Potential influence of interleukin-6 -174G/C gene polymorphism on kidney graft function and tacrolimus dose requirements: five-year follow-up.

1. Introduction: The study aimed to investigate the influence of interleukin (IL)-6 -174 G/C gene polymorphism on graft function (defined as estimated glomerular filtration rate, eGFR), as well as on the tacrolimus (Tac) pharmacokinetics during the five years after kidney transplantation.

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Impact of IL-6 and IL-10 genotypes on tacrolimus dose requirements in kidney transplant recipients: Monte Carlo analysis.

IL-6 and IL-10 may affect the activity of cytochrome P450 (CYP) 3A enzymes involved in tacrolimus (Tac) metabolism. Moreover, the effect of IL-6 and IL-10 on Tac pharmacokinetics may differ with respect to the genetic variations in their genes. To examine the influence of IL-6 and IL-10 gene polymorphisms on Tac dose requirements and exposure over a 5-year period following kidney transplantation.

The Impact of Opioid Receptor Gene Polymorphism on Fentanyl and Alfentanil's Analgesic Effects in the Pediatric Perioperative Period.

Introduction: The polymorphism of the gene coding mu-opioid receptor () is one of the factors contributing to the variability in the response to opioid analgesics in children. The goal of this study is to investigate its role in association with postoperative acute pain in children of various ages.

Methods: This prospective study analyzed 110 pediatric patients, after plastic or orthopedic surgery, who were genotyped and randomly assigned to receive fentanyl or alfentanil.

Utility of salivary mycophenolic acid concentration monitoring: Modeling and Monte Carlo validation approach.

The results of the previous studies demonstrated an association between mycophenolic acid (MPA) exposure, serum albumin level (ALB), and adverse effects in kidney transplant patients. The aim was the identification of mathematical correlation and association between both, total and unbound MPA concentration in relation to ALB, body mass (BM), age and estimated glomerular filtration rate (eGFR) in stable kidney transplant recipients. Furthermore, investigation was conducted with the aim to clarify the role of salivary concentration (C ) of MPA in adverse effect profile.

Beta Blockers can Mask not only Hypoglycemia but also Hypotension.

Background: Beta-adrenergic (β-AR) receptor blockers (BBs) are an essential class of drugs as they have numerous indications. On the other hand, they have numerous unwanted effects that decrease the compliance, adherence, and persistence of this very useful group of drugs.

Objective: The paper aims to analyze the possibility that an unnoticed side effect may contribute to a less favorable pharmacologic profile of BBs, e.

Rationale for the Concept of Impending Hypertension-Mediated Organ Damage.

Background: The number of patients with hypertension urgencies (HTN-Us) and emergencies (HTN-Es) in the emergency department is relatively constant despite improved detection, awareness and control of arterial hypertension.

Objective: This study analyses the precision of the often-used definition of HTN-E, particularly the phrase 'with the evidence of impending or progressive hypertension-mediated organ damage (HMOD)'. We then provide a rationale for the concept of impending HMOD.

Antibiotic utility and susceptibility changes of multidrug-resistant and spp: 5-year experience in a tertiary healthcare centre.

Objectives: Multiple studies have identified cross-sectional relationships between antibiotic use and bacterial resistance. The aim of this study was to analyse the susceptibility of multidrug-resistant (MDR) and non-MDR (nMDR) isolates of and spp to cephalosporins: ceftazidime (CTZ), ceftriaxone (CTX), cefepime (CEF) and fluoroquinolones: ciprofloxacin (CIP) and levofloxacin (LEV) in a tertiary healthcare centre from 2014 to 2018. In addition, we aimed to evaluate a correlation between the antibiotic utility and susceptibility of the selected enterobacteria.

Effect of the Interrelation between CYP3A5 Genotype, Concentration/Dose Ratio and Intrapatient Variability of Tacrolimus on Kidney Graft Function: Monte Carlo Simulation Approach.

: Tacrolimus (Tac) is characterized by large between- and within-patient (IPV) variability in pharmacokinetics and exposure. : This study aimed to assess and validate the effect of Tac IPV and trough concentration-to-dose ratio (C/D) over 6-12 months on reduced estimated glomerular filtration rate (eGFR) values in the late period after kidney transplantation (Tx), applying Monte Carlo (MC) simulation. : The previously published linear regression was the basis for MC simulation, performed to determine how variations in significant predictors affect the distribution of eGFR from 13 to 36 months post-transplantation.

The significant role of dietary intake of vitamin D in non-menopausal women health.

Optimal vitamin D status is very important for reflecting not only bone but overall woman's health. The aim of the study was to determine pharmacokinetic variability of 25-hydroxy vitamin D, to reveal and quantify the most significant factors that affect its variability in the population of healthy non-menopausal women using the population pharmacokinetic (PopPK) approach. The study population consisted of 74 healthy reproductive women aged from 35 to 50 years, without the use of any supplement.

