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Widespread and prolonged therapy with ganciclovir (GCV) may result in the emergence of GCV-resistant mutations in human cytomegalovirus (HCMV) genome. The aim of this study was to detect the UL97 mutations associated with GCV resistance in kidney transplant recipients.Forty-nine kidney recipients with positive HCMV DNAemia, who received GCV therapy were included in this study. A 707 bp fragment of UL97 gene spanning codons (436 to 655) was amplified by nested PCR and sequenced.Thirteen (26.5 %) out of 49 recipients contained mutations associated with amino acid changes. Two UL97 mutations related to GCV resistance were detected in 2 recipients (4 %), including alanine to valine (A594V) and proline to leucine (P521L). The D605E mutation was identified in 8 out of 49 (16.3 %) recipients. Silent mutations G598G, G503G, L553L, L634L, D456D and G579G were commonly observed.Our results indicate that mutations in the UL97 gene associated with GCV resistance may occur in 1 in 25 recipients treated with GCV. In addition, a higher mutation rate of D605E was detected in our recipients. This study provides the first evidence of the prevalence and pattern of GCV related mutations in Iranian Turkish recipients (Tab. 2, Fig. 1, Ref. 28).

The opioid system may exert positive direct and/or indirect effects on spermatogenesis at multiple levels including the levels of the central nervous system and at the testes/sperm levels. However, long term opioid use could be associated with several reproductive complications that place the users at risk of hypogonadism and even infertility. There is little available information regarding the contribution of opioids and their apoptotic effects on testis Sertoli cells. Here, the effects of DAMGO (mu opioid receptor’s agonist), DPDPE (delta opioid receptor’s agonist) and DYN 1-9 (kappa opioid receptor’s agonist) on Sertoli cell viability and apoptosis were investigated. METHODS: Cultured Sertoli cells were exposed to each agonist (0.1–100 μM, for 24 or 48 hours) and their apoptotic effects were investigated. RESULTS: Cell viability was decreased and apoptosis was increased in the cells exposed to DAMGO in a concentration- dependent manner, while in the cells exposed to DPDPE, no signifi cant changes were observed. In cells exposed to DYN 1-9, the viability did not signifi cantly change, however apoptosis increased signifi cantly, following the exposure to the high concentration of DYN 1-9. CONCLUSION: These data suggest that mu and Kappa, but not delta receptors mediated apoptosis in Sertoli cells may be involved, at least in part, in testicular homeostasis and/or reproductive dysfunction (Tab. 1, Fig. 3, Ref. 52). Text in PDF www.elis.sk

Background: Esophageal cancer (EC) is a common cancer worldwide. Despite epidemiological studies, the etiology of EC is undetected. It was recommended that tobacco, alcohol, food carcinogens, and infectious agents may be involved in the pathogenesis of EC. Accumulating evidence suggests the role of human papillomavirus (HPV) on EC. Objectives: The aim of this study was to evaluate the prevalence and association of HPV with EC. Methods: In this case-control study, 86 samples of formalin-fixed and paraffin-embedded esophageal tissues were gathered from the pathology laboratory, Imam Khomeini Hospital, Urmia, West Azerbaijan, Iran. A total of 43 samples were esophageal cancers (cases) and 43 samples were esophageal non-cancerous tissues (controls). The tissues were sectioned and deparaffinized, and deoxyribonucleic acid was extracted. The polymerase chain reaction test was conducted to detect HPV, using general (GP5+/GP6+) and type-specific (E6/E7) primers. HPV types were confirmed by sequencing. The data were analyzed by the SPSS software. Results: Out of 86 samples, 23 (26.74%) were positive for HPV (15 cases, and 8 controls). By type-specific primers, high-risk HPVs were detected in the cases (3 HPV-16, 10 HPV-18, 1 HPV-31, and 1 HPV-33) and the controls (6 HPV-18, 1 HPV-31, and 1 HPV-33). No significant association was observed between HPV and EC (P = 0.078). Conclusions: Although no significant association was observed between HPV and EC, high-risk HPV genotypes were found in esophageal cancers more than non-cancerous esophageal tissues. To confirm this result, more studies should be carried out in other populations.

Introduction: Klebsiella pneumoniae is an opportunistic pathogen accounting for 5-7% of hospital acquired infections. The emergence of carbapenem-resistant Klebsiella pneumoniae has been increasing rapidly over recent years causing many therapeutic problems worldwide. This study aimed to research the antimicrobial resistance profile, detect β-lactamase genes among clinical isolates of K. pneumoniae, and determine their clonal relatedness. Methodology: All Klebsiella pneumoniae isolates were obtained from teaching hospitals in Urmia, Iran. Antimicrobial susceptibility testing was done by the disk diffusion method. Furthermore, minimum inhibitory concentrations of imipenem were determined by applying Etest strips. Screening of β-lactamase-producing isolates was performed by the combined disk method and modified Hodge test. The detection of β-lactamase genes was conducted by polymerase chain reaction (PCR), and isolates’ clonal relatedness was evaluated by random amplified polymorphic DNA (RAPD)-PCR. Results: Overall, 45 out of 182 (24.7%) K. pneumoniae isolates were non-susceptible to imipenem. The combined disk method and modified Hodge test revealed that 93.3% and 71.1% of the imipenem non-susceptible isolates were β-lactamase producers, respectively. The presence of blaVIM, blaNDM, blaKPC, and blaIMP genes was confirmed in 48.9%, 15.6%, 11.1%, and 6.7% of the β-lactamase-producing isolates, respectively. RAPD-PCR revealed that 73% of these isolates were classified into six different clusters. Conclusions: A relatively high prevalence of β-lactamase genes was seen among multidrug-resistant isolates of K. pneumoniae. Most patients infected with β-lactamase-producing isolates had a history of long-term hospitalization and nosocomial infections. The predominance of β-lactamase genes in intensive care unit and internal units alarm clinicians to the growth of hospitalization and mortality rates.

