Pharmacological activity of the furfuryl amine salt of 4-chloro-N-(2-furylmethyl)-5-sulfamoyl anthranilic acid

Furfuryl amine salt of 4-chloro-N-(2-furylmethyl)-5-sulfamoyl anthranilic acid was shown to exert more pronounced diuretic and saluretic action in rats, mice and dogs than that of furosemide. The previous administration of furfuryl amine salt of furosemide promoted normalization of the excretory processes of the kidney and increased survival rate of rats in ischemia of the single kidney. The antiedema activity of the drug was found to be much more pronounced than that of furosemide.     

Nyctometric studies in argon laser coagulation in patients with diabetic retinopathy

Forty-two patients (57 eyes) with diabetic retinopathy at various stages have been examined by nyctometry before and over the course of the follow-up period after argon laser coagulation of the retina. The findings evidence a marked reduction of the adaptation ability of the central retinal area even in high vision acuity in the patients with diabetic retinopathy vs. normal subjects. A stable rise of the nyctometric parameters has been observed after argon laser coagulation; these parameters characterize the function of the pigmented epithelium and of the retinal cone, and these data may be considered as an evidence of the improved trophics of these tissues, resultant from such therapy.     

Regulation of Na+ excretion and arterial blood pressure by purinergic signalling intrinsic to the distal nephron: consequences and mechanisms

Discretionary control of Na⁺ excretion is a key component of the regulation of arterial blood pressure in mammals. Sodium excretion is fine‐tuned in the aldosterone‐sensitive distal nephron by the activity of the epithelial Na⁺ channel (ENaC). Here, ENaC functions as a final effector of the renin–angiotensin–aldosterone system (RAAS) during negative feedback control of blood pressure. Mutations affecting ENaC activity and abnormal regulation of this channel affect blood pressure through pathological changes to Na⁺ excretion. Recent evidence demonstrates that powerful signalling pathways function in parallel with the RAAS to modulate ENaC activity and blood pressure. An inclusive paradigm is emerging with respect to regulation of blood pressure where ENaC serves as a critical point of convergence for several important signalling systems that affect renal Na⁺ excretion. A robust inhibitory purinergic signalling system intrinsic to the distal nephron dynamically regulates ENaC through paracrine ATP signalling via the metabotropic P2Y₂ purinergic receptor to properly match urinary Na⁺ excretion to dietary Na⁺ intake. This enables blood pressure to be maintained within a normal range despite broad changes in dietary Na⁺ consumption. Loss of purinergic inhibition of ENaC increases blood pressure by causing inappropriate Na⁺ excretion. In contrast, stimulation of the P2Y₂ receptor promotes natriuresis and a decrease in blood pressure. Such observations identify purinergic signalling in the distal nephron as possibly causative, when dysfunctional, for certain forms of elevated blood pressure, and as a possible therapeutic target for the treatment of elevated blood pressure particularly that associated with salt sensitivity.     

Characteristics of the transcription factor HIF-1α expression in the rat brain during the development of a depressive state and the antidepressive effects of hypoxic preconditioning

The dynamics of HIF-1α expression during the development of stress-related depression, as well as after hypoxic preconditioning (HP), which has an antidepressant-like effect, were studied in the hippocampus, paraventricular hypothalamic nucleus, and neocortex of rats, using an immunocytochemical method. It has been found that the factor HIF-1α is induced in neurons in response to psychoemotional stress that causes the development of experimental depression in rats in the “learned helplessness” model. The profile of the stress-induced expression of HIF-1α in the hippocampus has a two-wave character: early expression on the first day and the delayed expression 10 days after the stress. No significant change was found in the neocortex. In the hypothalamus, up-regulation of HIF-1α expression was delayed (5–10 days). After HP by a moderate repetitive hypobaric hypoxia, which prevents the development of the depressive state in rats, the post-stress expression of HIF-1α was considerably altered in the brain regions studied. In the hippocampus of HP rats, the peak of the early expression lasted for about 5 days after the stress; we observed a multifold increase in its amplitude. In contrast, the HIF-1α delayed peak was eliminated. A similar but smaller effect of HP was also observed in the hypothalamus. The data obtained indicate that delayed HIF-1α expression in the hippocampus and hypothalamus was apparently involved in the mechanisms of pathogenesis of the depressive pathology. However, strong modifications in early and late post-stress expression of HIF-1α caused by HP obviously play an important role in increasing the brain’s tolerance to severe stresses and protection against the development of stress-induced depressive pathologies.     

