112 research outputs found
Short term effects of milrinone on biomarkers of necrosis, apoptosis, and inflammation in patients with severe heart failure
<p>Abstract</p> <p>Introduction</p> <p>Inotropes are associated with adverse outcomes in heart failure (HF), raising concern they may accelerate myocardial injury. Whether biomarkers of myocardial necrosis, inflammation and apoptosis change in response to acute milrinone administration is not well established.</p> <p>Methods</p> <p>Ten patients with severe HF and reduced cardiac output who were to receive milrinone were studied. Blood samples were taken just before initiation of milrinone and after 24 hours of infusion. Dosing was at the discretion of the patient's attending physician (range 0.25–0.5 mcg/kg/min). Plasma measurements of troponin, myoglobin, N-terminal-pro-BNP, interleukin-6, tumor necrosis factor-α, soluble Fas, and soluble Fas-ligand were performed at both time points.</p> <p>Results</p> <p>Troponin was elevated at baseline in all patients (mean 0.1259 ± 0.17 ng/ml), but there was no significant change after 24 hours of milrinone (mean 0.1345 ± 0.16 ng/ml, p = 0.44). There were significant improvements in interleukin-6, tumor necrosis factor-α, soluble Fas, and soluble Fas-ligand (all p < 0.05) indicative of reduced inflammatory and apoptotic signaling compared to baseline.</p> <p>Conclusion</p> <p>In conclusion, among patients with severe HF and low cardiac output, ongoing myocardial injury is common, and initiation of milrinone did not result in exacerbation of myocardial injury but instead was associated with salutary effects on other biomarkers.</p
Accreting Millisecond X-Ray Pulsars
Accreting Millisecond X-Ray Pulsars (AMXPs) are astrophysical laboratories
without parallel in the study of extreme physics. In this chapter we review the
past fifteen years of discoveries in the field. We summarize the observations
of the fifteen known AMXPs, with a particular emphasis on the multi-wavelength
observations that have been carried out since the discovery of the first AMXP
in 1998. We review accretion torque theory, the pulse formation process, and
how AMXP observations have changed our view on the interaction of plasma and
magnetic fields in strong gravity. We also explain how the AMXPs have deepened
our understanding of the thermonuclear burst process, in particular the
phenomenon of burst oscillations. We conclude with a discussion of the open
problems that remain to be addressed in the future.Comment: Review to appear in "Timing neutron stars: pulsations, oscillations
and explosions", T. Belloni, M. Mendez, C.M. Zhang Eds., ASSL, Springer;
[revision with literature updated, several typos removed, 1 new AMXP added
Oral treatment with a zinc complex of acetylsalicylic acid prevents diabetic cardiomyopathy in a rat model of type-2 diabetes: activation of the Akt pathway.
BACKGROUND: Type-2 diabetics have an increased risk of cardiomyopathy, and heart failure is a major cause of death among these patients. Growing evidence indicates that proinflammatory cytokines may induce the development of insulin resistance, and that anti-inflammatory medications may reverse this process. We investigated the effects of the oral administration of zinc and acetylsalicylic acid, in the form of bis(aspirinato)zinc(II)-complex Zn(ASA)2, on different aspects of cardiac damage in Zucker diabetic fatty (ZDF) rats, an experimental model of type-2 diabetic cardiomyopathy. METHODS: Nondiabetic control (ZL) and ZDF rats were treated orally with vehicle or Zn(ASA)2 for 24 days. At the age of 29-30 weeks, the electrical activities, left-ventricular functional parameters and left-ventricular wall thicknesses were assessed. Nitrotyrosine immunohistochemistry, TUNEL-assay, and hematoxylin-eosin staining were performed. The protein expression of the insulin-receptor and PI3K/AKT pathway were quantified by Western blot. RESULTS: Zn(ASA)2-treatment significantly decreased plasma glucose concentration in ZDF rats (39.0 +/- 3.6 vs 49.4 +/- 2.8 mM, P < 0.05) while serum insulin-levels were similar among the groups. Data from cardiac catheterization showed that Zn(ASA)2 normalized the increased left-ventricular diastolic stiffness (end-diastolic pressure-volume relationship: 0.064 +/- 0.008 vs 0.084 +/- 0.014 mmHg/microl; end-diastolic pressure: 6.5 +/- 0.6 vs 7.9 +/- 0.7 mmHg, P < 0.05). Furthermore, ECG-recordings revealed a restoration of prolonged QT-intervals (63 +/- 3 vs 83 +/- 4 ms, P < 0.05) with Zn(ASA)2. Left-ventricular wall thickness, assessed by echocardiography, did not differ among the groups. However histological examination revealed an increase in the cardiomyocytes' transverse cross-section area in ZDF compared to the ZL rats, which was significantly decreased after Zn(ASA)2-treatment. Additionally, a significant fibrotic remodeling was observed in the diabetic rats compared to ZL rats, and Zn(ASA)2-administered ZDF rats showed a similar collagen content