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1.
Crit Care ; 26(1): 3, 2022 01 05.
Artigo em Inglês | MEDLINE | ID: mdl-34983595

RESUMO

BACKGROUND: Previous randomized trials of vitamin C, hydrocortisone, and thiamine on sepsis were limited by short-term vitamin C administration, heterogeneous populations, and the failure to evaluate each component's effect. The purpose of this study was to determine whether vitamin C alone for ≥ 5 days or in combination with corticosteroids and/or thiamine was associated with decreased mortality across the sepsis population and subpopulation. METHODS: Nationwide population-based study conducted using the Korean National Health Insurance Service database. A total of 384,282 adult patients with sepsis who were admitted to the intensive care unit were enrolled from January 2017 to December 2019. The primary outcome was hospital mortality, while the key secondary outcome was 90-day mortality. RESULTS: The mean [standard deviation] age was 69.0 [15.4] years; 57% were male; and 36,327 (9%) and 347,955 did and did not receive vitamin C, respectively. After propensity score matching, each group involved 36,327 patients. The hospital mortality was lower by - 0.9% in the treatment group (17.1% vs 18.0%; 95% confidence interval, - 1.3 to - 0.5%; p < 0.001), a significant but extremely small difference. However, mortality decreased greater in patients who received vitamin C for ≥ 5 days (vs 1-2 or 3-4 days) (15.8% vs 18.8% vs 18.3%; p < 0.001). Further, vitamin C was associated with a lower hospital mortality in patients with older age, multiple comorbidities, pneumonia, genitourinary infection, septic shock, and mechanical ventilation. Consistent findings were found for 90-day mortality. Moreover, vitamin C alone or in combination with thiamine was significantly associated with decreased hospital mortality. CONCLUSIONS: Intravenous vitamin C of ≥ 5 days was significantly associated with decreased hospital and 90-day mortality in sepsis patients. Vitamin C combined with corticosteroids and/or thiamine in specific sepsis subgroups warrants further study.


Assuntos
Sepse , Choque Séptico , Adolescente , Adulto , Idoso , Ácido Ascórbico/uso terapêutico , Estudos de Coortes , Quimioterapia Combinada , Mortalidade Hospitalar , Humanos , Masculino , Sepse/tratamento farmacológico , Choque Séptico/tratamento farmacológico , Tiamina/uso terapêutico
2.
Spectrochim Acta A Mol Biomol Spectrosc ; 265: 120348, 2022 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-34507032

RESUMO

A label-free sensing strategy based on the enzyme-mimicking property of Glutathione-Ag nanoparticles (GSH-AgNPs) was demonstrated for colorimetric detection of vitamin B1 (VB1). Firstly, obvious blue color accompanied with an absorption peak at 652 nm was observed due to the high peroxidase-like activity of GSH-AgNPs towards 3,3',5,5'-tetramethylbenzidine (TMB). Then, in the presence of VB1, the mimetic activity of GSH-AgNPs could be strongly restrained, evidenced as a promiment colorimetric change to colorless, which can be used to achieve the visualization detection VB1. Linear relationship between absorbance response and VB1 concentration from 0 to 0.2 µM were obtained. The detection limit was calculated as low as 40 nM. The inhibition reasons were thoroughly discussed. Considering the advantages of rapid response, easy procedure and high selectivity, the proposed method possesses potential application in environment and biological analysis for VB1 detection.


Assuntos
Colorimetria , Nanopartículas Metálicas , Glutationa , Peroxidase , Peroxidases , Prata , Tiamina
3.
Meat Sci ; 184: 108698, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-34700177

RESUMO

Dry cured loins containing nitrogen (proline and ornithine) and sulfur (thiamine) compounds as precursors of aroma compounds at two concentration levels were manufactured. The effect of precursor addition on the microbiology and chemical parameters of loins was studied together with the aroma study performed by olfactometry and Free Choice Profile sensory analyses. Addition of precursors did not affect the microbial and chemical parameters, while aroma was affected when precursors were added at the highest level. The dry loin aroma profile was mainly composed by compounds 3-methylbutanal, methional, ethyl 3-methylbutanoate, 3-methylbutanoic acid, 1-octen-3-ol, 2-acetyl-1-pyrroline and 2-acetylpyrrole that contribute to musty, cooked potatoes, fruity, cheesy, mushroom, roasted and meaty odor notes. Proline and ornithine supplementation modified the loins aroma profile producing toasted odors, while the effect of thiamine supplementation on the aroma was revealed by the presence of sulfur derived compounds (methional and 2-methyl-3-(methylthio)furan) that contribute to the "cured meat odor".