Assessment of pharmacokinetic mycophenolic acid clearance models using Monte Carlo numerical analysis.

Previously, we performed population pharmacokinetic analysis and indicated age, mycophenolate mofetil (MMF)/mycophenolic acid (MPA) daily dose, and presence of nifedipine in patient therapy as significant predictors of MPA apparent clearance (CL/F) variability. This study aimed to determine the reliability of previously published population pharmacokinetic models derived from similar studies. Furthermore, this study investigated correspondence between chosen population models from the literature.

Combined Effect of Inter- and Intrapatient Variability in Tacrolimus Exposure on Graft Impairment Within a 3-Year Period Following Kidney Transplantation: A Single-Center Experience.

Background And Objective: Tacrolimus is a cornerstone of the most immunosuppressive protocols after kidney transplantation, but its use is complicated by notable interpatient and intrapatient variability (IPV). The goal of this study was to evaluate whether or not tacrolimus IPV, or average dose-adjusted trough concentration (C/D), during 6-12 months post-transplantation might have contributed to graft function decline in a 3-year period following kidney transplantation. After primary evaluation of individual effects of tacrolimus IPV and C/D, the study aimed to estimate the combined effect of tacrolimus IPV and C/D on composite endpoint (consisting of graft failure, chronic allograft dysfunction, chronic rejection, and doubling of serum creatinine concentration) in the period between 13 and 36 months after kidney transplantation.

Beta blocker rebound phenomenon is important, but we do not know its definition, incidence or optimal prevention strategies.

The aim of this review is to analyze whether there is a need for scientific information about the beta blocker (BB) rebound phenomenon; whether such information is available; and, if it is, how detailed is the BB rebound phenomenon explained in the guidelines and papers? A narrative review is used due to the lack of valid randomized clinical trials (RCTs) on the topic, which are needed for a meta-analysis. The BB rebound phenomenon can have dangerous consequences. The discontinuation of a BB leads to a fourfold increased risk of events related to coronary artery disease in hypertensive patients; it increases in-hospital mortality in heart failure patients; it can precipitate angina pectoris attack; and it increases the risk for death and rehospitalization in patients who survive acute myocardial infarction.

Metronidazole- and levofloxacin-induced psychotic disorders in chronic kidney patient.

We present a case which reports the occurrence of psychotic disorders after metronidazole and levofloxacin therapy in a chronic kidney patient while being treated for enterocolitis and urinary infection. A 48-year-old female was admitted to a hospital for the placement of a peritoneal dialysis catheter due to indicated peritoneal dialysis. During admission, symptoms of enterocolitis and urinary infection had occurred, so metronidazole and levofloxacin were introduced into therapy, respectively.

Chokeberry juice supplementation in type 2 diabetic patients - impact on health status.

Recent literature evidence indicates the potential use of chokeberry preparations in the prevention and treatment of some chronic noncommunicable diseases. The aim of the present study was to evaluate the effects of the three months oral chokeberry juice supplementation in type 2 diabetic patients, as well as its influence on hematological parameters and certain parameters of the renal dysfunction. The study was designed as an open-label trial, which included 35 patients who have received the herbal supplement, polyphenol-rich chokeberry juice (150 ml/day, three times a day for 50 ml), in addition to their standard therapy.

The predictive value of Klotho polymorphism, in addition to classical markers of CKD-MBD, for left ventricular hypertrophy in haemodialysis patients.

Purpose: Cardiovascular events are the major reasons for mortality in haemodialysis patients. Fibroblast growth factor 23 (FGF23), Klotho protein and G-395A Klotho gene polymorphism have been associated with effects on the cardiovascular system. Our study investigates the interrelationship between Klotho protein gene variations, mineral-bone metabolism and left ventricular hypertrophy in patients undergoing chronic haemodialysis programme.

Adverse effects of mycophenolic acid in renal transplant recipients: gender differences.

Background Mycophenolic acid is widely used immunosuppressive drug, associated with adverse effects which increase patient morbidity and decrease medication adherence. Objective To evaluate the adverse effects in renal transplant recipients under mycophenolate treatment with respect to gender. Setting University Clinical Centre of Nis, Clinic of Nephrology, Serbia.

Potentially inappropriate prescribing of drugs in elderly patients on chronic hemodialysis treatment .

Purpose: The aim of this study was to determine the prevalence of potentially inappropriate drug prescription (PIP) in older patients who were on chronic hemodialysis treatment and to explore the factors that lead to PIP.

