The interplay between local immune response and Epstein-Barr virus-infected tonsillar cells could lead to viral infection control.

Epstein Barr virus (EBV) gains access to the host through tonsillar crypts. Our aim was to characterize microenvironment composition around EBV+ cells in tonsils from pediatric carriers, to disclose its role on viral pathogenesis. LMP1 expression, assessed by immunohistochemistry (IHC), was used to discriminate EBV + and - zones in 41 tonsil biopsies. Three regions were defined: Subepithelial (SE), interfollicular (IF) and germinal center (GC). CD8, GrB, CD68, IL10, Foxp3, PD1, CD56 and CD4 markers were evaluated by IHC; positive cells/100 total cells were counted. CD8+, GrB+, CD68+ and IL10+ cells were prevalent in EBV+ zones at the SE region (p < 0.0001, p = 0.03, p = 0.002 and p = 0.002 respectively, Wilcoxon test). CD4+ and CD68+ cell count were higher in EBV + GC (p = 0.01 and p = 0.0002 respectively, Wilcoxon test). Increment of CD8, GrB and CD68 at the SE region could indicate a specific response that may be due to local homing at viral entry, which could be counterbalanced by IL10, an immunosuppressive cytokine. Additionally, it could be hypothesized that CD4 augment at the GC may be involved in the EBV-induced B-cell growth control at this region, in which macrophages could also participate.

Epstein-Barr virus lytic cycle involvement in diffuse large B cell lymphoma.

Epstein-Barr virus (EBV)-mediated B cell transformation is achieved predominantly through the action of latent proteins, but recent evidence suggests that lytic EBV replication has also a certain pathogenic role in lymphomagenesis, at least in the early phases of cell transformation. Particularly, in diffuse large B cell lymphoma (DLBCL), the EBV lytic cycle is by and large unexplored, so to disclose lytic cell contribution to lymphomagenesis, our aim was to evaluate viral early and late lytic gene expression in relation to several immune response markers in a series of EBV+ DLBCL from Argentina. An unexpected number of cells expressed lytic transcripts, being transcribed at the BZLF1, BHRF1, and BLLF1 locus, by real-time quantitative polymerase chain reaction. This lytic antigen expression was confirmed by immunohistochemical staining for BMRF1 early lytic protein, and a positive correlation between lytic and latent genes was confirmed, revealing a close link between their expressions in EBV+ DLBCL pathogenesis. Remarkably, BZLF1 displayed a negative correlation with CD4 cell counts, and this could be in part justified by the restriction of antigen presentation previously reported. The direct correlation for the late lytic gene BLLF1 and IFNγ in this series could represent a specific response directed towards this antigen. Interleukin 10 transcripts also displayed a positive correlation with lytic expression, indicating that regulatory mechanisms could be also involved on EBV-associated DLBCL pathogenesis in our series. Complete lytic reactivation in EBV-positive tumours could potentially kill EBV-positive malignant cells, providing a tool to promote tumour cell killing mediated by EBV as a complementary treatment strategy.

Cytotoxic response against Epstein Barr virus coexists with diffuse large B-cell lymphoma tolerogenic microenvironment: clinical features and survival impact.

Epstein-Barr Virus (EBV) is present in neoplastic cells of 15% of Asian and Latin-American diffuse large B-cell lymphoma (DLBCL) patients. Even though a tolerogenic microenvironment was recently described in DLBCL, little is known concerning immunomodulatory features induced by EBV. As suggested in Hodgkin lymphoma, EBV-specific cytotoxic T-cells are increased but showing immune exhaustion features. Hence, host immunity suppression may play a critical role in tumor progression. This study aimed to investigate, whether an association between tumor microenvironment features and EBV presence is taking place, and its clinical correlate. The incidence of EBV+DLBCL NOS was 12.6% in this cohort. Cytokine and chemokine transcripts expression and immunophenotype analysis showed that EBV infection was associated with increased gene expression of immunosuppressive cytokine (IL-10) together with increased CD8+ T-cells and granzyme B+ cytotoxic effector cells. However, this specific response coexists with a tolerogenic milieu, by PD-1 expression, in EBV+ and EBV-DLBCL cases. High PD-1+ cell counts, EBV presence and low CCL22 expression were associated with worse survival, supporting our hypothesis that EBV-specific response is mounted locally and its inhibition by, for example PD-1+ cells, may negatively affect outcome. The better understanding of the interplay between lymphoma cells and microenvironment in a viral framework could thereby facilitate the discovery of new targets for innovative anti-lymphoma treatment strategies.

Empleo profiláctico de benzodiazepínicos en pacientes con hipertensión candidatos a cirugía dentomaxilar: un estudio doble ciego / Prophylactic employment of benzodiazepine in hypertensive candidates for dentomaxillary surgery: a double-blind study

Tipo de estudio: clínico experimental, aleatorio controlado de tipo doble ciego y cruzado. Objetivos: determinar si el uso profiláctico de benzodiazepínicos mejora las condiciones en las que se ejecutan los procedimientos quirúrgicos. Materiales y métodos: se estudió los efectos hallados en las 20 extracciones dentales que fueron realizadas en los pacientes hipertensos esenciales controlados, en las cuales se analizaron las variables: presión arterial sistólica y diastólica, duración del acto quirúrgico y estado general del paciente. Resultados: al comparar el mayor incremento de la presión arterial sistólica del grupo fármaco y grupo placebo observamos una diferencia de 7.7mmHg, mientras que en la presión arterial diastólica fue de 2.2mmHg, lo cual nos muestra que la diferencia no es significativa. La administración benzodiazepínico fue irrelevante en cuanto a la duración del acto quirúrgico y del estado general del paciente. Conclusión: El uso del benzodiazepínico (alprazolam de 0.25mg) mostró un resultado irrelevante.

Type of study: clinic experimental, random controlled double-blind and crossed type. Objective: determine if the prophylactic use of benzodiazepine improves the conditions in which the surgical procedures are carried out. Materials and methods: the effects of 20 dental extractions, which were conducted on controlled essentially hypertensive patients, were studied in order to analyze the variables: systolic and diastolic blood pressure, duration of the surgical act and general state of the patient. Results: when the highest increase of the systolic blood pressure of drug and placebo groups were observed, there was a difference of 7.7 mmHg, while the diastolic blood pressure was of 2.2.mmHg, which shows us that the difference is not significant. The administration of benzodiazepine was irrelevant concerning the duration of the surgical act and the general state of patient. Conclusion: the use of benzodiazepine (alprazolam 0.25 mg) showed an irrelevant result.