[Ursodeoxycholic acid-enhanced efficiency and safety of statin therapy in patients with liver, gallbladder, and/or biliary tract diseases: the RACURS study].

AIM: To evaluate the efficiency and safety of using statins in combination with ursodeoxycholic acid (UDCA) in patients with this or another liver disease at high risk for cardiovascular events (CVE). SUBJECTS AND METHODS: A register of 262 patients at high risk for CCE who needed statin therapy and have concomitant chronic liver and biliary tract diseases was created in 5 cities of the Russian Federation. RESULTS: After addition of statins or adjustment of their doses, the patients were recommended to include UDCA into their therapy. Six months after stabilization of the dose of statins, the whole group showed a significant reduction in the levels of total cholesterol and low-density lipoprotein (LDL) cholesterol. Assessment of the laboratory parameters responsible for the safety of statin intake revealed no deterioration in the trend in the activity of alanine aminotransferase, aspartate aminotransferase, creatine phosphokinase, lactate dehydrogenase, as well as an increase in the serum level of bilirubin. The data obtained using a special questionnaire indicated that 196 patients had taken UDCA and 56 had not. The UDCA and non-UDCA subgroups did not differ in age, weight, or baseline lipid metabolic disturbances. An additional analysis showed that by the end of 6 months, the goal levels of LDL cholesterol in the UDCA and non-UDCA groups were reached in 37 and 20%, respectively (p = 0.01). CONCLUSION: UDCA added to statin therapy in patients at high risk for CVE and concurrent liver diseases contributes to an additional reduction in total cholesterol and LDL cholesterol and prevents enhanced hepatic transaminase activities.

Semaphorin3A regulates axon growth independently of growth cone repulsion via modulation of TrkA signaling.

Regulation of axon growth is a critical event in neuronal development. Nerve growth factor (NGF) is a strong inducer of axon growth and survival in the dorsal root ganglia (DRG). Paradoxically, high concentrations of NGF are present in the target region where axon growth must slow down for axons to accurately identify their correct targets. Semaphorin3A (Sema3A), a powerful axonal repellent molecule for DRG neurons, is also situated in their target regions. NGF is a modulator of Sema3A-induced repulsion and death. We show that Sema3A is a regulator of NGF-induced neurite outgrowth via the TrkA receptor, independent of its growth cone repulsion activity. First, neurite outgrowth of DRG neurons is more sensitive to Sema3A than repulsion. Second, at concentrations sufficient to significantly inhibit Sema3A-induced repulsion, NGF has no effect on Sema3A-induced axon growth inhibition. Third, Sema3A-induced outgrowth inhibition, but not repulsion activity, is dependent on NGF stimulation. Fourth, Sema3A attenuates TrkA-mediated growth signaling, but not survival signaling, and over-expression of constitutively active TrkA blocks Sema3A-induced axon growth inhibition, suggesting that Sema3A activity is mediated via regulation of NGF/TrkA-induced growth. Finally, quantitative analysis of axon growth in vivo supports the possibility that Sema3A affects axon growth, in addition to its well-documented role in axon guidance. We suggest a model whereby NGF at high concentrations in the target region is important for survival, attraction and inhibition of Sema3A-induced repulsion, while Sema3A inhibits its growth-promoting activity. The combined and cross-modulatory effects of these two signaling molecules ensure the accuracy of the final stages in axon targeting.

Topical matrix-based siRNA silences local gene expression in a murine wound model.

The ability to affect gene expression via topical therapy has profound therapeutic implications for conditions characterized by open wounds including cutaneous neoplasms, thermal injury, skin disorders and dysfunctional wound healing. Specifically targeting local gene expression avoids systemic toxicity and simplifies treatment. We have developed a new method of topical matrix-based short interfering RNA application to precisely and effectively silence local gene expression in nondelimited wounds.

[Effect of telmisartan on the psychological state and quality of life in stable hypertension patients]. / Vliianie Telmisartana na psikhologicheskii status i kachestvo zhizni bol'nykh so stabil'noi arterial'noi gipertenziei.

Effects of the standard doses of telmisartan (20-80 mg) and enalapril (5-10 mg) on the arterial pressure (AP, circadian monitoring), psychological state (Minnesota Multiphase Personality Inventory questionnaire, Russian version), and quality of life (General Well-Being Questionnaire) were studied in a randomized, parallel group trial in 30 patients with stable, soft-to-moderate arterial hypertension. The initial control 2-week period was followed by a 12-week period of active therapy. It was established that the long-term administration of both drugs in standard doses produced comparable antihypertensive effect, reliably reducing the averaged AP characteristics. Both drugs also improved the quality of life: enalapril influenced predominantly the psychological score, while telmisartan increased both psychological score and social score. Long-term administration of both drugs had a positive effect on the psychological state of hypertensive patients.

[Comparison of carvedilol and atenolol efficacy in patients with stable effort angina]. / Sravnenie éffektivnosti karvedilola i atenolola u bol'nykh so stabil'noi stenokardiei napriazheniia.

