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192. The expression levels of Notch-related signaling molecules in pulmonary microvascular endothelial cells in bleomycin-induced rat pulmonary fibrosis
- Creator:
- Yin, Q., Wang, W., Cui, G., Nan, H., Yan, L., Zhang, W., Zhang, S., and Wei, J.
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- article, články, journal articles, model:article, and TEXT
- Subject:
- Fyziologie člověka a srovnávací fyziologie, plicní fibróza, pulmonary fibrosis, Notch1, Jagged1, Dll4, beomycin, pulmonary microvascular endothelial cells, 14, and 612
- Language:
- English
- Description:
- Previous studies have suggested that the Notch signaling pathway plays a very important role in the proliferation and differentiation of pulmonary microvascular endothelial cells (PMVECs). Therefore, we aimed to investigate the expression level of Notch-related signaling molecules in PMVECs in bleomycin (BLM)-induced rat pulmonary fibrosis. Immunohistochemistry, immunofluorescence, Western blotting, and real-time PCR were used to analyze the differences in protein and mRNA expression levels of Notch-related signaling molecules, i.e. Notch1, Jagged1, Delta-like ligand 4 (Dll4), and hairy and enhancer of split homolog 1 (Hes1), between a control group treated with intratracheal instillation of saline and a study group treated with intratracheal instillation of BLM solution. Expression levels of the receptor Notch1 and one of its ligands, Jagged1, were upregulated, while the expression levels of the ligand Dll4 and the target molecule of the Notch signaling pathway, Hes1, were downregulated. The differences in protein and mRNA expression levels between the control and study groups were significant (p<0.001). The Jagged1/Notch1 signaling pathway is activated in the pathogenesis of BLM-induced rat pulmonary fibrosis, while the Dll4/Notch1 signaling pathway is inhibited, which inhibits the suppressive effect of Dll4/Notch1 signaling on PMVEC overproliferation, further causing PMVEC dysfunction in cell sprouting and maturation as well as abnormal differentiation of the cell phenotype. Conversely, the downexpression of Hes1 indicates that the Jagged1/Notch1 signaling pathway could be a non-canonical Notch signaling pathway independent of Hes1 activation, which differs from the canonical Dll4/Notch1 signaling pathway., Q. Yin, W. Wang, G. Cui, H. Nan, L. Yan, W. Zhang, S. Zhang, J. Wei., and Obsahuje bibliografii
- Rights:
- http://creativecommons.org/publicdomain/mark/1.0/ and policy:public
193. The impact of selected dytokines in the follow-up of normal pressure hydrocephalus
- Creator:
- Sosvorova, L., Milan Mohapl, Josef Včelák, Hill, M., Vítků, J., and Richard Hampl
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- article, články, model:article, and TEXT
- Subject:
- Fyziologie člověka a srovnávací fyziologie, cytokiny, mozkomíšní mok, neurodegenerace, cytokines, cerebrospinal fluid, neurodegeneration, normal pressure hydrocephalus, ventriculoperitoneal shung, 14, and 612
- Language:
- English
- Description:
- Cytokines are widely known mediators of inflammation accompanying many neurodegenerative disorders including normal pressure hydrocephalus (NPH). NPH is caused by impaired cerebrospinal fluid (CSF) reabsorption and treated by surgical shunt insertion. The diagnostics is still complicated and the shunt effect is not durable; after several years, dementia may develop. In the clinical practice, biomarkers support the diagnostics as well as the further time course of many neurodegenerative diseases. Until recently, no reliable biomarker for NPH was evaluated. The attempt of this review was to make a survey concerning cytokines as possible NPH markers. Among all reviewed cytokines, the most promising are CSF IL-10 and IL-33, enabling to follow-up the disease progression and monitoring the effectiveness of the shunt insertion., L. Sosvorova, M. Mohapl, J. Vcelak, M. Hill, J. Vitku, R. Hampl., and Obsahuje bibliografii
- Rights:
- http://creativecommons.org/publicdomain/mark/1.0/ and policy:public
194. The importance of the selection of appropriate reference genes for gene expression profiling in adrenal medulla or sympathetic ganglia of spontaneously hypertensive rat
- Creator:
