fac-{Ru(CO)3}2+-core complexes and design of metal-based drugs. synthesis, structure, and reactivity of Ru-thiazole derivative with serum proteins and absorption-release studies with acryloyl and silica hydrogels as carriers in physiological media.

The reaction of [Ru2(CO)6Cl4], 1, with excess THZ (1,3-thiazole) in absolute ethanol at 55 degrees C produces fac-[Ru(CO)3Cl2(THZ)], 2, in high yield. [Ru(CO)2Cl2(THZ)2], 3, is formed at higher temperature (ca 70 degrees C) and higher concentration of THZ. The X-ray structures of the new compounds have been determined, and density functional studies performed at the hybrid B3LYP/(Lanl2DZ, Ru; 6-311+G**, CHClNOS) level allowed the estimation of the structures of several conformers as well as that of their relative total electronic energies.

ESI mass spectrometry and X-ray diffraction studies of adducts between anticancer platinum drugs and hen egg white lysozyme.

The interactions of cisplatin and its analogues, transplatin, carboplatin and oxaliplatin, with hen egg white lysozyme were analysed through ESI mass spectrometry, and the resulting metallodrug-protein adducts identified; the X-ray crystal structure of the cisplatin lysozyme derivative, solved at 1.9 A resolution, reveals selective platination of imidazole Nepsilon of His15.

Antimalarial properties of green tea.

We show here that a crude extract of green tea as well as two of its main constituents, epigallocatechin-3-gallate (EGCG) and epicatechin gallate (ECG), strongly inhibit Plasmodium falciparum growth in vitro. Both these catechins are found to potentiate the antimalarial effects of artemisinin without interfering with the folate pathway. The importance of these findings and their mechanistic implications are discussed in view of future therapeutic strategies.

Coffee consumption and risk of coronary heart disease: a meta-analysis.

Background And Aims: During the past three decades the relationship between habitual coffee drinking and coronary heart disease (CHD) has been assessed in numerous studies, with conflicting results. The aim of this study was to systematically examine the data published on the association between habitual coffee consumption and risk of CHD.

Methods And Results: Thirteen case-control and 10 cohort studies were included.

Structural and solution chemistry, antiproliferative effects, and DNA and protein binding properties of a series of dinuclear gold(III) compounds with bipyridyl ligands.

A series of six dinuclear gold(III) oxo complexes with bipyridyl ligands, of general formula [Au2(N,N)2(mu-O)2][PF6]2 (Auoxo1-Auoxo6) [where N,N = 2,2'-bipyridine (1), 4,4'-di-tert-butyl- (2), 6-methyl- (3), 6-neopentyl- (4), 6-(2,6-dimethylphenyl)- (5), 6,6'-dimethyl-2,2'-bipyridine (6)], were investigated as potential cytotoxic and anticancer agents, and their antiproliferative properties were evaluated in vitro toward the reference A2780 human ovarian carcinoma cell line. While five compounds manifested moderate cytotoxic properties (with IC50 approximately 10-30 microM), the sixth one (Auoxo6), turned out to be approximately 5-15 times more active against both cell lines and will merit further pharmacological studies. The interactions of Auoxo1 and Auoxo6 with a few model proteins (serum albumin, cytochrome c, ubiquitin) and with calf thymus DNA were analyzed in detail by various spectroscopic methods.

A model of insulin resistance and nonalcoholic steatohepatitis in rats: role of peroxisome proliferator-activated receptor-alpha and n-3 polyunsaturated fatty acid treatment on liver injury.

Insulin resistance induces nonalcoholic fatty liver disease and nonalcoholic steatohepatitis (NASH). We used a high-fat, high-calorie solid diet (HFD) to create a model of insulin resistance and NASH in nongenetically modified rats and to study the relationship between visceral adipose tissue and liver. Obesity and insulin resistance occurred in HFD rats, accompanied by a progressive increase in visceral adipose tissue tumor necrosis factor (TNF)-alpha mRNA and in circulating free fatty acids.

Low adherence of a clinically healthy Italian population to nutritional recommendations for primary prevention of chronic diseases.

Background And Aim: Several data demonstrated that dietary habits significantly affect the health state of the population. During recent years all the major scientific associations have provided nutritional recommendations for primary prevention of chronic diseases but few data are available about prevalence of adherence to these recommendations in an otherwise healthy population. The aims of this study were to evaluate dietary habits, and to assess the adherence of the general population to the recommendations for correct nutritional behaviour.

[Cardiac morphology and performance alterations and analysis of determinant factors of left ventricular hypertrophy in 40 patients with acromegaly].

Acromegaly has a high mortality rate due mainly to cardiovascular complications. The aim was to evaluate the determinant factors of left ventricular hypertrophy (LVH) and cardiac alterations in 40 acromegalic patients submitted to clinical-laboratorial studies and echocardiogram. The variables analyzed were age, sex, disease duration, arterial hypertension (AH), impaired glucose tolerance/DM, previous treatment with octreotide, GH and %IGF-I.

Prolonged n-3 polyunsaturated fatty acid supplementation ameliorates hepatic steatosis in patients with non-alcoholic fatty liver disease: a pilot study.

Background: Recent studies suggest a role of n-3 long-chain polyunsaturated fatty acids (n-3 PUFA) as peroxisome proliferator-activated receptor-alpha ligands in improving non-alcoholic fatty liver disease (NAFLD) in rodents. However, data in humans are still lacking.

Aim: To evaluate the efficacy of prolonged PUFA supplementation in patients with NAFLD.

Changes in neuropeptide FF and NPY immunohistochemical patterns in rat brain under heroin treatment.

Immunohistochemical distribution patterns of neuropeptide FF (NPFF) and neuropeptide tyrosine (NPY) were studied in the brain of rats submitted to two different protocols of heroin treatment. In drug-naive rats, acutely injected heroin significantly depleted NPFF-immunoreactive material within the neurons of the nucleus of solitary tract (NTS), significantly decreased the density of NPFF-immunoreactive nerve fibers within the median eminence, pituitary stalk, and neurohypophysis, and markedly increased NPY-immunoreactive neurons and nerve fibers in the thalamic paraventricular nucleus and bed nucleus of stria terminalis. In drug-sensitized rats, heroin significantly increased the number and immunostaining intensity of the NPFF-immunoreactive neurons within the NTS and induced minor changes in the NPFF-immunoreactive nerve fiber network of the median eminence, pituitary stalk, and neurohypophysis and a relatively minor increase in NPY neurons in the thalamic paraventricular nucleus and bed nucleus of stria terminalis.

Etiologic aspects and management of acromegaly.

Acromegaly is a systemic disease with various etiologies. It can occur as a sporadic or, more rarely, as a familial disease. Numerous complications such as endocrine, cardiovascular, respiratory, metabolic, osteoarticular and neoplastic disturbances occur and must be taken into account when establishing a therapeutic strategy.

The reaction of artemisinins with hemoglobin: a unified picture.

The reactions with hemoglobin of artemisinin and of its parent compounds, sodium artesunate and dihydroartemisinin, were investigated by visible absorption spectroscopy under standard solution conditions (50 mM phosphate buffer, pH 7, 37 degrees C). Notably, these antimalarial drugs were found to react with hemoglobin (i.e.

Carbonic anhydrase inhibitors: Inhibition of the tumor-associated isozymes IX and XII with polyfluorinated aromatic/heterocyclic sulfonamides.

The tumor-associated transmembrane carbonic anhydrase (CA, EC 4.2.1.

Heroin sensitization induces circumventricular organ activation in the rat brain.

Using c-Fos protein immunohistochemistry we previously demonstrated various sites of activation in the rat forebrain according to the animal's drug history. This study originates from a more detailed evaluation ex-post of the same specimens. A discrete number of c-Fos protein immunoreactive nuclei could be observed in some circumventricular organs, including the vascular organ of terminal lamina (OVLT) and subfornical organ (SFO) and in the nucleus of solitary tract near the area postrema, but only in specimens from sensitized rats.

Carbonic anhydrase inhibitors: design of thioureido sulfonamides with potent isozyme II and XII inhibitory properties and intraocular pressure lowering activity in a rabbit model of glaucoma.

A new series of thioureido-substituted sulfonamides were prepared by reacting 4-isothiocyanato- or 4-isothiocyanatoethyl-benzenesulfonamide with amines, hydrazines, or amino acids bearing moieties that can lead to an enhanced hydrosolubility, such as 2-dimethylamino-ethylamine, fluorine-containing aromatic amines/hydrazines, an aminodiol, heterocyclic polyamines (derivatives of morpholine and piperazine), 4-aminobenzoic acid, or natural amino acids (Gly, Cys, Asn, Arg, and Phe). The new compounds showed good inhibitory properties against three physiologically relevant carbonic anhydrase (CA, EC 4.2.

The S-thiolating activity of membrane gamma-glutamyltransferase: formation of cysteinyl-glycine mixed disulfides with cellular proteins and in the cell microenvironment.

Previous studies have documented that activity of the plasma membrane enzyme gamma-glutamyltransferase (GGT) is accompanied by prooxidant processes, with production of reactive oxygen species and oxidation of cellular protein thiols. The present work was aimed to verify the occurrence and extent of S-thiolation mediated by GGT and characterize the molecular species involved in mixed disulfide formation. Experiments show that the cysteinyl-glycine (CG) originating from cellular GGT-mediated glutathione (GSH) metabolism can efficiently thiolate cellular proteins, as well as proteins present in the extracellular environment.

Endothelial nitric oxide synthase -786T>C, but not 894G>T and 4a4b, polymorphism influences plasma homocysteine concentrations in persons with normal vitamin status.

Background: Nitric oxide (NO) plays a relevant role in various events during atherogenesis. In vitro data suggest that NO may modulate homocysteine (Hcy) concentrations. The aim of this study was to investigate the role of endothelial nitric oxide synthase (eNOS) -786T>C, 894G>T, and 4a4b polymorphisms in influencing Hcy concentrations.

Oxidative stress stimulates proliferation and invasiveness of hepatic stellate cells via a MMP2-mediated mechanism.

Experimental evidence indicates that reactive oxygen species (ROS) are involved in the development of hepatic fibrosis; they induce hepatic stellate cells (HSC) proliferation and collagen synthesis. To address the role of matrix metalloproteinase (MMP)-2 in promoting HSC proliferation during hepatic injury, we investigated whether oxidative stress modulates the growth and invasiveness of HSC by influencing MMP-2 activation. Cell invasiveness and proliferation, which were studied using Boyden chambers and by counting cells under a microscope, were evaluated after treatment with a superoxide-producing system, xanthine plus xanthine oxidase (X/XO), in the presence or absence of antioxidants and MMP inhibitors.

Carbonic anhydrase inhibitors. Zonisamide is an effective inhibitor of the cytosolic isozyme II and mitochondrial isozyme V: solution and X-ray crystallographic studies.

The antiepileptic drug zonisamide was considered to act as a weak inhibitor of the zinc enzyme carbonic anhydrase (CA, EC 4.2.1.

Guanylin-immunoreactive cells in the female and male rat adenohypophysis and their changes under various physiological and experimental conditions.

The peptide guanylin, first isolated from rat small intestine, is involved in the regulation of water-electrolyte transport between the intracellular and extracellular compartments of the epithelia. The main sites of guanylin expression are the intestinal, airway, or exocrine gland ductal epithelia where guanylin acts in a paracrine/luminocrine fashion. Because guanylin also circulates in the blood, sources of this peptide were sought in endocrine glands.

Carbonic anhydrase inhibitors: X-ray crystal structure of a benzenesulfonamide strong CA II and CA IX inhibitor bearing a pentafluorophenylaminothioureido tail in complex with isozyme II.

N-1-(4-Sulfamoylphenyl)-N-4-pentafluorophenyl-thiosemicarbazide was prepared by the reaction of 4-isothiocyanato-benzenesulfonamide with pentafluorophenyl hydrazine, and proved to be an effective inhibitor of several isozymes of the zinc enzyme carbonic anhydrase (CA, EC 4.2.1.

Carbonic anhydrase inhibitors: synthesis and inhibition of cytosolic/membrane-associated carbonic anhydrase isozymes I, II, and IX with sulfonamides incorporating hydrazino moieties.

Targeting proteins overexpressed in hypoxic tumors is as an important means of controlling cancer disease. One such protein is the carbonic anhydrase (CA) isoenzyme IX, which in some types of tumors is overexpressed 150-200-fold. We report here a series of sulfonamide derivatives, prepared from 2-carbohydrazido- and 4-carbohydrazido-benzenesulfonamides, which were further derivatized by reaction with aryl isocyanates or arylsulfonyl isocyanates.

Dietary habits, lifestyle and cardiovascular risk factors in a clinically healthy Italian population: the 'Florence' diet is not Mediterranean.

Objective: To evaluate dietary habits and lifestyle of Italian subjects, to provide current data on adequacy of the nutritional guidelines and recommendations especially in relation to primary prevention of cardiovascular diseases and to assess the influence of dietary habits on lipid profile and homocysteine levels.

Design: Cross-sectional.

Setting: Population-based study.