Cardiac Complications in Patients with Community-Acquired Pneumonia: A Systematic Review and Meta-Analysis of Observational Studies

Vicente Corrales-Medina and colleagues report estimates of the risk of cardiac complications among patients with community-acquired pneumonia from a systematic review and meta-analysis

The lung cancer exercise training study: a randomized trial of aerobic training, resistance training, or both in postsurgical lung cancer patients: rationale and design

<p>Abstract</p> <p>Background</p> <p>The Lung Cancer Exercise Training Study (LUNGEVITY) is a randomized trial to investigate the efficacy of different types of exercise training on cardiorespiratory fitness (VO_2peak), patient-reported outcomes, and the organ components that govern VO_2peakin post-operative non-small cell lung cancer (NSCLC) patients.</p> <p>Methods/Design</p> <p>Using a single-center, randomized design, 160 subjects (40 patients/study arm) with histologically confirmed stage I-IIIA NSCLC following curative-intent complete surgical resection at Duke University Medical Center (DUMC) will be potentially eligible for this trial. Following baseline assessments, eligible participants will be randomly assigned to one of four conditions: (1) aerobic training alone, (2) resistance training alone, (3) the combination of aerobic and resistance training, or (4) attention-control (progressive stretching). The ultimate goal for all exercise training groups will be 3 supervised exercise sessions per week an intensity above 70% of the individually determined VO_2peakfor aerobic training and an intensity between 60 and 80% of one-repetition maximum for resistance training, for 30-45 minutes/session. Progressive stretching will be matched to the exercise groups in terms of program length (i.e., 16 weeks), social interaction (participants will receive one-on-one instruction), and duration (30-45 mins/session). The primary study endpoint is VO_2peak. Secondary endpoints include: patient-reported outcomes (PROs) (e.g., quality of life, fatigue, depression, etc.) and organ components of the oxygen cascade (i.e., pulmonary function, cardiac function, skeletal muscle function). All endpoints will be assessed at baseline and postintervention (16 weeks). Substudies will include genetic studies regarding individual responses to an exercise stimulus, theoretical determinants of exercise adherence, examination of the psychological mediators of the exercise - PRO relationship, and exercise-induced changes in gene expression.</p> <p>Discussion</p> <p>VO_2peakis becoming increasingly recognized as an outcome of major importance in NSCLC. LUNGEVITY will identify the optimal form of exercise training for NSCLC survivors as well as provide insight into the physiological mechanisms underlying this effect. Overall, this study will contribute to the establishment of clinical exercise therapy rehabilitation guidelines for patients across the entire NSCLC continuum.</p> <p>Trial Registration</p> <p>NCT00018255</p

Enhancement of 5-Aminolevulinic acid-induced oxidative stress on two cancer cell lines by gold nanoparticles

5-Aminolevulinic acid (5-ALA) and its methyl ester (5-ALA-Me) at mM concentration levels induce oxidative stress via the production of reactive oxygen species (ROS). Human cancer cell lines (MCF-7 and HepG2) incubated in the dark in the simultaneous presence of 5.0 mM or more 5-ALA or 5-ALA-Me (for MCF-7) and 7 g/mL of 15 nm citrate capped gold nanoparticles (AuNPs) were damaged more seriously compared to those in the presence of the levulinic acid alone. Damage is visible in electron micrographs which reveal similar morphology both in the presence or absence of AuNPs. Cytotoxicity was observed irrespective of the presence of serum and medium. Production of ROS in cell free samples containing 5-ALA-Me was monitored by EPR as the DMPO-OH spin adduct and also showed a catalytic effect of AuNPs. Both SOD and CAT inhibited the production of ROS and also reduced cytotoxicity in the cell samples. These observations can be explained by initial attack on the cell membrane by ROS produced in the medium outside the cell and provide insight into possible uses of 5-ALA in cancer chemotherapy

Biologically active metalindependent superoxide dismutase mimics. Biochemistry.

