Suppression of antifolate resistance by targeting the myosin Va trafficking pathway in melanoma.

Human melanoma is a significant clinical problem. As most melanoma patients relapse with lethal drug-resistant disease, understanding and preventing mechanism(s) of resistance is one of the highest priorities to improve melanoma therapy. Melanosomal sequestration and the cellular exportation of cytotoxic drugs have been proposed to be important melanoma-specific mechanisms that contribute to multidrug resistance in melanoma.

Periodontal status affects C-reactive protein and lipids in patients with stable heart disease from a tertiary care cardiovascular clinic.

Background: There are scarce data on the impact of the periodontal condition in the control of biomarkers in patients with cardiovascular disease (CVD). The aim of this study is to assess whether periodontal inflammation and tissue breakdown are associated with C-reactive protein (CRP) and lipids in patients with stable heart disease.

Methods: This cross-sectional study included 93 patients with stable coronary artery disease (57 males; mean age: 63.

Directed phenotype switching as an effective antimelanoma strategy.

Therapeutic resistance in melanoma and other cancers arises via irreversible genetic, and dynamic phenotypic, heterogeneity. Here, we use directed phenotype switching in melanoma to sensitize melanoma cells to lineage-specific therapy. We show that methotrexate (MTX) induces microphthalmia-associated transcription factor (MITF) expression to inhibit invasiveness and promote differentiation-associated expression of the melanocyte-specific Tyrosinase gene.

Contribution of hospital effluents to the load of pharmaceuticals in urban wastewaters: identification of ecologically relevant pharmaceuticals.

The impact of effluent wastewaters from four different hospitals: a university (1456 beds), a general (350 beds), a pediatric (110 beds) and a maternity hospital (96 beds), which are conveyed to the same wastewater treatment plant (WWTP), was evaluated in the receiving urban wastewaters. The occurrence of 78 pharmaceuticals belonging to several therapeutic classes was assessed in hospital effluents and WWTP wastewaters (influent and effluent) as well as the contribution of each hospital in WWTP influent in terms of pharmaceutical load. Results indicate that pharmaceuticals are widespread pollutants in both hospital and urban wastewaters.

Development of a simple analytical method for the simultaneous determination of paracetamol, paracetamol-glucuronide and p-aminophenol in river water.

Paracetamol is among the most worldwide consumed pharmaceuticals. Although its occurrence in the environment is well documented, data about the presence of its metabolites and transformation products is very scarce. The present work describes the development of an analytical method for the simultaneous determination of paracetamol, its principal metabolite (paracetamol-glucuronide) and its main transformation product (p-aminophenol) based on solid phase extraction (SPE) and high performance liquid chromatography coupled to diode array detection (HPLC-DAD).

Molecular characterization of calcineurin B from the non-virulent Trypanosoma rangeli kinetoplastid indicates high gene conservation.

Calcineurin B, the regulatory subunit of calcineurin, a serine/threonine protein phosphatase, is highly conserved throughout the evolutionary scale including trypanosomatids such as Trypanosoma cruzi, and Leishmania major. Thus, in these flagellates the protein is required for mammalian host cell invasion and virulence and stress responses. With the aim of determining the presence of calcineurin B in Trypanosoma rangeli, a non-virulent trypanosome for mammals, the respective gene was amplified by PCR, cloned and sequenced.

Fast and sensitive UHPLC methods with fluorescence and tandem mass spectrometry detection for the determination of tetracycline antibiotics in surface waters.

In this paper two fast and highly sensitive ultra-high performance liquid chromatography (UHPLC) methods for the determination of tetracycline antibiotics (oxytetracycline, tetracycline, doxycycline, demeclocycline, chlortetracycline, minocycline and degradation product epitetracycline) in surface waters have been developed using fluorescence (FL) and mass spectrometry (MS) detection. ACQUITY UPLC BEH C8 and ACQUITY CSH C18 columns were employed for FL and MS detection, respectively, both packed with 1.7μm particles.

Assessment of oxidative status markers and NO bioavailability in hypertensive disorders of pregnancy.

