Mental retardation in mucopolysaccharidoses correlates with high molecular weight urinary heparan sulphate derived glucosamine.

Mucopolysaccharidoses (MPS) are characterized by mental retardation constantly present in the severe forms of Hurler (MPS I), Hunter (MPS II) and Sanfilippo (MPS III) diseases. On the contrary, mental retardation is absent in Morquio (MPS IV) and Maroteaux-Lamy (MPS VI) diseases and absent or only minimal in the attenuated forms of MPS I, II and III. Considering that MPS patients affected by mental disease accumulate heparan sulfate (HS) due to specific enzymatic defects, we hypothesized a possible correlation between urinary HS-derived glucosamine (GlcN) accumulated in tissues and excreted in biological fluids and mental retardation. 83 healthy subjects were found to excrete HS in the form of fragments due to the activity of catabolic enzymes that are absent or impaired in MPS patients. On the contrary, urinary HS in 44 patients was observed to be composed of high molecular weight polymer and fragments of various lengths depending on MPS types. On this basis we correlated mental retardation with GlcN belonging to high and low molecular weight HS. We demonstrate a positive relationship between the accumulation of high molecular weight HS and mental retardation in MPS severe compared to attenuated forms. This is also supported by the consideration that accumulation of other GAGs different from HS, as in MPS IV and MPS VI, and low molecular weight HS fragments do not impact on central nervous system disease.

Rosiglitazone in the assistance of metabolic control during olanzapine administration in schizophrenia: a pilot double-blind, placebo-controlled, 12-week trial.

INTRODUCTION: Excessive body weight gain (BWG), hyperglycemia and dyslipidemia are important side effects of olanzapine. We assessed the effects of rosiglitazone on BWG, the insulin resistance index (HOMA-IR), lipids, glycated hemoglobin and fibrinogen in olanzapine-treated schizophrenia patients. METHODS: Thirty patients taking olanzapine (10-20 mg daily for 8 months) were randomly allocated to rosiglitazone (n=15; 4 to 8 mg daily) or placebo (n=15) in a 12-week double-blind protocol. Anthropometric and biochemical variables were evaluated at baseline, weeks 6 and 12. RESULTS: The rosiglitazone and placebo groups gained 3.2+/-4.5 and 2.2+/-2.3 kg, respectively (p=0.65). Insulin and the HOMA-IR significantly decreased after rosiglitazone (p<0.05). Rosiglitazone did not improve the lipid profile, fibrinogen and Hb1c levels. DISCUSSION: The positive impact of rosiglitazone was limited to improved glycemic control. It cannot be recommended for metabolic control during olanzapine treatment.

Prebiotics in human milk: a review.

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.

Effect of aluminium on lipid peroxidation of human high density lipoproteins.

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.

Prebiotics in infant formulas: biochemical characterisation by thin layer chromatography and high performance anion exchange chromatography.

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.

Increased susceptibility to peroxidation of VLDL from non-insulin-dependent diabetic patients: a possible correlation with fatty acid composition.

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.

Study of fluidity of low density lipoproteins from liver cirrhotic patients.

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.

Effect of aluminium ions on liposomal membranes as detected by Laurdan fluorescence.

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.

Reduced beta-strand content in apoprotein B-100 in smaller and denser low-density lipoprotein subclasses as probed by Fourier-transform infrared spectroscopy.

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.