Dušica Stojanović

QSAR modeling of the antimicrobial activity of peptides as a mathematical function of a sequence of amino acids

Antimicrobial peptides have emerged as new therapeutic agents for fighting multi-drug-resistant bacteria. However, the process of optimizing peptide antimicrobial activity and specificity using large peptide libraries is both tedious and expensive. Therefore, computational techniques had to be applied for process optimization. In this work, the representation of the molecular structure of peptides (mastoparan analogs) by a sequence of amino acids has been used to establish quantitative structure-activity relationships (QSARs) for their antibacterial activity. The data for the studied peptides were split three times into the training, calibration and test sets. The Monte Carlo method was used as a computational technique for QSAR models calculation. The statistical quality of QSAR for the antibacterial activity of peptides for the external validation set was: n=7, r(2)=0.8067, s=0.248 (split 1); n=6, r(2)=0.8319, s=0.169 (split 2); and n=6, r(2)=0.6996, s=0.297 (split 3). The stated statistical parameters favor the presented QSAR models in comparison to 2D and 3D descriptor based ones. The Monte Carlo method gave a reasonably good prediction for the antibacterial activity of peptides. The statistical quality of the prediction is different for three random splits. However, the predictive potential is reasonably well for all cases. The presented QSAR modeling approach can be an attractive alternative of 3D QSAR at least for the described peptides.

Chemopreventive potential of alpha lipoic acid in the treatment of colon and cervix cancer cell lines.

OBJECTIVES The nuclear factor κB regulates the expression of genes involved in many processes that play a key role in the development and progression of cancer. The aim of this study was to examine the influence of the alpha lipoic acid in the chemoprevention of colon and cervix carcinoma in vitro. BACKGROUND In recent years, special attention has been paid to the potential chemopreventive properties of antioxidants. There are no published data on the impact of alpha lipoc acid of chemoprevention of cervix and colon cancer. METHODS We examined the effect of alpha lipoic acid alone or in combination with cisplatin and 5-fluorouracil on proliferation of the two cell lines, HeLa (human cervical carcinoma cells) and Caco-2 (human colon cancer cells) by MTT test. The measurement of the level of transcription factor NF-κB was also performed in the cells of both cell lines. RESULTS At least one of the mechanisms of the antiproliferative and/or cytotoxic effect of alpha lipoic acid on Caco-2 and HeLa cells at high concentrations, the transcription factor NF-κB, may be involved, as well as the products of transcription of genes that are under its control. CONCLUSION The alpha lipoic acid has proven to be a promising candidate in the combat arena against cancer (Tab. 4, Ref. 31).

Maternal smoking during pregnancy and socioeconomic factors as predictors of low birth weight in term pregnancies in Nis

BACKGROUND/AIM Low birth weight (LBW) is a result of preterm birth or intrauterine growth retardation, and in both cases is the strongest single factor associated with perinatal and neonatal mortality. It is considered that socioeconomic factors, as well as mothers bad habits, play the most significant role in the development of LBW, which explains notable number of researches focused on this particular problem. The aim of this study was to characterize socioeconomic factors, as well as smoking habits of the mothers, and their connection with LBW. METHODS The questionnaire was carried out among mothers of 2 years old children (n = 956), born after 37 gestational weeks. The characteristics of mothers who had children with LBW, defined as < 2,500 g, (n = 50), were matched with the characteristices of mothers who had children > or = 2,500 g, (n = 906). For defining risk factors, and protective factors as well, we used univariant and multivariant logistic modeles. RESULTS As significant risk factors for LBW in an univariant model we had education level of the mothers, smoking during pregnancy, smoking before pregnancy, the number of daily cigarettes, the number of cigarettes used during pregnancy, paternal earnings and socioeconomic factors. In a multivariant model the most significant factors were socioeconomic factors, education level of the mothers, paternal earnings and mothers smoking during pregnancy. CONCLUSION Smoking during pregnancy and socioeconomic factors have great influence on LBW. Future studies should be carried out in different social groups, with the intention to define their influence on LBW and reproduction, as well. This should be the proper way of adequate health breeding planning for giving up smoking, the prevention of bad habits and melioration of mothers and children health, as the most vulnerable population.

