Prolonged cardioselective blockade of beta-1 adrenoreceptors in combination with increased diuresis as a method of choice in the treatment of hypertension]

The clinical effects of Tenoric, a long-acting combined drug (atenolol and chlorthalidone in a tablet), were studied in 31 patients with Stages I and II hypertensive disease, by using echocardiography, daily automatic blood pressure monitoring, bicycle ergometry, measurements of plasma renin and aldosterone. The drug was found to be highly clinically effective in labile and sustained hypertension. When given once or twice a day, it makes it possible to reliably monitor blood pressure, improve hemodynamic parameters, as reflected by lower cardiac output and decreased peripheral vascular resistance, reduce the estimated mass of the left myocardium, alleviate a pressor response to exercise and enhance its tolerance, lower plasma renin levels. The side effects of the drug are minimal and include moderate bradycardia. Peripheral vasospasm and systemic weakness were observed in single cases. There were no atherogenic changes in lipid spectrum and disturbed glucose and uric acid metabolism during the drug therapy.     

The role of EGF-stimulated epidermis in the regulation of wound healing

Sluggish wounds are characterized by impaired proportions of proinflammatory cytokines, deficiency of fibrogenic growth factors, imbalance in the system of matrix metalloproteinases and their inhibitors this preventing reparation. The study was made of biopsies obtained from patients with sluggish wounds before the treatment, 5, 10 and 15 days after transplantation on the wound of allogenic EGF-stimulated cryopreserved epidermis. The wound closure with biologically active coat was followed by the reduction of expression of proinflammatory cytokines and return to their normal correlations, higher production of fibrogenic growth factors, restoration of balance in the expression of MMP-9 and TIMP-1/TIMP-2.     

Ursodeoxycholic acid as a means of preventing atherosclerosis,steatosis and liver fibrosis in patients with nonalcoholic fatty liver disease

BACKGROUNDAtherosclerotic cardiovascular disease (ASCVD) is the leading cause of mortality in patients with nonalcoholic fatty liver disease (NAFLD). Weight loss is a key factor for successful NAFLD and CVD therapy. Ursodeoxycholic acid (UDCA), which is one of the first-line therapeutic agents for treatment of NAFLD, is reported to have a beneficial effect on dyslipidemia and ASCVD risk because of antioxidant properties.AIMTo evaluate the effects of 6 mo of UDCA treatment on hepatic function tests, lipid profile, hepatic steatosis and fibrosis, atherogenesis, and ASCVD risk in men and women with NAFLD, as well as to assess the impact of > 5% weight reduction on these parameters.METHODSAn open-label, multicenter, international noncomparative trial was carried out at primary health care settings and included 174 patients with ultrasound-diagnosed NAFLD who received 15 mg/kg/d UDCA for 6 mo and were prescribed lifestyle modification with diet and exercise. The efficacy criteria were liver enzymes, lipid profile, fatty liver index (FLI), noninvasive liver fibrosis tests (nonalcoholic fatty liver disease fibrosis score and liver fibrosis index), carotid intima-media thickness (CIMT), and ASCVD risk score. To test statistical hypotheses, the Wilcoxon test, paired t-test, Fisher’s exact test, and Pearson''s chi-squared test were used. RESULTSThe alanine aminotransferase (ALT) level changed by -14.1 U/L (-31.0; -5.3) from baseline to 3 mo and by -6.5 U/L (-14.0; 0.1) from 3 to 6 mo. The magnitude of ALT, aspartate transaminase, and glutamyltransferase decrease was greater during the first 3 mo of treatment compared to the subsequent 3 mo (P < 0.001, P < 0.01, P < 0.001, respectively). At 6 mo, in the total sample, we observed a statistically significant decrease in body weight and levels of FLI: 84.9 ± 10.4 vs 72.3 ± 17.6, P < 0.001, total cholesterol: 6.03 ± 1.36 vs 5.76 ± 1.21, Р < 0.001, low-density lipoprotein: 3.86 ± 1.01 vs 3.66 ± 0.91, Р < 0.001, and triglyceride: 3.18 (2.00; 4.29) vs 2.04 (1.40; 3.16), Р < 0.001. No effect on nonalcoholic fatty liver disease fibrosis score or liver fibrosis index was found. The CIMT decreased significantly in the total sample (0.985 ± 0.243 vs 0.968 ± 0.237, P = 0.013), whereas the high-density lipoprotein (Р = 0.036) and 10-year ASCVD risk (Р = 0.003) improved significantly only in women. Fifty-four patients (31%) achieved > 5% weight loss. At the end of the study, the FLI decreased significantly in patients with (88.3 ± 10.2 vs 71.4 ± 19.6, P < 0.001) and without > 5% weight loss (83.5 ± 10.3 vs 72.8 ± 16.7, P < 0.001). The changes in ALT, aspartate transaminase, glutamyltransferase, total cholesterol, and low-density lipoprotein levels were similar between the subgroups.CONCLUSIONUDCA normalizes liver enzymes greatly within the first 3 mo of treatment, improves lipid profile and hepatic steatosis independent of weight loss, and has a positive effect on CIMT in the total sample and 10-year ASCVD risk in women after 6 mo of treatment.     

