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CD Group (cd + group)
Selected AbstractsPredictive model for the outcome of infliximab therapy in Crohn's disease based on apoptotic pharmacogenetic index and clinical predictorsINFLAMMATORY BOWEL DISEASES, Issue 4 2007Tibor Hlavaty Abstract Background: Infliximab (IFX) is an effective therapy for refractory luminal and fistulizing Crohn's disease (CD). Predictors of response could improve selection of patients with a higher probability of favorable outcomes and could improve the safety profile. We aimed to develop a predictive model for the response to infliximab in CD. Methods: Genetic and clinical data collected in a previous pharmacogenetic study of apoptosis genes were analyzed using SAS Enterprise miner modeling software and SPSS 12.0. We proposed a novel apoptotic pharmacogenetic index (API) with a score ranging from 0 (low apoptotic response) to 3 (high apoptotic response) and subsequently developed a decision tree model. Results: Response and remission rates significantly increased with API score (P = 0.005 in the group of patients with luminal CD, P = 0.02 in the group of patients with fistulizing CD). Patients with an API , 1 (n = 59) had the lowest response and remission rates in both the luminal CD (50% and 39.5%, respectively) and fistulizing CD (61.9% and 28.6%, respectively) groups, compared to those with an API of 2 (n = 158), whose response and remission rates were 73.8% and 56.1%, respectively, in the luminal CD group and 85.7% and 44.9%, respectively, in the fistulizing CD group; and those with an API of 3 (n = 10), whose response and remission rates were 100% and 85.7%, respectively, in the luminal CD group and 100% and 0% in the fistulizing CD group. Response in patients with an API , 1 was significantly influenced by concurrent azathioprine therapy in the luminal CD (21.4% versus 78.9%, P < 0.001) and in the fistulizing CD (46.6% versus 100%, P = 0.04) groups. In patients with an API of 2, we saw an interaction with age older than 40 years and location of disease (response 52.2% versus 83.9%, P = 0.008) in the luminal CD group and with baseline CRP greater than 5 mg/L (73.9% versus 93.9%, P = 0.04) in the fistulizing CD group. Conclusions: From our newly proposed apoptotic pharmacogenetic index and clinical predictors, we developed a model for prediction of low, medium, and high responses to the first infusion of IFX in patients with CD. Further studies are needed to confirm the hypothesis generated by our study. (Inflamm Bowel Dis 2007) [source] Anti-inflammatory role of interleukin-15 in Crohn's diseaseINFLAMMATORY BOWEL DISEASES, Issue 3 2005Manuel A Silva MD Abstract Background: Interleukin (IL)-15 is overexpressed in intestinal tissue with active Crohn's disease (CD). However, its role in the pathogenesis of the disease remains uncertain. We studied the effects of IL-15 on colonic mucosal proinflammatory cytokine response in vitro using organ culture of human colonic explants. Methods: Colonic tissue was obtained from (1) resections in pediatric CD patients (inflamed and noninflamed) and (2) rectal biopsies in patients with CD undergoing colonoscopy (n = 31) and controls (n = 9). In preliminary experiments, explants from the resections were cultured in the presence or absence of a simulated TH1 stimulation using ionomycin (Io) and phorbol-myristate-acetate (PMA), with or without IL-15, or in medium alone. Rectal biopsies were cultured in the same conditions as above, with or without adding a monoclonal anti-IL-15 neutralizing antibody (mAb). Levels of interferon (IFN)-,, tumor necrosis factor (TNF)-,, and IL-2R, were measured by enzyme-linked immunosorbent assay. Results: IL-15, in the absence of Io + PMA, did not induce the expression of IFN-,, TNF-,, or IL-2R,. Only inflamed explants from resections stimulated with Io + PMA expressed IFN-,, TNF-,, and IL-2R,. This TH1 stimulatory effect was inhibited by IL-15 in a dose-dependent fashion. In rectal biopsy explants, inflamed, noninflamed CD, and control tissue responded to stimulation with Io + PMA (P < 0.05) with increased IFN-, and TNF-, (P < 0.05). This response was again inhibited by IL-15. The inhibitory effect of IL-15 was specifically reversed by anti-IL-15 mAb (P < 0.05). The data for the CD group were also analyzed according to the severity of colonic inflammation and medication use. Conclusions: Our results suggest a possible anti-inflammatory role for IL-15 in CD. We postulate that its overexpression in CD potentially represents a protective mechanism against the exaggerated TH1 immune response. [source] Chemokine receptor CXCR3 expression in inflammatory bowel diseaseINFLAMMATORY BOWEL