Strained meat formulas in allergic diseases of infants and children

Strained meat formulas containing approximately the protein, carbohydrate, fat and mineral content of cow's milk have proven valuable in the study of animal milk allergy in infants and children. Strained meat formulas have been given to over one hundred infants and children with bronchial asthma, eczema and gastrointestinal allergic disease. There were no instances of weight loss or anemia. Clinical improvement was evident in most cases.     

Effects of interleukin-8 on the developing human intestine

The human fetal/neonatal gastrointestinal tract is exposed to biologically significant concentrations of interleukin (IL)-8 swallowed with amniotic fluid and human milk. We hypothesized that IL-8 has a physiologic function in the developing human intestine. IL-8 was measured in preterm and term human milk, tested for stability under conditions simulating neonatal gastric and proximal small intestinal digestion, and its receptors were sought in human fetal bowel. The effect of IL-8 was then measured on intestinal cells in vitro. We observed that IL-8 is present in significant concentrations in human milk and that it is stable under conditions simulating digestion. Both IL-8 receptors, CXCR1 and CXCR2, are expressed extensively in the fetal intestine. When human fetal and adult intestinal cells are treated with rhIL-8 in vitro, there is a consistent increase in cell migration, proliferation, and differentiation. IL-8 also protects intestinal cells against chemical injury. These results suggest that besides its better-known role as a neutrophil chemoattractant, IL-8 has a trophic function in the developing human intestine.     

Feeding low-fat milk during infancy

Despite the widespread agreement that low-fat milk should not be used during infancy, there is a sizable portion of infants in the United States who were fed a diet that included low-fat milk (less than or equal to 2% fat). In 1985, 14% of infants 8 months old, 20% of infants 10 months old, and 32% of infants 12 months old were fed low-fat milk. The reasons given most often by mothers for low-fat milk use was their consideration that low-fat milk has less fat than whole cow's milk and that low-fat milk use was recommended/suggested by their physician. Nutrient intakes of infants fed low-fat milk are compared to those of infants fed whole cow's milk and infant formula. Except for fat, nutrient intakes of infants fed low-fat milk or whole cow's milk were similar. A majority of infants fed either low-fat milk or whole cow's milk received amounts of sodium, potassium, and chloride that exceeded the recommended safe and adequate ranges and amounts of iron below the RDA. These data are considered in relation to dietary requirements during infancy.     

The usefulness of casein-specific IgE and IgG4 antibodies in cow's milk allergic children

Background

Cow's milk allergy is one of the most common food allergies among younger children. We investigated IgE antibodies to milk, and IgE and IgG4 antibodies to casein, ??-lactalbumin and ??-lactoglobulin in cow's milk allergic (CMA) and non-allergic (non-CMA) children in order to study their clinical usefulness.

Methods

Eighty-three children with suspected milk allergy (median age: 3.5 years, range: 0.8-15.8 years) were diagnosed as CMA (n = 61) or non-CMA (n = 22) based on an open milk challenge or convincing clinical history. Their serum concentrations of allergen-specific (s) IgE and IgG4 antibodies were measured using ImmunoCAP^?. For the sIgG4 analysis, 28 atopic and 31 non-atopic control children were additionally included (all non-milk sensitized).

Results

The CMA group had significantly higher levels of milk-, casein- and ??-lactoglobulin-sIgE antibodies as compared to the non-CMA group. The casein test showed the best discriminating performance with a clinical decision point of 6.6 kU_A/L corresponding to 100% specificity. All but one of the CMA children aged > 5 years had casein-sIgE levels > 6.6 kU_A/L. The non-CMA group had significantly higher sIgG4 levels against all three milk allergens compared to the CMA group. This was most pronounced for casein-sIgG4 in non-CMA children without history of previous milk allergy. These children had significantly higher casein-sIgG4 levels compared to any other group, including the non-milk sensitized control children.

Conclusions

High levels of casein-sIgE antibodies are strongly associated with milk allergy in children and might be associated with prolonged allergy. Elevated casein-sIgG4 levels in milk-sensitized individuals on normal diet indicate a modified Th2 response. However, the protective role of IgG4 antibodies in milk allergy is unclear.     

