Peculiarities of the function of cardiomyocytes in patients with ischemic heart disease associated with diabetes mellitus type 2

The functional activity of myocardium in patients with type 2 diabetes mellitus(T2DM) and coronary heart disease (CAD) was studied. The study included patients with CAD with T2DM as representatives of the main group, the comparison group consisted of patients with univariant course of ischemic heart disease without violation of carbohydrate metabolism. Contractile activity of the myocardium was evaluated by the inotroic reaction of isolated trabeculae of patients according to the Protocol tests "Post-rest" and "Ekstrasistoliei test". As a result, it was found that rhythm-inotropic myocardial response in patients with comorbid pathology persists to a greater extent than in the one-dimensional flow of CAD

Derivation of a Myeloid Cell-Binding Adenovirus for Gene Therapy of Inflammation

The gene therapy field is currently limited by the lack of vehicles that permit efficient gene delivery to specific cell or tissue subsets. Native viral vector tropisms offer a powerful platform for transgene delivery but remain nonspecific, requiring elevated viral doses to achieve efficacy. In order to improve upon these strategies, our group has focused on genetically engineering targeting domains into viral capsid proteins, particularly those based on adenovirus serotype 5 (Ad5). Our primary strategy is based on deletion of the fiber knob domain, to eliminate broad tissue specificity through the human coxsackie-and-adenovirus receptor (hCAR), with seamless incorporation of ligands to re-direct Ad tropism to cell types that express the cognate receptors. Previously, our group and others have demonstrated successful implementation of this strategy in order to specifically target Ad to a number of surface molecules expressed on immortalized cell lines. Here, we utilized phage biopanning to identify a myeloid cell-binding peptide (MBP), with the sequence WTLDRGY, and demonstrated that MBP can be successfully incorporated into a knob-deleted Ad5. The resulting virus, Ad.MBP, results in specific binding to primary myeloid cell types, as well as significantly higher transduction of these target populations ex vivo, compared to unmodified Ad5. These data are the first step in demonstrating Ad targeting to cell types associated with inflammatory disease

Characterization of rat lines with normotensive and hypertensive status using genomic fingerprinting

The properties of normotensive and hypertensive rat lines were investigated by the DNA fingerprinting method using a multilocus micro-satellite (CAC)5 probe. The HaeIII and HinfI restriction endonucleases were found to be the most informative enzymes in this case. The high genetic homogeneity of the ISIAH line, a rat line with inherited stress-sensitive arterial hypertension created at the Institute of Cytology and Genetics, was demonstrated. The lack of intralinear polymorphism was also typical to Japanese SHR rats with spontaneous arterial hypertension. Normotensive WAG rats had identical fingerprinting patterns, while the relative intensity of some bands was different. The outbred normotensive Wistar line maintained at the Institute, appeared to carry 30% polymorphic alleles. Hypertensive lines differed from the normotensive by a number of genetic markers

Significant alterations of biodistribution and immune responses in Balb/c mice administered with adenovirus targeted to CD40(+) cells

CD40 ligation has been shown to promote antigen-presenting functions of dendritic cells, which express CD40 receptor. Here we reported significantly altered biodistribution and immune responses with the use of CD40-targeted adenovirus. Compared with unmodified adenovirus 5, the CD40-targeted adenovirus following intravenous administration (i.v.) resulted in increased transgene expressions in the lung and thymus, which normally do not take up significant amounts of adenovirus. Intradermal injection saw modified adenovirus being mainly processed in local draining lymph nodes and skin. Following intranasal administration (i.n.), neither unmodified nor targeted viruses were found to be in the liver or spleen, which predominantly took up the virus following i.v. administration. However, inadvertent infection of the brain was found with unmodified adenoviruses, with the second highest gene expression among 14 tissues examined. Importantly, such undesirable effects were largely ablated with the use of targeted vector. Moreover, the targeted adenovirus elicited more sustained antigen-specific cellular immune responses (up to 17-fold) at later time points (30 days post boosting), but also significantly hampered humoral responses irrespective of administration routes. Additional data suggest the skewed immune responses induced by the targeted adenoviruses were not due to the identity of the transgene but more likely a combination of overall transgene load and CD40 stimulation.NRC publication: Ye