Assuntos
Produtos da Carne/análise , Produtos da Carne/microbiologia , Odorantes/análise , Adulto , Animais , Comportamento do Consumidor , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Olfatometria , Ornitina/química , Prolina/química , Suínos , Tiamina/química , Compostos Orgânicos Voláteis/análise
4.
Food Chem ; 373(Pt A): 131447, 2022 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-34742049

RESUMO

Nanofibers were fabricated by using the electrospinning technique. The diameter of gelatin nanofibers was measured as 41.511 nm. When thiamine was integrated into the nanofibers, it was increased to 100.156 nm. After raw red meat and salmon samples were coated with the nanofibers, the samples were stored at cold storage conditions. The thiamine levels of raw uncoated red meat (RM, 400 to 379 µg/100 g: p < 0.05) and salmon meat (SM, 68 to 62 µg/100 g: p < 0.05) were decreased. The coating increased thiamine contents in raw (519 to 563 µg/100 g) and cooked (416 to 485 µg/100 g) RM samples. Thiamine contents of raw (75 to 78 µg/100 g) and cooked (67 to 75 µg/100 g) SM samples were increased (p < 0.05). The changes in the bioaccessibility of uncoated and coated RM samples were in the range of 85-76%, and 87-79%, respectively while salmon samples were increased from 79 to 94% (p < 0.05).


Assuntos
Nanofibras , Carne Vermelha , Animais , Culinária , Carne/análise , Salmão , Tiamina/análise
5.
Eur J Paediatr Neurol ; 36: 93-98, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34952263

RESUMO

OBJECTIVE: Thiamine (Vitamin B1) deficiency (TD), although reduced in incidence, is still seen in infants. We describe a rarely reported form of infantile TD with life-threatening pulmonary hypertensive crisis and severe encephalopathy, with dramatic response to thiamine supplementation. METHODS: Study design: Descriptive case series. Six young infants with mean age 76 days (range 1-3 months), manifesting rapidly progressive encephalopathy and cardio-pulmonary arrest were included. All infants underwent cardiac, neuroimaging and metabolic evaluations. RESULTS: All six infants had similar presentation with severe pulmonary arterial hypertension (PAH), hypotensive shock, metabolic acidosis and severe encephalopathy. All infants were exclusively breast-fed. Thiamine treatmwnt resulted in dramatic improvement in haemodynamic and neurological function in all the infants. There were no major neurological deficits on follow up. CONCLUSION: A high index of suspicion is warranted for this rarely described form of TD, as early identification helps in preventing mortality and morbidity.


Assuntos
Beriberi , Encefalopatias , Deficiência de Tiamina , Aleitamento Materno , Feminino , Humanos , Lactente , Tiamina/uso terapêutico , Deficiência de Tiamina/complicações , Deficiência de Tiamina/tratamento farmacológico
6.
Int J Mol Sci ; 22(24)2021 Dec 11.
Artigo em Inglês | MEDLINE | ID: mdl-34948135

RESUMO

Brain pathologies evoked by thiamine deficiency can be aggravated by mild zinc excess. Cholinergic neurons are the most susceptible to such cytotoxic signals. Sub-toxic zinc excess aggravates the injury of neuronal SN56 cholinergic cells under mild thiamine deficiency. The excessive cell loss is caused by Zn interference with acetyl-CoA metabolism. The aim of this work was to investigate whether and how astroglial C6 cells alleviated the neurotoxicity of Zn to cultured SN56 cells in thiamine-deficient media. Low Zn concentrations did not affect astroglial C6 and primary glial cell viability in thiamine-deficient conditions. Additionally, parameters of energy metabolism were not significantly changed. Amprolium (a competitive inhibitor of thiamine uptake) augmented thiamine pyrophosphate deficits in cells, while co-treatment with Zn enhanced the toxic effect on acetyl-CoA metabolism. SN56 cholinergic neuronal cells were more susceptible to these combined insults than C6 and primary glial cells, which affected pyruvate dehydrogenase activity and the acetyl-CoA level. A co-culture of SN56 neurons with astroglial cells in thiamine-deficient medium eliminated Zn-evoked neuronal loss. These data indicate that astroglial cells protect neurons against Zn and thiamine deficiency neurotoxicity by preserving the acetyl-CoA level.


