The global epidemic of diabetes is of significant concern. Diabetes associated vascular disease signifies the principal cause of morbidity and mortality in diabetic patients. It is also the most rapidly increasing risk factor for cognitive impairment, a silent disease that causes loss of creativity, productivity, and quality of life. Small vessel disease in the cerebral vasculature plays a major role in the pathogenesis of cognitive impairment in diabetes. Endothelin system, including endothelin-1 (ET-1) and the receptors (ETA and ETB), is a likely candidate that may be involved in many aspects of the diabetes cerebrovascular disease. In this review, we took a brain-centric approach and discussed the role of the ET system in cerebrovascular and cognitive dysfunction in diabetes., W. Li, Y. Abdul, R. Ward, A. Ergul., and Seznam literatury
Diabetes increases the risk and worsens the progression of cognitive impairment. The hippocampus is an important domain for learning and memory. We previously showed that endothelin-1 (ET-1) reduced diabetes-induced inflammation in hippocampal neurons, suggesting a neuroprotective effect. Given that neurons and endothelial cells within the neurovascular unit depend on each other for proper function, we investigated the effect of ET-1 on brain-derived neurotrophic factor (BDNF) synthesis, a key neurotrophin and prosurvival factor, in neuronal (HT22 hippocampal neurons) and brain microvascular endothelial (BMEC-5i) cells under normal and diabetes-mimicking (high glucose plus palmitate) conditions. Cells were treated with exogenous ET-1 or ET receptor antagonists including ETB receptor selective antagonist BQ788 (1 μM) or dual-receptor antagonist bosentan (10 μM). Mature (m)BDNF, proBDNF and caspase-3 levels were measured by Western blotting. Diabetic conditions reduced the prosurvival mBDNF/proBDNF ratio in both HT22 and BMEC-5i cells. Addition of exogenous ET-1 had no effect on the BDNF system in HT22 cells in diabetic conditions. Both HT22 and BMEC-5i cells had an increase in the mBDNF/proBDNF ratio when grown in diabetes-simulating conditions in the presence of endothelin receptor inhibition. These data suggest that blockade of ET-1 may provide neuroprotection to hippocampal cells through the modulation of the BDNF system., R. Ward, Y. Abdul, A. Ergul., and Seznam literatury
Endothelial cells (ECs) are primary targets of glucose-induced tissue damage. As a result of hyperglycemia, endothelin-1 (ET-1) is upregulated in organs affected by chronic diabetic complications. The objective of the present study was to identify novel transcriptional mechanisms that influence ET-1 regulation in diabetes. We carried out the investigation in microvascular ECs using multiple approaches. ECs were incubated with 5 mM glucose (NG) or 25 mM glucose (HG) and analyses for DNA methylation, histone methylation, or long non-coding RNA- mediated regulation of ET-1 mRNA were then performed. DNA methylation array analyses demonstrated the presence of hypomethylation in the proximal promoter and 5’ UTR/first exon regions of EDN1 following HG culture. Further, globally blocking DNA methylation or histone methylation significantly increased ET-1 mRNA expressions in both NG and HG-treated HRECs. While, knocking down the pathogenetic lncRNAs ANRIL, MALAT1, and ZFAS1 subsequently prevented the glucose-induced upregulation of ET-1 transcripts. Based on our past and present findings, we present a novel paradigm that reveals a complex web of epigenetic mechanisms regulating glucose-induced transcription of ET-1. Improving our understanding of such processes may lead to better targeted therapies., S. Biswas, B. Feng, A. Thomas, S. Chen, E. Aref-Eshghi, B. Sadikovic, S. Chakrabarti., and Seznam literatury
Enteral nutrition (EN) is a preferred way of feeding in critically ill patients unless obvious contraindications such as ileus or active gastrointestinal bleeding are present. Early enteral nutrition as compared to delayed EN or total parenteral nutrition decreases morbidity in postsurgical and trauma patients. The hepatosplanchnic region plays a pivotal role in the pathophysiology of sepsis and multiple organ dysfunction syndrome. The beneficial effects of EN on splanchnic perfusion and energy metabolism have been documented both in healthy volunteers and animal models of sepsis, hemorrhagic shock and burns. By contrast, EN may increase splanchnic metabolic demands, which in turn may lead to oxygen and/or energy demand/supply mismatch, especially when hyperemic response to EN is not preserved. Therefore, the timing of initiation and the dose of EN in patients with circulatory failure requiring vasoactive drugs are a matter of controversy. Interestingly, the results of recent clinical studies suggest that early enteral nutrition may not be harmful even in patients with circulatory compromise. Nevertheless, possible onset of serious complications, the non-occlusive bowel necrosis in particular, have to be kept in mind. Unfortunately, there is only a limited number of clinically applicable monitoring tools for the effects of enteral nutrition in critically ill patients., R. Rokyta Jr., M. Matějovič, A. Kroužecký, I. Novák., and Obsahuje bibliografii