Dendritic cells in intestinal immune regulation

A breakdown in intestinal homeostasis can result in chronic inflammatory diseases of the gut including inflammatory bowel disease, coeliac disease and allergy. Dendritic cells, through their ability to orchestrate protective immunity and immune tolerance in the host, have a key role in shaping the intestinal immune response. The mechanisms through which dendritic cells can respond to environmental cues in the intestine and select appropriate immune responses have until recently been poorly understood. Here, we review recent work that is beginning to identify factors responsible for intestinal conditioning of dendritic-cell function and the subsequent decision between tolerance and immunity in the intestine.     

INTESTINAL ATRESIA OR STENOSIS IN THE NEWBORN—Associated with Fibrocystic Disease of the Pancreas

In a review of cases of intestinal atresia or stenosis in the newborn at Children''s Hospital of Los Angeles it was noted that in approximately 10 per cent there was clinical or anatomic evidence of fibrocystic disease of the pancreas. Histologic sections of the bowel in all these cases showed the alterations of the mucosa commonly found in fibrocystic disease. Extensive ulceration, foreign body reaction and calcium deposition in the bowel wall were observed in five cases. Sections through the site of obstruction in one patient showed narrowing of the diameter of the bowel with preservation of muscular layers, but replacement of the central portion by a vascular, fibrous diaphragm in which giant cells, hemosiderin and calcium were prominent. This suggested that in certain instances obstruction of the intestine may be caused by fibrosis secondary to injury of the mucosa by abnormal meconium.Awareness of the common association of intestinal obstruction and fibrocystic disease of the pancreas and recognition of the histologic change in the bowel in fibrocystic disease may lead to early diagnosis of this disorder in some infants with intestinal obstruction.     

Germ-free status and altered caecal subdominant microbiota are associated with a high susceptibility to cow's milk allergy in mice

Studies suggesting that the development of atopy is linked to gut microbiota composition are inconclusive on whether dysbiosis precedes or arises from allergic symptoms. Using a mouse model of cow's milk allergy, we aimed at investigating the link between the intestinal microbiota, allergic sensitization, and the severity of symptoms. Germ-free and conventional mice were orally sensitized with whey proteins and cholera toxin, and then orally challenged with β-lactoglobulin (BLG). Allergic responses were monitored with clinical symptoms, plasma markers of sensitization, and the T-helper Th1/Th2/regulatory-T-cell balance. Microbiota compositions were analysed using denaturing gradient gel electrophoresis and culture methods. Germ-free mice were found to be more responsive than conventional mice to sensitization, displaying a greater reduction of rectal temperature upon challenge, higher levels of blood mouse mast cell protease-1 (mMCP-1) and BLG-specific immunoglobulin G1 (IgG1), and a systemic Th2-skewed response. This may be explained by a high susceptibility to release mMCP-1 even in the presence of low levels of IgE. Sensitization did not alter the microbiota composition. However, the absence of or low Staphylococcus colonization in the caecum was associated with high allergic manifestations. This work demonstrates that intestinal colonization protects against oral sensitization and allergic response. This is the first study to show a relationship between alterations within the subdominant microbiota and severity of food allergy.     

Bioavailability of lead from various milk diets studied in a suckling rat model

The bioavailability of lead from various milk diets was studied in 14 day old suckling rats. Human milk, infant formula, cow's milk, rat milk and deionized water labeled with ²⁰³Pb were given to rat pups by gastric intubation. Animals were killed after 2 or 6 h and the radioactivity in the tissues was measured. At 2 h after administration the lead bioavailability, defined as lead uptake in the body, excluding the gastrointestinal tract, was 47% from water, 42% from human milk, 40% from infant formula, 31% from cow's milk and 11% from rat milk. After 6 h the bioavailability of lead was about 50% from water and human milk, 45% from infant formula and cow's milk, and 36% from rat milk. The blood lead levels in the pups reflected the total body uptake and were also correlated to the brain lead levels. Thus, rat pups given lead in human milk had approximately twice as high lead levels in blood and brain than pups given lead in rat milk. The intestinal absorption of lead was dependent on the milk diet given to the sucklings. In duodenum, the highest uptake of lead was found in rats given water or human milk, whereas in rats given rat or cow's milk the highest uptake of lead was found in ileum. The distribution of lead in cream, whey and casein fractions of the milk diets after in vitro labeling with ²⁰³Pb was also studied. The casein fraction in cow's and rat milk contained 90–96% of the total amount of lead in the diet. In infant formula and human milk, 77 and 56% lead was found in the casein fraction, respectively. The higher lead bioavailability observed in the suckling rat fed human milk than in those fed rat and cow's milk may partly be explained by a lower proportion of lead bound to casein in human milk.     

