Adiponectin diminishes platelet aggregation and sCD40L release. Potential role in the metabolic syndrome

The proinflammatory and proatherogenic mediator, soluble CD40 ligand (CD40L), is increased in the metabolic syndrome (MS) and released from platelets. We hypothesized that adiponectin modulates platelet function, and we sought to evaluate the association of adiponectin and sCD40L levels with platelet aggregation in MS and the effects of adiponectin on platelet aggregation and activation. Platelet aggregation and circulating adiponectin, sCD40L and P-selectin were determined in 30 controls and 30 patients with MS. Also, in vitro studies were performed in platelet-rich plasma from nine healthy volunteers. Adiponectin receptors were demonstrated by Western blotting and flow cytometry. ADP and epinephrine platelet aggregation was measured after preincubation with adiponectin. sCD40L and P-selectin secretion was measured in the supernatants by ELISA. Patients with MS had higher sCD40L and P-selectin than controls (5.96 +/- 0.50 vs. 4.28 +/- 0.41 ng/ml, P < 0.05, and 151 +/- 8 vs. 122 +/- 9 ng/ml, P < 0.05). By contrast, adiponectin was lower in patients with MS than in controls (5.25 +/- 0.30 vs. 7.35 +/- 0.34 microg/ml, P < 0.001). Higher platelet aggregation was found in MS. Adiponectin inversely correlated with P-selectin (R = -0.35, P = 0.009), sCD40L (r = -0.24, P = 0.05) and epinephrine and collagen induced aggregation (r = -0.80, P = 0.005; r = -0.70, P = 0.011). Platelets express the receptors for adiponectin. Platelet aggregatory response to epinephrine and ADP significantly decreased following preincubation with adiponectin (96 +/- 4 vs. 23 +/- 3%, P < 0.001, and 102 +/- 9 vs. 85 +/- 9%, P = 0.004). Adiponectin prevented platelet sCD40L release (1.63 +/- 0.15 vs. 2.04 +/- 0.20 ng/ml, P < 0.001). Enhanced platelet aggregation and activation markers are found in MS associated with low adiponectin concentrations. Novel evidence is provided demonstrating that adiponectin has antithrombotic properties, since it inhibits platelet aggregation and platelet activation

The proinflammatory mediator CD40 ligand is increased in the metabolic syndrome and modulated by adiponectin

OBJECTIVES: We hypothesized that the CD40/CD40 ligand (CD40L) system is up-regulated in the metabolic syndrome (MS) and modulated by adiponectin (AN). The objectives were: 1) to compare plasma and monocyte CD40L in patients with MS and controls and its association with clinical and biochemical parameters, 2) to investigate platelets as a source of soluble CD40L (sCD40L), and 3) to analyze the effects of AN on CD40/CD40L. METHODS: Plasma sCD40L and AN were measured in 246 controls and 128 patients with MS by ELISA. Monocyte CD40/CD40L expression and platelet CD40L content and release were compared in patients with MS and controls. Monocytes and endothelial cells were cultured with AN and CD40/CD40L expression determined by real-time RT-PCR and Western blotting. RESULTS: Patients with MS had higher sCD40L and lower AN levels than controls (0.89 +/- 0.1 vs. 0.76 +/- 0.07 ng/ml and 10.10 +/- 0.65 vs. 12.99 +/- 0.80 microg /ml, P < 0.05). Monocyte CD40/CD40L expression was higher (P < 0.05) in patients than controls (CD40: 1.31 +/- 0.31 vs. 0.80 +/- 0.14 arbitrary units; CD40L: 1.24 +/- 0.85 vs. 0.43 +/- 0.14 pg/microg protein). No differences were observed on CD40L content between resting platelets from patients with MS and controls (7.7 +/- 3.5 vs. 7.2 +/- 2.2 pg/microg protein). Stimulated platelets from patients with the MS released more (P < 0.05) sCD40L than controls (582 +/- 141 vs. 334 +/- 60% change vs. nonstimulated platelets). AN reduced CD40L mRNA and protein expression in monocytes from MS patients and endothelial cells. CONCLUSIONS: The enhanced sCD40L and cellular CD40L expression in the MS suggests that CD40L is of pathophysiological relevance in MS. Also, a new antiinflammatory effect of AN is described through the modulation of the CD40/CD40L system