Assuntos
Neurônios Colinérgicos/metabolismo , Neuroglia/metabolismo , Deficiência de Tiamina/prevenção & controle , Zinco/toxicidade , Animais , Linhagem Celular Tumoral , Meios de Cultura , Camundongos , Tiamina/metabolismo , Tiamina/farmacologia , Deficiência de Tiamina/metabolismo
7.
Zhen Ci Yan Jiu ; 46(12): 1043-7, 2021 Dec 25.
Artigo em Chinês | MEDLINE | ID: mdl-34970882

RESUMO

OBJECTIVE: To observe the effect and safety of injection of vitamin B1 into Zusanli (ST36) and Hegu (LI4) in the treatment of functional dyspepsia (FD). METHODS: A total of 100 FD patients were equally divided into medication group and acupoint injection group (n=50/group) according to a random number table. Patients in the medication group were ordered to take mosapride citrate tablets (5 mg) orally 30 min before each of the three meals, while those in the acupoint injection group received injection of vitamin B1 into ST36 and LI4, once every other day, three times a week. One week later, the clinical symptom scores, total effective rates, serum gastrin (GAS) and plasma motilin (MTL) contents, and gastric emptying rates between the two groups were compared, followed by the observation of adverse reactions. Two weeks' follow-up survey was conducted after the end of treatment, and the clinical symptom scores and total effective rates of the two groups were further compared. RESULTS: Compared with the data before treatment in the same one group, the clinical symptom scores and serum GAS contents of post-treatment as well as the follow-up symptom scores were all significantly decreased (P<0.05,P<0.01), while the plasma MTL levels and gastric emptying rates were obviously increased in both groups (P<0.01). Comparison between the two groups showed that the clinical symptom score, serum GAS content after the treatment and follow-up symptom score were considerably lower (P<0.01), but the total effective rate, plasma MTL, gastric emptying rate after the treatment and total effective rate of follow-up notably higher in the acupoint injection group than those in the medication group (P<0.01,P<0.05). CONCLUSION: Injection of vitamin B1 into ST36 and LI4 is effective in improving symptoms of PD patients, which may be related to its functions in regulating the levels of GAS and MTL in blood, and facilitating gastrointestinal motility.


Assuntos
Terapia por Acupuntura , Dispepsia , Pontos de Acupuntura , Dispepsia/tratamento farmacológico , Humanos , Motilina , Tiamina
8.
Neurol India ; 69(5): 1402-1404, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34747824

RESUMO

Wernicke's encephalopathy (WE) is an acute neuropsychiatric disorder that results from thiamine (vitamin B1) deficiency. The typical clinical manifestations, which occur as triads in 20% of patients with the disorder, are acute mental status changes, ophthalmoplegia, and ataxia. Brain magnetic resonance imaging (MRI) has important value in diagnosis as it can reveal abnormalities in the thalamus, mammillary body, third and fourth ventricles, and periaqueductal area. Here we describe a 44-year-old female patient with WE, in the context of fasting following bowel surgery. The unique neuroimaging findings were symmetrical mammillary body and dorsal midbrain abnormalities, only evident on contrast-enhanced brain MRI.


Assuntos
Encefalopatia de Wernicke , Adulto , Encéfalo/diagnóstico por imagem , Feminino , Humanos , Imageamento por Ressonância Magnética , Neuroimagem , Tiamina , Encefalopatia de Wernicke/diagnóstico por imagem
9.
Zhonghua Wei Zhong Bing Ji Jiu Yi Xue ; 33(9): 1040-1046, 2021 Sep.
Artigo em Chinês | MEDLINE | ID: mdl-34839858

