Interactions among mitochondrial proteins altered in glioblastoma

Mitochondrial dysfunction is putatively central to glioblastoma (GBM) pathophysiology but there has been no systematic analysis in GBM of the proteins which are integral to mitochondrial function. Alterations in proteins in mitochondrial enriched fractions from patients with GBM were defined with label-free liquid chromatography mass spectrometry. 256 mitochondrially-associated proteins were identified in mitochondrial enriched fractions and 117 of these mitochondrial proteins were markedly (fold-change ≥2) and significantly altered in GBM (p ≤ 0.05). Proteins associated with oxidative damage (including catalase, superoxide dismutase 2, peroxiredoxin 1 and peroxiredoxin 4) were increased in GBM. Protein–protein interaction analysis highlighted a reduction in multiple proteins coupled to energy metabolism (in particular respiratory chain proteins, including 23 complex-I proteins). Qualitative ultrastructural analysis in GBM with electron microscopy showed a notably higher prevalence of mitochondria with cristolysis in GBM. This study highlights the complex mitochondrial proteomic adjustments which occur in GBM pathophysiology

Plasma protein C levels in immunocompromised septic patients are significantly lower than immunocompetent septic patients: a prospective cohort study

Introduction: Activated Protein C [APC] improves outcome in immunocompetent patients with severe sepsis particularly in those who are perceived to have high mortality risk. Before embarking on a trial of APC administration in immunocompromised septic patients, a preliminary study on plasma levels of protein C in this cohort is essential

Impact of contractile reserve on acute response to cardiac resynchronization therapy

Background: Cardiac resynchronization therapy (CRT) provides benefit for congestive heart failure, but still 30% of patients failed to respond to such therapy. This lack of response may be due to the presence of significant amount of scar or fibrotic tissue at myocardial level. This study sought to investigate the potential impact of myocardial contractile reserve as assessed during exercise echocardiography on acute response following CRT implantation. Methods: Fifty-one consecutive patients with heart failure (LV ejection fraction 27% ± 5%, 67% ischemic cardiomyopathy) underwent exercise Doppler echocardiography before CRT implantation to assess global contractile reserve (improvement in LV ejection fraction) and local contractile reserve in the region of the LV pacing lead (assessed by radial strain using speckle tracking analysis). Responders were defined by an increase in stroke volume ≥15% after CRT. Results: Compared with nonresponders, responders (25 patients) showed a greater exercise-induced increase in LV ejection fraction, a higher degree of mitral regurgitation and a significant extent of LV dyssynchrony. The presence of contractile reserve was directly related to the acute increase in stroke volume (r = 0.48, p<0.001). Baseline myocardial deformation as well as contractile reserve in the LV pacing lead region was greater in responders during exercise than in nonresponders (p<0.0001). Conclusions: Heart failure patients referred to CRT have less chance of improving under therapy if they have no significant mitral regurgitation, no LV dyssynchrony and no contractile myocardial recruitment at exercise

Observation of the radiative decay mode of the free neutron

The theory of quantum electrodynamics (QED) predicts that beta decay of the neutron into a proton, electron and antineutrino should be accompanied by a continuous spectrum of soft photons. While this inner bremsstrahlung branch has been previously measured in nuclear beta and electron capture decay, it has never been observed in free neutron decay. Recently, the photon energy spectrum and branching ratio for neutron radiative decay have been calculated using two approaches: a standard QED framework(1-3) and heavy baryon chiral perturbation theory(4) (an effective theory of hadrons based on the symmetries of quantum chromodynamics). The QED calculation treats the nucleons as point-like, whereas the latter approach includes the effect of nucleon structure in a systematic way. Here we observe the radiative decay mode of free neutrons, measuring photons in coincidence with both the emitted electron and proton. We determined a branching ratio of (3.13 +/- 0.34) x 10(-3) (68 per cent level of confidence) in the energy region between 15 and 340 keV, where the uncertainty is dominated by systematic effects. The value is consistent with the predictions of both theoretical approaches; the characteristic energy spectrum of the radiated photons, which differs from the uncorrelated background spectrum, is also consistent with the calculated spectrum. This result may provide opportunities for more detailed investigations of the weak interaction processes involved in neutron beta decay.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/62639/1/nature05390.pd

Search for rare quark-annihilation decays, B --> Ds(*) Phi

We report on searches for B- --> Ds- Phi and B- --> Ds*- Phi. In the context of the Standard Model, these decays are expected to be highly suppressed since they proceed through annihilation of the b and u-bar quarks in the B- meson. Our results are based on 234 million Upsilon(4S) --> B Bbar decays collected with the BABAR detector at SLAC. We find no evidence for these decays, and we set Bayesian 90% confidence level upper limits on the branching fractions BF(B- --> Ds- Phi) Ds*- Phi)<1.2x10^(-5). These results are consistent with Standard Model expectations.Comment: 8 pages, 3 postscript figues, submitted to Phys. Rev. D (Rapid Communications

High tidal volume mechanical ventilation-induced lung injury in rats is greater after acid instillation than after sepsis-induced acute lung injury, but does not increase systemic inflammation: an experimental study

