Immunological response in mice bearing LM3 breast tumor undergoing Pulchellin treatment

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

Immune Response Against Sporothrix schenckii in TLR-4-Deficient Mice

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

Susceptibility to Yersinia pseudotuberculosis Infection is Linked to the Pattern of Macrophage Activation

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

Cytokines and acute-phase serum proteins as markers of inflammatory regression during pulmonary tuberculosis treatment

Tuberculosis is still increasing and was declared a worldwide sanitary emergency by the World Health Organization (WHO) in 1995. Its control is difficult due to long treatment duration and lack of markers of treatment success or failure. Cytokines such as IFN-gamma and TNF-alpha, a central factor in immune response against Mycobacterium tuberculosis, are responsible for the interaction between T lymphocytes and the infected macrophage and are also produced during this interaction. As proinflammatory cytokines have a close relationship with mycobacteria clearance, in fact even preceding it, they could be used as markers for inflammatory activity and response to treatment. Proinflammatory cytokines act in the liver and stimulate a strong local and systemic acute-phase response as a result of homeostatic and physiological responses also induced by them. Acute-phase proteins produced by cytokine activity are useful diagnostic markers that could also be used to monitor treatment response as they can be serially quantified. The objective of this study was to evaluate IFN-gamma, TNF-alpha, IL-10 and TGF-beta production in supernatant of peripheral blood mononuclear cell (PBMC) and monocyte (MO) cultures, as well as serum acute-phase response through total protein, albumin, globulin, C-reactive protein (CRP), alpha-1-acid glycoprotein (AGP), and erythrocyte sedimentation rate (ESR) as regression markers of inflammatory response during pulmonary tuberculosis treatment. Twenty blood donors (G1) from the Blood Bank at Botucatu School of Medicine's University Hospital (BSM-UH) were evaluated once and 28 pulmonary tuberculosis patients (G2): 13 from BSM-UH and 15 from the Bauru State Health Secretariat. Patients were evaluated at three moments of treatment: before (M1), at three months (M2), and at the end (M3). Cytokines were determined in 20ml of peripheral blood (ELISA), with or without activation: lipopolysaccharide (LPS) for MO culture and phytohemagglutinin (PHA) for PBMC culture. Acute-phase protein behavior in G2 throughout treatment was: Globulins: M1> M2, M1> M3 (rho < 0.001); CRP: M1> M2> M3 (.< 0.001); AGP for men: M1> M2, M1> M3 (rho < 0.001); ESR for men: M1> M2, M1> M3 (rho < 0.0016) and for women: M1> M2 (.< 0.025). Comparison between cytokine levels found in supernatant of MO and PBMC cultures, with and without stimulus, in G1 and G2 during treatment showed: TNF-alpha (with/ without LPS) at M1: G2> G1; at M2: G2> G1 (rho < 0.001); (without LPS) at M3: G2> G1 (rho < 0.001), (with LPS) at M3: G2> G1 (rho < 0.028); IFN-. (with and without PHA) at M1: G2> G1; at M2: G2> G1 (rho < 0.001); IL-10 (with and without LPS) at M1: G2> G1; at M2: G2> G1; at M3: G2> G1 (rho < 0.001); TGF-beta (with and without LPS) at M1: G2> G1; at M2: G2> G1 (rho < 0.001), (without LPS) at M3: G2> G1 (rho < 0.001). In G2, all cytokines in supernatant of MO and PBMC cultures, with and without stimulus, showed: M1> M2> M3 (rho < 0.01). Levels of globulins, CRP, AGP, and ESR in patients with pulmonary tuberculosis before treatment (M1) were significantly higher than reference values, suggesting their use as diagnostic markers and indicators of treatment. The CRP decreasing values along treatment could be taken as a marker of the regression of inflammatory process and of response to treatment in patients with pulmonary tuberculosis.Regarding cytokines, there was significant increase in TNF-alpha, IFN-gamma, IL-10, and TGF-alpha levels before and at three months treatment, with and without stimulus; in TNF-a and IL-10 lvels, with and without stimulus, as well as in TGF-alpha levels without stimulus at six months. Patients had higher levels of all studied cytokines than controls before treatment, and these values decreased along treatment. In this study, pulmonary tuberculosis patients showed a Th0 cytokine profile before treatment, with the production of both Th1 (IFN-gamma) and Th2 (IL-10) cytokines, in addition to TNF-alpha inflammatory and TGF-alpha regulatory and fibrosis-inducer cytokines. At the end of treatment, all had evolved to Th2 profile, probably in an attempt to reduce the harmful effects of the proinflammatory activity of the Th1 cytokine profile and of the still above-normal levels of TNF-alpha. The high levels of TGF-alpha, also found in these patients, are related to its important role in the extracellular matrix deposition and fibrosis induction that characterize tuberculosis healing process. IFN-gamma was the only cytokine reaching normal levels at the end of treatment, which suggests its use as a marker of response to treatment.

