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1.
Int J Mol Sci ; 24(4)2023 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-36834957

RESUMO

Multiple sclerosis (MS) is a debilitating chronic disease of unknown etiology. There are limited treatment options due to an incomplete understanding of disease pathology. The disease is shown to have seasonal exacerbation of clinical symptoms. The mechanisms of such seasonal worsening of symptoms remains unknown. In this study, we applied targeted metabolomics analysis of serum samples using LC-MC/MC to determine seasonal changes in metabolites throughout the four seasons. We also analyzed seasonal serum cytokine alterations in patients with relapsed MS. For the first time, we can demonstrate seasonal changes in various metabolites in MS compared to the control. More metabolites were affected in MS in the fall season followed by spring, while summer MS was characterized by the smallest number of affected metabolites. Ceramides were activated in all seasons, suggesting their central role in the disease pathogenesis. Substantial changes in glucose metabolite levels were found in MS, indicating a potential shift to glycolysis. An increased serum level of quinolinic acid was demonstrated in winter MS. Histidine pathways were affected, suggesting their role in relapse of MS in the spring and fall. We also found that spring and fall seasons had a higher number of overlapping metabolites affected in MS. This could be explained by patients having a relapse of symptoms during these two seasons.


Assuntos
Esclerose Múltipla , Humanos , Estações do Ano , Citocinas , Doença Crônica , Recidiva
2.
Artigo em Inglês | MEDLINE | ID: mdl-35030474

RESUMO

Liquid chromatography (LC) - mass spectrometry quantitative analysis of substances in biological samples is usually performed in the multiple reaction monitoring (MRM) variant. In complex biological matrices, strong interferences can be observed when using the LC-MRM method. Interference levels can be significantly reduced by using LC - multiple reaction monitoring cubed (MRM3). 6-sulfatoxymelatonin (6-SM) is a metabolite of melatonin, an important regulator of many biological processes. The quantitative analysis of 6-SM in urine allows monitoring of the melatonin level in the blood. The aim of the present work was to evaluate the LC-MRM3 method for the quantitative determination of 6-SM in urine. We found that for 6-SM in aqueous solutions, under some parameters of the MRM3 experiment, the effect of degradation of the MRM3 signal is observed. When analyzing 6-SM in urine, this signal degradation effect was significantly reduced. We have shown that optimization of such parameters of the MRM3 method as the linear ion trap fill time, the number of scans to sum, and the range of triple-stage scan allows obtaining the LC-MRM3 method, which is comparable to the LC-MRM in sensitivity and significantly exceeds it in selectivity.


Assuntos
Cromatografia Líquida/métodos , Espectrometria de Massas/métodos , Melatonina/análogos & derivados , Humanos , Melatonina/metabolismo , Melatonina/urina
3.
Expert Opin Drug Discov ; 14(5): 455-468, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30884978

RESUMO

INTRODUCTION: The development of new antimicrobials has become an urgent priority because of a global challenge emerging from the rise of antimicrobial resistant pathogens. Areas covered: In this review, the authors discuss the opportunities offered by modern omics approaches to address the challenge and the use of this approach in antimicrobial development. Specifically, the authors focus on the role of omics technologies and bioinformatics for the revelation of the effects of antimicrobials in a variety of microbial cellular processes, as well as the identification of potential cellular targets, the mechanisms of antimicrobial resistance, and the development of new antimicrobials. Expert opinion: Prevention of antimicrobial resistance does not only depend on rational drug design such as narrow-spectrum antimicrobials but on several factors. It is the opinion of the authors that the use of a multi-omics bioinformatics approach should become an integral part of antimicrobial drug discovery as well as in the prevention of antimicrobial resistance.


Assuntos
Anti-Infecciosos/farmacologia , Desenho de Fármacos , Desenvolvimento de Medicamentos/métodos , Biologia Computacional , Descoberta de Drogas/métodos , Resistência Microbiana a Medicamentos , Humanos
4.
Biomed Res Int ; 2019: 9843781, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30733970

RESUMO

BACKGROUND: The aim of this study was to assess changes in skin microbiota of wrestlers during training sessions and to determine the sensitivity of hemolytic bacterial isolates to antiseptics. METHODS: The main skin bacterial isolates obtained from the skin of 15 wrestlers were identified by cultivation method, with the following MALDI Biotyper and 16S rRNA gene sequencing methods. The sensitivity of hemolytic isolates to antiseptics (Veltosept-2, Cutasept F, Chlorhexidine, Miramistin, and Hydrogen Peroxide) was evaluated by measuring the size of bacterial growth inhibition zone on agar plates. RESULTS: Opportunistic bacteria of the species Bacillus cereus, Staphylococcus aureus, S. epidermidis, and S. saprophyticus were the most commonly found species in skin microbiota of wrestlers before and after training sessions. Representatives of all these species mostly had a hemolytic activity. An alcohol-containing antiseptic Veltosept-2 showed the strongest inhibitory effect on the bacterial isolates of athletes' skin microbiota most frequently detected in this study. CONCLUSIONS: The general increase in the bacterial colonization of wrestlers' skin, as well as the presence of hemolytic forms of opportunistic bacteria in cutaneous microbiota, indicates dysbiotic changes and a decrease in the protective features of the host organism. Veltosept-2 application can reduce the incidence of skin infections in contact sports athletes with the highest efficiency.


Assuntos
Anti-Infecciosos Locais/farmacologia , Atletas , Higiene , Microbiota/efeitos dos fármacos , Pele/microbiologia , Esportes , Adolescente , Bactérias/efeitos dos fármacos , Bactérias/crescimento & desenvolvimento , Contagem de Colônia Microbiana , Humanos , Masculino , Testes de Sensibilidade Microbiana , Pele/efeitos dos fármacos , Luta Romana , Adulto Jovem
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