Mitochondrial reactive oxygen species generation triggers inflammatory response and tissue injury associated with hepatic ischemia-reperfusion: Therapeutic potential of mitochondrially targeted antioxidants.

Mitochondrial reactive oxygen species generation has been implicated in the pathophysiology of ischemia-reperfusion (I/R) injury; however, its exact role and its spatial-temporal relationship with inflammation are elusive. Herein we explore the spatial-temporal relationship of oxidative/nitrative stress and inflammatory response during the course of hepatic I/R and the possible therapeutic potential of mitochondrial-targeted antioxidants, using a mouse model of segmental hepatic ischemia-reperfusion injury. Hepatic I/R was characterized by early (at 2h of reperfusion) mitochondrial injury, decreased complex I activity, increased oxidant generation in the liver or liver mitochondria, and profound hepatocellular injury/dysfunction with acute proinflammatory response (TNF-α, MIP-1α/CCL3, MIP-2/CXCL2) without inflammatory cell infiltration, followed by marked neutrophil infiltration and a more pronounced secondary wave of oxidative/nitrative stress in the liver (starting from 6h of reperfusion and peaking at 24h). Mitochondrially targeted antioxidants, MitoQ or Mito-CP, dose-dependently attenuated I/R-induced liver dysfunction, the early and delayed oxidative and nitrative stress response (HNE/carbonyl adducts, malondialdehyde, 8-OHdG, and 3-nitrotyrosine formation), and mitochondrial and histopathological injury/dysfunction, as well as delayed inflammatory cell infiltration and cell death. Mitochondrially generated oxidants play a central role in triggering the deleterious cascade of events associated with hepatic I/R, which may be targeted by novel antioxidants for therapeutic advantage.

p.L1612P, a novel voltage-gated sodium channel Nav1.7 mutation inducing a cold sensitive paroxysmal extreme pain disorder.

BACKGROUND: Mutations in the SCN9A gene cause chronic pain and pain insensitivity syndromes. We aimed to study clinical, genetic, and electrophysiological features of paroxysmal extreme pain disorder (PEPD) caused by a novel SCN9A mutation. METHODS: Description of a 4-generation family suffering from PEPD with clinical, genetic and electrophysiological studies including patch clamp experiments assessing response to drug and temperature. RESULTS: The family was clinically comparable to those reported previously with the exception of a favorable effect of cold exposure and a lack of drug efficacy including with carbamazepine, a proposed treatment for PEPD. A novel p.L1612P mutation in the Nav1.7 voltage-gated sodium channel was found in the four affected family members tested. Electrophysiologically the mutation substantially depolarized the steady-state inactivation curve (V1/2 from -61.8 ± 4.5 mV to -30.9 ± 2.2 mV, n = 4 and 7, P < 0.001), significantly increased ramp current (from 1.8% to 3.4%, n = 10 and 12) and shortened recovery from inactivation (from 7.2 ± 5.6 ms to 2.2 ± 1.5 ms, n = 11 and 10). However, there was no persistent current. Cold exposure reduced peak current and prolonged recovery from inactivation in wild-type and mutated channels. Amitriptyline only slightly corrected the steady-state inactivation shift of the mutated channel, which is consistent with the lack of clinical benefit. CONCLUSIONS: The novel p.L1612P Nav1.7 mutation expands the PEPD spectrum with a unique combination of clinical symptoms and electrophysiological properties. Symptoms are partially responsive to temperature but not to drug therapy. In vitro trials of sodium channel blockers or temperature dependence might help predict treatment efficacy in PEPD.

