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Publikacije (14)

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Nina Čamdžić, V. Muzika, S. Čustović, M. Babić, Mirsad Dorić, Edina Lazović Salčin, Suada Kuskunović-Vlahovljak

Abstract Objective of this study was to identify the histopathological patterns and their frequency in testicular biopsy specimens from azoospermic patients and to categorize it according to Modified Johnsen scoring system. Methods: Testicular biopsies from male patients with clinical diagnosis of azoospermia were included in this study. All tissue samples were fixed in buffered 10% formalin, routinely processed and stained with Hematoxylin and Eosin. All cases were examined microscopically and categorized according to the histopathological patterns and Modified Johnsen scoring system. Results: Total 219 cases of testicular biopsies from 125 azoospermic male patients were evaluated, with 94 cases of bilateral testicular biopsy. The most prevalent age group was of 30-39 years (66.2%). The most common histological pattern was of Sertoli cell only syndrome (58.4%) while the least represented pattern was germ cell maturation arrest, seen in 4.6% cases. The most common Modified Johnsen score was 2 (66.7%). There was discordance in histologic pattern in both testes in 12.76% of patients who had bilateral testicular biopsy. Conclusion: Our study gives an insight on the most common histopathological patterns of azoospermic patients and emphasizes the need for a better national statistics and epidemiological studies of this entity. It also points out the significance of the bilateral testicular biopsy, as both, diagnostic and therapeutic procedure.

Maida Šahinović, Dina Kapić, E. Ćosović, S. Aličelebić, S. Čustović, V. Muzika, Eldan Kapur, Almira Lujinović et al.

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.

Asija Začiragić, V. Muzika, A. Valjevac, A. Dervišević, Maja Mitrašinović Brulić, M. Fočak, E. Ćosović, S. Aličelebić et al.

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.

V. Muzika, S. Čustović, S. Aličelebić, E. Ćosović, A. Zahirović, E. Kahrović

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).

Maida Šahinović, S. Aličelebić, Z. Mornjaković, E. Ćosović, Dina Kapić, Eldan Kapur, S. Mačkić, V. Muzika et al.

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

I. Susko, S. Aličelebić, E. Ćosović, Maida Šahinović, Dina Kapić, S. Čustović, V. Muzika

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.

E. Ćosović, Z. Mornjaković, S. Aličelebić, Dina Kapić, Maida Šahinović, Almira Lujinović, V. Muzika, S. Čustović

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.

S. Aličelebić, Fatima Gavrankapetanović Smailbegović, Alena Pehlić, V. Muzika, S. Čustović

Objectives: The aim of this study was to evaluate relation of preterm delivery with mother´s age, premature rupture of amniotic sac, number of spontaneous vaginal deliveries or Cesarean sections (C-sections), Apgar score in the first and the fifth minute, as well as birth weight of newborns. Methods: The study was retrospective, comparative, and data were obtained at the Clinic of Obstetrics and Gynecology of the University Clinical Centre Sarajevo for the period from October 2013 through February 2014. The sample was divided into two groups based on the timing of delivery: preterm delivery group (before 37th week of pregnancy) and term delivery group (after 37th week of pregnancy). The standard methods of descriptive statistics and the univariate analysis were performed. Results: Univariate analysis showed that there was no significant association of mother´s age with preterm delivery (OR=1.02, CI: 0.94, 1.10; p=0.72). Rupture of fetal membranes was 4.53 (OR=4.53, CI:1.95, 10.51, p<0.001) while C-section was 9.8 (OR=9.80, CI: 3.34, 36.14; p<0.001) times more frequent in preterm compared to term delivery group. Severely depressed Apgar score (0-3) was 84% (OR=1.84, CI: 1.01, 03.35; p=0.046) more frequent in the first and 52% (OR=1.52, CI: 0.72, 2.98; p=0.29) more frequent in the fifth minute after preterm compared to term delivery. Low birth weight (<2500g) was associated with preterm delivery group (OR=3.78, CI: 1.75, 9.33, p<0.001). Conclusion: Significant association of preterm deliveries with rupture of fetal membranes, C-section, severely depressed one-minute Apgar score (0-3) and low birth weight was documented. Keywords: premature membranes rupture, Apgar score, Cesarean section

V. Muzika, S. Čustović, Z. Mornjaković, E. Ćosović, Dina Kapić

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.

S. Čustović, V. Muzika, Z. Mornjaković, E. Ćosović, Dina Kapić

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

Almira Hadžović-Džuvo, A. Valjevac, O. Lepara, S. Čustović, A. Vatreš, Alma Agačević, Samra Rahmanović, Sabina Zukic

Objectives: Postmenopausal period is associated with the decline in antioxidant levels due to gradual loss of estrogen, increased body weight and central adiposity. The present study aimed to evaluate association of adiposity and regional fat distribution with total antioxidant capacity in postmenopausal women. Methods: This cross-sectional study included 90 apparently healthy postmenopausal women. We measured anthropometric indices including body mass index (BMI), waist circumference (WC) and waist-hip ratio (W/H ratio). Total fat mass (TFM), total lean mass (TLM), percentage fat mass (%FM), visceral fat diameter (VFD) and subcutaneous fat diameter (SFD) were measured using ultrasound. Serum total antioxidant capacity (TAC) was measured by quantitative colorimetric determination using Total antioxidant Capacity -QuantiCromAntioxidant Assay Kit (BioAssay systems, USA; DTAC-100). Results: Out of 90 postmenopausal women, 35.9% were overweight and 25.0% obese, while 60.9% had central obesity. Postmenopausal obese women had significantly lower median TAC level [308.3 (283.0-375.1)] mM Trolox equivalents compared to overweight [383.38 (356.5-389.4) mM Trolox equivalents; p<0.001] and normal weight women [376.3 (318.0-388.7) mM Trolox equivalents; p<0.005]. Serum logTAC level was inversely associated with BMI, TFM, TLM and WC in postmenopausal women. However, when stratified by central obesity, inverse associations between serum logTAC level and BMI (r=-0.503; p<0.001), TFM (r=-0.383, p=0.004) and WC (r=-0.408; p=0.002) were observed only in postmenopausal women with central obesity. Conclusion: Our results provide evidence that obesity and central obesity during postmenopausal period are associated with decreased total antioxidant capacity and depleted antioxidant defenses possibly due to elevated oxidative stress. Larger prospective studies are needed to evaluate whether obese postmenopausal women might benefit from antioxidants supplementation for the prevention of obesity related diseases. Keywords: total antioxidant capacity, oxidative stress, obesity, overweight

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