Wound healing mechanisms in rats with streptozotocin-induced diabetes mellitus

Background. Wound healing disorders and formation of diabetic foot, a severe disabling complication of diabetes mellitus, are accompanied by nervous system impairment and/or ischemia. Objective — the study was aimed at assessing the effect of peripheral innervation disorders on the regulation of tissue repair in the streptozotocin-induced rat model of diabetes mellitus. Material and methods. The study was carried out in male white outbred rats (n=70). The animals were wounded 42 days after induction of diabetes by injecting streptozotocin (diabetes group; this group received insulin Levemir at a dose of 2 units/kg in saline subcutaneously to reduce mortality), or after injection of citrate buffer (CB group). Skin samples were taken on day 8, 16, and 24 after wound modeling. Pain sensitivity was assessed in all animals. The resulting skin fragments were fixed, dehydrated, and embedded in paraffin according to standard procedures. Sections were stained with hematoxylin and eosin, antibodies specific for Ki-67, α1, β1, and β2-adrenoreceptors were used for immunohistochemical staining. Intact animals were used as an additional control group. Results. Tail withdrawal time measured on day 56 was higher in DM group rats as compared to the control group (p=0.017). CB group demonstrated a tendency towards more rapid wounds healing than diabetic animals, although the difference was not statistically significant due to wide scatter of data in the DM group (p=0.64). The intensity of staining for Ki67 was lower in the DM group (p=0.045). Reduced density of β2-adrenoreceptors was observed at the areas remote from the wound in CB group rats. Conclusion The results show no correlation between altered innervation and impaired tissue repair in rats with streptozotocin-induced diabetes.

Levosalbutamol as alternative to drugs on the basis of racemic salbutamol: Review of the results of pre-clinical research

The aim of the work is to conduct an analytical review of the results of preclinical studies of levosalbutamol. The review discusses the pharmacodynamic features of the R-stereoisomer of salbutamol in vitro. The chemical bases of interaction of levosalbutamol with β2-adrenoreceptors, intracellular signaling cascades associated with β2-adrenoreceptors, and structural features of clinically significant ligands of β2-adrenoreceptors are presented. Broncholytic activity, influence on the contractility of the diaphragmatic muscles, mucociliary clearance of R-salbutamol in comparison with racemic salbutamol are described. The data presented indicate that all known β2-adrenergic receptor-dependent effects of racemic salbutamol, including bronchodilation, are realized by its R-enantiomer. There is evidence that the regular inhalation administration of racemic salbutamol is accompanied by a partial decrease in the bronchoprotective effect and an increase in airway hyperreactivity in response to the action of provocative factors. It was found that the development of hyperreactivity of the respiratory tract is excluded in the case of regular inhalation of levosalbutamol. Possible mechanisms of the paradoxical bronchoconstrictor effect of the salbutamol dystomer are described. This article shows the beneficial effect of levosalbutamol on mucociliary clearance, its anti-inflammatory activity and antiallergic effect. The image data are compared between the enantiomers and the racemate of salbutamol. Special attention is paid to the pharmacokinetics of enantiomers of salbutamol. The data presented from the preclinical studies provide evidence of chiral inversion of stereoisomers of salbutamol.

GENETIC ASPECTS OF DEVELOPMENT AND PROGRESSION OF CONGESTIVE HEART FAILURE IN PATIENTS WITH ISCHEMIC HEART DISEASE AND OBESITY∗

In this article elucidated the influence of allelic polymorphism of Gln27Glu of β2-adrenoceptors gene on patients that have coronary heart disease and obesity on the expansion and progression of congestive heart failure and left ventricular systolic dysfunction by surveying 222 patients. Presence of C allel of polymorphous locus Gln27Glu of β2-adrenoreceptors gene in patients with ischemic heart disease and concomitant obesity was associated with decreased risk of development of congestive heart failure (p < 0.05). The obtained data shown the absence of influence of polymorphous variants of β2-adrenoreceptors gene on progression of congestive heart failure in patients with ischemic heart disease and obesity (p > 0.05).