Colon microflora in infants fed formula with galacto- and fructo-oligosaccharides: more like breast-fed infants

OBJECTIVES: The intestinal flora of breast-fed infants is generally dominated by Bifidobacteria. We aimed to investigate whether an infant formula supplemented with galacto-oligosaccharides and fructo-oligosaccharides (GOS/FOS) is able to establish a bifido-dominant microflora, not only in numbers but also with respect to the metabolic activity in the colon. METHODS: Two groups of infants fed infant formula with 0.8 g/100 ml GOS/FOS in a ratio of 9:1 (OSF group), or control formula (SF group) were evaluated in a randomised, double blind, placebo controlled intervention study. A breast-fed group was studied in parallel. At study onset and after 4 and 6 weeks, faecal samples were examined for the number of bifidobacteria, pH, short chain fatty acids and lactate. RESULTS: After 6 weeks, the mean proportion of bifidobacteria was significantly higher in the OSF group (59.6% versus 49.5% in the SF group; P < 0.05). Compared with controls, infants in the OSF group had a lower stool mean pH and an increased proportion of acetate and a decreased proportion of propionate. The mean pH in the OSF and SF groups were 5.7 and 6.3, respectively (P < 0.001). CONCLUSIONS: The addition of the prebiotic GOS/FOS mixture to an infant formula has a stimulating effect on the growth of bifidobacteria and on the metabolic activity of the total intestinal flora. The changes in short chain fatty acids, lactate and pH in the prebiotic group represent a fermentation profile that is closer to that observed in breast-fed infants compared to infants fed control formula.     

Familial influences on basal salivary cortisol in an adult population

To understand the underlying genetic and environmental sources of individual variation in basal cortisol levels, we collected salivary cortisol at awakening and at six fixed time points during the day in adult twins and their singleton siblings. Reported time of awakening was verified with heart rate and body movement recordings. Cortisol data were available for 199 MZ twins, 272 DZ twins and 229 singleton siblings from 309 twin families. No differences in cortisol means and variances were found between twins and singleton siblings. Additionally, the correlations for DZ twins and siblings were not significantly different, indicating generalizability of twin study results to the general population. Genetic model fitting showed heritability for cortisol levels during the awakening period (34% for cortisol level at awakening and 32% for cortisol level at 30 min after awakening) but not for cortisol levels later during the day. The current study shows that, while cortisol levels in the awakening period are influenced by genetic factors, cortisol levels throughout most of the day are not heritable, indicating that future gene finding studies for basal cortisol should focus on the first hour post-awakening.     

Endogenous central histamine-induced reversal of critical hemorrhagic hypotension in rats: studies with L-histidine

Activation of the histaminergic system is characteristic of response to the action of adverse or potentially dangerous stimuli that disturb circulatory homeostasis, such as dehydration and changes in blood pressure. Previous study demonstrates that inhibition of histamine N-methyltransferase, which catabolizes histamine released from neurons, leads to the increase in endogenous central histamine concentrations and to the reversal of critical hemorrhagic hypotension. In the present study, the influence of intraperitoneal loading with histamine precursor L-histidine on central cardiovascular regulation was studied in a model of irreversible pressure-controlled hemorrhagic shock. Experiments were carried out in male Wistar rats anesthetized with ketamine/xylazine subjected to critical hemorrhagic hypotension of 20 to 25 mmHg, which resulted in the death of all control saline-treated animals within 30 min. L-histidine administered in 5 min of critical hypotension produced dose-dependent increases in mean arterial pressure and heart rate (100-500 mg/kg), and a 100% survival rate of 2 h (500 mg/kg), whereas in normotensive animals, it did not influence cardiovascular parameters. The resuscitating effect of L-histidine (500 mg/kg) was associated with increases in histamine concentrations in the cerebral cortex (0.97 +/- 0.11 nmol/g of wet tissue vs. 0.67 +/- 0.22 nmol/g of wet tissue; P<0.05), hypothalamus (4.78 +/- 0.58 nmol/g of wet tissue vs. 4.08 +/- 0.43 nmol/g of wet tissue; P<0.01), and medulla oblongata (0.55 +/- 0.18 nmol/g of wet tissue vs. 0.34 +/- 0.09 nmol/g of wet tissue; P<0.05), as well as with no changes in plasma histamine concentrations in comparison with the saline-treated group 20 min after injection. Pretreatment with (S)-alpha-fluoromethylhistidine (alpha-FMH, 0.5 mg intracerebroventricularly), an irreversible inhibitor of L-histidine decarboxylase, produced a decrease in central histamine concentrations and diminished volumes of blood required to achieve critical hypotension. Moreover, alpha-FMH inhibited L-histidine-induced increases in central histamine concentrations and its resuscitating effect. In conclusion, the increase in central histamine concentrations after loading with L-histidine in rats subjected to critical hemorrhagic hypovolemia leads to the reversal of hypotension and the improvement in the survival rate of 2 h. On the other hand, inhibition of L-histidine decarboxylase activity, and thus histamine synthesis, produces a decrease in hemodynamic stability in hypotension, which suggests the histaminergic system-induced activation of compensatory mechanisms in hemorrhagic shock.     

Success of direct pulp capping after caries excavations

Direct pulp capping is not generally accepted as a routine dental procedure. It is claimed to be an unpredictable procedure with a low success rate. However, some clinical studies do show success of direct pulp cappings. The aim of this study was to make an inventory of the success rate of direct pulp cappings performed by dental students, and of the variables which influenced the outcome. The success rate for the first 18 months after treatment was 73.8%. Only the variable 'type of tooth' showed a statistical significant correlation: front teeth showed a higher percentage of success than premolars and molars.     

An entirely humanized CD3 zeta-chain signaling receptor that directs peripheral blood t cells to specific lysis of carcinoembryonic antigen-positive tumor cells

Recombinant T-cell receptors with antibody-like specificity for tumor-associated antigens are successfully used to direct the cytolytic activity of T cells toward tumor cells. Clinical application, however, needs to comply with the low immunogenicity of the recombinant receptor, efficient gene transfer into peripheral blood T cells, and enrichment of receptor-grafted cells. Here, we address these issues and describe an entirely humanized immune receptor for use in adoptive immunotherapy of colorectal carcinoma. The receptor consists of a single-chain antibody (scFv) binding domain specific for carcinoembryonic antigen (CEA), the IgG hinge and CH2/CH3 (Fc) joining region, and the transmembrane and intracellular CD3 zeta signaling chain. To express the receptor in peripheral blood T cells, both GALV envelope and MuLV 4070A pseudotyped retrovirus turned out to be equally efficient, with transduction efficiencies of about 5% to 40%, depending on the lymphocyte donor. Furthermore, receptor-grafted T cells could be 2- to 6-fold enriched by magnetic activated cell sorting, utilizing an antibody directed to the extracellular IgG domain of the receptor. Upon co-culture with CEA(+) tumor cells, receptor-grafted T cells are specifically and efficiently activated to cytolysis and IFN-gamma secretion, demonstrating their feasibility for the adoptive immunotherapy of CEA(+) carcinomas.