Browsing by Author "Magić, Zvonko (55942544600)"

Background/Aim: Diabetic nephropathy (DN) is a clinical syndrome characterized by persistent albuminuria, increasing arterial blood pressure and progressive decline in glomerular filtration rate (GFR). When persistent albuminuria is established, antihypertensive treatment becomes most important factor in slowing the progression of diabetic glomerulopathy. The aim of this study was to examine if renoprotective response to a short-term losartan therapy depends on 1166 A/C gene polymorphism for its target receptor. Method. The study included 35 patients with diabetes mellitus type 1 and persistently high urinary albumin excretion rate (UAE: > 30 mg/24 h), genotyped for the 1166 A/C gene polymorphism for the angiotensin II type 1 receptor (AT1R). The participants were segregated into 3 genotype groups according to combinations of A or C allele: AA(16%), AC(15%) and CC(11%). The patients received losartan 50 mg daily for 4 weeks, following 100 mg daily for another 8 weeks. At baseline and after 12 weeks of the treatment period UAE, blood pressure, GFR and filtration fraction (FF) were determined. Results. After 12 weeks of the treatment with losartan, albuminuria was reduced from baseline by 9% [95% confidence interval (CI): 1-17, p = 0.039] in the AA genotype, and by 11% (95% CI: 6-17, p = 0.0001) in the AC genotype. Losartan treatment reduced albuminuria in the CC group by 5% (95%CI: -13-22, p = 0.47). Glomerular filtration rate remained unchanged in all genotype groups. Filtration fraction was significantly reduced from baseline by 0.018 ± 0.024 (p = 0.012) only in the AC genotype. In the AA genotype, FF was reduced from baseline by 0.017 ± 0.03 (p = 0.052), and in the CC genotype by 0.01 ± 0.008 (p = 0.092). In the AA group, systolic blood pressure declined from 136 ± 24 mmHg at baseline, to an average of 121 ± 18 mmHg at the end of the study (p = 0.001). The AC group achived reduction from 131 ± 10 mmHg at baseline to 115 ± 7 mmHg (p = 0.001) during the investigation period. In the AA genotype group losartan reduced diastolic blood pressure from 86 ± 13 mmHg at baseline to 78 ± 8 mmHg (p = 0.004), and in the AC genotype from 88 ± 5 mmHg at baseline to 11.7 ± 5.6 mmHg during the investigation period (p = 0.001). In the CC genotype diastolic blood pressure reduction remained nonsignificant (p = 0.066). Conclusion. The results of our small sample size study provide the evidence that 1166 A/C AT1R polymorphism could be associated with the renoprotective response to losartan therapy.

Introduction. Synchronous multicentric cerebral gliomas are uncommon brain tumors, mostly malignant, with unknown pathogenesis, unfavorable prognosis and still controversial management. Preoperative differentiation from other multiple brain pathologies by conventional magnetic resonance imaging (MRI) is often difficult, but supplemental use of advanced magnetic resonance techniques should allow the tumor biology to be predicted and an appropriate treatment strategy planned. Case report. We reported a 59-yearold man with double synchronous multicentric cerebral lesions, which had initial MRI and diffusion-weighted imaging presentation as left parietal metastasis and ipsilateral amygdalo-hippocampal low-grade glioma. However, magnetic resonance spectroscopy (MRS) of both lesions showed different metabolite profiles of malignant glioma. En bloc resection of the easily accessible parietal lesion revealed glioblastoma with methylated O6-methylguanine-DNA methyltransferase (MGMT) gene promoter. Subsequently, the patient was treated with temozolomide (TMZ)-based chemoradiation according to Stupp’s protocol, with continuous standard (5/28) adjuvant TMZ in 12 courses. Despite prolonged stabilization of the disease with good life-quality during treatment, the patient died 19 months after diagnosis. The time to tumor progression estimated by MRI was 17 months. Conclusion. MRS significantly improved the differential diagnostic accuracy of conventional MRI in our patient. In accordance with reviewed literature data, the younger age, good initial performance status and methylated MGMT gene promoter were all favorable predictors of longer survival in the reported case. Resection of at least one easily accessible tumor lesion, followed by TMZ-based chemoradiation, with continuous adjuvant TMZ in more than 6 standard courses, seems currently to be the most beneficial therapeutic option for such cases. © 2018, Inst. Sci. inf., Univ. Defence in Belgrade. All rights reserved.