Risk factors for the occurrence of cardovascular system diseases in students

BACKGROUND/AIM Cardiovascular diseases are a leading cause of death in the majority of developed, as well as in many developing countries. The aim of this study was to determine cardiovascular risk factors in student population and to suggest possible measures for prevention. METHODS The study was carried out during 2007-2008 at the School of Medicine, University of Nis. It included 824 students in their final year (220 males, 604 females). RESULTS There was no significant difference in prevalence of hypertension among the male (1.81%) and female students (0%). The prevalence of obesity (Body Mass Index - BMI > 30 kg/m2) was significantly higher (p < 0.001) in the male (7.27%) than in the female population (1.32%). Abdominal obesity was also more frequently encountered (p < 0.01) in the male (9.09%) than in female population (1.32%). Every fourth student smoked cigarettes with no significant difference between the male and female students. Alcohol consumption was a significantly higher problem (p < 0.001) in the male population (18.18%) than in the female one (2.65%). Physical inactivity was more often found (p < 0.001) in the female students (65.56%), than in male ones (36.36%). By the bivariate correlation of cardiovascular risk factors, it was determined that in the male student population systolic blood pressure correlated significantly with diastolic blood pressure, BMI and waist size, whereas age correlated with sistolic blood pressure, waist size and smoking. In the female students sistolic blood pressure correlated with diastolic blood pressure, BMI and waist size; diastolic blood pressure correlated with BMI and physical inactivity; cigarette smoking correlated with alcohol consumption and age. CONCLUSION Cardiovascular risk factors are present in the final-year students of the School of Medicine, University of Nis. It is necessary to insist on decreasing obesity prevalence, cigarette and alcohol consumption, and on increasing physical activity of students in order to prevent cardiovascular diseases.

Crosstalk between possible cytostatic and antiinflammatory potential of ketoprofen in the treatment of culture of colon and cervix cancer cell lines.

OBJECTIVES The aim of this study was to test the cytostatic potential of ketoprofen in the in vitro treatment of cells derived from colon and cervix cancer. BACKGROUND NF-κB and cyclooxygenase can have a role in different stages of the development and progression of cancer. In recent years, special attention has been paid to the possible cytostatic potential of nonsteroidal anti-inflammatory drugs. There are no published data on the use of ketoprofen in pharmacotherapy of the colon and cervical carcinoma. METHODS We examined the effect of ketoprofen alone or in combination with cisplatin and 5-fluorouracil on proliferation of the two cell lines, HeLa (human cervical carcinoma cells) and Caco-2 (human colon cancer cells) by MTT test. Measurement of the level of NF-κB was also performed in the cells of both cell lines. RESULTS The results of present study have shown that at least one of the mechanisms of antiproliferating and/or cytostatic effects of different concentrations of ketoprofen on Caco-2 and HeLa cells could include the transcription factor NF-κB. CONCLUSIONS Since this transcription factor is controlled by the altered expression of COX-2, the inhibition of this enzyme by ketoprofen may represent a significant step in synergistic cascade of the therapy and prevention of colon and cervical cancer (Tab. 4, Ref. 31).

[Effects of air pollution on children's health in Nis and Niska Banja].

BACKGROUND Epidemiological studies point out that air pollution in the cities was a major risk for health of the exposed population. In particular, the effects of air pollutants were adverse to the respiratory tract. In Nis and Niska Banja, the concetrations of pollutants were mainly below the threshold values. However, according to the literature, even these concentrations could exert negative effects, especially the health of the most sensitive group, such as the preschool children. The aim of our study was to evaluate the effects of the current levels of air pollutants in the city of Nis on respiratory symptoms and diseases. METHODS A pilot, cohort, retrospective study included 1 385 children of 1-5 years of age from the zones with statistically significant concentrations of air pollutants, in the period after the birth of the children. The prevalence of respiratory symptoms and diseases was determined on the basis of a modified WHO standard questionnaire completed by the parents. RESULTS It was revealed that in the more polluted of the studed zones, the prevalence of some respiratory symptoms (cough with cold and phlegm), and the lower respiratory tract diseases was significantly higher. CONCLUSION The results of our study showed that the current concentrations of air pollutants in Nis and Niska Banja could represent the important etiological factor for the development of respiratory symptoms and diseases. Our study showed that in the children of up to 5 years of age, the frequency of respiratory symptoms and diseases was significantly higher in more polluted than in less polluted environments.

A tissue-implant reaction associated with subcutan implantation of alpha-tricalcium phosphate, dental ceramic and hydroxyapatite bioceramics in rats

Calcium phosphate ceramics are among the more commonly used and biocompatible ceramics. Recently, we have synthesized a new calcium phosphate ceramic, alpha tricalcium phosphate (aTCP). The aim of this study was to assess the biocompatibility of this original, in our laboratory modified, newly synthesized aTCP ceramic, by carefully evaluating the inflammatory reaction of soft tissue in response to its subcutaneous implantation, and by comparing this result with the results of already widely used virtually non-toxic, non-immunogenic, and almost chemically inert dental (DC) and hydroxy apatite (HAP) ceramics. Implants (diameter 5x2 mm) of aTCP, DC and HAP were implanted into 12 adult male rats subcutaneously. At 2 weeks and 12 weeks post-implantation, the animals were euthanized and the tissueimplant reactions were analyzed histologically. Evaluation of routine stained sections (5 _m, hematoxylin & eosin) of the cutis and subcutis surrounding the aTCP, DC and HAP ceramics revealed the following: 1) all the ceramic devices had fibrous connective tissue capsules; 2) there were significant differences in the tissue - implant reactions based on the estimated time, while there were no differences in the tissue-implant reaction based on the type of ceramic material; 3) two weeks after implantation hyperemia and cellular proliferation were the most expressive results, while twelve weeks after implantation extensive angiogenesis and collagen fibers production were the prominent findings for all types of implanted calcium phosphate ceramics.