Crude oil contamination has been shown to impair reproduction in aquatic animals through carcinogenic and genotoxic properties. Here, we assessed the endocrine-disrupting function of crude oil on male reproductive system based on testicular histology, sex steroid hormones, and fertility endpoints in adult male goldfish (Carassius auratus), which were exposed to 0.02- to 2-mg/L crude oil for 21 days (Experiment #1) or to 5- to 250-mg/L crude oil for 9 days (Experiment #2). The crude oil contained 0.22-mg/L nickel (Ni), 1.10-mg/L vanadium (V), and 12.87-mg/L polycyclic aromatic hydrocarbons (PAHs). Twenty-four hours after adding crude oil, the sum of PAHs ranged from 0.30 to 2.28 μg/L in the aquaria containing 0.02- and 250-mg/L crude oil, respectively. Water analyses for heavy metals in Experiment #2 showed high concentrations (mg/L) of Ni (0.07-0-09) and V (0.10-0.21). For both experiments, exposure to crude oil did not impact gonadosomatic index; however, testes showed histopathological defects including hyperplasia or hypertrophy of Sertoli cells, depletion of the Leydig cells, necrosis of germ cells, and fibrosis of lobular wall. In Experiment #1, sperm production and motility, testosterone (T), and 17β-estradiol (E2) were not significantly different among treatments. In Experiment #2, the number of spermiating males decreased by ~50% following exposure to 250-mg/L crude oil. Sperm production, motility kinematics, T, and the T/E2 ratio significantly decreased in males exposed to ≥ 50-mg/L crude oil; however, E2 remained unchanged. Results show crude oil-induced imbalance of sex steroid hormones disrupts spermatogenesis resulting in diminished sperm production and motility.

• MeSH
• Water Pollutants, Chemical * toxicity   MeSH
• Endocrine Disruptors * toxicity   MeSH
• Goldfish * physiology   MeSH
• Sperm Motility * drug effects   MeSH
• Gonadal Steroid Hormones * metabolism   blood   MeSH
• Petroleum * toxicity   MeSH
• Reproduction drug effects   MeSH
• Spermatozoa * drug effects   pathology   MeSH
• Testis * drug effects   pathology   MeSH
• Animals MeSH
• Check Tag
• Male MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH

Therapeutic plasma exchange (PLEX) is an adjunctive treatment for patients with anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis and kidney involvement. Little is known about the effect of PLEX on early changes in kidney function. This post-hoc analysis of the PEXIVAS trial investigated the effects of PLEX on changes in kidney function within 12 months. PEXIVAS was a randomized controlled trial recruiting 691 patients with ANCA-associated glomerulonephritis, of whom 349 underwent PLEX and 342 received no-PLEX. The primary outcomes of this post hoc study of PEXIVAS were change in estimated glomerular filtration rate (eGFR) from baseline and recovery of kidney function (defined as eGFR increase of 15ml/min/1.73m2 or more). Baseline eGFR was 21.7 ± 20.3 and 20.6 ± 18.7 ml/min/1.73m2 in the PLEX and no-PLEX groups, respectively. Mean improvements in eGFR at weeks two, four, and eight after initiation of therapy were greater for the PLEX vs. the no-PLEX groups. The greatest significant difference in recovery of kidney function in the PLEX compared to the no-PLEX groups was at week four (relative risk (RR): 1.41; 95% confidence interval:1.09-1.82). Increased eGFR or recovery of kidney function at week four were significantly associated with lower risk for end-stage kidney disease at week 52 (RR: 0.96: 0.95-0.97, and RR: 0.29: 0.16-0.52; respectively). Neither changes in eGFR nor recovery of kidney function differed by reduced- compared to standard-dose glucocorticoid group. Overall, our study indicates that PLEX improves early kidney function in patients with ANCA-associated glomerulonephritis.