Correlation between serum content of the main COPs (cholesterol oxidation products) from autoxidation and cardiovascular risk factors

BACKGROUND/AIMS: Risk factors for cardiovascular disease (CVD) have been proven to be associated with an increased oxidative stress. Several studies have considered cholesterol oxidation products (COPs) as specific in vivo markers of oxidative stress. The aim of this study was to investigate the association between the levels of COPs derived from autoxidation processes and established cardiovascular risk factors, comparing the levels of serum COPs in subjects with or without showing values out of the reference ranges. METHODS: It was a cross-sectional study in which 88 subjects were recruited and individual and total COPs from autoxidation origin was analyzed in serum by GC-MS. The simultaneous correlation of COPs with different CVD risk factors have been analyzed. RESULTS AND DISCUSSION: A great variability of total COPs concentrations were found. Subjects presented total COPs values from 0.091 to 2.052 μg/mL. Total COPs were significantly higher (p < 0.05) in patients with hypertriglycerolemia, hypertension, diabetes and overweight/ obesity status compared to those subjects who did not present those CVD risk factors. Moreover, 7α and 7β hydroxycholesterol and 7-ketocholesterol were significantly higher (p < 0.05) in patients with hypertension and diabetes. No significant differences in total COPs were found between patients with and without hypercholesterolemia. CONCLUSIONS: The obtained results showed that the analyzed COPs correlate well with at least 4 out of 6 risk factors of development of CVD

Gender Differences in Plasma Biomarker Levels in a Cohort of COPD Patients: A Pilot Study

Little is known about gender differences in plasma biomarker levels in patients with chronic obstructive pulmonary disease (COPD). HYPOTHESIS: There are differences in serum biomarker levels between women and men with COPD. OBJECTIVE: Explore gender differences in plasma biomarker levels in patients with COPD and smokers without COPD. METHODS: We measured plasma levels of IL-6, IL-8, IL-16, MCP-1, MMP-9, PARC and VEGF in 80 smokers without COPD (40 males, 40 females) and 152 stable COPD patients (76 males, 76 females) with similar airflow obstruction. We determined anthropometrics, smoking history, lung function, exercise tolerance, body composition, BODE index, co-morbidities and quality of life. We then explored associations between plasma biomarkers levels and the clinical characteristics of the patients and also with the clinical and physiological variables known to predict outcome in COPD. RESULTS: The plasma biomarkers level explored were similar in men and women without COPD. In contrast, in patients with COPD the median value in pg/mL of IL-6 (6.26 vs 8.0, p = 0.03), IL-16 (390 vs 321, p = 0.009) and VEGF (50 vs 87, p = 0.02) differed between women and men. Adjusted for smoking history, gender was independently associated with IL-16, PARC and VEGF levels. There were also gender differences in the associations between IL-6, IL-16 and VEGF and physiologic variables that predict outcomes. CONCLUSIONS: In stable COPD patients with similar airflow obstruction, there are gender differences in plasma biomarker levels and in the association between biomarker levels and important clinical or physiological variables. Further studies should confirm our findings

RAPID-retargetability for reusability of application-driven quadrature D/A interface block design

This paper describes ESPRIT 29648, concerning the development of an advanced methodology for the design of a mixed-signal application-driven quadrature D/A interface sub-system, aiming at its reusability by a retargetting procedure with minimal changes to their structural sub-blocks. The methodology is demonstrated, first, by developing a nominal design platform for the implementation in 0.35 /spl mu/m double-poly CMOS technology of a quadrature D/A interface block design for the GSM standard, and, then, by an automatic retargeting in an evolutionary technology through the realization of a silicon prototype in 0.25 /spl mu/m CMOS.European Community 2964

