Phospholipase A(2) myotoxins from Bothrops snake venoms: Structure-function relationship

Phospholipases A(2) constitute the major components from Bothrops snake venoms and have been extensively investigated not only because they are relatively very abundant in these venoms but mainly because they display a range of many relevant biological effects, including: myotoxic, cytotoxic, edema-inducing, artificial membrane disrupting, anticoagulant, neuromuscular, platelet aggregation inhibiting, hypotensive, bactericidal, anti-HIV, anti-tumoural, anti-malarial and anti-parasitic. The primary structures of several PLA(2)s have been elucidated through direct amino acid sequencing or, inderectly, through the corresponding nucleotide sequencing. Two main subgroups were thus described: (i) Asp49 PLA(2)s, showing low (basic, highly myotoxic) to relatively high (acidic, less or non myotoxic) Ca++-dependent hydrolytic activity upon artificial substrates; (ii) Lys49 PLA(2)s (basic, highly myotoxic) , showing no detectable hydrolytic activity on artificial substrates. Several crystal structures of Lys49 PLAs from genus Bothrops have already been solved, revealing very similar fold patterns. Lack of catalytic activity of myotoxic Lys49-PLA(2)s, first related solely with the fact that Lys49 occupies the position of the calcium ion in the catalyticly active site of Asp49 PLA(2)s, is now also attributed to Lys122 which interacts with the carbonyl of Cys29 hyperpolarising the peptide bond between Cys29 and Gly30 and trapping the fatty acid product in the active site, thus interrupting the catalytic cycle. This hypothesis, supported for three recent structures, is also discussed here. All Asp49 myotoxins showed to be pharmacologically more potent when compared with the Lys49 variants, but phospholipid hydrolysis is not an indispensable condition for the myotoxic, cytotoxic, bactericidal, anti-HIV, anti-parasitic, liposome disrupting or edema-inducing activities. Recent studies on site directed mutagenesis of the recombinant Lys49 myotoxin from Bothrops jararacussu revealed the participation of important amino acid residues in the membrane damaging and myotoxic activities.

Inner satellites of Neptune: I the disturbing function

In this work, we focus our attention to the expansion of the disturbing function (R) which governs the dynamics of a satellite (natural or artificial) in the Neptune-Triton system. What makes this problem quite unusual, is the fact that a small inner satellite can be strongly disturbed by Triton which is moving in a highly inclined and retrograde orbit. These features are unique in our solar system. Although a lot of retrograde satellites are currently known, all of them have negligible mass and the), do not offer almost any perturbation on the others satellites. However, in the case of the inner satellites of Neptune, Triton is an interesting exception. In a highly inclined orbit, the perturbation it exerts on the neighbouring satellites of Neptune cannot be ignored even for the present scenario. However, in the future, this perturbation will be much more important because due to the tides, the orbit of Triton is contracting, whereas the semi major axes of the remaining inner satellites of Neptune will remain almost unaffected by the tides. In this work we first obtain the disturbing function in the retrograde case. After that, we generalize R for arbitrary inclination. Several numerical tests are presented and a possible future case of resonant configuration is briefly discussed as well. (c) 2005 COSPAR. Published by Elsevier Ltd. All rights reserved.

Relative contributions of beta-cell function and tissue insulin sensitivity to fasting and postglucose-load glycemia

We performed hyperglycemic clamps in 283 nondiabetic Caucasians and, with multiple linear regression, determined the contribution of beta-cell function and tissue insulin sensitivity to variations in glycemia and insulinemia during oral glucose tolerance tests (OGTTs). Impaired glucose tolerance (IGT) subjects had reduced insulin sensitivity(P < .02) and beta-cell function (P < .0001). Normal glucose tolerance (NGT) subjects with first-degree type 2 diabetic relatives had reduced first and second phase insulin secretion (both, P < .05), but normal insulin sensitivity(P = .37). beta-Cell function and insulin sensitivity accounted for one fourth of the variability in glucose tolerance. Fasting plasma glucose in subjects with NGT (n = 185) was a function of both phases of insulin secretion and of insulin sensitivity tall, P < .05), whereas, in IGT subjects (n = 98), it was a function of first phase insulin secretion and insulin sensitivity(P < .01). Two-hour glycemia was a function of second phase secretion and insulin sensitivity (P < .01). Fasting and 2-hour plasma insulin levels were determined by insulin sensitivity land glycemia) in NGT subjects (P < .001), but by second phase secretion in IGT (P < .001). We conclude that beta-cell function is reduced in subjects with IGT; glycemia and insulinemia are not regulated by the same mechanisms in IGT and NGT; insulin sensitivity does not contribute to insulinemia in IGT; family history of diabetes influences beta-cell function, but not insulin sensitivity in Caucasians. Copyright (C) 2000 by W.B. Saunders Company.

