Association of organic cation transporter risk haplotype with perianal penetrating Crohn's disease but not with susceptibility to IBD

BACKGROUND & AIMS: Three years after the identification of NOD2/CARD15, 2 more genes for inflammatory bowel diseases (IBDs) were reported. The carnitine/organic cation transporter (OCTN) on 5q31 (IBD5) is associated with Crohn's disease (CD) and DLG5 (10q23), a member of membrane-associated guanylate kinase (MAGUK) family, with IBD. We studied mutation prevalence, assessed phenotypic expression, and performed conditional analysis to examine evidence for gene-gene interactions. METHODS: A cohort of 2032 individuals was genotyped for disease-associated OCTN and DLG5 variants, including 981 patients with IBD (CD, n = 769; ulcerative colitis, n = 186; indeterminate colitis, n = 26) followed up at a tertiary IBD center. For 373 patients, DNA from both parents was available (cohort 1) for transmission disequilibrium testing analysis; case-control analysis was performed in 608 patients and 305 controls (cohort 2). RESULTS: There was no distortion of transmission toward affected offspring for any of the variant alleles. Case-control analysis also failed to shown an association. A higher frequency of DLG5 113A was observed in CARD15-positive patients (12.2%) compared with CARD15-negative patients (8.7%; P = .033). The OCTN-TC risk haplotype was associated with penetrating disease (odds ratio, 1.474; 95% confidence interval, 1.028-2.114; P = .035). For DLG5, there were no associations with a particular phenotype. CONCLUSIONS:DLG5 and OCTN do not play a role in the susceptibility to IBD, CD, or ulcerative colitis in the Flemish population but play a role in the phenotypic expression of the disease. OCTN variants were associated with perianal and penetrating CD. More studies in independent populations are urgently needed to assess the validity of DLG5 and OCTN in the pathogenesis of IBD.     

Tomografia computorizada cardíaca prévia a ablação de fibrilhação auricular – efeitos da evolução tecnológica e otimização de protocolos

Background

Cardiac computed tomography (CT) can provide a precise tridimentional anatomic map and exclude intra‐cardiac thrombus. We aimed to access the impact of CT protocol optimization and technological evolution on the contrast and radiation dose as well as on image quality previous to atrial fibrillation (AF) ablation.

Epidemiology, genes and inflammatory bowel diseases in childhood

There is evidence that inflammatory bowel disease is immunologically mediated and that genetic factors play an important aetiological role. The identification of disease susceptibility genes has led to significant progress in our understanding of the pathogenesis of Crohn's disease. Genes linked to Crohn's disease play critical roles in the normal function of the innate immune system, and genes linked to epithelial integrity may play a role in the pathogenesis of inflammatory bowel disease as well. However, the dynamic epidemiology of both Crohn's disease and ulcerative colitis suggests that extrinsic environmental factors acting at the population level may be involved in their pathogenesis. These environmental factors may be responsible for the rising incidence of inflammatory bowel disease.     

Health-related quality of life in patients with systemic lupus erythematosus and its relationship with cyclophosphamide pulse therapy

OBJECTIVES: To examine health-related quality of life in Brazilian patients with systemic lupus erythematosus (SLE) and compare patients using cyclophosphamide (CP) pulse therapy with those who do not use it. METHODS: Patients with SLE using or not CP completed the SF-36 and SRQ-20 (psychological morbidity) questionnaire. The Lupus Activity Criteria Count (LAAC) assessed SLE disease activity. RESULTS: We studied 102 patients with SLE. The presence of psychological morbidity was associated with all the scores from SF-36. The physical component summary (PCS) of the SF-36 was significantly lower in patients with activity disease and the mental component summary (MCS) was significantly lower in the patients with psychological morbidity. Comparing patients using or not CP, it was not observed in a statistical significant difference in the 8 domains of the SF-36, nor in the PCS and MCS between the two groups. The prevalence of psychological morbidity evaluated by the SRQ-20 has not presented a statistical significant difference between the patients using or not CP. In the multivariate analysis, using the PCS and MCS as separate dependent variables, the most important variable associated with them was psychological morbidity. CONCLUSION: Cyclophosphamide pulse therapy does not worse health-related quality of life in patients with SLE. The presence of psychological distress is an important factor associated with worse quality of life.     

