Role of Nod2 in the development of Crohn's disease

Crohn's Disease (CD) is caused by a loss of the regulatory capacity of the immune apparatus. Nod2 is an intracellular bacterial sensor and its mutations are associated with the development of CD. Here we summarize recent and controversial findings about the role of the Nod2 mutants in the disease process.     

Relation of infant diet to childhood health: seven year follow up of cohort of children in Dundee infant feeding study.

OBJECTIVE: To investigate the relation of infant feeding practice to childhood respiratory illness, growth, body composition, and blood pressure. DESIGN: Follow up study of a cohort of children (mean age 7.3 years) who had detailed infant feeding and demographic data collected prospectively during the first two years of life. SETTING: Dundee. SUBJECTS: 674 infants, of whom 545 (81%) were available for study. Data on respiratory illness were available for 545 children (mean age 7.3 (range 6.1-9.9) years); height for 410 children; weight and body mass index for 412 children; body composition for 405 children; blood pressure for 301 children (mean age 7.2 (range 6.9-10.0) years). MAIN OUTCOME MEASURES: Respiratory illness, weight, height, body mass index, percentage body fat, and blood pressure in relation to duration of breast feeding and timing of introduction of solids. RESULTS: After adjustment for the significant confounding variables the estimated probability of ever having respiratory illness in children who received breast milk exclusively for at least 15 weeks was consistently lower (17.0% (95% confidence interval 15.9% to 18.1%) for exclusive breast feeding, 31.0% (26.8% to 35.2%) for partial breast feeding, and 32.2% (30.7% to 33.7%) for bottle feeding. Solid feeding before 15 weeks was associated with an increased probability of wheeze during childhood (21.0% (19.9% to 22.1%) v 9.7% (8.6% to 10.8%)). It was also associated with increased percentage body fat and weight in childhood (mean body fat 18.5% (18.2% to 18.8%) v 16.5% (16.0% to 17.0%); weight standard deviation score 0.02 (-0.02 to 0.06) v -0.09 (-0.16 to 0.02). Systolic blood pressure was raised significantly in children who were exclusively bottle fed compared with children who received breast milk (mean 94.2 (93.5 to 94.9) mm Hg v 90.7 (89.9 to 91.7) mm Hg). CONCLUSIONS: The probability of respiratory illness occurring at any time during childhood is significantly reduced if the child is fed exclusively breast milk for 15 weeks and no solid foods are introduced during this time. Breast feeding and the late introduction of solids may have a beneficial effect on childhood health and subsequent adult disease.     

Postpartum depression and infant feeding practices in a low income urban settlement in Nairobi-Kenya

Background

Postpartum depression can compromise caregiving activities, including infant feeding practices, resulting in child malnutrition. The purpose of this study was to examine the effects of postpartum depression on infant feeding practices and malnutrition among women in an urban low income settlement in Nairobi-Kenya. We conducted a cross-sectional study based in Kariobangi North Health Centre in Nairobi County. The study sample included 200 mother-infant pairs visiting the Maternal and Child Health clinics for infant immunization at 6–14 weeks postpartum. We assessed postpartum depression using the Edinburgh Postpartum Depression Scale. Infant feeding practices were assessed based on World Health Organization infant and young child feeding guidelines. Nutritional status (weight for age) was ascertained using infants’ growth monitoring card (percentiles and z-score). We conducted logistic regression analyses to determine the relative odds of non-exclusive breast feeding and infant underweight among mothers with postpartum depression.

Results

The prevalence of PPD was 13.0% (95% CI 8.3–17.7%). Taking into account differences in socioeconomic status of depressed and non-depressed mothers, non-depressed mothers had a 6.14 (95% CI 2.45–13.36) times higher odds of practicing exclusive breastfeeding than mothers who were depressed. Mothers with PPD had a 4.40 (95% CI 1.91–11.93) time higher odds of having an underweight infant than mothers without depression.

Conclusions

This study contributes towards filling the knowledge gap regarding the adverse effects of postpartum depression on infant health in sub-Saharan Africa. We recommend more research on PPD using longitudinal designs to establish temporal ordering of these important public health problems and development of community-based interventions to address post-partum depression.

     

Role of oxidative stress and antioxidant enzymes in Crohn's disease

There is increasing interest in oxidative stress being a potential aetiological factor and/or a triggering factor in Crohn's disease, rather than a concomitant occurrence during the pathogenesis of the disease. Recent research has shown that the immune mononuclear cells of Crohn's disease patients are induced to produce hydrogen peroxide (H2O2). Similarly, the regulation of antioxidant enzymes during disease in these cells has been unravelled, showing that SOD (superoxide dismutase) activity and GPx (glutathione peroxidase) activity is increased during active disease and returns to normal in remission phases. However, catalase remains constantly inhibited which supports the idea that catalase is not a redox-sensitive enzyme, but a regulator of cellular processes. ROS (reactive oxygen species) can be produced under the stimulus of different cytokines such as TNFα (tumour necrosis factor α). It has been shown in different experimental models that they are also able to regulate apoptosis and other cellular processes. The status of oxidative stress elements in Crohn's disease and their possible implications in regulating cellular processes are reviewed in the present paper.     

Metabolic acidosis and infant feeding.

Most cows'' milk based formulae for infant feeding present a greater acid load to the infant than breast milk. To determine the effect of this difference the acid base state of 180 healthy term infants was measured on the sixth day of life and related to the type of feed. Those infants fed on cows'' milk formula (SMA) had a mean pH of 7-34 +/- 0-05 and a base deficit of 8-8 +/- 3-1, while those fed on breast milk had a mean pH of 7-38 +/- 0-05 and a base deficit of 5-6 +/- 3-1. The difference between the two groups of infants was significant for both these measurements. Metabolic acidosis was defined as a base deficit greater than 10 mmol/l. Seventy-four per cent of the 34 infants who were acidotic at six days were bottle-fed. There was a significant correlation between the pH of the feed and the degree of acidosis in the infant as measured by the base deficit. The findings suggest that when breast milk is not available a pH-adjusted milk formula would be desirable for preventing and treating neonatal metabolic acidosis.     

Immunotherapy of Crohn's disease.

Although the initiating events of Crohn''s disease are unknown, models of experimental colitis have provided new insights in the immunologically mediated pathways of mucosal inflammation. In Crohn''s disease activated mucosal T lymphocytes produce proinflammatory cytokines within the mucosal compartment. With this understanding, there has been a shift in past years from the use of unspecific anti-inflammatory agents (corticosteroids, aminosalicylates) to the use of immunomodulatory drugs (azathioprine, methotrexate). Moreover, novel strategies have been designed for specific targets in Crohn''s disease, in particular T lymphocytes and cytokines. In an open label study treatment of steroid-refractory Crohn''s disease with anti- CD4+ antibodies was well tolerated and showed clinical benefit. However, a sustained depletion of the CD4+ cells precluded further clinical trials. In controlled clinical studies, anti-tumour necrosis factor (TNF-alpha) antibodies induced complete remissions and few side effects were observed. One study suggested efficacy in active Crohn''s disease of recombinant interleukin-10. Long term treatment studies will have to answer questions about the indications for use, benefit and toxicity. Altogether, these results hold promise for future management of Crohn''s disease, where disease-modifying interventions and strategies that effectively maintain disease remission will play a key role.