The mycotoxin zearalenone is often found in cereals and animal feeds. The intake of zearalenone through food can result in the hyperestrogenic syndrome, and is related to ovarian structural and functional alterations in mammals. It competitively binds to estrogen receptors and generates oxidative stress. Melatonin is a hormone produced by the pineal gland with a strong effect on reproduction as it inhibits the hypothalamic-pituitary-gonadal axis. It has also direct and indirect antioxidative effects in the ovarian tissues. Our aim was to explore the effect of melatonin on the histological changes of the ovary induced by zearalenone. Forty female Wistar rats were divided into five equal groups and treated for 28 days according to the following scheme: 1. Zearalenone vehiculum (sunflower oil)- treated group, 2. Melatonin vehiculum- (5% ethanol in Ringer) treated control group, 3. group treated with zearalenone (0.3 mg/kg b.w), 4. group treated with melatonin (10 mg/kg b.w) and 5. group of rats treated with zearalenone (0.3 mg/kg b.w) and melatonin (10 mg/kg b.w). Zearalenone induced degenerative changes in all developmental forms of ovarian follicles, hypertrophy of stroma with blood vessel dilatation and hyperemia. The concomitant application of melatonin and zearalenone resulted in milder morphological changes of the ovary, especially of preovulative follicles. Melatonin administration prevents the zaeralenone-induced structural alterations on an ovary. Keywords: zearalenone, melatonin, rat, ovary, histology

Previous studies linking the effect of certain pharmacological agents with the status of connective tissue and nerve fiber regeneration after traumatic transection were focused mainly on the proximal nerve stump. In our study, qualitative and quantitative histological analysis of the proximal and the distal nerve stump were done. Male Wistar rats underwent transection and excision of an 8-mm nerve segment of the left sciatic nerve. The vehiculum group of animals (n=7) was administered with 5% ethanol in Ringer solution (vehiculum), while the melatonin group (n=10) received 30mg/kg of melatonin dissolved in vehiculum, daily, intraperitoneally (i.p.) for 14 consecutive days. Then, intravital excision of the marginal zone of the proximal and distal nerve stump was performed and the samples were further processed for qualitative photomicroscopic and stereological analysis. Macroscopic and microscopic examinations of both nerve stumps showed absent or slight stump thickening in the melatonin group compared to the vehiculum group of animals, which is the result of reduced connective tissue proliferation. The mean epineurial volume density of the proximal nerve stump was statistically significantly lower (p=0,003) in the melatonin (0,36) than in the vehiculum group of animals (0,51). The difference in mean epineurial volume density of the distal stump was also statistically significant (p=0,039) with 0,33 in melatonin and 0,46 in the vehiculum group. Our study revealed that the administration of exogenous melatonin was effective in suppression of trauma-caused extrafascicular connective tissue proliferation in neuroma of the proximal nerve stump as well as fibroma formation in the distal nerve stump.

Introduction: Nephrotoxicity is a severe adverse effect of antituberculotics with acute renal failure as the most frequent clinical presentation. Associated patohistological feature is tubular necrosis or interstitial nephritis with or without glomerular lesions. The incidence of rifampicin induced kidney damage varies from 1,8% to 16% of all acute renal failures. A well defined clinical, patohistological and patophysiological features of rifampicin nephrotoxicity have not yet been determined and are generally missing. The aim of this study is to perform qualitative histological analysis of Wistar rat kidney after 21 day coadministration of rifampicin and isoniazid. Materials and methods: Twenty one adult male Wistar rats (210-280g) were divided into two groups: Control group (7 rats) and RIF+INH group (14 rats). The control group received 4ml/kg isotonic saline solution while animals in RIF+INH group were coadministered with rifampicin and isoniazid, dissolved in 4ml/kg of isotonic saline in dose of 50mg/kg. Dosing was performed intraperitoneally, daily, during 21 days. After that period animals were euthanized to obtain kidney tissue for histotechnological procedure. Kidney slides were stained with HE and PAS method and analysed using light microscopy. Results: The most important findings of our study were glomerular lesions while renal tubules were generally preserved. Lesions had patchy distribution, renal corpuscles were enlarged with possible mild mesangial hypertrophy. Glomerular capillary tufts showed shrinkage resulting in noticeably dilated Bowman’s space and sporadical lobulation of capillary loops. Conclusion: Intraperitoneal coadministration of rifampicin and isoniazid for 21 days, caused mild to moderate histological changes of kidney tissue in Wistar rats.

