ANTAGONISM OF THE MYOTOXIC EFFECTS OF BOTHROPS-JARARACUSSU VENOM AND BOTHROPSTOXIN BY POLYANIONS

The effects of heparin and other polyanions on the myotoxicity of Bothrops jararacussu venom and purified bothropstoxin (BthTX) were investigated. The release rate of creatine kinase (CK) from isolated extensor digitorum longus muscle and the plasma CK activity of mice were used to quantify the results. The myotoxic effects of B. jararacussu venom or BthTX were inhibited by preincubation of these agents with one of the following: a heterogeneous heparin preparation (designated 'heparin'), low mol. wt heparin (H-4500) or dextran sulfates (DS-8000 and DS-500,000). Non-sulfated dextran (D-40,000) and two chondroitin sulfates were ineffective. The antimyotoxic effects of the polyanions are ascribed to their forming inactive acid-base complexes with the basic myotoxins of Bothrops venoms. Gel-filtration experiments in Sephadex provided direct evidence for complex formation between heparin and BthTX. Intravenous (i.v.) administration of H-4500 or DS-8000 opposed the increase in plasma CK activity induced by a subsequent i.m. injection of venom or BthTX. In contrast, pretreatment with i.v. heparin or DS-500,000 enhanced the venom-induced increase in plasma CK activity. This effect was not observed (1) when the animals were treated with a polyvalent antivenom, which inhibits the coagulation and local stasis induced by Bothrops venoms, and (2) when BthTX, which has no thrombotic or hemorrhagic properties, was the myotoxic agent. The potentiation of the venom-induced increase in plasma CK activity by heparin and DS-500,000 is ascribed to improved washout of the CK released from damaged fibers, because of the anticoagulant properties of the drugs.

ESTUDO COMPARATIVO DUPLO-CEGO DA EFICACIA E SEGURANCA DO CILAZAPRIL COMPARADAS A NIFEDIPINE 'RETARD' NO TRATAMENTO DA HIPERTENSAO ARTERIAL LEVE E MODERADA

Purpose: To evaluate the antihypertensive efficacy and safety of cilazapril compared to nifedipine retard in mild to moderate hypertension. Methods: Forty randomized out-patients with mild moderate hypertension, diastolic pressure (DP) between 95 and 115 mmg/Hg, with placebo for 15 days were randomized and allocated for treatment, double-blind, once daily with cilazapril 2.5 mg (n = 20) or nifedipine retard 20 mg (20 = n) for four weeks. The non-responders (DP > 90 mmHg) had the dosage increased twice, b.i.d., while responders were maintained up to 10 weeks. Clinical visits were performed before, at baseline and every two weeks and the laboratory test was performed after placebo run-in, 4th and 10th weeks of treatment. Results: The blood pressure (BP) were similar between groups at the end of the placebo (cilazapril 151 ± 14/103 ± 5 - nifedipine 157 ± 17/108 ± 7 mmHg, p > 0.05). DP decreased already at second weeks (cilazapril 95 ± 9 - nifedipine 96 ± 11 mmHg, p < 0.05, compared to week 0) in both groups at the end of study with no differences inter groups. BP normalization was obtained in 58% of the patients with cilazapril and in 61% in the nifedipine group. Adverse biochemical effects were not observed in any group. Six (16%) patients of the cilazapril and 15 (39%) of nifedipine related collateral events, although no difference were observed between groups. Conclusion: Cilazapril 2.5 to 5 mg normalized BP in 58% of mild and moderate hypertension patients, and this efficacy was similar to sustained-release nifedipine 20 to 40 mg. Cilazapril had no adverse effects on the biochemical parameters with low incidence of collateral effects.

HIPERTENSAO ARTERIAL EM PACIENTES OBESOS COM HIPERTROFIA CARDIACA. EFEITOS DO CAPTOPRIL SOBRE A SENSIBILIDADE A INSULINA E HORMONIO DE CRESCIMENTO

Purpose. To evaluate the effects of captopril (Cpt) on carbohydrate metabolism and growth hormone (GH) in adults hypertensive obese patients with normal (NGT) or impaired (IGT) glucose tolerance and left ventricular hypertrophy. Methods. Ten patients (53 ± 8 years), 8 women and 2 men, white, body mass index (BMI) ≥ 26 kg/m2, left ventricular mass index (LVMI) > 135 g/m2 in man and > 110 g/m2 in woman, with diastolic blood pressure (DBP) 95-115 mmHg after 3 weeks of placebo, were identified by oral glucose tolerance test (OGTT-75 g) as either with NGT or IGT, and treated with Cpt 25 mg t.i.d. for 8 weeks. At the 8 weeks, dosage was increased to 50 mg b.i.d. if DBP > 90 mmHg or the decrease of the DBP < 10%, during the next 8 weeks. OGTT and clonidine tests (0,04 mg/kg) with determinations, every 30 minutes of glucose, insulin, and GH during 2 hours, were performed. Results. Cpt lowered SBP and DBP in the NGT group and IGT group. The LVMI and the left ventricular mass (LVM) decreased in the IGT group with no significant change in the NGT group. Cpt promoted in the IGT group decrease in the area under the curve (AUC) of glucose, and AUC of insulin, with increase of the AUC of the percent of the β cell function, AUC of HC, and insulin sensitivity index with no significantly change in the NGT group. Conclusion. Adults hypertensive obese patients with IGT had decreased significantly in mean fasting level of GH concentrations compared to age, race, and BMI matched hypertensive patients with NGT. Treatment with Cpt induced a significant increased of the GH, with improvement of the metabolism in patients with IGT.