Energy efficiency for standard penetration tests

The need for standardization of the measured blow count number N-spt into a normalized reference energy value is now fully recognized. The present paper extends the existing theoretical approach using the wave propagation theory as framework and introduces an analysis for large displacements enabling the influence of rod length in the measured N-spt values to be quantified. The study is based on both calibration chamber and field tests. Energy measurements are monitored in two different positions: below the anvil and above the sampler. Both experimental and numerical results demonstrate that whereas the energy delivered into the rod stem is expressed as a ratio of the theoretical free-fall energy of the hammer, the effective sampler energy is a function of the hammer height of fall, sampler permanent penetration, and weight of both hammer and rods. Influence of rod length is twofold and produces opposite effects: wave energy losses increase with increasing rod length and in a long rod composition the gain in potential energy from rod weight is significant and may partially compensate measured energy losses. Based on this revised approach, an analytical solution is proposed to calculate the energy delivered to the sampler and efficiency coefficients are suggested to account for energy losses during the energy transference process.

Perioperative administration of vedaprofen, tramadol or their combination does not interfere with platelet aggregation, bleeding time and biochemical variables in cats

A randomized double blind and placebo controlled design was used to investigate the hemostatic, biochemical, gastrointestinal and behavioral effects of pre- and postoperative administration of vedaprofen 0.5 mg/kg PO (V), tramadol 2 mg/kg SC (T), their association (VT) or placebo (P) in 40 adult female cats (3.0 +/- 0.32 kg; 1.8 +/- 0.7 years) distributed in groups of 10. Platelet aggregation and bleeding time were measured before and 52 11 after ovariohysterectomy. Serum urea, creatinine, alanine aminotransferase, alkaline phosphatase and gamma-glutamyl transferase concentrations were measured before and 7 days postoperatively. The occurrence of vomiting, frequency and consistency of feces, and behavior were observed for 7 days postoperatively. Morphine (0.5 mg/kg, IM) was used as rescue analgesic. Laboratory variables did not change. Vomiting was observed only after morphine administration. Mild euphoria was observed in T and VT. The perioperative use of vedaprofen and/or tramadol did not modify the hemostatic, biochemical and gastrointestinal function in cats. (C) 2009 ESFM and AAFP. published by Elsevier Ltd. All rights reserved.

A PZT-based technique for SHM using the coherence function

This paper presents a new approach for damage detection in structural health monitoring systems exploiting the coherence function between the signals from PZT (Lead Zirconate Titanate) transducers bonded to a host structure. The physical configuration of this new approach is similar to the configuration used in Lamb wave based methods, but the analysis and operation are different. A PZT excited by a signal with a wide frequency range acts as an actuator and others PZTs are used as sensors to receive the signal. The coherences between the signals from the PZT sensors are obtained and the standard deviation for each coherence function is computed. It is demonstrated through experimental results that the standard deviation of the coherence between the signals from the PZTs in healthy and damaged conditions is a very sensitive metric index to detect damage. Tests were carried out on an aluminum plate and the results show that the proposed methodology could be an excellent approach for structural health monitoring (SHM) applications.

Preoperative upper limb lymphatic function in breast cancer surgery.

To describe the preoperative upper limb lymphoscintigraphic pattern in women with breast cancer. Thirty-seven patients undergoing lymphoscintigraphy within 30 days of surgery were investigated. Lymphoscintigraphic studies of 37 upper limbs ipsilateral to surgery and 32 contralateral upper limbs were performed. The examination protocol consisted in obtaining static images of the upper limb in semi-flexion after 10 minutes, and 1 and 2 hours after subcutaneous injection of 1 mCi (37 MBq) of Tc-99m-dextran in the dorsum of the hand. The velocity of axillary lymph node visualization (I, visible at 10 minutes; II, 1 hour; III, 2 hours; and IV, invisible) and degree (intensity) of nodal uptake (a, marked; b, moderate; c,mild; and d, absent) were analyzed. Optimal lymphatic functional pattern (Ia) was observed in four (11%) patients, in the ipsilateral upper limb, and six (19%), in the contralateral upper limb. Worse condition was observed in three (8%) patients (IVd) in the ipsilateral upper limb and two (6%) patients in the contralateral upper limb. The remaining patients showed intermediate states of velocity and uptake intensity. This study found relevant changes in preoperative lymphoscintigraphy, demonstrating preexisting functional differences in the lymphatic system.

Performance of children with learning difficulties in fine motor function and handwriting

This study aimed to compare and characterize the fine, sensory and perceptive function performance and handwriting quality between students with learning difficulties and students with good academic performance. Methods: This study comprised 192 students from 2nd to 4th grades, both genders, whose ages ranged from 7 to 11 years old. The students were distributed into: GI, GII, GIII and GIV, comprising 96 students with learning difficulties, and groups GV, GVI, GVII, GVIII comprising 96 students with good academic performance. The students were submitted to evaluation of fine motor, sensorial and perception functions and handwriting evaluation under dictation. Results: The results showed that the students with learning difficulties, from 1st to 3rd grade, had lower performance on tests of fine motor, sensory and perceptive function, when compared to the students with good academic performance in the same grade; the students from 4th grade, both groups, did not show changes on fine motor, sensory and perceptive function; and only the students of GII showed dysgraphia. Conclusions: the results presented in this study suggest that the qualitative aspects of fine motor, sensory and perceptive skills reflect the integrity and maturity of central nervous system and can probably play an important role in early diagnosis of development disorders and consequently prevent academic disorders such as handwriting performance.

