluation of the mental health of pregnant women living in rural communities.
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Transtornos Mentais/epidemiologia , Complicações na Gravidez/epidemiologia , Gestantes , Deficiência de Tiamina/epidemiologia , Populações Vulneráveis , Adolescente , Adulto , Brasil/epidemiologia , Estudos de Casos e Controles , Feminino , Humanos , Transtornos Mentais/sangue , Transtornos Mentais/psicologia , Pobreza/psicologia , Pobreza/tendências , Gravidez , Complicações na Gravidez/sangue , Complicações na Gravidez/psicologia , Gestantes/psicologia , População Rural/tendências , Deficiência de Tiamina/sangue , Deficiência de Tiamina/psicologia , Populações Vulneráveis/psicologia , Adulto JovemRESUMO
SUMMARY Wernick's Encephalopathy (WE) is an acute neuropsychiatric syndrome caused by thiamine deficiency post hematopoietic stem cell transplant (HSCT). WE is associated with high mortality and morbidity rates, but due to its rare occurrence, it is rarely considered in patients submitted to this procedure. Considering that, the manuscript reports the clinical characteristics and the possible factors that predisposed the occurrence of WE in a patient with non-Hodgkin's lymphoma post-Autologous HSCT. We conclude that WE should be considered in patients submitted to autologous HSCT associated with prolonged use of TPN and malnutrition.
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Humanos , Feminino , Adulto , Deficiência de Tiamina/complicações , Encefalopatia de Wernicke/etiologia , Linfoma não Hodgkin/terapia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Transplante Autólogo , Encefalopatia de Wernicke/diagnóstico por imagem , Fatores de RiscoRESUMO
BACKGROUND: The previous studies have demonstrated the reduction of thiamine diphosphate is specific to Alzheimer's disease (AD) and causal factor of brain glucose hypometabolism, which is considered as a neurodegenerative index of AD and closely correlates with the degree of cognitive impairment. The reduction of thiamine diphosphate may contribute to the dysfunction of synapses and neural circuits, finally leading to cognitive decline. RESULTS: To demonstrate this hypothesis, we established abnormalities in the glucose metabolism utilizing thiamine deficiency in vitro and in vivo, and we found dramatically reduced dendrite spine density. We further detected lowered excitatory neurotransmission and impaired hippocampal long-term potentiation, which are induced by TPK RNAi in vitro. Importantly, via treatment with benfotiamine, Aß induced spines density decrease was considerably ameliorated. CONCLUSIONS: These results revealed that thiamine deficiency contributed to synaptic dysfunction which strongly related to AD pathogenesis. Our results provide new insights into pathogenesis of synaptic and neuronal dysfunction in AD.
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Doença de Alzheimer/etiologia , Doença de Alzheimer/metabolismo , Neurônios/fisiologia , Sinapses/fisiologia , Deficiência de Tiamina/complicações , Deficiência de Tiamina/metabolismo , Tiamina Pirofosfato/deficiência , Doença de Alzheimer/fisiopatologia , Peptídeos beta-Amiloides/metabolismo , Animais , Western Blotting , Espinhas Dendríticas/metabolismo , Difosfotransferases/metabolismo , Glucose/metabolismo , Hipocampo/metabolismo , Hipocampo/fisiopatologia , Masculino , Camundongos Endogâmicos C57BL , Distribuição Aleatória , Ratos Sprague-Dawley , Reação em Cadeia da Polimerase em Tempo Real , Transmissão Sináptica/fisiologia , Deficiência de Tiamina/fisiopatologia , Tiamina Pirofosfato/metabolismoRESUMO
Thiamine deficiency (TD) has been used as an experimental model in rodents to study the molecular mechanisms of neurodegeneration and its association with behavioral changes. The aims of the present study were to investigate the spatial cognitive performance of pyrithiamine-induced thiamine deficiency (PTD) in adult male rats and disclose the thalamic proteome alterations caused by a severe TD episode. After the onset of the neurological signs, such as seizure and/or loss of righting reflex, the TD treatment was interrupted. Following 15â¯days of recovery, all rats were submitted to the spatial cognitive tasks in the Morris Water Maze (MWM). The results show that the PTD rats exhibited deficits during the learning process, which was reverted by repeated training. However, despite the spatial cognitive recovery, some protein changes were not reversible. The proteomic analysis, using label-free quantification, revealed deregulation of 183 thalamic proteins. Using bioinformatic tools, these proteins were categorized according to Gene Ontology functional annotation and metabolic pathways. We show that a severe TD affects proteins involved in different biological processes, such as, oxidative stress, neurotransmitter synthesis and synaptic vesicle cycle. These could explain the outcome in neurotransmitter release changes caused by TD, previously observed by our group and by other authors. These findings disclose the role of key proteins and metabolic pathways probably involved in the neurodegeneration process induced by TD. These proteins represent relevant molecular targets for future studies focusing also on the molecular basis of selective vulnerability of some brain areas to TD insult.
