Tuberculosis and Immunosuppressive Treatment in Uveitis Patients

Uveitis is reported to be related to tuberculosis in 0.2–20% of cases. This large range reflects prevalence variations of tuberculosis around the globe as well as differences in diagnostic criteria. In addition, patients with noninfectious uveitis are frequently treated by immunomodulatory drugs and are thus at risk of TB reactivation. Search for tuberculosis infection is thus an important aspect in the work-up of patients with uveitis, even in low prevalence area. In the work up of such patients, the first question to ask is whether the patient has been infected by mycobacterium tuberculosis or not. The second question is to determine whether the uveitis is due or linked to this mycobacterial infection or not. Classical tuberculosis screening tools are used to answer the first question (TST, IGRA and chest X ray). The answer to the second question is much more challenging and will require the exclusion of other causes, to consider epidemiological data and clinical signs, polymerase chain reaction (PCR) on ocular fluids and therapeutically treatment trial. Disease prevalence will greatly influence all proposed tests and the final diagnosis. Tuberculosis prevalence in Western countries has progressively decreased during the twentieth century but remains elevated in cities with large migrating populations and drug addicts, with an increase of ultra-resistant cases. All those data must be carefully analyzed in order to collect enough evidences supporting tuberculosis uveitis before the initiation of a treatment with potential serious side and adapt the treatment to the increasing resistance

Discovery of a Novel Selective Kappa-Opioid Receptor Agonist Using Crystal Structure-Based Virtual Screening

Kappa-opioid (KOP) receptor agonists exhibit analgesic effects without activating reward pathways. In the search for non-addictive opioid therapeutics and novel chemical tools to study physiological functions regulated by the KOP receptor, we screened in silico its recently released inactive crystal structure. A selective novel KOP receptor agonist emerged as a notable result, and is proposed as a new chemotype for the study of the KOP receptor in the etiology of drug addiction, depression, and/or pain

Proteins Do Not Have Strong Spines After All

In this issue of Structure, Berkholz et al. show that the detailed backbone geometry of proteins depends on the local conformation and suggest how this information can be practically used in modeling and refining protein structures

Aquaporin expression in blood-retinal barrier cells during experimental autoimmune uveitis

PURPOSE: Blood-retinal barrier (BRB) breakdown and retinal edema are major complications of autoimmune uveitis and could be related to deregulation of aquaporin (AQP) expression. We have therefore evaluated the expression of AQP1 and AQP4 on BRB cells during experimental autoimmune uveitis (EAU) in mice. METHODS: C57Bl6 mice were immunized with interphotoreceptor retinoid-binding protein (IRBP) peptide 1-16. The disease was graded clinically, and double immunolabeling using glial fibrillary acidic protein (GFAP; a marker of disease activity) and AQP1 or AQP4 antibodies was performed at day 28. AQP1 expression was also investigated in mouse retinal pigment epithelium (RPE) cells (B6-RPE07 cell line) by reverse transcriptase PCR and western blot under basal and tumor necrosis factor alpha (TNF-alpha)-stimulated conditions. RESULTS: In both normal and EAU retina, AQP1 and AQP4 expression were restricted to the photoreceptor layer and to the Müller cells, respectively. Retinal endothelial cells never expressed AQP1. In vasculitis and intraretinal inflammatory infiltrates, decreased AQP1 expression was observed due to the loss of photoreceptors and the characteristic radial labeling of AQP4 was lost. On the other hand, no AQP4 expression was detected in RPE cells. AQP1 was strongly expressed by choroidal endothelial cells, rendering difficult the evaluation of AQP1 expression by RPE cells in vivo. No major differences were found between EAU and controls at this level. Interestingly, B6-RPE07 cells expressed AQP1 in vitro, and TNF-alpha downregulated AQP1 protein expression in those cells. CONCLUSIONS: Changes in retinal expression of AQP1 and AQP4 during EAU were primarily due to inflammatory lesions, contrasting with major modulation of AQP expression in BRB detected in other models of BRB breakdown. However, our data showed that TNF-alpha treatment strongly modulates AQP1 expression in B6-RPE07 cells in vitro.Journal ArticleResearch Support, Non-U.S. Gov'tSCOPUS: ar.jinfo:eu-repo/semantics/publishe

The genetic architecture of the human cerebral cortex

The cerebral cortex underlies our complex cognitive capabilities, yet little is known about the specific genetic loci that influence human cortical structure. To identify genetic variants that affect cortical structure, we conducted a genome-wide association meta-analysis of brain magnetic resonance imaging data from 51,665 individuals. We analyzed the surface area and average thickness of the whole cortex and 34 regions with known functional specializations. We identified 199 significant loci and found significant enrichment for loci influencing total surface area within regulatory elements that are active during prenatal cortical development, supporting the radial unit hypothesis. Loci that affect regional surface area cluster near genes in Wnt signaling pathways, which influence progenitor expansion and areal identity. Variation in cortical structure is genetically correlated with cognitive function, Parkinson's disease, insomnia, depression, neuroticism, and attention deficit hyperactivity disorder

Famciclovir efficacy in chronic herpetic keratitis following acyclovir treatment failure, Stepping beyond established therapy

info:eu-repo/semantics/nonPublishe

Immunosuppresseurs, indications, surveillance

info:eu-repo/semantics/nonPublishe

Intra-ocular inflammation due to tuberculosis and Lyme disease

info:eu-repo/semantics/nonPublishe

Ocular pathology in Tangier disease and in hyperlipoproteinemia

info:eu-repo/semantics/nonPublishe

Choroïdites serpigineuses

info:eu-repo/semantics/nonPublishe