The incidence of metabolic syndrome increases in the developed countries, therefore biomedical research is focused on the understanding of its etiology. The study of exact mechanisms is very complicated because both genetic and environmental factors contribute to this complex disease. The ability of environmental fac tors to promote phenotype changes by epigenetic DNA modifications (i.e. DNA methylation, histone modifications) was demonstrated to play an important role in the development and predisposition to particular symptoms of metabolic syndrome. There is no doubt that the early life, such as the fetal and perinatal periods, is critical for metabolic syndrome development and therefore critical for prevention of this disease. Moreover, these changes are visible not only in individuals exposed to environmental factor s but also in the subsequent progeny for multiple generations and this phenomenon is called transgenerational inheritance. The knowledge of molecular mechanisms, by which early minor environmental stimuli modify the expression of genetic information, might be the desired key for the understanding of mechanisms leading to the change of phenotype in adulthood. This review provides a short overview of metabolic syndrome epigenetics., J. Kuneš, I. Vaněčková, B. Mikulášková, M. Behuliak, L. Maletínská, J. Zicha., and Obsahuje bibliografii
We investigated how selected electromorphological parameters of myelinated axons influence the preservation of interspike intervals when the propagation of action potentials is corrupted by axonal intrinsic noise. Hereby we tried to determine how the intrinsic axonal noise influences the performance of axons serving as carriers for temporal coding. The strategy of this coding supposes that interspike intervals presented to higher order neurons would minimally be deprived of information included in interspike intervals at the axonal initial segment. Our experiments were conducted using a computer model of the myelinated axon constructed in a software environment GENESIS (GEneral NEural SImulation System). We varied the axonal diameter, myelin sheath thickness, axonal length, stimulation current and channel distribution to determine how these parameters influence the role of noise in spike propagation and hence in preserving the interspike intervals. Our results, expressed as the standard deviation of spike travel times, showed that by stimulating the axons with regular rectangular pulses the interspike intervals were preserved with a microsecond accuracy. Stimulating the axons with pulses imitating postsynaptic currents, greater changes of interspike intervals were found, but the influence of implemented noise on the jitter of interspike intervals was approximately the same., E. Kuriščák, S. Trojan, Z. Wünsch., and Obsahuje bibliografii
a_1 We sought to examine the association between maternal erythrocyte omega-3, omega-6 and trans fatty acids and risk of preeclampsia. We conducted a case-control study of 170 women with proteinuric, pregnancy-induced hypertension and 185 normotensive pregnant women who delivered at Harare Maternity Hospital, Harare, Zimbabwe. We measured erythrocyte omega-3, omega-6 and trans fatty acid as the percentage of total fatty acids using gas chromatography. After multivariate adjustment for confounding factors, women in the highest quartile group for total omega-3 fatty acids compared with women in the lowest quartile experienced a 14 % reduction in risk of preeclampsia (odds ratio 0.86, 95 % confidence interval 0.45 to 1.63). For total omega-6 fatty acids the odds ratio was 0.46 (95 % confidence interval 0.23 to 0.92), although there was suggestion of a slight increase in risk of preeclampsia associated with high levels of arachidonic acid. Among women in the highest quartile for arachidonic acid the odds ratio was 1.29 (95 % confidence interval 0.66 to 2.54). A strong