Steroid hormones have diverse roles in pregnancy; some help stabilise pregnancy and influence the stability of pregnancy and the onset of labour. Changes and disorders in steroidogenesis may be involved in several pregnancy pathologies. To date, only a few studies have performed a very limited steroid analysis in multiple pregnancies. Our teams investigated multiple pregnancies regarding the biosynthesis, transport, and effects of steroids. We recruited two groups of patients: pregnant women with multiple pregnancies as the study group, and a control singleton pregnancies group. Blood samples were drawn from the participants and analysed. Information about the mother, foetus, delivery, and newborn was extracted from medical records. The data were then analysed. The gestational age of twin pregnancies during delivery ranged from 35 + 3 to 39 + 3 weeks, while it was 38 + 1 to 41 + 1 weeks for the controls. Our findings provide answers to questions regarding the steroidome in multiple pregnancies. Results demonstrate differences in the steroidome between singleton and twin pregnancies. These were based on the presence of two placentae and two foetal adrenal glands, both with separate enzymatic activity. Since every newborn was delivered by caesarean section, analysis was not negatively influenced by changes in the steroid metabolome associated with the spontaneous onset of labour.
- MeSH
- císařský řez MeSH
- kojenec MeSH
- lidé MeSH
- metabolom MeSH
- novorozenec MeSH
- retrospektivní studie MeSH
- steroidy MeSH
- těhotenství s dvojčaty * MeSH
- těhotenství MeSH
- výsledek těhotenství * MeSH
- Check Tag
- kojenec MeSH
- lidé MeSH
- novorozenec MeSH
- těhotenství MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
BACKGROUND: Causative genetic variants cannot yet be found for many disorders with a clear heritable component, including chronic fatigue disorders like myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). These conditions may involve genes in difficult-to-align genomic regions that are refractory to short read approaches. Structural variants in these regions can be particularly hard to detect or define with short reads, yet may account for a significant number of cases. Long read sequencing can overcome these difficulties but so far little data is available regarding the specific analytical challenges inherent in such regions, which need to be taken into account to ensure that variants are correctly identified. Research into chronic fatigue disorders faces the additional challenge that the heterogeneous patient populations likely encompass multiple aetiologies with overlapping symptoms, rather than a single disease entity, such that each individual abnormality may lack statistical significance within a larger sample. Better delineation of patient subgroups is needed to target research and treatment. METHODS: We use nanopore sequencing in a case of unexplained severe fatigue to identify and fully characterise a large inversion in a highly homologous region spanning the AKR1C gene locus, which was indicated but could not be resolved by short-read sequencing. We then use GC-MS/MS serum steroid analysis to investigate the functional consequences. RESULTS: Several commonly used bioinformatics tools are confounded by the homology but a combined approach including visual inspection allows the variant to be accurately resolved. The DNA inversion appears to increase the expression of AKR1C2 while limiting AKR1C1 activity, resulting in a relative increase of inhibitory GABAergic neurosteroids and impaired progesterone metabolism which could suppress neuronal activity and interfere with cellular function in a wide range of tissues. CONCLUSIONS: This study provides an example of how long read sequencing can improve diagnostic yield in research and clinical care, and highlights some of the analytical challenges presented by regions containing tandem arrays of genes. It also proposes a novel gene associated with a novel disease aetiology that may be an underlying cause of complex chronic fatigue. It reveals biomarkers that could now be assessed in a larger cohort, potentially identifying a subset of patients who might respond to treatments suggested by the aetiology.
