EFFECTS OF SUPPLEMENTATION WITH VITAMIN E ON GENTAMYCIN-INDUCED ACUTE RENAL FAILURE IN RATS

A frequent administration of gentamicin in clinical practice has shown its bactericidal activity, and besides being vestibulotoxic it is highly nephrotoxic, which can further result in acute renal insufficiency. The study analyzed 24 Wistar rats, divided into three equal groups. GM group received gentamicin (100 mg/kg), GME group received vitamin E (100 mg/kg) and the same dose of gentamicin as GM rats, while the third group served as the control group and received saline (1 ml/24h) for 8 days. Pathohistological examination of the kidney tissues from GM group rats showed areas of coagulation-type necrosis in a large number of proximal tubules, while their glomeruli were considerably enlarged compared both to control and GME group rats. In GME rats, changes in glomeruli were less visible, while areas of coagulation-type necrosis were not found.  Biochemical analysis showed significantly higher values of blood urea and creatinine in GM group rats in comparison to C group and GME group (p<0.001). The concentrations of potassium in blood serum was significantly lower in GM group compared to control group (p<0.01), whereas the concentration of sodium was lower, however, without statistical significance. The concentrations of AOPP for GM group were significantly higher when compared to C group (p<0.001), whereas the values for GME group of rats were statistically significantly lower than AOPP recorded for GM group (p<0.001). Our experimental study has shown that gentamicin-induced nephrotoxicity can be significantly reduced by simultaneous administration of vitamin E.Key words: Gentamicin, vitamin E, nephrotoxicity, Wistar rat

Assessing the potential of para-donor and para-acceptor substituted 5-benzylidenebarbituric acid derivatives as push-pull electronic systems: Experimental and quantum chemical study

Electronic interactions in donor-pi-linker-acceptor systems with barbituric acid as an electron acceptor and possible electron donor were investigated to screen promising candidates with a push-pull character based on experimental and quantum chemical studies. The tautomeric properties of 5-benzylidenebarbituric acid derivatives were studied with NMR spectra, spectrophotometric determination of the pKa values, and quantum chemical calculations. Linear solvation energy relationships (LSER) and linear free energy relationships (LFER) were applied to the spectral data - UV frequencies and C-13 NMR chemical shifts. The experimental studies of the nature of the ground and excited state of investigated compounds were successfully interpreted using a computational chemistry approach including ab initio MP2 geometry optimization and time-dependent DFT calculations of excited states. Quantification of the push-pull character of barbituric acid derivatives was performed by the (CNMR)-C-13 chemical shift differences, Mayer pi bond order analysis, hole-electron distribution analysis, and calculations of intramolecular charge transfer (ICT) indices. The results obtained show, that when coupled with a strong electron-donor, barbituric acid can act as the electron-acceptor in push-pull systems, and when coupled with a strong electron-acceptor, barbituric acid can act as the weak electron-donor

The role of FasR/FasL system in pathogenesis of myeloprolyferative neoplasms

Mijeloproliferativne neoplazije (MPN) su hematološki maligniteti koji se karakterišu nekontrolisanom ćelijskom proliferacijom i poremećajem u procesu apoptoze. Sistem FasR/FasL je uključen u kontrolu apoptoze u različitim tipovima ćelija. U ovom radu je izučavana uloga sistema FasR/FasL u patogenezi mijeloproliferativnih neoplazija. Upoređena je ekspresija FasR i FasL između pacijenata sa MPN (24) i zdravih kontrola korišćenjem metode 'real-time' PCR. Detektovana je povećana ekspresija FasR kod pacijenata sa MPN. Nije utvrđena razlika u ekspresiji FasL. Mutacija B617F u JAK2 genu, karakteristična za MPN, je nađena kod 13 od 24 pacijenta. Pokazano je da ekspresija FasR i FasL nije povezana sa prisustvom B617F JAK2 mutacije.Myeloproliferative neoplasms (MPN) are hematological malignancies characterized by uncontrolled cell proliferation and impaired apoptosis. The FasR/FasL system is involved in the control of apoptosis in different cell types. Here we have investigated the role of FasR/FasL in the pathogenesis of MPNs. We compared FasR/FasL expression between MPN patients (24) and healthy individuals using the real-time PCR assay. We found an increase of FasR expression in MPN patients. No difference was detected in FasL expression. Mutation V617F in the JAK2 gene, a hallmark of MPN, was detected in 13/24 patients. We found that neither FasR nor FasL expression were related to the presence of JAK2 V617F mutation