Materials And Methods: The study was performed at the Department of Nephrology, Clinical Center Niš, Serbia. It included patients who were 65 years old and older who suffered from the end-stage of kidney failure and were treated by hemodialysis.

Current Biochemical Monitoring and Risk Management of Immunosuppressive Therapy after Transplantation.

Immunosuppressive drugs play a crucial role in the inhibition of immune reaction and prevention of graft rejection aswell as in the pharmacotherapy of autoimmune disorders. Effective immunosuppression should provide an adequate safety profile and improve treatment outcomes and the patients' quality of life. High-risk transplant recipients may be identified, but a definitive prediction model has still not been recognized.

Renalase Assessment With Regard to Kidney Function, Lipid Disturbances, and Endothelial Dysfunction Parameters in Stable Renal Transplant Recipients.

Background: Renal transplant dysfunction has been shown to be independent predictor for premature cardiovascular disease and mortality. Renalase, a flavoprotein secreted by several tissues, including the kidney, has been found to regulate sympathetic tone and blood pressure. The purpose of this secondary analysis was to explore relationships among parameters of endothelial dysfunction, lipids, glomerular filtration rate, and renalase in 2 groups: renal transplant patients with controlled hypertension and healthy volunteers.

Do Health Reforms Impact Cost Consciousness of Health Care Professionals? Results from a Nation-Wide Survey in the Balkans.

Background: Serbia, as the largest market of the Western Balkans, has entered socioeconomic transition with substantial delay compared to most of Eastern Europe. Its health system reform efforts were bold during the past 15 years, but their results were inconsistent in various areas. The two waves of global recession that hit Balkan economies ultimately reflected to the financial situation of healthcare.

Herbal self-medication use in patients with diabetes mellitus type 2.

Background/aim: A considerable number of patients suffering from diabetes mellitus (DM) turn to self-medication using medicinal plants, preparations, and medicine. The aim of this study was to investigate self-medication using medicinal plants and the potential influence of health care professionals' advice or media information regarding the use of herbal dietary supplements with hypoglycemic effect in a population of patients with type 2 DM.

Materials And Methods: This research, in the form of an analytic cross-sectional study, was conducted in 6 pharmacies in the territory of Nis, Serbia, during October 2013.

Pharmacogenetics may Influence Tacrolimus Daily Dose, but not Urinary Tubular Damage Markers in the Long-Term Period after Renal Transplantation.

Background: The primary goal of this study was to evaluate the influence of cytochrome P450 (CYP) 3A5 (6986A>G) and ABCB1 (3435C>T) polymorphisms on tacrolimus (TAC) dosage regimen and exposure. Second, we evaluated the influence of TAC dosage regimen and the tested polymorphisms on renal oxidative injury, as well as the urinary activities of tubular ectoenzymes in a long-term period after transplantation. Also, we aimed to determine the association between renal oxidative stress and tubular damage markers in the renal transplant patients.

Oxidative and Nitrosative Stress in Stable Renal Transplant Recipients with Respect to the Immunosuppression Protocol - Differences or Similarities?

Background: The aim of the study was to evaluate parameters of oxidative and nitrosative stress as well as antioxidative parameters in a group of renal transplant recipients with stable graft function and no clinical signs of cardiovascular disease. We also aimed to determine the correlations among these parameters and to evaluate potential differences in all the biomarkers with regard to the immunosuppression protocol.

Methods: We enrolled 57 renal transplant recipients and 31 controls who were age and sex matched with the renal transplant recipients.

Variability of mycophenolic acid elimination in the renal transplant recipients – population pharmacokinetic approach.

The aim of this study was to develop a population pharmacokinetic (PK) model for clearance of mycophenolic acid (MPA) in adult renal transplant recipients, to quantify the PK parameters and the influence of covariates on the MPA pharmacokinetic parameters. Parameters associated with plasma concentrations of MPA at steady-state were analyzed in 70 renal transplant recipients (mean age 42.97 years; mean total body weight 75.

Potential role of tacrolimus in erythrocytes' antioxidative capacity in long-term period after renal transplantation.

The main goal of this study was to evaluate the influence of tacrolimus daily dose (TDD) as well as cytochrome P450 (CYP) 3A5 6986A>G and ABCB1 3435C>T polymorphisms on the erythrocytes' oxidative stress parameters in long-term period after renal transplantation (Tx). Secondly, we investigated whether tacrolimus and/or oxidative injury might have affected renal function or it was independent from both. In order to evaluate erythrocytes' oxidative stress status in 72 renal transplant recipients and 62 healthy volunteers, we measured the levels of thiobarbituric acid reactive substances (TBARS) and reduced glutathione (GSH) and the activities of superoxide dismutase (SOD), glutathione peroxidase (GPX) and glutathione reductase (GR) as well.