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Comportamento Animal/fisiologia , Aprendizagem Espacial/fisiologia , Tálamo/metabolismo , Deficiência de Tiamina/metabolismo , Tiamina/metabolismo , Animais , Peso Corporal/fisiologia , Cognição/fisiologia , Ingestão de Alimentos/fisiologia , Masculino , Proteoma , Proteômica , Ratos , Ratos WistarRESUMO
BACKGROUND: The previous studies have demonstrated the reduction of thiamine diphosphate is specific to Alzheimer's disease (AD) and causal factor of brain glucose hypometabolism, which is considered as a neurodegenerative index of AD and closely correlates with the degree of cognitive impairment. The reduction of thiamine diphosphate may contribute to the dysfunction of synapses and neural circuits, finally leading to cognitive decline. RESULTS: To demonstrate this hypothesis, we established abnormalities in the glucose metabolism utilizing thiamine deficiency in vitro and in vivo, and we found dramatically reduced dendrite spine density. We further detected lowered excitatory neurotransmission and impaired hippocampal long-term potentiation, which are induced by TPK RNAi in vitro. Importantly, via treatment with benfotiamine, Aß induced spines density decrease was considerably ameliorated. CONCLUSIONS: These results revealed that thiamine deficiency contributed to synaptic dysfunction which strongly related to AD pathogenesis. Our results provide new insights into pathogenesis of synaptic and neuronal dysfunction in AD.
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Animais , Masculino , Sinapses/fisiologia , Deficiência de Tiamina/complicações , Deficiência de Tiamina/metabolismo , Tiamina Pirofosfato/deficiência , Doença de Alzheimer/etiologia , Doença de Alzheimer/metabolismo , Neurônios/fisiologia , Deficiência de Tiamina/fisiopatologia , Tiamina Pirofosfato/metabolismo , Distribuição Aleatória , Western Blotting , Peptídeos beta-Amiloides/metabolismo , Ratos Sprague-Dawley , Difosfotransferases/metabolismo , Transmissão Sináptica/fisiologia , Espinhas Dendríticas/metabolismo , Doença de Alzheimer/fisiopatologia , Reação em Cadeia da Polimerase em Tempo Real , Glucose/metabolismo , Hipocampo/fisiopatologia , Hipocampo/metabolismo , Camundongos Endogâmicos C57BLRESUMO
ABSTRACT We present a case report of motor and cognitive disorders in a 36-year-old woman with a history of twelve years of heavy alcohol abuse. The patient presented depressive symptoms over the course of one year after a loss in the family, evolving with ataxia, bradykinesia and choreiform movements. Progressive cognitive decline, sleep alterations and myalgia were also reported during the course of disease evolution. Physical examination revealed spastic paraparesis with fixed flexion of the hips and knees with important pain upon extension of these joints. Initial investigation suggested the diagnosis of thiamine deficiency by brain magnetic resonance imaging (MRI).