- Vavřínová, A., Michal Behuliak, and Josef Zicha
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- Subject:
- Fyziologie člověka a srovnávací fyziologie, sympatický nervový systém, sympathetic nervous system, adrenal medulla, gene expression profiling, reference gene selection, 14, and 612
- Language:
- English
- Description:
- Catecholaminergic system plays an important role in hypertension development. The available results on mRNA expression of catecholaminergic system genes in spontaneously hypertensive rats (SHR) are often contradictory. One of the possible causes might be the use of various reference genes as internal controls. In the present study, we searched for suitable reference genes in adrenal medulla or sympathetic ganglia of SHR and Wistar-Kyoto (WKY) rats, which would enable reliable comparison of mRNA expression between these two strains. The mRNA expression was measured by quantitative real-time PCR in adrenal medulla and superior cervical ganglia of 4-week-old or 24-week-old SHR and WKY rats. We evaluated 12 reference genes by three software tools (Normfinder, BestKeeper, geNorm) and compared them for the standardization of mRNA expression. Combination of reference genes Hprt1 and Ywhaz in adrenal medulla and Gapdh and 18S in sympathetic ganglia were chosen as the best ones. 18S was found as applicable reference gene in both tissues. We found many alterations in expression of catecholaminergic system genes in adrenal medulla and sympathetic ganglia of SHR. The usage of the most or the least stable reference gene as internal control changed results moderately in sympathetic ganglia but seriously in adrenal medulla. For example, tyrosine hydroxylase (Th) gene was underexpressed in adrenal medulla of adult SHR using the appropriate reference gene but unchanged after the standardization to the least stable reference gene. Our results indicate the importance of appropriate internal control. The suitability of reference genes should be checked again in the case of change in experimental conditions., A. Vavřínová, M. Behuliak, J. Zicha., and Obsahuje bibliografii
- Rights:
- http://creativecommons.org/publicdomain/mark/1.0/ and policy:public
195. The in vivo effects of adenine-induced chronic kidney disease on some renal and hepatic function and CYP450 metabolizing enzymes
- Creator:
- Al Za’abi, M., Shalaby, A., Manoj, P., and Ali, B. H.
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- article, články, journal articles, model:article, and TEXT
- Subject:
- Fyziologie člověka a srovnávací fyziologie, metabolismus léčiv, drug metabolism, adenine, cytochrome P450, chronic kidney disease, 14, and 612
- Language:
- English
- Description:
- Adenine-induced model of chronic kidney disease (CKD) is a widely used model especially in studies testing novel nephroprotective agents. We investigated the effects of adenineinduced CKD in rats on the activities of some xenobiotic metabolizing enzymes in liver and kidneys, and on some in vivo indicators of drug metabolism (viz pentobarbitone sleeping time, and plasma concentration of theophylline 90 min post administration). CKD was induced by orally feeding adenine (0.25 % w/w) for 35 days. Adenine induced all the characteristics of CKD, which was confirmed by biochemical and histological findings. Glutathione concentration and activities of some enzymes involved in its metabolism were reduced in kidneys and livers of rats with CKD. Renal CYP450 1A1 activity was significantly inhibited by adenine, but other measured isoenzymes (1A2, 3A4 and 2E1) were not significantly affected. Adenine significantly prolonged pentobarbitone-sleeping time and increased plasma theophylline concentration 90 min post administration. Adenine also induced a moderate degree of hepatic damages as indicated histologically and by significant elevations in some plasma enzymes. The results suggest that adenine-induced CKD is associated with significant in vivo inhibitory activities on some drug-metabolizing enzymes, with most of the effect on the kidneys rather than the liver., M. Al Za’abi, A. Shalaby, P. Manoj, B. H. Ali., and Obsahuje bibliografii
- Rights:
- http://creativecommons.org/publicdomain/mark/1.0/ and policy:public
196. The influence of smoking and cessation on the human reproductive hormonal balance
