Effect of formula composition on the development of infant gut microbiota.

OBJECTIVES: Breast-feeding induces a gut microbiota rich in bifidobacteria, whereas formula-fed babies have a more diverse colonization. This ecosystem contributes to the development of the immune response and the lower incidence of diarrhea and allergy in breast-fed infants. This randomized double-blind controlled trial aimed to evaluate the bifidogenic effect of a mainly whey protein study formula low in phosphate and protein, allowing a composition closer to that of human milk. PATIENTS AND METHODS: One hundred ninety healthy infants exclusively received study formula with or without Bifidobacterium longum (BL999), or a control formula for up to 4 months. Breast-fed infants served as a reference population. Stool samples collected at 2 months of age were analyzed for bacterial counts (log colony-forming unit [CFU]/g). RESULTS: Bifidobacteria counts were significantly higher in infants receiving the study formula alone (10.0[0.8], P < 0.0001, median [interquartile range]) or with BL999 (9.8[1.4], P < 0.01) than control (9.2[3.5]), and were similar to breast-fed infants (10.1[0.4], P > 0.05). The difference between the 2 study groups was 0.16 log CFU/g (90% confidence interval [CI] [0-0.4]), within the predefined equivalence margin. Microbiota profile, as a percentage of total bacteria counts, showed about 50% Bifidobacteria, 8% Enterobacteria, and <10% Clostridia in study formulae and breast-fed infants versus 22%, 13%, and 19% in controls, respectively. There were no significant differences in growth measurements, digestive tolerance, and adverse events between groups. CONCLUSIONS: This study showed that infant formula closer resembling human milk was more bifidogenic than the control formula and led to a microbiota profile similar to that for breast-fed infants.

Lithium chloride and staurosporine potentiate the accumulation of phosphorylated glycogen synthase kinase 3ß/Tyr216, resulting in glycogen synthase kinase 3ß activation in SH-SY5Y human neuroblastoma cell lines.

Glycogen synthase kinase 3ß (GSK3ß) activity is regulated by phosphorylation processes and regulates in turn through phosphorylation several proteins, including eukaryotic initiation factor 2B (eIF2B). Serine 9 phosphorylation of GSK3ß (pGSK3ßSer9), usually promoted by activation of the PI3K/Akt survival pathway, triggers GSK3ß inhibition. By contrast, tyrosine 216 phosphorylation of GSK3ß (pGSK3ßTyr216) increases under apoptotic conditions, leading to GSK3ß activation. Lithium chloride (LiCl) is usually described to increase pGSK3ßSer9 through the PI3K/Akt pathway, resulting in GSK3ß inhibition. The purpose of this study is to demonstrate that in some cases LiCl is also able to increase pGSK3ßTyr216, resulting in GSK3ß activation. For this, we used SH-SY5Y cells and primary neuronal cultures and investigated the effects of LiCl on the two phosphorylated forms of GSK3ß under staurosporine (STS)-intoxicated conditions. The ratios between the phosphorylated and total forms of GSK3ß and eIF2B were determined by Western blotting. Our results revealed that, besides its ability to increase pGSK3ßSer9, LiCl is also able to increase pGSK3ßTyr216 greatly in STS-intoxicated SH-SY5Y cells but not in STS-intoxicated primary neuronal cultures. This accumulation of both Ser9 and Tyr216 phosphorylation results in GSK3ß activation in STS-intoxicated SH-SY5Y cells in spite of the presence of LiCl. These findings indicate that LiCl treatment is not necessarily correlated with GSK3ß inhibition even though it generates Ser9 phosphorylation. Consequently, the ratio pGSK3ßSer9/pGSK3ßTyr216, which takes into account the balance between the two inactive (Ser9) and active (Tyr216) forms of GSK3ß, could be more useful for predicting GSK3ß inhibition.

[Infants of drug-addicted mothers: pitfalls of replacement therapy]. / Enfants de mères toxicomanes: les aléas de la substitution.

Maternal drug addiction can cause problems for the fetus and the newborn, and hamper long-term development. The prevalence of drug addiction during pregnancy varies from 1 % to more than 10 % depending on the country and the maternity unit. Management of these mothers can be further complicated by medical, social and psychological problems. Compared to methadone, heroin replacement therapy with buprenorphine provides better stabilization of the mother and causes fewer withdrawal symptoms in the newborn. Despite numerous publications on the effects of this partly preventive medication, data on buprenorphine pharmacology at birth are scarce. In this study, 20 newborns of mothers using oral buprenorphine were observed until the end of the withdrawal syndrome, when present. Buprenorphine plasma levels were determined with HPLC and mass spectrometry in the mother at delivery and in the newborn at birth (cord blood), 24 and 48 hours. Fifteen newborns were born at term (mean +/- SD birth weight 3029 +/- 273 g), and the other five between 32 and 36 weeks. All Apgar scores were > or =7. Withdrawal symptoms were observed in 8 of the 15 infants born to mothers taking buprenorphine alone, and lasted between 5 and 35 days. The newborns were classified in three groups. Groups I (N8) and II (N7) comprised newborns with and without withdrawal symptoms, respectively. In group III (N5), the mothers were polyintoxicated (as shown by urinary drug or neurotropic substance screening) and the newborns were symptomatic for 1 to 69 days. Buprenorphine plasma levels in the mothers ranged from 0 to 2.9 microg/L, suggesting large differences in adherence. At birth there was no significant difference in the mean plasma buprenorphine level between newborns with and without withdrawal symptoms; the respective values were 0.7 (0.4-1.3) and 0.5 (0-0.6) microg/L. In asymptomatic newborns (group II), buprenorphine was no longer detectable at 48 h, whereas in symptomatic newborns (group I), the mean level rose from 0.7 microg/l at birth to 1.5 microg/L at 48 h (+114 %). In the absence of breastfeeding, this increase appears to be related to tissue release of this strongly lipophilic compound. The difference in plasma buprenorphine kinetics between groups I and II might be explained by genetic polymorphism of drug-metabolizing enzymes. The paradoxically high plasma buprenorphine levels at 48 hours in infants with withdrawal symptoms are intriguing. One possibility is that the mothers missed one or several doses of buprenorphine around the time of delivery, in the same way that smoking mothers tend to cut down during the last days of their pregnancy. If buprenorphine plasma levels at birth appear to reflect maternal adherence, cord blood levels do not predict the risk of a withdrawal syndrome. In contrast, the level at 48 h might help to discriminate between high- and low-risk newborns. Pregnant women on opiate replacement therapy must be delivered in maternity units with adequate neonatal facilities.

[Drinking water and urinary stones. Which drinking water and which modalities of diuresis?]. / Eaux de boisson et lithiase calcique urinaire idiopathique. Quelles eaux de boisson et quelle cure de diurèse?

Urologists frequently advise a high fluid intake to their patients with calcium stones, but apart from this simple advice, they often have few convincing arguments. This article describes the various types of drinking water available in France (mineral water, spring water, tap water), the legislation concerning drinking water, and the ions that must be taken into account for long-term forced diuresis. After studying their composition and adapting the dietary advice (particularly concerning dairy foods) to this ionic composition, various types of water can be advised to patients, including tap water, most types of spring water, but not all mineral waters.