Epithelial stem cells and tissue engineered intestine

The intestinal mucosa has an amazing regenerative capacity, enabling rapid restoration of its physiological functions following injury. The ability to do this resides with the epithelial stem cells located within glandular invaginations in the mucosal surface. Recent advances toward the isolation and characterization of epithelial stem cells has paved the way for exploring novel therapeutic approaches for gastrointestinal disease. Possible stem cell-based therapy of gastrointestinal disorders range from the repair of damaged mucosa through to tissue engineering of artificial intestinal constructs for patients with short bowel syndrome. Before these benefits are realized further information is required on the biological characteristics of intestinal stem cells, their interactions with surrounding cells, and the environment in which they reside. This includes discovering markers to assist in the identification and purification of stem cell populations and techniques to manipulate the cells both in vivo and in vitro. Because intestinal transplantation for patients still represents a significant challenge, it is hoped that one day a tissue-engineered intestine will provide a feasible option for patients with short bowel syndrome. This review aims to introduce the reader to the main characteristics of epithelial stem cells and provide an overview of the current status of intestinal tissue engineering and the problems still being faced.     

Erythropoietin protects intestinal epithelial barrier function and lowers the incidence of experimental neonatal necrotizing enterocolitis

The impermeant nature of the intestinal barrier is maintained by tight junctions (TJs) formed between adjacent intestinal epithelial cells. Disruption of TJs and loss of barrier function are associated with a number of gastrointestinal diseases, including neonatal necrotizing enterocolitis (NEC), the leading cause of death from gastrointestinal diseases in preterm infants. Human milk is protective against NEC, and the human milk factor erythropoietin (Epo) has been shown to protect endothelial cell-cell and blood-brain barriers. We hypothesized that Epo may also protect intestinal epithelial barriers, thereby lowering the incidence of NEC. Our data demonstrate that Epo protects enterocyte barrier function by supporting expression of the TJ protein ZO-1. As immaturity is a key factor in NEC, Epo regulation of ZO-1 in the human fetal immature H4 intestinal epithelial cell line was examined and demonstrated Epo-stimulated ZO-1 expression in a dose-dependent manner through the PI3K/Akt pathway. In a rat NEC model, oral administration of Epo lowered the incidence of NEC from 45 to 23% with statistical significance. In addition, Epo treatment protected intestinal barrier function and prevented loss of ZO-1 at the TJs in vivo. These effects were associated with elevated Akt phosphorylation in the intestine. This study reveals a novel role of Epo in the regulation of intestinal epithelial TJs and barrier function and suggests the possible use of enteral Epo as a therapeutic agent for gut diseases.     

Bowel preparation before microvascular free colon transfer for head and neck reconstruction: is it necessary?

Mechanical bowel preparation before any intestinal operation, especially when the large intestine is involved, is routine practice for most surgeons. This practice has been questioned by many colorectal surgeons, with convincing data showing the lack of benefit of preoperative mechanical bowel preparation. Free microvascular transfer of the large intestine is occasionally performed for reconstruction of the upper esophagus, as it provides a better size match for the oropharynx than other visceral organs. Nine patients underwent reconstruction of the cervical esophagus and voice tube using a segment of ileocolon. In all patients, the cervical esophagus was reconstructed using the ascending colon and the voice tube was reconstructed using the ileal segment. Both were transferred as one free flap. All patients underwent the procedure without any form of preoperative mechanical bowel preparation. The patients were able to tolerate a solid diet at the end of the mean follow-up period of 7 months, and all esophagograms showed no evidence of stricture formation. One patient developed a fistula at the recipient site that was treated with a regional flap, one patient developed a superficial wound infection of the abdominal wall, and one patient developed a postoperative abdominal wound dehiscence after several episodes of excessive coughing. Microvascular transfer of a large intestinal segment without preoperative mechanical bowel preparation for the reconstruction of the esophagus is a safe procedure. It can avoid the discomfort and complications associated with mechanical bowel preparation. If preoperative mechanical bowel preparation is preferred, the results of this study, which are based on nine patients, demonstrate the safety of this practice in cases where the patient did not follow proper instructions or in cases where the use of the colon was not anticipated preoperatively.     