- MeSH
- biologické markery MeSH
- hydroxysteroidní dehydrogenasy MeSH
- lidé MeSH
- syndrom chronické únavy * MeSH
- tandemová hmotnostní spektrometrie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- kazuistiky MeSH
AIMS: Sufficient visibility of the mucosa during upper endoscopy is crucial for successful diagnosis, especially for early neoplastic lesions. Data documenting the effect of administration of mucolytic solution prior to gastroscopy in order to improve mucosal visibility are limited in Europe. The aim of the study was to assess the score of mucosal visibility in the upper gastrointestinal tract after administration of the mucolytic solution defined by us. PATIENTS AND METHODS: This is a monocentric, double-blind, randomized study involving 134 patients indicated for diagnostic upper endoscopy. Patients were randomly assigned to one of three arms, with mucolytic solution (100 mL water + 400 mg N-acetylcysteine + 20 mg simethicone), without the solution , and with 100 mL pure water. During the examination, 11 photographs were taken in defined areas. The visibility score was given by the sum of the score 0-5 from 5 defined localities evaluated by a blinded endoscopist and subsequently by two blinded endoscopists. Other parameters monitored were examination time and a semiquantitative evaluation of residual gastric fluid. RESULTS: The basic characteristics of the group (sex, age, indications for examination) were comparable between arms. The visibility score was similar in all arms - 17.4 ± 1.9 vs. 17.0 ± 2.0 vs. 17.6 ± 1.8 (P=0.32). The examination time and the amount of residual fluid in the stomach were comparable in all arms. CONCLUSIONS: Administration of the mucolytic solution in our study did not increase the mucosal visibility score in the esophagus, stomach and duodenum. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02967094.
- MeSH
- acetylcystein MeSH
- dvojitá slepá metoda MeSH
- expektorancia * MeSH
- gastrointestinální endoskopie * MeSH
- gastroskopie MeSH
- lidé MeSH
- voda MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- randomizované kontrolované studie MeSH
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.
UNLABELLED: The shape of the glycemic curve during the oral glucose tolerance test (OGTT), interpreted in the correct context, can predict impaired glucose homeostasis. Our aim was to reveal information inherent in the 3 h glycemic trajectory that is of physiological relevance concerning the disruption of glycoregulation and complications beyond, such as components of metabolic syndrome (MS). METHODS: In 1262 subjects (1035 women, 227 men) with a wide range of glucose tolerance, glycemic curves were categorized into four groups: monophasic, biphasic, triphasic, and multiphasic. The groups were then monitored in terms of anthropometry, biochemistry, and timing of the glycemic peak. RESULTS: Most curves were monophasic (50%), then triphasic (28%), biphasic (17.5%), and multiphasic (4.5%). Men had more biphasic curves than women (33 vs. 14%, respectively), while women had more triphasic curves than men (30 vs. 19%, respectively) (p < 0.01). Monophasic curves were more frequent in people with impaired glucose regulation and MS compared to bi-, tri-, and multiphasic ones. Peak delay was the most common in monophasic curves, in which it was also most strongly associated with the deterioration of glucose tolerance and other components of MS. CONCLUSION: The shape of the glycemic curve is gender dependent. A monophasic curve is associated with an unfavorable metabolic profile, especially when combined with a delayed peak.
- Publikační typ
- časopisecké články MeSH
Cílem této části pilotní studie základního výzkumu je objektivizace výsledků vlivu komplexní lázeňské léčebně rehabilitační péče (KLLRP) s přidaným koloběhem a bez něj na změnu délky vybraných kosterních svalů mladších školních dětí věku 6–12 let. K objektivizaci byly použity dva odlišné způsoby: vyšetření testy dle Jandy a vyšetření systémem Computer Kinesiology (CK). Autoři prezentují sumární výsledky z let 2020 a 2021. Shoda výsledků z obou vyšetření u většiny testů poskytuje možnost pro další výzkumy využít pouze systém CK. Sledování hladin slinného kortizolu bylo použito jako objektivního dokladu reaktivity dětí na pohybovou zátěž. Pilotní studie objektivně dle pravidel medicíny založené na důkazech prokázala pozitivní vliv KLLRP na pohybové chování dětí. Lepších výsledků dosahovaly děti s přidaným koloběhem. Statistické vyhodnocení korelačních koeficientů změn hladin slinného kortizolu neprokázaly vztah ke sledovanému parametru změny délky svalů (míře protažení).
