Differential effects of an anti-oxidant intervention on cardiomyocyte expression of adrenomedullin and intermedin and their receptor components in chronic nitric oxide deficiency

Background: Chronic inhibition of nitric oxide (NO) synthesis is associated with hypertension, myocardial oxidative stress and hypertrophic remodeling. Up-regulation of the cardiomyocyte adrenomedullin (AM) / intermedin (IMD) receptor signaling cascade is also apparent in NO-deficient cardiomyocytes: augmented expression of AM and receptor activity modifying proteins RAMP2 and RAMP3 is prevented by blood pressure normalization while that of RAMP1 and intermedin (IMD) is not, indicating that the latter is regulated by a pressure-independent mechanism. Aims: to verify the ability of an anti-oxidant intervention to normalize cardiomyocyte oxidant status and to investigate the influence of such an intervention on expression of AM, IMD and their receptor components in NO-deficient cardiomyocytes. Methods: NO synthesis inhibitor, NG-nitro-L-arginine methyl ester (L-NAME, 35mg/kg/day) was given to rats for 8 weeks, with/without con-current administration of antioxidants (Vitamin C (25mg/kg/day) and Tempol (25mg/kg/day)). Results: In left ventricular cardiomyocytes isolated from L-NAME treated rats, increased oxidative stress was indicated by augmented (3.6 fold) membrane protein oxidation, enhanced expression of catalytic and regulatory subunits of pro-oxidant NADPH oxidases (NOX1, NOX2) and compensatory increases in expression of anti-oxidant glutathione peroxidase and Cu/Zn superoxide dismutases (SOD1, SOD3). Vitamin C plus Tempol did not reduce systolic blood pressure but normalized augmented plasma levels of IMD, but not of AM, and in cardiomyocytes: (i) abolished increased membrane protein oxidation; (ii) normalized augmented expression of prepro-IMD and RAMP1, but not prepro-AM, RAMP2 and RAMP3; (iii) attenuated (by 42%) increased width and normalized expression of hypertrophic markers, skeletal-�-actin and prepro-endothelin-1 similarly to blood pressure normalization but in contrast to blood pressure normalization did not attenuate augmented brain natriuretic peptide (BNP) expression. Conclusion: normalization specifically of augmented IMD/RAMP1 expression in NO-deficient cardiomyocytes by antioxidant intervention in the absence of blood pressure reduction indicates that these genes are likely to be induced directly by myocardial oxidative stress. Although oxidative stress contributed to cardiomyocyte hypertrophy, induction of IMD and RAMP1 is unlikely to be secondary to cardiomyocyte hypertrophy.

Epipolar geometry estimation based on evolutionary agents

This paper presents a novel approach based on the use of evolutionary agents for epipolar geometry estimation. In contrast to conventional nonlinear optimization methods, the proposed technique employs each agent to denote a minimal subset to compute the fundamental matrix, and considers the data set of correspondences as a 1D cellular environment, in which the agents inhabit and evolve. The agents execute some evolutionary behavior, and evolve autonomously in a vast solution space to reach the optimal (or near optima) result. Then three different techniques are proposed in order to improve the searching ability and computational efficiency of the original agents. Subset template enables agents to collaborate more efficiently with each other, and inherit accurate information from the whole agent set. Competitive evolutionary agent (CEA) and finite multiple evolutionary agent (FMEA) apply a better evolutionary strategy or decision rule, and focus on different aspects of the evolutionary process. Experimental results with both synthetic data and real images show that the proposed agent-based approaches perform better than other typical methods in terms of accuracy and speed, and are more robust to noise and outliers.

