Acetyl-L-Carnitine Prevents Methamphetamine-Induced Structural Damage on Endothelial Cells via ILK-Related MMP-9 Activity

Methamphetamine (METH) is a potent psychostimulant highly used worldwide. Recent studies evidenced the involvement of METH in the breakdown of the blood-brain-barrier (BBB) integrity leading to compromised function. The involvement of the matrix metalloproteinases (MMPs) in the degradation of the neurovascular matrix components and tight junctions (TJs) is one of the most recent findings in METH-induced toxicity. As BBB dysfunction is a pathological feature of many neurological conditions, unveiling new protective agents in this field is of major relevance. AcetylL-carnitine (ALC) has been described to protect the BBB function in different paradigms, but the mechanisms underling its action remain mostly unknown. Here, the immortalized bEnd.3 cell line was used to evaluate the neuroprotective features of ALC in METH-induced damage. Cells were exposed to ranging concentrations of METH, and the protective effect of ALC 1 mM was assessed 24 h after treatment. F-actin rearrangement, TJ expression and distribution, and MMPs activity were evaluated. Integrin-linked kinase (ILK) knockdown cells were used to assess role of ALC in ILK mediated METHtriggered MMPs’ activity. Our results show that METH led to disruption of the actin filaments concomitant with claudin-5 translocation to the cytoplasm. These events were mediated by MMP-9 activation in association with ILK overexpression. Pretreatment with ALC prevented METH-induced activation of MMP-9, preserving claudin-5 location and the structural arrangement of the actin filaments. The present results support the potential of ALC in preserving BBB integrity, highlighting ILK as a new target for the ALC therapeutic use.

Heparin-antivenom association: differential neutralization effectiveness in Bothrops atrox and Bothrops erythromelas envenoming

Heparin, in some regions of Brazil has been used in the treatment of bothropic accidents, but the data found in the literature are inconclusive about its effectiveness. The venoms of Bothrops atrox and of B. erythromelas were characterized according to their biological activities. The capacity of heparin in neutralizing these activities was tested with doses of 3 and 6 IU in isolated form and associated to Antibothropic Serum (ABS). It was verified that heparin, in doses of 3 and 6 IU, was not effective in neutralizing the desfibrinating and edema-forming activities of B. atrox venom and the hemorrhagic and coagulant actions of both venoms. Heparin diminished the effectiveness of the ABS in the neutralization of the hemorrhagic and edema-forming activities of the B. atrox venom. However, heparin in the 6 IU dose was capable of neutralize the edema-forming of the B. erythromelas and increase the effectiveness of the ABS. Heparin also neutralized the phospholipasic A2 activity of B. atrox (14.3%) and B. erythromelas (28.0%) venoms. For B. erythromelas venom, the associated treatment, heparin and ABS, was more effective in the neutralization of its lethal activity.

Strategic Drivers for Implementing Sustainability Programs in Portuguese Organizations– Let’s Listen to Aristotle: From Triple to Quadruple Bottom Line

This article describes a study that investigated the main strategic drivers that influence the implementation of sustainability/social responsibility programs. An online survey was administered to managers of Portuguese organizations with certified management systems. The findings suggest that the implementation of such programs is mainly correlated to: 1.) the approach to understanding and working toward the satisfaction of the community’s needs (in the broad sense of social responsibility); 2.) how systematically sustainability within the organization is identified and managed (e.g., pollution prevention, improved environmental performance, and compliance with the applicable environmental laws); and 3.) the degree to which the organization tries to understand the needs of the employees and works toward satisfying them. In addition to the survey, five interviews with top managers of the surveyed organizations provided some useful insights. There was no consensus on the meaning of sustainability and social responsibility: some described it as an instrumental approach for obtaining better organizational results, while others regarded it as the right thing to do (i.e., it is values driven). In all cases, however, the managers supported a kind of umbrella construct under which different size corporations use different models (for example, the Dow Jones Sustainability Index (DJSI), Global Reporting Initiative (GRI), ISO 14001 environmental management systems), although some managers reported that they simply do not know what to do. All of those surveyed agreed that the lack of a systematic approach could represent a major threat to their organization, making them willing to pay more attention and take more action on the issue of sustainability. An additional suggestion made by managers was to change from a triple bottom line (economic dimension, environmental dimension, social equity dimension) to a quadruple bottom line by adding another dimension: personal and family happiness. This fourth dimension was recognized by the Greek philosopher/thinker Aristotle (384-322 BCE) who thought of happiness as the highest good (virtue) and ultimate goal and purpose of life, achieved through living well, in harmony. Such harmony suggests a balance and a lack of excess—in other words a sustainable existence.

