Providing monovalent oral polio vaccine type 1 to newborns: findings from a pilot birth-dose project in Moradabad district, India.

PROBLEM: Poliovirus transmission remained a public health challenge in western Uttar Pradesh, India in late 2005 and early 2006. In 2006, the India Expert Advisory Group for Polio Eradication concluded that, given the peak incidence of polio among children 6 to 12 months of age, a targeted birth dose of oral polio vaccine may be necessary to interrupt intense poliovirus transmission in high risk areas. APPROACH: The Government of Uttar Pradesh, the National Polio Surveillance Project and the United Nations Children's Fund (UNICEF) implemented a pilot birth-dose project aimed at identifying and vaccinating all newborns with a dose of oral polio vaccine within 72 hours of birth in an effort to evaluate operational feasibility and potential impact on population immunity. LOCAL SETTING: The project was piloted in Moradabad district: zone 7 in Moradabad City (urban setting), Kunderki block (rural setting) and in select birthing hospitals. RELEVANT CHANGES: Between July 2006 and February 2007, 9740 newborns were identified, of which 6369 (65%) were vaccinated by project personnel within 72 hours of birth. Project coverage (for total newborns vaccinated) ranged from 39% (in zone 7) to 76% (in Kunderki block) of the estimated number of newborns vaccinated during previous supplemental immunization activities. LESSONS LEARNED: Birth-dose coverage among newborns was lower than expected. Expansion costs were estimated to be high, with marginal impact. The project, however, provided opportunities to strengthen newborn tracking systems which have increased the number of newborns and young infants vaccinated during supplemental immunization activities and enrolled in routine programmes.

Enteral nutrition and keratinocyte growth factor regulate expression of glutathione-related enzyme messenger RNAs in rat intestine.

BACKGROUND: Malnutrition is associated with increased reactive oxygen species (ROS) formation and depletion of the critical antioxidant glutathione (GSH) in the intestine. The malnutrition-induced decrease in gut GSH levels is prevented by recombinant keratinocyte growth factor (KGF) administration. We investigated whether enzymes that are induced by oxidants and modulate tissue GSH supply are regulated by enteral nutrients or KGF at the messenger RNA (mRNA) level. METHODS: Adult rats were fasted for 3 days alone or fasted for 3 days then refed ad libitum. In a second model, rats were fasted for 3 days and then refed ad libitum or 25% of ad libitum intake with daily intraperitoneal saline or recombinant KGF (5 mg/kg/d) for 3 subsequent days. mRNA levels for gamma-glutamylcysteine synthetase (gamma-GCS), gamma-glutamyl transpeptidase (gamma-GT), glutathione-S-transferase Ya-subunit, gastrointestinal glutathione peroxidase (GI-GPx), and non-selenium-dependent glutathione peroxidase (ns-GPx) were determined in ileum and colon by ribonuclease protection assay. RESULTS: Fasting increased ileal gamma-GCS, ns-GPx, and glutathione-S-transferase mRNAs (by 36%, 165%, and 130% of controls) and decreased GI-GPx mRNA (to 55% of controls). In the colon, mRNAs for GSH-related enzymes were unchanged by fasting or refeeding. Prolonged enteral nutrient restriction (25% refeeding after a 3-day fast) increased gamma-GCS and glutathione-S-transferase mRNAs (by >270% of controls), decreased GI-GPx mRNA (to <50% of controls) in ileum and colon and increased ns-GPx mRNA (by 180%) in colon. KGF treatment increased ns-GPx mRNA in the ileum and colon and glutathione-S-transferase mRNA in the colon (by >200% of controls). CONCLUSIONS: Enteral nutrient intake regulates GSH-related enzyme mRNA levels in the intestine, which may contribute to the decrease in mucosal GSH during malnutrition. Increased ns-GPx and glutathione-S-transferase mRNA levels during malnutrition and with KGF administration may increase detoxifying functions in the gut under these conditions.

Regulation of keratinocyte growth factor (KGF) and KGF receptor mRNAs by nutrient intake and KGF administration in rat intestine.

The aim of this study was to investigate the regulation of keratinocyte growth factor (KGF) and KGF receptor mRNAs by diet and KGF treatment in rat intestine. Fasting for three days up-regulated KGF and KGF receptor mRNA levels in ileum and increased KGF receptor mRNA expression in colon. KGF and KGF receptor mRNA levels returned toward control values with ad libitum refeeding but remained elevated when refeeding was limited to 25% of ad libitum intake. KGF treatment during nutrient repletion did not alter intestinal KGF mRNA levels but increased KGF receptor mRNA abundance in ileum and colon. We conclude that the increase in KGF and KGF receptor mRNAs induced by malnutrition may be an adaptive response to attenuate gut mucosal atrophy in this setting. The gut-trophic effects of KGF treatment may be mediated, in part, by up-regulation of the KGF receptor mRNA in small bowel and colon.

