Epstein-Barr virus induces an oxidative stress during the early stages of infection in B lymphocytes, epithelial, and lymphoblastoid cell lines

The study investigates the direct effect of Epstein-Barr virus infection on the oxidative profile of in vitro cultivated human cells. For this purpose, a panel of human EBV target cells presenting heterogeneity in their cellular and culture types (epithelial cells or lymphocytes; primary culture or continuous cell culture) was selected. These cells are purified human B lymphocytes, DG75, 293, and HepG2 cell lines. The oxidative stress was evaluated during the early stages of infection (2, 12, and 24 h) by measuring malondialdehyde, the end product of the lipid peroxidation, as well as the activities of two antioxidant enzymes: catalase and superoxide dismutase. The obtained results were compared with those of the untreated cells and the K562 cell line which has no interaction with EBV. The incubation of the different target cells with EBV induced an oxidative stress in the purified B lymphocytes, DG75, and 293, but not in HepG2 and K562. This oxidative stress was highlighted by an increase in MDA level (P < 0.05), which began 2 h after the addition of the virus and persisted after 12 and 24 h. Simultaneously, a decrease in catalase and superoxide dismutase activities was observed (P < 0.05), suggesting an alteration of the molecular mechanisms promoting cellular resistance to reactive oxygen species (ROS). The efficiency of EBV infection, assessed by viral DNA PCR amplification, was confirmed in 293 and DG75 but not in HepG2, which was in total concordance with their oxidative profiles. In conclusion, the EBV infection of B and epithelial cells leads to the establishment of an oxidative stress which can play a key role during the viral transformation.     

Relationship Between Conformation and Antiviral Activity-III. 3′-Azidothymidine (AZT) and 3′-Azido-2′, 3′-dideoxy-5-hydroxymethyluridine

Abstract

3′-Azido-2′,3′-dideoxy-5-hydroxymethyluridine (AZHMddUrd) was synthesized to improve the potency of 5-hydroxymethyl-2′-deoxyuridine (HMdUrd) against human immunodeficiency virus (HIV). AZHMddUrd was a very poor inhibitor of HIV replication (ED₅₀ >200 μM) and was also nontoxic up to 400 μM (highest concentration tested) to HT4-6C (HeLa CD₄) cells. AZT was phosphorylated by human cellular thymidine kinase. In contrast, AZHMddUrd and HMdUrd were poor substrates for the kinase. The relationship between molecular conformation and antiretroviral activity for 3′-azidothymidine (AZT), HMdUrd and AZHMddUrd is discussed.     

Lipid Peroxidation and Antioxidant System in the Tumor and in the Blood of Patients with Nasopharyngeal Carcinoma

Reactive oxygen species play a key role in cancer development by inducing and maintaining the oncogenic phenotypes of cancer cells. In this study, we examined lipid peroxidation and antioxidant enzymes activities in the blood and in the tumor of nasopharyngeal carcinoma patients. Plasma malondialdehyde, conjugated dienes, erythrocytes catalase, and superoxide dismutase activities have been measured in 30 untreated nasopharyngeal carcinoma patients and 30 controls on one hand. On the other hand, tumor malondialdehyde level, catalase, and superoxide dismutase activities have been measured in five nasopharyngeal carcinoma patients and compared with four controls. The lipid peroxidation was confirmed in the plasma by the high levels of malondialdehyde and conjugated dienes (p?<?0.001, respectively). Additionally, significantly higher concentrations of malondialdehyde were found in biopsies compared to the control group (p?<?0.001). In erythrocytes, superoxide dismutase activity was higher in patients than in controls (p?<?0.05), while it was unchanged in the tumor (p?>?0.05). Both erythrocytes and tumor catalase activities were significantly lower in patients than in controls (p?<?0.001, respectively). Statistical studies have shown a positive correlation between malondialdehyde level and IgA antibodies level against Epstein–Barr virus capsid antigen (p?<?0.05). In conclusion, we reported the presence of an oxidative stress in the blood and in the biopsies of nasopharyngeal carcinoma patients where Epstein–Barr virus seems to play a role.     

Synthesis,conformation, and antiviral activity of 5-methoxymethyl-2'-deoxycytidine analogs

Analogs of 5-methoxymethyl-2'-deoxycytidine, MMdCyd (1) by substitution at N4 were synthesized to impart resistance against deamination. The anti HSV-1 activity and solution conformation of analogs were determined. N4-Butanoyl-MMdCyd (10) was a potent inhibitor of HSV-1 replication while N4-hexanoyl-MMdCyd (11), N4-propanoyl-MMdCyd (9) and N4-acetyl-MMdCyd (8) had good activity against HSV-1 replication. All other analogs were devoid of activity against HSV-1.     

Identification of novel candidate genes by exome sequencing in Tunisian familial male breast cancer patients

Molecular Biology Reports - Male Breast Cancer (MBC) is a rare and aggressive disease that is associated with genetic factors. Mutations in BRCA1&nbsp;and&nbsp;BRCA2&nbsp;account for...     