- Creator:
- Jandíková, H., Michaela Dušková, and Luboslav Stárka
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- Type:
- article, články, journal articles, model:article, and TEXT
- Subject:
- Fyziologie člověka a srovnávací fyziologie, kouření, steroidy, plodnost, smoking, steroids, fertility, anti-estrogenic effect, 14, and 612
- Language:
- English
- Description:
- Smoking is the most widespread substance dependence in the world. Nicotine and some other components of the cigarette smoke cause various endocrine imbalances, and have negative effects on pituitary, thyroid, adrenal, testicular and ovarian functions. Here, we examined studies that describe the influence of smoking and smoking cessation on the male and female reproductive systems. We also focused on studies providing an account of differences in cessation success rates between men and women. In men, the most common effects associated with smoking are erectile dysfunction and decreasing spermiogram quality. Several groups have studied the effects of cigarette smoking on testosterone levels in men. However, the results have been conflicting. In women, nicotine has an antiestrogen effect and increases the ratio of androgens to estrogens throughout life. Beside nicotine, other cigarette toxins also cause dysregulation of reproductive and hormonal system, and essentially influence the probability of a successful pregnancy not only in cases of assisted reproduction but also in healthy women. Tobacco addiction is one of the forms of addiction that are generally thought to be different for men and for women. Women are less successful than men in quitting smoking, and nicotine replacement therapy is less effective in female smokers. We also summarize recent studies that have indicated possible reasons., H. Jandíková, M. Dušková, L. Stárka., and Obsahuje bibliografii
- Rights:
- http://creativecommons.org/publicdomain/mark/1.0/ and policy:public
197. The labile iron pool in monocytes reflects the activity of the atherosclerotic process in men with chronic cardiovascular disease
- Creator:
- Riško, P., Jan Pláteník, Buchal, R., Jana Potočková, and Kraml, P. J.
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- article, články, model:article, and TEXT
- Subject:
- Fyziologie člověka a srovnávací fyziologie, záněty, inflammations, iron overload, monocytes, arterial stiffness, 14, and 612
- Language:
- English
- Description:
- The study investigates the relationship between the labile iron pool (LIP) in circulating monocytes and markers of iron metabolism, inflammation, oxidative stress, endothelial dysfunction and arterial elasticity in patients with chronic cardiovascular disease and in healthy volunteers. The patie nts with a history of CVEs had significantly higher LIP values tha n did the control group (1.94± 0.46 μM vs. 1.62 ±0.49 μM, p=0.02). Except for the leukocyte number (WBCs), the groups did not differ in other inflammatory markers (CRPus, CD 163, MPO, MMP-1). Similarly, there were no differences in the markers of endothelial dysfunction (ICAM, VCAM, E-selectin, vWF). The CVE group had higher pulse pressures, levels of markers of impaired arterial elasticity (AI, Young's modulus, pulsatility, stiffness index), I MT values and ABI values. The LIP concentration was significantly correlated with the transferrin receptor⁄ferritin ratio, hepcidin levels, VFT content and the ABI and ET values. Patients with a history of CVE have significantly higher concentrations of ir on in their intracellular LIP in circulating monocytes than do healthy controls. The independent and significant correlation of LIP with markers of the progression of atherosclerosis and arterial stiffness suggests LIP as a possible novel marker of atheros clerotic activity., P. Riško, J. Pláteník, R. Buchal, J. Potočková, P. J. Kraml., and Obsahuje bibliografii
- Rights:
- http://creativecommons.org/publicdomain/mark/1.0/ and policy:public
198. The molecular genetic background of familial hypercholesterolemia: data from the Slovak nation-wide survey
- Creator:
- Gabčová, D., Branislav Vohnout, Staníková, D., Hučkova, M., Kadurová, M., Debreová, M., Kozárová, M., Ľubomíra Fábryová, Juraj Staník, Iwar Klimeš, Katarína Rašlová, and Gašperiková, D.
