Прояви надмірної денної сонливості і рівень греліну при гастроезофагеалі-рефлюксній хворобі у пацієнтів з недиференційованими захворюваннями сполучних тканин

The aim of the study was to discover the interrelation between the severity of gastroesophageal reflux disease (GERD) symptoms, acid exposure time (AET), excessive daytime sleepiness (EDS) and the level of active blood plasma ghrelin in the patients with undifferentiated connective tissue disease (UCTD). Materials and methods: The study included 120 patients with GERD. All the patients were divided in two groups: Group I - GERD was not accompanied by the signs of connective tissue disease (n=45) and Group II - GERD developed on the background of UCTD syndrome (n=75). Daily transnasal pH monitoring wasperformed to determine the nature of pathological refluxes. EDS was detected by The Epworth Sleepiness Scale. Active ghrelin in blood plasma samples was determined by ELISA. Results:80% of the patients of Group II and 35.48% of Group I suffered from EDS (p<0.05). The mean daily AET index was 5.48±0.4% in Group II and 6±0.2% in Group I, in the night hours mostly when patients were in the upright position. This phenomenon contributed to a deterioration of sleep quality and the appearance of EDS and was supported by a connection between AET and EDS (r=+0.827 for Group I and r=+0.768 for Group II). The mean De Meester index was higher in the patients of Group II (23.01±2.24 in Group I vs 31.08±2.4 in Group II; p<0.05). Conclusions: GERD manifestationsare strongly related to the level to AET and intensity of EDS. The EDS symptoms depend on circulating ghrelin level.Метою дослідження було виявити взаємозв'язок між тяжкістю симптомів гастроезофагеальної рефлюксної хвороби (ГЕРХ), часом впливу кислоти (AET), надмірною денною сонливістю (ЕЦП) та рівень активного греліну в плазмі крові у пацієнтів з недиференційованим захворюваннями сполучної тканини (УКТД). Матеріали та методи: У дослідженні взяли участь 120 пацієнтів з ГЕРХ. Всі пацієнти були розділені на дві групи: I група - ГЕРХ не супроводжувалася ознаками сполучної захворювання тканин (n = 45) і II група - ГЕРХ, що розвивається на тлі синдрому UCTD (n = 75). Щоденний моніторинг приназального рН був проведений для визначення характеру патологічні рефлюкси. ЕЦП був виявлений за шкалою сонливості Епворта. Активний грелін у зразках плазми крові визначався методом ІФА. Результати: 80% пацієнтів ІІ групи та 35,48% І групи страждали на ЕДС (р<0,05). Середній добовий індекс AET становив 5,48±0,4% у ІІ групі та 6±0,2% у І групі в нічні години. переважно, коли пацієнти перебували у вертикальному положенні. Це явище сприяло погіршенню якості сну та появі ЕЦП і підтримувалося зв’язком між AET та EDS (r=+0,827 для групи I та r=+0,768 для групи II). Середній індекс Де Містера був вищим у пацієнтів ІІ групи (23,01±2,24 у І групі проти 31,08±2,4 у ІІ групі; p<0,05). Висновки. Прояви ГЕРХ тісно пов'язані з рівнем АЕТ та інтенсивністю ЕДС. Симптоми EDS залежать від рівня циркулюючого греліну

Impaired spatial performance in cerebellar-deficient Lurcher mice is not associated with their abnormal stress response

International audienceBoth humans and laboratory animals suffering from cerebellar lesions exhibit cognitive as well as many emotional and behavioral abnormalities. These latter have been already observed in the cerebellar mutant mice currently used to highlight some aspect of autism spectrum disorders. The aim of this study was to investigate the influence of cerebellar-related stress response abnormalities on spatial learning and memory. Cerebellar-deficient Lurcher mutant mice were exposed to water environment without active escape possibility and then tested for spatial learning in the Morris water maze. As a marker of stress intensity we measured corticosterone in urine. Finally, the volumes of individual components of the adrenal gland were estimated. Though having spatial navigation deficit in the water maze, Lurcher mice preserved a substantial residuum of learning capacity. Lurcher mutants had a higher increase of cor-ticosterone level after exposure to the water environment than wild type mice. We did not observe any decrease of this physiological stress marker between the start and the end of the spatial navigation task, despite significant improvement of behavioral performances. Furthermore, zona fasciculata and zona reticularis of the adrenal cortex as well as the adrenal medulla were larger in Lurcher mice, reflecting high stress reactivity. We conclude that for both genotypes water exposure was a strong stressor and that there was no habituation to the experiment independently to the increasing controllability of the stressor (e.g. ability to find the escape platform). Based on these findings, we suggest that the enhanced stress response to water exposure is not the main factor explaining the spatial deficits in these cerebellar mutant mice

Multi-Step Clustering Approach of Myelinated Nerve Fibers in Experimental Neuromorphology

Indexed keywords SciVal Topics Metrics Abstract One of the unresolved issues in experimental neuromorphology is searching for a solution for myelinated nerve fibers clustering on set of morphometric parameters. Therefore, in this article, a new approach for cluster analysis of myelinated fibers is proposed based on their morpho-functional features. The proposed clustering approach was developed in R software environment and uses model-based clustering, which is performed in few steps with increasing number of morphometric parameters on each next step. Applying the proposed clustering solution shown high similarity of identified groups' morphometric parameters with respective physiological types of myelinated A-fibers. This fact, in addition to the algorithm implementation simplicity, facilitates its use on identifying clusters of myelinated fibers that represent different myelinated fibers subpopulation in experimental neuromorphological research with high level of reliability. (c) 2021, IGI Global