Vasorelaxant effect of monoterpene carvacrol on isolated human umbilical artery

Carvacrol (CRV) is the main compound of essential oils extracted primarily from Thymus and Origanum species. Its various biological activities were confirmed: antioxidant, anti-inflammatory, antibacterial, antifungal, anti-tumour, antinematodal, and vasorelaxant action. Although vasodilation mediated by CRV was previously described, the exact mechanism of its action has not yet been established. Hence, the aim of this study was to investigate CRV vasoactivity on human umbilical arteries (HUA) and the different pathways involved in its mechanism of action using the tissue bath methodology. CRV caused a significant decrease in vascular tension of 5-HT-pre-contracted umbilical arteries, with EC50 of 442.13 ± 33.8 µmol/L (mean ± standard error of the mean—SEM). At 300 µmol/L, CRV shifted downward the 5-HT concentration–response curve with a statistical significance of p < 0.001 obtained for the four highest concentrations. At a concentration of 1 mmol/L, CRV completely abolished BaCl2-induced contraction in Ca2+-free Krebs–Ringer bicarbonate solution and the BAY K 8644-induced contraction in Krebs–Ringer bicarbonate solution (p < 0.001). Isopentenyl pyrophosphate, the antagonist of TRPV3 channel, was able to decrease the efficacy of CRV (p < 0.001). The blocking of L-type Ca2+ channels on smooth muscle cells is the most probable mechanism of CRV-induced vasorelaxation. However, the role of TRPV3 channels in CRV-induced vasodilation of HUA cannot be excluded either

Prenatal monitoring of pregnancies complicated by diabetes mellitus

Preconception and prenatal monitoring evaluate the condition of the mother's underlying disease and possible complications during pregnancy. Before conception, patients with diabetes should be informed that suboptimal glycoregulation is associated with reduced fertility and pregnancy losses. The task of the perinatologist in pregnancies affected by diabetes mellitus is to prevent complications of the underlying disease, such as hypoglycemic crises. Another important component of prenatal care in diabetic pregnancies is the recognition and prevention of pregnancy complications such as preeclampsia, polyhydramnios, congenital malformations, fetal macrosomia, and infections

Nutrition in pregnancy with diabetes mellitus

The nutritional needs of diabetic pregnancies are different from normal pregnancies. Differences in nutritional recommendations can also be seen between pregnant women who are using and who are not using insulin therapy. In this literature review, recommendations for different meal proportions of carbohydrates, proteins, and fats in the diets of pregnant women with diabetes mellitus are listed. Different meal plans were also addressed in this group of patients. The role of exercise in the management of diabetes in pregnancy is undeniable and different approaches found in the literature are presented

Theoretical basis of perinatology therapy in pregnant women with diabetes mellitus

Diabetes mellitus is a metabolic disorder that can occur before pregnancy, be detected during pregnancy, or develop during pregnancy. Therapeutic modalities available today significantly facilitate glycoregulation during pregnancy and childbirth. This review presents different insulin regimens, as well as the advantages and disadvantages of oral antidiabetic agents use with a special focus on hypoglycemia. The importance of maintaining optimal glycemic levels and educating patients in blood glucose self-measurement is explained

Liraglutide Protects Cardiomyocytes against Isoprenaline-Induced Apoptosis in Experimental Takotsubo Syndrome

Takotsubo syndrome (TTS) is a stress-induced cardiomyopathy, characterized by an increased concentration of catecholamines, free radicals, and inflammatory cytokines, endothelial dysfunction, and increased apoptotic activity. High doses of isoprenaline are used in animal models to induce Takotsubo (TT)-like myocardial injury. The aim of the study was to investigate the antiapoptotic effects of liraglutide in experimental TTS and its role in the NF-κB pathway. Wistar rats were pretreated with liraglutide for 10 days, and on days 9 and 10, TT-like myocardial injury was induced with isoprenaline. After the sacrifice on day 11, hearts were isolated for histopathological and immunohistochemical analysis. Liraglutide reduced isoprenaline-induced cardiomyocyte apoptosis by decreasing cleaved caspase-3 (CC3), BCL-2-associated X protein (BAX), and NF-κB and increasing B-cell lymphoma/leukemia-2 (BCL-2). An increase in NF-κB in isoprenaline-treated rats was in positive correlation with proapoptotic markers (BAX and CC3) and in negative correlation with antiapoptotic marker BCL-2. Liraglutide increased BCL-2 and decreased NF-κB, BAX, and CC3, preserving the same correlations of NF-κB to apoptotic markers. It is concluded that liraglutide protects cardiomyocytes against isoprenaline-induced apoptosis in experimental TT-like myocardial injury through downregulation of the NF-κB pathway