RESUMO
Alzheimer's disease (AD) is a complex neurodegenerative process, also considered a metabolic condition due to alterations in glucose metabolism and insulin signaling pathways in the brain, which share similarities with diabetes. This study aimed to investigate the therapeutic effects of benfotiamine (BFT), a vitamin B1 analog, in the early stages of the neurodegenerative process in a sporadic model of Alzheimer's-like disease induced by intracerebroventricular injection of streptozotocin (STZ). Supplementation with 150 mg/kg of BFT for 7 days reversed the cognitive impairment in short- and long-term memories caused by STZ in rodents. We attribute these effects to BFT's ability to modulate glucose transporters type 1 and 3 (GLUT1 and GLUT3) in the hippocampus, inhibit GSK3 activity in the hippocampus, and modulate the insulin signaling in the hippocampus and entorhinal cortex, as well as reduce the activation of apoptotic pathways (BAX) in the hippocampus. Therefore, BFT emerges as a promising and accessible intervention in the initial treatment of conditions similar to AD.
Assuntos
Doença de Alzheimer , Modelos Animais de Doenças , Hipocampo , Insulina , Transdução de Sinais , Estreptozocina , Tiamina , Animais , Doença de Alzheimer/tratamento farmacológico , Doença de Alzheimer/metabolismo , Insulina/metabolismo , Transdução de Sinais/efeitos dos fármacos , Masculino , Hipocampo/efeitos dos fármacos , Hipocampo/metabolismo , Tiamina/farmacologia , Tiamina/análogos & derivados , Tiamina/uso terapêutico , Ratos , Cognição/efeitos dos fármacos , Ratos Wistar , Aprendizagem em Labirinto/efeitos dos fármacosRESUMO
BACKGROUND: Musculoskeletal disorders are an important cause of work absence. Clinical practice guidelines recommend nonsteroidal anti-inflammatory drugs (NSAIDs) for grade I-II cervical sprains. The combination of thiamine + pyridoxine + cyanocobalamin vitamins has been used, alone and in combination with NSAIDs, for pain and inflammation in musculoskeletal disorders. OBJECTIVE: The objective of this study was to demonstrate the analgesic synergy of dexketoprofen, and the combination of vitamins thiamine + pyridoxine + cyanocobalamin in a fixed-dose combination (FDC) for the treatment of acute pain caused by grade I-II cervical sprains. METHODS: We conducted a multicentre, prospective, randomized, double-blind, phase IIIb clinical study comparing two treatment groups: (1) dexketoprofen 25 mg/vitamin B (thiamine 100 mg, pyridoxine 50 mg and cyanocobalamin 0.50 mg) in an FDC (two or more active ingredients combined in a single dosage form) versus (2) dexketoprofen 25 mg monotherapy (single drug to treat a particular disease), one capsule or tablet orally, every 8 h for 7 days. Final mean, average change, and percentage change in pain perception (measured using a visual analogue scale [VAS]) were compared with baseline between groups. A p value < 0.05 was considered statistically significant. Analyses were conducted using SPSS software, v.29.0. RESULTS: A statistically significant reduction in pain intensity was observed from the third day of treatment with the FDC compared with monotherapy (- 3.1 ± - 1.5 and - 2.6 ± - 1.1 cm, respectively) measured using the VAS (p = 0.011). Regarding the degree of disability, using the Northwick Park Neck Pain Questionnaire (NPQ), statistical difference was observed for the final measurement (7.5%, interquartile range [IQR] 2.5, 10.5; vs. 7.9%, IQR 5.0, 13.8; p = 0.028). A lower proportion of adverse events was reported when using the FDC. CONCLUSIONS: The FDC of dexketoprofen/thiamine + pyridoxine + cyanocobalamin vitamins demonstrated superior efficacy and a better safety profile compared with dexketoprofen monotherapy for pain treatment in patients with grade I-II cervical sprains. CLINICAL TRIALS REGISTRATION: NCT05001555, registered 29 July 2021 ( https://clinicaltrials.gov/study/NCT05001555 ).
