Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 7.782
Filtrar
1.
Sci Prog ; 105(2): 368504221096539, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35491726

RESUMO

Background: Thiamine, also known as vitamin B1, is an essential water-soluble micronutrient. Although thiamine has minimal safety concerns, parenteral administration has been associated with rare cases of anaphylactic shock, cardiac arrest, and injection site reaction. The objective of this analysis is to evaluate the incidence of anaphylaxis and injection site reactions associated with the administration of thiamine 500 mg as an intravenous (IV) push in adult patients. Method: This single-center, retrospective analysis was performed at Brigham and Women's Hospital in Boston, Massachusetts. Electronic health records were used to identify all adult patients who were ordered for thiamine 500 mg IV push between July 1, 2020, and December 31, 2020. For the major and minor endpoints, anaphylaxis and injection site reactions were assessed, respectively. Descriptive statistics were used as appropriate. Results: A total of 463 doses of thiamine in 69 patients were evaluated. Thiamine was administered peripherally for 392 (84.7%) doses and centrally for 68 (14.7) doses. No anaphylactic reactions were observed. A total of 4 injection site reactions (0.86%) were noted with 4 unique doses. All reactions were classified as low-grade based on our institutional grading system. All injection site reactions were classified as "possible" (Naranjo score of 1-4). Conclusion: Administration of IV push 500 mg thiamine was not associated with anaphylactic events and was associated with a low rate of injection site reactions.


Assuntos
Anafilaxia , Tiamina , Centros Médicos Acadêmicos , Adulto , Anafilaxia/induzido quimicamente , Anafilaxia/tratamento farmacológico , Anafilaxia/epidemiologia , Feminino , Humanos , Reação no Local da Injeção/complicações , Reação no Local da Injeção/tratamento farmacológico , Estudos Retrospectivos , Tiamina/efeitos adversos
2.
Neurol India ; 70(2): 733-736, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35532649

RESUMO

Background and Aims: Biotin-thiamine-responsive basal ganglia disease (BTBGD) is an autosomal recessive disorder due to mutations in the SLC19A3-gene, typically seen in early childhood. Materials and Methods: We report a 49-year-old lady presenting with rapidly progressive cognitive impairment, seizures, hypersomnolence, ataxia, and generalized dystonia of 3 weeks duration. The magnetic resonance imaging (MRI) of the brain revealed T2-hyperintensities in the basal ganglia, thalamus, cortical, subcortical regions with striatal necrosis suggestive of BTBGD that was confirmed by genetic analysis. She was treated with thiamine and biotin following which there was significant clinical and MRI improvement. Conclusions: BTBGD requires a high index of suspicion in any patient presenting with unexplained rapidly progressive dementia. High doses of biotin and thiamine are the mainstay of the treatment to achieve a favorable outcome.


Assuntos
Doenças dos Gânglios da Base , Demência , Doenças Metabólicas , Doenças dos Gânglios da Base/diagnóstico por imagem , Doenças dos Gânglios da Base/tratamento farmacológico , Doenças dos Gânglios da Base/genética , Biotina/genética , Biotina/metabolismo , Biotina/uso terapêutico , Pré-Escolar , Demência/tratamento farmacológico , Demência/genética , Feminino , Humanos , Imageamento por Ressonância Magnética , Proteínas de Membrana Transportadoras/genética , Proteínas de Membrana Transportadoras/metabolismo , Proteínas de Membrana Transportadoras/uso terapêutico , Pessoa de Meia-Idade , Mutação/genética , Tiamina/uso terapêutico
3.
WMJ ; 121(1): E10-E14, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35442587