Objectives: Tuberculosis is still a major public health problem in developing world and in Bosnia and Herzegovina. Treatment of tuberculosis requires a “standard” combination of antituberculotics for a 6-month period. Prolonged use of isoniazid and rifampicin is associated with hepatotoxicity. The pathophysiology of hepatotoxicity is not yet elucidated, and suggested mechanism is oxidative stress. Isoniazid metabolite is considered to be responsible for the tissue damage through formation of free radicals. Methods : Twenty one adult male Wistar rats (210-280 g) were randomized into two groups. In group I (14 rats) animals received rifampicin (50 mg/kg) and isoniazid (50 mg/kg) dissolved in 4 ml/kg isotonic saline. Group II (7 rats) served as control and the animals received 4 ml/kg isotonic saline. The administration was performed intraperitoneally, during 21 days. The animals were sacrificed at the end of that period. Blood samples were obtained for biochemical analysis and liver tissue was processed by histotechnological method. Liver tissue was stained with H&E and PAS method and qualitative histological analysis was performed using light microscopy. Results : Our study revealed changes in liver tissue in the isoniazid-rifampicin treated group including enlargement and swelling of hepatocytes with vacuolization in centrilobular area, dilatation of sinusoids and mononuclear infiltration in portal space. Biochemical analysis of liver enzymes did not show significant difference between groups. Conclusion : In the isoniazid-rifampicin treated group of animals qualitative histological analysis revealed mild changes in liver tissue. Keywords : liver injury, isoniazid, rifampicin, rats, histology

Objectives: Two main and the most common types of congenital abdominal wall defects are omphalocele and gastroschisis. According to the literature, the frequency of omphalocele is generally stable, the rate of gastroschisis has increased lately, and cloacal exstrophy is a very rare birth defect. Methods: A retrospective study was performed on the basis of clinical records for the period January 2000. to December 2008. and the standard methods of descriptive statistics were performed for the data analysis. Investigation was carried out to obtain the frequency and gender distribution of congenitalabdominal wall defects among patients surgically treated in the Clinic for Children’s Surgery, Clinical Center University of Sarajevo,Bosnia and Herzegovina. Results: A register-based data show that total of 26 abdominal wall defect cases were surgically treated in the investigated period. Out of that number 15 (60%) were male patients, while 11 (40%) were female patients; sex ratio – 1.5:1. Twenty patients had gastroschisis, five omphalocele and one patient were with cloacal exstrophy. Anomalies associated with abdominal wall defects were present in total of six patients (23%), four male (15%) and two female (8%) patients. Conclusion: The study allows the conclusion that abdominal wall defects are generally rare congenital anomalies of which cloacal exstrophy is the rarest, the gastroschisis is on the rising trend and omphalocele is generally stable. Keywords: omphalocele, gastroschisis, cloacal exstrophy, frequency

The aim of this research was to assess the reactive changes of rat proximal tubules caused by gentamicin and the effect of relatively low doses of melatonin. 48 adult male Wistar rats were distributed into six groups of equal size which all received one of the following daily intraperitoneal injections: vehicle (5% ethanol in Ringer solution) during 11 days (C); gentamicin (80 mg/kg) during 8 days (G), two groups which concomitantly received gentamicin (80 mg/kg) during 8 days and melatonin in two different test doses (5 or 20 mg/kg) during 11 days (GM1, GM2) and two groups treated only with melatonin in two different doses (5 or 20 mg/kg) during 11 days (M1, M2). Histological analysis included qualitative and semi-quantitative light microscopy analysis of proximal tubules. Exogenous melatonin had no significant effect on the microstructure, independently of dosis. The changes of proximal tubules microstructure induced by gentamicin were expressed in the form of granulovacuolar degeneration, necrosis and desquamation. The grade of proximal tubular changes was smaller in animals who besides gentamicin received melatonin. Melatonin has a dose dependent protective effect on the structural alterations of proximal tubules of the kidney induced by gentamicin.