Assuntos
Anti-Inflamatórios não Esteroides , Combinação de Medicamentos , Cetoprofeno , Piridoxina , Tiamina , Trometamina , Vitamina B 12 , Humanos , Método Duplo-Cego , Tiamina/administração & dosagem , Tiamina/análogos & derivados , Tiamina/uso terapêutico , Cetoprofeno/administração & dosagem , Cetoprofeno/análogos & derivados , Feminino , Adulto , Piridoxina/administração & dosagem , Piridoxina/uso terapêutico , Masculino , Anti-Inflamatórios não Esteroides/administração & dosagem , Vitamina B 12/análogos & derivados , Vitamina B 12/administração & dosagem , Vitamina B 12/uso terapêutico , Pessoa de Meia-Idade , Trometamina/administração & dosagem , Estudos Prospectivos , Complexo Vitamínico B/administração & dosagem , Complexo Vitamínico B/uso terapêutico , Medição da Dor/métodos , Adulto JovemRESUMO
Wernicke encephalopathy, which is caused by a thiamine deficiency, occurs in 0.8-2% of the population. Only 16% present the typical triad of this disease: nystagmus, confusion and ataxia. We present the case of a postoperative patient with a one anastomosis gastric bypass with reoperation undergoing a Roux-en-Y gastric bypass that begins with confusion and nystagmus on her third postoperative day. The diagnosis of Wernicke encephalopathy is made by imaging, and vitamin B1 is administered with total improvement of nystagmus and altered state of consciousness (lethargy, bradypsychia, bradylalia).
La encefalopatía de Wernicke se produce por una deficiencia de tiamina se presenta en un 0.8-2% de la población. Solo el 16% de los casos presentan la tríada típica de esta enfermedad: nistagmo, confusión y ataxia. Presentamos el caso de una paciente operada de bypass gástrico de una anastomosis con reintervención convirtiendo a bypass gástrico en Y de Roux que en su tercer día de posoperatorio comienza con confusión y nistagmo. Se realiza por imagen el diagnóstico de encefalopatía de Wernicke se administra vitamina B1 con mejoría total del nistagmo y alteración del estado de consciencia (letargia, bradipsiquia, bradilalia).
Assuntos
Derivação Gástrica , Encefalopatia de Wernicke , Humanos , Feminino , Encefalopatia de Wernicke/diagnóstico , Encefalopatia de Wernicke/tratamento farmacológico , Encefalopatia de Wernicke/etiologia , Derivação Gástrica/efeitos adversos , Derivação Gástrica/métodos , Tiamina/uso terapêuticoRESUMO
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.
Assuntos
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
Sepsis is a life-threatening condition characterized by multiorgan dysfunction due to an exaggerated host response to infection associated with a homeostatic failure. In sepsis, different interventions, aimed at improving clinical outcomes, have been tested over the past decades. Among these most recent strategies, intravenous high-dose micronutrients (vitamins and/or trace elements) have been investigated. According to current knowledge, sepsis is characterized by low thiamine levels, which are associated with illness severity, hyperlactatemia, and poor clinical outcomes. However, caution is needed about the clinical interpretation of thiamine blood concentration in critically ill patients, and the inflammatory status, based on C-reactive protein levels, should always be measured. In sepsis, parenteral thiamine has been administered as monotherapy or in combination with vitamin C and corticosteroids. Nevertheless, most of those trials failed to report clinical benefits with high-dose thiamine. The purpose of this review is to summarize the biological properties of thiamine and to examine current knowledge regarding the safety and efficacy of high-dose thiamine as pharmaconutrition strategy when administering singly or in combination with other micronutrients in critically ill adult patients with sepsis or septic shock. Our examination of the most up-to-date evidence concludes that Recommended Daily Allowance supplementation is relatively safe for thiamine-deficient patients. However, current evidence does not support pharmaconutrition with high-dose thiamine as a single therapy or as combination therapy aimed at improving clinical outcomes in critically ill septic patients. The best nutrient combination still needs to be determined, based on the antioxidant micronutrient network and the multiple interactions among different vitamins and trace elements. In addition, a better understanding of the pharmacokinetic and pharmacodynamic profiles of intravenous thiamine is needed. Future well-designed and powered clinical trials are urgently warranted before any specific recommendations can be made regarding supplementation in the critical care setting.
