No abstract

No abstract

What is known and objective: In Japan, ledipasvir/sofosbuvir, elbasvir/grazoprevir and glecaprevir/pibrentasvir are recommended as first-line treatments for patients with untreated hepatitis C virus genotype 1. Although they have demonstrated a high efficacy in clinical trials, there are no direct comparative studies. Clarification of their effectiveness and safety in real-world clinical practice is required. Therefore, we conducted a retrospective multicentre study on the effectiveness of these direct-acting antivirals in real-world clinical practice. Methods:We retrospectively evaluated the clinical data of untreated patients with persistent HCV genotype 1 infection who started first-line treatment with ledipasvir/ sofosbuvir, elbasvir/grazoprevir or glecaprevir/pibrentasvir between September 2015 and January 2019 at 11 medical institutions in Japan. The primary efficacy endpoint was a sustained virologic response after 12 weeks of treatment. The secondary endpoints included sustained virologic response after 24 weeks of treatment and end of treatment response. The safety endpoint was treatment completion rate. How to cite this article: Kaya M, Nakamura K, Sugiyama K, et al. Retrospective multicentre study on the effectiveness of first-line direct-acting antivirals against hepatitis C virus genotype-1.

ICR-derived strain with gulomerulonephrisis (ICGN) mouse derived from ICR mouse is a newly established mouse strain with hereditary nephrotic syndrome. The affected ICGN mice consistently show the clinical signs of nephrotic syndrome, developing various degrees. The lesions consist of thickened capillary basement membrane, enlarged mesangium without cellular proliferation, and tubulointerstitial fibrosis. Based on these histopathological findings and clinical biochemical data, ICGN strain mouse is considered to be a good experimental model for human idiopathic nephrotic syndrome. Extracellular matrix (ECM) components provide structural integrity to the tissues, and mediate regulation of cell growth, migration, differentiation, etc. The damaged cells have increased secretion of ECM components. This is a kind of self-protecting reaction that is associated with healing process against injury. However, the hyperaccumulation of ECM components leads to fibrosis, a pathological phenomenon. Therefore, it is very important to make clearly the process of fibrosis in ICGN strain mouse. In this study, the expression and localization of transforming growth factor beta1 (TGF-b1), TGF-b1 type I receptor (TGFR1), and bone morphogenic protein (BMP)-7, which regulate the signals of TGF-b1 negatively, were investigated by using immunohistochemical staining and Western blotting. High expression levels of TGF-b1 and TGFR1 were observed in tubular epithelial cells of middle stage-ICGN mice as compared with those of control ICR mice. BMP-7 was strongly expressed in tubular epithelium of ICR mice, but it decreased with the progression of renal disease in ICGN mice. Moreover, no localization of BMP-7 in expanded tubular epithelial cells in ICGN mice was seen. These data suggest that the increase of TGF-b1 and TGFR1 and the degradation of negative regulation of TGF-b1 by BMP-7 in middle and late stages of ICGN mice play an important role in renal fibrosis of ICGN mice. The present findings may contribute to elucidate the pathogenic mechanisms of human idiopathic nephrotic syndrome.Common Achilles tendon ruptures are usually not fixed by absorbable sutures due to limitations in their strength properties. Modern technology has made it possible to develop bioabsorbable sutures with prolonged strength retention. To evaluate histologically tissue reactions and biodegradation of poly-L/D-lactide (PLDLA) sutures implanted in Achilles tendon of rabbits. Fifteen rabbits were operated on and killed within a time schedule of 2, 6 and 12 weeks, with five rabbits in per period. PLDLA monofilament sutures (Tampere University of Technology, Tampere, Finland) were implanted inside the rabbit medial gastrocnemius tendon for biocompatibility testing. Polyglyconate (4.0) monofilament sutures (Maxon Ò , Cyanamid of Great Britain Ltd., Gosport, UK) with the same diameter were implanted in the contralateral tendon. The histology was studied in hard-resin embedded samples and the thickness of the encapsule membrane was determined histomorphometrically.PLDLA hav...