Brain natriuretic peptide and left ventricular dysfunction in Chagas' disease

Left ventricular dysfunction in Chagas' disease is common but can be difficult to detect. We investigated whether measurement of plasma brain natriuretic peptide (BNP) could identify patients with left ventricular dysfunction who need further investigation or treatment. Among patients with an abnormal electrocardiogram or chest radiograph, a BNP concentration of 60.7 pmol/L or higher has a sensitivity and positive predictive value of 80%, and specificity and negative predictive value of 97%. Measurement of plasma BNP concentration could be a useful method to screen patients with Chagas' disease.     

Emerging Concepts for Myocardial Late Gadolinium Enhancement MRI

Late gadolinium enhancement is a useful tool for scar detection, based on differences in the volume of distribution of gadolinium, an extracellular agent. The presence of fibrosis in the myocardium amenable to be detected with late gadolinium enhancement MRI is found not only in ischemic cardiomyopathy, in which it offers information regarding viability and prognosis, but also in a wide variety of non-ischemic cardiomyopathies. In the following review we will discuss the methodological aspects of gadolinium-based imaging, as well as its applications and anticipated future developments.     

Secondary metabolites from Chamaedora tepejilote (Palmae) are active against Mycobacterium tuberculosis

Due to the emergence of multi-drug resistant Mycobacterium tuberculosis strains, there is an urgent need to search for new antimycobacterial drugs. The present work describes the bioactivity-guided fractionation of Chamaedora tepejilote hexane extract which led to the isolation and the characterization of squalene, farnesol, methylic ester of hexadecanoic acid, beta-sitosterol and ursolic acid. Activity against Mycobacterium tuberculosis H37Rv, determined by radiorespirometric Bactec assay, showed ursolic acid, squalene and farnesol to produce a M. tuberculosis growth inhibition of 99% at a concentration of 100 microg/mL.     

A spatiotemporal statistical atlas of motion for the quantification of abnormal myocardial tissue velocities

In this paper, we present a new method for the automatic comparison of myocardial motion patterns and the characterization of their degree of abnormality, based on a statistical atlas of motion built from a reference healthy population. Our main contribution is the computation of atlas-based indexes that quantify the abnormality in the motion of a given subject against a reference population, at every location in time and space. The critical computational cost inherent to the construction of an atlas is highly reduced by the definition of myocardial velocities under a small displacements hypothesis. The indexes we propose are of notable interest for the assessment of anomalies in cardiac mobility and synchronicity when applied, for instance, to candidate selection for cardiac resynchronization therapy (CRT). We built an atlas of normality using 2D ultrasound cardiac sequences from 21 healthy volunteers, to which we compared 14 CRT candidates with left ventricular dyssynchrony (LVDYS). We illustrate the potential of our approach in characterizing septal flash, a specific motion pattern related to LVDYS and recently introduced as a very good predictor of response to CRT.     

The heterozygote advantage of the Chuvash polycythemia VHLR200W mutation may be protection against anemia

The germ-line loss-of-function VHL(R200W) mutation is common in Chuvashia, Russia and occurs in other parts of the world. VHL(R200W) homozygotes have elevated hypoxia inducible factor (HIF)-1 and HIF-2 levels, increased hemoglobin concentration, propensity to thrombosis and early mortality. Because the mutation persists from an ancient origin, we hypothesized that there is a heterozygote advantage. Thirty-four VHL(R200W) heterozygotes and 44 controls over 35 years of age from Chuvashia, Russia were studied. Anemia was defined as hemoglobin less than 130 g/L in men and less than 120 g/L in women. Mild anemia was present in 15% of VHL(R200W) heterozygotes and 34% of controls without a mutated VHL allele. By multivariate logistic regression, the odds of anemia were reduced an estimated 5.6-fold in the VHL(R200W) heterozygotes compared to controls (95% confidence interval 1.4-22.7; P=0.017). In conclusion, heterozygosity for VHL(R200W) may provide protection from anemia; such protection could explain the persistence of this mutation.     

Repair after myocardial infarction, between fantasy and reality: the role of chemokines

Despite considerable progress over the last decades, acute myocardial infarction continues to remain the major cause of morbidity and mortality worldwide. The present therapies include only cause-dependent interventions, which are not able to reduce myocardial necrosis and optimize cardiac repair following infarction. This review highlights the cellular and molecular processes after myocardial injury and focuses on chemokines, the main modulators of the inflammatory and reparatory events, as the most valuable drug targets.     

Neonatal maternal separation affects endocrine and metabolic stress responses to ether exposure but not to restraint exposure in adult rats

We investigated prolactin secretion and metabolic changes in stress response in adult male rats submitted to periodic maternal separation (MS; 180 min/day) at 2 weeks of life. Restraint and ether exposure were randomly performed when the animals were 10-12 weeks of age. Restraint exposure: the animals were placed into plastic tubes (21 cm long, 4.5 cm diameter) for 20 min. Ether exposure: the rats were exposed to ether for 10 min. Atrial cannulation for blood sampling was performed through the jugular vein 5 days before the experiments. In both protocols, blood samples were taken immediately before (0), and 5, 15 and 20 min after the beginning of stress exposure. Ours results showed attenuated endocrine and metabolic responses to ether exposure in the maternal separation (MS) group compared to the control group. The measured metabolic parameters, plasma glucose, prolactin, lactate, and insulin secretion, were 32%, 55%, 41%, 73% lower (P < 0.01), respectively, in MS than in control animals. On the other hand, the endocrine and metabolic stress responses to restraint exposure were not affected by maternal separation. There was no difference between the MS and the control groups in any of the parameters studied. Our data demonstrated that early life experiences affect the hormonal systems beyond the hypothalamic-pituitary-adrenal axis, such as the central neuronal pathways, and their activities related to hormonal and metabolic responses to stress in adulthood. More importantly, these modifications were specific, but dependent on stress situation affecting mainly the circuitry related to the stress response to ether exposure.     

Elevated homocysteine, glutathione and cysteinylglycine concentrations in patients homozygous for the Chuvash polycythemia VHL mutation

In Chuvash polycythemia, homozygous von Hippel-Lindau (VHL) 598C>T leads to increased hypoxia inducible factor-1alpha and 2alpha, thromboses and lower systemic blood pressures. Circulating homocysteine, glutathione, gamma-glutamyltransferase and cysteinylglycine concentrations were higher in 34 VHL598C>T homozygotes than in 37 normal controls and cysteine was lower. Multivariate analysis showed elevated homocysteine independently associated with higher mean systemic blood pressures and elevated glutathione was associated with lower pressures to a similar degree. Among VHL598C>T homozygotes, homocysteine was elevated with low and normal folate concentrations, consistent with a possible defect in the remethylation pathway. The elevated glutathione and gamma-glutamyltransferase levels correlated positively with cysteinylglycine, consistent with possible upregulation of a glutathione synthetic enzyme and gamma-glutamyltransferase. Cysteinylglycine correlated inversely with cysteine, consistent with possible reduced cysteinyldipeptidase activity. We conclude that up-regulated hypoxia-sensing may influence multiple steps in thiol metabolism. The effects of the resultant elevated levels of homocysteine and glutathione on systemic blood pressure may largely balance each other out.