RESUMO

OBJECTIVE: To systematically evaluate the effect of hydrocortisone combined with vitamin C and vitamin B1 on the efficacy of patients with sepsis or septic shock. METHODS: Databases including CNKI, Sino Med, VIP, Wanfang, PubMed, the Cochrane Library, and Embase were searched from inception to January 2021 for the randomized controlled trial (RCT) about hydrocortisone combined with vitamin C and vitamin B1 to treat sepsis or septic shock. The experimental group was given intravenous injection of hydrocortisone, vitamin B1 and vitamin C based on conventional treatment; the control group was given conventional treatment or placebo/hydrocortisone/hydrocortisone+vitamin B1 based on conventional treatment. Outcome indicators included sequential organ failure assessment (SOFA), mortality, the duration of vasoactive drugs, new acute kidney injury (AKI) patients, length of stay in intensive care unit (ICU) and in hospital. Two researchers independently screened the literature, extracted data, and evaluated the risk of bias in the included studies. RevMan 5.3 software was then used to perform Meta-analysis. Funnel plot was used to test publication bias. RESULTS: A total of 6 articles involving 816 patients were included, with 411 patients in the experimental group and 405 patients in the control group. The Meta-analysis results showed that the duration of vasoactive drugs in the experimental group was significantly shorter than that in the control group [mean difference (MD) = -24.02, 95% confidence interval (95%CI) was -32.36 to -15.68, P < 0.000 01]. However, there were no significant differences in SOFA, mortality, new AKI patients, the length of ICU stay and hospital stay between the two groups [SOFA: MD = -0.14, 95%CI was -1.15 to 0.87, P = 0.79; mortality: relative risk (RR) = 0.99, 95%CI was 0.81 to 1.21, P = 0.92; new AKI patients: RR = 1.10, 95%CI was 0.42 to 2.87, P = 0.84; length of ICU stay: MD = 1.33, 95%CI was -2.22 to 4.89, P = 0.46; length of hospital stay: MD = 1.02, 95%CI was -0.66 to 2.69, P = 0.23]. The funnel plot showed that most of the points were symmetrical and showed an inverted funnel shape, suggesting that the publication bias among the studies was small. There was no significant publication bias on this Meta-analysis. CONCLUSIONS: Hydrocortisone combined with vitamin C and vitamin B1 can shorten the duration of vasoactive drugs in patients with sepsis or septic shock, but it cannot effectively reduce the SOFA score, mortality, new AKI patients, length of stay in ICU and in hospital. Limited by the number and quality of the included studies, further large-scale, multi-center, blinded, RCT are still needed for verification.


Assuntos
Hidrocortisona , Sepse , Ácido Ascórbico/uso terapêutico , Humanos , Hidrocortisona/uso terapêutico , Unidades de Terapia Intensiva , Sepse/tratamento farmacológico , Tiamina
10.
Nutrients ; 13(10)2021 Sep 29.
Artigo em Inglês | MEDLINE | ID: mdl-34684464

RESUMO

As a precursor for a universal metabolic coenzyme, vitamin B1, also known as thiamine, is a vital nutrient in all living organisms. We previously found that high-dose thiamine therapy prevents overnutrition-induced hepatic steatosis in sheep by enhancing oxidative catabolism. Based on this capacity, we hypothesized that thiamine might also reduce whole-body fat and weight. To test it, we investigated the effects of high-dose thiamine treatment in sheep under overnutrition and calorie-restricted undernutrition to respectively induce positive energy balance (PEB) and negative energy balance (NEB). Eighteen mature ewes were randomly assigned to three treatment groups (n = 6 each). The control group (CG) was administered daily with subcutaneous saline, whereas the T5 and T10 groups were administered daily with equivoque of saline containing 5 mg/kg and 10 mg/kg of thiamine, respectively. Bodyweight and blood biochemistry were measured twice a week for a period of 22 days under PEB and for a consecutive 30 days under NEB. Surprisingly, despite the strong effect of thiamine on liver fat, no effect on body weight or blood glucose was detectable. Thiamine did, however, increase plasma concentration of non-esterified fatty acids (NEFA) during NEB (575.5 ± 26.7, 657.6 ± 29.9 and 704.9 ± 26.1 µEqL-1 for CG, T5, and T10, respectively: p < 0.05), thereby favoring utilization of fatty acids versus carbohydrates as a source of energy. Thiamine increased serum creatinine concentrations (p < 0.05), which paralleled a trending increase in urea (p = 0.09). This may indicate an increase in muscle metabolism by thiamine. Reduction of fat content by thiamine appears more specific to the liver than to adipose tissue. Additional studies are needed to evaluate the potential implications of high-dose vitamin B1 therapy in muscle metabolism.


