Diagnosis of herpetic esophagitis in the immunocompetent subject by PCR (Herpes Consensus Generique (R) - Argene). Report of six cases
PATHOLOGIE BIOLOGIE
Authors: Dekeyser, S.; El Nady, M.; Diaz, E.; Cassagnou, M.; Descamps, D.
Abstract
Aim of the work. - We have researched and identified Herpes viruses on the esophageal biopsies taken during the period between September 2006 and March 2008 for 15 suspected patients. Patients and methods. - The esophageal biopsies were transferred to the laboratory being conserved in physiological serum and frozen at -80 degrees C for PCR. A fragment was conserved for histopathological analysis. The specimen was defrozen and refrozen in liquid azote (to limit the inhibitors) and crushed to the powder form. Extraction was then done following the prerecognised protocol (Herpes Consensus Generique(R) - "Argene"). That kit allows the amplification consensus of the viral genome of the most frequently encountered Herpes family virus: HSV1, HSV2, CMV, VZV, EBV and HHV6. The identification of the implicated virus was done by the Hybridowell Herpes Identification (Argene) kit in parallel with the migration of SDS gel of the obtained amplifications. Results. - HSV1 was identified in seven esophageal biopsies between the 15 studied. HHV6 and the association HHV6/EBV for two patients and only one biopsy had inconclusive. The endoscopie and the histopathological examination had confirmed ulcerated esophagitis with cytopathogene aspect in favour of viral infection for six patients. Conclusion. - In absence of inhibitors, the adaptation of the extraction technique of the fragments of tissue for few millimetres and the amplifications by PCR had allowed rapid confirmation of the diagnosis of herpetic esophagitis secondary to HSV1 even before the results of the histopathological examination. Treatment by acyclovir entrained regression of the disease. (c) 2008 Elsevier Masson SAS.
Validation and Characterization of Five Distinct Novel Inhibitors of Human Cytomegalovirus
JOURNAL OF MEDICINAL CHEMISTRY
Authors: Kapoor, Arun; Ghosh, Ayan K.; Forman, Michael; Hu, Xin; Ye, Wenjuan; Southall, Noel; Marugan, Juan; Keyes, Robert F.; Smith, Brian C.; Meyers, David J.; Ferrer, Marc; Arav-Boger, Ravit
Abstract
The critical consequences of human cytomegalovirus (HCMV) infection in the transplant population and in congenitally infected infants, the limited treatment options for HCMV, and the rise of resistant mutants toward existing therapies has fueled the search for new anti-HCMV agents. A pp28-luciferase recombinant HCMV was used as a reporter system for high-throughput screening of HCMV inhibitors. Approximately 400 000 compounds from existing libraries were screened. Subsequent validation assays using resynthesized compounds, several virus strains, and detailed virology assays resulted in the identification of five structurally unique and selective HCMV inhibitors, active at sub to low micromolar concentrations. Further characterization revealed that each compound inhibited a specific stage of HCMV replication. One compound was also active against herpes simplex virus (HSV1 and HSV2), and another compound was active against Epstein-Barr virus (EBV). Drug combination studies revealed that all five compounds were additive with ganciclovir or letermovir. Future studies will focus on optimization of these new anti-HCMV compounds along with mechanistic studies.