Increasing of SIgA serum levels may reflect subclinical intestinal involvement in non-radiographic axial and peripheral spondyloarthritis

Clinical Rheumatology - The evidence shows that previous infection with enteric pathogens is a requirement to develop pSpA. Based on our previous results, variances on regulation of SIgA might...     

Infectious endocarditis caused by Candida. Presentation of 3 cases and review of the literature

We present 3 patients with infective endocarditis due to Candida sp. They were not immunodeficient subjects, but they had major surgery, longterm antimicrobial therapy and prosthetic implants. Candida endocarditis is a difficult diagnosis for biological and technical. There is also poor results with and therapeutic reasons. The combined treatment with amphotericin B and 5-fluorocytosine, plus surgical removal of the infected tissue is recommended widely in the literature.     

The Effect of Melatonin in Patients with Fibromyalgia: A Pilot Study

The aim of the study was to determine the possible effect of melatonin treatment on disturbed sleep, fatigue and pain symptoms observed in fibromyalgia (FM) patients. Twenty-one consecutive patients with FM were included in an open 4-week-duration pilot study. Before and after treatment with melatonin 3 mg at bedtime, patients were evaluated using tender point count by palpation of 18 classic anatomical regions, pain score in four predesignated areas, pain severity on a 10 cm visual analogue scale (VAS), sleep disturbances, fatigue, depression, anxiety, and patient and physician global assessments, also by a VAS. Urine 6-sulphatoxymelatonin levels (aMT-6S) were measured in the patients and 20 age- and sex-matched controls. Nineteen patients completed the study. One patient withdrew because of migraine and another was lost to follow-up. At day 30, median values for the tender point count and severity of pain at selected points, patient and physician global assessments and VAS for sleep significantly improved with melatonin treatment. Other variables improved but did not reach statistical significance. Adverse events were mild and transient. Lower levels of aMT-6S were found in FM patients compared with normal median controls (±SD, 9.16 ± 7.9 μg/24 h vs 16.8 ± 12.8 μg/24 h) (p= 0.06). Although this is an open study, our preliminary results suggest that melatonin can be an alternative and safe treatment for patients with FM. Double-blind placebo controlled studies are needed. Received: 14 September 1998 / Accepted: 14 May 1999     

Molecular basis and cellular mechanisms of eosinophilic esophagitis for the clinical practice

Introduction: Eosinophilic esophagitis (EoE) is a chronic, allergen-driven inflammatory esophageal disease characterized by predominantly eosinophilic inflammation leading to esophageal dysfunction. Recent efforts to understand EoE have increased our knowledge of the disease.

Areas covered: Multiple cells, molecules, and genes interplay with early life environmental factors in the pathophysiology of EoE to converge in the esophageal epithelium at the center of disease pathogenesis. Epithelial cells constitute a mayor cytokine source for TSLP and Calpain-14; an impaired epithelial barrier function allowing penetration of food and microbiota-derived antigens is involved in triggering and maintaining inflammation. Eosinophil and mast cell-derived products, including TGFβ, together with IL-1β and TNFα, promote epithelial mesenchymal transition in EoE, contributing to tissue remodeling by synthetizing and depositing extracellular matrix in subepithelial layers. This article aims to provide a state-of-the-art update on the pathophysiology of EoE applied to clinical practice, and latest research and developments with potential interest to improve the diagnosis and treatment of patients with EoE are revised.

Expert commentary: Preliminary approaches have provided promising results toward incorporating minimally invasive methods for patient diagnosis and monitoring in clinical practice. Early diagnosis and optimized therapies will allow for personalized medicine in EoE.     

A soluble mouse brain splice variant of type 2alpha corticotropin-releasing factor (CRF) receptor binds ligands and modulates their activity

Peptides of the corticotropin-releasing factor (CRF) family signal through the activation of two receptors, CRF receptor type 1 (CRFR1) and type 2 (CRFR2), both of which exist as multiple splice variants. We have identified a cDNA from mouse brain encoding a splice variant, soluble CRFR2alpha (sCRFR2alpha), in which exon 6 is deleted from the gene encoding CRFR2alpha. Translation of this isoform produces a predicted 143-aa soluble protein. The translated protein includes a majority of the first extracellular domain of the CRFR2alpha followed by a unique 38-aa hydrophilic C terminus resulting from a frame shift produced by deletion of exon 6. By using RT-PCR and Southern hybridization, the relative mRNA expression levels of full-length (seven transmembrane domains) CRFR2alpha and the soluble form (sCRFR2alpha) in the mouse brain were measured with a single reaction. The results demonstrate high levels of expression of sCRFR2alpha in the olfactory bulb, cortex, and midbrain regions. A rabbit antiserum raised against a synthetic peptide fragment encoding the unique C terminus revealed specific sCRFR2alpha immunoreactivity in mouse brain slices by immunohistochemistry and in extracts of brain regions by RIA. Interestingly, the sCRFR2alpha immunoreactivity distribution closely approximated that of CRFR1 expression in rodent brain. A protein corresponding to sCRFR2alpha, expressed and purified from either mammalian or bacterial cell systems, binds several CRF family ligands with low nanomolar affinities. Furthermore, the purified sCRFR2alpha protein inhibits cellular responses to CRF and urocortin 1. These data support a potential role of the sCRFR2alpha protein as a possible biological modulator of CRF family ligands.     

The unconditioned stimulus pre‐exposure effect in preweanling rats in taste aversion learning: Role of the training context and injection cues

The unconditioned stimulus pre‐exposure effect (US‐PE) refers to the interference paradigm in which acquisition of the conditioned response is retarded due to prior experience with the US. Most studies analyzing the psychological mechanisms underlying this effect have been conducted with adult rats. The most widely accepted hypothesis explains this effect as a contextual blocking effect. Contextual cues associated with the US block the conditioned stimulus (CS)‐US association during conditioning. The modulatory role of a context devoid of distinctive olfactory attributes is not observable until approximately PD23 in rats, including modulation of interference paradigms such as latent inhibition or extinction. In this study, we analyzed US‐PE in preweanling rats along with the role of the training context in this effect in terms of conditioned taste aversion preparation. Pre‐exposure to LiCl before conditioning retarded the acquisition of taste aversion. The US‐PE was observed in preweanling rats when, during pre‐exposure, subjects were exposed to the conditioning context, and this effect was not attenuated either by the administration of the US in a familiar environment (Experiment 1a), or by the presence of an alternative, more salient context during pre‐exposure (Experiment 1b). Additionally, the US‐PE was still observed when the route by which the US was administered was changed between the pre‐exposure and conditioning phases (Experiment 2a) as well as when the injection cues were removed during conditioning (Experiment 2b). These experiments show a strong US‐PE in preweanling rats and fail to support the contextual blocking hypothesis, at least in this stage of ontogeny. © 2012 Wiley Periodicals, Inc. Dev Psychobiol 55: 193–204, 2013