CARMA1 is a critical lipid raft-associated regulator of TCR-induced NF-kappa B activation.

CARMA1 is a lymphocyte-specific member of the membrane-associated guanylate kinase (MAGUK) family of scaffolding proteins, which coordinate signaling pathways emanating from the plasma membrane. CARMA1 interacts with Bcl10 via its caspase-recruitment domain (CARD). Here we investigated the role of CARMA1 in T cell activation and found that T cell receptor (TCR) stimulation induced a physical association of CARMA1 with the TCR and Bcl10. We found that CARMA1 was constitutively associated with lipid rafts, whereas cytoplasmic Bcl10 translocated into lipid rafts upon TCR engagement. A CARMA1 mutant, defective for Bcl10 binding, had a dominant-negative (DN) effect on TCR-induced NF-kappa B activation and IL-2 production and on the c-Jun NH(2)-terminal kinase (Jnk) pathway when the TCR was coengaged with CD28. Together, our data show that CARMA1 is a critical lipid raft-associated regulator of TCR-induced NF-kappa B activation and CD28 costimulation-dependent Jnk activation.

A Critical Review on Chagas Disease Chemotherapy

In this "Critical Review" we made a historical introduction of drugs assayed against Chagas disease beginning in 1912 with the works of Mayer and Rocha Lima up to the experimental use of nitrofurazone. In the beginning of the 70s, nifurtimox and benznidazole were introduced for clinical treatment, but results showed a great variability and there is still a controversy about their use for chronic cases. After the introduction of these nitroheterocycles only a few compounds were assayed in chagasic patients. The great advances in vector control in the South Cone countries, and the demonstration of parasite in chronic patients indicated the urgency to discuss the etiologic treatment during this phase, reinforcing the need to find drugs with more efficacy and less toxicity. We also review potential targets in the parasite and present a survey about new classes of synthetic and natural compounds studied after 1992/1993, with which we intend to give to the reader a general view about experimental studies in the area of the chemotherapy of Chagas disease, complementing the previous papers of Brener (1979) and De Castro (1993).

Epidemiological and Serological Aspects in Canine Toxoplasmosis in Animals with Nervous Symptoms

The presence of anti-Toxoplasma gondii IgM and IgG antibodies was studied in samples of blood serum taken from eighty dogs with nervous symptoms at the Serviço de Enfermidades Infecciosas dos Animais, Faculdade de Medicina Veterinária e Zootecnia, Unesp, Botucatu, São Paulo, Brazil. The frequency of IgG titers were 16 (13.7%), 64 (13.7%), and 256 (5%), and for IgM titers were 16 (7.5%), 64 (15%), and 256 (8.7%). Positive reactions were more frequent in the older animals, males, from a rural environment, in constant contact with small animals, principally birds and rodents. There was a higher frequency of a positive reaction in dogs fed with kitchen food, especially in those fed with raw ingredients. The most common neurological pictures were alterations in consciousness, in movement, and in the hand-cart test. The percentage of reagents with specific IgM antibodies was high, indicating active infections, but the possibility of co-infection with the distemper virus can not be discarded, and this may be a predisposing factor for toxoplasmosis infection, once the distemper virus has a potent immunosupressive action.

Some Morphological Aspects of Cylicocyclus brevicapsulatus (Nematoda: Cyathostominae) Parasite of Horse

This paper describes some morphological aspects of Cylicocyclus brevicapsulatus (Ihle, 1920) (Nematoda: Cyathostominae) from Equus caballus in Brazil. The worms were studied using an optical microscope (measurements and illustrations) and a scanning electron microscope for a more detailed examination of the external morphology. The buccal capsule is very short, with a very thin wall, and the dorsal gutter is absent. Other morphological aspects are described including measurement of the spicules and gubernaculum.

Ecological Aspects of Phebotomine (Diptera, Psychodidae) in an Endemic Area of Tegumentary Leishmaniasis in the Northeastern Argentina, 1993-1998

The first epidemic tegumentary leishmaniasis´ outbreak in the province of Misiones was recorded in 1998, in the locality of Puerto Esperanza. Phlebotominae collected in the region, previously or simultaneously to the outbreak (September 1993-December 1998) showed that the species Lutzomyia intermedia s. l. was prevalent (94%, n 6,150) at all the sites sampled with miniature light trap (10) and Shannon trap (3). L. pessoai, L. whitmani, L. migonei, L. shannoni, L. fischeri, L. misionensis, Brumptomyia avellari and B. guimaraesi were also captured. Sand fly distribution in time and space suggests that in the province of Misiones (1) the species already present before 1990 could give rise to the epidemic by the density/dispersion fluctuation of their local populations; (2) the abundance of L. intermedia s. l. was associated with environments with ecotones of primary-secondary vegetation, close to water bodies and with moderate human disturbance; (3) this species showed, towards the end of 1997, peaks of exceptional abundance, subsequent to rainfall peaks in 1996. This increase in abundance of potential vector sand fly populations close to houses with colonizable surroundings could have generated the 1998 epidemic outbreak.