The aim of this part of the pilot study of basic research is to objectify the results of the effect of complex spa and rehabilitation treatment with and without added kick scooter riding on the changes in the length of selected skeletal muscles of younger school children (6–12 years). Two different methods were used for objectification: examination by Janda’s tests and examination by the Computer Kinesiology (CK) system. The authors present the summary results from a two-year study (2020 and 2021). The concordance of the results from both examinations for most tests provides the possibility to use only the CK system for further research. Monitoring of salivary cortisol levels was used as objective evidence of children’s reactivity to exercise. A pilot study, according to the rules of evidence-based medicine, objectively showed a positive effect of comprehensive spa and rehabilitation care on children’s movement behavior. Children with added kick scooter activity achieved better results. Statistical evaluation of correlation coefficients of changes in salivary cortisol levels showed no relationship with the observed parameter of muscle length change (stretch rate).
Vitamin D is no longer considered an agent only affecting calcium phosphate metabolism. A number of studies over the past few years have demonstrated its role in immunomodulation and its influence on the development and functioning of the brain and nervous system. In the current epidemiological crisis caused by coronavirus disease 2019 (COVID-19), the immunoprotective role of vitamin D has been discussed by some authors regarding whether it contributes to protection against this serious disease or whether its use does not play a role. Non-standard approaches taken by laboratories in examining the serum levels of the vitamin D metabolite calcidiol have contributed to inconsistent results. We examined the serum of 60 volunteers in the spring and autumn of 2021 who declared whether they were taking vitamin D at the time of sampling. Furthermore, the tested participants noted whether they had experienced COVID-19. A newly developed liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was used to measure calcidiol levels. The analysis of variance (ANOVA) model of Statgraphics Centurion 18 statistical software from Statgraphics Technologies was used for calculations. The results of this study showed that those who took vitamin D suffered significantly less often from COVID-19 than those who did not take vitamin D.
V závislosti na místě jejich aktivity mohou být steroidy rozděleny do dvou skupin – intracelulární a extracelulární. Intracelulární působí jako transkripční faktory, potlačují nebo aktivují expresi genů – mají tzv. genomový efekt, a proto je jejich nástup účinku pomalý. Steroidy působící extracelulárně (negenomový účinek) se vážou na neurotransmiterové receptory umístěné na cytoplazmatické buněčné membráně, a ovlivňují tak propustnost iontových kanálů, přičemž jejich účinek je mnohem rychlejší a označujeme je jako neuroaktivní steroidy či neurosteroidy. Zatímco neuroaktivní steroidy mohou být produkovány v různých tkáních organizmu nebo mohou být aplikovány zvnějšku, neurosteroidy jsou syntetizovány v buňkách nervového systému. Některé neuroaktivní steroidy, jejichž hladiny jsou v těhotenství extrémně zvýšeny (progesteron a jeho metabolity), mají zásadní význam ve stabilizaci těhotenství a změny jejich koncentrace mohou ovlivňovat mechanizmus začátku porodu. Poruchy steroidogeneze se mohou podílet na vzniku celé řady těhotenských patologií, jako jsou předčasný porod, preeklampsie, intrahepatální cholestáza v těhotenství apod. Náš výzkum ve spolupráci s Oddělením steroidů a proteofaktorů Endokrinologického ústavu v Praze se zaměřuje také na zkoumání vícečetných těhotenství z hlediska bio syntézy, transportu a účinku steroidů. Dosavadní studie dostupné v literatuře zatím neposkytly ucelenou analýzu steroidomu u dětí a matek u vícečetného těhotenství. Cílem našeho výzkumu je proto objasnit vztahy mezi plody a matkou a mezi plody vzájemně z hlediska syntézy a transportu steroidů i z hlediska fyziologie a patofyziologie lidského těhotenství a porodu.