RESUMO

INTRODUCTION: Providing glucose before thiamine can cause or exacerbate Wernicke encephalopathy, a potentially life-threatening condition associated with a variety of neurological impairments. CASE PRESENTATION: An emaciated, middle-aged woman with a longstanding history of alcohol abuse and an undifferentiated seizure disorder presented to a local emergency department with altered mental status of unknown duration. Initial labs showed signs of acute kidney injury and she could not tolerate oral intake. Overnight, dextrose-containing maintenance fluids were started. The next day, she had an acute deterioration of mental status. Empiric therapy for Wernicke encephalopathy was begun, resulting in resolution of most of her symptoms over a matter of days. DISCUSSION: It is generally recommended to administer thiamine treatment prior to glucose in patients with suspected thiamine deficiency. The Caine criteria can assist in the decision to start empiric treatment to prevent delays in thiamine therapy. CONCLUSION: Wernicke encephalopathy is a disease with high morbidity that is usually treated with the generally benign therapy of thiamine. Given the risk of harm of untreated Wernicke encephalopathy and the benign nature of treatment, clinicians should have a low threshold to provide thiamine therapy.


Assuntos
Deficiência de Tiamina , Encefalopatia de Wernicke , Desidratação/complicações , Feminino , Glucose , Humanos , Pessoa de Meia-Idade , Tiamina/uso terapêutico , Deficiência de Tiamina/complicações , Deficiência de Tiamina/diagnóstico , Deficiência de Tiamina/tratamento farmacológico , Encefalopatia de Wernicke/complicações , Encefalopatia de Wernicke/diagnóstico , Encefalopatia de Wernicke/tratamento farmacológico
4.
J Assoc Physicians India ; 70(3): 11-12, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-35438278

RESUMO

INTRODUCTION: The global burden of sepsis is overwhelming and novel therapeutic agents is the need of the hour. The present study was designed to understand the role of Malondialdehyde as a marker of the oxidative stress in sepsis, as well as the effect of supplementation of Vitamin C and Thiamine in patients of sepsis. METHODS: 80 patients of sepsis were randomly divided into 4 groups of 20 each. Twenty age-sex matched healthy volunteers were chosen as controls. The first group received Vitamin C, the second group received Thiamine, the third group received both and the fourth group received neither. Vitamin C (2g 8 hourly) and Thiamine (200 mg 12 hourly) were given intravenously for five days. The outcome was recorded in terms of mortality in the various groups as well as by the improvement in SOFA scores (ΔSOFA). The serum levels of Vitamin C, Thiamine and Malondialdehyde were estimated. RESULTS: Among the 80 patients, 17 (21%) were in septic shock. The mortality rate was 10% overall, and 47% among patients of septic shock. No additional mortality benefit was observed in the groups supplemented with Vitamin C and Thiamine. However, the ΔSOFA score in patients who received both Vitamin C and Thiamine was significantly higher as compared to the other groups. The mean malondialdehyde level was higher in patients of sepsis (1.81±1.18 µmol/l) as compared with healthy controls (0.78 ± 0.36 µmol/l). The Vitamin C level and Thiamine level (estimated indirectly by TPP effect), at presentation were 5.14±4.19 ng/ml and 52.99±28.45 % in patients of sepsis, which was significantly lower than that in healthy controls, in whom the levels were 14.64±5.51 ng/ml and 27.55±13.67% respectively. CONCLUSION: Vitamin C and Thiamine supplementation is a cost-effective approach with a good safety profile. Additional studies including a larger population is required to study the mortality benefits and reaffirm our findings.


Assuntos
Sepse , Choque Séptico , Ácido Ascórbico/uso terapêutico , Suplementos Nutricionais , Humanos , Malondialdeído , Sepse/tratamento farmacológico , Tiamina/uso terapêutico , Vitaminas/uso terapêutico
5.
Biomolecules ; 12(4)2022 03 30.
Artigo em Inglês | MEDLINE | ID: mdl-35454115