Reliability of current estimates of schistosomiasis prevalence in the Rainforest Zone of the state of Pernambuco, Northeastern Brazil

The Program for Schistosomiasis Control within the Unified Health System (PCE-SUS) was implemented by 1999 in the Rainforest Zone or "Zona da Mata" of Pernambuco (ZMP) aiming to carry out biennial stool surveys of whole populations through municipal health organs followed by treatment of the positives through the local units of the Family Health Program (PSF). Yearly reports from the Health Department of Pernambuco State (SES/PE) from 2002 to 2004 on the PCE-SUS surveys were assessed to evaluate whether the current estimates of prevalence in the municipalities of the ZMP are based on reliable samples so as to allow considerations on the real situation of schistosomiasis in that area. The surveys carried out in that period did not follow the major principles underlying sampling design, thus posing problems in both precision and validity of the estimates. Only 12 out of 43 municipalities had minimally reliable estimates: five with moderate prevalence (10-50%) and seven with low prevalence (< 10%). Surveys with appropriate sampling procedures aimed either at representative target groups (school-aged children) or communities are recommended for the ZMP and other endemic areas not only to provide reliable information on the current situation of schistosomiasis but also to plan adequate control strategies.

J2EE : Generació automàtica de codi

Aquest projecte està enfocat a determinar l'estat actual de les principals eines de generació automàtica de codi que existeixen, analitzant les característiques principals de cada eina determinar-ne les funcionalitats.

The Evangelical Milieu : Defining Criteria and Reproduction across the Generation

The authors give the first description of evangelicalism in Switzerland using representative data. It is shown that evangelicalism can be conceived of as a "milieu" which is characterized by certain structural and cultural traits, boundaries and high internal communication. The relative success of the evangelical milieu compared to other religious milieus is explained by its remarkable ability to retain its own numerous offspring, while on the other hand providing a "religious product" that is also attractive to people without an evangelical familial background. Les auteurs utilisent des données représentatives afin de faire, pour la première fois, une description de l'évangélisme en Suisse. Ils montrent qu'on peut parler de l'évangélisme comme d'un "milieu'' qui se caractérise par certains attributs structurels et culturels, des frontières et une communication interne élevée. Le succès relatif du milieu évangélique comparé à d'autres milieux s'explique par sa capacité remarquable à retenir les enfants de ses membres dans le mouvement tout en offrant un "produit religieux'' attractif aux personnes sans arrière-fond évangélique.

Current situation of Chagas disease in Central America

Chagas disease in Central America is known since 1913 when the first human case was reported in El Salvador. The other Central American countries reported their first cases between 1933 and 1967. On October 1997 was launched the Central American Initiative for Chagas Disease Control (IPCA). The objectives of this sub-regional Initiative are: (1) the elimination of Rhodnius prolixus in Central America; (2) the reduction of the domiciliary infestation of Triatoma dimidiata; and (3) the elimination of the transfusion transmission of Trypanosoma cruzi. Significant advancements being close to the elimination of R. prolixus in Central America and the control of the transfusion transmission has been a transcendent achievement for the sub-region. The main challenges that the IPCA will have in the close future are: developing effective strategies for control and surveillance of T. dimidiata; and surveillance of other emerging triatominae species like R. pallescens, T. nitida, and T. ryckmani.

The ghost of social environments past: dominance relationships include current interactions and experience carried over from previous groups.

Dominance hierarchies pervade animal societies. Within a static social environment, in which group size and composition are unchanged, an individual's hierarchy rank results from intrinsic (e.g. body size) and extrinsic (e.g. previous experiences) factors. Little is known, however, about how dominance relationships are formed and maintained when group size and composition are dynamic. Using a fusion-fission protocol, we fused groups of previously isolated shore crabs (Carcinus maenas) into larger groups, and then restored groups to their original size and composition. Pre-fusion hierarchies formed independently of individuals' sizes, and were maintained within a static group via winner/loser effects. Post-fusion hierarchies differed from pre-fusion ones; losing fights during fusion led to a decline in an individual's rank between pre- and post-fusion conditions, while spending time being aggressive during fusion led to an improvement in rank. In post-fusion tanks, larger individuals achieved better ranks than smaller individuals. In conclusion, dominance hierarchies in crabs represent a complex combination of intrinsic and extrinsic factors, in which experiences from previous groups can carry over to affect current competitive interactions.