DISEASES, Issue 4 2001Yu-Hong Yuan Abstract CD4+ T lymphocytes in the lamina propria (LP) of the gut play a central role in the immune response in inflammatory bowel disease (IBD). CXCR3 is a chemokine receptor expressed on activated T lymphocytes, and a key component for the recruitment of T helper (Th1) effector cells to the site of inflammation. To determine if CXCR3 is involved in localization of T cells to the gut in IBD patients, we investigated the expression of CXCR3 on CD4+ T lymphocytes in the LP and in the submucosa of resection specimens from 51 IBD patients and 15 control patients. Positive cells were microscopically scored using a semiquantitative analysis on a five-point scale. We found that CD4+ T cells, CXCR3+ cells, and CD4+CXCR3+ T cells in the LP were slightly increased in both IBD groups compared with control non-IBD specimens. In addition, CD4+ and CXCR3+ cells in the submucosa were significant increased in the CD group compared with the control group. CD4+ and CXCR3+ expression was not statistically different between CD and UC. Flow cytometry was used to analyze the percentage of CXCR3+ cells within the CD4+ T-cell population isolated from biopsy specimens and peripheral blood from IBD patients and control patients. There was no difference in the percentage of CD4+CXCR3+ cells between the different groups in the gut as well as in the circulation. These results suggest that CD4+CXCR3+ T cells migrate to the normal and inflamed intestinal mucosa, indicating a role in maintaining normal gut homeostasis. The selective expression of CXCR3+ cells in the submucosa of CD patients might also indicate that these cells play a role in inflammation. [source] Treatment of Immune-Mediated Hemolytic Anemia with Individually Adjusted Heparin Dosing in DogsJOURNAL OF VETERINARY INTERNAL MEDICINE, Issue 3 2010S.E. Helmond Background: A major cause of death in dogs with immune-mediated hemolytic anemia (IMHA) is thromboembolism. Previous studies suggest unfractionated heparin (UH) is not effective in preventing thromboembolism in IMHA; however, subtherapeutic dosing could explain the seeming lack of efficacy. Hypothesis: Providing therapeutic plasma concentration of UH by individually adjusting doses based on antifactor Xa activity would improve survival in IMHA. Animals: Fifteen dogs with primary IMHA. Methods: Randomized, prospective, controlled clinical trial. Dogs received standardized therapy for IMHA and either constant dose (CD) (150 U/kg SC) (n = 7) or individually adjusted dose (IAD) (n = 8) UH, monitored via an anti-Xa chromogenic assay, adjusted according to a nomogram. UH was administered every 6 hours until day 7, and every 8 hours thereafter. UH dose was adjusted daily in IAD dogs until day 7, weekly until day 28, then tapered over 1 week. Dogs were monitored for 180 days. Results: At day 180, 7 dogs in the IAD group and 1 in the CD group were alive (P= .01). Median survival time for the IAD group was >180 days, and 68 days for the CD group. Thromboembolic events occurred in 5 dogs in the CD group and 2 dogs in the IAD group. Doses of UH between 150 and 566 U/kg achieved therapeutic anti-Xa activity (0.35,0.7 U/mL). Conclusions and Clinical Importance: This study suggests that IAD UH therapy using anti-Xa monitoring reduced case fatality rate in dogs with IMHA when compared with dogs receiving fixed low dose UH therapy. [source] Dietary histidine affects lens protein turnover and synthesis of N-acetylhistidine in Atlantic salmon (Salmo salar L.) undergoing parr,smolt transformationAQUACULTURE NUTRITION, Issue 5 2005O. BRECK Abstract This study was conducted to investigate protein synthesis rates and metabolism of histidine (His)-derivatives in lenses of Atlantic salmon (Salmo salar L.) of different dietary His background during parr,smolt transformation. Two populations of Atlantic salmon parr of equal origin were established in freshwater (FW), 3 months prior to transfer to seawater (SW). The populations were fed either a control diet (CD) containing 8.9 g kg,1 His or the same diet added crystalline His to a total level of 14.2 g kg,1 (HD). On the basis of these two populations, 14C His force-feeding studies were performed; in FW 3 weeks prior to sea transfer and in SW 6 weeks after transfer. The studies were conducted by force-feeding the respective diets enriched with 14C labelled His, with subsequent measurements of incorporation of 14C His into lens free amino acid pool, as well as into lens proteins and other free His pool fractions. The latter included the major lens imidazole N-acetylhistidine (NAH). Lens concentrations of His and NAH were clearly influenced by dietary His history, both in parr and smolt. The