RESUMO

Signs of impaired thiamine (vitamin B1) status in feeding-migrating Atlantic salmon (Salmo salar) were studied in three Baltic Sea areas, which differ in the proportion and nutritional composition of prey fish sprat (Sprattus sprattus) and herring (Clupea harengus). The concentration of n-3 polyunsaturated fatty acids (n-3 PUFAs) increased in salmon with dietary lipids and n-3 PUFAs, and the hepatic peroxidation product malondialdehyde (MDA) concentration increased exponentially with increasing n-3 PUFA and docosahexaenoic acid (DHA, 22:6n-3) concentration, whereas hepatic total thiamine concentration, a sensitive indicator of thiamine status, decreased with the increase in both body lipid and n-3 PUFA or DHA concentration. The hepatic glucose 6-phosphate dehydrogenase activity was suppressed by high dietary lipids. In salmon muscle and in prey fish, the proportion of thiamine pyrophosphate increased, and that of free thiamine decreased, with increasing body lipid content or PUFAs, or merely DHA. The thiamine status of salmon was impaired mainly due to the peroxidation of n-3 PUFAs, whereas lipids as a source of metabolic energy had less effect. Organochlorines or general oxidative stress did not affect the thiamine status. The amount of lipids, and, specifically, their long-chain n-3 PUFAs, are thus responsible for generating thiamine deficiency, and not a prey fish species per se.


Assuntos
Ácidos Graxos Ômega-3 , Salmo salar , Animais , Ácidos Docosa-Hexaenoicos/química , Ácidos Graxos/metabolismo , Ácidos Graxos Ômega-3/química , Ácidos Graxos Insaturados , Salmo salar/metabolismo , Tiamina
6.
Sci Rep ; 12(1): 6941, 2022 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-35484175

RESUMO

Alcohol withdrawal syndrome (AWS) occurs in 2% of patients admitted to U.K. hospitals. Routine treatment includes thiamine and benzodiazepines. Laboratory studies indicate that thiamine requires magnesium for optimal activity, however this has not translated into clinical practice. Patients experiencing AWS were randomized to three groups: (group 1) thiamine, (group 2) thiamine plus MgSO4 or (group 3) MgSO4. Pre- and 2-h post-treatment blood samples were taken. AWS severity was recorded using the Glasgow Modified Alcohol Withdrawal Score (GMAWS). The primary outcome measure was 15% change in erythrocyte transketolase activity (ETKA) in group 3. Secondary outcome measures were change in plasma lactate concentrations and time to GMAWS = 0. 127 patients were recruited, 115 patients were included in the intention-to-treat analysis. Pre-treatment, the majority of patients had normal or high erythrocyte thiamine diphosphate (TDP) concentrations (≥ 275-675/> 675 ng/gHb respectively) (99%), low serum magnesium concentrations (< 0.75 mmol/L) (59%), and high plasma lactate concentrations (> 2 mmol/L) (67%). Basal ETKA did not change significantly in groups 1, 2 or 3. Magnesium deficient patients (< 0.75 mmol/L) demonstrated less correlation between pre-treatment basal ETKA and TDP concentrations than normomagnesemic patients (R2 = 0.053 and R2 = 0.236). Median plasma lactate concentrations normalized (≤ 2.0 mmol/L) across all three groups (p < 0.001 for all groups), but not among magnesium deficient patients in group 1 (n = 22). The median time to achieve GMAWS = 0 for groups 1, 2 and 3 was 10, 5.5 and 6 h respectively (p < 0.001). No significant difference was found between groups for the primary endpoint of change in ETKA. Co-administration of thiamine and magnesium resulted in more consistent normalization of plasma lactate concentrations and reduced duration to achieve initial resolution of AWS symptoms.ClinicalTrials.gov: NCT03466528.


Assuntos
Alcoolismo , Síndrome de Abstinência a Substâncias , Proteínas de Ligação a DNA , Eritrócitos , Humanos , Ácido Láctico , Magnésio , Sulfato de Magnésio , Tiamina , Tiamina Pirofosfato , Transcetolase
7.
Artigo em Russo | MEDLINE | ID: mdl-35485062

RESUMO

Based on the data of foreign and domestic literature, the question of the possible carcinogenesis of vitamin B12 and the expediency of its administration to patients with cancer who have neurological complications due to chemotherapy is analyzed. The absence of convincing direct evidence of the carcinogenic effect of cyanocobalamin has been demonstrated, as well as the reasonableness of drug correction of vitamin B12 deficiency in cancer patients in order to prevent the development of characteristic deficient neurological disorders. The question of the effectiveness of oral administration of cyanocobalamin at a dose of 1 mg per day is considered.