Target cell-induced apoptosis of interleukin-2-activated human natural killer cells: roles of cell surface molecules and intracellular events

We previously reported that natural killer (NK)-sensitive target cells, K562, kill interleukin-2-stimulated (lymphokine-activated killer [LAK]) but not unstimulated NK cells. We have now investigated the molecular basis of this phenomenon. Soluble monoclonal antibody (MoAb) to CD18 inhibited 75% of K562-induced DNA fragmentation and membrane disruption, whereas blocking MoAb to Fas partially inhibited only the DNA fragmentation. MoAbs to CD2, CD11a, CD11b, B7, or CD16 had limited or no effect on K562-induced death of LAK cells. Receptor ligation with either immobilized MoAb to CD18 or Fas induced membrane disruption and DNA degradation in LAK cells independently of K562, and MoAb to CD18, CD11a, or CD11b enhanced DNA fragmentation induced by anti-Fas. Fas-L- transfected Raji cells also killed LAK cells, but only if Fas-L expression was amplified. K562 cells rapidly triggered protein phosphorylation in LAK cells, and the tyrosine kinase inhibitor, Herbimycin A, inhibited DNA fragmentation and membrane disruption. Protease inhibitors strongly suppressed K562-mediated DNA fragmentation of LAK cells, but not membrane disruption. In conclusion, (1) K562- induced death of LAK cells involves primarily CD18, although other molecules, such as Fas, may also be involved; (2) K562-mediated apoptosis of LAK cells requires tyrosine phosphorylation and protease activity; (3) engagement of Fas by immobilized MoAb or Fas-L on target cells can also kill LAK cells; and (4) Fas-immobilized MoAb synergizes with coimmobilized MoAb to CD11a, CD11b, or CD18 for LAK cell killing. Activation-induced death of NK cells may represent a mechanism for NK cell regulation.     

Hard palate hyperpigmentation secondary to chronic chloroquine therapy: report of five cases

Antimalarials are commonly prescribed in medical practice for conditions such as rheumatoid arthritis, lupus erythematosus, as well as malaria. They are generally well‐tolerated, but side effects, although infrequent, are well known. The antimalarial chloroquine diphosphate may be associated with a bluish‐gray to black hyperpigmentation of the oral mucosa, mainly on the hard palate. In this report we described five additional cases of palate hyperpigmentation related to the chronic use of chloroquine diphosphate. Professionals must be aware of the adverse effects of antimalarials as chloroquine diphosphate in order to make the correct diagnosis and appropriate management of the patient. Early diagnosis of oral pigmentation by antimalarials may be of great relevance, because it might be an early sign of ocular involvement, and therefore it may be helpful to prevent further complications of antimalarial therapy for the patient.     

Caloric restriction or catalase inactivation extends yeast chronological lifespan by inducing H2O2 and superoxide dismutase activity

The free radical theory of aging posits oxidative damage to macromolecules as a primary determinant of lifespan. Recent studies challenge this theory by demonstrating that in some cases, longevity is enhanced by inactivation of oxidative stress defenses or is correlated with increased, rather than decreased reactive oxygen species and oxidative damage. Here we show that, in Saccharomyces cerevisiae, caloric restriction or inactivation of catalases extends chronological lifespan by inducing elevated levels of the reactive oxygen species hydrogen peroxide, which activate superoxide dismutases that inhibit the accumulation of superoxide anions. Increased hydrogen peroxide in catalase-deficient cells extends chronological lifespan despite parallel increases in oxidative damage. These findings establish a role for hormesis effects of hydrogen peroxide in promoting longevity that have broad implications for understanding aging and age-related diseases.     

Craniocervical posture and bruxism in children

Aim. The aim of this study was to investigate, using photogrammetry, the relationship between head posture and bruxism in children with complete deciduous dentition. Material and Methods. Forty‐two children aged between 3 and 6 years, with complete deciduous dentition, participated in the study. Twenty‐one children diagnosed with bruxism according to the diagnostic criteria of the American Academy of Sleep Medicine were selected for the bruxism group, and 21 children without bruxism were selected for the control group. Markers were placed on three anatomical landmarks (spinous process of the seventh cervical vertebra, manubrium of the sternum and mental protuberance) and photographic measurements were made to evaluate head posture. Angles between markers were determined using the ALCimagem® software for quantitative image analysis. The Student's t‐test was used at a significance level of 0.05 for the comparison of head posture (mean cervical angle) between the bruxism and control groups. Results. There was a significant difference (p < 0.005) in the mean cervical angle between the control (89.58° ± 8.03°) and bruxism (98.99° ± 8.15°) groups. Conclusion. In the present study, children with bruxism showed greater alterations in head posture than controls. Copyright © 2010 John Wiley & Sons, Ltd.