Efeitos do tratamento oral com sulfato de vanadila em ratos diabeticos jovens

This work intends to evaluate the effects of oral vanadyl treatment (VOSO 4, 1 mg/mL) in young streptozotocin-diabetic rats during 19 and 29 days. In several times of treatment the rats were monitored to determine body weight, food and water intakes, glycemia, and the urinary excretion of glucose and urea. The animals were killed in the 19(th) and 29(th) days, and the glycemia level was determined again, as well as the weight of pancreas, muscles (Soleus and Extensor digitorum longus - EDL) and adipose tissues (epididymal and retroperitoneal). The results showed that the treatment of young diabetic rats with VOSO 4 promotes the reduction of hyperglycemia (p < 0.01), food (p < 0.01) and water intakes (p < 0.05) and body weight (p < 0.05). Neither the tissues and pancreas weights nor the urinary urea level of the treatment group varied in comparison to the control group. In conclusion, the vanadyl treatment in the studied period is able to reduce the main metabolic alterations often found in diabetes. These data are very useful and important for the future experiments to verify the effects of vanadyl sulfate on muscle protein metabolism in diabetic rats.

The no-central chi-square chart with two-stage samplings

Throughout this article, it is assumed that the no-central chi-square chart with two stage samplings (TSS Chisquare chart) is employed to monitor a process where the observations from the quality characteristic of interest X are independent and identically normally distributed with mean μ and variance σ2. The process is considered to start with the mean and the variance on target (μ = μ0; σ2 = σ0 2), but at some random time in the future an assignable cause shifts the mean from μ0 to μ1 = μ0 ± δσ0, δ >0 and/or increases the variance from σ0 2 to σ1 2 = γ2σ0 2, γ > 1. Before the assignable cause occurrence, the process is considered to be in a state of statistical control (defined by the in-control state). Similar to the Shewhart charts, samples of size n 0+ 1 are taken from the process at regular time intervals. The samplings are performed in two stages. At the first stage, the first item of the i-th sample is inspected. If its X value, say Xil, is close to the target value (|Xil-μ0|< w0σ 0, w0>0), then the sampling is interrupted. Otherwise, at the second stage, the remaining n0 items are inspected and the following statistic is computed. Wt = Σj=2n 0+1(Xij - μ0 + ξiσ 0)2 i = 1,2 Let d be a positive constant then ξ, =d if Xil > 0 ; otherwise ξi =-d. A signal is given at sample i if |Xil-μ0| > w0σ 0 and W1 > knia:tl, where kChi is the factor used in determining the upper control limit for the non-central chi-square chart. If devices such as go and no-go gauges can be considered, then measurements are not required except when the sampling goes to the second stage. Let P be the probability of deciding that the process is in control and P 1, i=1,2, be the probability of deciding that the process is in control at stage / of the sampling procedure. Thus P = P1 + P 2 - P1P2, P1 = Pr[μ0 - w0σ0 ≤ X ≤ μ0+ w 0σ0] P2=Pr[W ≤ kChi σ0 2], (3) During the in-control period, W / σ0 2 is distributed as a non-central chi-square distribution with n0 degrees of freedom and a non-centrality parameter λ0 = n0d2, i.e. W / σ0 2 - xn0 22 (λ0) During the out-of-control period, W / σ1 2 is distributed as a non-central chi-square distribution with n0 degrees of freedom and a non-centrality parameter λ1 = n0(δ + ξ)2 / γ2 The effectiveness of a control chart in detecting a process change can be measured by the average run length (ARL), which is the speed with which a control chart detects process shifts. The ARL for the proposed chart is easily determined because in this case, the number of samples before a signal is a geometrically distributed random variable with parameter 1-P, that is, ARL = I /(1-P). It is shown that the performance of the proposed chart is better than the joint X̄ and R charts, Furthermore, if the TSS Chi-square chart is used for monitoring diameters, volumes, weights, etc., then appropriate devices, such as go-no-go gauges can be used to decide if the sampling should go to the second stage or not. When the process is stable, and the joint X̄ and R charts are in use, the monitoring becomes monotonous because rarely an X̄ or R value fall outside the control limits. The natural consequence is the user to pay less and less attention to the steps required to obtain the X̄ and R value. In some cases, this lack of attention can result in serious mistakes. The TSS Chi-square chart has the advantage that most of the samplings are interrupted, consequently, most of the time the user will be working with attributes. Our experience shows that the inspection of one item by attribute is much less monotonous than measuring four or five items at each sampling.