Assuntos
Neoplasias , Deficiência de Vitamina B 12 , Administração Oral , Humanos , Neoplasias/complicações , Neoplasias/tratamento farmacológico , Tiamina/uso terapêutico , Vitamina B 12/uso terapêutico , Deficiência de Vitamina B 12/induzido quimicamente , Deficiência de Vitamina B 12/complicações , Deficiência de Vitamina B 12/tratamento farmacológico , Vitaminas
8.
J Bacteriol ; 204(4): e0050321, 2022 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-35357164

RESUMO

Microbial communities occupy diverse niches in nature, and community members routinely exchange a variety of nutrients among themselves. While large-scale metagenomic and metabolomic studies shed some light on these exchanges, the contribution of individual species and the molecular details of specific interactions are difficult to track. In this study, we follow the exchange of vitamin B1 (thiamin) and its intermediates between microbes within synthetic cocultures of Escherichia coli and Vibrio anguillarum. Thiamin contains two moieties, 4-amino-5-hydroxymethyl-2-methylpyrimidine (HMP) and 4-methyl-5-(2-hydroxyethyl)thiazole (THZ), which are synthesized by distinct pathways using enzymes ThiC and ThiG, respectively, and then coupled by ThiE to form thiamin. Even though E. coli ΔthiC, ΔthiE, and ΔthiG mutants are thiamin auxotrophs, we observed that cocultures of ΔthiC-ΔthiE and ΔthiC-ΔthiG mutants are able to grow in a thiamin-deficient medium, whereas the ΔthiE-ΔthiG coculture does not. Further, the exchange of thiamin and its intermediates in V. anguillarum cocultures and in mixed cocultures of V. anguillarum and E. coli revealed that there exist specific patterns for thiamin metabolism and exchange among these microbes. Our findings show that HMP is shared more frequently than THZ, concurrent with previous observations that free HMP and HMP auxotrophy is commonly found in various environments. Furthermore, we observe that the availability of exogenous thiamin in the media affects whether these strains interact with each other or grow independently. These findings collectively underscore the importance of the exchange of essential metabolites as a defining factor in building and modulating synthetic or natural microbial communities. IMPORTANCE Vitamin B1 (thiamin) is an essential nutrient for cellular metabolism. Microorganisms that are unable to synthesize thiamin either fully or in part exogenously obtain it from their environment or via exchanges with other microbial members in their community. In this study, we created synthetic microbial cocultures that rely on sharing thiamin and its biosynthesis intermediates and observed that some of them are preferentially exchanged. We also observed that the coculture composition is dictated by the production and/or availability of thiamin and its intermediates. Our studies with synthetic cocultures provide the molecular basis for understanding thiamin sharing among microorganisms and lay out broad guidelines for setting up synthetic microbial cocultures by using the exchange of an essential metabolite as their foundation.


Assuntos
Escherichia coli , Tiamina , Técnicas de Cocultura , Escherichia coli/genética , Escherichia coli/metabolismo , Nutrientes , Tiazóis/metabolismo , Vitaminas/metabolismo
9.
Biosci Biotechnol Biochem ; 86(5): 672-680, 2022 Apr 21.
Artigo em Inglês | MEDLINE | ID: mdl-35238897

RESUMO

Recently, a yellow Maillard pigment named pyrizepine was identified from a heated solution containing thiamine and glucose. Here, we examined the formation scheme of this pigment and some biological properties. The mass spectrometry and nuclear magnetic resonance data of pyrizepine prepared from [6-13C] glucose showed that the carbon at 6-position of glucose was inserted at 2 different positions of pyrizepine. 5-(Aminomethyl)-2-methylpyridin-4-amine (AMPA), a degradation product of thiamine, was detected in the reaction solution. The pigment also formed in the solution containing AMPA in place of thiamine. These results showed that pyrizepine formed from AMPA and C4 fragments derived from glucose. Pyrizepine showed antioxidative activities in the superoxide dismutase, 2,2-diphenyl-1-picrylhydrazyl, and H-ORAC assays. The pigment did not show mutagenicity with the Ames test. A trace amount of the pigment was detected in a pan-fried ground pork sample added glucose using liquid chromatography-tandem mass spectrometry.