The association between serum potassium at hospital admission and the case-fatality rate of leptospirosis in men

Severe leptospirosis affects predominantly males and presents a high susceptibility to hypokalemic acute renal failure. As hypokalemia and hyperkalemia induce severe complications, it is important to evaluate if the initial serum potassium is an independent risk factor for death in leptospirosis. The medical records of 1016 patients hospitalized with the diagnosis of leptospirosis were reviewed. The analysis was restricted to 442, according to the following criteria: male, 18 years or older, information about death or hospital discharge and recorded values of serum potassium, serum creatinine and duration of symptoms at admission. Potassium values lower than 3.5 mEq/L (hypoK), 3.5-5 mEq/L (normoK) and above 5 mEq/L (hyperK) were detected in 180, 245 and 17 patients, respectively. The death rate increased with serum potassium: 11.1% in the hypoK, 14.7% in the normoK and 47.1% in the hyperK group (p = 0.002). In a logistic regression model (normoK as referent), including age, creatinine and duration of symptoms, hypoK was not associated with increased death rate (odds ratio (OR) = 0.80; p > 0.1). On the other hand, hyperK showed a significant association with increased risk of death (OR = 3.95, p = 0.021). In conclusion, in this sample of men with leptospirosis initial serum potassium was positively and independently correlated with the risk of in-hospital death.

Association between human parvovirus B19 and arthropathy in Belém, Pará, north Brazil

A total of 220 patients with arthropathy were selected in Belém, Pará between January 1994 and December 2000, and screened for the presence of human parvovirus B19 IgM and IgG antibodies by enzyme-linked immunosorbent assay (ELISA). A subgroup (n = 132) of patients with high levels of antibodies (either IgM+/IgG+ or IgM-/IgG+) were examined for the presence of DNA by polymerase chain reaction/nested PCR. Recent/active infection (detection of IgM and/or IgG-specific antibodies and presence of viral DNA) was identified in 47.7% of the 132 individuals with arthropathy. In our study, women were significantly more affected (59.7%) than men (35.4%) (P = 0.0006). The age group of 11-20 years (84.6%), among female patients, and 21-30 years (42.1%), among male, were those with the highest incidence rates. The analysis of the temporal distribution of B19-associated arthropaties showed a cyclic pattern, with peak incidence rates occuring at 3-5 year intervals. Significant diference (P = 0.01) was observed when comparing both the highest (39.0%) and the lowest (11.0%) seropositivity rates for the years of 1995 and 2000, respectively. The interfalangial joints of hands and feet were mostly affected, with 50.0% and 48.0% of cases among both women and men, respectively. In a smaller proportion, other joints such as those of knee, ankle, pulse and shoulder were affected. As for the duration, symptoms lasted 1 to 5 days in 54.0% of the individuals, whereas in 46.0% of them the disease lasted 6-10 days, if considered the subgroup (n = 63) of patients with recent/active infection by parvovirus B19. In our study, joint clinical manifestations occurred symmetrically. Our results indicate that B19 may be an important agent of arthropathies in our region, and this underscores the need for specific laboratory diagnosis when treating patients suffering from acute arthropathy, mainly pregnant women.