Research in this study had the character of retrospective study for which we used 24 adult female Wistar rats, who we reared under standardized laboratory conditions and divided into two groups: experimental and control. The experimental group consisted of a total of 12 animals who were classified into 2 subgroups: Z1 and Z2. The control group consisted of 12 untreated animals who were divided into 2 subgroups: K1 and K2. Once a day at regular intervals we applied by the gastric probe mycotoxin zearalenone previously dissolved in sunflower oil. To the animals in the control group we applied sunflower oil only. Dose of toxin administered was 0,5 mg/kg body weight, and a period of observation spanned two different time intervals-14 and 28 days. After completing the application of toxins, the animals were sacrificed under the general ether anesthesia and by the rules of autopsy techniques. Taken ovaries were prepared for histological and stereological analysis. Structural changes in the ovaries of treated animals were observed as degenerative changes, primarily at the level of the ovarian follicles and corpora lutea. The apparent findings in the stroma were in terms of its hipercelularity and marked hyperemia of the blood vessels. The longer the application period, the more pronounced the changes. The resulting qualitative histological changes in the ovaries of treated rats were objectified quantitatively - by stereology. We found changes in terms of decreasing volume density of functional elements of the parenchyma (ovarian follicles and corpora lutea), and increased volume density of ovarian stroma with blood vessels. Key words: zearalenone, rat, ovary, qualitative changes, stereology

We have investigated heart type fatty acid binding protein (H-FABP) rat serum values at different time point following subcutaneous (s.c) isoproterenol (ISO) administration and their correlation with severity of myocardial lesion. Thirty adult, male, Wistar rats were used for this study. Six rats per group were treated with a single dose of either ISO (ISO groups, dose 100 mg/kg, s.c.) at different time point (30', 60', 120', 240') or with saline (control group). Serum H-FABP was determined by enzyme-linked immunosorbent assay (ELISA) and histological analysis was performed by hematoxylin-eosin (HE) method of staining. The first serum H-FABP increase was obtained 30' following ISO administration, but maximal value was reached after 240'. Myocardial histological changes were time-dependent and correlated with serum H-FABP values (p<0.001). The results of the study suggest that H-FABP is sensitive marker for acute rat myocardial injury and its possible inclusion in myocardial injury screening studies in rats.

AIM To develop a rat model of myocardial infarction induced by isoproterenol (ISO). We investigated a type of histological myocardial changes and cardiac troponin I (TnI) kinetic. METHODS The study has used adult, male, Wistar strain rats. Rats were distributed in ISO and control groups. Rats treated with ISO were divided into groups according to the time of cTnI and myocardial lesion analyses: ISO I (30'), ISO II (60'), ISO III (120') and ISO IV (240'). We determined cTnI (Life Diagnostics Inc. West Chester PA, USA) in the serum by ELISA method. We performed histological analysis on the specimens of left ventricular wall stained by hematoxillin-eosin (HE) method. RESULTS The first statistically significant rise of cTnI was noted 30 minutes after the ISO administration. There was no statistically significant difference between cTnI mean values among the ISO groups. Observed myocardial histological changes were time dependent. CONCLUSIONS This model can be suitable for cardioprotective and cardiotoxicity supstance investigations followed by cTnI measurement in blood. The similarity between induced myocardial lesion on animal model in our study and human myocardial lesion in ischemia give us sufficient impulse for further preclinical researches of new cardiac markers.