Steroid biosynthesis occurs in adrenal, gonadal, brain, liver, and placental tissues. Depending on the location of their activity, steroids can be divided into two groups – intracellular and extracellular. Intracellular ones act as transcription factors, suppressing or activating gene expression – they have a so-called genomic effect and therefore their onset of action is slow. Steroids acting extracellularly (non-genome effect) bind to neurotransmitter receptors located on the cytoplasmic cell membrane and thus affect the permeability of the ion channels, the effect of which is much faster, and we refer to them as neuroactive steroids or neurosteroids. While neuroactive steroids can be produced in different tissues of the body, or can be administered externally, neurosteroids are synthetized in cells of the nervous system. Some neuroactive steroids whose levels are extremely elevated in pregnancy (progesterone and its metabolites) are crucial in stabilizing pregnancy and changes in their concentration may influence the onset of parturition. Steroidogenic disorders may be involved in a number of pregnancy pathologies such as premature birth, pre-eclampsia, intrahepatic cholestasis in pregnancy, etc. Our research in collaboration with the Department of Steroids and Proteofactors of the Institute of Endocrinology in Prague also focuses on the investigation of multiple pregnancies in terms of biosynthesis, transport, and the effects of steroids. Studies available in the literature so far have not provided a comprehensive analysis of the steroidome in children and mothers in multiple pregnancies. The aim of our research is therefore to clarify the relationships between fetuses and mothers and between fetuses from the point of view of steroid synthesis and transport as well as the physiology and pathophysiology of human pregnancy and childbirth.
- MeSH
- komplikace těhotenství MeSH
- lidé MeSH
- neurosteroidy * MeSH
- steroidy * metabolismus MeSH
- těhotenství mnohočetné * MeSH
- těhotenství MeSH
- Check Tag
- lidé MeSH
- těhotenství MeSH
- ženské pohlaví MeSH
- Publikační typ
- přehledy MeSH
Progesterone is a steroid hormone traditionally linked with female fertility and pregnancy. In current reproductive medicine, progesterone and its analogues play crucial roles. While the discovery of its effects has a long history, over recent decades, various novel actions of this interesting steroid have been documented, of which its neuro- and immunoprotective activities are the most widely discussed. Discoveries of the novel biological activities of progesterone have also driven research and development in the field of progesterone analogues used in human medicine. Progestogen treatment has traditionally and predominately been used in maintaining pregnancy, the prevention of preterm labor, various gynecological pathologies, and in lowering the negative effects of menopause. However, there are also various other medical fields where progesterone and its analogues could find application in the future. The aim of this work is to show the mechanisms of action of progesterone and its metabolites, the physiological and pharmacological actions of progesterone and its synthetic analogues in human medicine, as well as the impacts of its production and use on the environment.
- MeSH
- hormony MeSH
- lidé MeSH
- novorozenec MeSH
- progesteron * farmakologie fyziologie MeSH
- progestiny * farmakologie terapeutické užití MeSH
- těhotenství MeSH
- Check Tag
- lidé MeSH
- novorozenec MeSH
- těhotenství MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
The fatty acid composition is associated with obesity. Omega 3 polyunsaturated fatty acid (PUFA) could have a beneficial role in the prevention and treatment of many disorders, including cardiometabolic diseases. A cohort of 84 men and 131 women were examined in adolescence and after 8 years. Body weight (BW) and fat mass (FM) were measured. The composition of fatty acids (FAs) of serum phospholipids was assessed using gas chromatography. Statistics: PLS method. Aim: to determine the relationships between FAs in adolescence and FM (explanatory variable 1, EV1) and BW (explanatory variable 2, EV2) in adulthood. In the predictive models, a cluster of FAs in boys explained 47.2 % of EV1 and a cluster of 6 FAs in girls explained 32.3 % of EV1 measured in adulthood. FAs measured in adolescents explained 23.7 % of EV2 in early adults regardless of gender. A significant negative association was found between 18:1n-9c and EV1 in males and EV2 in both genders. We found a significant negative association between 18:2n-6 and 20:0 and both EV1 and EV2. In all analyses, we found a significant negative association of 20:1n-9 and 18:3n-3 with EV1-2 in both genders. A significant positive association was found in 20:3n-6 with EV1 and EV2 in males. 20:4n-6 was positively associated with EV1 in females and EV2 in both genders. A positive association between FM and very long chain n- 6 PUFAs was also observed. It is concluded that serum MUFAs and essential PUFAs in adolescence are associated with lower BW and FM in adulthood.
- MeSH
- dospělí MeSH
- fosfolipidy MeSH
- kyseliny mastné omega-3 * MeSH
- lidé MeSH
- mastné kyseliny * MeSH
- mladiství MeSH
- následné studie MeSH
- nenasycené mastné kyseliny MeSH
- složení těla MeSH
- tělesná hmotnost MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- mladiství MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
