Genotoxic effects of inorganic molecule dipotassium-trioxohydroxytetrafluorotriborate, K2(B3O3F4OH), a promising new therapeutic for the epidermal changes treatment, have been evaluated. In vitro analysis included evaluation of genotoxic and cytotoxic potential of K2(B3O3F4OH) in concentrations of 0.01, 0.02, 0.05 and 0.06 mg/mL applying cytokinesis-block micronucleus cytome assay in human lymphocyte culture. With the increase of concentration the frequency of micronuclei elevated but the differences were not significant. Also, there were no significant differences among the frequencies of nuclear buds and nucleoplasmic bridges between controls and treated cultures. Nuclear division index and nuclear division cytotoxycity index values did not reveal significant cytotoxic effect of K2(B3O3F4OH). In vivo genotoxic effects were analyzed on BALB/c mice applying reticulocytes micronucleus assay. K2(B3O3F4OH) was administrated intraperitoneally in final concentrations of 10, 20, 50 and 55 mg/kg. Significant decrease of reticulocytes ratio and increase of micronuclei frequencies against pre-treatments were found for both sampling periods of 48 and 72 hours of the highest applied concentration. This study confirmed that K2(B3O3F4OH) is not genotoxic in tested concentrations in vitro as well as in concentrations lower than 55 mg/kg in vivo. This study presents a reliable basis for further pre-clinical and potential clinical investigations.

Enkorten is a new potential drug for the treatment of rheumatoid arthritis, with an immunomodulatory and anti-inflammatory effect. It is a combination of two peptide components of endogenous origin: methionine-enkephalin of 5 mg and tridecactide of 1 mg (Picture 1 and 2). According to the chemical structures, these components correspond to amino acid sequences of the neuropeptide precursor proopiomelanocortin.

Exposure to the lead is public health problem and threat to environment with proven harmful impact on human, including industrial workers and general population. Harmful impacts of exposition to nervous, endocrine, hematological, cardiovascular, immune and reproductive system to the lead are well known. This article addresses the results of retrospective research carried out with attendants at gas station and those who are professionally exposed to inorganic lead (n=73; n=81), during the course of two periodic reviews performed in 2003 and 2008. All subjects underwent physical examination, ECG, were measured blood pressure and laboratory tests encompassing basic hematological parameters, including measuring of blood lead level (BLL), as bioindicators of exposure and biomarkers of toxic impact of the lead, by the means of determining concentration of 6-aminolevulinic acid in urine (ALA).Valued obtained included (arithmetic mean +/- standard deviation): for BLL 42.5 +/- 26.2 microg/L(-1), for ALA 35.2 +/- 10.6 micromol/L(-1). Quoted values are within normal values for general population. Correlation test established positive correlation between BLL and hematological parameters, number of erythrocytes, concentration of hemoglobin and MCV, and the same correlation ratio was established between BLL and years of age, years of service and exposition years of service as well as BLL and GGT. There was not established correlation between ALA and observed hematological parameters, BLL and systole pressure. Data from our research indicate unification between professional exposure to lead and duration of exposure and increase of concentration of BLL, which are far bellow marginalvalue, but do exceed average values of BLL for people of industrial countries with possible generation of harmful impact of lead. Likewise, the results suggest the increase of overall lead load in the body does not have to be necessarily only the result of professional exposure, but of the intake through other channels as well.

Xenobiotic solutions of different concentrations were analyzed by TLC method before and after passing trough the column with adsorbent M and compared with adsorption on the active charcoal. The efficiency of adsorption on adsorbent M was higher, compared to active charcoal. The best adsorption, in the value 90 - 100%, have shown certain organochlorine and organophosphorus pesticides, that were dissolved in non-aqueous solvents. Efficiency of adsorbent M was also proven in vivo, when solutions of tested xenobiotics before adsorption have caused death of experimental animals, and after the adsorption on adsorbent M, all treated animals have survived and had just mild symptoms of poisoning.

