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Dina Lagumdžija, Aida Hamzić Mehmedbašić, D. Jesenković, Bakir Kudić, Dina Kapić, E. Ćosović, O. Lepara, Belma Pehlivanović Kelle et al.

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.

The purpose of this study was to explore possible protective effects of vitamin D3 on serum glucose concentration, body weight and histopathology of pancreas and liver. Animals were divided into 3 groups: Control group (n=6), streptozotocin (STZ) group (n=6) and streptozotocin + vitamin D3 (STZ+D3) group (n=6). Rats in the STZ+D3 group starting from the 7th day of experiment were given vitamin D3 for 14 days. Glucose levels and body weight were measured on the 1, 7, 14 and 21st day of experiment. Qualitative histological analysis of pancreas and liver was done using the light microscope with a digital camera. Differences between the groups were tested by one-way analysis of variance (ANOVA) followed by Dunnett's posttest. Differences in repeated measures were tested using paired t-test. On day 14 and 21, blood glucose level in STZ+D3 group was significantly higher compared to the control group of animals but significantly lower than the glucose level registered in STZ group of rats. On day 14 and day 21, body weight in STZ rats was significantly lower compared to weight in STZ+D3 and control groups of rats. Morphological changes, such as shrinkage of islets, vacuolation of both endocrine and exocrine cells, were observed in pancreas of STZ group of animals but were nearly absent in STZ+D3 rats. Similarly, STZ+D3 group of rats showed preserved liver histoarchitecture. Obtained results suggest that vitamin D3 treatment reduces hyperglycemia, exerts beneficial effects on body weight and alleviates histopathological changes in pancreas and liver in STZ-induced diabetic rats.

Introduction: High opening injection pressure (> 15 psi) can detect needle nerve contact. However, the reliability of injection pressure monitoring to detect needle – nerve or impingement may be affected by syringe size. We hypothesized that monitoring of opening injection pressure (the pressure at which injectate is detected by US) is affected by the size of the syringe used for injection. Methods: After Ethics Commitee approval, 22 gauge 50 mm needles were inserted under US to contact the C5, C6 and C7 nerve roots of fresh human cadavers. Hand-held injections were made using 3 different syringe sizes (5, 10, 20 mL) at a rate commensurate with typical clinical practice. Injections were made bilaterally at each of the above nerve roots. Opening injection pressure data were aquired with an in-line digital pressure recorder using a 60 mL syringe (10ml/min), and injection halted when spread was detected. Results: A total of 48 injection measurements were made. The peak (opening) pressures at which injection commenced in two cadavers were 30.50 psi and 34.07 psi with 5 mL syringe, 29.20 psi and 34.95 psi for 10 mL syringe, 26.03 psi and 29.42 psi for 20 mL syringe, all han-held injection. In automated pump injection 60 mL syringe was used, and maximum achieved pressures were 23.42 psi and 34.03 psi. Opening injection pressures were similar regarless of syringe size (p>0.05). Conclusion: The size of the syringe commonly used in clinical practice of peripheral nerve blockade did not significantly affect the monitoring of the open injection pressure. All injection with the needle – nerve contact resulted in injetion pressure > 20 psi, regardless of syringe size or method of injection. Our findings ate thus consistent with the fluid mechaminc described by Pascal's Law, where pressure exerted anywhere in a confined incompressible fluid system is transmited equally throughout until the opening pressure is reached and injection begins.

OBJECTIVES Dinuclear ruthenium(II) Schiff base complex was selected for in vivo study among many other novel metal-based compounds, because of its previously proved in vitro anticancer and antibacterial properties. The aim was to investigate the potential toxicity of this compound in animal model through biochemical and histopathological assessment. METHODS Adult Swiss albino mice of both sexes were divided into high-dose and low-dose group that received a single intraperitoneal dose of ruthenium complex (175 mg/kg and 25 mg/kg, respectively) and one control group (vehicle only). After a follow-up period of 14 days, animals were sacrificed to obtain blood samples and organs. RESULTS The test compound was well tolerated in a low-dose group and did not cause any mortality. The histological findings and serum biochemistry suggested a reversible character of alterations found in vital organs of this group. However, in the high-dose group, adverse effects were more severe and indicated dose and gender-related toxicity. CONCLUSION Mild side effects found in a low-dose group together with excellent in vitro properties, made dinuclear ruthenium(II) Schiff base complex a promising candidate for further investigation and development as anticancer and antimicrobial agent (Tab. 4, Fig. 6, Ref. 32).

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

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.

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