The prevalence of herpesvirus infections in children and young adults transplant recipients - kidney and hematopoetic stem cells

Introduction: Viruses are the most important and common cause of opportunistic infections following transplantation. The risk correlates with the virus encountered, transplanted tissue and organ, intensity of immune suppression, and other host factors governing susceptibility. Infections caused by the human herpesviruses, continue to challenge the clinical management of transplant recipients. Aim: The aim of this study was to investigate the prevalence of herpesvirus infections among pediatric hematopoetic stem cell and renal transplant recipients (HSCTR and RTR). Material and methods: This is a retrospective study of 150 pediatric HSCTR and RTR investigated in plasma samples by PCR in multiple testings, on the presence of cytomegalovirus (CMV), Epstein-Barr virus (EBV), herpes simplex virus type 1 and 2 (HSV1/2) and human herpes virus 6 (HHV6) during 2015/2016 period. Visualization of PCR products was performed by electrophoresis on 2% agarose gel with ethidium bromide. For statistical analyses T test, McNemar's test, Chi -square and Fisher's exact test were used. Results: During 2015, statistical significance was reached at the follow ups, where 33.3% (p=0.031) and 46.7% (p=0.016) of HSCTR, and 4.3% and 28.0% of RTR, had positive CMV and EBV results, respectively, in regard to the first test. During 2016, similar finding was observed where HSCT recipients had 70.6% CMV (p=0.002) and 29.4% EBV positive results during the follow ups. Cytomegalovirus (CMV) finding was negative in all RTR, but 12.5 and 4.0% of investigated kidney recipients were EBV positive during the first test and follow ups, respectively. Conclusion: The results demonstrated that HSCTR are in a greater risk of CMV and EBV infections, compared to RTR. Therefore, the importance of permanent post - transplant monitoring of herpesviruses is in timely diagnosis and prevention of overt infections from occurring

The prevalence of the most important viral infections in renal transplant recipients in Serbia

Viruses are the main cause of opportunistic infections after kidney transplantation. The aim of this study was to determine the prevalence of cytomegalovirus (CMV), Epstein-Barr virus (EBV), B. K. virus (BKV) and John Cunningham virus (JCV) infections in renal transplant recipients (RTR). This retrospective study of 112 RTR investigated the presence of CMV, EBV and polyomaviruses DNA in plasma and/or urine by PCR. The visualization of PCR products was performed by electrophoresis on 2% agarose gel stained with ethidium bromide and photographed under a UV light. The chi-square test was used for statistical analysis. CMV DNA was detected in 14/112 (12.5%), EBV DNA in 4/49 (8.16%), BKV DNA in 10/31 (32.26%) and JCV DNA in 3/31 (9.68%) RTR. These results show that CMV infection is more often present in RTR compared to other investigated viral infections. In the light of these results, molecular testing could be useful in identifying recipients at high risk of symptomatic post-transplant viral infection. [Projekat Ministarstva nauke Republike Srbije, br. 175073, br. 175038 and br. 175089

Oncogenic viruses and their role in tumor formation

Oncogenic viruses trigger persistent infections, which can stimulate uncontrolled cell growth by inducing cell transformation. Different oncogenic viruses use different mechanisms for infecting cells. Most oncogenic DNA viruses integrate transforming sets of genes into the host chromosome and encode proteins that bind and inactivate cell growth regulatory proteins, such as p53 and retinoblastoma gene product. Tumorous RNA viruses use different oncogenic mechanisms. Some of them encode oncogenic proteins that are almost identical to the cellular proteins involved in the control of cellular growth. The overproduction or altered function of these oncogenic materials stimulates cell growth. These RNA viruses can cause tumors rapidly. The second group of oncoviruses integrates their promoter sequences and viral enhancers near to the cellular growth-stimulating gene, initiating the transformation of the cell. The third group of RNA tumor viruses encodes a protein tax that transactivates the expression of cellular genes. Virus-induced malignant transformation of the cell represents the first step in the complex process of oncogenesis

The prevalence of human polyomaviruses in urine samples of immunocompetent individuals in the Serbian population

The BK (BKV) and JC viruses (JCV) are human polyomaviruses. After primary infection, they persist as latent infection in the kidneys. Immunosuppression leads to their reactivation, which is associated with life-threatening diseases such as polyomavirus-induced nephropathy and progressive multifocal leukoencephalopathy. However, the behavior of these viruses in immunocompetent individuals is still an open question with no right answer. The aim of this study was to determine the prevalence of BKV and JCV shedding in the urine of immunocompetent individuals from the Serbian population. Sixty-five urine samples were collected and tested for the presence of BKV and JCV DNA by PCR. JCV DNA was detected in 19/65 (29.2%) and BKV DNA in 3/65 (4.6%) of the urine samples. Forty-three (66.2%) urine samples of the immunocompetent donors were negative for both viruses. The present study provides the first results of urinary excretion of human polyomaviruses in the Serbian population. [Projekat Ministarstva nauke Republike Srbije, br. 175073