AIM: To compare effectiveness of carvedilol--beta-adrenoblocker with vasodilating action--with atenolol which is beta-adrenoblocker having no vasodilating activity in coronary heart disease (CHD) patients with stable effort angina. MATERIAL AND METHODS: The trial entered 28 CHD patients with a history of myocardial infarction (MI). All the patients had no contraindications to beta-adrenoblockers, had positive exercise tolerance test. After the control period of 7-10 days the patients received either carvedilol (14 patients) or atenolol (14 patients) in a mean daily dose 20.5 mg (6.25 to 50 mg) and 25.9 mg (12.5 to 100 mg), respectively, twice a day. The course of the treatment took 4 weeks. The effect was evaluated at treadmill exercise test. RESULTS: Both drugs diminished heart rate, carvedilol was less effective in this respect. Both drugs significantly prolonged time of exercise to the anginal attack and ST depression by 1.0 mm. Side effects arose in 6 and 4 patients, respectively. CONCLUSION: Carvedilol and atenolol are equally effective in the treatment of stable effort angina.

[The effect of long-term uncontrolled antihypertensive therapy on the echocardiographic signs of left-heart hypertrophy in patients with mild and moderate arterial hypertension]. / Vliianie dlitel'noi nekontroliruemoi antigipertenzivnoi terapii na ékhokardiograficheskie priznaki gipertrofii levykh otdelov serdtsa u bol'nykh miagkoi i umerennoi arterial'noi gipertoniei.

The data are presented on the absence of a stable positive trend in echocardiographic characteristics of the left heart and intracardiac hemodynamics after 8 months of controlled antihypertensive therapy, 12-month follow-up and uncontrolled outpatient treatment. 12 months after discontinuation of controlled antihypertensive therapy arterial pressure was much higher than it was at the end of the treatment in patients taking antihypertensive drugs irregularly or not taking them at all. Intracardiac hemodynamics returned to the baseline. As shown by echo-CG, frequency of left ventricular hypertrophy 12 months after the end of antihypertensive treatment rose from 25.8 to 45.2% (p < 0.01), of right ventricular hypertrophy from 14.5 to 17.7%.

Retinoic acid induces adult muscle cell differentiation mediated by the retinoic acid receptor-alpha.

Retinoic acid (RA) is known to induce differentiation in many cell systems. This induction is mediated by nuclear RA receptors (RARs), which act as transactivating factors belonging to the superfamily of steroid/thyroid nuclear receptors. In this study, effects of RA were studied in a mouse myogenic C2 cell line and in primary chicken satellite cells, the myogenic precursor cells in adult muscle. Addition of RA decreased the rate of DNA synthesis in a dose-dependent manner in both cultures. Differentiation was more rapid in cells treated with RA, and these cells exhibited large myotubes after 48 hr of incubation as compared to untreated cells, which were still proliferating. Addition of 10(-8) M RA to C2 cells elevated mRNA levels of myogenin, a skeletal muscle-specific transcription factor. In parallel, activity levels of the muscle-specific creatine kinase were enhanced in the RA-treated cells nearly twofold as compared to the untreated cells. RA treatment of both mouse C2 and chicken satellite cells caused rapid induction of the RAR-alpha mRNA levels. Maximal mRNA levels were observed after 2 to 5 hr followed by a sharp reduction to nearly zero levels at 9 hr. The RAR-alpha mRNA levels augmented in a dose-dependent manner between concentrations of 10(-10) M and 10(-8) M RA, whereas higher concentrations caused mRNA levels to decrease. These results indicate that RA induces differentiation in both adult skeletal muscle primary satellite cells and a myogenic cell line. The rapid and specific induction of RAR-alpha mRNA in these cells upon exposure to RA may suggest that this receptor is the primary target and a mediator of RA.

[Differences in hemodynamic effects of the cardioselective beta-adrenoblocker acebutolol and non-selective beta-adrenoblocker propranolol in long-term antihypertensive therapy]. / Osnovnye razlichiia gemodinamicheskikh éffectov kardioselektivnogo beta-adrenoblokatora atsebutolola i neselektivnogo beta-adrenoblokatora propranolola pri dlitelnoi antigipertenzivnoi terapii.

The cardioselective beta-adrenoblocker acebutolol used as a course therapy for 12 weeks was found to be a highly beneficial antihypertensive agent. The antihypertensive effect of the agent given in doses of 400-800 mg/day was as pronounced and prolonged as that of propranolol, 80-160 mg/day, though there is a tendency for acebutolol to show its complete or partial antihypertensive effect rather at the end of monotherapy than propranolol. At the same time the bradycardiac effect was more pronounced in propranolol therapy. The antihypertensive effect of acebutolol, 400-800 mg/day, was revealed after 2 weeks of its use and persisted within the entire 12 weeks of therapy. The drug was well tolerated. In contrast to propranolol, a non-selective beta-adrenoblocker having no intrinsic sympathomimetic activity, acebutolol failed to produce adverse effects, such as by decreasing cardiac output and increasing total peripheral vascular resistance. The agent had a less negative chronotropic effect.