• MeSH
• Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis * physiopathology   therapy   drug therapy   complications   immunology   diagnosis   MeSH
• Adult MeSH
• Glomerulonephritis * physiopathology   immunology   therapy   blood   MeSH
• Glucocorticoids * therapeutic use   administration & dosage   MeSH
• Glomerular Filtration Rate * MeSH
• Kidney * physiopathology   drug effects   MeSH
• Middle Aged MeSH
• Humans MeSH
• Recovery of Function MeSH
• Aged MeSH
• Plasma Exchange * MeSH
• Treatment Outcome MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Multicenter Study MeSH
• Randomized Controlled Trial MeSH

The endorsement of conspiracy theories may be increased by subjectively perceived stress. Yet, it is not known whether this correlation is caused by the effects of the acute stress reaction on the brain or other psychological, social, or methodological factors. The effect of an experimentally induced acute stress reaction on conspiracy thinking was tested on a sample (n = 115) of students of medicine. Although the stress procedure caused a substantial increase in salivary cortisol, there was no significant effect on endorsing conspiracy theories or adopting conspiracy interpretations of novel information. The results confirmed no effect of the acute stress reaction on conspiracy thinking, suggesting it may be absent or weaker than expected. The study demonstrated the viability of psychophysiological experimental design in conspiracy research and may inspire further examination of the physiological mechanisms underlying susceptibility to conspiracy theories.

• MeSH
• Adult MeSH
• Hydrocortisone analysis   metabolism   MeSH
• Humans MeSH
• Young Adult MeSH
• Stress, Psychological * psychology   MeSH
• Saliva chemistry   MeSH
• Check Tag
• Adult MeSH
• Humans MeSH
• Young Adult MeSH
• Male MeSH
• Female MeSH
• Publication type
• Journal Article MeSH

PURPOSE: High-dose intravenous glucocorticoids are the standard first-line treatment in active, moderate to severe and severe thyroid eye disease (TED). We evaluate the usefulness of clinical activity score (CAS) and thyroid-stimulating immunoglobulin (TSI) as predictors and/or post-treatment markers of corticoresistance in patients with TED and the effect of rituximab in second-line treatment. METHODS: We enrolled 236 patients with an active TED into this retrospective single-tertiary-center cohort study. All patients were initially treated with high-dose systemic glucocorticoids. Rituximab was later administered to 29 of 42 corticoresistant patients. RESULTS: The CAS of the corticoresistant patients was significantly higher both before (p = 0.0001) and after (p = <0.0001) first-line treatment compared to the corticosensitive group. ROC analysis established the cut-point value as CAS ≥ 2.5 with a sensitivity of 96.3%, specificity of 57.5% and area under the curve of 82.8%. In 22 patients treated with rituximab, CAS gradually decreased to zero values without reactivation during extended follow-up. There was no difference in the TSI of corticosensitive and corticoresistant patients before or after first-line therapy. CONCLUSION: CAS ≥ 2, after first-line treatment, could be used as a corticoresistance marker. Corticoresistant patients should be subject to long-term follow-up for early detection of reactivation to reduce the delay to second-line treatment. Rituximab is a well-tolerated choice of second-line treatment and has a long-lasting effect on disease activity. Although TSI is a valuable biomarker of Graves' disease and TED activity, according to our results, TSI cannot be used as a marker of corticoresistance.

• MeSH
• Adult MeSH
• Glucocorticoids therapeutic use   MeSH
• Graves Ophthalmopathy * drug therapy   blood   MeSH
• Immunoglobulins, Thyroid-Stimulating blood   MeSH
• Immunologic Factors therapeutic use   MeSH
• Drug Resistance * MeSH
• Middle Aged MeSH
• Humans MeSH
• Retrospective Studies MeSH
• Rituximab * therapeutic use   MeSH
• Aged MeSH
• Treatment Outcome MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH

INTRODUCTION: Alopecia areata is a common autoimmune disease which results in reversible hair loss. Janus kinase inhibitors are prescribed for severe alopecia areata with encouraging results. There are no studies comparing the efficacy and safety of Janus kinase inhibitors to traditional treatment options, such as topical immunomodulators and traditional immunosuppressants. AIMS: To retrospectively compare the efficacy and safety of baricitinib, an approved Janus kinase inhibitor, to other treatments for severe AA during a 6-month treatment period. MATERIALS/METHODS: We included patients with newly presenting, relapsing or treatment-resistant alopecia areata with Severity of Alopecia Tool (SALT) score ≥ 50, for the period between July 2021 and July 2023. Medical histories were reviewed and possible side effects were recorded. Primary endpoints were SALT ≤ 20 and SALT ≤ 10 after 6 months of treatment. RESULTS: Seventy-five patients (53 females) were divided into three groups: topical immunomodulators (51 patients); baricitinib (19 patients); and a group receiving pulsed intramuscular corticosteroids or traditional immunosuppressants (11 patients). Twenty-one patients received more than one treatment options within 2 years. After 6 months, the baricitinib group showed superior efficacy with 32% and 26% of patients achieving SALT ≤ 20 and SALT ≤ 10, compared to 12% and 9% in both other groups. Baricitinib demonstrated better secondary outcomes (50% and 90% reduction from initial SALT scores). All treatments exhibited mild-to-moderate and expected side effects. Weight gain, which had not been reported in clinical trials for alopecia areata, was observed in three baricitinib-treated patients. CONCLUSION: Baricitinib was superior to traditional treatments for severe alopecia areata after 6 months. Weight gain concerned 16% of patients receiving baricitinib.

• MeSH
• Alopecia Areata * drug therapy   MeSH
• Azetidines * adverse effects   therapeutic use   administration & dosage   MeSH
• Adult MeSH
• Adrenal Cortex Hormones therapeutic use   administration & dosage   adverse effects   MeSH
• Immunologic Factors administration & dosage   adverse effects   therapeutic use   MeSH
• Immunosuppressive Agents * adverse effects   therapeutic use   administration & dosage   MeSH
• Janus Kinase Inhibitors * adverse effects   administration & dosage   therapeutic use   MeSH
• Middle Aged MeSH
• Humans MeSH
• Adolescent MeSH
• Young Adult MeSH
• Purines * adverse effects   administration & dosage   therapeutic use   MeSH
• Pyrazoles * adverse effects   administration & dosage   therapeutic use   MeSH
• Retrospective Studies MeSH
• Severity of Illness Index * MeSH
• Sulfonamides * adverse effects   administration & dosage   therapeutic use   MeSH
• Treatment Outcome MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Adolescent MeSH
• Young Adult MeSH
• Male MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Comparative Study MeSH

The small airways, also referred to as the lung's silent zone, are closely associated with poor symptom control and more frequent asthma exacerbations. The oscillometry technique superimposes sound or airwaves onto normal tidal breathing and provides information on resistance and reactance, that is, obstacles to airflow occurring inside and outside of the bronchi. More recently, a management paradigm based on so-called "treatable traits" has been proposed to personalize and improve asthma care for individuals by proactively identifying and targeting modifiable pulmonary, extrapulmonary, and behavioral traits affecting asthma control. In this review article, we evaluate the literature on small airways dysfunction as a potential treatable trait in persistent asthma. In particular, we discuss whole- and intrabreath oscillometry and the impact of extrafine inhaled corticosteroids and systemic biologics on the peripheral airways.