Reabilitação do Aeroporto de Ondjiva em Angola

Com o progresso da tecnologia aeronáutica, a deslocação de pessoas e bens tornou-se bastante acessível para variados pontos de mundo, com espaço de tempo muito reduzido. Um dos motores essenciais deste avanço, concernente à mobilidade, é o transporte aéreo e a sua evolução. Este tipo de transporte requer a máxima segurança, sendo que um único acidente pode gerar centenas de vítimas. Atendendo a estas condições, a qualidade dos pavimentos aeroportuários é de grande importância para a segurança da movimentação das aeronaves em solo. Mas, por razões económicas e por vezes de espaço, perspetivas de novas construções perdem viabilidade comparativamente a soluções de reabilitação. A posição geográfica do aeroporto de Ondjiva faz com que seja um importante ponto de passagem entre a África do Sul e a Namíbia e, prevê-se que o número de voos que se efetuam no aeroporto cresça, sendo que o país está numa fase de grande evolução. O presente trabalho visa o conhecimento do processo de dimensionamento para pavimentos aeroportuários e soluções de correção para anomalias que possam apresentar, aplicando-os ao aeroporto de Ondjiva, em Angola. Atualmente, o aeroporto revela um grande desgaste das pistas de táxi, inadaptabilidade das cabeceiras face às cargas estáticas a que são submetidas e, largura insuficiente da pista para a aeronave de projeto, ou aeronave crítica, atendendo ao regulamento da ICAO (International Civil Aviation Organization). Para melhorar o conforto, a segurança e eficiência dos serviços aéreos, o dimensionamento do aeroporto deve obedecer aos princípios e regras da ICAO. Pretende-se também a modelação de uma solução de reforço para o pavimento existente, para que não seja necessário construir um aeroporto de raiz, minimizando custos. Após a realização do dimensionamento, foi estudada a sinalização horizontal e luminosa da pista, para que esteja em conformidade com as suas novas medidas.

European Union emissions trading scheme impact on the Spanish electricity price during phase II and phase III implementation

The European Union Emissions Trading Scheme (EU ETS) is a cornerstone of the European Union's policy to combat climate change and its key tool for reducing industrial greenhouse gas emissions cost-effectively. The purpose of the present work is to evaluate the influence of CO2 opportunity cost on the Spanish wholesale electricity price. Our sample includes all Phase II of the EU ETS and the first year of Phase III implementation, from January 2008 to December 2013. A vector error correction model (VECM) is applied to estimate not only long-run equilibrium relations, but also short-run interactions between the electricity price and the fuel (natural gas and coal) and carbon prices. The four commodities prices are modeled as joint endogenous variables with air temperature and renewable energy as exogenous variables. We found a long-run relationship (cointegration) between electricity price, carbon price, and fuel prices. By estimating the dynamic pass-through of carbon price into electricity price for different periods of our sample, it is possible to observe the weakening of the link between carbon and electricity prices as a result from the collapse on CO2 prices, therefore compromising the efficacy of the system to reach proposed environmental goals. This conclusion is in line with the need to shape new policies within the framework of the EU ETS that prevent excessive low prices for carbon over extended periods of time.

McCoy cell line as a possible model containing CD4+ receptors for the study of HIV-1 replication

Several studies have recently shown the use of recombinant rabies virus as potential vector-viral vaccine for HIV-1. The sequence homology between gp 120 and rabies virus glycoprotein has been reported. The McCoy cell line has therefore been used to show CD4+ or CD4+ like receptors. Samples of HIV-1 were isolated, when plasma of HIV-1 positive patients was inoculated in the McCoy cell line. The virus infection was then studied during successive virus passages. The proteins released in the extra cellular medium were checked for protein activity, by exposure to SDS Electrophoresis and blotting to nitro-cellulose filter, then reacting with sera of HIV positive and negative patients. Successive passages were performed, and showed viral replication, membrane permeabilization, the syncytium formation, and the cellular lysis (cytopathic effect). Flow cytometry analysis shows clear evidence that CD4+ receptors are present in this cell line, which enhances the likelihood of easy isolation and replication of HIV. The results observed allow the use of this cell line as a possible model for isolating HIV, as well as for carrying out studies of the dynamics of viral infection in several situations, including exposure to drugs in pharmacological studies, and possibly studies and analyses of the immune response in vaccine therapies.