The influence of host factors and sequence variability of the p7 region on the response to pegylated interferon/ribavirin therapy for chronic hepatitis C genotype 1b in patients from Serbia

The goal of this study was to identify host and viral factors affecting the response to pegylated interferon/ribavirin (PEG-IFN/RBV) treatment in patients with chronic hepatitis C genotype 1b. Baseline characteristics of the patients and sequences within the p7 region were analyzed in pre-treatment serum samples from 53 individuals with chronic hepatitis C genotype 1b and related to the outcome of therapy. We found a significant correlation between age and response to therapy (p LT 0.001). Furthermore, the pre-treatment viral load was closely associated with the stage of liver fibrosis (p LT 0.001). The presence of fewer than 4 mutations and age above 40 were significantly associated with non-response (NR) (p LT 0.001). Our findings may be useful for estimating the likelihood of achieving a sustained virologic response (SVR) in patients who are chronically infected with hepatitis C virus genotype 1b

What happens after application of thiamine in the brain of Japanese quailstreated with chlorpyrifos

The aim of this study was to investigate the influence of vitamin B1 (thiamine) following thepathohystologycalchanges in the hippocampus, cerebellum and cerebral cortex of Japanese quail (Coturnix japanica) treated with chlorpyrifos.In this study we also assessed the antioxidative activity of thiamine in the brain by monitoring the nitrite concentration(NO2-), parameter of oxidative/nitrosative stress and activities of agents of cellular detoxification such as glutathione(GSH) and glutathione S-transferase(GST). The study was conducted onforty male Japanese quails (2 controls and 2 experimental groups, n= 10), 3-4 weeks old. One controlgroup was treated only with vitamin B1, while the second one receivedpurecorn oil.CPFdissolved in corn oil was administeredto quails by gavage for 7 consecutive days at dose of 3 mg/kg BW while another groups wastreated with 10 mg/kg BWof vitamin B1 i.m. 30 min after CPF administration for 7 consecutive days. Our studies have shown that CPF has ledto increase in the concentration of NO2-,but after thiamine treatment there has been a decrease. Also CPF has led to small changes in GSH and GST levels, while groups treated with vitamin B1showedsignificantly (p< 0.0001)increased activity of these parameteres, proving very important role of thiamine in the detoxification and elimination of pesticides. In hippocampus groups that received CPF showed signs of edema with numerous damaged neurons, especially in pyramidal layer, while in groups that received vitamin B1 along with CPF, pathological changes were similar, but less prominent.In cerebellum groups that received CPF showed large number of degenerated Purkinje cells, while with vitamin B1 the reduction of degenerated neurons is present.Cerebral cortex showed degeneration with pycnotic nuclei of many neurons, edema and congestion in groups which received CPF and also similar changes were found after application of B1. Overall these results confirm that CPF causes oxidative stress and degenerative changes, but also support the hypothesis that thiamine belongs to the group of "antistress vitamins"

Locally advanced rectal cancers with simultaneous occurrence of KRAS mutation and high VEGF expression show invasive characteristics

In this study, we investigated the mutation status of KRAS gene in pretherapeutic and preoperative biopsies in 63 specimens of locally advanced rectal cancers in order to evaluate its potential predictive and/or prognostic role. Regions of interest of KRAS exon 2 were amplified and visualized on 2% agarose gel. Obtained PCR products were subjected to direct sequencing. KRAS mutations were detected in 35% of patients, 91% of which were located in codon 12 and 9% in codon 13. In general, KRAS mutation status did not affect the response to neoadjuvant chemoradiotherapy (CRT). However, patients harboring mutated KRAS gene, simultaneously with high vascular endothelial growth factor (VEGF) expression, exhibited a worse response to CRT (p = 0.030), a more frequent appearance of local recurrences and distant metastasis (p = 0.003), and shorter overall survival (p = 0.001) compared to all others. On the contrary, patients with GGT GT GCT KRAS mutation exhibited a significantly better response to CRT than those with any other type of KRAS mutation (p = 0.017). Moreover, the presence of GGT GT GCT mutation was associated with low VEGF and Ki67 expression (p = 0.012 in both cases), parameters related to less aggressiveness of the disease. Our results suggest that KRAS mutation status could have some predictive and prognostic importance in rectal cancer when analyzed together with other parameters, such as VEGF and Ki67 expression. In addition, it seems that not only the presence but the type of KRAS mutation is important for examining its impact on CRT response. (C) 2016 Elsevier GmbH. All rights reserved