Amina Valjevac

Connexin-dependent signaling in neuro-hormonal systems.

The advent of multicellular organisms was accompanied by the development of short- and long-range chemical signalling systems, including those provided by the nervous and endocrine systems. In turn, the cells of these two systems have developed mechanisms for interacting with both adjacent and distant cells. With evolution, such mechanisms have diversified to become integrated in a complex regulatory network, whereby individual endocrine and neuro-endocrine cells sense the state of activity of their neighbors and, accordingly, regulate their own level of functioning. A consistent feature of this network is the expression of connexin-made channels between the (neuro)hormone-producing cells of all endocrine glands and secretory regions of the central nervous system so far investigated in vertebrates. This review summarizes the distribution of connexins in the mammalian (neuro)endocrine systems, and what we know about the participation of these proteins on hormone secretion, the life of the producing cells, and the action of (neuro)hormones on specific targets. The data gathered since the last reviews on the topic are summarized, with particular emphasis on the roles of Cx36 in the function of the insulin-producing beta cells of the endocrine pancreas, and of Cx40 in that of the renin-producing juxta-glomerular epithelioid cells of the kidney cortex. This article is part of a Special Issue entitled: The Communicating junctions, composition, structure and characteristics.

Elevated serum C-reactive protein concentration in Bosnian patients with probable Alzheimer's disease.

Studies indicate that inflammatory mechanisms may play an important role in the pathogenesis of Alzheimers disease (AD). C-reactive protein (CRP), marker and mediator of inflammation, has been detected in lesions typical for the affected areas of AD brain. There have been conflicting reports on serum CRP concentration in AD. Scarce data exist on association of CRP and measures of adiposity in AD patients. Thus, we investigated serum CRP concentration in fifteen overweight institutionalized patients with probable AD and fifteen age-matched control subjects. Body mass index (BMI) and waist/hip ratio (WHR) were calculated for each subject included in the study. Age, systolic and diastolic blood pressure, BMI and WHR did not differ significantly between the two groups. Serum CRP concentration was significantly higher in patients with AD compared to controls (p<0.0001). Although not significant, positive correlations between serum levels of CRP and BMI and WHR were found. Obtained results support the notion that low-grade inflammation is present in patients with AD. Absence of significant association between CRP and measures of total and central adiposity in overweight AD patients needs further investigation and explanation.

Is γ-glutamyl transferase activity a potential marker of left ventricular function during early postmyocardial infarction period?

AIM γ-glutamyl transferase (GGT) is an independent prognostic marker for cardiac death and reinfarction in patients with coronary artery disease, but its clinical significance during early postmyocardial infarction period is unclear. PATIENTS & METHODS This short-term prospective study included 40 patients with acute myocardial infarction (AMI) in whom we determined GGT activity, lipids, uric acid, homocysteine (Hcy), high sensitivity C-reactive protein (hsCRP) and left ventricular (LV) function on admission and on day 5 following AMI. RESULTS In AMI patients on admission, logGGT was associated with logHcy (r = 0.36), uric acid (r = 0.48) and CK-MB activity (r = -0.41). Uric acid remained an independent determinant of serum GGT activity on admission. Significant increase in GGT activity (77.7%) was observed following AMI. On day 5 serum logGGT was significantly associated with LV relative wall thickness (r = -0.37), LV end-diastolic diameter (r = 0.41) and LV fractional shortening (r = -0.36). In addition, a significant positive correlation was found between serum logGGT and loghsCRP (r = 0.41) and logHcy values (r = 0.395), but only LV end-diastolic diameter remained independently associated with serum GGT activity on day 5 following AMI. CONCLUSION GGT is associated with oxidative/inflammatory markers and LV diastolic diameter suggesting its potential role in predicting LV dilatation and dysfunction during the early postmyocardial infarction period.

Renalase Gene rs2576178 Polymorphism in Hemodialysis Patients: Study in Bosnia and Herzegovina -

Introduction: Renalase is a protein secreted in kidneys and considered as a blood pressure modulator. High rates of hypertension and its regulation in patients on hemodialysis demands search for potential cause and treatment. The aim of this study was to determine the genotype and allele frequencies of renalase gene rs2576178 polymorphism in population from Bosnia and Herzegovina. Also, the objective of present study was to find the possible association between renalase gene rs2576178 polymorphism and hypertension in patients on hemodialysis. Material and Methods: The genotype of renalase gene rs2576178 polymorphism was determined in 137 participants (100 patients on hemodialysis and 37 controls), using polymerase chain reaction (PCR) and subsequent cleavage with MspI restriction endonuclease. Genotype and allele frequencies were assessed for Hardy-Weinberg equilibrium using a Chi-squared test. The value of P<0.05 was considered as statistically significant. Results: Comparison of genotype distribution and allele frequency in participants on hemodialysis with and without hypertension, and healthy control showed no statistical difference. Conclusion: The results of the study suggest that renalase gene rs2576178 polymorphism is not a factor that influences blood pressure in patients on hemodialysis.