Epidemiological Aspects of Head Lice in Children Attending Day Care Centres, Urban and Rural Schools in Uberlândia, Central Brazil

From November 1996 to March 2000, a total of 884 children between 0 and 15 years, from 11 institutions including day care centres, public urban and public rural schools in Uberlândia, State of Minas Gerais, central Brazil, were examined for head louse infestation. Children's sex, race, age and some hairs characteristics were shown to be associated to parasite infestation. A prevalence rate of 35% was found and the highest rates were observed in black, female children, with long, dark, wavy hairs. Hairs density and thickness did not seem to influence significantly the distribution of this pediculosis in Uberlândia's schoolchildren. Differences observed between the prevalence rates of head lice in children from the urban institutions suggest there is a greater epidemiological heterogeneity in this group when compared to the rural schoolchildren.

Revue critique d'instruments pour evaluer la douleur chez les personnes cérébrolésées non communicantes aux soins intensifs [Critical review of instruments to assess pain in the non communicative brain injured persons in intensive care].

The purpose of this review is to critically appraise the pain assessment tools for non communicative persons in intensive care available in the literature and to determine their relevance for those with brain injury. Nursing and medical electronic databases were searched to identify pain tools, with a description of psychometric proprieties, in English and French. Seven of the ten tools were considered relevant and systematically evaluated according to the criteria and the indicators in the following five areas: conceptualisation, target population, feasibility and clinical utility, reliability and validity. Results indicate a number of well designed pain tools, but additional work is necessary to establish their accuracy and adequacy for the brain injured non communicative person in intensive care. Recommendations are made to choose the best tool for clinical practice and for research.

Aspects of the Maintenance of the Life Cycle of Fasciola hepatica in Lymnaea columella in Minas Gerais, Brazil

Fascioliasis is a parasitic disease of domestic ruminants that occurs worldwide. The lymnaeid intermediate hosts of Fasciola hepatica include Lymnaea columella, which is widely distributed in Brazil. A colony of L. columella from Belo Horizonte, MG, was reared in our laboratory to be used in studies of the F. hepatica life cycle, the intermediate host-parasite relationship and development of an anti-helminthic vaccine. In the first experiment 1,180 snails were exposed to miracidia of F. hepatica eggs removed from the biliary tracts of cattle from the State of Rio Grande do Sul. In the second and third experiments the snails were exposed to miracidia that had emerged from F. hepatica eggs from Uruguay, maintained in rabbits. The rates of infection in the first, second and third experiments were 0, 42.1 and 0% respectively. Over 15,806 metacercariae were obtained and stored at 4ºC. Four rabbits weighing 1.5 kg each were infected with 32-44 metacercariae and two with 200. Three rabbits begin to eliminate eggs of the parasite in the feces from 84 days after infection onwards. The biological cycle of F. hepatica in L. columella and the rabbit was completed within 124 days.

Some Aspects of Protozoan Infections in Immunocompromised Patients: A Review

Protozoa are among the most important pathogens that can cause infections in immunocompromised hosts. These microorganisms particularly infect individuals with impaired cellular immunity, such as those with hematological neoplasias, renal or heart transplant patients, patients using high doses of corticosteroids, and patients with acquired immunodeficiency syndrome. The protozoa that most frequently cause disease in immunocompromised patients are Toxoplasma gondii, Trypanosoma cruzi, different Leishmania species, and Cryptosporidium parvum; the first two species cause severe acute meningoencephalitis and acute myocarditis, Leishmania sp. causes mucocutaneous or visceral disease, and Cryptosporidium can lead to chronic diarrhea with hepatobiliary involvement. Various serological, parasitological, histological and molecular methods for the diagnosis of these infections are currently available and early institution of specific therapy for each of these organisms is a basic measure to reduce the morbidity and mortality associated with these infections.