Paracoccidioidomycosis in children: clinical presentation, follow-up and outcome

From February, 1981 to May, 2001, 63 children under 15 y old (ages 2 - 15 y, median = 8 y, mean ± 1 SD = 8 ± 3 y) presenting 70 episodes of Paracoccidioidomycosis were admitted. The main clinical manifestations and laboratory features observed upon admission were: lymph node enlargement (87.1%), fever (75.7%), weakness (48.6%), pallor (41.4%), hepatomegaly (40%), splenomegaly (35.7%), anemia (90%), hypergammaglobulinemia (88.5%), eosinophilia (75.5%) and hypoalbuminemia (72.5%). Moderate to severe malnutrition was detected in 35.7% of the episodes (Gomez's criterion). Radiographic and technetium studies showed bone lesions in 20 of the episodes, most of them being multiple lytic lesions, involving both long (70%) and plain bones (30%). First line treatment consisted of an association of sulfametoxazole-trimethoprin, which was used, exclusively, in 50 episodes. Follow-up of hemoglobin levels, number of eosinophils in the peripheral blood, albumin and gammaglobulin serum levels revealed significant sequential improvement one and six months after hospital admission, being quite useful to evaluate treatment effectiveness. Six patients died (9.3%) and four developed sequelae (6.3%) . In conclusion, the juvenile and disseminated forms can be observed in about 70% of the episodes of PCM occurring in children younger than 15 y old, most of them presenting with a febrile lymphoproliferative syndrome associated to anemia, eosinophilia and hypergammaglobulinemia.

Erythema induratum of Bazin and renal tuberculosis: report of an association

Erythema induratum of Bazin is a disease that usually affects women, in whom erythematous subcutaneous nodules and plaques appear on the posterior part of the lower extremities, some of which ulcerate. In many countries, tuberculosis is still the main etiologic factor. We report a case of a 40-year-old woman who presented a course of protracted and recurrent episodes over five years of cutaneous lesions on her legs. These tend to involute, but new crops appear at irregular intervals. It was painful, erythematous-violaceous nodules, some of which drained a reddish secretion. The histopathologic features of the lesions demonstrated inflammatory infiltration, with predominance of neutrophils in dermis and hypodermis, necrotizing vasculitis in the arterioles and septal fibrosis. There was no granuloma. The Ziehl-Neelsen stain did not revealed acid-fast bacilli, and the culture of biopsy specimen was negative. The tuberculin skin test was strongly positive (17 mm). The chest X-ray was normal. Few months later she presented adynamia and urinary complaints, such as polacyuria and dysuria. It has been done an urynalysis, which demonstrated acid pH urine, sterile pyuria and microscopic hematuria. It was then raised the diagnostic hypothesis of renal tuberculosis. The urine culture for M. tuberculosis was positive in two out of ten samples. The treatment was instituted with rifampin, isoniazid and pyrazinamide, with complete regression. This case illustrates a clear association between erythema induratum and renal tuberculosis, demonstrated by the remission of the cutaneous lesions after the treatment of the renal tuberculosis.

Detection of EBV-DNA in serum samples of an immunosuppressed child during a three years follow-up: association of clinical and PCR data with active infection

Twenty-four whole blood and serum samples were drawn from an eight year-old heart transplant child during a 36 months follow-up. EBV serology was positive for VCA-IgM and IgG, and negative for EBNA-IgG at the age of five years old when the child presented with signs and symptoms suggestive of acute infectious mononucleosis. After 14 months, serological parameters were: positive VCA-IgG, EBNA-IgG and negative VCA-IgM. This serological pattern has been maintained since then even during episodes suggestive of EBV reactivation. PCR amplified a specific DNA fragment from the EBV gp220 (detection limit of 100 viral copies). All twenty-four whole blood samples yielded positive results by PCR, while 12 out of 24 serum samples were positive. We aimed at analyzing whether detection of EBV-DNA in serum samples by PCR was associated with overt disease as stated by the need of antiviral treatment and hospitalization. Statistical analysis showed agreement between the two parameters evidenced by the Kappa test (value 0.750; p < 0.001). We concluded that detection of EBV-DNA in serum samples of immunosuppressed patients might be used as a laboratory marker of active EBV disease when a Real-Time PCR or another quantitative method is not available.

