Effects of soy isoflavones on endothelial function in healthy postmenopausal women

OBJECTIVE: To evaluate the effects of soy isoflavone administration on endothelial function in healthy postmenopausal women. DESIGN: Sixty naturally postmenopausal women were randomly assigned to receive isoflavone or placebo tablets for 6 months. Endothelium-dependent vasodilatation was measured by brachial reactivity technique along with levels of plasma soluble intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), E-selectin, P-selectin and soluble thrombomodulin, von Willebrand factor, and tissue plasminogen activator. Differences between endothelium-dependent and endothelium-independent vasodilatation were assessed by evaluating brachial reactivity parameters after reactive hyperemia and after sublingual administration of nitroglycerin; furthermore, in the active group, the effect of isoflavones was also evaluated during the intra-arterial infusion of N-monomethyl-L-arginine. Serum levels of lipids [high-density lipoprotein and low-density lipoprotein cholesterol, triglycerides and lipoprotein(a)] and hemostatic factors (prothrombin, fibrinogen, plasminogen activator inhibitor-1, and fibrin D-dimer) were also measured. To confirm the absorption of isoflavones, their blood concentrations were determined. RESULTS: Isoflavone treatment versus placebo was associated with a significant improvement in endothelium-dependent vasodilatation but had no impact on endothelial-independent arterial diameter and flow. Intra-arterial infusion of N-monomethyl-L-arginine inhibited the significant effect of isoflavones on endothelium-mediated vasodilatation. Furthermore, isoflavone group experienced statistically significant reductions in plasma concentrations of ICAM-1, VCAM-1, and E-selectin. Levels of soluble thrombomodulin, von Willebrand factor, tissue plasminogen activator, lipids, and hemostatic factors did not change significantly throughout the study in both groups. CONCLUSIONS: Our findings suggest a positive influence of soy isoflavones on endothelial function in healthy postmenopausal women as evidenced by an improvement in endothelium-dependent vasodilatation and a reduction in plasma adhesion molecule levels.     

Physiological unloading of cardiopulmonary mechanoreceptors by posture changes does not influence the pressor response to isometric exercise in healthy humans

Summary In recent studies in humans the role of cardiopulmonary baroreflexes in modulating the cardiovascular responses to isometric exercise (somatic pressor reflex) has been investigated by performing static hand-grip exercise during deactivation of cardiopulmonary receptors produced by low levels of lower body negative pressure; however, findings from these studies have not been consistent. The purpose of this study was to investigate whether a more physiological unloading stimulus of cardiopulmonary baroreceptors, obtained by sequentially changing posture, could influence the pressor response to somatic afferent stimulation induced by isometric, exercise. To accomplish this, ten healthy subjects performed a 2-min isometric handgrip (IHG) at 30% maximal voluntary contraction after 10 min of supine rest and, in rapid sequence, after 10 min of sitting and 10 min of standing, at the time when, owing to their transitory nature, the cardiovascular effects, due to arterial baroreceptor intervention should have been minimal. During IHG arterial pressure (BP_a) was continuously and noninvasively measured to quantify accurately the blood pressure response to IHG both in magnitude and time course. Results showed that the pressor response to IHG was not significantly influenced by change in posture, either in magnitude or in time course. The mean arterial pressure increased by 17.4 (SEM 2.5), 18.6 (SEM 1.2) and 17.0 (SEM 1.3) mmHg in supine, sitting and standing [2.3 (SEM 0.3), 2.5 (SEM 0.2) and 2.3 (SEM 0.2) kPa] positions, respectively. Also the heart rate response to IHG was unaffected by change in posture. Most important, the sum of the separate BP_a responses induced by supine IHG and by posture change from supine to sitting (summation of reflexes) was not significantly different from the pressor response observed during sitting IHG (interaction of reflexes). Likewise, the sum of the separate BP_a. responses induced by sitting IHG and by changing postures from sitting to standing was not significantly different from the pressor response to standing IHG. These data indicate that, under physiological conditions, cardiopulmonary baroreflexes do not exert a significant role in modulating the reflex pressor drive from muscles during isometric exercise in healthy humans.     

N19 polyepitope as a carrier for enhanced immunogenicity and protective efficacy of meningococcal conjugate vaccines

N19, a string of human universal CD4 T-cell epitopes from various pathogen-derived antigens, was shown to exert a stronger carrier effect than CRM197 for the induction of anti-group C Neisseria meningitidis capsular polysaccharide (MenC), after immunization of mice with various dosages of N19-MenC or CRM-MenC conjugate vaccines. After two immunizations, the N19-based construct induced anti-MenC antibody and protective bactericidal antibody titers higher than those induced by three doses of the CRM-MenC conjugate and required lower amounts of conjugate. N19-based conjugates are superior to CRM-based conjugates to induce protective immune responses to MenC conjugates.     