Search for supersymmetry in pp collisions at √s = 7 TeV in events with a single lepton, jets, and missing transverse momentum

Results are reported from a search for physics beyond the standard model in proton-proton collisions at a center-of-mass energy of 7TeV, focusing on the signature with a single, isolated, high-transverse-momentum lepton (electron or muon), energetic jets, and large missing transverse momentum. The data sample comprises an integrated luminosity of 36 pb-1, recorded by the CMS experiment at the LHC. The search is motivated by models of new physics, including supersymmetry. The observed event yields are consistent with standard model backgrounds predicted using control samples obtained from the data. The characteristics of the event sample are consistent with those expected for the production of tt̄ and W+jets events. The results are interpreted in terms of limits on the parameter space for the constrained minimal supersymmetric extension of the standard model.

J/ψ and ψ (2S) production in pp collisions at √s = 7 TeV

A measurement of the J/ ψ and ψ (2S) production cross sections in pp collisions at √s = 7TeV with the CMS experiment at the LHC is presented. The data sample corresponds to an integrated luminosity of 37 pb -1. Using a fit to the invariant mass and decay length distributions, production cross sections have been measured separately for prompt and non-prompt charmonium states, as a function of the meson transverse momentum in several rapidity ranges and integrated in the kinematical regions considered in this study. In addition, cross sections restricted to the acceptance of the CMS detector are given, which are not affected by the polarization of the charmonium states. The ratio of the differential production cross sections of the two states, where systematic uncertainties largely cancel, is also determined. The branching fraction of the inclusive B → ψ (2S)X decay is extracted from the ratio of the non-prompt cross sections to be: B(B → ψ (2S)X) = (3:08 ± 0:12 (stat.+syst.) ± 0:13 (theor.) ± 0:42 (BPDG)) × 10 -3: B(B → ψ(2S)X) = (3.08 ± 0.12 (stat.+syst.) ± 0.13 (theor.) ± 0.42 (B PDG)) × 10 -3.

Search for microscopic black holes in pp collisions at √ s = 7 TeV

A search for microscopic black holes in pp collisions at a center-of-mass energy of 7TeV is presented. The data sample corresponds to an integrated luminosity of 4.7 fb1 recorded by the CMS experiment at the LHC in 2011. Events with large total transverse energy have been analyzed for the presence of multiple energetic jets, leptons, and photons, which are typical signals of evaporating semiclassical and quantum black holes, and string balls. Agreement with the expected standard model backgrounds, which are dominated by QCD multijet production, has been observed for various combined multiplicities of jets and other reconstructed objects in the final state. Model-independent limits are set on new physics processes producing high-multiplicity, energetic final states. In addition, new model-specific indicative limits are set excluding semiclassical and quantum black holes with masses below 3.8 to 5.3TeV and string balls with masses below 4.6 to 4.8TeV . The analysis has a substantially increased sensitivity compared to previous searches.

Search for stopped long-lived particles produced in pp collisions at √s = 7 TeV

A search has been performed for long-lived particles that have stopped in the CMS detector, during 7TeV proton-proton operations of the CERN LHC. The existence of such particles could be inferred from observation of their decays when there were no protonproton collisions in the CMS detector, namely during gaps between LHC beam crossings. Using a data set in which CMS recorded an integrated luminosity of 4.0 fb -1, and a search interval corresponding to 246 hours of trigger live time, 12 events are observed, with a mean background prediction of 8:6 ± 2:4 events. Limits are presented at 95% confidence level on long-lived gluino and stop production, over 13 orders of magnitude of particle lifetime. Assuming the cloud model of R-hadron interactions, a gluino with mass below 640 GeV and a stop with mass below 340 GeV are excluded, for lifetimes between 10 μs and 1000 s.

Search for heavy bottom-like quarks in 4.9 fb-1 of pp collisions at √s = 7 TeV

Results are presented from a search for heavy bottom-like quarks, pair-produced in pp collisions at √s = 7TeV, undertaken with the CMS experiment at the LHC. The b′ quarks are assumed to decay exclusively to tW. The b′b̄′ → tW-t̄W+ process can be identified by its distinctive signatures of three leptons or two leptons of same charge, and at least one b-quark jet. Using a data sample corresponding to an integrated luminosity of 4.9 fb-1, observed events are compared to the standard model background predictions, and the existence of b′ quarks having masses below 611 GeV/c2 is excluded at 95% confidence level.

