The objective of this study was to confirm the effects of curcumin and to investigate the effects of its combination with a reduced dose of rosuvastatin in an adenine-induced model of chronic kidney disease (CKD) and associated dyslipidemia in rats. Renal function and morphology, as well as lipid status, were assessed using laboratory parameters and histopathological analysis. Male Wistar rats (n=36) randomly divided into six groups, were treated for 24 days: normal control (standard diet), CKD control (adenine diet, 0.75% w/w adenine-supplemented diet), curcumin (100 mg/kg/day + adenine diet), rosuvastatin minimal therapeutic dose (MTD) (5 mg/day + adenine diet), rosuvastatin reduced dose (RD, 25% of rosuvastatin MTD + adenine diet), and rosuvastatin RD + curcumin (25% of rosuvastatin MTD + curcumin 100 mg/kg/day + adenine diet) group. While rosuvastatin alone showed only antilipemic action, both curcumin alone and its combination with a reduced dose of rosuvastatin showed better renal protection with lower serum creatinine levels and milder renal morphological alterations, as well as better antilipemic action with lower levels of triglycerides, very low-density lipoprotein (VLDL), and low-density lipoprotein (LDL) cholesterols compared with the levels in CKD control rats. Treatment with curcumin alone also resulted in a significantly higher estimated glomerular filtration rate, lower uric acid levels, and higher high-density lipoprotein (HDL) cholesterol, while the combined therapy additionally resulted in higher serum albumin levels, lower total cholesterol, and both atherogenic and coronary risk indexes compared with CKD control rats. The results of this study confirmed the beneficial effects of curcumin alone and provided new evidence for the beneficial effects of its combination with a reduced dose of rosuvastatin in rats with CKD and associated dyslipidemia.

Aim To determine the value of angles between the left coronary artery main trunk (LMT) and its branches, the anterior interventricular branch (LAD) and the circumflex branch (CX), and their possible relationship with the LMT length. Methods A total of 29 cadaveric hearts were used. The left coronary artery and its branches were dissected. The hearts were then classified according to the number of branches. The LMT length was measured with a digital gauge, and the LAD-CX angle, LMTLAD angle and LMT-CX angle with a manual goniometer. Results The average value of the LMT length was 9.0 mm (6.0-13.5). In 20 (68.97%) samples, the LMT was divided into two terminal branches. There was no statistically significant difference (p=0.321) in LMT length between the hearts with a bifurcation and without it. The average value of the LAD-CX angle was 89.0⁰ (74.5-93.0), with a statistically significant difference (p=0.020) comparing to hearts with trifurcation. The mean value of the LMT-LAD angle was 30.83±9.23⁰ and it was significantly lower (p=0.006) in the group of hearts with bifurcation compared to the group with trifurcation of the main trunk. Conclusion The LMT length shows great variability and is not related to the LAD-CX, LMT-LAD or the LMT-CX angle. Knowledge of the left coronary variation is essential in order to avoid misinterpretation of arteriogram.

Introduction: The human heart is in most cases vascularized by two coronary arteries, the right coronary artery (RCA) and the left coronary artery. The supernumerary coronary artery, which arises independently from the right aortic sinus and passes through sub-epicardial adipose tissue of the pulmonary conus and anterior side of the right ventricle is called the third coronary artery (TCA). Methods: This study consisted of 28 formalin-fixed adult human cadaveric hearts. The presence of the TCA was determined. The position of the orifice of the right and excess arteries in relation to the sinotubular junction was determined, and then also the position of the orifice of the excess arteries “on the o’clock level” in relation to the orifice of the RCA. The radius of these orifices and their distance from the orifice of the RCA were measured. The angle between the aorta and TCA, as well as RCA and conus branch, was measured. Results: A total 11 of specimens had supernumerary arteries. A supernumerary artery was found in two hearts. The angle formed by the aorta with the TCA was 60.09 ± 17.57, while the angle between the aorta and the conus branch had an average value of 89.88 ± 15.92. The orifices of all supernumerary arteries were located below the level of the sinotubular junction. The average diameter of the TCA was 1.49 mm ± 0.41. The average distance between the TCA orifice and the RCA orifice was 2.21 mm ± 1.03. In 45.45% cases, the orifice of TCA was located at the 10 o’clock level. Conclusion: The present study highlights the presence of the TCA. It may constitute a significant collateral circulation contributing to apical and septal perfusion. Interpretation of signs and symptoms of coronary occlusion should therefore include possible contribution of this vascular channel.

Background: Zearalenone is a widely spread mycotoxin, contaminant of most cereal grains. It has uterotropic, estrogenic and anabolic activity in farm animals. The results are hormonal disbalances as hyperestrogenism, Zearalenone inhibits follicle-stimulating hormone production, thus supressing ovarian follicle development and ovulation. Also, it induces oxidative stress. Melatonin acts as a potent natural antioxidant and regulates the reproductive function by modification of steroidogenesis. Objective: The present study was conducted to provide detailed qualitative histological analysis of uterus of female rats treated with zearalenone and melatonin and contribute to better understanding of the topic. Methods: Forty adult, female Wistar rats were equally divided into five groups: Z group – zearalenone, 0,3 mg/kg, i.g.; M group – melatonin, 10 mg/kg, i.p.; ZM group –concomitant application of zearalenone and melatonin in the same dosing regimen, VZ group–zearalenone vehiculum/sunflower oil, i.g. and MZ group–melatonin vehiculum/5% ethanol in Ringer, i.p. Animals were treated daily for 28 consecutive days. After that period, all animals were sacrificed to obtain samples for qualitative histological analysis using the light microscope. Results: Zearalenone led to the alterations of the uterine structures, predominantly in the endometrium that were characterized by metaplasia and hypertrophy of the epithelial cells and hypercellularity of the stroma. In the myometrium, zearalenone induced hypertrophy and hyperplasia of the myocytes. Conclusion: Melatonin, when applied together with zearalenone, blocked the adverse effects of the zearalenone.

Objectives The aim of this study was to investigate the effects of pinealectomy and melatonin treatment on the rat thymus gland characteristics, taking into consideration possible gender differences. Materials and methods Thirty adult Wistar rats of both sexes were divided into three groups. Group C and group PX served as control groups and included sham-pinealectomized and pinealectomized animals that were treated with 10% ethanol solution (0,1ml/daily, subcutaneous). Animals from third group (group PXM) underwent pinealectomy and seven days after surgery started receiving melatonin dissolved in 10% ethanol solution (3mg/kg/daily, subcutaneous). All animals were treated for 4 weeks. Results Volume density of the thymus cortex showed statistically significant (p<0,05) decrease while the volume density of the thymus medulla was increased in the pinealectomized compared to the sham-pinealectomized female rats. Numerical density of macrophages as well as the distribution of blood vessels showed no gender differences. The numerical density of lymphocytes was statistically significantly decreased in female in comparison to the male pinealectomized rats. Melatonin treatment was proved to cause reverse effects in the sense that the results from the melatonin treated group corresponded to the results obtained from the control group of animals. Conclusion The results of this study suggest that the pinealectomy causes gender-related changes in the rat thymus. Short-term melatonin treatment showed reverse effect, equally in both sexes.

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