Development of non-peptide ACE inhibitors as novel and potent cardiovascular therapeutics: An in silico modelling approach.

Angiotensin-converting enzyme (ACE) inhibitors have been acknowledged as first-line agents for the treatment of hypertension and a variety of cardiovascular disorders. In this context, quantitative structure-activity relationship (QSAR) models for a series of non-peptide compounds as ACE inhibitors are developed based on Simplified Molecular Input-Line Entry System (SMILES) notation and local graph invariants. Three random splits into the training and test sets are used. The Monte Carlo method is applied for model development. Molecular docking studies are used for the final assessment of the developed QSAR model and the design of novel inhibitors. The statistical quality of the developed model is good. Molecular fragments responsible for the increase/decrease of the studied activity are calculated. The computer-aided design of new compounds, as potential ACE inhibitors, is presented. The predictive potential of the applied approach is tested, and the robustness of the model is proven using different methods. The results obtained from molecular docking studies are in excellent correlation with the results from QSAR studies. The presented study may be useful in the search for novel cardiovascular therapeutics based on ACE inhibition.

Gender analysis of sexual behaviour of senior high-school students in Skopje, R. Macedonia - cross-sectional study.

UNLABELLED: (Full text is available at http://www.manu.edu.mk/prilozi). The aim of the study was to assess the gender influence on the main determinants of sexual behaviour of senior high-school students in Skopje, R. Macedonia (prevalence and age of onset of sexual activity, duration of the relationship before and the contraceptive method used during the first sexual intercourse, and number of lifetime sexual partners). METHODS: After ensuring privacy and confidentiality, a cross-sectional study was carried out in Skopje by enrolling 310 high-school students (49.7% males, 49% females, 1.3% unknown) from 5 randomly selected high-schools, from the 4th grade, using a 32-item paper-and-pencil self administered questionnaire. RESULTS: The prevalence of sexual activity was higher among boys than girls (when reaching grade 4 of the study 62.7% of the boys and 26.7% of the girls are sexually active) (p < 0.01). In addition, a significant gender difference was found in the following: the mean age of onset of sexual activity is 16 years for boys and 17 years for girls; concerning the duration of the relationship before the first sexual intercourse 33% of the boys and 2.5% of the girls had experienced one-night stand relationship (p < 0.01); and concerning the number of partners, having four or more sexual partners was reported by 29.8% of the boys and 5% of the girls (p < 0.01). Of those sexually non-active, 62.5% of the boys and 15.5% of the girls did not start with sexual activity because they did not have a chance (p < 0.01); 17.9% of the boys and 79.1% of the girls felt unprepared (p < 0.01). CONCLUSION: The data indicates substantial gender differences in sexual initiation patterns and sexual conduct. Boys and girls are vulnerable at different times in their development and hence need to be reached with different public health interventions for improving their sexual and reproductive health, adapted to local cultural and gender norms. Key words: Macedonia, high-school students, sexual behaviour, gender.

[Treatment of chronic resistant tuberculosis]. / Lecenje hronicne rezistentne tuberkuloze.

Two groups of patients with chronic pulmonary tuberculosis are presented. The first group of 92 patients were unsuccessfully treated according to current principles of treatment of chronic, resistant pulmonary tuberculosis. In the second group of 11 patients, unsuccessfully treated according to current methods, a new combination of drugs was applied so that a drug of the aminoglycoside group or chinolon group (Amikacin 1000 mg every second day or Ciprofloxacin 750 mg daily) was added to conventional therapy. Applying such therapy during 4 months encouraging results have been obtained.