Differential Pharmacokinetics of Digoxin in Elderly Patients

Digoxin remains one of the most commonly prescribed of all cardiac medications. The main indications for digoxin usage include atrial fibrillation and heart failure; both these conditions are more prevalent in older patients. Given the aging population and the increasing incidence of heart failure we would expect prescribing of digoxin to remain as frequent or to even increase in older patients. Older patients are also more likely to develop toxicity and diagnosis of digoxin toxicity can be difficult in this group. Numerous components contribute to the development of toxicity in older patients, ranging from aging-related changes in renal function or body mass to polypharmacy and possible interactions with digoxin. It is therefore important to understand how the pharmacokinetics of digoxin may be altered in the older population. Application of basic pharmacological principles may be helpful in anticipating these problems. This review describes the pharmacokinetics of digoxin, the changes in pharmacokinetics with increasing age and how concomitant disease states or drug interactions may affect the pharmacokinetics of digoxin. Greater knowledge about the causes and prevention of digoxin toxicity should further reduce the morbidity and mortality arising from digoxin toxicity, especially in the elderly population.
For over 200 years debate has raged regarding the use of digitalis glycosides in cardiac disease. At present digoxin is the most commonly prescribed digitalis compound. This review describes the pharmacokinetics of digoxin and in particular how they are altered with increasing age. When considering the elderly population it is important to recognise the heterogeneity of response in this group, therefore there are no rules, with regards to prescribing, that can apply to the entire elderly population.

An exploratory non-LTE model atmosphere analysis of B-type supergiants in the Small Magellanic Cloud

A preliminary differential non-LTE model atmosphere analysis of moderate resolution (R ~ 5 000) and signal-to-noise ratio spectra of 48 Small Magellanic Cloud B-type supergiants is presented. Standard techniques are adopted, viz. plane-parallel geometry and radiative and hydrostatic equilibrium. Spectroscopic atmospheric parameters (T_eff, log g and v_turb), luminosities and chemical abundances (He, C, N, O, Mg and Si) are estimated. These are compared with those deduced for a comparable sample of Galactic supergiants. The SMC targets appear to have similar atmospheric parameters, luminosities and helium abundances to the Galactic sample. Their magnesium and silicon underabundances are compatible with those found for main sequence SMC objects and there is no evidence for any large variation in their oxygen abundances. By contrast both their carbon and nitrogen lines strengths are inconsistent with single abundances, while their nitrogen to carbon abundance ratios appear to vary by at least as much and probably more than that found in the Galactic sample.

Differential cross section measurements for elastic scattering of electrons from Ar2+ and Xe2+

A crossed-beams energy-loss spectrometer has been used to investigate angular distributions for electron scattering from Ar2+ and Xe2+ ions, at a collision energy of 16 eV. For Ar2+ the measurements are compared with the predictions of a partial waves calculation based on a semi-empirical potential, where it is shown that the interference term governs the position of the observed minimum in the angular distribution.

Quasi-isochoric ion beam heating using dynamic confinement in spherical geometry for X-ray scattering experiments in WDM regime

Extreme states of matter such as Warm Dense Matter “WDM” and Dense Strongly Coupled Plasmas “DSCP” play a key role in many high energy density experiments, however creating WDM and DSCP in a manner that can be quantified is not readily feasible. In this paper, isochoric heating of matter by intense heavy ion beams in spherical symmetry is investigated for WDM and DSCP research: The heating times are long (100 ns), the samples are macroscopically large (mm-size) and the symmetry is advantageous for diagnostic purposes. A dynamic confinement scheme in spherical symmetry is proposed which allows even ion beam heating times that are long on the hydrodynamic time scale of the target response. A particular selection of low Z-target tamper and x-ray probe radiation parameters allows to identify the x-ray scattering from the target material and use it for independent charge state measurements Z* of the material under study.

Analytical description of stochastic field-Line wandering in magnetic turbulence

A nonperturbative nonlinear statistical approach is presented to describe turbulent magnetic systems embedded in a uniform mean magnetic field. A general formula in the form of an ordinary differential equation for magnetic field-line wandering (random walk) is derived. By considering the solution of this equation for different limits several new results are obtained. As an example, it is demonstrated that the stochastic wandering of magnetic field-lines in a two-component turbulence model leads to superdiffusive transport, contrary to an existing diffusive picture. The validity of quasilinear theory for field-line wandering is discussed, with respect to different turbulence geometry models, and previous diffusive results are shown to be deduced in appropriate limits.