A learning environment for robotic production line simulation

This paper presents a framework for a robotic production line simulation learning environment using Autonomous Ground Vehicles (AGV). An eLearning platform is used as interface with the simulator. The objective is to introduce students to the production robotics area using a familiar tool, an eLearning platform, and a framework that simulates a production line using AGVs. This framework allows students to learn about robotics but also about several areas of industrial management engineering without requiring an extensive prior knowledge on the robotics area. The robotic production line simulation learning environment simulates a production environment using AGVs to transport materials to and from the production line. The simulator allows students to validate the AGV dynamics and provides information about the whole materials supplying system which includes: supply times, route optimization and inventory management. The students are required to address several topics such as: sensors, actuators, controllers and an high level management and optimization software. This simulator was developed with a known open source tool from robotics community: Player/Stage. This tool was extended with several add-ons so that students can be able to interact with a complex simulation environment. These add-ons include an abstraction communication layer that performs events provided by the database server which is programmed by the students. An eLearning platform is used as interface between the students and the simulator. The students can visualize the effects of their instructions/programming in the simulator that they can access via the eLearning platform. The proposed framework aims to allow students from different backgrounds to fully experience robotics in practice by suppressing the huge gap between theory and practice that exists in robotics. Using an eLearning platform eliminates installation problems that can occur from different computers software distribution and makes the simulator accessible by all students at school and at home.

Utilização das urgências hospitalares e acesso aos cuidados de saúde primários : o impacto da implementação das USF na procura dos serviços de urgência : estudo preliminar

RESUMO - A sobrelotação das urgências resultante da utilização inadequada tem como consequências a diminuição na qualidade dos cuidados. As causas da utilização inadequada são várias. Entre elas, a utilização dos Cuidados de saúde Primários merece uma atenção particular. De facto, as barreiras no acesso aos cuidados de saúde primários estão associadas com uma maior inadequação. Assim, ter um prestador regular, acessível, que presta cuidados contínuos e regulares está associado com uma menor utilização inadequada dos csp. Contudo, é necessário ter em conta as características dos utilizadores de forma a desenvolver estratégias que permitam a prestação de cuidados acessíveis. Em Portugal, foi implementada em 2006 uma Reforma dos CSP cuja face mais visíveis são as USF, que deverão prestar cuidados personalizados, garantido a acessibilidade, globalidade e continuidade dos mesmos. Assim, da revisão da literatura e existindo uma associação entre a utilização inadequada das urgências observou-se a variação das urgências hospitalares entre 2005 (ano anterior à implementação das USF) e 2008 (últimos dados disponibilizados) e o nº de USF implementadas. Ao contrário do expectável, verificou-se haver uma associação positiva entre o nº de USF e o nº de urgências hospitalares. Os hospitais com maior nº de USF tiveram um aumento da utilização das urgências hospitalares, enquanto nos hospitais sem nenhuma USF associada, houve uma diminuição das urgências hospitalares. Contudo, existiram factores que não considerados, como criação da Linha Saúde 24, encerramento dos SAP, dimensão dos hospitais, etc., que poderão ter influenciado os resultados. Os resultados em saúde resultantes da implementação das USF não foram considerados. Assim sugere- se futura investigação. ------------------------------ABSTRACT - Crowded emergency department resulting from inappropriate use may compromise the quality of care . Several causes explain the inadequate use of emergency care. Among them, the association between primary care and inappropriate use of emergency departments is of particular interest. Indeed, studies show that fact, barriers in access to Primary Health Care ( PHC) are associated with more inappropriate use. Therefore having a regular, accessible, continuous, source of care is associated with a decrease in inappropriate use of Emergency department. Though, patient’s preferences have to be considered in order to develop strategies that allow accessible care. In Portugal, a reform of primary care has been launched in 2006, through the implementation of Family Health Units ( FHU) that are responsible for giving personalized, accessible, global and continuous care. A vast literature shows an association between inappropriate use of emergency departments and primary health care access. In the present work we observed the variation in emergency department use between 2005 (previous year to Family Health Units implementation) and 2008 (last available data) and the number of Family Health Units implemented. Contrary to our expectations, results showed a positive association between the number of Health Family Units and emergency department use. The Hospitals with more Health Family Units experienced an increase of emergency department use while hospitals with none Health Family units experienced a decrease of emergency department use. Although there were several factors that could have influenced the results (creation of Health 24 Line, SAP closure, Hospital Dimension, etc) .Health outcomes that result fr