Stress cardiomyopathy in thromboembolic arterial disease.

Apical ballooning is a novel clinical entity reported in different contexts of physical and psychological stress, which is more common in middle-aged women. Of unknown etiology, the syndrome is characterized by a sudden and transient dilatation of the left ventricular apex in the absence of obstructive atherosclerotic coronary disease or evidence of myocardial necrosis, with total late recovery of ventricular function. The authors report the case of a 53-year-old woman who was admitted to the emergency room with left arm ischemia and low cardiac output, requiring ventilatory support. Left catheterization showed typical medial and apical myocardial dysfunction, with normal coronary arteries. Transesophageal echocardiography revealed a thrombus attached to the lower face of the aortic arch, which probably explained the thromboembolism of the arm but was unlikely to be the cause of the left ventricular dysfunction since there were no enzymatic or electrocardiographic signs of myocardial necrosis and normal wall motion was fully recovered.     

Catalase enzyme mutations and their association with diseases.

Enzyme catalase seems to be the main regulator of hydrogen peroxide metabolism. Hydrogen peroxide at high concentrations is a toxic agent, while at low concentrations it appears to modulate some physiological processes such as signaling in cell proliferation, apoptosis, carbohydrate metabolism, and platelet activation. Benign catalase gene mutations of 5' noncoding region (15) and intron 1 (4) have no effect on catalase activity and are not associated with disease.Catalase gene mutations have been detected in association with diabetes mellitus, hypertension, and vitiligo. Decreases in catalase activity in patients with tumors is more likely to be due to decreased enzyme synthesis rather than to catalase mutations.Acatalasemia, the inherited deficiency of catalase has been detected in 11 countries. Its clinical features might be oral gangrene, altered lipid, carbohydrate, homocysteine metabolism and the increased risk of diabetes mellitus. The Japanese, Swiss, and Hungarian types of acatalasemia display differences in biochemical and genetic aspects. However, there are only limited reports on the syndrome causing these mutations.These data show that acatalasemia may be a syndrome with clinical, biochemical, genetic characteristics rather than just a simple enzyme deficiency.     

Albumin nanoparticles improved the stability, nuclear accumulation and anticytomegaloviral activity of a phosphodiester oligonucleotide.

The goal of this study was to evaluate the potential of albumin nanoparticles as a delivery system for antisense oligonucleotides. Nanoparticles were prepared by a coacervation process and cross-linkage with glutaraldehyde. Phosphodiester (PO) and phosphorotioate (PS) oligonucleotides were either adsorbed on the surface of nanoparticles (PO-NPA and PS-NPA) or incorporated in the nanoparticle matrix (PO-NPB and PS-NPB). When PO-loaded nanoparticles were incubated with phosphodiesterase, only NPB was able to keep the oligonucleotide hybridization capability for at least 60 min. The antiviral activity was evaluated in MRC-5 fibroblasts infected with human cytomegalovirus at a MOI of 0.0035. Both PO nanoparticle formulations significantly increased the antiviral activity of free PO (P<0.001) and NPB showed slightly higher efficacies than NPA (P<0.05). On the other hand, PS exhibited significant higher activity than free PO (P<0.001), however, no significant differences were found between PS-nanoparticle and PO-nanoparticle formulations. These findings were well correlated with the intracellular distribution observed for fluorescent oligonucleotide-loaded albumin nanoparticles. Even these carriers delayed and decreased the uptake of PO by MRC-5 cells, they finally induced a diffused cytoplasmic distribution and major nuclear accumulation. In summary, albumin nanoparticles partially protected a PO against enzymatic degradation and improved their presence in the nucleus and thus, increased its efficiency.     

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Interactions between alcohol and gastric metabolizing enzymes: practical implications.

It has been demonstrated recently that some portion of ingested alcohol does not enter the systemic circulation and is not retained in the gastrointestinal tract; instead, gastric oxidation or first-pass metabolism of ethanol occurs in the stomach, catalyzed by gastric alcohol dehydrogenase. First-pass metabolism of ethanol is minimal in the fasting state; it is lower in women than in men, and in alcoholics than in nonalcoholics; and it is abolished in patients after subtotal gastrectomy. In addition, some drugs may affect first-pass ethanol metabolism. Studies of the effects of H2-receptor antagonists on blood ethanol levels are reviewed. It is concluded that some H2-receptor antagonists (cimetidine and nizatidine, in particular) can inhibit gastric ethanol oxidation and thus increase blood alcohol levels after drinking. The clinical and medicolegal implications of these findings are discussed.     

