Molecular and functional characterization of a new non-hemorrhagic metalloprotease from Bothrops jararacussu snake venom with antiplatelet activity

BjussuMP-II is an acidic low molecular weight metalloprotease (Mr similar to 24,000 and pI similar to 6.5), isolated from Bothrops jararacussu snake venom. The chromatographic profile in RP-HPLC and its N-terminal sequence confirmed its high purity level. Its complete cDNA was obtained by RT-PCR and the 615 bp codified for a mature protein of 205 amino acid residues. The multiple alignment of its deduced amino acid sequence and those of other snake venom metalloproteases showed a high structural similarity, mainly among class P-I proteases. The molecular modeling analysis of BjussuMP-II showed also conserved structural features with other SVMPs. BjussuMP-II did not induce hemorrhage, myotoxicity and lethality, but displayed dose-dependent proteolytic activity on fibrinogen, collagen, fibrin, casein and gelatin, keeping stable at different pHs, temperatures and presence of several divalent ions. BjussuMP-II did not show any clotting or anticoagulant activity on human citrated plasma, in contrast to its inhibitory effects on platelet aggregation. The aspects broached, in this work, provide data on the relationship between structure and function, in order to better understand the effects elicited by snake venom metalloproteases. (c) 2007 Elsevier B.V. All rights reserved.

Snake venom phospholipase A(2) inhibitors: Medicinal chemistry and therapeutic potential

Phospholipases A(2) (PLA(2)s) are commonly found in snake venoms from Viperidae, Hydrophidae and Elaphidae families and have been extensively studied due to their pharmacological and physiopathological effects in living organisms. This article reports a review on natural and artificial inhibitors of enzymatic, toxic and pharmacological effects induced by snake venom PLA(2)s. These inhibitors act on PLA(2)S through different mechanisms, most of them still not completely understood, including binding to specific domains, denaturation, modification of specific amino acid residues and others. Several substances have been evaluated regarding their effects against snake venoms and isolated toxins, including plant extracts and compounds from marine animals, mammals and snakes serum plasma, in addition to poly or monoclonal antibodies and several synthetic molecules. Research involving these inhibitors may be useful to understand the mechanism of action of PLA(2)s and their role in envenomations caused by snake bite. Furthermore, the biotechnological potential of PLA(2) inhibitors may provide therapeutic molecular models with antiophidian activity to supplement the conventional serum therapy against these multifunctional enzymes.

Insights into the role of oligomeric state on the biological activities of crotoxin: crystal structure of a tetrameric phospholipase A(2) formed by two isoforms of crotoxin B from Cratalus durissus terrificus venom

Crotoxin B (CB or Cdt PLA(2)) is a basic Asp49-PLA(2) found in the venom of Crotalus durissus terrificus and it is one of the subunits that constitute the crotoxin (Cro). This heterodimeric toxin, main component of the C. d. terrificus venom, is completed by an acidic, nontoxic, and nonenzymatic component (crotoxin A, CA or crotapotin), and it is related to important envenomation effects such as neurological disorders, myotoxicity, and renal failure. Although Cro has been crystallized since 1938, no crystal structure of this toxin or its subunits is currently available. In this work, the authors present the crystal structure of novel tetrameric complex formed by two dimers of crotoxin B isoforms (CB1 and CB2). The results suggest that these assemblies are stable in solution and show that Ser1 and Glu92 of CB1 and CB2, respectively, play an important role in the oligomerization. The tetrameric and dimeric conformations resulting from the association of the isoforms may increase the neurotoxicity of the toxin CB by the creation of new binding sites, which could improve the affinity of the molecular complexes to the presynaptic membrane.