Assuntos
Desnutrição/metabolismo , Hipernutrição/metabolismo , Ovinos/metabolismo , Tiamina/metabolismo , Tecido Adiposo/metabolismo , Animais , Biomarcadores , Glicemia , Peso Corporal , Creatinina/sangue , Metabolismo Energético , Ácidos Graxos/metabolismo , Metabolismo dos Lipídeos , Lipólise , Micronutrientes/metabolismo , Minerais/sangue , Tiamina/administração & dosagem , Tiamina/uso terapêutico
11.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 38(9): 873-876, 2021 Sep 10.
Artigo em Chinês | MEDLINE | ID: mdl-34487534

RESUMO

OBJECTIVE: To report the clinical manifestation and genetic characteristics of a child with Thiamine metabolism dysfunction syndrome 5. METHODS: Clinical data and genetic results were collected and analyzed. Peripheral blood samples of the child and their parents were collected for whole exome sequencing, and the functional effect of the variants on the TPK1 enzyme activity was verified by an in vitro assay. RESULTS: A four-year-old boy presented with preschool onset of ataxia were characterized. High-throughput sequencing identified a novel homozygous variant of TPK1 gene c.382G>A (p.Leu128Phe). His father and mother were both found carrying the variant. The variant protein showed a 30.9% reduction in TPK1 enzyme activity compared with the wildtype. CONCLUSION: A novel pathogenic variant has been identified in a boy with thiamine metabolic dysfunction syndrome type 5.


Assuntos
Testes Genéticos , Tiamina , Pré-Escolar , Homozigoto , Humanos , Masculino , Mutação , Sequenciamento Completo do Exoma
12.
Int J Mol Sci ; 22(17)2021 Aug 31.
Artigo em Inglês | MEDLINE | ID: mdl-34502400

RESUMO

Giardiasis represents a latent problem in public health due to the exceptionally pathogenic strategies of the parasite Giardia lamblia for evading the human immune system. Strains resistant to first-line drugs are also a challenge. Therefore, new antigiardial therapies are urgently needed. Here, we tested giardial arginine deiminase (GlADI) as a target against giardiasis. GlADI belongs to an essential pathway in Giardia for the synthesis of ATP, which is absent in humans. In silico docking with six thiol-reactive compounds was performed; four of which are approved drugs for humans. Recombinant GlADI was used in enzyme inhibition assays, and computational in silico predictions and spectroscopic studies were applied to follow the enzyme's structural disturbance and identify possible effective drugs. Inhibition by modification of cysteines was corroborated using Ellman's method. The efficacy of these drugs on parasite viability was assayed on Giardia trophozoites, along with the inhibition of the endogenous GlADI. The most potent drug against GlADI was assayed on Giardia encystment. The tested drugs inhibited the recombinant GlADI by modifying its cysteines and, potentially, by altering its 3D structure. Only rabeprazole and omeprazole decreased trophozoite survival by inhibiting endogenous GlADI, while rabeprazole also decreased the Giardia encystment rate. These findings demonstrate the potential of GlADI as a target against giardiasis.


Assuntos
Giardia lamblia/efeitos dos fármacos , Giardíase/tratamento farmacológico , Hidrolases/metabolismo , Animais , Antiprotozoários/farmacologia , Simulação por Computador , Cisteína/química , Avaliação Pré-Clínica de Medicamentos/métodos , Reposicionamento de Medicamentos/métodos , Giardia lamblia/patogenicidade , Giardíase/imunologia , Tiomalato Sódico de Ouro/farmacologia , Humanos , Hidrolases/efeitos dos fármacos , Hidrolases/ultraestrutura , Omeprazol/farmacologia , Inibidores da Bomba de Prótons/farmacologia , Rabeprazol , Tiamina/análogos & derivados , Tiamina/farmacologia , Trofozoítos/efeitos dos fármacos
13.
Pan Afr Med J ; 38: 16, 2021.
Artigo em Francês | MEDLINE | ID: mdl-34567343

RESUMO

Gayet-Wernicke encephalopathy is a neuropsychiatric emergency due to thiamine deficiency (vitamin B1), secondary to several factors. We here report a case of Gayet-Wernicke encephalopathy in a 43-year-old woman who didn't consume alcoholic beverages, presenting with disorders of consciousness and diplopia with normal thiamine level. Classic triad of symptoms and Magnetic resonance imaging (MRI) played an important role, in particular, in the diagnosis of Gayet-Wernicke encephalopathy with normal thiamine levels in the absence of alcohol abuse.