• MeSH
• Asthma * physiopathology   drug therapy   diagnosis   MeSH
• Adrenal Cortex Hormones therapeutic use   MeSH
• Humans MeSH
• Oscillometry * methods   MeSH
• Lung physiopathology   MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Review MeSH

The aim of the present study was to assess systemic circulatory and tissue activities of both the classical arm and of the alternative arm of the renin-angiotensin system (RAS) in a new transgenic rat line (TG7371) that expresses angiotensin-(1-7) (ANG 1-7)-producing fusion protein; the results were compared with the activities measured in control transgene-negative Hannover Sprague-Dawley (HanSD) rats. Plasma and tissue concentrations of angiotensin II (ANG II) and ANG 1-7, and kidney mRNA expressions of receptors responsible for biological actions of ANG II and ANG 1-7 [i.e. ANG II type 1 and type 2 (AT1 and AT2) and Mas receptors] were assessed in TG7371 transgene-positive and in HanSD rats. We found that male TG7371 transgene-positive rats exhibited significantly elevated plasma, kidney, heart and lung ANG 1-7 concentrations as compared with control male HanSD rats; by contrast, there was no significant difference in ANG II concentrations and no significant differences in mRNA expression of AT1, AT2 and Mas receptors. In addition, we found that in male TG7371 transgene-positive rats blood pressure was lower than in male HanSD rats. These data indicate that the balance between the classical arm and the alternative arm of the RAS was in male TGR7371 transgene-positive rats markedly shifted in favor of the latter. In conclusion, TG7371 transgene-positive rats represent a new powerful tool to study the long-term role of the alternative arm of the RAS in the pathophysiology and potentially in the treatment of cardio-renal diseases.

• MeSH
• Angiotensin I * metabolism   MeSH
• Angiotensin II * MeSH
• Cardiovascular Diseases metabolism   genetics   MeSH
• Blood Pressure physiology   MeSH
• Rats MeSH
• Kidney metabolism   MeSH
• Kidney Diseases metabolism   genetics   MeSH
• Peptide Fragments * metabolism   MeSH
• Rats, Sprague-Dawley * MeSH
• Rats, Transgenic * MeSH
• Proto-Oncogene Mas MeSH
• Receptor, Angiotensin, Type 1 genetics   metabolism   MeSH
• Receptors, G-Protein-Coupled genetics   metabolism   MeSH
• Recombinant Fusion Proteins metabolism   MeSH
• Renin-Angiotensin System * physiology   MeSH
• Animals MeSH
• Check Tag
• Rats MeSH
• Male MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH

Publikace se zaměřuje na steroidní hormony, metabolismus a na jejich diagnostiku pomocí různých metod. Určeno odborné veřejnosti.; Steroidní hormony mají klíčový význam napříč celou moderní medicínou, od endokrinologie přes hormonální antikoncepci až k autoimunitám či transplantačním technikám. Steroidy jsou standardní součásti farmakoterapie v kardiologii, dermatologii, gynekologii a porodnictví, imunologii, možnosti zákroku v akutních krizových stavech, oslabování pochodů stárnutí a v dalších lékařských i veterinárních oborech. Porozumět problematice steroidních hormonů není lehkým úkolem. Pro lékaře-endokrinologa nejsou ve steroidní patologii takovým problémem nedostatečná produkce nebo nadprodukce některých steroidních hormonů, jako právě poruchy v oblasti steroidních enzymopatií, kde jsou indikátorem onemocnění různé sobě blízké steroidy a kdy lékař o diagnóze a léčbě má rozhodnout na základě analýzy spektra steroidů dodaného laboratoří.

• MeSH
• Chromatography, Liquid MeSH
• Chromatography, Gas MeSH
• Mass Spectrometry MeSH
• Immunoassay MeSH
• Metabolism MeSH
• Gonadal Steroid Hormones MeSH

• Conspectus
• Biochemie. Molekulární biologie. Biofyzika
• NML Fields
• biochemie
• endokrinologie
• NML Publication type
• kolektivní monografie