Gentamicin is still widely used in clinical practice in spite of its renal toxicity. The role of nitric oxide (NO) in that process is not completely elucidated. The aim of this study was to investigate the relationship between plasma level of NO and the histopathological changes of kidney in acute tubular necrosis (ATN) induced by gentamicin in rats. Study was carried out in Albino-Wistar rats, both sexes (n=16), average body weight 200-250 g. divided in two equal groups: control and gentamicin group. The control group was injected with 0.9% NaCl i.p. and gentamicin group was injected with gentamicin in the dose of 80 mg/kg/day i.p. in a period of 5 consecutive days. NO plasma level was determined by the production of nitrates and nitrites using classical colorimetrical Griess reaction. Kidney specimens were stained with hematoxylin-eosin (H-E) and Periodic acid-Schiff (PAS) stain. Semiquantitative histological analysis was used for the evaluation of the level of kidney damage. Both, the plasma NO level and the level of kidney damage were statistically higher in rats with gentamicin-induced ATN in comparison to the control group. In spite of that the correlation between plasma NO level and the level of kidney damage was not found. The rise of plasma level NO in gentamicin induced ATN in rats could possibly indicate on the role of NO in renal damage caused by gentamicin.

BACKGROUND AND PURPOSE Clinical research of drugs is a researching step subsequent to the preclinical studies in experimental animals. The aim of our research was to evaluate animal model of wound healing process after the burn inducement and effects of the ointment containing natural plants on the process of burn healing. MATERIAL AND METHODS Burn wounds were experimentally induced in two species of experimental animals which were treated with topically applied herbal preparation with concomitant monitoring of the healing process. Experimental groups (1) of 15 animals each (mice and rats), while control group (2) of 10 animals each (mice and rats) that were not being treated with herbal ointment. After the hair removal, burn was induced on the back of animals by heated brass seal. Different clinical symptoms including oedema of surrounding tissue, redness, exudation, size of the burn surface, histological and microbiological findings were monitored on the days 1, 3, 7, 14 and 21. A statistically significant difference was observed throughout descriptive statistics and paired Student's t-test. CONCLUSION Physiological healing processes of the acute burn wound following the topical application of herbal preparation can be monitored on the utilized animal model. A three-week treatment resulted in the 90% of completed epithelization in both animal species, indicating the effectiveness of topically applied herbal preparation.

Experimental studies of burns require the use of different animal models with the aim to imitate and reproduce pathophysiological conditions. The aim of this work was to establish experimental model of thermal injury. New Zealand rabbits, weighted from 1.8 kg to 2.3 kg, were utilised during our study. Another, also utilized, animal types were laboratory Rattus rats, species Wistar, albino type, females with body weight of about 232 g. All animals were from our own litter (Institute of Pharmacology, Clinical Pharmacology and Toxicology, Faculty of Medicine in Sarajevo). During the experiment, animal were properly situated in adequate cages and rooms, at the controlled temperature (22 +/- 2 degrees C), and in the air with normal humidity level. All animals took food and water ad libitum. Rabbits received anesthesia--intravenous pentobarbital sodium in a dose of 60 mg/kg, and then, hair from the upper side of the each rabbit ear was removed and burns were caused by a metal seal in the same manner as in rats. Rats were primarily anesthesied by intraperitoneal pentobarbital sodium in a dose of 35 mg/kg, and then, their hair was removed from the scapula zone (5 cm x 5 cm). Burns were caused by contact with a round metal seal, heated at 80 degrees C in a water bath, during the period of 14 seconds together with contact thermometer control. Round metal seal (radius: 2.5 cm; weight: 100 g; surface: 5 cm2) was just placed on the rat skin without any additional pressure. In order to maintain the microcirculation in the burn wound and to reduce the conversion of partial-thickness skin burns to the burns of the full-thickness skin, all burn wounds were immediately sunk in the 4 degrees C water. Subsequent to that procedure, all animals were individually situated in the proper cages, and left to rest for 4 hours with a constant cautious monitoring of the wound development and animal general state.