Relationship Between Conformation and Antiviral Activity -IV. 5-Ethyl-2′-Deoxyurldine and 5-Ethyl-2′-Deoxycytidine +

Abstract

5-Ethyl-2′-deoxyuridine(EtdUrd), though a potent inhibitor of herpes simplex virus (HSV) replication, is rapidly catabolized to produce an inactive pyrimidine base by thymidine and/or uridine phosphorylases. 5-Ethyl-2′-deoxycytidine (EtdCyd) was synthesized to confer metabolic stability and thus improve efficacy against systemic HSV infections. EtdCyd was inactive against HSV in the presence or absence of deaminase inhibitors in VERO cells up to 2 mM. The relationship between molecular conformation and antiherpes activity for EtdUrd and EtdCyd is discussed.

     

Reliability and validity of a new repeated agility test as a measure of anaerobic and explosive power

The aim of this study was to evaluate the reliability and validity of a repeated modified agility test (RMAT) to assess anaerobic power and explosiveness. Twenty-seven subjects (age: 20.2 ± 0.9 years, body mass: 66.1 ± 6.0 kg, height: 176 ± 6 cm, and body fat: 11.4 ± 2.6%) participated in this study. After familiarization, subjects completed the RMAT consisting of 10 × 20-m maximal running performances (moving in forward, lateral, and backward) with ~25-second recovery between each run. Ten subjects performed the RMAT twice separated by at least 48 hours to evaluate relative and absolute reliability and usefulness of the test. The criterion validity of the RMAT was determined by examining the relationship between RMAT indices and the Wingate anaerobic test (WAT) performances and both vertical and horizontal jumps. Reliability of the total time (TT) and peak time (PT) of the RMAT was very good, with intraclass correlation coefficient > 0.90 and SEM < 5% and low bias. The usefulness of TT and PT of the RMAT was rated as "good" and "OK," respectively. The TT of the RMAT had significant correlations with the WAT (peak power: r = -0.44; mean power: r = -0.72), vertical jumps (squat jump: r = -0.50; countermovement jump: r = -0.61; drop jump (DJ): r = -0.55; DJ with dominant leg: r = -0.72; DJ with nondominant leg: r = -0.53) and 5 jump test (r = -0.56). These findings suggest that the RMAT is a reliable and valid test for assessing anaerobic power and explosiveness in multisprint sport athletes. Consequently, the RMAT is an easily applied, inexpensive field test and can provide coaches and strength and conditioning professionals with relevant information concerning the choice and the efficacy of training programs.     

Dynamic service deployment in a distributed heterogeneous cluster based router (DHCR)

This paper presents the design, implementation and evaluation of an extensible, scalable and distributed heterogeneous cluster based programmable router, called DHCR (Distributed Heterogeneous Cluster based Router), capable of supporting and deploying network services at run time. DHCR is a software IP router relying on heterogeneous cluster composed of separated computers with different hardware and software architecture capabilities, running different operating systems and interconnected through a high speed network connection. The DHCR ensures dynamic deployment of services and distributed control of router components (forwarding and routing elements) over heterogeneous system environments. The DHCR combines the IETF ForCES (Forwarding and Control Element Separation) architecture with software component technologies to meet the requirements of the next generation software routers. To ensure reliable and transparent communication between separated, decentralized and heterogeneous router components, the CORBA based middleware technology is used to support the DHCR internal communication. The paper also explores the use of the CORBA Component Model (CCM) to design and implement a modular, distributed and heterogeneous forwarding path for the DHCR router architecture. The CCM based forwarding plane ensures dynamic reconfiguration of the data path topology needed for low-level service deployment. Results on achievable performance using the proposed DHCR router are reported.

Synthesis,Molecular Conformation and Activity Against Herpes Simplex Virus of (E)-5-(2-Bromovinyl)-2′-Deoxycytidine Analogs

Analogs of (E)-5-(2-bromovinyl)-2 ′-deoxycytidine (BrVdCyd) (1) by substitution at N⁴ were synthesized to impart resistance against deamination. The anti-HSV-1 activity and solution conformation of these analogs were determined. N⁴-Acetyl-BrVdCyd (2) was a potent inhibitor of HSV-1 replication whereas N⁴-propanoyl-BrVdCyd (3) had good activity and N⁴-Butanoyl-BrVdCyd (4) had only low activity against HSV-1 replication. N⁴-Methyl-BrVdCyd (5) was devoid of activity against HSV-1.     

Susceptibility of Iraqi fresh water snails to infection with Schistosoma haematobium and Schistosoma mansoni Egyptian strains

A great number of Egyptian workers and farmers are seeking settlement in Iraq and some of them proved to have either Schistosoma Haematobium (S.h.) or Schistosoma mansoni (S.m) or even mixed infection. Besides, there is the possibility that some of the Iraqi fresh water snails may prove to be susceptible to infection by one or both of the Schistosoma Egyptian strains. The present study deals with investigations on the susceptibility of Iraqi B. truncatus, Gyranaulus ehrenbergi, Physa c.f. fontinalis, Lymnea lagetis, Melanoides tuberculata and Melanopsis nodes by these parasites. Egyptian S. haematobium but not Egyptian S. mansoni infect Iraqi B. truncatus and both proved to be unable to infect any of the other snails included in the study. Yet, the number of cercariae shedded by B. truncatus snails infected with the Egyptian S. haematobium strain, was much less that the number of cercariae shedded by these snails when infected with the Iraqi S. Haematobium strain.