Low detection rate of HPV in oral and laryngeal carcinomas

The presence of human papillomaviruses (HPVs) in 38 oral and 16 laryngeal lesions (verrucous hyperplasia, carcinoma in situ and carcinomas) was investigated using the polymerase chain reaction (PCR) technique. All biopsies were fresh frozen and a set of consensus and type-specific primers was used for PCR detection and HPV typing. In oral biopsies a low proportion of HPV-positive cases was found, despite the sensitive techniques. Only one case out of 38, a carcinoma in situ was positive (2.6%). It is thought that this finding reflects a minimal presence of HPV in the oral lesions, but a transient role of virus in the induction of carcinomas cannot be ruled out. Differences in relation to other studies may be geographical and/or methodological. In laryngeal carcinomas (and dysplasias), 3 out of 16 cases were HPV positive. This frequency (19%) concurs with most other studies

A microdose study of 14C-AR-709 in healthy men: pharmacokinetics, absolute bioavailability and concentrations in key compartments of the lung

Purpose: To explore, in a microdose (phase-0) study, the pharmacokinetics, bioavailability and concentrations in key compartments of the lung, of AR-709, a novel diaminopyrimidine antibiotic for the treatment of respiratory infection. Methods: Four healthy men each received two single, 100 μg microdoses of 14C-AR-709, 7 days apart: the first was administered intravenously (IV), the second orally. Plasma pharmacokinetics of 14C and unchanged AR-709 were obtained by high-performance liquid chromatography and accelerator mass spectrometry (AMS). Next, 15 healthy men received a single, 100 μg microdose of 14C-AR-709 IV. Plasma, bronchoalveolar lavage fluid, alveolar macrophages and bronchial mucosal biopsy samples were analysed by AMS. Results: After IV administration, clearance of AR-709 was 496 mL/min, volume of distribution was 1,700 L and the absolute oral bioavailability was 2.5 . Excretion in urine was negligible. At 8-12 h after IV dosing, 14C concentrations in lung samples were 15- (bronchial mucosa) to 200- (alveolar macrophages) fold higher than in plasma. In alveolar macrophages, 14C was still mostly associated with AR-709 at 12 h after dosing. Conclusions: The results of this microdose study indicate that AR-709 attains concentrations appreciably higher within the lung than in plasma. Its low oral bioavailability however, precludes oral administration. Although IV administration would appear to be an effective route of administration, this would limit the use of AR-709 to a clinical setting and would therefore be economically unsustainable. If further clinical development were to be undertaken, therefore, an alternative route of administration would be necessary. © 2013 Springer-Verlag Berlin Heidelberg

En undersøkelse av Vossevassdraget 1977

Rapporten presenterer resultater fra undersøkelser i Vossevassdraget 1977 som var et samarbeidsprosjekt mellom NIVA og Zoologisk Institutt ved Universitetet i Oslo. Det går fram av disse undersøkelsene at området ved Vangen er sterkt belastet med utslipp av urenset husholdningskloakk og at vassdragsreguleringer frarås inntil utslippene er samlet opp og renset i kloakkrenseanleg

A microdose study of 14C-AR-709 in healthy men: pharmacokinetics, absolute bioavailability and concentrations in key compartments of the lung

Purpose: To explore, in a microdose (phase-0) study, the pharmacokinetics, bioavailability and concentrations in key compartments of the lung, of AR-709, a novel diaminopyrimidine antibiotic for the treatment of respiratory infection. Methods: Four healthy men each received two single, 100 μg microdoses of 14C-AR-709, 7 days apart: the first was administered intravenously (IV), the second orally. Plasma pharmacokinetics of 14C and unchanged AR-709 were obtained by high-performance liquid chromatography and accelerator mass spectrometry (AMS). Next, 15 healthy men received a single, 100 μg microdose of 14C-AR-709 IV. Plasma, bronchoalveolar lavage fluid, alveolar macrophages and bronchial mucosal biopsy samples were analysed by AMS. Results: After IV administration, clearance of AR-709 was 496 mL/min, volume of distribution was 1,700 L and the absolute oral bioavailability was 2.5 . Excretion in urine was negligible. At 8-12 h after IV dosing, 14C concentrations in lung samples were 15- (bronchial mucosa) to 200- (alveolar macrophages) fold higher than in plasma. In alveolar macrophages, 14C was still mostly associated with AR-709 at 12 h after dosing. Conclusions: The results of this microdose study indicate that AR-709 attains concentrations appreciably higher within the lung than in plasma. Its low oral bioavailability however, precludes oral administration. Although IV administration would appear to be an effective route of administration, this would limit the use of AR-709 to a clinical setting and would therefore be economically unsustainable. If further clinical development were to be undertaken, therefore, an alternative route of administration would be necessary. © 2013 Springer-Verlag Berlin Heidelberg.</p

Engineered expression of the Coxsackie B and adenovirus receptor (CAR) in human dendritic cells enhances recombinant adenovirus-mediated gene transfer

Dendritic cells (DCs) are key antigen-presenting cells (APCs) that act as central modulators of cellular immune responses. Genetic modification of DCs has considerable therapeutic potential in the treatment of a wide spectrum of diseases, including cancer and persistent viral infection. In this report, we show that pre-treatment of DCs with a recombinant adenovirus encoding the major adenovirus receptor, Coxsackie B and adenovirus receptor (CAR), significantly increased the uptake of recombinant adenoviruses (Ads) by primary immature monocyte-derived DCs. This could be correlated with CAR mRNA and surface protein expression. Transduction of DCs by recombinant adenoviruses did not significantly alter cellular viability. Therefore, we propose that pre-treatment of DCs with Ad5-CAR is one strategy to increase the susceptibility of DCs to transduction by recombinant Ads

Detection of human papillomavirus and adenovirus in benign and malignant lesions of the larynx

OBJECTIVE: To investigate the role of human papillomavirus (HPV) and adenovirus (AdV) infections in the oncogenesis of squamous cell carcinomas of the larynx and of laryngeal dysplasia. STUDY DESIGN: Cross-sectional study with planned data collection. SETTING: Department of Otorhinolaryngology G. Ferreri and Department of Experimental Medicine and Pathology-Section of Virology, Sapienza University of Rome. SUBJECTS AND METHODS: Biopsy samples were taken from 68 patients with benign and malignant lesions of the larynx. All tissue samples were analyzed by means of polymerase chain reaction with two groups of primers for HPV and with a pair of primers for AdV. RESULTS: All cases of carcinomas and dysplasia as well as all control cases were negative for both viruses. Four of the five cases of laryngeal papillomas were positive for only HPV, confirming the role of these viral types in the origin of papillomas. CONCLUSION: The absence of viral genomes in laryngeal carcinomas as in the other cases studied suggests the existence of other factors that play a more important role than viral infection in the carcinogenesis of these lesions. (c) 2009 American Academy of Otolaryngology-Head and Neck Surgery Foundation. All rights reserved