Alterations in the extracellular catabolism of nucleotides are involved in the antiproliferative effect of quercetin in human bladder cancer T24 cells

Bladder cancer is the most prevalent tumor in the genitourinary tract and the current treatments are not efficient to prevent recurrence and progression of tumor cases. Studies have revealed evidence of the involvement of the purinergic system in bladder tumorigenesis, particularly ecto-5′-NT/CD73, the enzyme responsible for AMP hydrolysis. Quercetin (3,3′,4′,5,7-pentahydroxyflavone) is a plant-derived flavonoid that has been shown to exert a broad range of pharmacologic properties, including potential anticancer activity. Here, we investigated the quercetin effect on the E-NTPDases and ecto-5′-nucleotidase/CD73, which catalyzes the introversion of the extracellular purine nucleotides in T24 human bladder cancer cells. The results showed that this flavonoid was able to increase ADP hydrolysis and inhibit the ecto-5′-nucleotidase/CD73 activity, with no effect on protein expression. The treatment with APCP (α,β-methyleneadenosine-5′-diphosphate), another ecto-5′-NT/CD73 inhibitor, led to a significant reduction in cell proliferation. In addition, we showed that AMP, which can be accumulating by enzyme inhibition, had an antiproliferative effect on T24 cells, which was enhanced when its hydrolysis was inhibited by APCP treatment. Otherwise, adenosine did not cause any significant effect on cell proliferation and the quercetin effects were not altered by the simultaneous presence of adenosine. Taken together, the results suggest that the antiproliferative effect of quercetin on tumor cells may occur, at least in part, via alterations in the extracellular catabolism of nucleotides, that could be by AMP accumulation, or could be due to blocked adenosine receptors by this flavonoid, supporting the potential use of quercetin in bladder cancer treatment.     

Photodynamic antimicrobial chemotherapy (PACT) inhibits biofilm formation by Candida albicans,increasing both ROS production and membrane permeability

The opportunistic fungal Candida albicans is able to produce both superficial and systemic infections in immunocompromised patients. Photodynamic antimicrobial chemotherapy (PACT) is a process that combines visible light and a photosensitizer, producing reactive oxygen species (ROS) that can kill the treated cells and has been presented as a potential antimicrobial therapy. In this work, we study the effects of PACT, using toluidine blue (TB) as a photosensitizer drug, on ROS production and cell damage and the ability of C. albicans to form biofilm. A significant decrease was observed in the cell growth after PACT in a TB concentration-dependent manner. This effect was dependent on the incubation time after PACT. In addition, an increase in both the ROS production and cell permeability, after PACT, in a TB concentration-dependent manner was observed. PACT, using 0.1 mg/ml TB was able to reduce biofilm formation in 30, 50, and 62 %, in cells submitted to incubation times of 1, 2, and 3 h, respectively. These results suggested that PACT, using TB, is able to decrease both growth and biofilm formation by C. albicans, possibly by a mechanism evolving both ROS production and the increase in the cell permeability.     

Genetic Variation of North American Triatomines (Insecta: Hemiptera: Reduviidae): Initial Divergence between Species and Populations of Chagas Disease Vector

The triatomines vectors of Trypanosoma cruzi are principal factors in acquiring Chagas disease. For this reason, increased knowledge of domestic transmission of T. cruzi and control of its insect vectors is necessary. To contribute to genetic knowledge of North America Triatominae species, we studied genetic variations and conducted phylogenetic analysis of different triatomines species of epidemiologic importance. Our analysis showed high genetic variations between different geographic populations of Triatoma mexicana, Meccus longipennis, M. mazzottii, M. picturatus, and T. dimidiata species, suggested initial divergence, hybridation, or classifications problems. In contrast, T. gerstaeckeri, T. bolivari, and M. pallidipennis populations showed few genetics variations. Analysis using cytochrome B and internal transcribed spacer 2 gene sequences indicated that T. bolivari is closely related to the Rubrofasciata complex and not to T. dimidiata. Triatoma brailovskyi and T. gerstaeckeri showed a close relationship with Dimidiata and Phyllosoma complexes.     

Toriello Carey syndrome: genetic,clinical, and oral considerations: a case report

Toriello Carey syndrome is a rare recessive autosomal disease whose clinical manifestations are more evident in males. Some authors report that the general characteristics of this disease are agenesis of the corpus callosum, mental disability, convulsions, atrial septal defect, pulmonary artery stenosis, pyloric stenosis, and hypospadias. Facial and cranial alterations may occur, including hypertelorism, telecanthus, divergent strabismus, malformed ears, anteverted nares, retrognathism, and cleft palate. This paper reports on a 13‐year‐old male with Toriello Carey syndrome and leucoderma, and describes his oral problems and his dental care.     

