Autocrine TNF is critical for the survival of human dendritic cells by regulating BAK, BCL-2, and FLIPL.

The life span of dendritic cells (DCs) is determined by the balance of pro- and antiapoptotic proteins. In this study, we report that serum-free cultured human monocyte-derived DCs after TLR stimulation with polyinosinic acid-polycytidylic acid or LPS underwent apoptosis, which was correlated with low TNF production. Apoptosis was prevented by the addition of exogenous TNF or by concomitant stimulation with R-848, which strongly amplified endogenous TNF production. Neutralization of TNF confirmed that DC survival was mediated by autocrine TNF induced either by stimulation with R-848 or by ligation of CD40. DCs stimulated by polyinosinic acid-polycytidylic acid or IFN-ß, another known inducer of DC apoptosis, were characterized by high levels and activation of the proapoptotic protein BAK. The ratio of antiapoptotic BCL-2 to BAK correlated best with the survival of activated DCs. Addition of TNF increased this ratio but had little effect on BAX and XIAP. Knockdown experiments using small interfering RNAs confirmed that the survival of activated and also of immature DCs was regulated by BAK and showed that TNF was protective only in the presence of FLIP(L). Together, our data demonstrate that the survival of DCs during differentiation and activation depends on autocrine TNF and that the inhibition of BAK plays an important role in this process.

Obesity related programming statements in infant feeding policies in five European countries.

The aim of this study was to know how the early nutrition programming concept and its relation with long-term diseases such as obesity is reflected in policy recommendations on infant nutrition in five European countries (Finland, Germany, Hungary, Spain and England). After collating and evaluating infant nutrition policy documents, statements about early nutrition programming, as the origin of diseases such as obesity, were analysed. The number of policy documents analysed were 38 (England: 10, Finland: 2, Germany: 11, Hungary: 8, Spain: 7) with a total of 455 statements identified and categorized into 53 different health outcomes. Obesity was mentioned in 5.5% (n = 25) of the statements, the third most frequent outcome after allergy (14.1%, n = 64) and health in general (5.7%, n = 26). Twenty six percent (n = 6) of the obesity related statements referred to short-term duration of the effects, 48% (n = 12) to medium-term, 24% (n = 6) to long-term effects and the rest were not identified. Only 22% of the obesity statements were evidence based. The link between infant feeding and obesity is integrated into policy documents, but most of the statements did not fully specify the short, medium and long term health implications. Action may be required to keep documents up to date as new evidence emerges and to ensure the evidence base is properly recorded.

Obesity related programming statements in materials on infant feeding aimed at parents in five European countries.

Early nutrition programming as an origin of obesity is well acknowledged, but to what extent is this concept communicated to parents? In five European countries, UK, Finland (FI), Germany (DE), Hungary (HU) and Spain (ES), a total of 130 stand alone leaflets and 161 articles from parenting magazines providing information on feeding of healthy infants aged 0-12 months were identified and screened for nutrition programming statements. Obesity was mentioned in 8.5% (54/638) of the statements, and was the fourth most frequent outcome after allergy (20.7%), risk of infections (15.5%) and growth and development (11.4%). A temporal prognosis was given in 39% of obesity related statements, 6% referring to short- (< 5 years), 13% to medium- (5-15 years) and 20% to long-term (>15 years) duration of effects. So advice on obesity focuses on the intrinsic long-term perspective of programming in contrary to other surveyed health-outcomes where only 8- considered a lifelong approach. The major programming related behaviour concerned breast-feeding compared to formula and complementary feeding with meaningful differences concerning the recommended duration: for ES and HU the predominant advice was for exclusive breast-feeding for 6 months, for DE exclusive breast-feeding for 4-6 months and for UK and FI breast-feeding without further specification. In summary, statements relating to the programming of later obesity have been partially integrated into feeding information in five European countries. These countries have slightly different breastfeeding recommendations, but consistently refer to the preventive potential of breastfeeding in general. This is important as obesity and its resulting morbidity are of increasing public health concern in developed countries.

Infant feeding and the concept of early nutrition programming: a comparison of qualitative data from four European countries.

The concept of early nutrition programming is appearing in policy documents, leaflets and magazine articles with different types of statements. However, the level of representation and influence of this concept is unknown in the area of infant nutrition. We established the degree of reflection and the impact of the concept of nutrition programming among the different government stakeholders of infant nutrition in four European countries. In each country, a list of stakeholders in the area of infant feeding was established and key persons responsible for the remit of infant nutrition were identified. We conducted standardised face-to-face or phone interviews from January 2006 to January 2007. The interview guide included questions about the concept of nutrition programming. All interviews were digitally recorded and qualitative data analysis was done using QRS NVivo V2. In total, we analyzed 17 interviews from government organizations in England (5 interviews), Germany (4 interviews), Hungary (3 interviews) and Spain (5 interviews). The concept of nutrition programming was recognized from 4/5 English and 3/4 German interviewees, whereby one organisation reflected the concept in their documents in both countries. In Hungary, 1/3 interviewees recognised the concept and reflected it in their documents. All interviewed Spanish governmental bodies (5/5) recognised the concept of nutrition programming and three of them reflected the concept in their documents. The concept of early nutrition programming was widely recognized among the key persons of government bodies in all four European countries. However, the concept was not necessarily represented in the produced documents.

Intervention with traditional food as a major source of energy, protein, iron, vitamin C and vitamin A for rural Dalit mothers and young children in Andhra Pradesh, South India.

Intakes of energy, protein, iron and vitamin A in India are usually reported as inadequate. Recognizing that traditional food systems are sustainable, high in species variety, and have rich nutrient sources, we compared dietary intakes and nutrient sources of Dalit mothers and their children living in villages with and without an intervention based on improved access to the traditional Dalit food system. 24-hour recalls were conducted with Dalit mothers and their children aged 6-39 months during summer and rainy seasons in 2003. We found that mothers from intervention villages had significantly higher intakes of energy (mean +/- SD: 12,197 +/- 3,515 kJ vs. 11,172 +/- 3,352 kJ; p =0.02) and protein (77.5 +/- 25.1 g vs. 71.1 +/- 25.2 g; p =0.05) in summer, and higher intakes of energy (11,168 +/- 3,335 kJ vs. 10,168 +/- 3,730 kJ; p = 0.04), protein (68.9 +/- 22.6 g vs. 60.4 +/- 23.8 g; p <0.01) and iron (15.8 +/- 6.6 mg vs. 13.7 +/- 9.1 mg; p <0.01) during rainy season. There were no differences in children's intakes between intervention and control villages. In mothers, sorghum contributed 29% of energy, 33% of protein and 53% of iron, and green leafy vegetables contributed 21% of vitamin C and 38% of vitamin A. Our results indicate that traditional food such as sorghum, pulses and green leafy vegetables are major sources of energy, protein, iron, vitamin C and vitamin A, and that mothers from villages with the traditional food intervention had higher intakes of energy, protein and iron.