statistically significant positive association of diunsaturated fatty acids with a trans double bond with risk of preeclampsia was observed. Women in the upper quartile of 9-cis 12-trans octadecanoic acid (C18:2n6ct) compared with those in the lowest quartile experienced a 3-fold higher risk of preeclampsia (odds ratio = 3.02, 95 % confidence interval 1.41 to 6.45). Among women in the highest quartile for 9-trans 12-cis octadecanoic acid (C18:2n6tc) the odds ratio was 3.32 (95 % confidence interval 1.55 to 7.13)., a_2 Monounsaturated trans fatty acids were also positively associated with the risk of preeclampsia, although of much reduced magnitude. We observed a strong positive association of trans fatty acids, particularly diunsaturated trans fatty acids, with the risk of preeclampsia. We found little support for the hypothesized in verse association between omega-3 fatty acids and preeclampsia risk in this population. Polyunsaturated fatty acids, particularly omega-3 fatty acids, were comparatively lower in Zimbabwean than among US pregnant women. Given the limited inter-person variation in omega-3 fatty acids among Zimbabwean women, our sample size may be too small to adequately assess the relation in this population., K. Mahomed, M. A. Williams, I. B. King, S. Mudzamiri., and Obsahuje bibliografii a bibliografické odkazy
Escherichia coli (2x104 bacteria) of the non-pathogenic O86 strain or enteropathogenic O55 strain were administered into the pig amniotic cavity at 79 to 86 days of gestation for six or ten hours. Translocation of bacteria into fetal lungs was confirmed by cultivation as well as by light and electron microscopy. Infection caused an influx of macrophages that were immunostained in cryostat sections by monoclonal antibody recognizing calprotectin., I. Šplíchal, I. Trebichavský, A. Šplíchalová, L. Dítětová, M. Zahradníčková., and Obsahuje bibliografii
There is an overlap of carrier-mediated L-amino acid transport and apparent simple diffusion when measured in intestinal brush border membrane vesicles. Using L-threonine and L-glutamine as representative amino acids, this study was undertaken to estimate apparent simple diffusion of L-amino acids and to establish the effective dosage of HgCl2 for completely blocking carrier-mediated L-amino acid transport in porcine jejunal enterocyte brush border membrane vesicles. Jejunal mucosa was scraped from three pigs weighing 26 kg. Enterocyte brush border membrane vesicles, with an average enrichment of 24-fold in sucrase specific activity, were prepared by Mg2+-precipitation and differential centrifugation. In vitro uptake was measured by the fast filtration manual procedure. HgCl2 blocked the carrier-mediated initial transport of L-threonine and L-glutamine under Na+-gradient condition in a dose-dependent manner. At the minimal concentration of 0.165 mmol HgCl2 mg-1 protein, carrier-mediated L-threonine and L-glutamine transport was completely inhibited. The apparent L-threonine and L-glutamine diffusion was estimated to be 8.6±0.7 and 12.4±1.0 % of the total uptake at the substrate concentrations of 5 mM (L-threonine) and 50 mM (L-glutamine). Therefore, the treatment of porcine brush border membrane vesicles with a minimum of 0.165 mmol HgCl2 mg-1 protein completely blocks carrier-mediated L-amino acid transport and enables the direct estimation of apparent L-amino acid diffusion in enterocyte brush border membrane vesicles., M. Z. Fan, O. Adeola, E. K. Asem., and Obsahuje bibliografii
The study investigates the effect of administered estrogen on plasma creatine kinase (CK) and lactate dehydrogenase (LD) levels in female ovariectomized rats after downhill running. Rats ovariectomized before sexual maturity were subcutaneously implanted with pellets containing 17β-estradiol or placebo. Three weeks later they were subjected to a 90-min intermittent downhill running protocol. Blood samples were obtained from the jugular vein immediately after and 72 h after exercise for determination of plasma CK, LD and 17β-estradiol levels. A two-way analysis of variance was used for data evaluation. Plasma CK and LD levels were significantly lower (p<0.05) in the estrogen-supplemented, ovariectomized animals which suggests that less muscle damage occurred compared to the controls immediately and 72 h after exercise. Estrogens may have a protective effect on muscle tissue possibly due to their antioxidant and membrane stabilizing properties., S. Sotiriadou, A. Kyparos, V. Mougios, Ch. Trontzos, G. Sidiras, Ch. Matziari., and Obsahuje bibliografii