Retinoic acid metabolism blocking agents (RAMBAs) to treat osteoarthritis of the hand: A 2-arm double-blind randomised controlled proof of concept study

开始日期2024-01-04

申办/合作机构

University of Oxford

NCT00719121 / Completed临床1期

Placebo-Controlled, Investigator Blinded, Explorative Trial to Evaluate the Anti-inflammatory Effect of Multiple Topical Applications of R115866 Gel (0.35%) in Two Models of Cutaneous Inflammation in Healthy Male Subjects

The purpose of this exploratory trial is to assess the anti-inflammatory effect(s) of topical R115866 in a model of UVB-induced inflammation and in a model of cutaneous irritation.

开始日期2006-11-01

申办/合作机构

Stiefel Laboratories, Inc.

NCT00716144 / Completed临床2期

A Randomized, Evaluator-Blind, Placebo-Controlled, Parallel-Group Dose-Ranging Study of the Safety and Efficacy of Oral R115866 and R115866 Placebo in the Treatment of Plaque Psoriasis

Eligible subjects will be randomly assigned to one of three dose regimens of oral R115866 or placebo for the treatment of severe plaque psoriasis for 12 twelve weeks. The safety and efficacy of R115866 will be evaluated during the treatment period and the 8-week post treatment follow-up period.

开始日期2006-06-01

申办/合作机构

Stiefel Laboratories, Inc.

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100 项与 Cytochrome P450 26 相关的临床结果

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100 项与 Cytochrome P450 26 相关的转化医学

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0 项与 Cytochrome P450 26 相关的专利（医药）

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项与 Cytochrome P450 26 相关的文献（医药）

2023-07-01·Digestive diseases and sciences

Incorporating the Molecular Mimicry of Environmental Antigens into the Causality of Autoimmune Hepatitis.

Review

作者: Czaja, Albert J.

A review.Mol. mimicry between foreign and self-antigens has been implicated as a cause of autoimmune hepatitis in exptl. models and cross-reacting antibodies in patients.This review describes the exptl. and clin. evidence for mol. mimicry as a cause of autoimmune hepatitis, indicates the limitations and uncertainties of this premise, and encourages investigations that assess diverse environmental antigens as sources of disease-relevant mol. mimics.Pertinent articles were identified in PubMed using multiple search phrases.Several pathogens have linear or conformational epitopes that mimic the self-antigens of autoimmune hepatitis.The occurrence of an acute immune-mediated hepatitis after vaccination for severe acute respiratory syndrome (SARS)-associated coronavirus 2 (SARS-CoV-2) has suggested that vaccine-induced peptides may mimic disease-relevant tissue antigens.The intestinal microbiome is an under-evaluated source of gut-derived antigens that could also engage in mol. mimicry.Chaperone mols. may enhance the pathogenicity of mol. mimics, and they warrant investigation.Mol. mimics of immune dominant epitopes within cytochrome P 450 IID6, the autoantigen most closely associated with autoimmune hepatitis, should be sought in diverse environmental antigens and assessed for pathogenicity.Avoidance strategies, dietary adjustments, vaccine improvement, and targeted manipulation of the intestinal microbiota may emerge as therapeutic possibilities.In conclusion, mol. mimicry may be a missing causality of autoimmune hepatitis.Mol. mimics of key immune dominant epitopes of disease-specific antigens must be sought in diverse environmental antigens.The ubiquity of mol. mimicry compels rigorous assessments of peptide mimics for immunogenicity and pathogenicity in exptl. models.Mol. mimicry may complement epigenetic modifications as causative mechanisms of autoimmune hepatitis.

2020-08-01·Development2区 · 生物学

Retinoic acid synthesis and autoregulation mediate zonal patterning of vestibular organs and inner ear morphogenesis

2区 · 生物学

Article

作者: Wu, Doris K. ; Ono, Kazuya ; Trainor, Paul A. ; Sandell, Lisa L.

ABSTRACTRetinoic acid (RA), a vitamin A (retinol) derivative, has pleiotropic functions during embryonic development. The synthesis of RA requires two enzymatic reactions: oxidation of retinol into retinaldehyde by alcohol dehydrogenases (ADHs) or retinol dehydrogenases (RDHs); and oxidation of retinaldehyde into RA by aldehyde dehydrogenases family 1, subfamily A (ALDH1as), such as ALDH1a1, ALDH1a2 and ALDH1a3. Levels of RA in tissues are regulated by spatiotemporal expression patterns of genes encoding RA-synthesizing and -degrading enzymes, such as cytochrome P450 26 (Cyp26 genes). Here, we show that RDH10 is important for both sensory and non-sensory formation of the vestibule of the inner ear. Mice deficient in Rdh10 exhibit failure of utricle-saccule separation, otoconial formation and zonal patterning of vestibular sensory organs. These phenotypes are similar to those of Aldh1a3 knockouts, and the sensory phenotype is complementary to that of Cyp26b1 knockouts. Together, these results demonstrate that RDH10 and ALDH1a3 are the key RA-synthesis enzymes involved in vestibular development. Furthermore, we discovered that RA induces Cyp26b1 expression in the developing vestibular sensory organs, which generates the differential RA signaling required for zonal patterning.

2011-03-01·Nature Reviews Urology1区 · 医学

Novel biomarkers for overactive bladder

1区 · 医学

Review

作者: Alexandros Derpapas ; Vik Khullar ; Rufus Cartwright ; Iram Afshan ; Gopalan Vijaya

Biomarkers constitute any objectively measurable indicator of a biological process. The classic biomarker used in the diagnosis of overactive bladder (OAB) has been detrusor overactivity, which is assessed urodynamically. In the search for a reliable, noninvasive alternative to urodynamics, interest has focused on genetic, imaging, and urinary factors. Along with other cytokines detectable in urine, prostaglandin E2 and nerve growth factor are indicators of low-grade inflammation. Although they correlate with OAB symptom severity, they have not been shown to have independent prognostic benefit. Imaging biomarkers have been investigated since the earliest days of video urodynamics. Despite extensive research on the ultrasonographic estimation of bladder wall thickness, further standardization of the technique is required before conclusions can be reached regarding diagnostic accuracy. Genetic factors contribute approximately half of the total risk for urgency incontinence. Functional polymorphisms of the cytochrome P450 IID6 gene significantly alter the metabolism of some commonly used anticholinergic drugs, but no genetic loci that influence risk of OAB have been definitively identified. The first genome-wide association studies for OAB are in progress, and should identify new susceptibility genes. Although current putative biomarkers correlate with OAB severity, much future work is required to assess their prognostic value, and establish their role in clinical practice.