Antibody Responses to Asian and American Genotypes of Dengue 2 Virus in Immunized Mice

The possibility of a correlation between dengue virus genotype groups and disease severity is currently under discussion. The objective of this investigation was to identify any immunogenic difference between the American and Asian dengue 2 virus genotypes through the study of antibody development (virus-binding immunoglobulin G and neutralizing antibodies) in mice. Differences in the neutralization pattern between the strains studied were observed, suggesting the presence of slight antigenic variations among them. The lack of recognition of one of the Asian genotype strains was remarkable.     

In-vitro model for the ultrastructural study of the formation of thrombi in human platelets.

Platelets are cell fragments with dynamic properties involved in clot formation after tissue damage. Platelet activation causes a change in shape, secretion of intracellular granules and aggregation with each other through the cytoskeleton components and biochemical changes. Platelet adhesion, considered as the major event in haemostasis, has been studied in several in-vitro and in-vivo models to evaluate the feasible thrombogenicity of some materials, the dynamics of specific receptors, as well as the effect of different buffers and inhibitors in this process. In spite of the numerous reports about platelet activation, to date there is no information available about the fine structure of the platelet-platelet and platelet-substrate interactions. In the present report we describe an in-vitro system that allows the visualization of these interactions: platelets are adhered to an inert substrate, and interactions with suspended platelets as a process to initiate the formation of thrombi was followed by ultramicrotomy and transmission electron microscopy.     

Brachial endothelial function in subjects with familial combined hyperlipidemia and its relationships to carotid artery intima-media thickness.

AIM: The aim of this study was to quantify the flow-mediated dilatation (FMD) of brachial artery in asymptomatic members of families with familial combined hyperlipidemia (FCH) and to determine the relation between FMD and risk factors accompanying FCH. We also investigated the association between FMD and the intima-media thickness (IMT) of the common carotid artery. METHODS: Eighty-two members of 29 FCH families were divided into two groups: probands and hyperlipidemic first-degree relatives (HL) (n=47) and normolipidemic first-degree relatives (NL) (n=35). The control (C) groups, C-HL (n=20) and C-NL (n=20), consisted of sex- and age-matched healthy individuals. FMD was assessed in the brachial artery by measuring the change in brachial artery diameter in response to reactive hyperemia. RESULTS: Both hyperlipidemic subjects and their NL had significantly lower FMD (3.4+/-3% vs 6.3+/-2.8%, P<0.001, 5.2+/-2.3% vs 7.8+/-2.8%, P<0.01, respectively) compared to controls. In multivariate backward stepwise regression analysis, FMD in members of FCH families was independently associated with sex (P<0.001), age (P<0.01), C-peptide (P<0.05) and borderline with glycemia (P=0.052). FMD correlated inversely with IMT in all subjects of FCH families and in hyperlipidemic members. In multivariate backward stepwise regression analysis this relation remained independent (P<0.001, P<0.01, respectively). CONCLUSIONS: Members of FCH families showed impaired FMD, which was independently associated with markers of insulin resistance. FMD and IMT were independently associated in hyperlipidemic, but not in normolipidemic members of FCH families.     

Modulation of arterial stiffness with intensive competitive training.

BACKGROUND: Aerobic exercise training has been associated with beneficial effects on the cardiovascular system, improving arterial compliance, possibly related to a positive impact on the endothelium. The effects of competitive aerobic exercise are not so well documented. This prompted us to evaluate the possible modulation of arterial properties in a group of athletes and their response to the aging process. METHODS: 423 healthy males were enrolled in a cross-sectional study, 212 of whom were competitive athletes and 211 were controls. All underwent carotid-femoral pulse wave velocity (PWV) evaluation, and casual blood pressure and other relevant anthropometric data were evaluated. RESULTS: To control the effects of age, each group was divided into two subgroups with an age cut-point of 20 years. PWV was 6.3 +/- 0.9 m/s (athletes) vs. 7.0 +/- 1.0 m/s (controls) for ages <20 years, and 7.6 +/- 1.2 m/s (athletes) vs. 8.1 +/- 0.9 m/s (controls) for ages >20 years, with statistically significant differences in both comparisons. A linear regression model with logarithmic tendency analysis with age as the independent determinant of PWV revealed a different progression of age-related deterioration of aortic compliance between the two groups (athletes and controls). CONCLUSIONS: Our data documented better compliance indices in competition athletes compared with controls, which may reflect optimization of endothelial function. This improvement was age-dependent, being less pronounced as the athletes grow older, which could be due partially to sustained stretching effects on the arterial walls in long-term competitors.