GI Symptoms in Infants Are a Potential Target for Fermented Infant Milk Formulae: A Review

Besides pre- and pro-biotic-containing infant formulae, fermented infant formulae are commonly used to relieve or prevent symptoms of gastrointestinal (GI) discomfort in young infants. During the fermentation process in cow’s milk-based formulae, the beneficial bacteria modulate the product by forming several beneficial compounds, which contribute to the alleviation of the symptoms observed. This review summarizes the clinical evidence on the impact of fermented infant formulae on common pediatric GI-symptoms. The potential mechanisms involved are discussed: i.e., the lactose and protein (in-) digestibility, effects on gastric emptying and gut transit and modulation of the colonic microbiota. Although initial evidence indicates a beneficial effect of fermented formulae on GI discomfort in newborns, validation and confirmation of the clinical proof obtained so far is warranted, as well as further research to (more fully) understand the mode of action.     

Pharmacological assessment of the site of action of opioids on the release of vasopressin and oxytocin in the rat.

Naloxone and its congener, methyl naloxone, were given subcutaneously (s.c.) or centrally (i.c.v.) to 24-h water-deprived male rats 30 min prior to decapitation and the effect on plasma levels of vasopressin (VP) and oxytocin (OT) was studied. The potency of s.c. applied methyl naloxone to increase plasma OT levels did not differ from that of naloxone. Injected i.c.v., neither methyl naloxone nor naloxone had a clear effect and they antagonized i.c.v. co-administered dynorphin A-(1-13) equipotently. Methyl naloxone or naloxone, s.c., antagonized the inhibitory action of simultaneous dynorphin A-(1-13) and beta-endorphin-(1-31) given i.c.v., although higher doses of methyl naloxone were required. The data indicate that the sites of inhibition of neurohypophysial hormone release due to beta-endorphin-(1-31) are more likely to be located mostly within the blood-brain barrier, to which methyl naloxone has less ready access, than are the sites of inhibition due to dynorphin A-(1-13).     

The opioid receptor subtypes mu and kappa, but not delta, are involved in the control of the vasopressin and oxytocin release in the rat.

The effects of highly selective agonists and antagonists to the mu-, delta- and kappa-opioid receptor subtypes were studied on the vasopressin and oxytocin release in 24 h water-deprived male rats. The delta-agonist [D-Pen2,D-Pen5]enkephalin (dose range 0.01-5 mg/kg) did not affect plasma levels of either hormone 30 min after s.c. administration, whereas the mu-agonist DALDA (H-Tyr-D-Arg-Phe-Lys-NH2) over the same dose range strongly inhibited the release of both vasopressin and oxytocin, an effect that was maximal 30-60 min after s.c. injection. The same effect was found for s.c. administration of the kappa-agonist U-69,593. Intracerebroventricular (i.c.v.) administration of DALDA (0.5 and 5 micrograms/kg) but not U-69,593 suppressed both plasma hormone levels 30 min after injection. Also the effects of selective antagonists were tested over the s.c. dose range of 0.01-1 mg/kg. Whereas both the kappa-selective antagonist nor-binaltorphimine and the relatively mu-selective antagonist naloxone elevated oxytocin plasma levels (peak at 15 and 30 min after injection, respectively), the delta-selective antagonist naltrindole was without any effect. Nor-binaltorphimine, naloxone, and naltrindole did not affect vasopressin release. When the antagonists were administered i.c.v. (dose range 2.5-25 micrograms/kg), only the kappa-antagonist nor-binaltorphimine enhanced oxytocin and vasopressin release 30 min after injection. In conclusion, both mu- and kappa-opioid receptors are involved in the regulation of the secretion of vasopressin and oxytocin from the rat neural lobe; in contrast, delta-opioid receptors do not play a role.(ABSTRACT TRUNCATED AT 250 WORDS)     

Dynorphin-A and vasopressin release in the rat: A structure-activity study

The effects on vasopressin (VP) release of three dynorphin-A fragments and two antidynorphin antisera were tested in vivo and in vitro.In vivo, the order of potency to inhibit VP release 30 min upon i.c.v. injection was: dynorphin-A-(1–17) > dynorphin-A-(1–13) > dynorphin-A-(1–8).l.c.v. co-administration of 10 nmoles of the specific endopeptidase-inhibitor cFPAAF-pAB and dynorphin-A-(1–8) also suppressed VP secretion. Dynorphin-A-(1–17) antiserum enhanced VP release 20 and 60 min after i.c.v. injection. The antiserum that recognized dynorphin-A-(1–13) elevated VP plasma levels at 60 min post-injection.In vitro, dynorphin-A-(1–8) suppressed electrically evoked VP release from the isolated neuroal lobe. VP release was not affected by dynorphin-A-(1–13), dynorphin-A-(1–17), naloxone, or by the anti-dynorphin antisera.These data indicate that dynorphin-A-(1–17), rather than dynorphin-A-(1–8), plays a role in the centrally located control of neurohypophysial VP release, whereas dynorphin-A-(1–8) is involved in the control located in the posterior pituitary. The synthetic intermediate fragment dynorphin-A-(1–13) appears to affect VP release both centrally and peripherally.     

