Oral administration of a novel octreotide formulation enabled its absorption to the systemic circulation, exhibiting blood concentrations comparable those observed with injected and maintaining biological activity.The aim study was determine oral effects on pituitary GH secretion compared sc injection.Four single-dose studies were conducted in 75 healthy volunteers.Oral doses 3, 10, or 20 mg single injection 100 μg administered.We measured pharmacokinetic profile orally administrated effect...

Medium chain fatty acid salts promote absorption by increasing paracellular permeability of the intestinal epithelium. Novel oily suspension (OS) formulation disperses a powder containing sodium caprylate and macromolecules such as octreotide or fluorescent dextran (FD). Formulation safety, macromolecule pharmacokinetic (PK)/pharmacodynamic (PD) were evaluated.Octreotide/OS toxicity was evaluated in monkeys following 9 months daily oral enteric-coated capsule administration. The OS...

Gaucher disease is a glycosphingolipid storage caused by defects in the activity of lysosomal hydrolase, glucocerebrosidase (GlcCerase), resulting accumulation glucocerebroside (glucosylceramide, GlcCer) lysosomes. The acute neuronopathic type characterized severe loss neurons central nervous system, suggesting that neurotoxic agent might be responsible for cellular disruption and neuronal death. We now demonstrate upon incubation with chemical inhibitor GlcCerase, conduritol-B-epoxide...

We recently demonstrated that elevation of intracellular glucosylceramide (GlcCer) levels results in increased functional Ca2+ stores cultured neurons, and suggested this may be due to modulation ryanodine receptors (RyaRs) by GlcCer (Korkotian, E., Schwarz, A., Pelled, D., Schwarzmann, G., Segal, M. Futerman, A. H. (1999) J. Biol. Chem. 274, 21673–21678). now systematically examine the effects exogenously added GlcCer, other glycosphingolipids (GSLs) their lyso-derivatives on release from...

Gangliosides are found at high levels in neuronal tissues where they play a variety of important functions. In the gangliosidoses, gangliosides accumulate because defective activity lysosomal proteins responsible for their degradation, usually resulting rapidly progressive neurodegenerative disease. However, molecular mechanism(s) leading from ganglioside accumulation to neurodegeneration is not known. We now examine effect GM2 mouse model Sandhoff disease (one gangliosidoses), Hexb–/–...

Treatment of cultured hippocampal neurons with high concentrations short-chain acyl ceramide derivatives, such as N-hexanoyl-D-sphingosine (C(6)-Cer), results in apoptotic cell death. We now show that death-associated protein (DAP) kinase plays an important role mediating this effect. Upon incubation C(6)-Cer, DAP levels are elevated early 1 h after treatment, reaching 2-3-fold higher than untreated cells 4 h. Neurons from kinase-deficient mice were significantly less sensitive to apoptosis...

Glucosylceramide (GlcCer) accumulates in the inherited metabolic disorder, Gaucher disease, because of defective activity lysosomal glucocerebrosidase. We previously demonstrated that upon GlcCer accumulation, cultured hippocampal neurons exhibit modified growth patterns, altered endoplasmic reticulum density, and calcium release from intracellular stores. here examined relationship between accumulation phospholipid synthesis. After treatment with an active site-directed inhibitor...

Consumption of plant sterol (PS) esters lower low-density lipoprotein (LDL)-cholesterol levels by suppressing intestinal absorption cholesterol. Commercially available PS are mainly esterified to omega-6 fatty acid (FA), such as sunflower oil (SO) FA. Emerging trends include using other sources olive (OO) or omega-3 FA from fish (FO), known exert potent hypotriglyceridemic effects. Our objective was compare the actions different on blood lipids, carotenoid bioavailability well inflammatory...

Plant sterols (PS) and MUFA are well-documented cholesterol lowering agents. We aimed to determine the effect of PS esterified olive oil fatty acids (PS-OO) on blood lipid profile peroxidation in hypercholesterolaemic subjects. Twenty-one moderately overweight, subjects consumed three consecutive treatment diets, each lasting 28 d separated by 4-week washout periods, using a randomized crossover design. Diets contained 30 % energy as fat, 70 which was provided (OO), differed only oils: OO,...

Recently, we demonstrated that the GSL (glycosphingolipid), GlcCer (glucosylceramide), modulates Ca2+ release from intracellular stores and microsomes by sensitizing RyaR (ryanodine receptor), a major Ca2+-release channel of endoplasmic reticulum, whereas lyso derivative GlcCer, namely GlcSph (glucosylsphingosine), induced via mechanism independent [Lloyd-Evans, Pelled, Riebeling, Bodennec, de-Morgan, Waller, Schiffmann Futerman (2003) J. Biol. Chem. 278, 23594-23599]. We now systematically...

Elucidating the potential contribution of specific autoantibodies (Ab's) to etiology and/or pathology some human epilepsies.Six epilepsy patients with Rasmussen's encephalitis (RE) and 71 other epilepsies were tested for Ab's "B" peptide (amino acids 372-395) glutamate/AMPA subtype 3 receptor (GluR3B peptide), double-stranded DNA (dsDNA), additional autoimmune disease-associated autoantigens, ability their serum cerebrospinal-fluid (CSF) kill neurons.Elevated anti-GluR3B Ab' s found in CSF...

The performances of compression and stapled devices were compared previously in porcine colorectal anastomosis. anastomosis was associated with elevated bursting strength anastomotic patency this model as the anastomosis.The purpose work to compare histopathologic features between methods healing anastomoses using a model.This blinded comparison study.The study conducted at single university surgery department.Fifty crossbred pigs used study.Fifty underwent rectal transection 20 cm from anal...

Abstract : Lesch‐Nyhan syndrome is a pediatric metabolic‐neurological caused by the X‐linked deficiency of purine salvage enzyme hypoxanthine‐guanine phosphoribosyltransferase (HGPRT). The cause metabolic consequences HGPRT has been clarified, but connection between and neurological manifestations still unknown. In search for this connection, in present study, we characterized nucleotide metabolism primary astroglia cultures from HGPRT‐deficient transgenic mice. exhibited basic abnormalities...

Sandhoff disease is a lysosomal storage in which ganglioside GM2 accumulates because of defective β‐subunit β‐hexosaminidase. This characterized by neurological manifestations, although the pathogenic mechanisms leading from accumulation to neuropathology are largely unknown. We now examine viability, development and rates neurite growth embryonic hippocampal neurones cultured mouse model disease, Hexb –/– mouse. was detected metabolic labelling at low levels wild type ( +/+) neurones,...

Methods for isolation of neutral lysoglycosphingolipids (n-lys20) such as glucosylsphingosine and galactosylsphingosine normally involve mild alkaline or acid hydrolysis followed by multiple chromatography steps, yielding relatively low recoveries n-lyso-GSLs glycosphingolipids (n-GSLs). We now describe a new technique isolating these compounds using one step, resulting in quantitative recovery n-GSLs n-lyso-GSLs. Lipids are extracted modified Folch procedure which is optimized reextracting...

Metabolic syndrome is associated with subsequent development of cardiovascular diseases and type 2 diabetes. It characterized by reduced response to insulin, central obesity, dyslipidemia. Intake plant sterols (PS) has been shown confer a healthier lipid profile ameliorate disease risk factors in experimental animals humans. In this study we used an animal model diabetes assess the effects preparation PS esterified high oleic sunflower oil fatty acids mixed dietary diacylglycerol (PS-HOSO)...