Oral cleft prevention program (OCPP)

Background: Oral clefts are one of the most common birth defects with significant medical, psychosocial, and economic ramifications. Oral clefts have a complex etiology with genetic and environmental risk factors. There are suggestive results for decreased risks of cleft occurrence and recurrence with folic acid supplements taken at preconception and during pregnancy with a stronger evidence for higher than lower doses in preventing recurrence. Yet previous studies have suffered from considerable design limitations particularly non-randomization into treatment. There is also well-documented effectiveness for folic acid in preventing neural tube defect occurrence at 0.4 mg and recurrence with 4 mg. Given the substantial burden of clefting on the individual and the family and the supportive data for the effectiveness of folic acid supplementation as well as its low cost, a randomized clinical trial of the effectiveness of high versus low dose folic acid for prevention of cleft recurrence is warranted.Methods/design: This study will assess the effect of 4 mg and 0.4 mg doses of folic acid, taken on a daily basis during preconception and up to 3 months of pregnancy by women who are at risk of having a child with nonsyndromic cleft lip with/without palate (NSCL/P), on the recurrence of NSCL/P. The total sample will include about 6,000 women (that either have NSCL/P or that have at least one child with NSCL/P) randomly assigned to the 4 mg and the 0.4 mg folic acid study groups. The study will also compare the recurrence rates of NSCL/P in the total sample of subjects, as well as the two study groups (4mg, 0.4 mg) to that of a historical control group. The study has been approved by IRBs (ethics committees) of all involved sites. Results will be disseminated through publications and presentations at scientific meetings.Discussion: The costs related to oral clefts are high, including long term psychological and socio-economic effects. This study provides an opportunity for huge savings in not only money but the overall quality of life. This may help establish more specific clinical guidelines for oral cleft prevention so that the intervention can be better tailored for at-risk women.

The distribution of agglutinins and lytic activity against Trypanosoma rangeli and erythrocytes in Rhodnius prolixus and Triatoma infestans tissue extracts and haemolymph

Haemolymph, heads, salivary glands, crops, midguts, hindguts, and Malpighian tubules from Rhodnius prolixus and Triatoma infestans were extracted in phosphate or Tris buffer saline with calcium, and tested for agglutination and lytic activities by microtitration against both vertebrateerythrocytes and cultured epimatigote forms of Trypanosoma rangeli. Haemagglutination activity against rabbit erythrocytes was found in the crop, midgut and hindgut extracts of T. infestans but only in the haemolymph of R. prolixus. Higher titres of parasite agglutinins were found in R. prolixus haemolymph than T. infestans, whilst the converse occurred for the tissue extracts. In addition, the extracts of T. infestans salivary glands, but not those of R. prolixus, showed a trypanolytic activity that was heat-inactivated and was not abolished by pre-incubation with any of the sugars or glycoproteins tested. T. infestans, which is refractory to infection by T. rangeli, thus appears to contain a much wider distribution of agglutinating and trypanolytic factors in its tissues than the more susceptible species, R. prolixus

Aerobic biodegradation of butanol and gasoline blends

This work aimed to assess the aerobic biodegradation of butanol/gasoline, blends (5; 10; 15 and 20% v/v), being the latter compared to the ethanol/gasoline blend (20% v/v). Two experimental techniques were employed, namely the respirometric method and the redox indicator DCPIP test. in the former, experiments simulating the contamination of natural environments (addition of 50 mL of fuel kg(-1) of soil from a non-contaminated site and 20 mL of fuel L(-1) of water from a river) were carried out in biometer flasks (250 mL), used to measure the microbial CO(2) production. The DCPIP test assessed the capability of four inocula to biodegrade the blends of 20%. The addition of butanol at different concentrations enhanced the biodegradation of gasoline in soil. However, no practical gains were observed for concentrations of butanol above 10%. Ethanol showed to have a much faster biodegradation rate than butanol, particularly in water, and the following order of biodegradability was found: ethanol > butanol > gasoline. The addition of the alcohols to the gasoline resulted in positive synergic effects on the biodegradation of the fuels in soil and water matrices. Furthermore, results suggest that, in soil, butanol better enhanced the biodegradation of gasoline than ethanol. (C) 2009 Elsevier Ltd. All rights reserved

Aerobic biodegradation of butanol and diesel oil blends

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Commissioning and performance of the CMS silicon strip tracker with cosmic ray muons