Assuntos
Sepse , Choque Séptico , Oligoelementos , Adulto , Humanos , Tiamina/uso terapêutico , Oligoelementos/uso terapêutico , Estado Terminal/terapia , Sepse/complicações , Sepse/tratamento farmacológico , Sepse/diagnóstico , Vitaminas/uso terapêutico , Ácido Ascórbico/uso terapêutico , Micronutrientes/uso terapêuticoRESUMO
Pain is a complex sensory and emotional experience with nociceptive, nociplastic, and neuropathic components. An involvement of neurotropic B vitamins (B1 - thiamine, B6 - pyridoxine, and B12 - cyanocobalamin) as modulators of inflammation and pain has been long discussed. New evidence suggests their therapeutic potential in different pain conditions. In this review, we discuss the main role of neurotropic B vitamins on different nociceptive pathways in the nervous system and to describe their analgesic action mechanisms. The performed literature review showed that, through different mechanisms, these vitamins regulate several inflammatory and neural mediators in nociceptive and neuropathic pain. Some of these processes include aiming the activation of the descending pain modulatory system and in specific intracellular pathways, anti-inflammatory, antioxidative and nerve regenerative effects. Moreover, recent data shows the antinociceptive, antiallodynic, and anti-hyperalgesic effects of the combination of these vitamins, as well as their synergistic effects with known analgesics. Understanding how vitamins B1, B6, and B12 affect several nociceptive mechanisms can therefore be of significance in the treatment of various pain conditions.
Assuntos
Neuralgia , Complexo Vitamínico B , Humanos , Piridoxina/uso terapêutico , Vitamina B 12/uso terapêutico , Tiamina/uso terapêutico , Complexo Vitamínico B/uso terapêutico , Analgésicos/uso terapêutico , Neuralgia/tratamento farmacológicoRESUMO
The microsporidia are a large group of intracellular parasites with a broad range of hosts, including humans. Encephalitozoon intestinalis is the second microsporidia species most frequently associated with gastrointestinal disease in humans, especially immunocompromised or immunosuppressed individuals, including children and the elderly. The prevalence reported worldwide in these groups ranges from 0 to 60%. Currently, albendazole is most commonly used to treat microsporidiosis caused by Encephalitozoon species. However, the results of treatment are variable, and relapse can occur. Consequently, efforts are being directed toward identifying more effective drugs for treating microsporidiosis, and the study of new molecular targets appears promising. These parasites lack mitochondria, and oxidative phosphorylation therefore does not occur, which suggests the enzymes involved in glycolysis as potential drug targets. Here, we have for the first time characterized the glycolytic enzyme triosephosphate isomerase of E. intestinalis at the functional and structural levels. Our results demonstrate the mechanisms of inactivation of this enzyme by thiol-reactive compounds. The most striking result of this study is the demonstration that established safe drugs such as omeprazole, rabeprazole and sulbutiamine can effectively inactivate this microsporidial enzyme and might be considered as potential drugs for treating this important disease.
Assuntos
Albendazol/uso terapêutico , Proteínas Fúngicas/antagonistas & inibidores , Microsporídios/efeitos dos fármacos , Microsporidiose/tratamento farmacológico , Triose-Fosfato Isomerase/antagonistas & inibidores , Sequência de Aminoácidos , Encephalitozoon/efeitos dos fármacos , Encephalitozoon/enzimologia , Encephalitozoon/genética , Proteínas Fúngicas/genética , Proteínas Fúngicas/metabolismo , Gastroenteropatias/tratamento farmacológico , Gastroenteropatias/microbiologia , Regulação Enzimológica da Expressão Gênica/efeitos dos fármacos , Regulação Fúngica da Expressão Gênica/efeitos dos fármacos , Humanos , Microsporídios/enzimologia , Microsporídios/genética , Microsporidiose/microbiologia , Omeprazol/uso terapêutico , Rabeprazol/uso terapêutico , Homologia de Sequência de Aminoácidos , Tiamina/análogos & derivados , Tiamina/uso terapêutico , Triose-Fosfato Isomerase/genética , Triose-Fosfato Isomerase/metabolismoRESUMO
Systemic lupus erythematosus (SLE) is a chronic inflammatory disease that involves many organs and systems. Nervous system involvement in SLE encompasses neurological and psychiatric disorders, and remains a diagnostic and therapeutic challenge. Wernicke's encephalopathy (WE) is a neurological disorder that occurs as a consequence of thiamine deficiency, and its clinical presentation resembles the neuropsychiatric events attributed to SLE (NPSLE). Differentiation between these two entities is crucial because their treatment differs greatly and can change prognosis. We describe three cases of patients with SLE who presented with initial clinical findings suggestive of NPSLE that, at the end of a thorough clinical investigation, were actually found to represent WE. In all of these cases, treatment with thiamine resulted in significant improvement. WE should be considered as a differential diagnosis in SLE patients with neuropsychiatric signs and symptoms, especially when risk factors for thiamine deficiency are present.