Prevention and Treatment of Diabetic Nephropathy with Vitamin D

The number of people suffering from diabetes mellitus, especially Type 2 diabetes mellitus, is increasing every year. Approximately one-third of the patients with diabetes mellitus will develop diabetic nephropathy and chronic kidney disease. Diabetic nephropathy represents the main cause of end-stage renal disease. Vitamin D deficiency is often present in patients with diabetes mellitus and could present a risk factor for a higher incidence of cardiovascular events. Vitamin D supplementation could have a renoprotective effect and the potential to delay occurrence and slow down the progression of diabetic nephropathy. The renoprotective effect is reflected in better glycoregulation, reduction of proteinuria and proinflammatory cytokines, and improved lipid regulation. New research shed the light on the important role of vitamin D in reducing renal fibrosis and stabilization of podocyte function. If we take into consideration the cost of end-stage renal disease treatment and the quality of life of patients on dialysis, any delay in end-stage renal disease is significant

Tacrolimus Utilization and Expenditure in Serbia

BackgroundIncreasing immunosuppressant consumption and expenditure is a quite a challenge in transplantation medicine. The aim of the study was to characterize the utilization and expenditure of tacrolimus, backbone, and standard of care in immunosuppression regimen in Serbian solid organ transplant recipients.MethodsThis study was performed as retrospective cross-sectional study during a 3-year period (from 2013 to 2015) in Serbia. The Anatomical Therapeutic Chemical Classification/Defined Daily Doses (ATC/DDD) international system was used for consumption evaluation.ResultsTwo hundred and sixty-nine patients were transplanted in Serbia from 2013 to 2015 (185 recipients from deceased donors and 84 recipients from living donors). Total number of deceased donors in this period was 81. The consumption of tacrolimus increased (from 0.051 DDD/1,000 inhabitants/day to 0.069 DDD/1,000 inhabitants/day in 2013 and 2015, respectively). The total cost of tacrolimus was also increased; from 1,206,816€ to 1,483,472€ in 2013 and 2015, respectively. On the other hand, the number of all new solid organ transplants (from deceased and living donors) per million population per year was decreased from 17.39 to 10.02, from 2013 to 2015, respectively.ConclusionIn spite downward trend in the number of solid organ transplants, tacrolimus consumption and expenditure in the examined 3-year period in Serbia increased. Since tacrolimus is a high-cost and life-preserving drug, its increasing utilization and expenditure will most likely continue consuming an enhancing share of Serbian pharmaceutical expenditure, as well as its health care, as a whole

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

Two new dinuclear bimetallic complexes, [{PdCl(bipy)}{mu-(pyrazine)}{PtCl(bipy)}]Cl(ClO4) (1) (bipy is 2,2-=bipyridine) and [{PdCl(en)}{mu-(pyrazine)}{PtCl(en)}]Cl(ClO4) (2) (en is ethylenediamine), have been synthesized and characterized by elemental microanalysis, IR, H-1 NMR spectroscopy and MALDI-TOF mass spectrometry. The pK(a) 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 GT L-Met GT L-Cys GT L-His GT 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)}{mu-(NH2(CH2)(6)H2N)} {PtCl(bipy)}] Cl(ClO4) (3), has shown that all the complexes exhibit high intrinsic binding constants (K-b = 10(4)-10(5) 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