酶解乳蛋白对初生仔猪小肠组织学结构及隐窝细胞增殖的影响(英文)

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Neuroimmune interactions in guinea pig stomach and small intestine

Enteric neuroimmune interactions in gastrointestinal hypersensitivity responses involve antigen detection by mast cells, mast cell degranulation, release of chemical mediators, and modulatory actions of the mediators on the enteric nervous system (ENS). Electrophysiological methods were used to investigate electrical and synaptic behavior of neurons in the stomach and small intestine during exposure to beta-lactoglobulin in guinea pigs sensitized to cow's milk. Application of beta-lactoglobulin to sensitized preparations depolarized the membrane potential and increased neuronal excitability in small intestinal neurons but not in gastric neurons. Effects on membrane potential and excitability in the small intestine were suppressed by the mast cell stabilizing drug ketotifen, the histamine H(2) receptor antagonist cimetidine, the cyclooxygenase inhibitor piroxicam, and the 5-lipoxygenase inhibitor caffeic acid. Unlike small intestinal ganglion cells, gastric myenteric neurons did not respond to histamine applied exogenously. Antigenic exposure suppressed noradrenergic inhibitory neurotransmission in the small intestinal submucosal plexus. The histamine H(3) receptor antagonist thioperamide and piroxicam, but not caffeic acid, prevented the allergic suppression of noradrenergic inhibitory neurotransmission. Antigenic stimulation of neuronal excitability and suppression of synaptic transmission occurred only in milk-sensitized animals. Results suggest that signaling between mast cells and the ENS underlies intestinal, but not gastric, anaphylactic responses associated with food allergies. Histamine, prostaglandins, and leukotrienes are paracrine signals in the communication pathway from mast cells to the small intestinal ENS.     

Infant gut microbiota is protective against cow's milk allergy in mice despite immature ileal T-cell response

Faecal microbiota of healthy infant displays a large abundance of Bifidobacterium spp. and Bacteroides spp. Although some studies have reported an association between these two genera and allergy, these findings remain a subject of debate. Using a gnotobiotic mouse model of cow's milk allergy, we investigated the impact of an infant gut microbiota – mainly composed of Bifidobacterium and Bacteroides spp. – on immune activation and allergic manifestations. The transplanted microbiota failed to restore an ileal T-cell response similar to the one observed in conventional mice. This may be due to the low bacterial translocation into Peyer's patches in gnotobiotic mice. The allergic response was then monitored in germ-free, gnotobiotic, and conventional mice after repeated oral sensitization with whey proteins and cholera toxin. Colonized mice displayed a lower drop of rectal temperature upon oral challenge with b-lactoglobulin, lower plasma mMCP-1, and lower anti-BLG IgG1 than germ-free mice. The foxp3 gene was highly expressed in the ileum of both colonized mice that were protected against allergy. This study is the first demonstration that a transplanted healthy infant microbiota mainly composed of Bifidobacterium and Bacteroides had a protective impact on sensitization and food allergy in mice despite altered T-cell response in the ileum.     

Enhancement of CGRP sensory afferent innervation in the gut during the development of food allergy in an experimental murine model

Recent advances in neuroscience and immunology have revealed a bidirectional interaction between the nervous and immune systems. Therefore, the gastrointestinal tract may be modulated by neuro–immune interactions, but little information about this interaction is available. Intrinsic and extrinsic primary afferent neurons play an important role in this interaction because of their abilities to sense, process and transmit various information in the intestinal microenvironment. Calcitonin gene-related peptide (CGRP) is exclusively contained in intrinsic and extrinsic primary afferent neurons in the mouse intestine. Therefore, we investigated CGRP-immunoreactive nerve fibers in the colonic mucosa of mice induced to develop food allergy. CGRP-immunoreactive nerve fibers were specifically increased with the development of food allergy, and the fibers were juxtaposed to mucosal mast cells in the colonic mucosa of food allergy mice. Denervation of the extrinsic afferent neurons using neonatal capsaicin treatment did not affect the development of food allergy or the density and distribution of CGRP-immunoreactive nerve fibers in the colonic mucosa of food allergy mice. Furthermore, the mRNA and plasma level of CGRP was increased in food allergy mice. These results suggest that the activation of intrinsic primary afferent neurons in the intestine contributes to the development and pathology of food allergy.     