Polysaccharide fraction of Agaricus brasiliensis avoids tumor-induced IL-10 production and changes the microenvironment of subcutaneous Ehrlich adenocarcinoma

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

Interleukin-10 but not Transforming Growth Factor beta inhibits murine activated macrophages Paracoccidioides brasiliensis killing: Effect on H2O2 and NO production

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

Myostatin and follistatin expression in skeletal muscles of rats with chronic heart failure

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

Search for first-generation scalar leptoquarks in p(p)over-bar collisions at root s=1.96 TeV

We report on a search for pair production of first-generation scalar leptoquarks (LQ) in p (p) over bar collisions at root s=1.96 TeV using an integrated luminosity of 252 pb(-1) collected at the Fermilab Tevatron collider by the D0 detector. We observe no evidence for LQ production in the topologies arising from LQ(LQ) over bar -> eqeq and LQ(LQ) over bar -> eq nu q, and derive 95% C.L. lower limits on the LQ mass as a function of beta, where beta is the branching fraction for LQ -> eq. The limits are 241 and 218 GeV/c(2) for beta=1 and 0.5, respectively. These results are combined with those obtained by D0 at root s=1.8 TeV, which increases these LQ mass limits to 256 and 234 GeV/c(2).

Search for pair production of second generation scalar leptoquarks in p(p)over-bar collisions at root s-=1.96 TeV

We report on a search for the pair production of second generation scalar leptoquarks (LQ(2)) in p (p) over bar collisions at the center-of-mass energy, root s = 1.96 TeV, using data corresponding to an integrated luminosity of 294 19 pb(-1) recorded with the DO detector. No evidence for a leptoquark signal in the LQ(2)LQ(2) -> mu q mu q channel has been observed, and upper bounds on the product of cross section times branching fraction were set. This yields lower mass limits of m(LQ2) > 247 GeV/c(2) for beta = B(LQ(2) -> mu q) = 1 and m(LQ2) > 182 GeV/c(2) for beta = 1/2. Combining these limits with previous DO results, the lower limits on the mass of a second generation scalar leptoquark are m(LQ2) > 251 GeV/c(2) and m(LQ2) > 204 GeV/c(2) for beta = I and beta = 1/2, respectively. (c) 2006 Elsevier B.V. All rights reserved.

Scalar field theory at finite temperature in D=2+1

We discuss the phi(6) theory defined in D=2+1-dimensional space-time and assume that the system is in equilibrium with a thermal bath at temperature beta(-1). We use the 1/N expansion and the method of the composite operator (Cornwall, Jackiw, and Tomboulis) for summing a large set of Feynman graphs. We demonstrate explicitly the Coleman-Mermin-Wagner theorem at finite temperature.

Scalar field theory at finite temperature in D=2+1

We discuss the phi(6) theory defined in D = 2 + 1-dimensional space-time and assume that the system is in equilibrium with a thermal bath at temperature beta(-1). We use the 1/N expansion and the method of composite operator (CJT) for summing a large set of Feynman graphs. We demonstrate explicitly the Coleman-Mermin-Wagner theorem at finite temperature.

Search for pair production of first-generation leptoquarks in p(p)over-bar collisions at root s=1.96 TeV

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

beta Phase transformations in the Cu-11mass%Al alloy with Ag additions

In the Cu-Al system, due to the sluggishness of the beta a dagger" (alpha + gamma(1)) eutectoid reaction, the beta phase can be retained metastably. During quenching, metastable beta alloys undergo a martensitic transformation to a beta' phase at Al low content. The ordering reaction beta a dagger" beta(1) precedes the martensitic transformation. The influence of Ag additions on the reactions containing the beta phase in the Cu-11mass%Al alloy was studied using differential scanning calorimetry and in situ X-ray diffractometry. The results indicated that, on cooling, two reactions are occurring in the same temperature range, the beta -> (alpha + gamma(1)) decomposition reaction and the beta -> beta(1) reaction, with different reaction mechanisms (diffusive for the former and ordering for the latter) and, consequently, with different reaction rates. For lower cooling rates, the dominant is the decomposition reaction and for higher cooling rates the ordering reaction prevails. on heating, the (alpha + gamma(1)) -> beta reverse eutectoid reaction occurs with a resulting beta phase saturated with alpha. The increase of Ag concentration retards the beta -> (alpha + gamma(1)) decomposition reaction and the beta -> beta(1) ordering reaction, which occurs in the same temperature range, becomes the predominant process.

