Search

Claudins regulate paracellular permeability in different tissues. The claudin-binding domain of Clostridium perfringens enterotoxin (cCPE) is a known modulator of a claudin subset. However, it does not efficiently bind to claudin-1 (Cldn1). Cldn1 is a pharmacological target since it is (i) an essential co-receptor for hepatitis C virus (HCV) infections and (ii) a key element of the epidermal barrier limiting drug delivery. In this study, we investigated the potential of a Cldn1-binding cCPE mutant (i) to inhibit HCV entry into hepatocytes and (ii) to open the epidermal barrier. Inhibition of HCV infection by blocking of Cldn1 with cCPE variants was analyzed in the Huh7.5 hepatoma cell line. A model of reconstructed human epidermis was used to investigate modulation of the epidermal barrier by cCPE variants. In contrast to cCPEwt, the Cldn1-binding cCPE-S305P/S307R/S313H inhibited infection of Huh7.5 cells with HCV in a dose-dependent manner. In addition, TJ modulation by cCPE variant-mediated targeting of Cldn1 and Cldn4 opened the epidermal barrier in reconstructed human epidermis. cCPE variants are potent claudin modulators. They can be applied for mechanistic in vitro studies and might also be used as biologics for therapeutic claudin targeting including HCV treatment (host-targeting antivirals) and improvement of drug delivery.

Goal: Recent studies suggest an increasing prevalence of atypical initial symptoms in patients with celiac disease (CD). The aim of this study was to compare the presenting symptoms of CD at 2 comparable referral institutions in South Florida, and in Ankara, Turkey. We retrospectively reviewed the records of patients with an initial diagnosis of CD by small bowel biopsy during the same (1991 to 2001) 10-year period at Cleveland Clinic Florida and University of Ankara, Turkey. A numerical score was assigned to presenting symptom and signs. Results: There were 28 patients in the South Florida group (51% men) and 40 patients in the Turkish group (35% men) (P = NS). The Turkish patients were significantly younger at diagnosis (36 ± 2y vs. US patients 66 ± 3y) (P