Multiple sclerosis (MS) is a chronic inflammatory neurodegenerative disease of the central nervous system. The manifestation of MS is related to steroid changes during the menstrual cycle and pregnancy. As data focusing on the effect of anti-MS drug treatment on steroidome are scarce, we evaluated steroidomic changes (79 steroids) in 61 female MS patients of reproductive age 39 (29, 47) years (median with quartiles) after treatment with anti-MS drugs on the GC-MS/MS platform and immunoassays (cortisol and estradiol). The changes were assessed using steroid levels and steroid molar ratios (SMRs) that may reflect the activities of steroidogenic enzymes (SMRs). A repeated measures ANOVA, followed by multiple comparisons and OPLS models, were used for statistical analyses. The anti-MS treatment decreased steroid levels in the follicular phase. Anti-CD20 monoclonal antibodies (mAb), such as ofatumumab and ocrelizumab; inhibitors of the sphingosine-1-phosphate receptor (S1PRI); and IFNβ-1a decreased circulating 17-hydroxy-pregnanes and shifted the CYP17A1 functioning from the hydroxylase- toward the lyase step. Decreased conjugated/unconjugated steroid ratios were found after treatment with anti-MS drugs, especially for glatiramer acetate and anti-CD20 mAb. In the luteal phase, IFN-β1a treatment increased steroidogenesis; both IFN-β1a and ocrelizumab increased AKR1D1, and S1PRI increased SRD5A functioning. Anti-CD20 mAb reduced the functioning of enzymes catalyzing the synthesis of immunomodulatory 7α/β and 16α-hydroxy-androgens, which may affect the severity of MS. The above findings may be important concerning the alterations in bioactive steroids, such as cortisol; active androgens and estrogens; and neuroactive, neuroprotective, and immunomodulatory steroids in terms of optimization of anti-MS treatment.

• Klíčová slova
• GC-MS/MS, anti-MS drugs, multiple sclerosis, multivariate statistics, steroidomics,
• MeSH
• dospělí MeSH
• glatiramer acetát terapeutické užití   MeSH
• lidé středního věku MeSH
• lidé MeSH
• menstruační cyklus účinky léků   MeSH
• roztroušená skleróza * farmakoterapie   metabolismus   krev   MeSH
• steroidy * metabolismus   krev   MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• glatiramer acetát MeSH
• steroidy * MeSH

Gestational diabetes mellitus (GDM) is a common complication of pregnancy in which women without previously diagnosed diabetes develop chronic hyperglycemia during pregnancy. It is associated with a number of maternal and fetal/neonatal complications. The role of the adipokines retinol binding protein-4, resistin and nesfatin-1 in the development of GDM is relatively poorly understood, but their role in glucose metabolism is suspected and their use as early markers to predict the development of GDM is being sought. The aim of study was to determine the correlation between the levels of selected adipokines (retinol binding protein-4, resistin, nesfatin-1) in women with gestational diabetes mellitus (GDM) and healthy pregnant women and to compare their levels with other clinical and biochemical parameters. Patients with GDM had significantly higher BMI (28.4±4.5 vs. 24.6±4 kg/m2), total cholesterol (6±1.3 vs. 5.3±1.4 mmol/l) and triacylglycerols (1.9±0.8 vs. 1.4±0.7 mmol/l) than women in the control group. RBP4 confirms the significant difference between the groups, it is higher in the control group of healthy pregnant women. The adipokines resistin and nesfatin-1 show no differences between the control and GDM groups, but their ratios with BMI, cholesterol and triacylglycerols, resistin shows elevated levels in the control group. In women with GDM, RBP4 was significantly positively correlated with C-peptide and negatively correlated with total, LDL, and non-HDL cholesterol. Resistin was also negatively correlated with total, LDL, HDL, and non-HDL cholesterol. Nesfatin-1 was only moderately positively correlated with glycated hemoglobin (HbA1C) and fasting glycemia. There is ambiguity in the results of previous studies on the levels of the investigated adipokines in pregnant women with GDM and the interpretation depends on many factors. Keywords: Gestational diabetes, Adipokines, Retinol-binding protein 4, Resistin, Nesfatin-1.

• MeSH
• adipokiny * krev   MeSH
• biologické markery krev   MeSH
• DNA vazebné proteiny * krev   MeSH
• dospělí MeSH
• gestační diabetes * krev   diagnóza   MeSH
• krevní glukóza metabolismus   MeSH
• lidé MeSH
• nukleobindiny * krev   MeSH
• plazmatické proteiny vázající retinol * metabolismus   analýza   MeSH
• proteiny vázající vápník * krev   MeSH
• resistin * krev   MeSH
• studie případů a kontrol MeSH
• těhotenství MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• těhotenství MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• adipokiny * MeSH
• biologické markery MeSH
• DNA vazebné proteiny * MeSH
• krevní glukóza MeSH
• NUCB2 protein, human MeSH Prohlížeč
• nukleobindiny * MeSH
• plazmatické proteiny vázající retinol * MeSH
• proteiny vázající vápník * MeSH
• RBP4 protein, human MeSH Prohlížeč
• resistin * MeSH
• RETN protein, human MeSH Prohlížeč

Epidemiological studies suggest an association between Alzheimer's disease (AD) and type 2 diabetes mellitus (T2DM). This study aimed to investigate the pathophysiological markers of AD vs. T2DM for each sex separately and propose models that would distinguish control, AD, T2DM, and AD-T2DM comorbidity groups. AD and T2DM differed in levels of some circulating steroids (measured mostly by GC-MS) and in other observed characteristics, such as markers of obesity, glucose metabolism, and liver function tests. Regarding steroid metabolism, AD patients (both sexes) had significantly higher sex hormone binding globulin (SHBG), cortisol, and 17-hydroxy progesterone, and lower estradiol and 5α-androstane-3α,17β-diol, compared to T2DM patients. However, compared to healthy controls, changes in the steroid spectrum (especially increases in levels of steroids from the C21 group, including their 5α/β-reduced forms, androstenedione, etc.) were similar in patients with AD and patients with T2DM, though more expressed in diabetics. It can be assumed that many of these steroids are involved in counter-regulatory protective mechanisms that mitigate the development and progression of AD and T2DM. In conclusion, our results demonstrated the ability to effectively differentiate AD, T2DM, and controls in both men and women, distinguish the two pathologies from each other, and differentiate patients with AD and T2DM comorbidities.

• Klíčová slova
• Alzheimer’s disease, GC-MS, differential diagnostics, multivariate statistics, steroidome, type 2 diabetes mellitus,
• MeSH
• Alzheimerova nemoc * metabolismus   MeSH
• androstendion MeSH
• diabetes mellitus 2. typu * diagnóza   epidemiologie   MeSH
• komorbidita MeSH
• lidé MeSH
• steroidy metabolismus   MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• androstendion MeSH
• steroidy MeSH