Assuntos
Diplopia/etiologia , Tiamina/sangue , Encefalopatia de Wernicke/diagnóstico , Adulto , Feminino , Humanos , Imageamento por Ressonância Magnética , Encefalopatia de Wernicke/fisiopatologia
15.
Chem Pharm Bull (Tokyo) ; 69(9): 832-839, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34470947

RESUMO

Thiamine (vitamin B1), which is synthesized only in bacteria, fungi and plants and which humans should take with diet, participates in basic biochemical and physiological processes in a versatile way and its deficiency is associated with neurological problems accompanied by cognitive dysfunctions. The rat glioblastoma (C6) model was used, which was exposed to a limited environment and toxicity with glutamate. The cells were stressed by exposure to glutamate in the presence and absence of thiamine. The difference in cell proliferation was evaluated in the XTT assay. Oxidative stress (OS) markers malondialdehyde (MDA), superoxide dismutase (SOD), and catalase (CAT) levels, as well as endoplasmic reticulum (ER) stress markers 78-kDa glucose-regulated protein (GRP78), activating transcription factor-4 (ATF-4), and C/EBP homologous protein (CHOP) levels, were measured with commercial kits. Apoptosis determined by flow cytometry was confirmed by 4',6-diamidino-2-phenylindole (DAPI) staining. At all concentrations, thiamine protects the cells and increased the viability against glutamate-induced toxicity. Thiamine also significantly decreased the levels of MDA, while increasing SOD and CAT levels. Moreover, thiamine reduced ER stress proteins' levels. Moreover, it lessened the apoptotic cell amount and enhanced the live-cell percentage in the flow cytometry and DAPI staining. As a result, thiamine may be beneficial nutritional support for individuals with a predisposition to neurodegenerative disorders due to its protective effect on glutamate cytotoxicity in glioblastoma cells by suppressing OS and ER stress.


Assuntos
Glioblastoma/tratamento farmacológico , Substâncias Protetoras/farmacologia , Tiamina/farmacologia , Animais , Sobrevivência Celular/efeitos dos fármacos , Estresse do Retículo Endoplasmático/efeitos dos fármacos , Glioblastoma/induzido quimicamente , Glioblastoma/patologia , Ácido Glutâmico , Estresse Oxidativo/efeitos dos fármacos , Substâncias Protetoras/química , Ratos , Tiamina/química , Células Tumorais Cultivadas
16.
Orphanet J Rare Dis ; 16(1): 403, 2021 09 29.
Artigo em Inglês | MEDLINE | ID: mdl-34587972

RESUMO

BACKGROUND: Thiamine metabolism dysfunction syndrome 4 (THMD4, OMIM #613710) is an autosomal recessive inherited disease caused by the deficiency of SLC25A19 that encodes the mitochondrial thiamine pyrophosphate (TPP) transporter. This disorder is characterized by bilateral striatal degradation and progressive polyneuropathy with the onset of fever of unknown origin. The limited number of reported cases and lack of functional annotation of related gene variants continue to limit diagnosis. RESULTS: We report three cases of encephalopathy from two unrelated pedigrees with basal ganglia signal changes after fever of unknown origin. To distinguish this from other types of encephalopathy, such as acute necrotizing encephalopathy, exome sequencing was performed, and four novel heterozygous variations, namely, c.169G>A (p.Ala57Thr), c.383C>T (p.Ala128Val), c.76G>A (p.Gly26Arg), and c.745T>A (p.Phe249Ile), were identified in SLC25A19. All variants were confirmed using Sanger sequencing. To determine the pathogenicity of these variants, functional studies were performed. We found that mitochondrial TPP levels were significantly decreased in the presence of SLC25A19 variants, indicating that TPP transport activities of mutated SLC25A19 proteins were impaired. Thus, combining clinical phenotype, genetic analysis, and functional studies, these variants were deemed as likely pathogenic. CONCLUSIONS: Exome sequencing analysis enables molecular diagnosis as well as provides potential etiology. Further studies will enable the elucidation of SLC25A19 protein function. Our investigation supplied key molecular evidence for the precise diagnosis of and clinical decision-making for a rare disease.