鼠伤寒沙门氏菌诱导昆明小鼠肠道感染模型的建立

目的:建立鼠伤寒沙门氏菌诱导昆明小鼠肠道感染模型。方法:先用5 mg/mL链霉素预处理2 d,提高小鼠对鼠伤寒沙门氏菌的敏感性,然后正常饲养1 d,攻毒前禁水禁食4 h,再分别以不同剂量灌胃攻毒2次,间隔24 h。观察小鼠临床症状,并通过组织病理切片、透射电镜和免疫组织化学的方法,分别观察小鼠肠道组织病理变化、小肠上皮细胞超微结构变化及肠道淋巴细胞增殖状况。结果:攻毒后昆明小鼠会出现昏睡、食欲不振、寒颤,甚至死亡的现象,解剖后发现小鼠肠道充血膨胀。组织病理切片显示小鼠肠粘膜受损,小肠绒毛肿胀,排列杂乱,炎性细胞浸润;透射电镜观察超微结构显示小肠上皮细胞线粒体空泡化,嵴和膜发生融合消失,粗面内质网发生扩张;免疫组织化学的方法显示肠道感染后,淋巴结肿大,T淋巴细胞大量增殖。结论:该模型对探索鼠伤寒沙门氏菌引发肠炎的发病机制、病理生理、免疫等方面作用具有重要意义,并为特异性卵黄抗体被动免疫保护效果的后续评价奠定基础。     

Evaluation of dairy allergy among ulcerative colitis patients

The intestine is the largest mucosal organ of the body and also the first line immune homeostasis. Inflammatory bowel disease or IBD is divided into ulcerative colitis and Crohn''s disease. One of the problems that can occur with UC is dietary allergy to some foods. This study aimed to evaluated the dairy allergy among patients with ulcerative colitis. This study is a Case - control study, that studied 72 patients with Ulcerative Colitis, after recording history of the disease, colonoscopy and confirmed by biopsy and 72 person without history of colitis. In this study, in order to investigate of food allergy, used of the EUROMMUM kit with an international code number DP3420-1601-11E. We used chi-square and Monte Carlo method for analysis of data. Among UC patients, 30.6% mild, 52.8% moderate and 16.6% of cases were in sever stage. 9.7% of them reported a history of abdominal surgery due to disease. According to the chi-square and Monte Carlo methods, dairy allergy (including: cow milk, cow milk UHT and casein) in UC group was significant (P=0.00). This study indicated that there is significant relationship between UC and cow milk, cow milk UHT and casein. UC patients who are allergic to dairy products and the use of dairy products can increase the severity of UC.     

Bioactive molecules in milk and their role in health and disease: the role of transforming growth factor-beta

Human breast milk is rich in nutrients, hormones, growth factors and immunoactive molecules, which influence the growth, development and immune status of the newborn infant. Although several of these factors are also present in bovine milk, the greater susceptibility of the formula-fed infant to infection and disease and the development of allergy is often attributed to the reduced level of protective factors in milk formulas. Nevertheless, modifying manufacturing processes may preserve the biological activity of some bioactive molecules in end products. Transforming growth factor (TGF)-beta is one such molecule. TGF-beta is a polypeptide, which has been described in both human and bovine milk. It is implicated in many processes, including epithelial cell growth and differentiation, development, carcinogenesis and immune regulation. The present article discusses the biological activity of TGF-beta2 that has been preserved and activated in a cow's milk-based product. More specifically, it addresses possible mechanisms of action in the intestinal lumen and speculates on how milk products containing naturally occurring TGF-beta2 could be exploited in functional foods for the infant or as therapies for specific intestinal diseases.     

Human milk oligosaccharides: the novel modulator of intestinal microbiota

Human milk, which nourishes the early infants, is a source of bioactive components for the infant growth, development and commensal formulation as well. Human milk oligosaccharide is a group of complex and diverse glycans that is apparently not absorbed in human gastrointestinal tract. Although most mammalian milk contains oligosaccharides, oligosaccharides in human milk exhibit unique features in terms of their types, amounts, sizes, and functionalities. In addition to the prevention of infectious bacteria and the development of early immune system, human milk oligosaccharides are able to facilitate the healthy intestinal microbiota. Bifidobacterial intestinal microbiota appears to be established by the unilateral interaction between milk oligosaccharides, human intestinal activity and commensals. Digestibility, membrane transportation and catabolic activity by bacteria and intestinal epithelial cells, all of which are linked to the structural of human milk oligosaccharides, are crucial in determining intestinal microbiota. [BMB Reports 2012; 45(8): 433-441].