The relationship of cytokine status with left ventricular hypertrophy in patients with arterial hypertension

Aim. To study the relationship of tumor necrosis factor α and interleukin-10 levels with the presence of left ventricular hypertrophy and myocardial remodeling in patients with arterial hypertension. Metods. 156 patients with hypertension aged 40 to 75 years (mean age 55.8±7.5 years), including 57 women and 99 men were examined. All patients were divided into two groups. Group 1 included 83 patients without left ventricular hypertrophy (55.5±7.5 years), group 2 included 73 patients with left ventricular hypertrophy (56.2±7.8 years), established by echocardiographic signs. All patients in addition to the general clinical examination and biochemical studies had echocardiography and Doppler echocardiography performed, as well as measurement of the concentration of tumor necrosis factor α and interleukin-10 by solid-phase enzyme immunoassay using specialized «Cytokine-Stimulus-Best» kit (Novosibirsk, Russia). Results. The concentration of tumor necrosis factor α in patients without left ventricular hypertrophy was 8.43±1.36 pg/ml and was comparable with the concentration of this cytokine in patients with left ventricular hypertrophy (8.54±1.58 pg/ml, p >0.05). This pattern was typical for both men and women. The concentration of interleukin-10 in both groups was also comparable (15.4±3.6 pg/ml in group 1 and 14.7±3.4 pg/ml in group 2, p >0.05). However, we identified gender-specific features in the relationship of interleukin-10 with the presence of left ventricular hypertrophy in patients with hypertension. Thus, while in women the concentration of cytokine in groups with/without left ventricular hypertrophy did not differ significantly, in men without hypertrophy the level of interleukin-10 of 15.7±3.6 pg/ml, was significantly higher than the value of the same indicator in the group of men with left ventricular hypertrophy (14.8±2.9 pg/ml, p <0.025). Multivariate regression analysis showed that tumor necrosis factor α and interleukin-10 concentrations correlated to left ventricular wall thickness in patients without left ventricular hypertrophy. No such pattern was revealed for patients with hypertrophy. Conclusion. The results demonstrate the modulating role of tumor necrosis factor α and interleukin-10 in myocardial remodeling processes in arterial hypertension

Age and gender aspects of the association of generalized obesity with development of fatal and nonfatal cardiovascular events (results of the prospective cohort study “Interepepid”)

Background. Currently, obesity has become one of the most important medical and social problems in the world due to its high prevalence. Numerous literature data indicate that high BMI is associated with increased mortality from cardiovascular diseases.The aim: to study the relationship between overweight and generalized obesity with the development of fatal and non-fatal cardiovascular events among residents of the Chui region of the Kyrgyz Republic, taking into account gender and age.Material and methods. This study was carried out as part of the international crosssectional epidemiological study “Interepid”. The total follow-up period was 7 years. Life status at the end of the follow-up period was monitored in 1096 respondents out of 1341 initial cohorts (response – 82.1 %). The endpoints were cases of fatal and non-fatal cardiovascular events. The frequency of events was assessed using methods of analysis of survival (Cox proportional hazard regression model, parametric survival models, survival by the Kaplan – Meier method).Results. A total of 181 cases of fatal and non-fatal cardiovascular events (16.44 %) were recorded during the follow-up. In persons with normal body weight, the incidence of cardiovascular complications was 10 %. In overweight individuals, the value of this indicator increased and reached 17.99 % (p˂ 0.001), and in individuals with obesity – 24.5 % (p˂ 0.0001). The increase in the frequency of events with the increase in body mass index did not depend on the gender of the respondents but was typical only for people under 60 years of age. For elderly patients, there was no relationship between BMI and the development of cardiovascular complications. In contrast, the relative risk had an insignificant tendency to decrease by 2.6 % for every 1 kg/m2 increase in body mass index (RR – 0.974; 95% CI: 0.924–1.025).Conclusion. The increase of body mass index above 25 kg/m2 is an independent risk factor for the development of fatal and non-fatal cardiovascular events in the analyzed cohort of the Chui region residents, regardless of gender, but only in persons under 60 years of age

Pichia pastoris regulates its gene-specific response to different carbon sources at the transcriptional, rather than the translational, level

Background: The methylotrophic, Crabtree-negative yeast Pichia pastoris is widely used as a heterologous protein production host. Strong inducible promoters derived from methanol utilization genes or constitutive glycolytic promoters are typically used to drive gene expression. Notably, genes involved in methanol utilization are not only repressed by the presence of glucose, but also by glycerol. This unusual regulatory behavior prompted us to study the regulation of carbon substrate utilization in different bioprocess conditions on a genome wide scale. Results: We performed microarray analysis on the total mRNA population as well as mRNA that had been fractionated according to ribosome occupancy. Translationally quiescent mRNAs were defined as being associated with single ribosomes (monosomes) and highly-translated mRNAs with multiple ribosomes (polysomes). We found that despite their lower growth rates, global translation was most active in methanol-grown P. pastoris cells, followed by excess glycerol- or glucose-grown cells. Transcript-specific translational responses were found to be minimal, while extensive transcriptional regulation was observed for cells grown on different carbon sources. Due to their respiratory metabolism, cells grown in excess glucose or glycerol had very similar expression profiles. Genes subject to glucose repression were mainly involved in the metabolism of alternative carbon sources including the control of glycerol uptake and metabolism. Peroxisomal and methanol utilization genes were confirmed to be subject to carbon substrate repression in excess glucose or glycerol, but were found to be strongly de-repressed in limiting glucose-conditions (as are often applied in fed batch cultivations) in addition to induction by methanol. Conclusions: P. pastoris cells grown in excess glycerol or glucose have similar transcript profiles in contrast to S. cerevisiae cells, in which the transcriptional response to these carbon sources is very different. The main response to different growth conditions in P. pastoris is transcriptional; translational regulation was not transcript-specific. The high proportion of mRNAs associated with polysomes in methanol-grown cells is a major finding of this study; it reveals that high productivity during methanol induction is directly linked to the growth condition and not only to promoter strength

Multichannel carrier scattering at quantum-well heterostructures

An efficient combined numerical–analytical technique is developed for calculating states of the continuum spectrum in systems with quantum wells (QWs) with an arbitrary potential shape, described by a system of coupled Schrödinger equations, e.g., hole states in semiconductor QWs. Continuum-spectrum states are found exactly using the approach similar to the scattering theory. Scattering states (the in/out-solutions) and the S-matrix for the case of multichannel scattering in one-dimensional systems with QWs are constructed, and their symmetry is determined and analyzed. The method is applied to studying the hole scattering by GaInAs–InGaAsP QWs with strained layers. The hole transmission and reflection coefficients and the delay-time energy dependence are calculated in relation to parameters of the structuresand values of the transversal momentum components. In the energy range in which the channel with heavy hole conversion into a propagating light hole is closed, scattering of the heavy hole on a QW has a resonant nature.6 page(s