Aedes aegypti, Aedes albopictus, and dengue in Argentina: current knowledge and future directions

Since the reinfestation of South American countries by Ae. aegypti, dengue fever (DF) and dengue hemorrhagic fever (DHF) have become a major public health concern. The aim of this paper was to review the information related with Aedes vectors and dengue in Argentina since the reintroduction of Ae. aegypti in 1986. The geographic distribution of Ae. albopictus is restricted to the Northeast, and that of Ae. aegypti has expanded towards the South and the West in comparison with the records during the eradication campaign in the 1960s. Since 1998, 4,718 DF cases have been reported concentrated in the provinces of Salta, Formosa, Misiones, Jujuy and Corrientes. Despite the circulation of three dengue virus serotypes (DENV-1, -2 and -3) in the North of the country, DHF has not occurred until the present. The information published over the last two decades regarding mosquito abundance, temporal variations, habitat characteristics, competition, and chemical and biological control, was reviewed. Considering the available information, issues pending in Argentina are discussed. The presence of three DENV, the potential spread of Ae. albopictus, and the predicted climate change suggest that dengue situation will get worse in the region. Research efforts should be increased in the Northern provinces, where DHF is currently an actual risk.

Speciation of antimony (III) and antimony (V) using hydride generation for meglumine antimoniate pharmaceutical formulationsquality control

The pentavalent antimonies, mainly the meglumine antimoniate, are recommends as first-choice medicines for leishmaniasis therapy. In this work we described the development of formulations of meglumine antimoniate injectable medication, as well as the analytical methodology used in the selective determination of Sb(III) and Sb(Total) by hydride generation - inductively coupled plasma atomic emission spectrometry (HG-ICP-AES) and ICP-AES, respectively. On that purpose the analytical methodology was developed focusing on the HG-ICP-AES technique. The formulations using propylene glycol/water as vehicles in a 20:80 proportion were more appropriate for subsequent use in industrial scale. These formulations also showed a lower variation on Sb(III) percentage, no need of buffer solution to stabilize the formulation and no influence of the autoclaving in the quality of the product. The results of the development of the analytical methodology point out the proposed method as an efficient alternative for the determination of Sb(III) in the presence of large quantities of Sb(V) in injectable solutions of meglumine antimoniate, in a selective, linear, accurate and precise manner. In addition, the method showed a low limit of quantification, less interference of the matrix, and more resilience than batch techniques proposed in the Brazilian Pharmacopeia.

Current profile of Mansonella ozzardi (Nematoda: Onchocercidae) in communities along the Ituxi river, Lábrea municipality, Amazonas, Brazil

The objective of this paper was to describe the current status of Mansonella ozzardi prevalence among the inhabitants of 12 communities along the Ituxi river, in Lábrea municipality, state of Amazonas. The prevalence of M. ozzardi was determined using thick blood smears obtained by digital punctures. M. ozzardi was found in 30.23% of the samples collected (39/129), with similar prevalence between genders (males: 30.30%; females: 30.16%); the highest prevalence was found in homemakers (45.45%) followed by farmers (38.77%). Among age groups, males and females older than 48 exhibited the highest rates. These results show a significative increase in the prevalence when compared to a epidemiological study made 26 years ago in the same area as well as a different epidemiological profile (gender and occupation) in relation to other areas in Amazonas.

Treating ocular toxoplasmosis: current evidence

The current treatment of ocular toxoplasmosis is controversial. The mainstay of treatment has been pyrimethamine and sulphonamides with or without systemic corticosteroids, but the actual evidence that antibiotics have a beneficial effect in recurrent toxoplasmic retinochoroiditis is unsupported by randomised placebo controlled trials. Thus far there have only been three studies looking at the efficacy of antibiotic treatment, all of which were methodologically weak and two of which were perfomed more than 30 years ago. All studies reported adverse effects from treatment. There is an urgent need for further randomised, double blind, placebo controlled studies for lesions in all parts of the retina and to test the efficacy of adjunctive corticosteroid treatment.