Assuntos
Encefalopatias , Proteínas de Transporte da Membrana Mitocondrial , Deficiência de Tiamina/genética , Humanos , Proteínas de Membrana Transportadoras/genética , Proteínas de Transporte da Membrana Mitocondrial/genética , Mutação/genética , Fenótipo , Tiamina
17.
Microb Pathog ; 160: 105209, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34563611

RESUMO

People living with HIV have a high incidence of cardiovascular and neurological diseases as comorbid disorders that are commonly linked to inflammation. While microbial translocation can augment inflammation during HIV infection, functional microbiome shifts that may increase pro-inflammatory responses have not been fully characterized. In addition, defining HIV-induced microbiome changes has been complicated by high variability among individuals. Here we conducted functional annotation of previously-published 16S ribosomal RNA gene sequences of 305 HIV positive and 249 negative individuals, with adjustment for geographic region, sex, sexual behavior, and age. Metagenome profiles were inferred from these individuals' 16S data. HIV infection was associated with impaired microbial vitamin B synthesis; around half of the gene families in thiamine and folate biosynthesis pathways were significantly less abundant in the HIV positive group than the negative control. These results are consistent with the high prevalence of thiamine and folate deficiencies in HIV infections. These HIV-induced microbiota shifts have the potential to influence cardiovascular and neurocognitive diseases, given the documented associations between B-vitamin deficiencies, inflammation, and these diseases. We also observed that most essential amino acid biosynthesis pathways were downregulated in the microbiome of HIV-infected individuals. Microbial vitamin B and amino acid synthesis pathways were not significantly recovered by antiretroviral treatment when we compared 262 ART positive and 184 ART negative individuals. Our meta-analysis provides a new outlook for understanding vitamin B and amino acid deficiencies in HIV patients, suggesting that interventions for reversing HIV-induced microbiome shifts may aid in lessening the burdens of HIV comorbidities.


Assuntos
Microbioma Gastrointestinal , Infecções por HIV , Ácido Fólico , Infecções por HIV/complicações , Humanos , Metagenoma , RNA Ribossômico 16S/genética , Tiamina
18.
Animal ; 15(10): 100370, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34583314

RESUMO

Ruminant animals are generally fed with starch-rich grain as the main energy source, and the incidence of metabolic diseases such as subacute ruminal acidosis (SARA) is high due to the intensive farming. Thiamin has been reported to alleviate SARA caused by high-concentrate diets, but the exact mechanism is not well understood. The goal of this study was to examine the role of thiamine in intestinal inflammation and microbiota caused by high-concentrate diets. The SARA model was induced by low neutral detergent fibre/starch ration to study the effects of thiamine on intestinal tissue structure and microbiota. 18 mid-lactation (148 ± 3 d in milk; milk yield = 0.71 ± 0.0300 kg/d) Saanen goats (BW = 36.5 ± 1.99 kg; body condition score = 2.73 ± 0.16, where 1 = emaciated and 6 = obese) in parities 1 or 2 were selected. The goats were randomly divided into three groups with six replicates: (1) control diet (C; concentrate:forage 30:70), (2) high-concentrate diet (H; concentrate:forage 70:30), and (3) high-concentrate diet with 200 mg of thiamine/kg of DM intake (H + T;concentrate:forage 70:30). The experimental period was lasted for 56 d. The small and large intestine, expression of inflammatory factor genes, tight junction protein genes, total antioxidant capacity, and intestinal microbiota were measured. The results showed that SARA was observed in treatment H, whereas rumen fluid pH was improved in treatment H + T. Treatment H + T also significantly repaired the intestinal tissue structure damaged by SARA, improved the total antioxidant capacity of the small intestinal mucosa, reduced mRNA expression of inflammatory factors in the small intestine tissue, and increased the mRNA expression of tight junction genes in small intestine tissue. The high-concentrate diet reduced the diversity of intestinal microbiota. When thiamine is added to the high-concentrate diet, the relative abundance of intestinal Firmicutes and beneficial bacteria represented by Lactobacilli were upregulated, and the relative abundance of Proteus, a marker of intestinal dysbacteriosis, returned to normal. In conclusion, thiamine supplementation could alleviate the damage to the intestinal tissue structure and microbial environment caused by SARA condition in dairy goats fed a high-concentrate diet.


