Ischemia and reperfusion of the soleus muscle of rats with pentoxifylline

BACKGROUND: Reperfusion of the skeletal muscle worsens existing lesions during ischemia, since the production of reactive oxygen species, associated with intense participation of neutrophils, increases the inflammatory reaction that induces tissue changes. OBJECTIVE: To evaluate the morphological and immunohistochemical changes of the skeletal (soleus) muscle of rats submitted to ischemia and reperfusion with pentoxifylline. METHODS: Sixty rats were submitted to ischemia of the pelvic limb for 6 hours induced by clamping the left common iliac artery. After ischemia, group A animals (n = 30) were observed for 4 hours and group B animals (n = 30) for 24 hours. Six animals constituted the sham group. Pentoxifylline was applied only in the reperfusion period A2 (n = 10) and B2 (n = 10), and in ischemia and reperfusion periods in A3 (n = 10) and B3 (n = 10). The soleus muscle was evaluated by histological (fiber disruption, leukocyte infiltrate, necrosis) and immunohistochemical (apoptosis through caspase-3 expression) analysis. The non-parametric tests Kruskal-Wallis and Mann-Whitney (p < 0.05) were applied. RESULTS: The changes were more intense in group B1, with fiber disruption mean scores of 2.16±0.14; neutrophilic infiltrate of 2.05±0.10; and caspase-3 expression in the perivascular area of 4.30±0.79; and less intense in group A3, with means of 0.76±0.16; 0.92±0.10; 0.67±0,15, respectively (p < 0.05). Caspase-3 was more expressive in group B1 in the perivascular area, with mean of 4.30±0.79 when compared with group B1 in the perinuclear area, with mean of 0.91±0.32 (p < 0.05) CONCLUSIONS: The lesions were more intense when observation time was longer after reperfusion, and pentoxifylline attenuated these lesions, above all when used in the beginning of ischemia and reperfusion phases.CONTEXTO: A reperfusão de músculo esquelético piora as lesões já presentes no período de isquemia, pois a produção de espécies reativas de oxigênio, associadas à intensa participação de neutrófilos, amplia a reação inflamatória que induz alterações teciduais. OBJETIVO: Avaliar as alterações morfológicas e imuno-histoquímicas de músculo esquelético (sóleo) de ratos submetidos a isquemia e reperfusão com pentoxifilina. MÉTODOS: Sessenta ratos foram submetidos a isquemia do membro pélvico, por 6 horas, pelo clampeamento da artéria ilíaca comum esquerda. Após isquemia, os animais do grupo A (n = 30) foram observados por 4 horas, e os do grupo B (n = 30), por 24 horas. Seis animais constituíram o grupo simulado. Administrou-se pentoxifilina apenas no período de reperfusão em A2 (n = 10) e B2 (n = 10) e nos períodos de isquemia e reperfusão em A3 (n = 10) e B3 (n = 10). O músculo sóleo foi avaliado por análise histológica (dissociação de fibras, infiltrado leucocitário, necrose) e imuno-histoquímica (apoptose pela expressão da caspase-3). Foram aplicados os testes não-paramétricos de Kruskal-Wallis e Mann-Whitney (p < 0,05). RESULTADOS: As alterações foram mais intensas no grupo B1, com médias de escore da dissociação de fibras musculares de 2,16 ± 0,14, infiltrado neutrofílico de 2,05 ± 0,10 e expressão da caspase-3 na área perivascular de 4,30 ± 0,79; e menos intensas no grupo A3, com respectivas médias de 0,76 ± 0,16, 0,92 ± 0,10 e 0,67 ± 0,15 (p < 0,05). A caspase-3 mostrou-se mais expressiva no grupo B1 na área perivascular, com média de 4,30 ± 0,79, em comparação com o grupo B1 na área perinuclear, com média de 0,91 ± 0,32 (p < 0,05). CONCLUSÕES: As lesões são mais intensas quando o tempo de observação é maior após a reperfusão, e a pentoxifilina atenua essas lesões, sobretudo quando usada no início das fases de isquemia e de reperfusão.SBACVUniversidade Federal de Mato Grosso do Sul Hospital UniversitárioUniversidade Federal de São Paulo (UNIFESP) Escola Paulista de MedicinaUFMSUNIFESP-EPM Departamento de PatologiaUFMS Departamento de Clínica CirúrgicaUFMS Hospital Universitário Comissão de Residência MédicaUNIFESP, EPM, Depto. de PatologiaSciEL