Interactions between nutrients and peptide growth factors in intestinal growth, repair, and function.

Several lines of evidence demonstrate that general nutritional status, specific nutrients (eg, zinc, glutamine), and certain trophic growth factors (eg, growth hormone, insulin-like growth factor I, keratinocyte growth factor, and glucagon-like peptide-2) have important interactions relevant for intestinal growth and function. Adequate nutritional status is critical for endogenous growth factor synthesis in the gut and other tissues and is an important mediator of organ responsiveness to exogenous growth factor administration. Both endogenously synthesized and exogenously administered growth factors upregulate nutrient uptake and utilization by gut mucosa, skeletal muscle, and other organs. Emerging data from both animal and human studies indicate that combinations of selected growth factors and specific nutrients may improve the growth, adaptation, and repair of the intestinal mucosa. Additional studies to determine basic mechanisms of nutrient-growth factor interactions and the safety and efficacy of treatment with combinations of specific nutrients and recombinant growth factors are needed. Results of these investigations should define new methods for support of the intestinal tract during short bowel syndrome (SBS), catabolic illness, and malnutrition.

Keratinocyte growth factor enhances glutathione redox state in rat intestinal mucosa during nutritional repletion.

Malnutrition decreases tissue levels of glutathione (GSH), a major endogenous antioxidant that detoxifies reactive oxygen species and promotes cell growth. This study determined the effects of the gut trophic peptide keratinocyte growth factor (KGF) on intestinal mucosal GSH concentrations and redox state in malnourished rats. Adult rats were food-deprived for 3 d, then consumed food ad libitum or 25% of ad libitum intake for 3 d with daily intraperitoneal administration of saline or KGF (5 mg.kg-1.d-1). Mucosal GSH and glutathione disulfide (GSSG) concentrations, crypt depth and total mucosal height were measured in the jejunum, ileum and colon. In the 25% of ad libitum-refed, saline-treated group, mucosal GSH was lower in all gut tissues (42% in jejunum, 38% in ileum, and 57% in colon), and the GSH/GSSG ratio was lower in the jejunum and ileum compared to that in the ad libitum-refed controls. KGF treatment with ad libitum refeeding increased GSH/GSSG in the jejunum, ileum and colon. Furthermore, in 25% of ad libitum refeeding, KGF normalized jejunal, ileal and colonic mucosal GSH content and significantly increased the mucosal GSH/GSSG ratio relative to rats treated with saline. Increased crypt depth and total mucosal height induced by KGF and feeding could be explained in part by increased mucosal GSH content. KGF treatment improved gut mucosal glutathione redox state in malnourished, refed rats. These data provide evidence that gut trophic hormones and food intake may independently support gut mucosal glutathione antioxidant capacity during nutritional repletion.

Gut-trophic effects of keratinocyte growth factor in rat small intestine and colon during enteral refeeding.

BACKGROUND: Keratinocyte growth factor (KGF) induces proliferation of gut epithelium in rat models, but KGF-nutrient interactions have not been studied. An experimental model of fasting-induced gut atrophy followed by different levels of enteral refeeding was used to investigate the influence of nutrient availability on the gut-trophic effects of exogenous KGF. METHODS: After a 3-day fast, rats were enterally refed either ad libitum or at 25% of ad libitum intake for 3 subsequent days. Either intraperitoneal KGF (5 mg/kg/d) or saline was given in each dietary regimen. Wet weight, DNA, and protein content were measured as indices of full-thickness cellularity in duodenum, jejunum, ileum, and colon. Villus height in small bowel segments and crypt depth in all gut tissues were measured as specific indices of mucosal growth. RESULTS: Refeeding at 25% of ad libitum intake significantly decreased full-thickness cellularity and mucosal growth indices in duodenum, jejunum, and ileum. In the colon, only protein content fell significantly and crypt depth was maintained. KGF administration during 25% refeeding did not alter full-thickness indices in any small bowel segment or affect jejunal mucosal growth. In contrast, KGF normalized duodenal villus height (p < .01) and duodenal and ileal crypt depth (p < .05) only in the 25%-refed model. KGF significantly increased ileal villus height in both ad libitum and 25%-refed rats (by 43% and 48%, respectively, p < .05) and markedly increased colonic cellularity and mucosal crypt depth with both levels of refeeding (p < .01). CONCLUSIONS: Rat small bowel growth is more sensitive than colon to the level of enteral refeeding after a 3-day fast. KGF administration does not affect jejunal growth, but specifically prevents atrophy of duodenal and ileal mucosa during hypocaloric, hyponitrogenous refeeding. In ileum and colon, some KGF-mediated growth responses are independent of the level of enteral refeeding. Thus gut-trophic effects of KGF and KGF interactions with the level of nutrient intake are tissue-specific.