BK polyomavirus (BKV) as a member of polyomavirus family is prevalent in the human population. BKV persists in renal tissue after asymptomatic infection in childhood. The reactivation of BKV in renal transplant recipients sometimes can lead to BKV associated nephropathy. BKV isolates are classified into four serologically distinct subtypes. Present study was carried out to investigate the distribution pattern of BKV subtypes in Iranian Turkish renal transplant recipients.Urine samples from 12 kidney transplant recipients infected with BKV were analyzed by RFLP-PCR technique for classification of subtypes.Our analysis showed that all samples were infected with BKV type I. BK virus types II, III, and IV were not detected in our patients.Based on the results of the present study, BKV subtype I was the most frequently detected subtype in renal transplant recipients. To our knowledge, the present study provides the first data regarding distribution of BKV subtypes in Iranian renal transplant recipients.

Viral infections are a real threat in kidney transplant recipients because of their immunocompromised condition. This study aimed to evaluate herpes simplex virus-2 (HSV-2) seropositivity among kidney transplant recipients.Serum samples of 91 kidney transplant recipients from Urmia, Iran, were examined serologically for antibodies against HSV-2 using an enzyme-linked immunosorbent assay.The mean time from transplantation at HSV-2 testing was 5.04 +/- 4.45 years. The anti-HSV-2 immunoglobulin G antibody was positive in 5.4% of the kidney transplant recipients. Seropositive patients did not present any clinical manifestations of genital herpes infection. There was no association between HSV-2 seropositivity and age, gender, history of hemodialysis and transplantation, blood transfusion, or immunosuppressive regimen.Seroprevalence of HSV-2 is not high among our kidney transplant recipients. However, it remains a source of concern, considering the compromised immune system in this specific population.

While many adjuvants have been discovered and used in research, only a few adjuvants have been permitted for use with human vaccination. We have previously shown that the administration of naloxone (NLX), a general opioid antagonist, during infection with a non-virulent strain of herpes simplex virus type 1 (HSV-1) could enhance protection against HSV-1 challenge. Here, the adjuvant activity of NLX has been evaluated using a DNA vaccine for HSV-1 as a model. BALB/c mice were divided into four groups; for experimental groups, mice received the glycoprotein D1 (gD1) DNA vaccine alone or in combination with the adjuvant NLX. A positive control group received the KOS strain of HSV-1, and a negative control group received PBS. All mice were immunized three times on days 0, 21 and 42. Three weeks after the last immunization, immune responses against HSV-1 were assessed. Our results indicate that the administration of NLX as an adjuvant increased the ability of the gD1 DNA vaccine to enhance cytolytic T lymphocyte activity, lymphocyte proliferation, delayed-type hypersensitivity and shifting the immune response toward a T helper (Th)1 pattern and improved protective immunity against HSV-1. NLX also increased the IgG2a/IgG1 ratio, though it did not affect the production of HSV-1 antiserum. In conclusion, administration of NLX as an adjuvant in combination with the gD1 DNA vaccine can enhance cell-mediated immunity and shift the immune responses to Th1.

The effects of combined radiotherapy (RT) and chemotherapy in the severity of cytogenetic alterations expressed as micronucleus (MN) in peripheral blood lymphocytes of patients treated for esophageal cancer was evaluated. To do this, blood was obtained from 23 and 15 esophageal cancer patients scheduled for chemo-radiotherapy and RT alone, respectively, before, during, and after treatment. Blood samples were cultured in RPMI-1640 complete medium containing 1% phytohemagglutinin and incubated in a CO2 incubator. Cytochalasin-B was added to the cultures at a final concentration of 5 μg/ml. Finally, harvesting, slide making, and analysis were performed according to standard procedures. Results indicate that there was no significant difference between the frequencies of MN in lymphocytes of individuals before being treated with RT alone or chemo-radiotherapy. In the middle of treatment, (after 12 fractions of RT) the frequency of MN increased significantly compared with their concurrent pre-treatment samples in both groups (four-fold). However, the frequency of MN observed for RT patients was not significantly different with those received chemo- and radiotherapy. At the end of treatment, (after 24 fractions of radiotherapy) an increase in the MN frequency was observed for chemo-radiation group significantly higher than RT group (P=0.022). Mild increase in MN frequency in lymphocytes of patients receiving chemoradiation only after the completion of treatment course might be indicative of resistance induced by chemotherapeutics to the clastogenic effects of radiation. Therefore, using these agents repeatedly for cancer treatment in combination with radiation might not cause severe adverse biological effects in normal tissues.