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

The CMS experiment at the CERN LHC

The Compact Muon Solenoid (CMS) detector is described. The detector operates at the Large Hadron Collider (LHC) at CERN. It was conceived to study proton-proton (and lead-lead) collisions at a centre-of-mass energy of 14 TeV (5.5 TeV nucleon-nucleon) and at luminosities up to 10(34)cm(-2)s(-1) (10(27)cm(-2)s(-1)). At the core of the CMS detector sits a high-magnetic-field and large-bore superconducting solenoid surrounding an all-silicon pixel and strip tracker, a lead-tungstate scintillating-crystals electromagnetic calorimeter, and a brass-scintillator sampling hadron calorimeter. The iron yoke of the flux-return is instrumented with four stations of muon detectors covering most of the 4 pi solid angle. Forward sampling calorimeters extend the pseudo-rapidity coverage to high values (vertical bar eta vertical bar <= 5) assuring very good hermeticity. The overall dimensions of the CMS detector are a length of 21.6 m, a diameter of 14.6 m and a total weight of 12500 t.

Combination of Tevatron Searches for the Standard Model Higgs Boson in the W+W- Decay Mode

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Combined Tevatron upper limit on gg -> H -> W+W- and constraints on the Higgs boson mass in fourth-generation fermion models

We combine results from searches by the CDF and D0 collaborations for a standard model Higgs boson (H) in the process gg -> H -> W+W- in p (p) over bar collisions at the Fermilab Tevatron Collider at root s = 1.96 TeV. With 4.8 fb(-1) of integrated luminosity analyzed at CDF and 5.4 fb(-1) at D0, the 95% confidence level upper limit on sigma(gg -> H) x B(H -> W+W-) is 1.75 pb at m(H) = 120 GeV, 0.38 pb at m(H) = 165 GeV, and 0.83 pb at m(H) = 200 GeV. Assuming the presence of a fourth sequential generation of fermions with large masses, we exclude at the 95% confidence level a standard-model-like Higgs boson with a mass between 131 and 204 GeV.

Glioma cordoide do terceiro ventrículo: descrição de um novo caso

O glioma cordoide é um tumor cerebral raro, recentemente descrito, localizado na região do terceiro ventrículo e com características histológicas, imuno-histoquímicas e ultraestruturais peculiares. Este estudo ilustra um caso de glioma cordoide do terceiro ventrículo em uma paciente de 59 anos de idade.

A experiência da toxicomania e da reincidência a partir da fala dos toxicômanos

Este estudo teve como objetivo examinar o fenômeno da toxicomania e sua reincidência a partir da fala dos toxicômanos. Foi realizado em instituição especializada no tratamento da dependência química e problemas relacionados ao uso de álcool e outras drogas, contando com dados do acompanhamento de onze sujeitos. Utilizou-se o referencial teórico psicanalítico para a escuta de indivíduos em situação de toxicomania, com o dispositivo das entrevistas preliminares, dentro do referencial da clínica da urgência em psicanálise. Os resultados do trabalho de escuta e da reflexão apontaram uma série de características psicológicas dos indivíduos estudados de clara relevância para o planejamento de estratégias individuais ou coletivas de atenção ao problema. Destacamos a hipótese de duas modalidades de toxicomania relacionadas com as formas particulares da subjetividade em que ocorre. A questão da reincidência na toxicomania aparece como um falso problema para os sujeitos, que demonstraram que a desintoxicação, concomitante à abstinência e provocada pela internação, é somente um momento de privação, simultaneamente necessária e forçada, do gozo propiciado pela droga. Finda a internação segue-se, geralmente, um novo período de uso. A aceitação da abstinência não significa que os sujeitos fazem uma renúncia, correlata, ao desejo pela droga. É apenas uma parada provavelmente ligada à menor tolerância psíquica à modalidade de gozo em ação na toxicomania, um gozo capaz de confrontar o sujeito com a morte. A abstinência forçada, como estratégia da política pública de saúde, presente no tratamento comum da toxicomania, mostrou conseqüências altamente negativas para o resultado do tratamento, parecendo indicar a necessidade de sua revisão urgente. Procurou-se problematizar a questão da abertura à dimensão subjetiva da experiência dos toxicômanos como estratégia capaz de interferir na trajetória dos sujeitos na relação com as drogas a partir do momento em que buscam ajuda.

Estudo das poliaminas na morfogênese in vitro de Hemerocallis sp.

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Historical land-cover/use in different slope and riparian buffer zones in watersheds of the state of São Paulo, Brazil

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)