Prevalence of genetic prothrombotic risk factors: 1691G > A FV, 20210G > A PT and 677C > T MTHFR mutations in the Bosnian population

Abstract Background: Venous thrombosis (VT) affects 1–2 out of 103 individuals each year. Mutations of 1691G > A FV gene, 20210G > A PT gene and 677C > T gene MTHFR are common in Europe and increase the risk of venous thrombosis. To the authors’ knowledge, this is the first report on the prevalence of these mutations in the general population of Bosnia and Herzegovina. Aim: The aim of this study was to simultaneously analyse main VT associated polymorphisms and compare the results with those published for other European populations. Data sources: Electronic databases including Medline and Embase were searched from 1995 to December 2013. Subjects and methods: The subjects of the study consisted of 100 unrelated healthy people from Bosnia and Herzegovina (82 female and 18 male). The mean age of the cohort was 58.8 (±10.7) years. PCR-RFLP was used for measurement of allele frequencies. Results: All three SNPs were found to be polymorphic, with allele frequencies of 6.0%, 6.0% and 37.5% for 1691A FV, 20210A PT and 677T MTHFR, respectively. Conclusion: Further studies on larger cohorts with an adequate female-to-male ratio are necessary to confirm a high prevalence of hereditary thrombophilia in the Bosnian population.

Frequency of CCR5Δ32 allele in healthy Bosniak population

Recent evidence has demonstrated the role of CCR5Δ32 in a variety of human diseases: from infectious and inflammatory diseases to cancer. Several studies have confirmed that genetic variants in chemokine receptor CCR5 gene are correlated with susceptibility and resistance to HIV infection. A 32-nucleotide deletion within the CCR5 reading frame is associated with decreased susceptibility to HIV acquisition and a slower progression to AIDS. Mean frequency of CCR5Δ32 allele in Europe is approximately 10%. The highest allele frequency is observed among Nordic populations (about 12%) and lower in the regions of Southeast Mediterranean (about 5%). Although the frequency of CCR5Δ32 was determined in numerous European populations, there is a lack of studies on this variant in the Bosnia and Hercegovina population. Therefore, the aim of our study was to assess the frequency of CCR5Δ32 allele in the cohort of Bosniaks and compare the results with European reports. CCR5Δ32 was detected by sequence-specific PCR in a sample of 100 healthy subjects from Bosnia and Herzegovina (DNA collected 2011-2013). Mean age of the cohort being 58.8 (± 10.7) years, with 82% of women. We identified 17 heterozygotes and one mutant homozygote in study group, with mean ∆32 allele frequency of 9.5%. CCR5∆32 allele frequency among Bosniaks is comparable to that found in Caucasian populations and follows the pattern of the north-southern gradient observed for Europe. Further studies on larger cohorts with adequate female-to-male ratio are necessary.

Increased serum C-reactive protein concentration is associated with body mass index but not with glycated haemoglobin in patients with type 1 diabetes mellitus with body mass index within normal range

This study investigated whether serum C-reactive protein (CRP) concentration is increased in patients with type 1 diabetes mellitus with a normal body mass index (BMI) and whether BMI, glycated haemoglobin (HbA1c) and CRP are correlated in patients with type 1 diabetes. High-sensitivity CRP was determined by immunonephelometry and HbA1c by an immunoturbidimetric method in 30 patients with type 1 diabetes and 30 healthy individuals matched for age, sex and BMI. Median serum CRP concentration in patients with type 1 diabetes (1.34 mg/L) was significantly higher than healthy individuals (0.2 mg/L; p<0.0001). Positive correlation between CRP and BMI was observed (rho=0.598; p<0.0001), but no significant correlation was observed between CRP and HbA1c (rho=0.285; p=NS) in patients with type 1 diabetes. Increased CRP levels in type 1 diabetes patients do not appear to be associated with glycaemic control, and may reflect low-grade inflammation associated with atherosclerosis, as well as activation of innate immune activity. Br J Diabetes Vasc Dis 2011;11:249-252