Parametric VaR with goodness-of-fit tests based on EDF statistics for extreme returns

Parametric VaR (Value-at-Risk) is widely used due to its simplicity and easy calculation. However, the normality assumption, often used in the estimation of the parametric VaR, does not provide satisfactory estimates for risk exposure. Therefore, this study suggests a method for computing the parametric VaR based on goodness-of-fit tests using the empirical distribution function (EDF) for extreme returns, and compares the feasibility of this method for the banking sector in an emerging market and in a developed one. The paper also discusses possible theoretical contributions in related fields like enterprise risk management (ERM). © 2013 Elsevier Ltd.

Determinação do teste padrão para o diagnóstico de cães com doença de von willebrand

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Optimizing urban traffic flow using genetic algorithm with petri net analysis as fitness function

This paper describes a new methodology adopted for urban traffic stream optimization. By using Petri net analysis as fitness function of a Genetic Algorithm, an entire urban road network is controlled in real time. With the advent of new technologies that have been published, particularly focusing on communications among vehicles and roads infrastructures, we consider that vehicles can provide their positions and their destinations to a central server so that it is able to calculate the best route for one of them. Our tests concentrate on comparisons between the proposed approach and other algorithms that are currently used for the same purpose, being possible to conclude that our algorithm optimizes traffic in a relevant manner.

Improvements in the sensibility of MSA-GA tool using COFFEE objective function

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

Location, morphology and function of nephrocytes in termites

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Platelet-rich plasma (PRP) applied during total knee arthroplasty

To evaluate the efficacy of platelet-rich plasma regarding healing, pain and hemostasis after total knee arthroplasty, by means of a blinded randomized controlled and blinded clinical study. Forty patients who were going to undergo implantation of a total knee prosthesis were selected and randomized. In 20 of these patients, platelet-rich plasma was applied before the joint capsule was closed. The hemoglobin (mg/dL) and hematocrit (%) levels were assayed before the operation and 24 and 48 h afterwards. The Womac questionnaire and a verbal pain scale were applied and knee range of motion measurements were made up to the second postoperative month. The statistical analysis compared the results with the aim of determining whether there were any differences between the groups at each of the evaluation times. The hemoglobin (mg/dL) and hematocrit (%) measurements made before the operation and 24 and 48 h afterwards did not show any significant differences between the groups (p > 0.05). The Womac questionnaire and the range of motion measured before the operation and up to the first two months also did not show any statistical differences between the groups (p > 0.05). The pain evaluation using the verbal scale showed that there was an advantage for the group that received platelet-rich plasma, 24 h, 48 h, one week, three weeks and two months after the operation (p < 0.05). In the manner in which the platelet-rich plasma was used, it was not shown to be effective for reducing bleeding or improving knee function after arthroplasty, in comparison with the controls. There was an advantage on the postoperative verbal pain scale.

Thrombocytopenia and platelet hypoaggregation induced by Bothrops asper snake venom Toxins involved and their contribution to metalloproteinase-induced pulmonary hemorrhage

Thrombocytopenia and platelet dysfunction occur in patients bitten by Bothrops sp snakes in Latin America. An experimental model was developed in mice to study the effects of B. asper venom in platelet numbers and function. Intravenous administration of this venom induces rapid and prominent thrombocytopenia and ex vivo platelet hypoaggregation. The drop in platelet numbers was primarily due to aspercetin, a protein of the C-type lectin family which induces von Willebrand factor-mediated platelet aggregation/agglutination. In addition, the effect of class P-III hemorrhagic metalloproteinases on the microvessel wall also contributes to thrombocytopenia since jararhagin, a P-III metalloproteinase, reduced platelet counts. Hypoaggregation was associated with the action of procoagulant and defibrin(ogen)ating proteinases jararacussin-1 (a thrombin-like serine proteinase) and basparin A (a prothrombin activating metalloproteinase). At the doses which induced hypoaggregation, these enzymes caused defibrin(ogen)ation, increments in fibrin(ogen) degradation products and D-dimer and prolongation of the bleeding time. Incubation of B. asper venom with batimastat and α 2-macroglobulin abrogated the hypoaggregating activity, confirming the role of venom proteinases in this effect. Neither aspercetin nor the defibrin(ogen)ating and hypoaggregating components induced hemorrhage upon intravenous injection. However, aspercetin, but not the thrombin-like or the prothrombin-activating proteinases, potentiated the hemorrhagic activity of two hemorrhagic metalloproteinases in the lungs. © 2005 Schattauer GmbH, Stuttgart.