Maternally delivered nutritive allergens in cord blood and in placental tissue of term and preterm neonates

BACKGROUND: The proliferation of cord blood mononuclear cells in response to nutritive and inhalant allergens implies intrauterine exposure with resulting T cell priming. However, the mechanisms triggering these fetal allergen-specific immune responses are incompletely understood. METHODS: We studied the placental release of endogenous beta-lactoglobulin (BLG) and ovalbumin (OVA) by the use of an open ex vivo placental perfusion model. Preterm and term placentas were obtained immediately after delivery to recover functionally active fetal and maternal circulations. Fetal and maternal perfusate samples were collected throughout the perfusion experiments with medium. Matched cord blood samples were collected separately. All samples were tested for the presence of OVA and BLG by allergen-specific ELISAs. RESULTS: In 16 out of 19 placentas, the nutritive allergens could be detected both in fetal and maternal perfusate samples. Fetal wash out levels of the allergens BLG and OVA from the placental tissue of preterm and term deliveries were observed in traces and up to 44.4 and 2.6 ng/mL, respectively. In cord blood of preterm and term neonates, BLG and OVA could be detected at concentrations up to 16.7 and 5 ng/mL, respectively. CONCLUSION: These findings provide direct evidence for the release of tiny amounts of nutritive allergens from placental tissue indicating diaplacental allergen transfer and fetal exposure to nutritive allergens in vivo.     

板蓝根中丁香酸的抗内毒素作用

目的 研究从板蓝根中分离出的丁香酸的抗内毒素作用。方法将丁香酸配成1％水溶液，鲎试验法做抗内毒素定量测定；用内毒素致兔发热实验检测丁香酸体内抗内毒素作用；内毒素致小鼠死亡实验测定丁香酸保护作用。结果0.334mg／mL丁香酸可使4EU内毒素降为0．777EU，破坏率为83．16％；1％丁香酸溶液可使内毒素引起的兔热显著降低；使同等剂量脂多糖引起的小鼠死亡率由68％降为20%。结论 丁香酸有抗内毒素作用。     

板蓝根中丁香酸的抗内毒素作用

目的 研究从板蓝根中分离出的丁香酸的抗内毒素作用。方法将丁香酸配成1％水溶液，鲎试验法做抗内毒素定量测定；用内毒素致兔发热实验检测丁香酸体内抗内毒素作用；内毒素致小鼠死亡实验测定丁香酸保护作用。结果0.334mg／mL丁香酸可使4EU内毒素降为0．777EU，破坏率为83．16％；1％丁香酸溶液可使内毒素引起的兔热显著降低；使同等剂量脂多糖引起的小鼠死亡率由68％降为20%。结论 丁香酸有抗内毒素作用。     

Enhanced levels of cow's milk antibodies in infancy in children who develop type 1 diabetes later in childhood

Background: Early exposure to cow’s milk (CM) proteins have been implicated in the pathogenesis of type 1 diabetes (T1D). Objective: We analyzed the development of the humoral immune response to dietary CM proteins in early childhood and its relation to later T1D. Subjects and methods: We studied a subgroup of 94 children randomized to be weaned to a CM‐based infant formula in the trial to reduce insulin‐dependent diabetes mellitus in the genetically at risk (TRIGR) pilot study. All subjects carried human leukocyte antigen‐conferred T1D susceptibility and had an affected first‐degree relative. After 7 years of follow‐up, 8 subjects had progressed to T1D, 15 had at least one disease‐associated autoantibody, and 71 remained autoantibody negative (controls). Immunoglobulin (Ig) G and IgA class antibodies to whole CM formula, beta‐lactoglobulin (BLG), bovine serum albumin, and alpha‐casein and IgG antibodies to bovine insulin (BI) were measured with enzyme‐linked immunosorbent assays from sequential samples. Results: The children with later T1D showed increased IgG levels to BLG from 3 to 18 months of age (p = 0.028) and enhanced IgA levels to CM formula at the age of 9 months (p = 0.022) compared with controls. In the children with an affected father or sibling, IgG antibodies to BI were higher in autoantibody‐positive subjects than in autoantibody‐negative subjects at 18 months of age (p = 0.022). Conclusion: An enhanced humoral immune response to various CM proteins in infancy is seen in a subgroup of those children who later progress to T1D. Accordingly, a dysregulated immune response to oral antigens is an early event in the pathogenesis of T1D.     

Enhancement of dietary protein digestion by conjugated bile acids

BACKGROUND & AIMS: Conjugated bile acids promote absorption of dietary lipids by solubilizing them in mixed micelles. Bile acids are not considered to facilitate the digestion of other nutrients. METHODS: The effect of conjugated bile acids on the rate of protein hydrolysis by trypsin and chymotrypsin was examined in vitro. Common dietary proteins and 2 bacterial glutenases (proposed oral therapies for celiac sprue) were proteolyzed in the absence or presence of a 10 mmol/L conjugated bile acid mixture, simulating human bile composition. Lipolysis products (monoolein) and fatty acid were also evaluated to simulate postprandial intestinal contents. RESULTS: Conjugated bile acids dramatically enhanced the proteolysis of several dietary proteins, including beta-lactoglobulin, bovine serum albumin, myoglobin, and a commercially available dietary protein supplement. For beta-lactoglobulin, a cow's milk allergen that is resistant to pepsin cleavage, bile acids enhanced its proteolysis by pancreatic proteases even after incubation under gastric conditions. Exposure of prolyl endopeptidases to bile acids made them more susceptible to pancreatic proteases under simulated intestinal conditions. The conjugated bile acid effect was most pronounced in the presence of dihydroxy bile acids and was observable at bile concentrations below the critical micellar concentration but to a much greater extent at concentrations above the critical micellar concentration. CONCLUSIONS: We propose that, in addition to promoting lipid absorption, conjugated bile acids affect the digestion and assimilation of dietary proteins by accelerating hydrolysis by pancreatic proteases. These findings have implications for intraluminal protein breakdown and assimilation in the upper small intestine.