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Dina Kapić

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Sanja Jovičić, Ivan R Nikolić, L. Božić, M. Jović, Dina Kapić, R. Škrbić

Background: Hofbauer cells (HBCs) are the only immunocompetent cells within the stroma of chorionic villi and play a key role in immune regulation and placental development throughout gestation. Their phenotype, abundance, and proliferative activity change in accordance with the needs of the fetoplacental unit. Methods: Thirty healthy human placentas across all three trimesters were analyzed. Samples were processed using standard histological protocols and immunohistochemically stained with CD45, CD68, CD86, and Ki-67 markers. Morphometric analysis was performed to determine the following parameters: percentage of HBCs, numerical areal density, and proliferative index. Results: HBCs were immunoreactive for CD45 and CD68, while CD86 immunoreactivity was not observed in any trimester. The proportion of HBCs was highest in the second trimester and lowest in the third. Numerical areal density was highest in the second trimester (22.21 ± 3.86) and lowest in the first (8.27 ± 4.18). The proliferative index was highest in the first trimester (82.45 ± 10.19%), decreased significantly in the second, and was completely absent in the third trimester. Conclusions: During physiological placental development, Hofbauer cells maintain a predominantly non-M1 macrophage phenotype, accompanied by a gradual reduction in proliferative activity.

ABSTRACT Diabetic nephropathy (DN) is a major microvascular complication of diabetes mellitus and the leading cause of end‐stage renal disease. Oxidative stress and inflammation are central drivers of DN progression, yet no effective therapies exist to prevent or delay renal injury. This study investigated the renoprotective effects of glycine (GLY), N‐acetylcysteine (NAC), and their combination administered at early versus late stages of streptozotocin induced diabetes. Forty‐eight male Wistar rats (n = 48) were allocated into five groups: healthy controls (Group 1, n = 6), untreated diabetic rats (Group 2, n = 6), and three treatment groups (Groups 3–5, each n = 12). Diabetes was induced by a single intraperitoneal streptozotocin injection (55 mg/kg). Group 3 received NAC (100 mg/kg), Group 4 received GLY (250 mg/kg), and Group 5 received NAC + GLY. Each treatment group was subdivided into early (6 week, n = 6) and late (12 week, n = 6) intervention subgroups. Treatments were administered orally. Renal tissue was evaluated using classic histology, geometric morphometric analysis, and biochemical assays of superoxide dismutase (SOD) and myeloperoxidase (MPO). Statistical analyzes were performed using ANOVA with appropriate post hoc tests (p < 0.05). Untreated diabetic rats (Group 2) showed significantly decreased SOD activity, increased MPO levels, marked mesangial matrix expansion, glomerular hypercellularity, tubular epithelial degeneration, and interstitial inflammation with fibrosis. NAC (Group 3) and GLY (Group 4) each improved oxidative stress markers and partially restored glomerular and tubular morphology, with early treatment subgroups exhibiting more substantial benefit than late subgroups. The combined NAC + GLY therapy (Group 5) demonstrated the strongest renoprotective effect, preserving renal structure and biochemical parameters closest to healthy controls. To conclude, early combined administration of glycine and N‐acetylcysteine yields superior protection against diabetes‐induced renal injury compared with individual treatments. These findings support the therapeutic potential of antioxidant‐amino acid combinations in preventing or delaying diabetic nephropathy.

Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by inflammation and destruction of cartilage, as well as by extra-articular manifestations. Rheumatoid nephropathy is a common complication of RA and its principal target is the renal corpuscle. Vitamin D and its analogs exert immunomodulatory actions throughout the body due to the widespread of their receptors. Our study aimed to compare the effects of cholecalciferol (vitamin D3) and alfacalcidol on renal corpuscle changes in pristane-induced RA model following a 28-day treatment, using geometric morphometrics. Forty female Wistar rats (190–210 g; 12–13 weeks old) were randomly assigned to four groups: the control (Cont) group (n = 10) received saline i.c., the PIA group (n = 10) was administered pristane i.c., PIA-ALF group (n = 10) was administered pristane i.c. and alfacalcidol orally, and the PIA-CH group (n = 10) was injected i.c. with pristane and received cholecalciferol orally. Pristane administration was used for RA induction. At the end of the experiment, the left kidneys were removed and processed by standard histological procedures for geometric morphometric analysis. Geometric morphometric analysis demonstrated that, compared with the control group, the architecture of the renal corpuscles was altered in the PIA (p < 0.0001) and PIA-CH (p = 0.0065) groups. In contrast, no statistically significant differences were observed in the PIA-ALF group (p = 0.3011). Geometric morphometric analysis demonstrated that alfacalcidol, but not cholecalciferol, exertedaprotective effect on the renal corpuscle architecture in pristane-induced rheumatoid arthritis in rats.

Background: Different dietary components can affect hematological and biochemical profiles, potentially causing pathohistological changes in liver and kidney tissue. Aim: The animals in the experiment consumed various bakery and meat products, and ultimately, the potential effects on hematological, biochemical, and pathological parameters were evaluated. Methods: The study involved 24 clinically healthy adult rats, randomized into three groups of eight rats each, as follows: rats that consumed meat products (group M), rats that consumed bakery products (group H), and a control group that consumed conventional rodent food (group K) for 7 weeks. After 7 weeks, hematological and biochemical blood analyses were conducted along with pathohistological examinations of the liver and kidneys. Results: Significant differences (p < 0.05) were observed among groups for several hematological and biochemical parameters, including creatinine (CREA), urea, blood urea nitrogen /CREA, calcium, alanine transaminase, alkaline phosphatase, and lipase. Consuming meat products had a less favorable impact on the occurrence of kidney function disorders. Group H exhibited significant differences in leukocyte and platelet counts compared with groups M and K. Extreme echinocytosis was recorded in group M, whereas sideropenic anemia was prominent in group H. Analysis of the livers of rats in groups K and H did not show significant differences in the observed parameters (gamma-glutamyl transferase and total bilirubin), whereas group M had a significantly higher degree of hepatocyte degeneration and steatosis, and the observed infiltrate was also more pronounced, but not significantly. The kidneys of group M showed discrete alterations of the microstructure, i.e., slightly increased cellularity of renal corpuscles and hypertrophy of proximal nephrocyte, whereas the kidney tissue of group K had a regular appearance. Conclusion: Consuming meat products was associated with adverse liver and kidney changes, whereas bakery products led to sideropenic anemia and altered hematological values.