The systemic oxidative status in hypertensives disorders of pregnancy (HDP) and its association with endothelial dysfunction is controversial. In the present study, we evaluated systemic plasma levels of oxidative stress markers (TBARS (thiobarbituric acid-reactive substances) and carbonyl) and total antioxidant status (FRAP (ferric reducing ability of plasma (ferric reducing/antioxidant power) and reduction of MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide))), as well as assessed the impact these markers have on nitric oxide (NO) status in healthy pregnant (HP, n=38), gestational hypertensive (GH, n=33) and preeclamptic pregnant women (PE, n=28). We found similar values of TBARS among all groups, and reduced carbonyl levels in HDP between the PE and GH.

Reactivation of the tumour suppressor RASSF1A in breast cancer by simultaneous targeting of DNA and E2F1 methylation.

Background: Tumour suppressor genes are often transcriptionally silenced by promoter hypermethylation, and recent research has implicated alterations in chromatin structure as the mechanistic basis for this repression. In addition to DNA methylation, other epigenetic post-translational modifications that modulate the stability and binding of specific transcription factors to gene promoters have emerged as important mechanisms for controlling gene expression. The aim of this study was to analyse the implications of these mechanisms and their molecular connections in the reactivation of RASSF1A in breast cancer.

[Family violence and mental health in adolescence: complex trauma as a developmental disorder].

Aim: To highlight the harmfulness and pervasive of early and repeated exposure to family violence from the theoretical perspective of complex trauma as a developmental disorder.

Method: A study carried out on a sample of 22 adolescents between the ages of 15 and 18, who have been entrusted to Il Faro Bologna, a Specialist Centre for child abuse and neglect. Specific areas of psychological functioning were examined.

[Mortality due to Road Traffic Accidents in Brazil in the last decade: trends and risk clusters].

Objective: To analyze the temporal trends of mortality due to Road Traffic Accidents (RTA) as well as identify the existence and location of high risk death clusters for RTA using spatial analysis.

Methodology: Descriptive study of temporal trends by RTA, pedestrians, motorcyclists, motorists and passengers and spatial analysis for 2000 and 2010. The data was obtained from the Mortality Information System, and standardized rates were calculated by age in Brazilian states and municipalities grouped by population size.

Clinical and neuropsychological correlation in patients with rolandic epilepsy.

Objectives: To evaluate the presence of neurological soft signs (NSS) and to correlate them with the Wechsler Intelligence Scale for Children (WISC III) in patients with rolandic epilepsy (RE).

Methods: Forty children and adolescents aged between 9 and 15 years were studied. They were divided into two groups: G1 - patients with RE (n=20) - and G2 - healthy controls without epilepsy (n=20).

Pilot monitoring study of ibuprofen in surface waters of north of Portugal.

Ibuprofen is amongst the most worldwide consumed pharmaceuticals. The present work presents the first data in the occurrence of ibuprofen in Portuguese surface waters, focusing in the north area of the country, which is one of the most densely populated areas of Portugal. Analysis of ibuprofen is based on pre-concentration of the analyte with solid phase extraction and subsequent determination with liquid chromatography coupled to fluorescence detection.

The AChE membrane-binding tail PRiMA is down-regulated in muscle and nerve of mice with muscular dystrophy by merosin deficiency.

Since Duchenne muscular dystrophy was attributed to mutations in the dystrophin gene, more than 30 genes have been found to be causally related with muscular dystrophies, about half of them encoding proteins of the dystrophin-glycoprotein complex (DGC). Through laminin-2, the DGC bridges the muscle cytoskeleton and the extracellular matrix. Decreased levels of PRiMA-linked acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) have been observed in dystrophic muscle and nerve of dystrophin-deficient (mdx) and laminin-2 deficient (Lama2dy) mice.

Increase in gastric pH reduces hypotensive effect of oral sodium nitrite in rats.

The new pathway nitrate-nitrite-nitric oxide (NO) has emerged as a physiological alternative to the classical enzymatic pathway for NO formation from l-arginine. Nitrate is converted to nitrite by commensal bacteria in the oral cavity and the nitrite formed is then swallowed and reduced to NO under the acidic conditions of the stomach. In this study, we tested the hypothesis that increases in gastric pH caused by omeprazole could decrease the hypotensive effect of oral sodium nitrite.

Neuropsychological assessment of children with rolandic epilepsy: executive functions.

