New bimetallic palladium(II) and platinum(II) complexes: Studies of the nucleophilic substitution reactions, interactions with CT-DNA, bovine serum albumin and cytotoxic activity

© 2016 The Royal Society of Chemistry. Two new dinuclear bimetallic complexes, [{PdCl(bipy)}{μ-(pyrazine)}{PtCl(bipy)}]Cl(ClO4) (1) (bipy is 2,2′-bipyridine) and [{PdCl(en)}{μ-(pyrazine)}{PtCl(en)}]Cl(ClO4) (2) (en is ethylenediamine), have been synthesized and characterized by elemental microanalysis, IR, 1H NMR spectroscopy and MALDI-TOF mass spectrometry. The pKa values of the coordinated water molecules of the diaqua species were determined as well. Substitution reactions of complexes (1) and (2) with thiourea (Tu), l-methionine (l-Met), l-cysteine (l-Cys), l-histidine (l-His) and guanosine-5′-monophosphate (5′-GMP) were studied under the pseudo-first order conditions as a function of nucleophile concentration and temperature. The order of reactivity of nucleophiles was: Tu > l-Met > l-Cys > l-His > 5′-GMP. Substitution reactions with Tu, l-Cys and l-His were followed by decomposition of bimetallic complexes to the corresponding substituted mononuclear complexes [Pd(N-N)(Nu)2] and [Pt(N-N)(Nu)2] (N-N = bipy, en), releasing the bridging ligand. However, the structures of starting bimetallic complexes were preserved during the reactions with l-Met and 5′-GMP. The absorption spectroscopic study of interactions of calf-thymus DNA (CT-DNA) with complexes (1), (2) and [{PdCl(bipy)}{μ-(NH2(CH2)6H2N)} {PtCl(bipy)}]Cl(ClO4) (3), has shown that all the complexes exhibit high intrinsic binding constants (Kb = 104-105 M-1). DNA-ethidium bromide (DNA-EB) fluorescence was quenched after addition of complexes (1), (2) or (3), indicating displacement of intercalating EB by complexes. All complexes have shown good binding affinity to bovine serum albumin protein (BSA). Chemosensitivity of A375 (human melanoma) and HeLa (human cervical cancer) cell lines toward complexes (1), (2) and (3) was analyzed by SRB assay. Complex (1) displayed significant inhibitory effect on the growth of both cell lines

Successful treatment of idiopathic retroperitoneal fibrosis with combined immunosuppressive therapy

© 2019 Inst. Sci. inf., Univ. Defence in Belgrade. All rights reserved. Background/Aim. Idiopathic retroperitoneal fibrosis (IRF) is characterized by the fibroinflammatory periaortic tissue that affects the ureters, causing obstructive nephropathy and variable impairment of renal function. The findings strongly suggest an autoimmune etiology. The optimal treatment has not been established. The aim of this study was to analyze a long-term efficacy of combined corticosteroid therapy with mycophenolate mofetil (MMF) in the patients with IRF. Methods. We retrospectively followed 13 patients (8 males and 5 females) with IRF. All patients received corticosteroids and MMF. For the patients with severe renal failure, an initial ureteral decompression was made and prednisone was started orally 0.5 mg/kg with fast tapering. In cases with a mild renal failure corticosteroids were administrated as intravenous methylprednisolone pulses for 3 days, followed by oral prednisone. The dose of MMF was 1000 mg twice a day. MMF was stopped after 18 months and prednisone after 48 months. Results. Systemic symptoms resolved in all patients. Erythrocyte sedimentation (SE) rate declined from the mean of 67.6 to 26.3 mm/h and C-reactive protein (CRP) from the mean of 18.5 to 6.3 mg/L. In 7 out of 8 patients, the ureteral stents were successfully removed 13 weeks on average. Seven patients had 100% of reduction in the periaortic mass, and the average percent reduction was 76.9%. The kidney function improved and remained normal in 6 treated patients. In 4 patients a mild chronic renal failure remained due to afunction of one kidney. Three patients, with a prior chronic renal failure, did not get worse renal function. The disease recurred in 3 patients. There were no treatment side effects noted. Conclusion. Combination of corticosteroids and MMF is a potentially effective treatment in restoring the renal function and reducing the fibrotic tissue in the patients with idiopathic retroperitoneal fibrosis. It could prevent the need for ureteral stenting and surgery. Longer treatment may reduce a possibility of recurrence

Effect of Vitamin D on proteinuria, lipid status, glycoregulation and C-reactive protein in patients with type-2 diabetes mellitus

© 2020 Inst. Sci. inf., Univ. Defence in Belgrade. All rights reserved. Background/Aim: Vitamin D insufficiency/deficiency is often present in patients with type-2 diabetes mellitus (DM) and could present a risk factor for rapid progression of diabetic nephropathy and for higher incidence of cardiovascular events. The aim of this study was to examine the influence of vitamin D supplementation on proteinuria, cholesterol, triglycerides, C-reactive protein (CRP) and hemoglobin A1c in patients with type-2 DM and vitamin D insufficiency/deficiency. Methods: This prospective, cohort study included 90 patients with type-2 DM and vitamin D insufficiency/deficiency divided into 3 equal groups: with normal proteinura, with microproteinuria and with macroproteinuria. Therapy included six months of supplementation with cholecalciferol drops: first two months with 20,000 IU twice weekly, than if level of vitamin D was below normal the same dose was given next four months. If the level of vitamin D was normal 5,000 IU was given twice weekly. At the begining and at the end of the study the levels of urea, creatinine, fasting blood glucose, calcium, phosphorus, cholesterol, triglycerides, CRP, hemoglobin A1c, intact parathyroid hormone, 24-hour urine protein and creatinine clearance were determined. Levels of calcium, phosphorus and vitamin D were also checked 2 months after beginning of therapy due to possible correction of cholecalciferol dose. Results: The lowest level of vitamin D before therapy was found in patients with macroproteinuria, while at the end of the study the significantly higher level of vitamin D was found in all three groups. After 6 months of therapy a significant decrease of 24-hour urine protein, cholesterol, triglycerides, hemoglobin A1c in all three groups, and CRP in patients with normal proteinuria and microproteinuria were found. Significantly negative correlation between vitamin D and 24-hour urine protein, cholesterol and CRP was found in patients with macroproteinuria. Also, significantly negative correlation was found between vitamin D and hemoglobin A1c, in patients with normal proteinuria, vitamin D and CRP in patients with microproteinuria. Conclusion: A preventive use of high-dose cholecalciferol supplementation in patients with type-2 DM (with or without proteinuria) decreases cholesterol, triglycerides, proteinuria, CRP and hemoglobin A1c