as ZL animals. In diabetic hearts Zn(ASA)2 significantly decreased DNA-fragmentation, and nitro-oxidative stress, and up-regulated myocardial phosphorylated-AKT/AKT protein expression. Zn(ASA)2 reduced cardiomyocyte death in a cellular model of oxidative stress. Zn(ASA)2 had no effects on altered myocardial CD36, GLUT-4, and PI3K protein expression. CONCLUSIONS: We demonstrated that treatment of type-2 diabetic rats with Zn(ASA)2 reduced plasma glucose-levels and prevented diabetic cardiomyopathy. The increased myocardial AKT activation could, in part, help to explain the cardioprotective effects of Zn(ASA)2. The oral administration of Zn(ASA)2 may have therapeutic potential, aiming to prevent/treat cardiac complications in type-2 diabetic patients
The epidemiology of bacterial vaginosis in relation to sexual behaviour
<p>Abstract</p> <p>Background</p> <p>Bacterial vaginosis (BV) has been most consistently linked to sexual behaviour, and the epidemiological profile of BV mirrors that of established sexually transmitted infections (STIs). It remains a matter of debate however whether BV pathogenesis does actually involve sexual transmission of pathogenic micro-organisms from men to women. We therefore made a critical appraisal of the literature on BV in relation to sexual behaviour.</p> <p>Discussion</p> <p><it>G. vaginalis </it>carriage and BV occurs rarely with children, but has been observed among adolescent, even sexually non-experienced girls, contradicting that sexual transmission is a necessary prerequisite to disease acquisition. <it>G. vaginalis </it>carriage is enhanced by penetrative sexual contact but also by non-penetrative digito-genital contact and oral sex, again indicating that sex <it>per se</it>, but not necessarily coital transmission is involved. Several observations also point at female-to-male rather than at male-to-female transmission of <it>G. vaginalis</it>, presumably explaining the high concordance rates of <it>G. vaginalis </it>carriage among couples. Male antibiotic treatment has not been found to protect against BV, condom use is slightly protective, whereas male circumcision might protect against BV. BV is also common among women-who-have-sex-with-women and this relates at least in part to non-coital sexual behaviours. Though male-to-female transmission cannot be ruled out, overall there is little evidence that BV acts as an STD. Rather, we suggest BV may be considered a sexually enhanced disease (SED), with frequency of intercourse being a critical factor. This may relate to two distinct pathogenetic mechanisms: (1) in case of unprotected intercourse alkalinisation of the vaginal niche enhances a shift from lactobacilli-dominated microflora to a BV-like type of microflora and (2) in case of unprotected and protected intercourse mechanical transfer of perineal enteric bacteria is enhanced by coitus. A similar mechanism of mechanical transfer may explain the consistent link between non-coital sexual acts and BV. Similar observations supporting the SED pathogenetic model have been made for vaginal candidiasis and for urinary tract infection.</p> <p>Summary</p> <p>Though male-to-female transmission cannot be ruled out, overall there is incomplete evidence that BV acts as an STI. We believe however that BV may be considered a <it>sexually enhanced disease</it>, with frequency of intercourse being a critical factor.</p
Relativistic Binaries in Globular Clusters
Galactic globular clusters are old, dense star systems typically containing
10\super{4}--10\super{7} stars. As an old population of stars, globular
clusters contain many collapsed and degenerate objects. As a dense population
of stars, globular clusters are the scene of many interesting close dynamical
interactions between stars. These dynamical interactions can alter the
evolution of individual stars and can produce tight binary systems containing
one or two compact objects. In this review, we discuss theoretical models of
globular cluster evolution and binary evolution, techniques for simulating this
evolution that leads to relativistic binaries, and current and possible future
observational evidence for this population. Our discussion of globular cluster
evolution will focus on the processes that boost the production of hard binary
systems and the subsequent interaction of these binaries that can alter the
properties of both bodies and can lead to exotic objects. Direct {\it N}-body
integrations and Fokker--Planck simulations of the evolution of globular
clusters that incorporate tidal interactions and lead to predictions of
relativistic binary populations are also discussed. We discuss the current
observational evidence for cataclysmic variables, millisecond pulsars, and
low-mass X-ray binaries as well as possible future detection of relativistic
binaries with gravitational radiation.Comment: 88 pages, 13 figures. Submitted update of Living Reviews articl
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