Staurosporine-induced apoptosis in Chang liver cells is associated with down-regulation of Bcl-2 and Bcl-XL

A potent inhibitor of serine/threonine kinases, staurosporine exerts antiproliferative and apoptotic effects in many cancer cells, although the exact mechanism of its action is still unclear. This study examines the effects of staurosporine on Chang liver cells, an immortalized non-tumor cell line, in comparison with those caused in HuH-6 and HepG2 cells, two human hepatoma cell lines. Our results provide evidence that staurosporine promotes apoptosis in Chang liver cells as observed by flow cytometric analysis and acridine orange/ethidium bromide staining. The effect appeared already after 8 h of treatment and increased with treatment time and dose. After 48 h of exposure to 200 nM staurosporine clear apoptotic signs were observed in about 50% of the cells. Western blotting analysis showed that in Chang liver cells staurosporine induced a marked decrease in the levels of the antiapoptotic factors Bcl-2 (-75%) and Bcl-XL (-50%). Staurosporine also caused loss of mitochondrial transmembrane potential, release of cytochrome c from mitochondria and activation of caspase-3. The involvement of caspases in staurosporine-induced cell death was also suggested by the observation that the addition of z-VAD-fmk, a general inhibitor of caspases, suppressed apoptosis. In HuH-6 and HepG2 cells treatment with staurosporine induced the arrest of cells in G2/M phase of cell cycle. This effect was not modified by z-VAD-fmk and was not accompanied by the appearance of biochemical signs of apoptosis. We conclude that staurosporine induced apoptosis in Chang liver cells by a mitochondria-caspase-dependent pathway which was closely correlated with a decrease in Bcl-2 and Bcl-XL levels, while in HuH-6 and HepG2 hepatoma cells the drug caused only an antiproliferative effect.     

Allergy to pigeon tick (Argas reflexus): demonstration of specific IgE-binding components

BACKGROUND: The European tick, Argas reflexus, is an urban pest parasitizing urban pigeons and may cause a wide range of allergic reactions. METHODS: Specific IgE to A. reflexus, SDS-PAGE and IgE immunoblotting, performed with tick extract, were carried out in the sera of 6 patients who reported allergic reactions after tick bite. RESULTS: Specific IgE to A. reflexus (RAST class ranging from 1 to 3) were detected in the sera of 6 patients who reported allergic reactions (urticaria and angioedema in 2 and anaphylaxis in the other 4 patients) after tick bite. IgE reactivity to two bands of 22 and 40 kDa were identified in the patient sera. CONCLUSIONS: Allergy to A. reflexus has to be considered in allergic patients living in buildings where pigeons have their nests. The powerful sensitizing property of tick allergen is underlined by the observation that none of our patients was atopic.     

Comparison of LCx with other current viral load assays for detecting and quantifying human immunodeficiency virus type 1 RNA in patients infected with the circulating recombinant form A/G (CRF02)

LCx was compared to other assays in measuring human immunodeficiency virus type 1 (HIV-1) CRF02 viremia. LCx showed significant but low correlation with the other methods. Values of <2.60 log(10) cp/ml were observed in 29.6% of specimens with LCx and in only 14.8% with bDNA and PCR, suggesting suboptimal performance of LCx with CRF02.     

Genotype-phenotype relationship in human ATP6i-dependent autosomal recessive osteopetrosis

Autosomal-recessive osteopetrosis is a severe genetic disease caused by osteoclast failure. Approximately 50% of the patients harbor mutations of the ATP6i gene, encoding for the osteoclast-specific a3 subunit of V-ATPase. We found inactivating ATP6i mutations in four patients, and three of these were novel. Patients shared macrocephaly, growth retardation and optic nerve alteration, osteosclerotic and endobone patterns, and high alkaline phosphatase and parathyroid hormone levels. Bone biopsies revealed primary spongiosa lined with active osteoblasts and high numbers of tartrate-resistant acid phosphatase (TRAP)-positive, a3 subunit-negative, morphologically unremarkable osteoclasts, some of which located in shallow Howship lacunae. Scarce hematopoietic cells and abundant fibrous tissue containing TRAP-positive putative osteoclast precursors were noted. In vitro osteoclasts were a3-negative, morphologically normal, with prominent clear zones and actin rings, and TRAP activity more elevated than in control patients. Podosomes, alphaVbeta3 receptor, c-Src, and PYK2 were unremarkable. Consistent with the finding in the bone biopsies, these cells excavated pits faintly stained with toluidine blue, indicating inefficient bone resorption. Bone marrow transplantation was successful in all patients, and posttransplant osteoclasts showed rescue of a3 subunit immunoreactivity.