Nutrition and the insulin-like growth factor system.

Nutritional status is a key regulator of the circulating and tissue insulin-like growth factor (IGF) system. IGF-I mRNA and protein levels decrease in tissues such as liver and intestine with fasting and are restored with refeeding. Additional studies suggest that the level of protein and calorie intake independently regulate plasma IGF-I concentrations in man. The level of nutrition effects the biological actions of recombinant growth hormone (GH) and IGF-I administration in humans. Limited data demonstrate that plasma and tissue levels of the insulin-like growth factor binding proteins (IGFBPs) are also sensitive to nutrient intake. Specific micronutrients, such as potassium, magnesium and zinc also appear to be important for optimal IGF-I synthesis and anabolic effects in animal models. Malnutrition is common in elderly patients, however, the interaction between specific nutrients, general nutritional status and the aging process on the IGF system is incompletely understood. Mechanisms of nutrient-IGF system interactions which may affect the biological actions of IGF-I, IGF-II, and the IGFBPs are increasingly being determined in basic studies. The effects of underlying nutritional status and responses to dietary intake will be important to evaluate in clinical studies of the IGF system and exogenous growth factor therapy.

[Consumption of sweets and snacks by a population of school children in the Autonomous Community of Madrid. The CAENPE Group]. / Consumo de alimentos del grupo "dulces y golosinas" en la población infantil escolarizada de la Comunidad Autónoma de Madrid. Grupo CAENPE.

BACKGROUND: In our society advertising compaigns promote consumption of superfluous foods, such as sweets and snacks, displacing the intake of other basic nutrients. The aim of this study is to assess the intake of these foods by children, their relative contribution to overall macronutrient intake and their effects on health. SUBJECTS AND METHODS: A dietary assessment was performed on a representative sample of scholar children from the Autonomous Community of Madrid. It reflects food consumption for a 4-days period (3 week-days and 1 weekend day) in 2,698 boys and girls aged 6 to 15 years. The intake is expressed as grams per 1,000 kcal to standardize nutrient consumption in boys and girls. Lipid profile and several markers of nutritional status are also determined. RESULTS: The consumption of sweets and snacks items per 1,000 kcal is higher in boys than in girls (35.8 +/- 20.0 and 34.2 +/- 19.6 g/1,000 kcal, respectively; p = 0.01) and increases during adolescence (12 and 13 years) in both sexes. Sweets and snacks provide 16.1% of dietary total caloric intake, 7.1% of saturated fatty acids, 10.7% of monounsaturated fatty acids, 10.4% of polyunsaturated fatty acids and 11.3% of cholesterol. Children of ages 6, 7, 8 and 9 years with high calculated LDL-cholesterol levels (> or = 120 mg/dl) consume significative higher amounts of sweet foods than children with low calculated LDL-cholesterol levels (< or = 90 mg/dl). CONCLUSIONS: Children from the Autonomous Community of Madrid, Spain consume excessive sweets, which could be responsible for a higher prevalence of diseases related to this intake, such as caries, obesity and obesity-related associate diseases.

Glutamine: from basic science to clinical applications.

Glutamine (Gln) has been one of the most intensively studied nutrients in the field of nutrition support in recent years. Interest in provision of Gln derives from animal studies in models of catabolic stress, primarily in rats. Enteral or parenteral Gln supplementation improved organ function and/or survival in most of these investigations. These studies have also supported the concept that Gln is a critical nutrient for the gut mucosa and immune cells. Recent molecular and protein chemistry studies are beginning to define the basic mechanism involved in Gln action in the gut, liver and other cells and organs. Double-blind prospective clinical investigations to date suggest that Gln-enriched parenteral or enteral feedings are generally safe and effective in catabolic patients. Intravenous Gln (either as the L-amino acid or as Gln-dipeptides) has been shown to increase plasma Gln levels, exert protein anabolic effects, improve gut structure and/or function and reduce important indices of morbidity, including infection rates and length of hospital stay in selected patients subgroups. Additional blinded studies of Gln administration in catabolic patients and increasing clinical experience with Gln-enriched nutrient products will determine whether routine Gln supplementation should be given in nutrition support, and to whom. Taken together, the data obtained over the past decade or so of intensive research on Gln nutrition demonstrate that this amino acid is an important dietary nutrient and is probably conditionally essential in humans in certain catabolic conditions.