Quantifying the Universality of the Stellar Initial Mass Function in Old Star Clusters

We present a new technique to quantify cluster-to-cluster variations in the observed present-day stellar mass functions of a large sample of star clusters. Our method quantifies these differences as a function of both the stellar mass and the total cluster mass, and offers the advantage that it is insensitive to the precise functional form of the mass function. We applied our technique to data taken from the ACS Survey for Globular Clusters, from which we obtained completeness-corrected stellar mass functions in the mass range 0.25-0.75 M$_{\odot}$ for a sample of 27 clusters. The results of our observational analysis were then compared to Monte Carlo simulations for globular cluster evolution spanning a range of initial mass functions, total numbers of stars, concentrations, and virial radii. We show that the present-day mass functions of the clusters in our sample can be reproduced by assuming an universal initial mass function for all clusters, and that the cluster-to-cluster differences are consistent with what is expected from two-body relaxation. A more complete exploration of the initial cluster conditions will be needed in future studies to better constrain the precise functional form of the initial mass function. This study is a first step toward using our technique to constrain the dynamical histories of a large sample of old Galactic star clusters and, by extension, star formation in the early Universe.Comment: 11 pages, 4 figures, 4 tables, accepted for publication in MNRAS, proof corrections made in updated versio

A cardinal role for cathepsin D in co-ordinating the host-mediated apoptosis of macrophages and killing of pneumococci

The bactericidal function of macrophages against pneumococci is enhanced by their apoptotic demise, which is controlled by the anti-apoptotic protein Mcl-1. Here, we show that lysosomal membrane permeabilization (LMP) and cytosolic translocation of activated cathepsin D occur prior to activation of a mitochondrial pathway of macrophage apoptosis. Pharmacological inhibition or knockout of cathepsin D during pneumococcal infection blocked macrophage apoptosis. As a result of cathepsin D activation, Mcl-1 interacted with its ubiquitin ligase Mule and expression declined. Inhibition of cathepsin D had no effect on early bacterial killing but inhibited the late phase of apoptosis-associated killing of pneumococci in vitro. Mice bearing a cathepsin D-/- hematopoietic system demonstrated reduced macrophage apoptosis in vivo, with decreased clearance of pneumococci and enhanced recruitment of neutrophils to control pulmonary infection. These findings establish an unexpected role for a cathepsin D-mediated lysosomal pathway of apoptosis in pulmonary host defense and underscore the importance of apoptosis-associated microbial killing to macrophage function

A search for the decay modes B+/- to h+/- tau l

We present a search for the lepton flavor violating decay modes B+/- to h+/- tau l (h= K,pi; l= e,mu) using the BaBar data sample, which corresponds to 472 million BBbar pairs. The search uses events where one B meson is fully reconstructed in one of several hadronic final states. Using the momenta of the reconstructed B, h, and l candidates, we are able to fully determine the tau four-momentum. The resulting tau candidate mass is our main discriminant against combinatorial background. We see no evidence for B+/- to h+/- tau l decays and set a 90% confidence level upper limit on each branching fraction at the level of a few times 10^-5.Comment: 15 pages, 7 figures, submitted to Phys. Rev.