Current status of pediatric home enteral nutrition in Spain: the importance of the NEPAD register.

Home enteral nutrition (HEN) is a type of enteral nutrition (EN) which is becoming progressively more widespread in pediatrics due to the benefits it affords to patients, their families and to reducing hospital costs. However, the true extent of its use is unknown in Spain as the data-base set up for this purpose is still underused (Registro de Nutrición Enteral Pediátrica Ambulatoria y Domiciliaria -NEPAD-). More thorough registration of patients in the NEPAD online register will provide information about the characteristics of HEN in Spain: prevalence, diagnosis, the population sector being administered HEN, complications and developments. Likewise, forecast and planning of the necessary resources could be made while those in use could be analysed.

Current epidemiological trends for Chagas disease in Latin America and future challenges in epidemiology, surveillance and health policy

Chagas disease, named after Carlos Chagas, who first described it in 1909, exists only on the American Continent. It is caused by a parasite, Trypanosoma cruzi, which is transmitted to humans by blood-sucking triatomine bugs and via blood transfusion. Chagas disease has two successive phases: acute and chronic. The acute phase lasts six-eight weeks. Several years after entering the chronic phase, 20-35% of infected individuals, depending on the geographical area, will develop irreversible lesions of the autonomous nervous system in the heart, oesophagus and colon, and of the peripheral nervous system. Data on the prevalence and distribution of Chagas disease improved in quality during the 1980s as a result of the demographically representative cross-sectional studies in countries where accurate information was not previously available. A group of experts met in Brasilia in 1979 and devised standard protocols to carry out countrywide prevalence studies on human T. cruzi infection and triatomine house infestation. Thanks to a coordinated multi-country programme in the Southern Cone countries, the transmission of Chagas disease by vectors and via blood transfusion was interrupted in Uruguay in 1997, in Chile in 1999 and in Brazil in 2006; thus, the incidence of new infections by T. cruzi across the South American continent has decreased by 70%. Similar multi-country initiatives have been launched in the Andean countries and in Central America and rapid progress has been reported towards the goal of interrupting the transmission of Chagas disease, as requested by a 1998 Resolution of the World Health Assembly. The cost-benefit analysis of investment in the vector control programme in Brazil indicates that there are savings of US$17 in medical care and disabilities for each dollar spent on prevention, showing that the programme is a health investment with very high return. Many well-known research institutions in Latin America were key elements of a worldwide network of laboratories that carried out basic and applied research supporting the planning and evaluation of national Chagas disease control programmes. The present article reviews the current epidemiological trends for Chagas disease in Latin America and the future challenges in terms of epidemiology, surveillance and health policy.

Sustainability of vector control strategies in the Gran Chaco Region: current challenges and possible approaches

Sustainability has become a focal point of the international agenda. At the heart of its range of distribution in the Gran Chaco Region, the elimination of Triatoma infestans has failed, even in areas subject to intensive professional vector control efforts. Chagas disease control programs traditionally have been composed of two divorced entities: a vector control program in charge of routine field operations (bug detection and insecticide spraying) and a disease control program in charge of screening blood donors, diagnosis, etiologic treatment and providing medical care to chronic patients. The challenge of sustainable suppression of bug infestation and Trypanosoma cruzi transmission can be met through integrated disease management, in which vector control is combined with active case detection and treatment to increase impact, cost-effectiveness and public acceptance in resource-limited settings. Multi-stakeholder involvement may add sustainability and resilience to the surveillance system. Chagas vector control and disease management must remain a regional effort within the frame of sustainable development rather than being viewed exclusively as a matter of health pertinent to the health sector. Sustained and continuous coordination between governments, agencies, control programs, academia and the affected communities is critical.