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Background: Excessive body weight gain (BWG) is a clinically relevant side effect of olanzapine administration. The primary objective of this study was to assess whether metformin prevents or reverses BWG in patients with schizophrenia or bipolar disorder under olanzapine administration. Secondarily we evaluated diverse metabolic variables., Methods: Eighty patients taking olanzapine (5-20 mg daily for more than 4 consecutive months) were randomly allocated to metformin (n=40; 850 to 2550 mg daily) or placebo (n=40) group in a 12-week double-blind protocol. Waist circumference (WC) body weight (BW), body mass index (BMI) fasting glucose, glycated hemoglobin (Hb1c), insulin, an insulin resistance index (HOMA-IR) lipids, leptin, c-reactive protein, fibrinogen, cortisol and the growth hormone (GH) were evaluated at baseline and at week 12 of treatment., Results: The metformin group lost 1.4+/-3.2 kg (p=0.01) and tended to decrease its leptin levels, whereas the placebo group maintained a stable weight: -0.18+/-2.8 kg (p=0.7). The HOMA-IR significantly increased after placebo (p=0.006) and did not change after metformin (p=0.8). No ostensible differences were observed in the other variables, even though metformin did not improve the lipid profile and the Hb1c levels., Conclusions: Metformin may safely assist olanzapine-treated patients in body weight and carbohydrate metabolism control.

In this study, the Authors assessed some insulin counter-regulatory factors, fibrinogen and C-reactive protein after olanzapine administration, and the effect of metformin on these variables, 37 patients with chronic schizophrenia were given olanzapine (10 mg/day for 14 weeks). Nineteen patients received metformin (850-2550 mg/day) and 18 received placebo in a randomized, double-blind protocol. The following variables were quantified before and after olanzapine: cortisol, leptin, tumor necrosis factor-alpha, glucagon, growth hormone, fibrinogen and C-reactive protein. Results were correlated with the changes in body weight and the insulin resistance index. We have reported elsewhere that metformin did not prevent olanzapine-induced weight gain, and the insulin resistance index significantly decreased after metformin and placebo; Baptista T, et al. Can J Psychiatry 2006; 51: 192-196. Cortisol, tumor necrosis factor-alpha and fibrinogen levels significantly decreased in both groups. Glucagon significantly increased after metformin (P=0.03). Leptin tended to increase after placebo (P=0.1) and displayed a small nonsignificant reduction after metformin. The C-reactive protein did not change significantly in any group. Contrarily to most published studies, olanzapine was associated with decreased insulin resistance. Decrements in cortisol, fibrinogen and tumor necrosis factor-alpha levels point to an improvement in the metabolic profile. The trend for leptin to increase after placebo, but not after metformin in spite of similar weight gain suggests a beneficial effect of this antidiabetic agent.

The microbic colonization of human intestine begins at birth, when from a sterile state the newborn is exposed to an external environment rich in various bacterial species. The kind of delivery has an important influence on the composition of the intestinal flora in the first days of life. Thereafter, the microflora is mainly influenced by the kind of feeding: breast-fed infants show a predominance of bifidobacteria and lactobacilli, whereas bottle-fed infants develop a mixed flora with a lower number of bifidobacteria. The "bifidogenic effect" of human milk is not related to a single growth-promoting substance, but rather to a complex of interacting factors. In particular the prebiotic effect has been ascribed to the low concentration of proteins and phosphates, the presence of lactoferrin, lactose, nucleotides and oligosaccharides. The real prebiotic role of each of these substances is not yet clearly defined, with the exception of oligosaccharides which undoubtedly promote a bifidobacteria-dominant microflora.

Breast-fed children, compared with the bottle-fed ones, have a lower incidence of acute gastroenteritis due to the presence of several antiinfective factors in human milk. The aim of this work is to study the ability of human milk oligosaccharides to prevent infections related to some common pathogenic bacteria. Oligosaccharides of human milk were fractionated by gel-filtration and characterized by thin-layer chromatography and high-performance anion exchange chromatography. Fractions obtained contained, respectively, 1) acidic oligosaccharides, 2) neutral high-molecular-weight oligosaccharides, and 3) neutral low-molecular-weight oligosaccharides. Experiments were carried out to study the ability of oligosaccharides in inhibiting the adhesion of three intestinal microorganisms (enteropathogenic Escherichia coli serotype O119, Vibrio cholerae, and Salmonella fyris) to differentiated Caco-2 cells. The study showed that the acidic fraction had an antiadhesive effect on the all three pathogenic strains studied (with different degrees of inhibition). The neutral high-molecular-weight fraction significantly inhibited the adhesion of E. coli O119 and V. cholerae, but not that of S. fyris; the neutral low-molecular-weight fraction was effective toward E. coli O119 and S. fyris but not V. cholerae. Our results demonstrate that human milk oligosaccharides inhibit the adhesion to epithelial cells not only of common pathogens like E. coli but also for the first time of other aggressive bacteria as V. cholerae and S. fyris. Consequently, oligosaccharides are one of the important defensive factors contained in human milk against acute diarrheal infections of breast-fed infants.