Assuntos
Reação de Maillard , Tiamina , Glucose/química , Espectrometria de Massas , Tiamina/química , Ácido alfa-Amino-3-hidroxi-5-metil-4-isoxazol Propiônico
10.
BMJ Case Rep ; 15(3)2022 Mar 23.
Artigo em Inglês | MEDLINE | ID: mdl-35321913

RESUMO

We report a case of Wernicke encephalopathy (WE) in a woman in her 20s who had Roux-en-Y gastric bypass surgery for severe obesity, which resulted in a severe depletion of the patient's thiamine reserve and development of WE syndrome, we also emphasise the importance of prompt diagnosis of this serious complication in addition to the importance of adequate therapy.


Assuntos
Derivação Gástrica , Síndrome de Korsakoff , Obesidade Mórbida , Encefalopatia de Wernicke , Feminino , Derivação Gástrica/efeitos adversos , Derivação Gástrica/métodos , Humanos , Obesidade Mórbida/complicações , Obesidade Mórbida/cirurgia , Tiamina/uso terapêutico , Encefalopatia de Wernicke/diagnóstico , Encefalopatia de Wernicke/tratamento farmacológico , Encefalopatia de Wernicke/etiologia
12.
Molecules ; 27(5)2022 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-35268702

RESUMO

There is a very vital antioxidant extracted from microgreen alga. Chlorella vulgaris has major advantages and requires high yield worldwide. Some microalgae require vitamins for their growth promotion. This study was held to determine the impact of different vitamins including Thiamine (B1), Riboflavin (B2), Pyridoxine (B6), and Ascorbic acid (c) at concentrations of 0.02, 0.04, 0.06, and 0.08 mg/L of each. Each vitamin was added to the BG11 growth medium to determine the effect on growth, total carbohydrate, total protein, pigments content, antioxidant activities of Chlorella vulgaris. Moreover, antitumor effects of methanol extract of C. vulgaris without and with the supplement of thiamine against Human prostate cancer (PC-3), Hepatocellular carcinoma (HEPG-2), Colorectal carcinoma (HCT-116) and Epitheliod Carcinoma (Hela) was estimated in vitro. C. vulgaris supplemented with various vitamins showed a significant increase in biomass, pigment content, total protein, and total carbohydrates in comparison to the control. Thiamine was the best vitamin influencing as an antioxidant. C. vulgaris supplemented with thiamine had high antitumor effects in vitro. So, it's necessary to add vitamins to BG11 media for enhancement of the growth and metabolites.


Assuntos
Chlorella vulgaris , Microalgas , Antioxidantes/metabolismo , Antioxidantes/farmacologia , Biomassa , Chlorella vulgaris/metabolismo , Humanos , Masculino , Tiamina , Vitaminas/metabolismo , Vitaminas/farmacologia
13.
Diabetes Metab Syndr ; 16(3): 102443, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-35272175

RESUMO

BACKGROUND AND AIMS: There is growing evidence that thiamine supplementation could reverse non-communicable diseases such as diabetes and cardiovascular diseases. However, the role of thiamine in metabolic syndrome (MetS) remains unclear. We hypothesized whether an increased intake of thiamine diminishes the risk of MetS in the Korean population with various comorbidities. This study aimed to assess the association between thiamine intake and MetS among adults with comorbidities. METHODS: 57,523 eligible participants aged over 18 years between 2009 and 2019 were recruited to obtain data on sociodemographic characteristics, medical history, current medications, lifestyle, and family history. A 24-h recall was used to determine thiamine intake. Odds ratio (OR) for MetS was calculated for log2-transformed thiamine intake values, subsequently predicting the risk of MetS based on the marginal effect. RESULTS: The risk of MetS was significantly higher in subjects with comorbidities than in those without comorbidities. A doubling of daily thiamine intake was significantly associated with a decrease in MetS among adults with comorbidities by 7% (OR 0.93; 95%CI 0.89-0.97). CONCLUSIONS: The potential health benefits result from the intake of thiamine through an ordinary diet in the clinical management of MetS. Therefore, there is an ongoing need to look into these links between thiamine supplementation and MetS in well-characterized cohorts of participants with comorbidities.