ABSTRACT: Superoxide dismutase (SOD) is an enzyme that detoxifies superoxide (02&apos;-), a potentially toxic oxygen-derived species. Attempts to increase intracellular concentrations of SOD by direct application are complicated because SOD, being a relatively large molecule, does not readily cross cell membranes. We have identified a set of stable nitroxides that possess SOD-like activity, have the advantage of being low molecular weight, membrane permeable, and metal independent, and at pH 7.0 have reaction rate constants with 02&apos;-ranging from 1.1 X IO3 to 1.3 X IO6 M-&apos; s-l. These S O D mimics protect mammalian cells from damage induced by hypoxanthine/xanthine oxidase and H202, although they exhibit no catalase-like activity. In addition, the nitroxide SOD mimics rapidly oxidize DNA-Fe&quot; and thus may interrupt the Fenton reaction and prevent formation of deleterious OH radicals and/or higher oxidation states of metal ions. Whether by SOD-like activity and/or interception of an electron from redox-active metal ions they protect cells from oxidative stress and may have use in basic and applied biological studies. I n an oxygen-containing environment, cellular metabolism results in the production of several potentially harmful oxygen-derived species. The first in this cascade of active oxygen metabolites is the one-electron reduction product, superoxide (02*-). The function of the superoxide-detoxifying metalloenzyme superoxide dismutase (SOD)&apos; in protecting against oxygen-mediated biological damage is well documented EXPERIMENTAL PROCEDURES Chemicals. Desferrioxamine (DF) was a gift from Ciba Geigy; hypoxanthine (HX) was purchased from CalbiochemBoehringer Co.; 2,2,6,6-tetramethylpiperidine-1 -oxy1 (TEM-PO), 4-hydroxy-2,2,6,6-tetramethylpiperidine-I-oxy1 (TEM-POL), 4-hydroxypyrazolo[3,4,-d]pyrimidine (allopurinol), p-toluenesulfonic acid, 2-amino-2-methyl-1 -propanol, 2-butanone, and cyclohexanone were purchased from Aldrich Chemical Co.; tris(oxalato)chromat

The evolution of Santa María volcano, Guatemala

Samples of 26 successive lavas from the high composite volcano of Santa María in southwestern Guatemala, demonstrate variations in magnetic declination and inclination which can be roughly-correlated with similar data from cores in the Gulf of Mexico and lake sediments near Tlapacoya, Mexico, and suggest that Santa María\u27s constructive history goes back to approximately 30,000 years B.P. The basaltic andesites and associated pyroclastics, which make up this volcanic succession and comprise the latter 40% of the volcano\u27s eruptive output, show systematic increases in , and Zr, and decreases in MgO and CaO, up the succession. These evolutionary changes anticipate the dacites which first appeared after a period of repose in Santa María, first as pyroclastic debris in the catastrophic flank eruption of 1902, and later as the endogenous dacite dome of Santiaguito which appeared in 1922 and has continued to grow to the present day. The increasing effects of crystal fractionation in the latter part of Santa María\u27s history, as reflected in the compositional changes in the basaltic andesites and its culmination in the Santiaguito dacites, is thought to be due to the inhibiting effect which increasing cone height has had on the volcano\u27s eruptive frequency through time, so progressively increasing the lengths of the repose periods when fractionation could proceed undisturbed in the top of the feeding magma column. Data from other high composite cones in Guatemala suggests that 3,500-4,200 meters represents a threshold cone height above which basaltic andesite is not erupted in this region, and it is believed that this limitation led to the historically documented dormancy of Santa María during which the Santiaguito dacites evolved. A peridotitic mantle source, rather than eclogite, for the basaltic andesites is consistent with their chemistry, provided that the primary liquids have been depleted in Ni and Cr by approximately 10% olivine and clinopyroxene fractionation

The cytotoxicity of nitroxyl: possible implications for the pathophysiological role of NO

In addition to the broad repertoire of regulatory functions nitric oxide (NO) serves in mammalian physiology, the L-arginine:NO pathway is also involved in numerous pathophysiological mechanisms. While NO itself may actually protect cells from the toxicity of reactive oxygen radicals in some cases, it has been suggested that reactive nitrogen oxide species formed from nitric oxide synthase (NOS) can be cytotoxic. In addition to NO, the one electron reduction product NO- has been proposed to be formed from NOS. We investigated the potential cytotoxic role of nitroxyl (NO-), using the nitroxyl donor Angelis's salt, (AS; sodium trioxodinitrate, Na2N2O3) as the source of NO-. As was found to be cytotoxic to Chinese hamster V79 lung fibroblast cells over a concentration range of 2-4 mM. The presence of equimolar ferricyanide (Fe(III)-(CN6)3-), which converts NO- to NO, afforded dramatic protection against AS-mediated cytotoxicity. Treatment of V79 cells with L-buthionine sulfoximine to reduce intracellular glutathione markedly enhanced AS cytotoxicity, which suggests that GSH is critical for cellular protection against the toxicity of NO-. Further experiments showed that low molecular weight transition metal complexes associated with the formation of reactive oxygen species are not involved in AS-mediated cytotoxicity since metal chelators had no effect. However, under aerobic conditions, AS was more toxic than under hypoxic conditions, suggesting that oxygen dramatically enhanced AS-mediated cytotoxicity. At a molecular level, AS exposure resulted in DNA double strand breaks in whole cells, and this effect was completely prevented by coincubation of cells with ferricyanide or Tempol. The data in this study suggest that nitroxyl may contribute to the cytotoxicity associated with an enhanced expression of the L-arginine:NO pathway under different biological conditions