RESUMO Um relato de caso de transtornos motor e cognitivo em uma mulher de 36 anos, com história de doze anos de abuso de álcool. A paciente apresentou sintomas depressivos ao longo de um ano após uma perda na família, evoluindo com ataxia, bradicinesia e movimentos coreiformes. O declínio cognitivo progressivo, alterações do sono e mialgia também foram relatados durante o curso da evolução da doença. O exame físico demonstrou paraparesia espástica com flexão fixa dos quadris e joelhos com dor importante na extensão dessas articulações. A investigação inicial sugeriu o diagnóstico de deficiência de tiamina por ressonância magnética cerebral (MRI).
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Humanos , Deficiência de Tiamina , Encefalopatia de Wernicke , Coreia , Demência , Transtornos dos MovimentosRESUMO
Vitamin B1 (thiamine) plays a fundamental role in the proper functioning of the nervous and cardiovascular systems and in glucose metabolism. Because of the inability of the human body to store large amounts of vitamin, continuous restoration through diet is necessary. In the pediatric population, thiamine deficiency has a broad spectrum of clinical presentations, making diagnosis difficult. In this article, we report the case of a 7-month-old child with thiamine deficiency presented with neurological symptoms and simulation of acute abdomen. The patient received thiamine replacement, which resulted in rapid reversal of metabolic alterations and significant improvement in the signs and symptoms. A detailed investigation of dietary history and careful nutritional assessment of every critically ill pediatric patient is necessary, regardless of the primary cause of hospitalization.
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Beriberi/etiologia , Encéfalo/diagnóstico por imagem , Nutrição Parenteral Total/efeitos adversos , Encefalopatia de Wernicke/etiologia , Abdome Agudo/etiologia , Dor Abdominal/complicações , Administração Oral , Beriberi/tratamento farmacológico , Feminino , Humanos , Lactente , Imageamento por Ressonância Magnética , Masculino , Tiamina/uso terapêutico , Deficiência de Tiamina , Tomógrafos Computadorizados , Resultado do Tratamento , Encefalopatia de Wernicke/diagnóstico , Encefalopatia de Wernicke/tratamento farmacológicoAssuntos
Hemorragia Cerebral/diagnóstico , Ventrículos Cerebrais , Deficiência de Tiamina/diagnóstico , Encefalopatia de Wernicke/diagnóstico , Alcoolismo/complicações , Hemorragia Cerebral/diagnóstico por imagem , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Deficiência de Tiamina/diagnóstico por imagem , Deficiência de Tiamina/etiologia , Tomografia Computadorizada por Raios X , Encefalopatia de Wernicke/complicações , Encefalopatia de Wernicke/diagnóstico por imagemRESUMO
The purposes of the present study were to investigate the effects of perinatal thiamine deficiency, from the 11th day of gestation until the 5th day of lactation, on motor behavior and neurochemical parameters in adult rat offspring, using 3-month-old, adult, male Wistar rats. All rats were submitted to motor tests, using the rotarod and paw print tasks. After behavioral tests, their thalamus, cerebellum and spinal cord were dissected for glutamate and GABA quantifications by high performance liquid chromatography. The thiamine-restricted mothers (RM) group showed a significant reduction of time spent on the rotarod at 25 rpm and an increase in hind-base width. A significant decrease of glutamate concentration in the cerebellum and an increase of GABA concentrations in the thalamus were also observed. For the offspring from control mothers (CM) group there were significant correlations between thalamic GABA concentrations and both rotarod performance and average hind-base width. In addition, for rats from the RM group a significant correlation between stride length and cerebellar GABA concentration was found. These results show that the deficiency of thiamine during an early developmental period affects certain motor behavior parameters and GABA and glutamate levels in specific brain areas. Hence, a thiamine deficiency episode during an early developmental period can induce motor impairments and excitatory and inhibitory neurotransmitter changes that are persistent and detectable in later periods of life.