Cross Sections for the Reactions e+e- --> K+ K- pi+pi-, K+ K- pi0pi0, and K+ K- K+ K- Measured Using Initial-State Radiation Events

We study the processes e+e- --> K+ K- pi+pi-gamma, K+ K- pi0pi0gamma, and K+ K- K+ K-gamma, where the photon is radiated from the initial state. About 84000, 8000, and 4200 fully reconstructed events, respectively, are selected from 454 fb-1 of BaBar data. The invariant mass of the hadronic final state defines the \epem center-of-mass energy, so that the K+ K- pi+pi- data can be compared with direct measurements of the e+e- --> K+ K- pi+pi- reaction. No direct measurements exist for the e+e- --> K+ K-pi0pi0 or e+e- --> K+ K-K+ K- reactions, and we present an update of our previous result with doubled statistics. Studying the structure of these events, we find contributions from a number of intermediate states, and extract their cross sections. In particular, we perform a more detailed study of the e+e- --> phi(1020)pipigamma reaction, and confirm the presence of the Y(2175) resonance in the phi(1020) f0(980) and K+K-f0(980) modes. In the charmonium region, we observe the J/psi in all three final states and in several intermediate states, as well as the psi(2S) in some modes, and measure the corresponding product of branching fraction and electron width.Comment: 35 pages, 42 figure

Pan-Cancer Analysis of lncRNA Regulation Supports Their Targeting of Cancer Genes in Each Tumor Context

Long noncoding RNAs (lncRNAs) are commonly dys-regulated in tumors, but only a handful are known toplay pathophysiological roles in cancer. We inferredlncRNAs that dysregulate cancer pathways, onco-genes, and tumor suppressors (cancer genes) bymodeling their effects on the activity of transcriptionfactors, RNA-binding proteins, and microRNAs in5,185 TCGA tumors and 1,019 ENCODE assays.Our predictions included hundreds of candidateonco- and tumor-suppressor lncRNAs (cancerlncRNAs) whose somatic alterations account for thedysregulation of dozens of cancer genes and path-ways in each of 14 tumor contexts. To demonstrateproof of concept, we showed that perturbations tar-geting OIP5-AS1 (an inferred tumor suppressor) andTUG1 and WT1-AS (inferred onco-lncRNAs) dysre-gulated cancer genes and altered proliferation ofbreast and gynecologic cancer cells. Our analysis in-dicates that, although most lncRNAs are dysregu-lated in a tumor-specific manner, some, includingOIP5-AS1, TUG1, NEAT1, MEG3, and TSIX, synergis-tically dysregulate cancer pathways in multiple tumorcontexts

Study of Upsilon(3S,2S) -> eta Upsilon(1S) and Upsilon(3S,2S) -> pi+pi- Upsilon(1S) hadronic trasitions

We study the Upsilon(3S,2S)->eta Upsilon(1S) and Upsilon(3S,2S)->pi+pi- Upsilon(1S) transitions with 122 million Upsilon(3S) and 100 million Upsilon(2S) mesons collected by the BaBar detector at the PEP-II asymmetric energy e+e- collider. We measure B[Upsilon(2S)->eta Upsilon(1S)]=(2.39+/-0.31(stat.)+/-0.14(syst.))10^-4 and Gamma[Upsilon(2S)->eta Upsilon(1S)]/Gamma[Upsilon(2S)-> pi+pi- Upsilon(1S)]=(1.35+/-0.17(stat.)+/-0.08(syst.))10^-3. We find no evidence for Upsilon(3S)->eta Upsilon(1S) and obtain B[Upsilon(3S)->eta Upsilon(1S)]<1.0 10^-4 and Gamma[Upsilon(3S)->eta Upsilon(1S)]/Gamma[Upsilon(3S)->pi+pi- Upsilon(1S)]<2.3 10^-3 as upper limits at the 90% confidence level. We also provide improved measurements of the Upsilon(2S) - Upsilon(1S) and Upsilon(3S) - Upsilon(1S) mass differences, 562.170+/-0.007(stat.)+/-0.088(syst.) MeV/c^2 and 893.813+/-0.015(stat.)+/-0.107(syst.) MeV/c^2 respectively.Comment: 8 pages, 16 encapsulated postscript figures, submitted to Phys.Rev.