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- Subject:
- Fyziologie člověka a srovnávací fyziologie, familiární hypercholesterolémie, familial hypercholesterolemia, Slovensko, Slovakia, FH, LDLR, APOB, 14, and 612
- Language:
- English
- Description:
- Familial hypercholesterolemia (FH) is most frequently caused by LDLR or APOB mutations. Therefore, the aim of our study was to examine the genetic background of Slovak patients suspected of FH. Patients with clinical suspicion of FH (235 unrelated probands and 124 family relatives) were recruited throughout Slovakia during the years 2011-2015. The order of DNA analyses in probands was as follows: 1. APOB mutation p.Arg3527Gln by real-time PCR method, 2. direct sequencing of the LDLR gene 3. MLPA analysis of the LDLR gene. We have identified 14 probands and 2 relatives with an APOB mutation p.Arg3527Gln, and 89 probands and 75 relatives with 54 different LDLR mutations. Nine of LDLR mutations were novel (i.e. p .Asp90Glu, c.314-2A>G, p.Asp136Tyr, p.Ser177Pro, p.Lys225_Glu228delinsCysLys, p.Gly478Glu, p.Gly675Trpfs*42, p.Leu680Pro, p.Thr832Argfs*3). This is the first study on molecular genetics of FH in Slovakia encompassing the analysis of whole LDLR gene. Geneti c etiology of FH was confirmed in 103 probands (43.8 %). Out of them, 86.4 % of probands carried the LDLR gene mutation and remaining 13.6 % probands carried the p.Arg3527Gln APOB mutation., D. Gabčová, B. Vohnout, D. Staníková, M. Hučkova, M. Kadurová, M. Debreová, M. Kozárová, Ľ. Fábryová, Slovak FH Study Group, J. Staník, I. Klimeš, K. Rašlová, D. Gašperiková., and Obsahuje bibliografii
- Rights:
- http://creativecommons.org/publicdomain/mark/1.0/ and policy:public
199. The origin of 7α-hydroxy-dehydroepiandrosterone and its physiological role: a history of discoveries
- Creator:
- Luboslav Stárka
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- article, články, journal articles, model:article, and TEXT
- Subject:
- Fyziologie člověka a srovnávací fyziologie, fyziologie, physiology, 11β-hydroxysteroid dehydrogenase, CYP7B, immunomodulatory effects, occurrence, dehydroepiandrosterone, 7α-hydroxy-dehydroepiandrosterone, neurosteroid, 14, and 612
- Language:
- English
- Description:
- Nearly 60 years has elapsed since the first isolation and identification of 7α-hydroxy-dehydroepiandrosterone, and in that time much information has been gained on its occurrence, metabolism, ontogeny, immunomodulatory activity, cell proliferation, cortisol control in local tissues and neuroactivity. Additional knowledge about this steroid may elucidate its role in obesity, neurodegenerative disturbances such as Alzheimer’s disease, or psychiatric disorders such as schizophrenia or depression. This review aims to provide a comprehensive summary of the available literature on 7α-hydroxydehydroepiandrosterone., L. Stárka., and Obsahuje bibliografii
- Rights:
- http://creativecommons.org/publicdomain/mark/1.0/ and policy:public
200. The pH-dependent and enzymatic release of cytarabine from hydrophilic polymer conjugates
- Creator:
- Pola, R., Olga Janoušková, and Tomáš Etrych
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- Subject:
- Fyziologie člověka a srovnávací fyziologie, fyziologie, physiology, HPMA copolymers, drug delivery system, nucleoside analogues, cytarabine, 14, and 612
- Language:
- English
- Description:
- Cytarabine is one of the most efficient drugs in the treatment of hematological malignancies. In this work, we describe the synthesis and characterization of two different polymer conjugates of cytarabine that were designed for the controlled release of cytarabine within the leukemia cells. Reactive copolymers of N-(2-hydroxypropyl)methacrylamide (HPMA) and 3-(3-methacrylamidopropanoyl)thiazolidine-2-thione) or 3-(Nmethacryloylglycyl- phenylalanylleucylglycyl)thiazolidine-2-thione were used in the study as reactive polymer precursors for reaction with cytarabine. The enzymatic release of cytarabine from the conjugate containing a GFLG spacer utilizing cathepsin B was verified. In addition to enzymolysis, the pH-dependent hydrolysis of cytarabine from both copolymers was also confirmed. Approximately 40 % and 20 % of the drug was released by spontaneous hydrolysis at pH 7.4 within 72 h from the polymer conjugates with the GFLG and β-Ala spacers, respectively. At pH 6.0, the spontaneous hydrolysis slowed down, and less than 10 % of the drug was liberated within 72 h. The results of the cytotoxicity evaluation of the polymer conjugates in vitro against various cell lines showed that the cytotoxicity of the polymer conjugates is approximately three times lower in comparison to free cytarabine., R. Pola, O. Janoušková, T. Etrych., and Obsahuje bibliografii
- Rights:
- http://creativecommons.org/publicdomain/mark/1.0/ and policy:public