Interaction of a beta-sheet breaker peptide with lipid membranes.

Aggregation of beta-amyloid peptides into senile plaques has been identified as one of the hallmarks of Alzheimer's disease. An attractive therapeutic strategy for Alzheimer's disease is the inhibition of the soluble beta-amyloid aggregation using synthetic beta-sheet breaker peptides that are capable of binding Abeta but are unable to become part of a beta-sheet structure. As the early stages of the Abeta aggregation process are supposed to occur close to the neuronal membrane, it is strategic to define the beta-sheet breaker peptide positioning with respect to lipid bilayers.

Synthesis and biological evaluation of new potential inhibitors of N-acylethanolamine hydrolyzing acid amidase.

N-Acylethanolamines, including N-palmitoyl-ethanolamine (PEA), are hydrolyzed to the corresponding fatty acids and ethanolamine by fatty acid amide hydrolase (FAAH). Recently, N-acylethanolamine-hydrolyzing acid amidase (NAAA) was identified as being able to specifically hydrolyze PEA. In order to find selective and effective inhibitors of this enzyme, we synthesized and screened several amides, retroamides, esters, retroesters and carbamates of palmitic acid (1-21) and esters with C15 and C17 alkyl chains (22-27).

Assessment of fluid-responsiveness parameters for off-pump coronary artery bypass surgery: a comparison among LiDCO, transesophageal echochardiography, and pulmonary artery catheter.

Objective: To verify the reliability of different markers of fluid-responsiveness during off-pump cardiac surgery (OPCAB).

Design: A clinical prospective, nonblinded, nonrandomized study.

Setting: A community hospital.

Chemistry and biology of chromatin remodeling agents: state of art and future perspectives of HDAC inhibitors.

Chromatin remodeling is a fundamental phenomenon in the life of eukaryotic cells, bearing implications to numerous physiological and pathological phenomena. This review outlines the chemistry of natural and synthetic agents endowed with the ability to interfere with such biological function, with a particular emphasis on histone deacetylase (HDAC) inhibitors. Other aspects covered in this article comprise structure activity relationships (SAR) and modes of action at molecular level, including the description of crystal structures of enzyme-inhibitor complexes.

New metabolically stable fatty acid amide ligands of cannabinoid receptors: Synthesis and receptor affinity studies.

We investigated the structure-activity relationships for the interactions of fatty acid amide analogs of the endocannabinoid anandamide with human recombinant cannabinoid receptors. Thirty-five novel fatty acid amides were synthesized using five different types of acyl chains and 11 different aromatic amine 'heads.' Although none of the new compounds was a more potent ligand than anandamide, we identified three amine groups capable of improving the metabolic stability of arachidonoylamides and their CB(1)/CB(2) selectivity ratio to over 20-fold, and several aromatic amines capable of improving the affinity of short chain or monosaturated fatty acids for cannabinoid CB(1) receptors.

[What's the best assessment of preload after cardiac surgery?].

Objective: The assessment of the role of transesophageal echocardiography and invasive tests with pulmonary modified catheter to monitor the preload indexes in patients in intensive-care-unit after cardiac coronary surgery.

Materials And Methods: Between January and December 2004 24 patients (14 male, 10 female) with coronary artery disease were prospectively enrolled for preload assessment during off-pump myocardial revascularization. Pulmonary Capillary Wedge Pressure (PCWP), Left Ventricular End Diastolic Indexed Area (LVEDAI), delta Aortic Velocity (deltaVAo), Right Ventricular End Diastolic Volume (RVEDVI) as preload indexes were evaluated.

Synthesis and biological evaluation of 3-benzyl-1-methyl- and 1-methyl-3-phenyl-isothioureas as potential inhibitors of iNOS.

Novel benzyl- and phenyl-isothioureidic derivatives have been synthesised and evaluated as inhibitors of nitric oxide synthesis, induced in lipopolysaccharide (LPS)-activated J774.A1 macrophage cell line. The most potent iNOS inhibitor resulting was 1-methyl-3-phenyl-S-methyl isothiourea 5l.

Antioxidant activity of thioureidic derivatives I.

Recent developments in biomedical science have shown that free radicals are involved in many diseases. They attack the unsaturated fatty acids in the biomembrane resulting in membrane lipid peroxidation, which is strongly connected to aging, carcinogenesis and atherosclerosis. Free radicals also attack DNA and cause mutation leading to cancer.

In vitro anti-acanthamoeba action by thioureidic derivatives.

The anti-amoebic power of a series of bis-thioureidic derivatives against amoeba, responsible for a serious form of keratitis of the cornea, has been analysed. The synthesis of these products is also described.

Pharmacological studies and synthesis of morpholino alkyl derivatives.

Seven morpholin derivatives were synthesized (compounds 1-7) and their behavioural effects were evaluated; the elements considered were locomotor activity, motor coordination, catalepsy, stereotyped behaviour and antinociception. All the compounds, at doses of 10-20-40 mg/kg/i.p.