Molecular sieve of the rat glomerular basement membrane: a transmission electron microscopic study of enzyme-treated specimens.

Isolated rat glomerular basement membrane was treated with elastase and observed by transmission electron microscopy. The treatment with elastase revealed the fundamental structure of the glomerular basement membrane quite clearly, and enabled the observation of a sieve structure within the glomerular basement membrane. This sieve structure may play a major role in the filtration of blood as well as in the production of urine. Treatment with antibody showed that the sieve was mainly constituted of type IV collagen.</p

Fibrillar ultrastructure of the glomerular basement membrane of the rat kidney as revealed by digestive treatment.

Rat kidney glomerular basement membrane (GBM) was isolated and digested with alpha-amylase and elastase. Electron microscopy revealed a meshwork structure composed of fibrils 3 nm in width. They appeared to be type IV collagen fibrils. We succeeded in clarifying a significant ultrastructural aspect of the GBM which had been unclear until now. The findings are consistent with our previously proposed GBM molecular sieve theory.</p

Efficacy and safety of nintedanib in Japanese patients with early-stage idiopathic pulmonary fibrosis: a study protocol for an observational study

Introduction: Idiopathic pulmonary fibrosis (IPF) is a fibrotic disease of unknown aetiology with a poor prognosis. Several clinical trials of nintedanib in patients with IPF have reported its inhibitory effect on reduced lung function, incidence of acute exacerbation of IPF and worsened health-related quality of life. Although nintedanib has a manageable safety and tolerability profile over long-term use, it was discontinued in over 20% of patients because of adverse events such as diarrhoea and liver dysfunction. This might explain why nintedanib use in patients with IPF is not widespread, especially among patients with early-stage IPF. In the present study, we aimed to clarify the efficacy, safety and tolerability of nintedanib in patients with stage I/II IPF, based on the Japanese IPF disease severity staging classification system.Methods and analysis: This is an ongoing, prospective, multicentre observational cohort study of patients with stage I/II IPF who will start receiving nintedanib. Totally, 215 patients at 35 sites in Kyushu and Okinawa, Japan will be enrolled and followed up for 3 years. Nintedanib therapy would be initiated at the discretion of the investigator. The primary endpoint, change in forced vital capacity (FVC) at 156 weeks, will be shown as the mean change in FVC from baseline to week 156 with 95% CIs estimated using the Wald method. The safety endpoint—occurrence of adverse events—will be assessed in each system organ class/preferred term.Ethics and dissemination: The study protocol and informed consent documents were approved by the Institutional Review Board at Nagasaki University Hospital (approval number 19102146) and each participating site. Written informed consent was obtained from all participants. Patient recruitment has begun. The results will be disseminated through scientific peer-reviewed publications and national and international conferences.Trial registration number: UMIN000038192

Ultrastructure of the rat glomerular basement membrane after enzymatic digestion

Although various hypotheses have been proposed about the ultrastructure of the glomerular basement membrane (GBM) of the kidney, it has not clearly revealed. At present, it is thought to be composed of a meshwork of fibrils as reported by Ota et al. We successfully observed the meshwork structure of the GBM under an electron microscope after enzymatic treatment with α-amylase and elastase. The fibrils were about 30nm in width and were thought to be composed of type Ⅳ collagen