Low Doses of Bisphenol S Affect Post-translational Modifications of Sperm Proteins in Male Mice

Background: Bisphenol S (BPS) is increasingly used as a replacement for bisphenol A in the manufacture of products containing polycarbonates and epoxy resins. However, further studies of BPS exposure are needed for the assessment of health risks to humans. In this study we assessed the potential harmfulness of low-dose BPS on reproduction in male mice. Methods: To simulate human exposure under experimental conditions, 8-week-old outbred ICR male mice received 8 weeks of drinking water containing a broad range of BPS doses [0.001, 1.0, or 100 µg/kg body weight (bw)/day, BPS1-3] or vehicle control. Mice were sacrificed and testicular tissue taken for histological analysis and protein identification by nano-liquid chromatography/mass spectrometry (MS) and sperm collected for immunodetection of acetylated lysine and phosphorylated tyrosine followed by protein characterisation using matrix-assisted laser desorption ionisation time-of-flight MS (MALDI-TOF MS). Results: The results indicate that compared to vehicle, 100 µg/kg/day exposure (BPS3) leads to 1) significant histopathology in testicular tissue; and, 2) higher levels of the histone protein γH2AX, a reliable marker of DNA damage. There were fewer mature spermatozoa in the germ layer in the experimental group treated with 1 µg/kg bw (BPS2). Finally, Western blot and MALDI-TOF MS studies showed significant alterations in the sperm acetylome and phosphorylome in mice treated with the lowest (BPS1) exposure (0.001 µg/kg/day). Conclusions: In summary, this range of qualitative and quantitative findings in young male mice raise the possibility that relatively low doses of BPS may impair mammalian reproduction through epigenetic modifications of sperm proteins

Mesenchymal Stromal Cell Therapy in Novel Porcine Model of Diffuse Liver Damage Induced by Repeated Biliary Obstruction

In liver surgery, biliary obstruction can lead to secondary biliary cirrhosis, a life-threatening disease with liver transplantation as the only curative treatment option. Mesenchymal stromal cells (MSC) have been shown to improve liver function in both acute and chronic liver disease models. This study evaluated the effect of allogenic MSC transplantation in a large animal model of repeated biliary obstruction followed by partial hepatectomy. MSC transplantation supported the growth of regenerated liver tissue after 14 days (MSC group, n = 10: from 1087 ± 108 (0 h) to 1243 ± 92 mL (14 days); control group, n = 11: from 1080 ± 95 (0 h) to 1100 ± 105 mL (14 days), p = 0.016), with a lower volume fraction of hepatocytes in regenerated liver tissue compared to resected liver tissue (59.5 ± 10.2% vs. 70.2 ± 5.6%, p &lt; 0.05). Volume fraction of connective tissue, blood vessels and bile vessels in regenerated liver tissue, serum levels of liver enzymes (AST, ALT, ALP and GGT) and liver metabolites (albumin, bilirubin, urea and creatinine), as well as plasma levels of IL-6, IL-8, TNF-α and TGF-β, were not affected by MSC transplantation. In our novel, large animal (pig) model of repeated biliary obstruction followed by partial hepatectomy, MSC transplantation promoted growth of liver tissue without any effect on liver function. This study underscores the importance of translating results between small and large animal models as well as the careful translation of results from animal model into human medicine

Low doses of Bisphenol S affect post-translational modifications of sperm proteins in male mice

[Background]: Bisphenol S (BPS) is increasingly used as a replacement for bisphenol A in the manufacture of products containing polycarbonates and epoxy resins. However, further studies of BPS exposure are needed for the assessment of health risks to humans. In this study we assessed the potential harmfulness of low-dose BPS on reproduction in male mice.[Methods]: To simulate human exposure under experimental conditions, 8-week-old outbred ICR male mice received 8 weeks of drinking water containing a broad range of BPS doses [0.001, 1.0, or 100 μg/kg body weight (bw)/day, BPS1–3] or vehicle control. Mice were sacrificed and testicular tissue taken for histological analysis and protein identification by nano-liquid chromatography/mass spectrometry (MS) and sperm collected for immunodetection of acetylated lysine and phosphorylated tyrosine followed by protein characterisation using matrix-assisted laser desorption ionisation time-of-flight MS (MALDI-TOF MS).[Results]: The results indicate that compared to vehicle, 100 μg/kg/day exposure (BPS3) leads to 1) significant histopathology in testicular tissue; and, 2) higher levels of the histone protein γH2AX, a reliable marker of DNA damage. There were fewer mature spermatozoa in the germ layer in the experimental group treated with 1 μg/kg bw (BPS2). Finally, western blot and MALDI-TOF MS studies showed significant alterations in the sperm acetylome and phosphorylome in mice treated with the lowest exposure (0.001 μg/kg/day; BPS1), although the dose is several times lower than what has been published so far.[Conclusions]: In summary, this range of qualitative and quantitative findings in young male mice raise the possibility that very low doses of BPS may impair mammalian reproduction through epigenetic modifications of sperm proteins.This study was supported by the Czech Health Research Council (grant no. NV18–01-00544); the Charles University Research Fund (Progres Q39); the National Sustainability Programme I (NPU I) Nr. LO1503 provided by the Ministry of Education, Youth and Sports of the Czech Republic (MEYS CR); project no. SVV 02690 awarded by MEYS CR; and project no. CZ.02.1.01/0.0/0.0/16_019/0000787 “Fighting Infectious Diseases“, awarded by MEYS CR and financed by The European Regional Development Fund, European Human Biomonitoring Initiative HBM4EU provided by H2020, and the United States Fulbright Commission (P001496 grant to P.R.M.).Peer reviewe