Early-Life Metabolic and Hormonal Markers in Blood and Growth until Age 2 Years: Results from a Randomized Controlled Trial in Healthy Infants Fed a Modified Low-Protein Infant Formula

Background: High protein intake in early life is associated with an increased risk of childhood obesity. Dietary protein intake may be a key mechanistic modulator through alterations in endocrine and metabolic responses. Objective: We aimed to determine the impact of different protein intake of infants on blood metabolic and hormonal markers at the age of four months. We further aimed to investigate the association between these markers and anthropometric parameters and body composition until the age of two years. Design: Term infants received a modified low-protein formula (mLP) (1.7 g protein/100 kcal) or a specifically designed control formula (CTRL) (2.1 g protein/100 kcal) until 6 months of age in a double blinded RCT. The outcomes were compared with a breast-fed (BF) group. Glucose, insulin, leptin, IGF-1, IGF-BP1, -BP2, and -BP3 levels were measured at the age of 4 months. Anthropometric parameters and body composition were assessed until the age of 2 years. Groups were compared using linear regression analysis. Results: No significant differences were observed in any of the blood parameters between the formula groups (n = 53 mLP; n = 44 CTRL) despite a significant difference in protein intake. Insulin and HOMA-IR were higher in both formula groups compared to the BF group (n = 36) (p < 0.001). IGF-BP1 was lower in both formula groups compared to the BF group (p < 0.01). We found a lower IGF-BP2 level in the CTRL group compared to the BF group (p < 0.01) and a higher IGF-BP3 level in the mLP group compared to the BF group (p = 0.03). There were no significant differences in glucose, leptin, and IGF-1 between the three feeding groups. We found specific associations of all early-life metabolic and hormonal blood parameters with long-term growth and body composition except for IGF-1. Conclusions: Reducing protein intake by 20% did not result in a different metabolic profile in formula-fed infants at 4 months of age. Formula-fed infants had a lower insulin sensitivity compared to breast-fed infants. We found associations between all metabolic and hormonal markers (except for IGF-1) determined at age 4 months and growth and body composition up to two years of age.     

Acute and Chronic Effects of Dietary Lactose in Adult Rats Are not Explained by Residual Intestinal Lactase Activity

Neonatal rats have a high intestinal lactase activity, which declines around weaning. Yet, the effects of lactose-containing products are often studied in adult animals. This report is on the residual, post-weaning lactase activity and on the short- and long-term effects of lactose exposure in adult rats. Acutely, the postprandial plasma response to increasing doses of lactose was studied, and chronically, the effects of a 30% lactose diet fed from postnatal (PN) Day 15 onwards were evaluated. Intestinal lactase activity, as assessed both in vivo and in vitro, was compared between both test methods and diet groups (lactose vs. control). A 50%–75% decreased digestive capability towards lactose was observed from weaning into adulthood. Instillation of lactose in adult rats showed disproportionally low increases in plasma glucose levels and did not elicit an insulin response. However, gavages comprising maltodextrin gave rise to significant plasma glucose and insulin responses, indicative of a bias of the adult GI tract to digest glucose polymers. Despite the residual intestinal lactase activity shown, a 30% lactose diet was poorly digested by adult rats: the lactose diet rendered the animals less heavy and virtually devoid of body fat, whereas their cecum tripled in size, suggesting an increased bacterial fermentation. The observed acute and chronic effects of lactose exposure in adult rats cannot be explained by the residual intestinal lactase activity assessed.     

Effects of Ursodeoxycholic Acid Therapy on In Vitro Gallbladder Contractility in Patients with Cholesterol Gallstones

During treatment with ursodeoxycholic acid(UDCA), the fasting gallbladder volume increases by ayet unknown mechanism. The present study tests whetherin vitro human gallbladder contractility in response to acetylcholine and cholecystokinin isaffected by UDCA therapy. Gallbladder tissue wasobtained from 15 patients treated with UDCA (10mg/kg/day) during three weeks prior to surgery, and from15 comparable patients not treated. Data were correlated within vivo contractility, bile composition, and gallbladderwall inflammation. The inflammation score was lower inthe treated patient group. UDCA treatment enhanced gallbladder contractility in vitro:Dose-response curves for acetylcholine andcholecystokinin were both shifted to the left, and themaximal contractile stress generated in response tocholecystokinin was higher in the treated group, whereas themaximal acetylcholine-induced stress was not increased.Maximal cholecystokinin-induced stress correlatedpositively with fasting gallbladder volume andnegatively with the biliary cholesterol saturation index,but not with bile salt hydrophobicity or gallbladderwall inflammation score. In conclusion, UDCA treatmentimproves in vitro gallbladder contractility, possibly related to a reduced biliary cholesterolsaturation. Increased fasting gallbladder volumes duringUDCA treatment thus do not appear to result fromdecreased gallbladder muscle contractilestrength.     

A specific blend of intact protein rich in aspartate has strong postprandial glucose attenuating properties in rats

Three studies were carried out to help define an optimal protein blend for use in a nutritional product for diabetic patients. To this end, we tested the effects of coinfusions of combinations of different types of carbohydrates and proteins on the postprandial glycemic plasma response in healthy rats. Expt. 1 compared the effects of administering different forms of soy protein (intact protein, its hydrolysate, or an equivalent amount of the same amino acids), all in combination with a fixed amount of glucose (Glu), on postprandial Glu and insulin plasma concentrations. Intact soy protein (SI) had stronger insulinogenic properties compared with its hydrolysate but was equally potent in reducing the postprandial Glu response. In Expt. 2, we compared the effect of replacing 50% of the SI with the whey-derived protein alpha-lactalbumin when coingested with maltodextrin as the carbohydrate source. Only the specific aspartate-rich blend of SI and alpha-lactalbumin significantly improved the postprandial Glu response. In Expt. 3, we studied the effect of using the blend of SI and alpha-lactalbumin combined with a slowly digestible carbohydrate. The protein blend was still capable of significantly decreasing the postprandial Glu response even when a slow-release carbohydrate source was included. Combining this aspartate-rich protein blend with a slow-release carbohydrate might therefore lead to a low-glycemic nutritional product beneficial for dietary management in diabetic patients.