Le conseil génétique: aspects théoriques et pratique en prénatal [Genetic counselling: theoretical aspects and prenatal practice]

Le conseil génétique doit fournir aux individus une information médicale précise et un soutien psychologique. L'importance des principes d'autonomie et de confidentialité, dogmes du conseil génétique, est renforcée par la nouvelle loi suisse (LAGH). Dans certains pays, une grande partie du conseil génétique est assurée par des conseillers en génétique non médecins ayant une formation postgraduée spécifique. Le conseil génétique joue un rôle grandissant dans différents domaines de la médecine. En particulier, il est indispensable dans le contexte du prénatal où les couples reçoivent des informations complexes et doivent bénéficier d’un soutien pour prendre une décision. Genetic counselling provides families with accurate medical information and psychological support. Respect and concern for the emotional well-being should be taken into account while discussing genetics aspects and recurrence risks. The importance of autonomy and confidentiality, central to genetic counselling, is reinforced by the new Swiss law (LAGH). In many countries, most of the genetic counselling is provided by genetic counsellors who have a specialised post-graduate training. Genetic counselling plays an increasing role in different medical specialities. In particular, it is essential in the context of prenatal and pre-conceptual care, where couples are confronted to complex information and should have access to appropriate support during the decision-making process

Clinical and epidemiological aspects of human parvovirus B19 infection in an urban area in Brazil (Niterói city area, State of Rio de Janeiro, Brazil)

This study was designed to analyse the clinical and epidemiological data from human parvovirus B19 cases in a six-year study of rash diseases conduct in an urban area in Brazil (Niterói city area, State of Rio de Janeiro). A total of 673 patients with acute rash diseases were seen at two primary health care units and at a general hospital. A clotted blood sample was collected from all subjects at the time of consultation. Forty-nine per cent (330 cases) of the patients were negative for dengue, rubella and measles IgM or for low avidity IgG to HHV-6. Of these 330, 105 (31.8%) were identified as IgM positive to parvovirus B19 by using an antibody capture EIA. During the study period, three distinct peaks of parvovirus infection were detected, suggesting that the disease appears to cycle in approximately 4-5 years. B19 infection was characterized by variable combinations of fever, flu-like symptoms, arthropathy, and gastrointestinal symptoms. Frequency of fever and arthropathy was substantially higher in adults, 75% [chi2 (1 D.F.) = 11.39, p = 0.0007] and 62.5% [chi2 (1 D.F.) = 29.89, p = 0.0000], respectively. "Slapped-cheek" appearance and reticular or lace-like rash were seen in only 30.1% of the children. No adult presented this typical rash. The lack of the typical rash pattern in a large proportion of parvovirus B19 and the similarity of clinical manifestations to other rash diseases, specially to rubella, highlight the difficulty of diagnosing B19 infection on clinical grounds alone.

Epidemiological and immunological aspects of human visceral leishmaniasis on Margarita Island, Venezuela

Sixty-five patients were diagnosed with visceral leishmaniasis (VL) on Margarita Island in the decade from 1990 to1999; 86.2% were <= 3 years old. All were leishmanin-negative at diagnosis. Evaluation of 23 cured patients in 1999 revealed that 22/23 had converted to leishmanin-positive; five had persisting antibodies to rK39 antigen, with no clinical evidence of disease. Leishmanin tests were positive in 20.2% of 1,643 healthy individuals from 417 households in endemic areas. Of the positive reactors, 39.8% were identified in 35 (8.4%) of the households, 15 of which had an antecedent case of VL, a serologically positive dog or both. Weak serological activity to rK39 antigen was detected in 3 of 488 human sera from the endemic areas. The presence of micro-foci of intense peri-urban transmission and the apparent absence of other Trypanosomatidae causing human disease offer a unique opportunity for the study of reservoirs, alternative vectors and evaluation of control measures on the Island.

Tropical cyclones as a critical phenomenon

It has been proposed that the number of tropical cyclones as a function of the energy they release is a decreasing power-law function, up to a characteristic energy cutoff determined by the spatial size of the ocean basin in which the storm occurs. This means that no characteristic scale exists for the energy of tropical cyclones, except for the finite-size effects induced by the boundaries of the basins. This has important implications for the physics of tropical cyclones. We discuss up to what point tropical cyclones are related to critical phenomena (in the same way as earthquakes, rainfall, etc.), providing a consistent picture of the energy balance in the system. Moreover, this perspective allows one to visualize more clearly the effects of global warming on tropical-cyclone occurrence.