Characteristics and mortality following primary percutaneous coronary intervention for acute myocardial infarction in Spain. Results from the TRIANA 1 (TRatamiento del Infarto Agudo de miocardio eN Ancianos) Registry

INTRODUCTION AND OBJECTIVES: Although more elderly patients will experience acute myocardial infarction (AMI) in coming years, the best reperfusion strategy in these patients remains unknown. PATIENTS AND METHOD: The Spanish TRIANA (TRatamiento del Infarto Agudo de miocardio eN Ancianos) registry was set up to determine the feasibility of performing a randomized study of percutaneous coronary intervention (PCI) versus thrombolysis in AMI patients aged > or =75 years. The TRIANA 1 subregistry included consecutive patients of all ages with ST-segment-elevation AMI (< or =12 h from onset) who underwent PCI in selected hospitals. RESULTS: In total, 459 TRIANA-1 patients were included at 25 hospitals over 3 months. Some 11% had cardiogenic shock. PCI was performed as rescue therapy in 24% and, in 15% because thrombolysis was contraindicated. After PCI, 83% had TIMI grade-3 flow without significant residual stenosis. Mortality at 1 month was 10.8%. Independent predictors of mortality identified by multivariate analysis were: cardiogenic shock at admission (OR, 7.2, 95% CI, 2.2-23.3), age (OR, 1.05 per year, 95% CI, 1.005-1.100), maximum creatine kinase MB fraction (OR, 1.01, 95% CI, 1.004-1.270) and post-PCI TIMI grade <3 (OR, 2.8, 95% CI, 1.0-8.3). Of 104 participants aged > or =75 years (mortality, 24%), 58 (55.7%) fulfilled criteria for inclusion in a randomized study. CONCLUSIONS: 1) The TRIANA 1 subregistry probably reflects the reality of PCI for AMI in Spain. 2) Mortality at 1 month was associated with classic predictive factors. 3) Some 50% of patients > or =75 years old who underwent PCI could be included in a randomized study. These findings indicate that randomized study to determine the best reperfusion strategy in elderly AMI patients is feasible.     

Decrease in Gastric Sensitivity to Distension by 5-HT1A Receptor Agonists in Rats

Using an in vivo model for evaluation of gastricsensitivity in awake rats, we aimed to determine whether5-hydroxytryptamine 1A (5-HT_1A) agonistsmodify pain threshold and gastric compliancespecifically through 5-HT_1A receptors. Isobaricgastric distensions were performed with a barostat usingsteps of 5 mm Hg in male rats equipped with a gastricballoon and electrodes implanted in the neck muscles.Gastric distension at 15 or 20 mm Hg induced a typicalposture associated with contractions of the neckmuscles. Rats received drugs 30 min before gastricdistension. The 5-HT receptor agonist8-hydroxy-2-(di-n-propylamino)tetra1A lin (8-OH-DPAT),administered intraperitoneally (0.5 mg/kg) increasedgastric pain threshold and gastric tone. These effectswere reproduced when administered centrally (0.05 mg/kg) and blocked by intracerebroventricularadministration of the 5-HT_1A antagonist WAY100635. Flesinoxan (4 mg/kg, intraperitoneally), another5-HT_1A agonist reproduced the effects of8-OH-DPAT on pain threshold and gastric tone and the alpha-receptorantagonist yohimbine did not modify the action of8-OH-DPAT. Our results indicate that activation of5-HT_1A receptors at the level of the centralnervous system increases gastric tone and decreases gastric sensitivityto distension.     

Autoradiographic localization of sigma opioid receptors in the gastrointestinal tract of the guinea pig

The distribution of sigma and phencyclindine binding sites in the gastrointestinal tract of the guinea pig was studied by autoradiography after in vitro incubation of tissue slices with (+)3H-SKF 10,047 and 3H-1-1-[(2-thienyl)cyclohexyl] piperidine to locate sigma and phencyclidine receptors, respectively. A dense distribution of sigma binding sites was observed in the mucosa and in the submucosal plexus, particularly at the level of the fundus and duodenum. Muscular layers were only marginally labeled. No phencyclidine binding site could be demonstrated in any area. This selective distribution suggests a functional role of sigma receptors mainly in the control of endocrine or exocrine secretions, or both.