Biomarkers of Cardiovascular Remodeling in Patients on Peritoneal Dialysis

Objectives: The purpose of this study was to determine endothelin (ET)-1 and nitric oxide (NO) serum concentration levels at baseline and after 1 year of peritoneal dialysis (PD) treatment. A further aim was to evaluate the association between ET-1 and NO with parameters of echocardiography and the common carotid artery (CCA) ultrasound, and to assess their impact on cardiovascular remodeling. We also aimed to evaluate the influence of dialysis adequacy and residual renal function (RRF) on cardiovascular remodeling. Methods: This study included 40 PD patients in whom we measured serum ET-1 and NO concentrations, echocardiography and CCA ultrasound parameters. Results: ET-1 decreased and NO serum concentration levels increased (p < 0.01) after 12 months of PD treatment compared to baseline values. Left ventricular (LV) hypertrophy was observed in 77.5% of patients at baseline with significant reduction in LV mass index (LVMI), CCA intima media thickness (IMT) and plaque score after 12 months of PD treatment (p < 0.001). The dialysis adequacy and RRF were significantly associated with LVMI and CCA IMT after 12 months on PD. Conclusion: In our study, ET-1 significantly decreased while NO increased during PD treatment and both were independently related to the cardiovascular remodeling parameters in PD patients.

Association Between - 675 ID, 4G/5G PAI-1 Gene Polymorphism and Pregnancy Loss: A Systematic Review -

Introduction: Several analysis for different population conclude that endothelial plasminogen activator inhibitor 1 gene polymorphism, -675 ID, 4G/5G PAI-1 (ref SNP ID: rs1799889, also described as rs34857375, has merged into rs1799762) may increase risk of pregnancy loss (PL). However, there is a disagreement as to the association 4G allele with pregnancy loss. Aim: Therefore, we decided to investigate the -675 ID, 4G/5G PAI-1 as a potential genetic factor linked to PL in European and worldwide populations. A systematic review of the scientific literature was conducted with the use of the PubMed and Scopus electronic databases (1991-present), using the following search terms: pregnancy loss, miscarriage, genetic risk of thrombophilia, rs1799889 PAI-1 gen, 4G/5G PAI-1 gene polymorphism, PAI-1 gene locus 4G/5G polymorphism. Results: Among European populations, the statistically significant association between 4G allele and recurrent PL only in Czechs and Bulgarian women was found (p<0.002 and p=0.018, respectively); while, among populations outside Europe in Iranian, Tunisian and Turkish women (each p<0.001). Conclusions: We concluded, that both in Europe and elsewhere in the world, the high frequency of 4G allele in population, is not unambiguously linked with the risk of pregnancy loss.

Prevalence of F5 1691G>A, F2 20210G>A, and MTHFR 677C>T polymorphisms in Bosnian women with pregnancy loss

The relationship between genetic risk factors of thrombophilia and pregnancy loss (PL) is being discussed. The focus has been on F5 1691G>A, F2 20210G>A, and MTHFR 677C>T polymorphisms that may predispose women to microthrombosis during the stages of embryo implantation and placentation. Although, the frequencies of these polymorphisms were reported in different populations, such studies have not yet been performed in Bosnian population. In this study, we determined the prevalence of F5 G>A (rs6025), F2 G>A (rs1799963) and MTHFR C>T (rs1801133) polymorphisms in Bosnian women. A total of 154 women with PL, mean age 33 (±5.4) years, were enrolled in the study. As a control group, 154 mothers [mean age 31.4 (±6.7) years] with at least one live-born child were included. We used real-time polymerase chain reaction (PCR) to determine the frequencies of F5 G>A and F2 G>A genotypes, and PCR-restriction fragment length polymorphism (RFLP) for analyzing MTHFR C>T genotypes. The frequency of heterozygotes for F5 and F2 was significantly higher in women with venous thrombosis (VT) compared to women without VT (p = 0.047 and p = 0.001, respectively). There was no significant difference in the distribution of MTHFR genotypes and alleles between these two groups. In addition, we observed no significant differences in the genotype and allele frequencies between the group with PL and control group, for all investigated polymorphisms. The allele frequencies for 1691A (F5), 20210A (F2), and 677T (MTHFR) reported in this study are consistent with the data obtained for other European countries, however, we were not able to confirm the association between the three polymorphisms and PL in Bosnian women.