The aim: To establish the role of allelic polymorphisms NOS3-T-786C, MTHFR-C667T, P2RY12--744C, (GPIbα)-C482T in the development of vascular lesions in patients with hypertension and diabetes mellitus type 2. Materials and methods: The study included 100 patients with hypertension and diabetes mellitus type 2 (main group) and 50 patients without type 2 diabetes (control group). Patients underwent echocardiography, color duplex scanning of extracranial, brachiocephalic and femoral vessels. The distribution of allelic polymorphisms was investigated by isolation DNA from leukocytes and polymerase chain reaction (PCR). Results: The risk of vascular damages increases 2-fold when carrying all 4 risk alleles in monozygotic genotypes of polymorphic loci in patients with hypertension with concomitant type 2 diabetes (p<0,05). In gene-gene interaction, the values of contributions and directions of interaction between alleles of polymorphic loci are established (p<0,05). Genes create a paired hierarchy of interaction according to their functional activity; the largest contribution to the probable vascular damage depends on the allelic polymorphism NOS3-786CT (p<0,05), the lowest - on the allelic polymorphism P2RY12-744CC (H2H2). The genetic polymorphism of the MTHFR gene is independent of the influence of other studied polymorphisms (p<0,05); the genes P2RY12-744CT and GPIbα 482CT act synergistically with the gene NOS3-786CT, being in a weak negative interaction with each other. Conclusions: Phenotypic manifestations of endothelial dysfunction may be modified by allelic polymorphism of genes associated with endothelial and platelet functions with the risk of vascular complications.

The aim of the research was to determine the influence of low surface tension water load on the excretory function of kidneys and the urine surface tension compared to induced diuresis by ordinary tap water. In the experiments on 40 white nonlinear male rats weighing 0.16–0.18 kg the effect of low surface tension water load (43 dyn/cm) was studied, which was obtained by treating tap water with coral calcium (Sango Coral, Okinawa, Japan). The excretory function of kidneys was studied under the conditions of water-induced diuresis and low surface tension water loading, for which the fluids in the amount of 5% of body weight were injected into the stomach of rats with the help of a metal probe with further urine collection after 2 hours. Urinary creatinine concentrations were determined based on the reaction with picric acid. Concentrations of sodium and potassium ions were studied by using flame photometry on PFP-1. The concentration of urinary protein was estimated by the method with sulphosalicylic acid. The urine pH as well as the concentrations of titratable acids and ammonia was determined. We calculated the excretion of potassium and sodium ions, protein, titratable acids, ammonia, and ammonium coefficient. The urine surface tension was determined by the Harkinson method of stalagmometric droplet counting, based on the determination of the weight of the droplet which is detached from the capillary due to gravity. As a result of the experiments on 40 white nonlinear pubertal male rats with induced diuresis under low surface tension water load (43 dyn/cm) compared to conventional tap water (the surface tension is 73 dyn/cm) a systemic effect was found on inhibition of the surface tension of urine from 75.00±0.000 dynes/cm to 74.05±0.260 dyn/cm (p<0.01), a decrease in the loss of urinary protein from 0/36±0.0074 mg/2h×100g to 0.012±0.0024 mg/2h×100g (p<0.01), sodium ions and the presence of significant interdependencies between the urinary surface tension, the concentrations of sodium ions and urinary protein. The low surface tension water load (43 dyn/cm) compared to the diuresis induced by ordinary tap water (surface tension 73 of dyn/cm) is characterized by the systemic impact along with the inhibition of the urine surface tension (p<0.01), reduction of urinary protein losses and presence of reliable interdependencies between the urine surface tension, concentrations of sodium ions and urinary protein. Thus, the use of water treated with the Coral-mine preparation may be recommended as a rehabilitation remedy with a view of improving the functional condition of the kidneys both in health and damaged tubules of the nephron.

The role of the transcription factor Hif-1α in pathogenesis of hypoxic lesions and diabetes mellitus (DM) has been confirmed, though molecular mechanisms underlying dysfunctions of the factor in the association of DM with ischemic-reperfusion lesion of the brain remain unknown. Objective: the investigation of Hif-1α protein content in the neurons of the hippocampus fields of rats with experimental DM in the dynamics of ischemic-reperfusion lesion of the brain. The study was conducted on 60 6-month rats with DM simulated at the age of 2 months by means of a single administration of streptozotocin (60 mg/kg of the body weight) (Sigma, USA). Disorders of the cerebral circulation were simulated by means of occlusion of both carotid arteries for 20 minutes. The content of Hif1-α protein was determined by means of fluoroimmunoassay after 20-minute ischemia with one hour reperfusion, and on the 12th day of the post-ischemic period in the hippocampus fields: СА1, СА2, СА3, СА4. In rats without DM 20-minute ischemia with one hour reperfusion increases the content of Hif-1α protein in all the hippocampus fields. On the 12th day of ischemic-reperfusion period in СА2-СА4 hippocampus fields the values of certain examined activity indices of the transcription factor Hif-1α continue to increase, and in СА1 field they are normalized or come closer to the values of animals from the control group. In rats with DM at the early post-ischemic period changes of Hif-1α protein content are lacking in СА1 field, the signs of its reduced activity are found in СА2 field, in СА3 field they are limited by the response of one index, and in СА4 field they are similar to those of the control rats under the experimental conditions. On the 12th day of ischemic-reperfusion period all the activity indices of the transcription factor Hif-1α increase in СА1 filed. They are higher than the corresponding indices in animals from the control group by absolute values under similar experimental conditions; changes of the examined parameters are limited in СА2 and СА3 fields in comparison with those from the control group; the parameters, which increased in the control group of animals, decreased in СА4 field. DM restricts Hif-1α protein response to ischemia-reperfusion in the neurons of СА1-СА3 field at the early ischemic-reperfusion period and in the neurons of СА2-СА4 fields — on the 12th day of the observation.

Dedicated to Prof. Girolamo Cirrincione in recognition of his outstanding contributions to the fields of organic and medicinal chemistry on the occasion of his retirement