We investigated the effect of aluminium (Al3+) on lipid peroxidation and physico-chemical properties of high density lipoproteins (HDL) isolated from human plasma. Our results demonstrated that Al3+ enhances lipid peroxidation of human HDL as shown by the significant increase in lipid hydroperoxides in Al-treated HDL with respect to control HDL. The oxidative effect was higher at acid pH (pH 5.5) with respect to pH 7.4. Moreover, a stimulating effect of Al3+ on iron-induced lipid peroxidation of HDL was demonstrated. The study of the effect of Al3+ on the physico-chemical properties of HDL, using the fluorescence polarization (Pf) of the probes TMA-DPH (1-(4-trimethylammoniumphenyl)-6-phenyl-1,3,5-hexatriene iodide) and DPH (1,6-diphenyl-1,3,5-hexatriene), showed a significant decrease of Pf in Al-treated HDL with respect to control. These results suggest that Al3+ induces a decrease of molecular order at the lipoprotein surface. Moreover, the study of tryptophan (Trp) fluorescence demonstrated that aluminium induces structural modifications of HDL apoproteins and on HDL physico-chemical properties. The effect of Al3+ on lipid peroxidation of HDL was observed at aluminium concentrations similar to those observed in the brain of patients affected by neurological diseases. Aluminium-induced oxidative damage of HDL could be involved in the development of neurological diseases.

Background: Breast-fed infants, unlike bottle-fed babies, have a microbic intestinal flora characterised by a marked predominance of bifidobacteria and lactic acid bacteria. This is essentially due to the prebiotic effect of oligosaccharides in human milk. Recently, oligosaccharides with a prebiotic effect have been added to formulas. Aim. To characterise the mixture of oligosaccharides contained in these new formulas., Materials and Methods: The characterisation of oligosaccharides was performed using thin layer chromatography as well as high performance anion exchange chromatography., Results: The mixture of oligosaccharides used in the formulas analysed was made up of oligosaccharides with low molecular weight (transgalactosylated oligosaccharides) and polysaccharides with high molecular weight (inulin)., Conclusion: With the methods employed, it was possible to characterise the mixture of oligosaccharides used as prebiotics in the formulas now available on the market.

Background and Aim: Liver disease is accompanied by major quantitative and qualitative modifications in plasma lipoprotein metabolism. Alterations in plasma lipoprotein composition and a lower susceptibility to in vitro peroxidation of low density lipoprotein (LDL) and erythrocyte membranes have been observed in liver cirrhosis. The main objective of the present work was to investigate LDL chemical composition and fluidity in liver cirrhosis using the fluorescence polarization (Pf) of the 1,6-diphenyl-1,3,5-hexatriene (DPH) probe., Methods and Results: The chemical composition of LDL was studied in 12 cirrhotic patients and 22 controls by conventional methods and its fatty acid composition by gas chromatography. LDL fluidity was determined by measuring the DPH Pf values. A decrease in molecular order was demonstrated by the significant (p < 0.05) decrease in Pf values in the cirrhotics. Modifications in LDL fluidity are correlated with its composition. A significant increase in triglyceride content (p < 0.05), and significant increases in triglyceride/protein and triglyceride/phospholipid ratios were observed in the cirrhotics., Conclusions: Our results demonstrate that the higher LDL fluidity of cirrhotic patients may be due to an increased triglyceride content.

Recent studies suggested that both oxidized very low density lipoproteins (VLDL) and oxidized high density lipoproteins (HDL) might play a role in the pathogenesis of atherosclerosis. The aim of the present work was to analyse the susceptibility to in vitro peroxidation of VLDL and HDL from apparently normolipidemic subjects affected by insulin-dependent diabetes mellitus (IDDM) and non-insulin-dependent diabetes mellitus (NIDDM) in good metabolic control and to examine the possible relations between oxidisability and lipoprotein fatty acid composition. VLDL and HDL were isolated from 13 IDDM patients, 12 NIDDM patients and 18 healthy subjects. The degree of lipoprotein oxidation was determined by the measurement of hydroperoxide levels and thiobarbituric acid-reactive substances (TBARS) before and after in vitro peroxidative stress with CuSO4. Fatty acid analysis was performed by gas chromatography. VLDL and HDL from NIDDM patients showed a decrease in the saturated fatty acid content with a concomitant increase in unsaturated fatty acids and higher basal peroxide levels compared with healthy subjects. Oxidisability of VLDL from NIDDM subjects was higher than in controls and was significantly related with the unsaturated fatty acid content. The present work suggests that alterations in the composition and functions of both VLDL and HDL able to produce more atherogenic lipoproteins are present in NIDDM.

We report here an investigation of the influence of aluminium on iron-induced peroxidation in brain model membranes. Laurdan fluorescence emission spectra and generalised polarisation measurements have been used to investigate how ferrous and aluminium ions can affect the phase components of phospholipid membranes. An increase in the generalised polarisation of oxidised liposomes with respect to controls has been observed, which reveals the presence of a less polar environment surrounding the probe that changes the properties of the bilayer. Aluminium has been shown to facilitate iron-mediated oxidation as detected from emission fluorescence spectra. However, no quantitative influence has been calculated relative to general polarisation and derived phase state determinations. The structural influence of aluminium on membranes may therefore be less significantly marked than initially expected.

The secondary structure of apolipoprotein B-100 in low-density lipoprotein (LDL) subfractions was analysed by Fourier-transform IR spectroscopy. LDLs were isolated in three density ranges by gradient centrifugation of human plasma from healthy volunteers. The spectra revealed differences in the lipid content and composition of the three LDL fractions. The secondary structure of apolipoprotein B-100 was the same in the two fractions corresponding to the large less-dense LDL particles, whereas a lower content of beta-strands was found in the third fraction corresponding to the smaller denser LDL particles. Analysis of the spectroscopic data suggests that, in the same set of LDL subfractions, the particle size is probably the cause of the observed differences in apolipoprotein B-100 secondary structure.