Background/Aim. Polymorphisms of genes which encode transporter P-glycoprotein and most important enzymes for tacrolimus pharmacokinetics can have significant influence reflecting on blood concentrations of this drug. The aim of this study was to examine the distribution of polymorphisms of CYP3A5, CYP3A4 and ABCB1 genes in patients subjected to renal transplantation, for the first time in our transplantation center. Methods. The research was designed as a prospective cross-sectional study which included 211 patients subjected to renal transplantation in the Centre for Solid Organ Transplantation of the university tertiary health care hospital, Military Medical Academy, Belgrade, Serbia. Patients of both genders, 22−69-year-old, Caucasians, subjected to immunosuppressive regimen, including tacrolimus, were recruited for the study. CYP3A5 6986A>G (the *3 or *1, rs776746), CYP3A4 - 392A>G (the *1 or *1B, rs2740574) and ABCB1 3435C>T (rs1045642) genotypes were determined by TaqMan® SNP genotyping assays. Results. Most of our patients (94.8%) had functional CYP3A4 enzyme, while 87.7% of all the patients had diminished CYP3A5 enzymatic activity. On the other hand, about one third of them, 31.3%, had functional ABCB1 transporter. Conclusion. A total of 84.8% of our patients were found to express both the CYP3А5*3*3 genotype (associated with diminished CYP3А5 enzymatic activity) and CYP3А4*1*1/*1*1B (associated with functional CYP3А4 enzymatic activity), while out of all the patients with diminished CYP3A5 enzymatic activity, 68.7% had diminished activity of ABCB1 transporter. However, further studies are necessary in order to show the influence of these genetic polymorphisms on tacrolimus blood concentrations in patients after renal transplantation. © 2016, Institut za Vojnomedicinske Naucne Informacije/Documentaciju. All rights reserved.

Background/Aim. Tacrolimus concentration-dose ratio as a potential therapeutic drug monitoring strategy was suggested to be used for the patients subjected to renal trans-plantation. The aim of this study was examining the relationship between tacrolimus concentration-dose ratio, suggested to be used as a therapeutic drug monitoring strategy and the polymorphisms of genes encoding the most important enzymes, such as CYP3A5 and CYP3A4, as well as the transporter P-glycoprotein, for its metabolism and elimination. Methods. The study was designed as a prospective case series study, in which the unit of monitoring was the outpatient examination of 54 patients subjected to renal transplantation. Genotyping was performed by 7500 Real-Time PCR System by assessing allelic discrimination based on TaqMan® methodology. Results. Patients (n = 13) who were treated with less than 2 mg of tacrolimus/day (0.024 ± 0.006 mg/kg/day) had the tacrolimus concentration-dose ratio larger than 150 ng/mL/mg/kg. In this group, 84.62% patients had CYP3А5 *3*3 allele. All of these patients had CYP3А4 *1*1/*1*1B allele. Regarding ABCB1 C3435T gene, 30.77% of patients had the TT gene variant, while 69.23% of our patients had CC and CT gene variants. Conclusion. Tacrolimus concentration-dose ratio greater than 150 ng/mL/mg/kg is cut-off value in patients subjected to renal transplantation which might point to patients who are poor CYP3A5 metabolizers and/or with dysfunctional P-glycoprotein. © 2018, Institut za Vojnomedicinske Naucne Informacije/Documentaciju. All rights reserved.