Assuntos
Síndrome Metabólica , Adulto , Humanos , Síndrome Metabólica/epidemiologia , Síndrome Metabólica/prevenção & controle , Pessoa de Meia-Idade , República da Coreia/epidemiologia , Fatores de Risco , Tiamina
14.
Nutrients ; 14(3)2022 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-35276844

RESUMO

This review summarizes the current knowledge on essential vitamins B1, B2, B3, and B5. These B-complex vitamins must be taken from diet, with the exception of vitamin B3, that can also be synthetized from amino acid tryptophan. All of these vitamins are water soluble, which determines their main properties, namely: they are partly lost when food is washed or boiled since they migrate to the water; the requirement of membrane transporters for their permeation into the cells; and their safety since any excess is rapidly eliminated via the kidney. The therapeutic use of B-complex vitamins is mostly limited to hypovitaminoses or similar conditions, but, as they are generally very safe, they have also been examined in other pathological conditions. Nicotinic acid, a form of vitamin B3, is the only exception because it is a known hypolipidemic agent in gram doses. The article also sums up: (i) the current methods for detection of the vitamins of the B-complex in biological fluids; (ii) the food and other sources of these vitamins including the effect of common processing and storage methods on their content; and (iii) their physiological function.


Assuntos
Deficiência de Vitaminas , Complexo Vitamínico B , Humanos , Tiamina , Vitamina A , Vitamina K
15.
Yakugaku Zasshi ; 142(3): 295-302, 2022.
Artigo em Japonês | MEDLINE | ID: mdl-35228382

RESUMO

Three forms of pseudo-crystalline polymorph of thiamine chloride hydrochloride are dependent on hydration states. We investigated how the measurement environment affects the transition of the pseudo-crystalline polymorph, and aimed to establish a reliable method of identifying the forms clearly by IR spectrophotometry. We prepared three pseudo-crystalline forms and compared their IR spectra. In the IR spectra obtained by the potassium chloride (KCl) disk method, Form II was identified based on its characteristic absorption, but Forms I and III could not be distinguished clearly. Form I transformed to Form III after mixing with undried KCl powder, and Form III transformed to Form I by simply being left in the laboratory environment. These results suggested that the reversible transformation between Forms I and III occurred depending on the hydration status during the process of measurement, as measured by the shift in the absorption wavenumber of the primary alcohol stretching vibration. In addition, Forms I and III could not be distinguished clearly by the X-ray powder diffraction and their crystalline forms were similar plate crystals. However, in the IR spectra by the attenuated total reflection (ATR) method, the three forms could be identified based on each characteristic absorption. In summary, the ATR method does not require pretreatment for sample analysis, can be performed quickly, and is thus suitable to identify crystalline polymorph forms such as pseudo-crystalline polymorphs of thiamine chloride hydrochloride, which transform easily depending on the hydration status in a measurement environment.


Assuntos
Tiamina/análogos & derivados , Fenômenos Químicos , Cristalização , Meio Ambiente , Laboratórios , Cloreto de Potássio , Difração de Pó , Pós , Espectrofotometria Infravermelho/métodos , Tiamina/química , Água/química , Difração de Raios X
16.
Nutrients ; 14(3)2022 Feb 08.
Artigo em Inglês | MEDLINE | ID: mdl-35277069

RESUMO

This study aimed to investigate the direct influence of a decrease in the cellular thiamin level, before the onset of anorexia (one of the symptoms of thiamin deficiency) on glycogen metabolism and the AMP-activated protein kinase (AMPK) activation levels in skeletal muscle at rest and in response to exercise. Male Wistar rats were classified as the control diet (CON) group or the thiamin-deficient diet (TD) group and consumed the assigned diets for 1 week. Skeletal muscles were taken from the rats at rest, those that underwent low-intensity swimming (LIS), or high-intensity intermittent swimming (HIS) conducted immediately before dissection. There were no significant differences in food intake, locomotive activity, or body weight between groups, but thiamin pyrophosphate in the skeletal muscles of the TD group was significantly lower than that of the CON group. Muscle glycogen and lactate levels in the blood and muscle were equivalent between groups at rest and in response to exercise. The mitochondrial content was equal between groups, and AMPK in the skeletal muscles of TD rats was normally activated by LIS and HIS. In conclusion, with a lowered cellular thiamin level, the exercise-associated glycogen metabolism and AMPK activation level in skeletal muscle were normally regulated.