<p>Abstract</p> <p>Background</p> <p>To examine whether acute lung injury from direct and indirect origins differ in susceptibility to ventilator-induced lung injury (VILI) and resultant systemic inflammatory responses.</p> <p>Methods</p> <p>Rats were challenged by acid instillation or 24 h of sepsis induced by cecal ligation and puncture, followed by mechanical ventilation (MV) with either a low tidal volume (Vt) of 6 mL/kg and 5 cm H₂O positive end-expiratory pressure (PEEP; LVt acid, LVt sepsis) or with a high Vt of 15 mL/kg and no PEEP (HVt acid, HVt sepsis). Rats sacrificed immediately after acid instillation and non-ventilated septic animals served as controls. Hemodynamic and respiratory variables were monitored. After 4 h, lung wet to dry (W/D) weight ratios, histological lung injury and plasma mediator concentrations were measured.</p> <p>Results</p> <p>Oxygenation and lung compliance decreased after acid instillation as compared to sepsis. Additionally, W/D weight ratios and histological lung injury scores increased after acid instillation as compared to sepsis. MV increased W/D weight ratio and lung injury score, however this effect was mainly attributable to HVt ventilation after acid instillation. Similarly, effects of HVt on oxygenation were only observed after acid instillation. HVt during sepsis did not further affect oxygenation, compliance, W/D weight ratio or lung injury score. Plasma interleukin-6 and tumour necrosis factor-α concentrations were increased after acid instillation as compared to sepsis, but plasma intercellular adhesion molecule-1 concentration increased during sepsis only. In contrast to lung injury parameters, no additional effects of HVt MV after acid instillation on plasma mediator concentrations were observed.</p> <p>Conclusions</p> <p>During MV more severe lung injury develops after acid instillation as compared to sepsis. HVt causes VILI after acid instillation, but not during sepsis. However, this differential effect was not observed in the systemic release of mediators.</p

Preventive and curative effect of melatonin on mammary carcinogenesis induced by dimethylbenz[a]anthracene in the female Sprague–Dawley rat

INTRODUCTION: It has been well documented that the pineal hormone, melatonin, which plays a major role in the control of reproduction in mammals, also plays a role in the incidence and growth of breast and mammary cancer. The curative effect of melatonin on the growth of dimethylbenz [a]anthracene-induced (DMBA-induced) mammary adenocarcinoma (ADK) has been previously well documented in the female Sprague–Dawley rat. However, the preventive effect of melatonin in limiting the frequency of cancer initiation has not been well documented. METHODS: The aim of this study was to compare the potency of melatonin to limit the frequency of mammary cancer initiation with its potency to inhibit tumor progression once initiation, at 55 days of age, was achieved. The present study compared the effect of preventive treatment with melatonin (10 mg/kg daily) administered for only 15 days before the administration of DMBA with the effect of long-term (6-month) curative treatment with the same dose of melatonin starting the day after DMBA administration. The rats were followed up for a year after the administration of the DMBA. RESULTS: The results clearly showed almost identical preventive and curative effects of melatonin on the growth of DMBA-induced mammary ADK. Many hypotheses have been proposed to explain the inhibitory effects of melatonin. However, the mechanisms responsible for its strong preventive effect are still a matter of debate. At least, it can be envisaged that the artificial amplification of the intensity of the circadian rhythm of melatonin could markedly reduce the DNA damage provoked by DMBA and therefore the frequency of cancer initiation. CONCLUSION: In view of the present results, obtained in the female Sprague–Dawley rat, it can be envisaged that the long-term inhibition of mammary ADK promotion by a brief, preventive treatment with melatonin could also reduce the risk of breast cancer induced in women by unidentified environmental factors

Zootherapeutics utilized by residents of the community Poço Dantas, Crato-CE, Brazil

<p>Abstract</p> <p>Background</p> <p>Animals have been used as a source of medicine in Brazil since ancient times, and have played a significant role in healing practices. Specifically in Northeast Brazil, zootherapy is a very common practice, and together with medicinal plants, it plays an important role as a therapeutic alternative. In the state of Ceara, no works have been carried out on rural communities with regard to use of zootherapeutics, even though the practice of zootherapy is common in this region. Therefore, the aim of this study was to analyze the use of medicinal animals in a rural community (Poco Dantas) in the municipality of Crato, Ceara, Brazil.</p> <p>Methods</p> <p>The field survey was carried out from October 2008 to January 2009 by conducting interviews using structured questionnaires with 72 people (33 men and 39 women), who provided information on animal species used as remedies, body parts used to prepare the remedies, and ailments for which the remedies were prescribed. We calculated the informant consensus factor (ICF) to determine the consensus over which species are effective for particular ailments, as well as the species use value (UV) to determine the extent of utilization of each species.</p> <p>Results</p> <p>A total of 29 species, distributed in 17 families were categorized as having some medicinal property. The taxa most represented were: mammals (9), insects (7), reptiles and birds (4). <it>Progne chalybea</it>, a species not previously recorded as being of medicinal use, was cited in the present work, where it is utilized in the treatment of alcoholism. The animals are used in the treatment of 34 diseases or symptoms, where sore throat, inflammations and cough are the ailments with the greatest number of citations.</p> <p>Conclusion</p> <p>The data show that zootherapy represents an important therapeutic alternative for the inhabitants of the community. New studies on medicinal fauna should be conducted with the aim of determining the exploitation level of the species utilized, promoting sustainable development of medicinal species that are eventually threatened, and preserving and disseminating the knowledge developed by traditional individuals of the community.</p