The pH of the skin surface and its impact on the barrier function

The `acid mantle' of the stratum corneum seems to be important for both permeability barrier formation and cutaneous antimicrobial defense. However, the origin of the acidic pH, measurable on the skin surface, remains conjectural. Passive and active influencing factors have been proposed, e. g. eccrine and sebaceous secretions as well as proton pumps. In recent years, numerous investigations have been published focusing on the changes in the pH of the deeper layers of the stratum corneum, as well as on the influence of physiological and pathological factors. The pH of the skin follows a sharp gradient across the stratum corneum, which is suspected to be important in controlling enzymatic activities and skin renewal. The skin pH is affected by a great number of endogenous factors, e. g. skin moisture, sweat, sebum, anatomic site, genetic predisposition and age. In addition, exogenous factors like detergents, application of cosmetic products, occlusive dressings as well as topical antibiotics may influence the skin pH. Changes in the pH are reported to play a role in the pathogenesis of skin diseases like irritant contact dermatitis, atopic dermatitis, ichthyosis, acne vulgaris and Candida albicans infections. Therefore, the use of skin cleansing agents, especially synthetic detergents with a pH of about 5.5, may be of relevance in the prevention and treatment of those skin diseases. Copyright (c) 2006 S. Karger AG, Base

results of large prospective study in Berlin Screening Colonoscopy practices ; (Berlin Colonoscopy Project 6, BECOP-6)

Die Vorsorgekoloskopie ist eine etablierte Methode zur Prävention kolorektaler Karzinome. In Deutschland wird die Vorsorgekoloskopie begleitet durch ein Qualitätssicherungsprogramm des Zentralinstitutes der Kassenärztlichen Bundesvereinigung (ZI der KBV) in Berlin, in dem Outcome-Parameter, wie die Adenomdetektionsrate und die Komplikationen registriert werden. Um die Validität dieses Qualitätssicherungsprogramms zu analysieren, wurden die ZI- Outcome-Daten mit denen unserer prospektiven Studie verglichen. Die Vorsorgekoloskopiedaten von 21 niedergelassenen Gastroenterologen wurden in einem Zeitraum von 18 Monaten in Bezug auf Adenomrate (ADR, Rate der Patienten mit mindestens einem Adenom) und Komplikationen analysiert. Sie wurden verglichen mit denen einer prospektiven Studie, welche dieselben Gastroenterologen während desselben Zeitraumes durchführten. Die Komplikationen wurden in drei Schritten dokumentiert: Die Endoskopiker füllten in einem ersten Schritt einen Fragebogen (CRF = Case Record Form) über unmittelbare Komplikationen aus, die während und sofort nach der Koloskopie bis zur Entlassung der Patienten aus der Praxis auftraten (Ärzte-CRF Koloskopie. CRF 1). Ein zweiter Fragebogen enthielt Komplikationsdaten nur für bekanntgewordene Komplikationen nach Entlassung aus der Praxis bis zu einem Zeitintervall von 30 Tagen hiernach (Ärzte-CRF mit Nachbeobachtungsphase. CRF 2). Den Patienten wurden nach der Untersuchung Fragebögen mitgegeben, die sie innerhalb eines Monats zurücksendeten (Patienten-CRF. CRF 3), mit Fragen zu Komplikationen, interventionsbedingten Beschwerden, einem möglichen Krankenhausaufenthalt, Akzeptanz der Koloskopiedurchführung und der Vorbereitung zur Koloskopie (Darmreinigung), sowie anderen logistischen Details (Rücklaufquote: 90,1%). 12.134 Studien-Vorsorgekoloskopien und 12.148 ZI-Registrierungsfälle wurden verglichen (mittleres Alter 64.5 Jahre; 47% Männer, 53% Frauen). Die ADR war ähnlich zwischen den Studien- und den ZI- Daten (21.0% vs. 20.5%; p=0.18). Hingegen war die Komplikationsrate in der prospektiven Studie dreifach höher (0.46% vs. 0.15%). Das bisher in Deutschland durchgeführte nationale Qualitätssicherungsprogramm für die Vorsorgekoloskopie liefert zwar annährend genaue Outcome-Daten in Bezug auf die Adenomrate. Bei den Komplikationen werden allerdings nicht alle Fälle adäquat erfasst. Wie unsere Arbeit zeigt, existiert eine nicht unerhebliche Dunkelziffer. Es sind also standardisierte Methoden auch für die nachteiligen Ereignisse nach der Koloskopie vonnöten. Diese sollten entsprechend dokumentiert werden.Screening-Colonoscopy is an established modality for the prevention of colorectal cancer. In Germany screening-colonoscopy is accompanied by a quality assurance programme by the Central Research Institute of Ambulatory Health Care, Berlin (Zentralinstitut (ZI) der Kassenärztlichen Vereinigung), within outcome data as adenoma detection rate and complication are registered. To analyze the validity of this quality assurance programme, the ZI-data were compared with those of our prospective study. The screening-colonoscopy data of 21 physicians were analyzed during a time period of 18 months in relation to adenoma rate (ADR – rate of patients with at least one adenoma) and complications. The Data was compared with those of a prospective study that had been supplied by the same physicians during the same time period. The complications were recorded in three steps: After colonoscopy, physicians filled out a case report form (CRF) on immediate complications during and immediately after colonoscopy until patient discharge (physician CRF colonoscopy; CRF-1). A second CRF included complication data that were brought to the attention of the gastroenterologists after the patient had left the practice, within 30 days (CRF-2). Patients were sent a questionnaire, which they returned within a month (patient CRF; CRF-3) with questions on complications, intervention-related troubles, hospital admissions, acceptability to patients of preparation, colonoscopy and other logistical details (reply rate: 90.1%). 12.134 screening-colonoscopy and 12.148 ZI- register-data were compared (mean age 64.5 years; 47 % men, 53 % women). The adenoma rate was similar between this study and the ZI-data (21.0 % vs. 20.5 %; p=0.18). The complication rate of the prospective study was three times higher (0.46 % vs. 0.15 %). The German quality assurance programme for screening-colonoscopy provides approximate outcome-data in relation of the adenoma rate, but the complications are under-represented. As our study points, a number of unrecorded cases exists. Standardised methods are needed to document and record adverse events after colonoscopy

Virus-induced gene silencing of Argonaute genes in Nicotiana benthamiana demonstrates that extensive systemic silencing requires Argonaute1-like and Argonaute4-like genes

Several distinct pathways of RNA silencing operate in plants with roles including the suppression of virus accumulation, control of endogenous gene expression, and direction of DNA and chromatin modifications. Proteins of the Dicer-Like and Argonaute (AGO) families have key roles within these silencing pathways and have distinct biochemical properties. We are interested in the relationships between different silencing pathways and have used Nicotiana benthamiana as a model system. While not being an amenable plant for traditional genetics, N. benthamiana is extensively used for RNA-silencing studies. Using virus-induced gene silencing technology we demonstrate that both NbAGO1- and NbAGO4-like genes are required for full systemic silencing but not for silencing directed by an inverted repeat transgene. Phenotypic differences between the virus-induced gene silencing plants indicate that NbAGO1 and NbAGO4 like act at different stages of the silencing pathways. Suppression of NbAGO1 expression recapitulated the hypomorphic mutant phenotype of certain Arabidopsis (Arabidopsis thaliana) ago1 alleles, however, suppression of NbAgo4 like resulted in phenotypes differing in some respects from those reported for Arabidopsis ago4. We suggest that the small interfering RNA amplification step required for full systemic silencing is dependent upon a nuclear event requiring the activity of NbAGO4 like