Assuntos
Proteínas Quinases Ativadas por AMP , Tiamina , Proteínas Quinases Ativadas por AMP/metabolismo , Animais , Glicogênio/metabolismo , Masculino , Músculo Esquelético/metabolismo , Ratos , Ratos Wistar , Tiamina/metabolismo
17.
J Pak Med Assoc ; 72(3): 550-553, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-35320243

RESUMO

Wernicke's encephalopathy (WE) is an acute neurological condition characterized by a triad of ophthalmoplegia, ataxia and altered mental status. The underlying cause is thiamine deficiency, which may be due to multiple aetiologies. Thiamine is essential for carbohydrate and amino acid metabolism. Its deficiency shunts glucose to anaerobic pathways producing metabolic abnormalities. Diagnosing WE relies heavily on clinical suspicion. Magnetic Resonance Imaging can show some specific findings. We report this case of a 35 year old pregnant woman with gestational diabetes who was admitted in hospital for high blood sugar levels and electrolyte abnormalities. She had a history of ten miscarriages. From undergoing laparoscopic cholecystectomy for intractable vomiting to spontaneous expulsion of the foetus to being intubated for acidosis, her hospital stay was prolonged and eventful. Although the cause of her repeated miscarriages could not be established despite extensive workup, thiamine deficiency leading to Wernicke's encephalopathy was the most probable cause.


Assuntos
Hiperêmese Gravídica , Deficiência de Tiamina , Encefalopatia de Wernicke , Adulto , Feminino , Humanos , Hiperêmese Gravídica/complicações , Imageamento por Ressonância Magnética , Gravidez , Tiamina/uso terapêutico , Deficiência de Tiamina/complicações , Deficiência de Tiamina/diagnóstico , Encefalopatia de Wernicke/diagnóstico por imagem , Encefalopatia de Wernicke/etiologia
18.
Br J Haematol ; 197(2): 156-170, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35146746

RESUMO

The 100th anniversary of the first description of Thrombotic Thrombocytopenic Purpura (TTP) as a disease by Dr. Eli Moschcowitz approaches. For many decades, TTP remained mostly a mysterious fatal condition, where diagnosis was often post-mortem. Initially a pentad of symptoms was identified, a pattern that later revealed to be fallible. Sporadic observations led to empiric interventions that allowed for the first impactful breakthrough in TTP treatment, almost 70 years after its first description: the introduction of plasma exchange and infusions as treatments. The main body of knowledge within the field was gathered in the latest three decades: patient registries were set and proved crucial for advancements; the general mechanisms of disease have been described; the diagnosis was refined; new treatments and biomarkers with improvements on prognosis and management were introduced. Further changes and improvements are expected in the upcoming decades. In this review, we provide a brief historic overview of TTP, as an illustrative example of the success of translational medicine enabling to rapidly shift from a management largely based on empiricism to targeted therapies and personalized medicine, for the benefit of patients. Current management options and present and future perspectives in this still evolving field are summarized.