Background: Gentamicin is a potent, broad-spectrum aminoglycoside antibiotic used in the treatment of many infections. Gentamicin can induce hepatotoxicity through oxidative stress and apoptosis. Since melatonin has antioxidant properties, its protective effects on liver tissue damage were evaluated in this study. Objective: The aim of this study was to conduct our investigation to assess the hepatoprotective effects of melatonin in rats treated with gentamicin. Methods: Forty eight adult male Wistar rats were used. The animals were randomly distributed into six groups of equal size. During the period of 11 days, three control groups of rats were daily injected i.p. with the vehicle or with melatonin at a dose of 5 or 10 mg/kg. The gentamicin group was injected with gentamicin at a dose of 80 mg/kg during 8 days and vehicle for 11 days. The other two experimental groups were administered gentamicin (80 mg/kg during) 8 days and melatonin (doses of 5 and 10 mg/kg) 3 days before and 8 days concomitantly with melatonin. Obtained liver sections were analyzed using qualitative, semi-quantitative, and stereological analysis. Results: Gentamicin expressed hepatotoxic effects inducing congestion of lobular blood vessels, hydropic degeneration of periportal hepatocytes and mononuclear infiltration in the portal tract. Treatment with gentamicin resulted in an increase in the Vv of blood vessels, a decrease in the Vv of hepatocytes, and a decrease in the glycogen content in all three lobular zones. Melatonin administration reduced the liver alterations induced by gentamicin; the higher dose had a more potent protective effect. Conclusion: Melatonin has a beneficial effect on gentamicin-induced liver damage and the effect is dose-dependent.

Introduction: Diabetes mellitus is associated with systemic complications, including the development of pulmonary injury, characterized mainly by excessive accumulation of extracellular matrix components and inflammatory cell infiltration in lung tissue. This process is driven by oxidative stress and chronic inflammation, both caused and exacerbated by hyperglycemia. N-acetylcysteine (NAC) and glycine, known for their antioxidant and anti-inflammatory effects, offer potential therapeutic benefits in mitigating diabetes-induced lung injury. Objective: The study aimed to investigate the effects of supplementation by either NAC or glycine or their combination on reducing lung injury in rats with type 1 diabetes Materials and methods: The study used 30 adult Wistar albino rats (10 weeks old, weighing between 180 g and 380 g). Six of them were used as controls, while 24 adult rats (10 weeks old, 180-380 g) with type 1 diabetes, induced through a single intraperitoneal injection of streptozotocin (STZ) at a dose of 55 mg/kg, were randomly assigned to four experimental groups: control (CTL), diabetic (Db), NAC treatment (diabetic+NAC), glycine treatment (diabetic+glycine), and combined NAC and glycine treatment (diabetic+NAC+glycine). NAC (100 mg/kg) and glycine (250 mg/kg) were administered orally for 12 weeks. At the end of the study, lung tissues were collected for histopathological examination. Qualitative, semi-quantitative, and stereological histological analysis was used to analyze structural changes in the lung tissue. Semi-quantitative scoring was carried out to evaluate the extent of inflammation, while stereological analysis was performed to determine the volume density of alveolar spaces and septal connective tissue. The semi-quantitative scoring included scores ranging from 0 (absent), 1 (minimal), 2 (mild), 3 (moderate), to 4 (severe). Results: Qualitative histological analysis revealed pronounced inflammation and fibrosis in the lungs of untreated diabetic rats, characterized by thickened alveolar septa and immune cell infiltration. Both treatments with NAC and glycine individually reduced inflammation and fibrosis compared to untreated diabetic rats. The greatest improvement was observed in the NAC+glycine group, where the alveolar structure appeared almost normal, with minimal inflammation. Semiquantitative analysis showed statistically significant differences in peribronchial and peribrochiolar infiltrates between the diabetic group (2.16±0.47) and the control group (0.33±0.21, p=0.026). The combination of NAC and glycine significantly reduced peribronchial and peribronchiolar infiltrates (0.33±0.33, p=0.026) compared to the diabetic group. Similarly, septal inflammatory infiltrates were significantly lower in the NAC+glycine group (1±0.36) compared to diabetic rats (3.33±0.33, p=0.004). Total airway inflammatory infiltration was also significantly reduced in the NAC+glycine group (1.33±0.33, p=0.002) compared to the diabetic group (5.5±0.5). Conclusion: As the combination of NAC and glycine demonstrated protective effects against lung inflammation and fibrosis in diabetic rats, a synergistic effect of NAC and glycine in mitigating pulmonary complications associated with type 1 diabetes may be suggested. These findings warrant further exploration of the combination for managing diabetic lung disease and potentially other fibrotic conditions.

Dina Lagumdžija, Aida Hamzić Mehmedbašić, D. Jesenković, B. Kudić, Dina Kapić, E. Ćosović, O. Lepara, Belma Pehlivanović Kelle, Jasminka Prguda-Mujic 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 (RD) 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 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 an RD 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, and low-density lipoprotein 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 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 an RD 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.

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