The importance of tests applied to evaluate the effectiveness of antiplatelet therapy in patients with recurrent coronary stent thrombosis

Background. Stent thrombosis is potentially lethal complication with huge economic burden. The role of insufficient response to antiplatelet therapy is still unclear reason for its occurrence. Case report. We presented 54-year-old man with recurrent stent thrombosis on the 4th, 9th and 12th day after the primary percutaneous coronary intervention in spite of double antiaggregation therapy (aspirin+ clopidogrel). All possible procedural causes were excluded and reimplantation of intracoronary stent was insufficient to resolve the problem, so four platelet tests were performed: flow cytometry, Platelet Function Analyzer-100 test, aggregometry, and determination of gene polymorphism for P2Y12 receptor (directly involved in the mechanism of thienopyridine), and GPIIbIIIa receptor (final receptor in aggregation). The patient was the carrier of the major haplotype H1H1 for P2Y12 receptor and minor A1A2 for GPIIbIIIa receptor. The results of all the performed tests showed insufficient antiplatelet effect of aspirin and sufficient response to thienopyridin (not to clopidogrel, but to ticlopidine). Conclusion. Performance of platelet function tests is necessary in the case of major adverse cardiac events especially stent thrombosis, after implantation of intracoronary stent

Analysis of job stress in workers employed by three public organizations in Serbia

Objectives: The present study analyzes job stress in terms of education, age and the presence of cardiovascular and endocrine/metabolic diseases. Material and Methods: A total of 411 workers employed by three public organizations completed the Job Content Questionnaire to classify their jobs based on the job strain model. Data about health condition, education and habits was obtained by the use of medical examinations and an interview. Results: The analysis of the completed Job Content Questionnaires indicates that workers with high education have significantly higher decision latitude (DL) than low-educated workers (one-way ANOVA, p < 0.0001). DL was also different between age groups (one-way ANOVA, p < 0.0001) - the highest DL values were observed in the oldest group, while the lowest DL mean was found in the youngest group. Psychological job demands (PJD) and social support (SS) were not significantly different between educational and age groups. The frequency of job stress categories was significantly different between low and highly-educated workers (χ2 test, df = 3, p < 0.0001) and also between different age groups (χ2 test, df = 6, p < 0.0001). The majority of highly-educated men were exposed to "active" jobs (high PJD and high DL). Most frequently, men older than 45 years experienced jobs with high DL ("active" and "low strain"), men aged 35 to 45 years were exposed to jobs with high PJD ("high strain" and "active") while the majority of men younger than 35 years were exposed to jobs with low DL ("high strain" and "passive"). No association between cardiovascular and endocrine/metabolic disorders and different job stress categories was observed. Conclusion: "High strain" and "passive" jobs were most frequently identified among low-educated and young men. Despite the absence of association between job stress and cardiovascular and endocrine/metabolic diseases, we recommend prevention of work stress, particularly in the case of low-educated workers and workers younger than 45 years exposed to unfavorable job stress categories

The relationship between tacrolimus concentration-dose ratio and genetic polymorphism in patients subjected to renal transplantation

Background/Aim. Tacrolimus concentration-dose ratio as a potential therapeutic drug monitoring strategy was suggested to be used for the patients subjected to renal transplantation. 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

The distribution of genetic polymorphism of CYP3A5, CYP3A4 and ABCB1 in patients subjected to renal transplantation

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