Assuntos
Púrpura Trombocitopênica Trombótica , Proteína ADAMTS13 , Empirismo , Humanos , Terapia de Alvo Molecular , Troca Plasmática , Púrpura Trombocitopênica Trombótica/diagnóstico , Púrpura Trombocitopênica Trombótica/terapia , Tiamina
19.
Blood ; 139(16): 2523-2533, 2022 Apr 21.
Artigo em Inglês | MEDLINE | ID: mdl-35157766

RESUMO

Microvascular thrombosis in patients with thrombotic thrombocytopenic purpura (TTP) is initiated by GPIbα-mediated platelet binding to von Willebrand factor (VWF). Binding of VWF to GPIbα causes activation of the platelet surface integrin αIIbß3. However, the mechanism of GPIbα-initiated activation of αIIbß3 and its clinical importance for microvascular thrombosis remain elusive. Deletion of platelet C-type lectin-like receptor 2 (CLEC-2) did not prevent VWF binding to platelets but specifically inhibited platelet aggregation induced by VWF binding in mice. Deletion of platelet CLEC-2 also inhibited αIIbß3 activation induced by the binding of VWF to GPIbα. Using a mouse model of TTP, which was created by infusion of anti-mouse ADAMTS13 monoclonal antibodies followed by infusion of VWF, we found that deletion of platelet CLEC-2 decreased pulmonary arterial thrombosis and the severity of thrombocytopenia. Importantly, prophylactic oral administration of aspirin, an inhibitor of platelet activation, and therapeutic treatment of the TTP mice with eptifibatide, an integrin αIIbß3 antagonist, reduced pulmonary arterial thrombosis in the TTP mouse model. Our observations demonstrate that GPIbα-mediated activation of integrin αIIbß3 plays an important role in the formation of thrombosis in TTP. These observations suggest that prevention of platelet activation with aspirin may reduce the risk for thrombosis in patients with TTP.


Assuntos
Hipertensão Pulmonar , Púrpura Trombocitopênica Trombótica , Trombose , Aspirina , Plaquetas/metabolismo , Humanos , Lectinas Tipo C/genética , Lectinas Tipo C/metabolismo , Ativação Plaquetária , Complexo Glicoproteico GPIIb-IIIa de Plaquetas/metabolismo , Púrpura Trombocitopênica Trombótica/metabolismo , Tiamina , Trombose/etiologia , Fator de von Willebrand/metabolismo
20.
BMJ Open ; 12(2): e057142, 2022 Feb 03.
Artigo em Inglês | MEDLINE | ID: mdl-35115359

RESUMO

INTRODUCTION: Diabetic sensorimotor polyneuropathy (DSPN) affects approximately 30% of people with diabetes, while around half of cases are symptomatic. Currently, there are only few pathogenetically oriented pharmacotherapies for DSPN, one of which is benfotiamine, a prodrug of thiamine with a high bioavailability and favourable safety profile. While benfotiamine has shown positive effects in preclinical and short-term clinical studies, no long-term clinical trials are available to demonstrate disease-modifying effects on DSPN using a comprehensive set of disease-related endpoints. METHODS AND ANALYSIS: The benfotiamine on morphometric, neurophysiological and clinical measures in patients with type 2 diabetes trial is a randomised double-blind, placebo-controlled parallel group monocentric phase II clinical trial to assess the effects of treatment with benfotiamine compared with placebo in participants with type 2 diabetes and mild to moderate symptomatic DSPN. Sixty participants will be 1:1 randomised to treatment with benfotiamine 300 mg or placebo two times a day over 12 months. The primary endpoint will be the change in corneal nerve fibre length assessed by corneal confocal microscopy (CCM) after 12 months of benfotiamine treatment compared with placebo. Secondary endpoints will include other CCM measures, skin biopsy and function indices, variables from somatic and autonomic nerve function tests, clinical examination and questionnaires, general health, health-related quality of life, cost, safety and blood tests. ETHICS AND DISSEMINATION: The trial was approved by the competent authority and the local independent ethics committee. Trial results will be published in peer-reviewed journals, conference abstracts, and via online and print media. TRIAL REGISTRATION NUMBER: DRKS00014832.


Assuntos
Diabetes Mellitus Tipo 2 , Neuropatias Diabéticas , Polineuropatias , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/tratamento farmacológico , Neuropatias Diabéticas/complicações , Método Duplo-Cego , Humanos , Polineuropatias/complicações , Polineuropatias/tratamento farmacológico , Qualidade de Vida , Tiamina/análogos & derivados , Tiamina/uso terapêutico
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...