AIM: Despite the high sensitivity of neonatal screening in detecting the classical form of congenital adrenal hyperplasia due to 21-hydroxylase deficiency, one of the unclear issues is identifying asymptomatic children with late onset forms. The aim of this nationwide study was to analyse the association between genotype and screened level of 17-hydroxyprogesterone in patients with the late onset form of 21-hydroxylase deficiency and to quantify false negativity. METHODS: In the Czech Republic, 1,866,129 neonates were screened (2006-2022). Among this cohort, 159 patients were confirmed to suffer from 21-hydroxylase deficiency, employing the 17-hydroxyprogesterone birthweight/gestational age-adjusted cut-off limits, and followed by the genetic confirmation. The screening prevalence was 1:11,737. Another 57 patients who were false negative in neonatal screening were added to this cohort based on later diagnosis by clinical suspicion. To our knowledge, such a huge nationwide cohort of false negative patients has not been documented before. RESULTS: Overall, 57 patients escaped from neonatal screening in the monitored period. All false negative patients had milder forms. Only one patient had simple virilising form and 56 patients had the late onset form. The probability of false negativity in the late onset form was 76.7%. The difference in 17-hydroxyprogesterone screening values was statistically significant (p<0.001) between severe forms (median 478.8 nmol/L) and milder (36.2 nmol/L) forms. Interestingly, the higher proportion of females with milder forms was statistically significant compared with the general population. CONCLUSIONS: A negative neonatal screening result does not exclude milder forms of 21-hydroxylase deficiency during the differential diagnostic procedure of children with precocious pseudopuberty.

• MeSH
• 17-alpha-Hydroxyprogesterone * blood   MeSH
• False Negative Reactions MeSH
• Adrenal Hyperplasia, Congenital * diagnosis   blood   MeSH
• Humans MeSH
• Infant, Newborn MeSH
• Neonatal Screening * methods   MeSH
• Steroid 21-Hydroxylase genetics   MeSH
• Age of Onset MeSH
• Check Tag
• Humans MeSH
• Male MeSH
• Infant, Newborn MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Geographicals
• Czech Republic MeSH

INTRODUCTION: Depression therapy has been linked to negative effects on energy metabolism, which can be attributed to various factors, including an ongoing inflammatory process commonly seen in metabolic disorders. Unhealthy lifestyle choices of patients and the impact of antidepressants on body weight and lipid and glucose metabolism also contribute to these metabolic side effects. Although not as pronounced as other psychopharmaceuticals, the increasing use of antidepressants raises concerns about their potential impact on public health. The study aimed to evaluate the short- and long-term effects of the antidepressant citalopram and its long-term combination with a special diet on metabolic parameters in mice. METHODS: Animals were randomly divided into 5 groups - control, control + special diet, citalopram (10 mg/kg for 35 days), citalopram + special diet (10 mg/kg for 35 days), and citalopram (10 mg/kg for 7 days). After a described time of administration, animals were anesthetized, blood and fat and liver tissues were collected. Biochemical parameters of lipid metabolism (total cholesterol, HDL cholesterol, LDL cholesterol, triglycerides) and glucose were analyzed using spectrophotometry and relevant adipokines and cytokines were evaluated by ELISA. RESULTS: After a week of application of citalopram, we observed dyslipidemia that persisted even at the end of the 5-week experiment. Furthermore, after 5 weeks of citalopram administration, we observed a significant decrease in body weight gain and decreased leptin levels. Changes in lipid metabolism, higher levels of adipokines leptin and PAI-1 were observed due to the special diet after 5 weeks. CONCLUSIONS: Our research suggests that the effects of citalopram and a diet on the metabolism of mice can be significant, both in the short term (1 week) and in the long term (5 weeks).

• MeSH
• Citalopram * adverse effects   administration & dosage   pharmacology   MeSH
• Diet, High-Fat adverse effects   MeSH
• Dyslipidemias * chemically induced   blood   metabolism   MeSH
• Glucose * metabolism   MeSH
• Liver metabolism   drug effects   MeSH
• Blood Glucose metabolism   drug effects   MeSH
• Leptin * blood   metabolism   MeSH
• Lipids * blood   MeSH
• Lipid Metabolism * drug effects   MeSH
• Mice MeSH
• Animals MeSH
• Check Tag
• Male MeSH
• Mice MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH