Molecular mechanisms of endothelial dysfunction: from nitric oxide synthesis to ADMA inhibition.

Endothelial dysfunction symbolizes several pathological conditions, including altered anticoagulant and anti-inflammatory properties of the endothelium, impaired modulation of vascular growth, and dysregulation of vascular remodeling. Nevertheless, this term has been used commonly to refer to an impairment of endothelium-dependent vasorelaxation caused by a loss of nitric oxide bioactivity. The clinical and scientific relevance of nitric oxide synthesis and bioavailability in endothelial dysfunction is based on the fact that it is a common factor in the pathogenesis of cardiovascular diseases.

Efficient inhibition of iron superoxide dismutase and of Trypanosoma cruzi growth by benzo[g]phthalazine derivatives functionalized with one or two imidazole rings.

The synthesis and trypanosomatic behavior of a new series of 1,4-bis(alkylamino)benzo[g]phthalazines 1- 4 containing the biologically significant imidazole ring are reported. In vitro antiparasitic activity against Trypanosoma cruzi epimastigotes is remarkable, especially for compound 2, whereas toxicity against Vero cells is very low. Conversion of epimastigotes to metacyclic forms in the presence of the tested compounds causes significant decreases in the amastigote and trypomastigote numbers.

Fuzzy association rules for biological data analysis: a case study on yeast.

Background: Last years' mapping of diverse genomes has generated huge amounts of biological data which are currently dispersed through many databases. Integration of the information available in the various databases is required to unveil possible associations relating already known data. Biological data are often imprecise and noisy.

Tumor protein 53-induced nuclear protein 1 expression is repressed by miR-155, and its restoration inhibits pancreatic tumor development.

Pancreatic cancer is a disease with an extremely poor prognosis. Tumor protein 53-induced nuclear protein 1 (TP53INP1) is a proapoptotic stress-induced p53 target gene. In this article, we show by immunohistochemical analysis that TP53INP1 expression is dramatically reduced in pancreatic ductal adenocarcinoma (PDAC) and this decrease occurs early during pancreatic cancer development.

Discovery of 1,1-dioxo-1,2,6-thiadiazine-5-carboxamide derivatives as cannabinoid-like molecules with agonist and antagonist activity.

A series of new 2-substituted 1,1-dioxo-1,2,6-thiadiazine-5-carboxylate derivatives have been prepared from monosubstituted sulfamides in order to obtain N-substituted 1,1-dioxo-1,2,6-thiadiazine-5-carboxamides as novel cannabinoid derivatives, analogues of Rimonabant (SR141716A). Their potential functional activity on cannabinoid receptors has been evaluated in vitro and in vivo in mice, showing that two compounds (37 and 39) behave as cannabinoid agonists in vitro. Their potency is lower than that of the reference compound, WIN 55,212-2, but their efficacy is similar to that of this cannabinoid agonist, although no in vivo activity is observed.

[Reflections on 250 interventions for colorectal carcinoma metastases to the liver].

Introduction: The best results in the treatment of colorectal cancer metastases to the liver are currently achieved with surgical resection performed under high quality standards. OBJECTIVES. To analyze the results and quality standards of the surgical treatment of colorectal cancer liver metastases in a referral liver unit over an 11-year period.

Metformin plus low-dose glimeperide significantly improves Homeostasis Model Assessment for insulin resistance (HOMA(IR)) and beta-cell function (HOMA(beta-cell)) without hyperinsulinemia in patients with type 2 diabetes mellitus.

Objective: Type 2 diabetes mellitus is characterized by insulin resistance and defects in insulin secretion from pancreatic beta-cells, which have been studied by using euglycemic/hyperinsulinemic clamps. However, it is difficult to study insulin resistance and beta-cell failure by these techniques in humans. Therefore, the aim of this study was to evaluate the effect of three different antidiabetic therapeutic regimens on insulin resistance and beta-cell activity by using a mathematical model, Homeostasis Model Assessment for insulin resistance (HOMA(IR)) and beta-cell function (HOMA(beta-cell)).

Effect of cigarette smoking on the oxidant/antioxidant balance in healthy subjects.

Background And Purpose: Cigarette smoking has been associated with the development of cardiovascular disease and cancer. Even though the molecular mechanism(s) are not clear, the pathology has been related to oxygen free radicals present in cigarette smoke. Thus, the main objective of this study was to establish the changes in the oxidation/antioxidation balance induced by cigarette smoking.

Possibilistic approach for biclustering microarray data.

Biclustering has emerged as an important method for analyzing gene expression data from microarray technology. It allows to identify groups of genes which behave similarly under a subset of conditions. As a gene may play more than one biological role in conjunction with distinct groups of genes, non-exclusive biclustering algorithms are required.

GintMT1 encodes a functional metallothionein in Glomus intraradices that responds to oxidative stress.

A full-length metallothionein (MT) gene (GintMT1) was isolated from Glomus intraradices extraradical mycelium. This is the first MT gene reported in the genus Glomus, third in the Glomeromycota. Functional analysis of GintMT1 in a MT-defective Saccharomyces cerevisiae strain indicates that it encodes a functional MT.

Colitis and colitis-associated cancer are exacerbated in mice deficient for tumor protein 53-induced nuclear protein 1.

Tumor protein 53-induced nuclear protein 1 (TP53INP1) is an antiproliferative and proapoptotic protein involved in cell stress response. To address its physiological roles in colorectal cancer and colitis, we generated and tested the susceptibility of Trp53inp1-deficient mice to the development of colorectal tumors induced by injection of the carcinogen azoxymethane followed by dextran sulfate sodium (DSS)-induced chronic colitis. Trp53inp1-deficient mice showed an increased incidence and multiplicity of tumors compared to those of wild-type (WT) mice.

Novel sulfamide analogs of oleoylethanolamide showing in vivo satiety inducing actions and PPARalpha activation.

Long chain saturated and unsaturated alkyl sulfamide and propyl sulfamide derivatives, analogs of oleoylethanolamide, have been synthesized and evaluated in vivo and in vitro as peroxisome proliferator activated receptor alpha (PPARalpha) activators. Additionally, the anorexic effects of the new compounds have been studied in vivo in food-deprived rats. Among the active compounds N-octadecyl-N'-propylsulfamide (7) has been identified as a potent hypolipidemic compound, a potent feeding suppressant, and a concentration-dependent activator of PPARalpha.

1,4-Bis(alkylamino)benzo[g]phthalazines able to form dinuclear complexes of Cu(II) which as free ligands behave as SOD inhibitors and show efficient in vitro activity against Trypanosoma cruzi.

The synthesis of a new series of 1,4-bis(alkylamino)benzo[g]phthalazines 1-3 is reported, and their ability to form dinuclear complexes with Cu(II) assayed. The geometry of the complexes is dependent on the nature of the electron-donor sites at the sidechains. Compounds 1 and 2, that contain sp3 or sp2 nitrogens at the end of the alkylamino groups, originate monopodal dinuclear complexes which seem to include endogenous OH bridges, and the sidechains seem to actively participate in complexation.

Identification of a gene from the arbuscular mycorrhizal fungus Glomus intraradices encoding for a 14-3-3 protein that is up-regulated by drought stress during the AM symbiosis.

In the present study, a 14-3-3 protein-encoding gene from Glomus intraradices has been identified after differential hybridization of a cDNA library constructed from the fungus growing in vitro and subjected to drought stress by addition of 25% PEG 6000. Subsequently, we have studied its expression pattern under drought stress in vitro and also when forming natural symbioses with different host plants. The results obtained suggest that Gi14-3-3 gene may be involved in the protection that the arbuscular mycorrhizal (AM) symbiosis confers to the host plant against drought stress.

Competition and substrate colonization strategies of three polyxenically grown arbuscular mycorrhizal fungi.

Intra- and extraradical colonization competition and hyphal interactions among arbuscular mycorrhizal fungi (AMF) Glomus intraradices, Glomus proliferum and Gigaspora margarita were investigated in two in vitro experimental systems. AMF were polyxenically cultured with a Ri T-DNA transformed carrot root organ culture (ROC) in either big Petri plates containing three culture compartments and a common hyphal compartment (i.e.

Interactions between the arbuscular mycorrhizal (AM) fungus Glomus intraradices and nontransformed tomato roots of either wild-type or AM-defective phenotypes in monoxenic cultures.

Monoxenic symbioses between the arbuscular mycorrhizal (AM) fungus Glomus intraradices and two nontransformed tomato root organ cultures (ROCs) were established. Wild-type tomato ROC from cultivar "RioGrande 76R" was employed as a control for mycorrhizal colonization and compared with its mutant line (rmc), which exhibits a highly reduced mycorrhizal colonization (rmc) phenotype. Structural features of the two root lines were similar when grown either in soil or under in vitro conditions, indicating that neither monoxenic culturing nor the rmc mutation affected root development or behavior.

An integral approach to substance abuse.

There is a pressing need in the substance abuse field for more comprehensive models of etiology and treatment that address the complex issues of addiction, including the biological, social, cultural, spiritual and developmental needs of individuals and groups. This article presents a theoretical framework for an integral approach to substance abuse that expands on the existing biopsychosocial model. One contribution of the model is an integrated approach to spirituality from a cross-cultural perspective.

Differential morphogenesis of the extraradical mycelium of an arbuscular mycorrhizal fungus grown monoxenically on spatially heterogeneous culture media.

A new in vitro experimental system was developed to study the morphogenesis of discrete regions of a single extraradical mycelium of the arbuscular mycorrhizal (AM) fungus Glomus intraradices, growing simultaneously in six different agar-based media. The media were (i) unamended water agar (WA), (ii) WA+PO(4)(3-) (PO(4)(3-)), (iii) WA+NO(3)(-) (NO(3)(-)), (iv) WA+NH(4)(+) (NH(4)(+)), (v) WA+NH(4)(+)+MES (NH(4)(+)+MES) and (vi) minimal medium (M, complete nutrients). Each medium was amended with the pH indicator bromocresol purple.

Increased serum malondialdehyde and decreased nitric oxide within 24 hours of thrombotic stroke onset.

Background And Purpose: Ischemia/reperfusion generates free oxygen radicals, which react with the unsaturated lipids of biomembranes resulting in the generation products such as malondialdehyde. Malondialdehyde could be a sensor for tissue damage and reperfusion. Nitric oxide, released due to the early arrival of leukocytes in the brain parenchyma, could be a sensor for nonflow phenomenon.

Trimetazidine diminishes fasting glucose in rats with fasting hyperglycemia: a preliminary study.

Trimetazidine is a drug with cardioprotective properties used in coronary artery disease. Its effect has been attributed to the inhibition of the long chain fatty acids intramitochondrial transport via carnitine-palmitoyl-transferase-1. Clinical evidence supports the possibility that trimetazidine is able to improve the fasting glycemia in diabetic patients.

Sweeteners and beta-glucans improve metabolic and anthropometrics variables in well controlled type 2 diabetic patients.

Unlabelled: The introduction of fat and carbohydrates replacers has been a revolutionary advance in treating obesity and diabetes mellitus. Since these materials have shown to have beneficial effects on the metabolic profiles of diabetic patients, they should be useful in designing specific foods for patients with diabetes.

Objective: To compare metabolic and anthropometric improvements elicited by a diet based on the American Diabetic Association's nutrition recommendations with a modified, low-energy diet incorporating fat replacers and non-sucrose sweeteners.

Resolution of epiphora with nasolacrimal stents: results of long-term follow-up in a multicenter prospective study.

Purpose: To evaluate in a prospective, multicenter setting the long-term effectiveness of polyurethane stents in the percutaneous management of epiphora.

Materials And Methods: Patients (n = 426; age range, 19-88 years, mean, 48; 91 men, 335 women) with severe epiphora had stents (470 eyes/496 stents) inserted to treat unilateral or bilateral and complete or partial obstruction of the nasolacrimal system. The etiology of the obstruction was idiopathic in 280 cases (59.

Fentanyl and its analogue N-(1-phenylpyrazol-3-yl)-N-[1-(2-phenylethyl)-4-piperidyl]propanamide: 1H- and 13C-NMR spectroscopy, X-ray crystallography, and theoretical calculations.

The oxalate salts and free bases of fentanyl and N-[1-(2-phenylethyl)-4-piperidyl]-N-(1-phenyl-4-pyrazolyl)propanamide, a new lead compound for long-acting analgesia, have been characterized by (1)H- and (13)C-NMR spectroscopy. The crystal structure of the hydrochloride of N-[1-(2-phenylethyl)-4-piperidyl]-N-(1-phenyl-4-pyrazolyl)propanamide monohydrate has been determined. Two centrosymmetrically related cations, joined through C(phenyl)-H em leader pi contacts, encapsulate a large void that contains pairs of anions and bridged water molecules into a zero-dimensional (0D) supramolecular motif.