lens His and NAH concentrations in the CD population were considerably lower in SW than in FW, while in the HD group the His level was equal and the NAH level 50% higher in SW than in FW. Fractional synthesis rate for NAH, KS (NAH), in FW was 8.2 and 4.2 ,mol g,1 day,1 for fish in the CD and HD populations, respectively. The corresponding KS (NAH) values in SW were 5.1 and 33.0 ,mol g,1 day,1. Our data show that free His is rapidly converted to NAH in the lens, and that NAH seems to have a very high turnover, especially in salmon reared in SW. Fractional synthesis rate for lens proteins, KS (PROTEIN), ranged between 1.8 and 17.3% day,1 (182 and 2791 ,g g,1 day,1, respectively), and was generally higher in SW than in FW (P < 0.01). In SW, KS (PROTEIN) was highest in fish in the HD population (P < 0.05), whereas lens protein retention in the HD group was significantly lower than the CD group (P = 0.01). In a second model assuming that His from lens NAH is available for protein synthesis, calculated values of KS (PROTEIN) ranged between 0.17% day,1 (17.6 ,g g,1 day,1) and 0.48% day,1 (70.2 ,g g,1 day,1). Cataract scores recorded in the His populations at a later point (day 204), showed that the CD fish had significantly higher mean cataract scores than individuals in the HD population (P < 0.01), confirming that low levels of lens His and NAH are associated with cataract development. [source] Cognitive biases in depressed and non-depressed referred youthCLINICAL PSYCHOLOGY AND PSYCHOTHERAPY (AN INTERNATIONAL JOURNAL OF THEORY & PRACTICE), Issue 5 2008Benedikte Timbremont This study examined cognitive vulnerability in both depressed and non-depressed referred youngsters. Formerly depressed (FD) children and adolescents (n = 16) were compared to a currently depressed (CD) group (n = 18) on a self-referent encoding and memory task imbedded in a mood induction paradigm. In order to test the specificity of the findings to depression, the results of the FD were further compared with those of a clinical but never depressed (ND) group (n = 39) diagnosed with anxiety and/or disruptive behaviour disorders. The study confirmed the hypothesized differences between the groups in terms of self-referent encoding bias. Both the ND (p < 0.001) and FD (p < 0.001) group rated more positive words than negative words as self-descriptive while the CD endorsed a closer balance of positive and negative words (non-significant difference). No interaction effect was found for the recall task. The FD group evinced a similar memory bias than the CD group. However, also in the ND group, the number of proportional recalled positive words did not differ from the proportional recalled negative words. The findings yielded no evidence for a depression-specific information-processing bias. However, all subjects (FD, CD as well as ND) exhibited a memory bias and therefore ,clinical status' is considered as a cognitive vulnerability risk factor for developing a depressive disorder in the future.,Copyright © 2008 John Wiley & Sons, Ltd. [source] British Society of Gerodontology and BDA CDS group combined winter meetingGERODONTOLOGY, Issue 1 2005Gerodontic challenges First page of article [source] Egg and larval quality, and egg fatty acid composition of Eurasian perch breeders (Perca fluviatilis) fed different dietary DHA/EPA/AA ratiosAQUACULTURE RESEARCH, Issue 9 2010Emilie Henrotte Abstract In Eurasian perch (Perca fluviatilis), the variability in spawning quality is a major limiting factor for successful production, especially when breeders are fed with an artificial diet. The influence of the dietary DHA/EPA/AA ratio on the egg and larval quality and on the fatty acid and lipid class composition of eggs has been investigated in perch broodstock. Two experimental diets (16% lipids) with two different DHA/EPA/AA ratios, D1 (3/2/2) and D2 (23/9/1), were compared with a natural diet consisting of cultured carp juveniles, CC (10/10/1) and with a commercial diet for salmonids, CDS (14/16/1). Percentages of fertilization and hatching were comparable between fish fed D1, D2 and CC, with the highest hatching rate observed for D1 (63.5 ± 3.8%). These diets supported better values than the CDS. Larval survival and TL50 observed after osmotic stress were higher for the D1 group, followed by larvae produced by fish fed D2 and CC. Larvae from fish fed D1, D2 and CC were significantly more robust than larvae from the CDS group. Differences were observed regarding the fatty acid (FA) profile in the eggs, which was related to the dietary FA composition. The results indicate that a ratio of 3/2/2 seemed to be effective for obtaining eggs and larvae of good quality. [source] | |||||||||||||