Clinical course of respiratory tuberculosis relapses in the Kazakh population depending on HLA-DRB1 gene alleles.

The study aimed to ascertain the prevalence and frequency of relapses of respiratory tuberculosis (TB) and examine the characteristics of its clinical progression in members of the Kazakh population based on the alleles of the HLA-DRB1 gene. Methods of clinical and genetic research, statistical processing and analysis of the obtained data were used to achieve this goal. The research led to an analysis of the statistical processing of clinical and genetic investigations that found out how often TB in the respiratory tract is found and how different HLA-DRB1 gene alleles affect the disease's progression. To find out how exposure to certain HLA-DRB1 gene alleles affects the chance of relapse, the number of times they were found was compared between people who had relapsed and people who had just been diagnosed with TB. The impact of these alleles on the progression of the disease was assessed based on their frequency of detection of different clinical forms of TB (infiltrative, fibro-cavernous, generalised, disseminated), unilateral and bilateral lung damage, lung tissue deterioration, and the presence of bacterial secretions. The highest detection rate for all comparisons had gene alleles HLA-DRB1*01 (9.5%), *08 (4.2%), *15 (3.9%), *09 (1.6%), *12 (1.3%), *13 (0.9%), *11 (0.2%). The study found that Kazakhs with the HLA-DRB1*01, *08, and 15 gene alleles are more likely to develop recurrent respiratory TB. The study's practical value lies in its potential to utilise its findings for the prompt identification and eradication of genetic variables contributing to the recurrence of TB.

Selective screening for inborn errors of metabolism using tandem mass spectrometry in West Kazakhstan children: study protocol.

Data on the prevalence of most inborn errors of metabolism are still unavailable in Kazakhstan. The study aims to perform selective screening for hereditary metabolic diseases among patients aged from 1 day to 18 years in western Kazakhstan using the LC-MS/MS method, with establishing the reference values for the content of amino acids, acylcarnitines, and succinylacetone in blood samples of healthy children. Tasks: 1. To assess the burden of metabolic disorders detected by LC-MS/MS in western Kazakhstan by examination of children at clinical risk in pediatric clinics throughout the region; https://www.frontiersin.org/register?returnUrl=https://loop.frontiersin.org 2. To set the reference values of metabolites in the child population; 3. To analyze the age distribution, prevalence, and age of onset for each identified IEM, further comparing the obtained findings with those from previously published reports in other populations. METHODS: To set the reference values of 51 metabolites in the child population, 750 healthy children will be included. The selective screening will be performed among 1,500 patients aged 1 day to 18 years with suspected hereditary metabolic disorders. ANTICIPATED RESULTS: The results of selective screening will be interpreted by comparison with the reference values established. Diagnosis will be based on clinical signs, blood levels of amino acids, acylcarnitines, succinylacetone, and urine levels of organic acids and tests for gene mutations. An assessment of 37 inborn errors of metabolism frequencies in high-risk children will be performed. The research will further develop the national as selective as expanded newborn screening programs. The study was registered in clinicaltrials. gov (https://www. CLINICALTRIALS: gov/study/NCT05910151) on 16 June 2023.

Extracellular Nampt (eNampt/visfatin/PBEF) directly and indirectly stimulates ACTH and CCL2 protein secretion from isolated rat corticotropes.

BACKGROUND: Nicotinamide phosphoribosyltransferase (Nampt/visfatin/PBEF) acts both as an enzyme in the nicotinamide adenine dinucleotide (NAD) synthesis pathway as well as an extracellular hormone (eNampt). Among its effects, eNampt exerts potent pro-inflammatory effects. We have recently shown that, in rats, eNampt stimulates corticosterone secretion by acting through the pituitary rather than the hypothalamus. OBJECTIVES: To investigate the mechanism of action of eNampt on the secretion of adrenocorticotropic hormone (ACTH) and chemokine (C-C motif) ligand 2 (CCL2), which are cytokines secreted by pituitary neuroendocrine tumors. MATERIAL AND METHODS: The research was carried out on the AtT-20 murine cell line, primary rat pituitary cell culture, isolated pituitary corticotropes, and in vivo. The effects of the performed experiments were examined using the following methods: gene expression profiling using microarrays, quantitative polymerase chain reaction (qPCR) and enzyme-linked immunosorbent assay (ELISA). RESULTS: The results suggest that eNampt stimulates ACTH secretion from rat corticotropes both directly and indirectly. Indirect action most likely occurs through interleukin (IL)-6 secreted by folliculostellate cells of the pituitary gland. In isolated ACTH cells of the rat pituitary gland, eNampt stimulates the expression of genes involved in the immune response. Among them, the protein encoded by the CCL2 gene seems to also be involved in the regulation of corticotropin-releasing hormone (CRH)-dependent metabolism. Unlike rat corticotropes, murine AtT-20 corticotropic cells do not react to either eNampt or Fk866 (the inhibitor of Nampt enzymatic action). CONCLUSIONS: The eNampt stimulates the secretion of ACTH from rat corticotropes indirectly and directly, likely by stimulating IL-6 secretion from folliculostellate cells of the pituitary gland. This effect was not observed in the AtT-20 corticotropic cell cancer cell line.

Prognostic role of increased serum homocysteine concentration in preeclampsia.

Objective: To assess homocysteine (Hcy) concentration in women with preeclampsia (PE).Methods: Hcy concentrations were detected by ELISA in 305 pregnancies.Results: Hcy concentration in patients with PE was 16.07 umol/L at 10-14 weeks as compared to 7.19 umol/L in normotensive pregnancies (p < 0.0001). Optimal cutoff level for Hcy in the first trimester of pregnancy was >9.55 umol/L with area under curve of 0.859, sensitivity of 91.67%, specificity of 72.24%.Conclusion: Assessment of serum Hcy concentration may be used as a predictor of PE, with the highest diagnostic utility in the first trimester of pregnancy.