Immunoendocrine findings in patients with eating disorders.

Immune changes may occur in patients with anorexia nervosa (AN) or bulimia nervosa (BN), and a role for proinflammatory cytokines has been proposed in the pathogenesis of both disorders. We measured plasma levels of interleukin (IL)-1beta, IL-6, tumor necrosis factor-alpha (TNF-alpha), soluble forms of the cytokine receptor proteins gp130 and leukemia inhibitory factor receptor (LIF-R), the anti-inflammatory Clara cell 16-kD protein (CC16), prolactin (PRL), cortisol and 17beta-estradiol in 21 anorexic women, 21 bulimic women and 21 healthy females. As compared to healthy subjects, anorexics exhibited significantly increased plasma levels of gp130 and LIF-R, whereas bulimics had significantly decreased blood concentrations of CC16. No significant differences emerged in the blood levels of the remaining immune parameters. Both patient groups manifested higher plasma levels of cortisol and reduced plasma concentrations of PRL and 17beta-estradiol. In anorexics, a significant negative correlation was found between plasma levels of gp130 or LIF-R and the body mass index. These findings do not support the hypothesis that proinflammatory cytokines may play a pathogenetic role in eating disorders.     

Elevated serum interleukin-6 (IL-6) and IL-6 receptor concentrations in posttraumatic stress disorder following accidental man-made traumatic events.

BACKGROUND: Recently, it has been reported that serum interleukin-1 beta (IL-1 beta), but not soluble IL-2 receptor (sIL-2R), concentrations were significantly higher in patients with posttraumatic stress disorder (PTSD) than in normal volunteers, and that psychological stress in humans is associated with increased secretion of proinflammatory cytokines, such as IL-6. METHODS: The aim of the present study was to examine the inflammatory response system in patients with PTSD through measurements of serum IL-6, sIL-6R, sgp130 (the IL-6 signal transducing protein), sIL-1R antagonist (sIL-1RA; an endogenous IL-1 receptor antagonist), CC16 (an endogenous anticytokine), and sCD8 (the T suppressor-cytotoxic antigen). RESULTS: Serum IL-6 and sIL-6R, but not sgp130, sIL-RA, CC16, or sCD8, concentrations were significantly higher in PTSD patients than in normal volunteers. Serum sIL-6R concentrations were significantly higher in PTSD patients with concurrent major depression than in PTSD patients without major depression and normal volunteers. There were no significant relationships between serum IL-6 or sIL-6R and severity measures of PTSD. CONCLUSIONS: The results suggest that PTSD is associated with increased IL-6 signaling. It is hypothesized that stress-induced secretion of proinflammatory cytokines is involved in the catecholaminergic modulation of anxiety reactions.     

Evaluating the Quality of the Interaction Between Persons with Profound Intellectual and Multiple Disabilities and Direct Support Staff: A Preliminary Application of Three Observation Scales from Parent–Infant Research

Background Affective and reciprocal interactions with others are essential for persons with profound intellectual and multiple disabilities (PIMD), but it is a challenge to assess their quality. This study aimed to investigate the usefulness of instruments from parent–infant research to evaluate these interactions. Method Eighteen videotaped staff–client interactions were coded with the Emotional Availability Scales, the Maternal/Child Behavior Rating Scales, and the Revised Erickson Scales. Results The scales could generally be applied to persons with PIMD and substantial interobserver agreement was found. The tools’ subscales appeared to be distinct but there was also evidence that they measure an overarching construct. Client and staff interactive behaviours were highly related. Convergent validity was demonstrated by strong correlations between theoretically related dimensions. An acceptable range in scores, a ceiling‐effect, and relative high mean scores occurred. Conclusions The instruments’ applicability and usefulness was demonstrated in this study, which offers directions for future research and intervention.     

Meat and Fish Consumption, APCGene Mutations and hMLH1 Expression in Colon and Rectal Cancer: a Prospective Cohort Study (The Netherlands)

Objective:The aim of this study was to investigate the associations between meat and fish consumption and APC mutation status and hMLH1 expression in colon and rectal cancer. Methods:The associations were investigated in the Netherlands Cohort Study, and included 434 colon and 154 rectal cancer patients on whom case-cohort analyses (subcohort n = 2948) were performed. Results:Total meat consumption was not associated with the endpoints studied. Meat product (i.e. processed meat) consumption showed a positive association with colon tumours harbouring a truncating APC mutation, whereas beef consumption was associated with an increased risk of colon tumours without a truncating APC mutation (incidence rate ratio (RR) highest versus lowest quartile of intake 1.61, 95% confidence interval (CI) 0.96–2.71, p-trend = 0.04 and 1.58, 95% CI 1.10–2.25, p-trend = 0.01, respectively). Consumption of other meat (horsemeat, lamb, mutton, frankfurters and deep-fried meat rolls) was associated with an increased risk of rectal cancer without a truncating APC mutation (RR intake versus no intake 1.79, 95% CI 1.10–2.90). No associations were observed for meat consumption and tumours lacking hMLH1 expression. Conclusions:Our data indicate that several types of meat may contribute differently to the aetiology of colon and rectal cancer, depending on APC mutation status but not hMLH1 expression of the tumour.     

Mice lacking multidrug resistance protein 3 show altered morphine pharmacokinetics and morphine-6-glucuronide antinociception

Glucuronidation is a major detoxification pathway for endogenous and exogenous compounds in mammals that results in the intracellular formation of polar metabolites, requiring specialized transporters to cross biological membranes. By using morphine as a model aglycone, we demonstrate that multidrug resistance protein 3 (MRP3/ABCC3), a protein present in the basolateral membrane of polarized cells, transports morphine-3-glucuronide (M3G) and morphine-6-glucuronide in vitro. Mrp3(-/-) mice are unable to excrete M3G from the liver into the bloodstream, the major hepatic elimination route for this drug. This results in increased levels of M3G in liver and bile, a 50-fold reduction in the plasma levels of M3G, and in a major shift in the main disposition route for morphine and M3G, predominantly via the urine in WT mice but via the feces in Mrp3(-/-) mice. The pharamacokinetics of injected morphine-glucuronides are altered as well in the absence of Mrp3, and this results in a decreased antinociceptive potency of injected morphine-6-glucuronide.     

Possible nociceptive structures in the sacroiliac joint cartilage: An immunohistochemical study

The sacroiliac joint (SI joint) is a known source of low back pain. In the absence of validated physical signs and imaging studies, the diagnosis of SI joint pain can be secured by positive response to SI joint intra‐articular infiltration with local anesthetics. The current anatomical and histological knowledge concerning intra‐articular structures of the sacroiliac joint is insufficient to explain the efficacy of this infiltration. Consequently, this study was undertaken to detect the intra‐articular presence of substance P and calcitonin gene‐related peptide (CGRP) positive nerve fibers, providing indirect evidence of nociceptive innervation of the SI joint. Free‐floating sections, obtained from iliac and sacral cartilage and subchondral bone of the SI joint and adjacent ligamentous tissue, of 10 human cadavers were studied immunohistochemically. Tissue of nine human cadavers showed the presence of substance P and CGRP immunoreactivity in the superficial layer of sacral and iliac cartilage, and the surrounding ligamentous structures. Subchondral bone reacted weakly to the antisera used. These findings support the view that the SI joint may be capable of intra‐articular nociception and may explain the positive response to the intra‐articular deposition of local anesthetic. Clin. Anat. 23:192–198, 2010. © 2009 Wiley‐Liss, Inc.