Use of frozen native feces for fecal microbiota transplantation in recurrent infection: a simple way to improve the efficiency of donor feces preparation.

Preparing fecal microbiota transplants immediately after donation is resource-intensive, and a proportion are destroyed following abnormal screening results. We retrospectively compared two processes, frozen fecal preparation (FFP) and fresh native frozen preparation (FNFP), for clinical efficacy in the treatment of recurrent infection (rCDI). FFP and FNFP were similarly effective with clinical success rates of 76.

ISABELA Studies: Plasma Exposure and Target Engagement Do Not Explain the Lack of Efficacy of Ziritaxestat in Patients with Idiopathic Pulmonary Fibrosis.

Autotaxin (ATX) contributes to the production of lysophosphatidic acid (LPA), which is associated with fibrosis development in idiopathic pulmonary fibrosis (IPF). The ATX inhibitor ziritaxestat failed to reduce decline in forced vital capacity (FVC) in patients with IPF in ISABELA 1 and 2 (NCT03711162 and NCT03733444), two identically designed phase III studies. In the current analysis, we evaluated pharmacokinetic and pharmacodynamic data from the pooled ISABELA studies to determine whether the lack of efficacy could be attributed to insufficient exposure and/or target engagement.

Safety, Pharmacokinetics, and Pharmacodynamics of the ADAMTS-5 Inhibitor GLPG1972/S201086 in Healthy Volunteers and Participants With Osteoarthritis of the Knee or Hip.

GLPG1972/S201086 is a disintegrin and metalloproteinase with thrombospondin motif-5 (ADAMTS-5) inhibitor in development as an osteoarthritis disease-modifying therapy. We report the safety, tolerability, pharmacokinetics, and pharmacodynamics (turnover of plasma/serum ARGS-aggrecan neoepitope fragments [ARGS]) of GLPG1972 in 3 randomized, double-blind, placebo-controlled phase 1 trials. Study A, a first-in-human trial of single (≤2100 mg [fasted] and 300 mg [fed]) and multiple (≤1050 mg once daily [fed]; 14 days) ascending oral (solution) doses, investigated GLPG1972 in healthy men (N = 41; NCT02612246).

Pharmacokinetics and Metabolism of Ziritaxestat (GLPG1690) in Healthy Male Volunteers Following Intravenous and Oral Administration.

Ziritaxestat is a novel inhibitor of autotaxin, an enzyme responsible for the production of lysophosphatidic acid, the downstream signaling of which mediates responses to tissue injury and has been implicated in the pathogenesis of fibrotic conditions such as idiopathic pulmonary fibrosis and systemic sclerosis. This study (Clinical Trial Registration: NCT03787186) was designed to assess the absorption, distribution, metabolism, and excretion of orally administered 600-mg ziritaxestat labeled with a carbon-14 tracer ( C-ziritaxestat). To understand the absolute bioavailability of ziritaxestat, an intravenous 100-μg microdose, labeled with a microtracer amount of C radiation, was administered in a separate part of the study, following an unlabeled 600-mg therapeutic oral dose of ziritaxestat.

The predicted collagen-binding domains of Drosophila SPARC are essential for survival and for collagen IV distribution and assembly into basement membranes.

The assembly of basement membranes (BMs) into tissue-specific morphoregulatory structures requires non-core BM components. Work in Drosophila indicates a principal role of collagen-binding matricellular glycoprotein SPARC (Secreted Protein, Acidic, Rich in Cysteine) in larval fat body BM assembly. We report that SPARC and collagen IV (Col(IV)) first colocalize in the trans-Golgi of hemocyte-like cell lines.

[Retinal detachment after surgery of congenital cataract].

We conducted a retrospective study of retinal detachments after congenital cataract surgery managed during the last twelve years so as to determine whether the surgical prognosis has been improved by the use of vitreoretinal microsurgery. The study included 25 eyes of 23 consecutive patients. The time interval between cataract surgery and the onset of retinal detachment ranged from 1 month to 46 years.

Increased protein kinase C alpha expression in human colonic Caco-2 cells after insertion of human Ha-ras or polyoma virus middle T oncogenes.

The proteins encoded by ras and src protooncogenes are frequently activated in a constitutive state in human colorectal cancers. To investigate the mechanism(s) whereby oncogenic p21ras and pp60c-src contribute to malignant transformation of intestine, human colonic Caco-2 cells transfected with an activated (Val 12) human Ha-ras gene (Caco-2-T cells) or Py-MT oncogene, a constitutive activator of pp60c-src tyrosine kinase activity (Caco-2-MT cells), were analyzed for tumorigenicity, protein kinase C (PKC) isoform expression, and PKC activity. As compared with control vector Caco-2-H cells, Caco-2-T and Caco-2-MT cells displayed: (a) an enhanced tumorigenicity in nude mice; (b) a 4-fold increase in the level of PKC-alpha mRNA which was not due to enhanced mRNA stability and was mediated through a PKC-independent pathway since it persisted after PKC depletion; (c) increased PKC-alpha immunoreactive protein content (3-fold), total PKC catalytic activity (3.

[Microsurgery of retinal detachment in children].

We conducted a retrospective study of 84 retinal detachments in 69 consecutive children under 15 years of age, operated using microsurgical techniques. The goal of this study was to evaluate the prognosis following this surgical approach. Trauma was the most frequent etiology (34.