Platelet adhesion and thrombus formation on subendothelium in platelets deficient in glycoproteins IIb-IIIa, Ib, and storage granules

Patients whose platelets are deficient in glycoprotein (GP) Ib, IIb- IIIa (thrombasthenia), or granule substances (storage pool deficiency, SPD) were studied to define further the properties of platelets that mediate platelet adhesion and thrombus formation on subendothelium. Both nonanticoagulated and citrated blood were exposed to everted, de- endothelialized rabbit vessel segments under controlled flow conditions and shear rates varying from 650 to 3,300 sec-1. Morphometry was used to measure platelet thrombus dimensions and the percentage of the subendothelial surface covered with contact (C) or spread (S) platelets. Adhesion was defined as C + S. The results in SPD demonstrated (1) reduced thrombus dimensions in delta-SPD (pure dense granule deficiency) in proportion to the magnitude of the dense granule defect; (2) an even greater reduction in thrombus dimensions in patients with combined deficiencies of alpha and dense granules (alpha delta-SPD); and (3) impaired platelet adhesion at several conditions in alpha delta-SPD and, in delta-SPD, a hematocrit-dependent impairment of adhesion in citrated blood at 2,600 sec-1. In thrombasthenia, platelets were present as a monolayer on the subendothelial surface in both nonanticoagulated and citrated blood, indicating an absolute requirement for GPIIb-IIIa in promoting platelet-platelet interaction at all shear rates and perfusion times. Two types of abnormalities in platelet-vessel wall interactions were observed. In nonanticoagulated blood, the percentage of platelets in the C phase was consistently increased at all shear rates, but C + S values were normal. These observations indicate that platelets deficient in GPIIb-IIIa do not spread normally on the subendothelial surface exposed to nonanticoagulated blood. With citrated blood, the C + S value in thrombasthenia was reduced at both 800 and 2,600 sec-1, as in von Willebrand's disease, and a similar degree of reduction (about 50%) was observed in normal blood treated with a monoclonal antibody to GPIIb- IIIa. The findings, together with theoretical considerations, are consistent with an hypothesis that GPIIb-IIIa mediates the spreading of platelets on subendothelium following the initial attachment through GPIb and that GPIIb-IIIa may be considered an adhesion site on the platelet membrane. Abnormalities of GPIIb-IIIa may, depending on the conditions of study, result in either increased values of C platelets or decreased values of C + S. The results of the study further suggest that a complex interaction of platelet granule factors and membrane GP mediate platelet adhesion and thrombus formation.     

Application of viable cryopreserved alloderm transplants in the treatment of wound defects of soft tissues

An original method is proposed for treatment of long-standing intractable wounds and trophic ulcers using viable cryopreserved allodermotransplants and a distant air-plasma treatment. The main source of the allodermotransplants is the cadaverous skin. It was shown that the cadaverous skin taken during 17 hours after the donor's death was viable. The maximum period for storage of the viable skin when the worked out preservative is used at the temperature regimen -18 degrees C is 10 days, and at -70 degrees C it can be as long as 45 days. The analysis performed included 101 patients with long-standing intractable wounds and trophic ulcers. In 51 of them the new worked out method was used. An analysis of clinical and histomorphological data has proved that the application of the viable cryopreserved allodermotransplants and distant air-plasma treatment favor the better course of reparative processes. By the end of the forth week the wounds were completely closed in 19.7% of patients, the wound areas were considerably less (more than by 50% of the initial size) in 43.1%, less reduction of the wound area (less than 50% of the initial size) in 27.4%, in 9.8% there was no effect. No negative results were noted. It should be noted that closure of the tissue defect can be achieved by stimulation of the physiological regeneration of the patient's tissues. This method of regeneration of the skin is effective in trophic ulcers, long-standing intractable wounds and is also recommended in case of deficit of donor resources or when the severe state of the patient does not allow active surgical treatment.     

The typical features and clinical characteristics of Reiter's syndrome with a nonvenereal origin

Analysis of the clinical picture in 37 patients with Reiter's syndrome unrelated to venereal urethritis showed that in the majority of cases, it was preceded by acute intestinal infection which occasionally ran an unmarked course. The difficulties in diagnosing Reiter's syndrome were caused in some patients by the fact that in the disease debut, conjunctivitis and urethritis were little manifest and of short duration or occurred at the later stages, especially where the triad was preceded by the provoking factors, such as supercooling and nasopharyngeal infection. Also, in the acute phase of the disease, the patients demonstrated catarrh of the upper respiratory tract, the signs of myocardial injury and some symptoms characteristic of other rheumatological diseases. In this connection attention is drawn to the necessity of inquiring after the patients' health and sensations in doubtful cases, including the elucidation of the epidemiological anamnesis, thorough examination of the patients on admission to hospital and during the treatment to specify both the main and additional signs of Reiter's syndrome, and analysis of the disease course.