Pharmacological evidence for beta(2)-adrenoceptor in right atria from stressed female rats

The purpose of the present study was to demonstrate a physiological response to TA2005, a potent beta(2)-adrenoceptor (beta(2)-AR) selective agonist, in right atria isolated from stressed female rats under the influence of the estrous cycle. We obtained concentration-response curves to the agonist in the presence and in the absence of selective antagonists in right atria isolated from female rats submitted to three daily foot-shock sessions (30 min duration, 120 pulses of 1.0 mA, 1.0 s, applied at random intervals of 5-25 s) and sacrificed at estrus or diestrus. Our results showed that the pD(2), values of TA2005 were not influenced by estrous cycle phase or foot-shock stress. However, in right atria from stressed rats sacrificed during diestrus, the concentration-response curve to TA2005 was biphasic, with a response being obtained at concentrations of 0.1 nM, whereas during estrus no response was observed at doses lower than 3 nM. ICI118,551, a beta(2)-AR antagonist, abolished the response to nanomolar concentrations of TA2005 in right atria from stressed rats at diestrus, with no changes in a,agonist pot values in right atria from control rats (7.47 +/- 0.09, p > 0.05) but a 3-fold decrease in pD(2), values of TA2005 in right atria from foot shock stressed rats (7.90 +/- 0.07, p less than or equal to 0.05). Concentration-response curves to TA2005 in the presence of ICI118,551 were best fitted by a one-site model equation. The beta(1)-AR antagonist, CGP20712A, shifted to the right only the second part of the concentration-response curves to the agonist, unmasking the putative Pz-AR-mediated response to the agonist in tissues isolated from stressed rats at diestrus. Under this condition, concentration-response curves to the agonist were best fitted by a two-site model equation. pot and maximum response of TA2005 interaction with beta(1)- and putative Pz-adrenoceptor components were calculated. Schild analyses gave a pK(B) value for CGP20712A that was typical for the interaction with beta(1)-AR in each experimental group. pK(B), values for ICI118,551 could not be obtained in stressed rats sacrificed at diestrus since Schild plot slopes were lower than 1.0. In right atria from control rats, ICI118,551 pK(B), values were similar to reported values for the interaction of the antagonist with beta(1)-AR. These results confirm that a heterogenous PAR population mediating the chronotropic response to catecholamines can be demonstrated in right atria from foot shock stressed female rats sacrificed at diestrus. The stress-induced response seems to be mediated by the beta(2)-AR subtype. Right atria from rats sacrificed during estrus are protected against stress-induced alterations on the homogeneity of PAR population.

cDNA cloning and 1.75 angstrom crystal structure determination of PPL2, an endochitinase and N-acetylglucosamine-binding hemagglutinin from Parkia platycephala seeds

Parkia platycephala lectin 2 was purified from Parkia platycephala (Leguminosae, Mimosoideae) seeds by affinity chromatography and RP-HPLC. Equilibrium sedimentation and MS showed that Parkia platycephala lectin 2 is a nonglycosylated monomeric protein of molecular mass 29 407 +/- 15 Da, which contains six cysteine residues engaged in the formation of three intramolecular disulfide bonds. Parkia platycephala lectin 2 agglutinated rabbit erythrocytes, and this activity was specifically inhibited by N-acetylglucosamine. In addition, Parkia platycephala lectin 2 hydrolyzed beta(1-4) glycosidic bonds linking 2-acetoamido-2-deoxy-beta-D-glucopyranose units in chitin. The full-lengthamino acid sequence of Parkia platycephala lectin 2, determined by N-terminal sequencing and cDNA cloning, and its three-dimensional structure, established by X-ray crystallography at 1.75 angstrom resolution, showed that Parkia platycephala lectin 2 is homologous to endochitinases of the glycosyl hydrolase family 18, which share the (beta alpha)(8) barrel topology harboring the catalytic residues Asp125, Glu127, and Tyr182.