Assuntos
Acidose , Doenças dos Bovinos , Doenças das Cabras , Microbiota , Acidose/veterinária , Animais , Bovinos , Dieta/veterinária , Feminino , Cabras , Concentração de Íons de Hidrogênio , Lactação , Leite , Rúmen , Tiamina
19.
Int J Mol Sci ; 22(18)2021 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-34576015

RESUMO

In this work, we firstly presented a simple encapsulation method to prepare thiamine hydrochloride (vitamin B1)-loaded asolectin-based liposomes with average hydrodynamic diameter of ca. 225 and 245 nm under physiological and acidic conditions, respectively. In addition to the optimization of the sonication and magnetic stirring times used for size regulation, the effect of the concentrations of both asolectin carrier and initial vitamin B1 on the entrapment efficiency (EE %) was also investigated. Thermoanalytical measurements clearly demonstrated that after the successful encapsulation, only weak interactions were discovered between the carriers and the drug molecules. Moreover, the dissolution profiles under physiological (pH = 7.40) and gastric conditions (pH = 1.50) were also registered and the release profiles of our liposomal B1 system were compared with the dissolution profile of the pure drug solution and a manufactured tablet containing thiamin hydrochloride as active ingredient. The release curves were evaluated by nonlinear fitting of six different kinetic models. The best goodness of fit, where the correlation coefficients in the case of all three systems were larger than 0.98, was reached by application of the well-known second-order kinetic model. Based on the evaluation, it was estimated that our liposomal nanocarrier system shows 4.5-fold and 1.5-fold larger drug retention compared to the unpackaged vitamin B1 under physiological conditions and in artificial gastric juice, respectively.


Assuntos
Tiamina/administração & dosagem , Preparações de Ação Retardada/química , Concentração de Íons de Hidrogênio , Lipossomos
20.
Crit Care Med ; 49(12): 2112-2120, 2021 12 01.
Artigo em Inglês | MEDLINE | ID: mdl-34582409

RESUMO

OBJECTIVES: Sepsis is a common condition in the ICU. Despite much research, its prognosis remains poor. In 2017, a retrospective before/after study reported promising results using a combination of thiamine, ascorbic acid, and hydrocortisone called "metabolic resuscitation cocktail" and several randomized controlled trials assessing its effectiveness were performed. DESIGN: We conducted a systematic review and meta-analysis of randomized controlled trials in septic ICU patients to assess the effects of this combination therapy. SETTING: PubMed, Embase, and the Cochrane library databases were searched from inception to March of 2021. Data were extracted independently by two authors. The main outcome was the change in Sequential Organ Failure Assessment score within 72 hours. Secondary outcomes included renal composite endpoints (acute kidney injury) Kidney Disease - Improving Global Outcome organization stage 3 or need for renal replacement therapy, vasopressor duration, and 28-day mortality. SUBJECTS: We included randomized controlled trials with patients admitted to the ICU with sepsis or septic shock. INTERVENTION: The trials compared a combination of thiamine, ascorbic acid, and hydrocortisone to standard care or placebo in patients admitted to ICU with sepsis or septic shock. MEASUREMENTS AND MAIN RESULTS: We included eight randomized controlled trials (n = 1,335 patients). Within 72 hours, the median of mean improvement was -1.8 and -3.2 in the control and intervention groups, respectively (eight randomized controlled trials, n = 1,253 patients); weighted mean difference -0.82 (95% CI, -1.15 to -0.48). Data were homogeneous and the funnel plot did not suggest any publication bias. Duration of vasopressor requirement was significantly reduced in the intervention group (six randomized controlled trials). There was no evidence of a difference regarding the ICU mortality and the renal composite outcome (acute kidney injury KDIGO 3 or need for renal replacement therapy, seven randomized controlled trials). CONCLUSIONS: Metabolic resuscitation cocktail administrated in ICU septic patients improves change in Sequential Organ Failure Assessment score within 72 hours. However, this improvement is modest and its clinical relevance is questionable. The impact on renal failure and mortality remains unclear.


Assuntos
Ácido Ascórbico/metabolismo , Hidrocortisona/metabolismo , Metabolismo/efeitos dos fármacos , Sepse/tratamento farmacológico , Tiamina/metabolismo , Ácido Ascórbico/farmacologia , Ácido Ascórbico/uso terapêutico , Combinação de Medicamentos , Humanos , Hidrocortisona/farmacologia , Hidrocortisona/uso terapêutico , Ontário , Ensaios Clínicos Controlados Aleatórios como Assunto/estatística & dados numéricos , Sepse/fisiopatologia , Tiamina/farmacologia , Tiamina/uso terapêutico
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