Action of acyclovir on cytomegalovirus in tissue culture and in chronic infection in women

Acyclovir was capable to delay for some time the development of the cytopathic effect in cell cultures. When acyclovir was added to the infected tube cultures in a concentration of 250 micrograms/ml, virus reproduction was inhibited for 6 days. Then foci of lesions were observed, and by the 12-13th days the intensity of involvement of the cell layer was 80-90% and did not differ from that in control tubes infected with cytomegalovirus (CMV). No significant differences were observed in the inhibiting effect of acyclovir on the freshly isolated strains or the reference Ad-169 strain. A course of therapy with acyclovir showed the inhibiting effect of this drug on CMV reproduction in women with the CMV infection to be of short duration. The temporary improvement observed on the first day after treatment was accompanied by reduced virus excretion with both the urine and saliva. Antibody titres remained the same before and after treatment. After 1-2 months virus excretion was observed practically in all the women similarly to that before the treatment.     

Remote results of alloplastic reconstruction of cruciform ligaments of the knee joint]

The results of plastic reconstruction of genicular crucial ligaments with a Lavsan implant are reported. The results obtained were estimated basing on the analysis of clinico-roentgenological findings in 120 patients within the terms from 1 to 12 years following surgical therapy. The issues of reconstruction of one of crucial ligaments are reported as well as the results of operations for the damage to several ligaments of the knee joint. The data obtained were assessed using the 2 mark system and in 94.6% the results were regarded as being favourable and satisfactory.     

Carvedilol in combined therapy of patients with Q myocardial infarction

AIM: To evaluate effects of carvedilol (Akridilol, AKRIKHIN, Russia) on central hemodynamics, microvascular bed, hemorheology, von Willebrand factor (VWF) activity, clinical efficacy of the drug and influence on exercise tolerance in patients with Q myocardial infarction (QMI) compared to therapy with atenolol. MATERIAL AND METHODS: The trial covered 90 patients with acute QMI. All the patients had cardiac failure and were divided into 3 comparable groups. Group 1 received carvedilol in a dose 6.25-50 mg/ day. Group 2 received atenolol in a dose 12.5-50 mg/day. Group 3 had contraindications to therapy with beta-adrenoblockers. The patients were followed up for 60 +/- 2 days. The following methods were employed in the study: clinical examination, echocardiography, laser Doppler flowmetry (LDF), Holter ECG monitoring, examination of platelet-vessel hemostasis, VWF activity, treadmill-test, statistical processing with the program Excel 7.0. RESULTS: Inclusion of beta-adrenoblockers in combined therapy of QMI patients with cardiac failure considerably improves treatment efficacy. These drugs, carvedilol in particular, inhibit postinfarctional remodeling and thus development and progress of cardiac failure. Carvedilol reduces stasis in the microcirculatory bed, corrects abnormal response of microhemodynamics to sympathic activation and operation of venuloarteriolar mechanisms of capillary blood flow regulation. High clinical efficacy of the combined therapy of QMI patients is explained by marked antianginal and antiischemic effects of carvedilol. Treadmill test showed that the addition of beta-adrenoblockers to therapy raised exercise tolerance in the postinfarctional period.     

Vascular endothelial growth factor and insulin-like-growth factors in prostate cancer.

To study the levels of vascular endothelium growth factor (VEGF), insulin-like growth factor of type I and II (IGF-I and IGF-II), prostate-specific antigen (PSA) and their correlations in prostatic cancer (PC) and benign prostatic hyperplasia (BPH), we examined 38 PC patients (mean age 66.6 +/- 5.5 years) and 80 BPH patients (mean age 60.3 +/- 2.5 years). Serum concentrations of VEGF, IGF-I and IGF-II were measured using kits made by R&D (USA), PSA by Boehringer Mannheim (Germany). Sensitivity and specificity of the tests were analysed by plotting the curves. The serum VEGF concentration in PC patients was 518.9 +/- 60.7 pkg/ml, in BPH patients--267.9 +/- 99.9 pkg/ml (p < 0.001). The IGF-I and IGF-II it was 178 +/- 19 and 136 +/- 9 ng/ml (p < 0.05), 400 +/- 31 and 351 +/- 23 ng/ml (p < 0.05), respectively. The ratio of growth factor concentration to PSA concentration in the blood serum in BPH patients was higher than in PC patients (p < 0.01). Sensitivity and specificity of PSA (4 ng/ml) made up 85.7 and 57%, VEGF (151.5 pg/ml)--76.2 and 57.6%, IGF-I (157 ng/ml)--57.6 and 50%; IGF-II (392 ng/ml)--57.5 and 50%, respectively. Sensitivity and specificity VEGF/PSA was 85.7 and 70%; IGF-I/PSA--84.2 and 75%; IGF-II/PSA--84.2 and 79.6%, respectively. Thus, the ratio of concentrations of IGF-I, IGF-II and VEGF to PSA level in blood serum has high sensitivity and specificity for PC detection. Clinical implications of serum levels of VEGF, IGF-I and IGF-II for prediction of PC course and detection is to be elicited.     

Antihypertensive efficacy and tolerability of nebivolol

Nebivolol was given to 59 patients with hypertension for 8 weeks. This was accompanied by augmentation of amplitude of photoplethysmogram in all and normalization of blood pressure in 67% of patients. Nebivolol did not cause orthostatic hypotension or bronchial spasm.