Search for resonant t̄t production in lepton+jets events in pp collisions at √s=7 TeV

A model-independent search for the production of heavy resonances decaying into top-antitop quark pairs is presented. The search is based on events containing one lepton (muon or electron) and at least two jets selected from data samples corresponding to an integrated luminosity of 4.4-5.0 fb -1 collected in pp collisions at √s =7 TeV. Results are presented from the combination of two dedicated searches optimized for boosted production and production at threshold. No excess of events is observed over the expected yield from the standard model processes. Topcolor Z′ bosons with narrow (wide) width are excluded at 95% confidence level for masses below 1.49 (2.04) TeV and an upper limit of 0.3 (1.3) pb or lower is set on the production cross section times branching fraction for resonance masses above 1 TeV. Kaluza-Klein excitations of a gluon with masses below 1.82 TeV (at 95% confidence level) in the Randall-Sundrum model are also excluded, and an upper limit of 0.7 pb or lower is set on the production cross section times branching fraction for resonance masses above 1 TeV.[Figure not available: See fulltext.] © 2012 CERN for the benefit of the CMS collaboration.

Measurement of the single-top-quark t-channel cross section in pp collisions at √s=7 TeV

A measurement of the single-top-quark t-channel production cross section in pp collisions at √s=7 TeV with the CMS detector at the LHC is presented. Two different and complementary approaches have been followed. The first approach exploits the distributions of the pseudorapidity of the recoil jet and reconstructed top-quark mass using background estimates determined from control samples in data. The second approach is based on multivariate analysis techniques that probe the compatibility of the candidate events with the signal. Data have been collected for the muon and electron final states, corresponding to integrated luminosities of 1.17 and 1.56 fb-1, respectively. The single-top-quark production cross section in the t-channel is measured to be 67.2±6.1 pb, in agreement with the approximate next-to-next-to-leading- order standard model prediction. Using the standard model electroweak couplings, the CKM matrix element |V tb| is measured to be 1.020 ± 0.046 (meas.) ± 0.017 (theor.). © 2012 CERN for the benefit of the CMS collaboration.

Search for third-generation leptoquarks and scalar bottom quarks in pp collisions at √s=7Tev

Results are presented from a search for third-generation leptoquarks and scalar bottom quarks in a sample of proton-proton collisions at √s=7Tev collected by the CMS experiment at the LHC, corresponding to an integrated luminosity of 4.7 fb-1. A scenario where the new particles are pair produced and each decays to a b quark plus a tau neutrino or neutralino is considered. The number of observed events is found to be in agreement with the standard model prediction. Upper limits are set at 95% confidence level on the production cross sections. Leptoquarks with masses below ~450 GeV are excluded. Upper limits in the mass plane of the scalar quark and neutralino are set such that scalar bottom quark masses up to 410 GeV are excluded for neutralino masses of 50 GeV. © 2012 CERN for the benefit of CMS collaboration.

Forward-backward asymmetry of Drell-Yan lepton pairs in pp collisions at s=7TeV

A measurement of the forward-backward asymmetry (AFB) of Drell-Yan lepton pairs in pp collisions at s=7TeV is presented. The data sample, collected with the CMS detector, corresponds to an integrated luminosity of 5fb-1. The asymmetry is measured as a function of dilepton mass and rapidity in the dielectron and dimuon channels. Combined results from the two channels are presented, and are compared with the standard model predictions. The AFB measurement in the dimuon channel and the combination of the two channels are the first such results obtained at a hadron collider. The measured asymmetries are consistent with the standard model predictions. © 2012 CERN.

Search for new physics in events with opposite-sign leptons, jets, and missing transverse energy in pp collisions at s=7 TeV

A search is presented for physics beyond the standard model (BSM) in final states with a pair of opposite-sign isolated leptons accompanied by jets and missing transverse energy. The search uses LHC data recorded at a center-of-mass energy s=7 TeV with the CMS detector, corresponding to an integrated luminosity of approximately 5 fb-1. Two complementary search strategies are employed. The first probes models with a specific dilepton production mechanism that leads to a characteristic kinematic edge in the dilepton mass distribution. The second strategy probes models of dilepton production with heavy, colored objects that decay to final states including invisible particles, leading to very large hadronic activity and missing transverse energy. No evidence for an event yield in excess of the standard model expectations is found. Upper limits on the BSM contributions to the signal regions are deduced from the results, which are used to exclude a region of the parameter space of the constrained minimal supersymmetric extension of the standard model. Additional information related to detector efficiencies and response is provided to allow testing specific models of BSM physics not considered in this Letter. © 2012 CERN.