Rolandic epilepsy (RE) is the most common type of childhood focal epilepsy. Although there is no intellectual deficit, children with RE may have specific cognitive impairments. The aims of this study were to identify changes in executive functions in children with RE and to verify the influence of epilepsy and seizure variables.

Pain pressure threshold algometry of the abdominal wall in healthy women.

The objective of this study was to determine the inter- and intra-examiner reliability of pain pressure threshold algometry at various points of the abdominal wall of healthy women. Twenty-one healthy women in menacme with a mean age of 28 ± 5.4 years (range: 19-39 years) were included.

Melanoma coordinates general and cell-specific mechanisms to promote methotrexate resistance.

Melanoma, the most aggressive form of skin cancer, is notoriously resistant to all current modalities of cancer therapy, including to the drug methotrexate. Melanosomal sequestration and cellular exportation of methotrexate have been proposed to be important melanoma-specific mechanisms that contribute to the resistance of melanoma to methotrexate. In addition, other mechanisms of resistance that are present in most epithelial cancer cells are also operative in melanoma.

Optimizing potentiometric ionophore and electrode design for environmental on-site control of antibiotic drugs: application to sulfamethoxazole.

Potentiometric sensors are typically unable to carry out on-site monitoring of environmental drug contaminants because of their high limits of detection (LODs). Designing a novel ligand material for the target analyte and managing the composition of the internal reference solution have been the strategies employed here to produce for the first time a potentiometric-based direct reading method for an environmental drug contaminant. This concept has been applied to sulfamethoxazole (SMX), one of the many antibiotics used in aquaculture practices that may occur in environmental waters.

Percutaneous occlusion of left atrial appendage with the Amplatzer Cardiac PlugTM in atrial fibrillation.

Background: Atrial fibrillation is associated with embolic strokes that often result in death or disability. Effective in reducing these events, anticoagulation has several limitations and has been widely underutilized. Over 90% of thrombi identified in patients with atrial fibrillation without valvular disease originate in the left atrial appendage, whose occlusion is investigated as an alternative to anticoagulation.

Antihypertensive and antioxidant effects of a single daily dose of sodium nitrite in a model of renovascular hypertension.

Dietary nitrite and nitrate have been reported as alternative sources of nitric oxide (NO). In this regard, we reported previously that sodium nitrite added to drinking water was able to exert antihypertensive effects in an experimental model of hypertension in a dose-dependent manner. Taking into consideration that nitrite is continuously converted to nitrate in the bloodstream, here we expanded our previous report and evaluate whether a single daily dose of sodium nitrite could exert antihypertensive effects in 2 kidney-1 clip (2K1C) hypertensive rats.

Hard palate dimensions in nasal and mouth breathers from different etiologies.

Purpose: To compare the hard palate dimensions of nasal-breathing children, mouth breathers from obstructive etiology, and habitual mouth breathers.

Methods: The sample comprised 76 children, 37 boys and 39 girls, with mean age of 9.32±1.

Influence of the enzyme phosphorylation state and the substrate on PKA enzyme dynamics.

cAMP-dependent protein kinase (PKA) is one of the simplest and best understood members of the protein kinase family. In a previous study, we have theoretically studied the complex between PKA and the heptapeptide substrate Kemptide by classical molecular dynamics. On the basis of the results obtained for Kemptide, the aim of the present work is to explore how the different conditions, such as phosphorylation state, substrate, and mutations of key residues affect the enzyme dynamics.

Trichilemmal carcinoma: case report.

The trichilemmal carcinoma is a rare tumor that usually occurs on sun-exposed skin, especially on the face, scalp, neck and back of hands, mainly in elderly subjects but commonly between the 4th and 9th decades of life. It is not a gender-based illness. This study shows a difficult to treat case of recurrent trichilemmal carcinoma on the same location of a basal-cell carcinoma previously treated with surgery and radiotherapy.

Identification, characterization and antigenicity of the Plasmodium vivax rhoptry neck protein 1 (PvRON1).

Background: Plasmodium vivax malaria remains a major health problem in tropical and sub-tropical regions worldwide. Several rhoptry proteins which are important for interaction with and/or invasion of red blood cells, such as PfRONs, Pf92, Pf38, Pf12 and Pf34, have been described during the last few years and are being considered as potential anti-malarial vaccine candidates. This study describes the identification and characterization of the P.