Trabecular bone score in active or former smokers with and without COPD

Background Smoking is a recognized risk factor for osteoporosis. Trabecular bone score (TBS) is a novel texture parameter to evaluate bone microarchitecture. TBS and their main determinants are unknown in active and former smokers. Objective To assess TBS in a population of active or former smokers with and without Chronic Obstructive Pulmonary Disease (COPD) and to determine its predictive factors. Methods Active and former smokers from a pulmonary clinic were invited to participate. Clinical features were recorded and bone turnover markers (BTMs) measured. Lung function, low dose chest Computed Tomography scans (LDCT), dual energy absorptiometry (DXA) scans were performed and TBS measured. Logistic regression analysis explored the relationship between measured parameters and TBS. Results One hundred and forty five patients were included in the analysis, 97 (67.8%) with COPD. TBS was lower in COPD patients (median 1.323; IQR: 0.13 vs 1.48; IQR: 0.16, p = 0.003). Regression analysis showed that a higher body mass index (BMI), younger age, less number of exacerbations and a higher forced expiratory volume-one second (FEV1%) was associated with better TBS (β = 0.005, 95% CI:0.000–0.011, p = 0.032; β = -0.003, 95% CI:-0.007(-)-0.000, p = 0.008; β = -0.019, 95% CI:-0.034(-)-0.004, p = 0.015; β = 0.001, 95% CI:0.000–0.002, p = 0.012 respectively). The same factors with similar results were found in COPD patients. Conclusions A significant proportion of active and former smokers with and without COPD have an affected TBS. BMI, age, number of exacerbations and the degree of airway obstruction predicts TBS values in smokers with and without COPD. This important information should be considered when evaluating smokers at risk of osteoporosis

Exacerbation of hepatitis C induced subclinical hypoadrenalism by Interferon-alpha2beta: A case report

Adrenal disease is an uncommon manifestation of hepatitis C infection and its related treatment regimen. This is a case of subclinical hypoadrenalism, probably induced by hepatitis C infection and further exacerbated by interferon-α2β and Ribavirin therapy. The adrenal deterioration during the treatment course was observed closely with 24-hour salivary profiles and 250 μg adrenocorticotropin stimulation tests using parallel serum and salivary cortisol concentrations. A number of possible pathogenic mechanisms are discussed, and the controversy over its management is emphasized

An RF-to-DC energy harvester for co-integration in a low-power 2.4 GHz transceiver frontend

Comunicación presentada al "ISCAS 2012" celebrado en Seúl (Corea del Sur) del 20 al 23 de Mayo del 2012.A 2.4 GHz energy harvester for co-integration into a low-power transceiver (TRx) operating at the same frequency is presented. An RF switch decouples the harvester from the TRx and keeps the performance degradation of the TRx low, i.e. 0.2 dB reduced output power in Tx-mode and 0.4 dB reduced sensitivity in Rx-mode. In order to enable the harvester to operate without a DC power supply, an RF switch is used that is passively turned on. The circuit is implemented in a 130 nm CMOS process, and requires a minimum input RF power of -10 dBm. Based on post-layout simulation results the proposed energy harvester achieves a peak efficiency of 22.7% at an input power level of -3 dBm.This work has been supported by the Spanish Ministry of Science and Innovation under grant TEC2009-08447, the Junta de Andalucía under grant TIC-02818 and the 2007-2013 FEDER Program.Peer Reviewe

Estudio de la díada CD40/CD40L y su modulación por la adiponectina en el síndrome metabólico

En el contexto del concepto actual del Síndrome Metabólico como una enfermedad inflamatoria y protrombótica, el presente estudio muestra que la vía del CD40/CD40L puede desempeñar un papel en el mayor riesgo cardiovascular de estos pacientes. Hemos encontrado concentraciones elevadas de la forma soluble del ligando de CD40 en pacientes con Síndrome Metabólico, posiblemente procedente de las plaquetas. Estos niveles, se ha demostrado ampliamente en la bibliografía disponible que se asocian con un aumento del riesgo cardiovascular. Otro hallazgo de este estudio es el incremento en la liberación paquetar de Scd40l EN PACIENTES CON Síndrome Metabólico, lo que podría ser responsable de la elevación de la concentración observada en el plasma. Además de la forma soluble, en nuestros pacientes observamos un aumento de la expresión en los monocitos circulantes. Esta forma celular, puede directamente como ya se ha publicado, activar y desencadenar procesos proaterogénicos en otros monocitos y en células endoteliales. Asimismo, el aumento de la expresión del receptor CD40 en monocitos de pacientes, indica que estos son más ¿susceptibles? De ser activados por su ligando, lo cual, podría contribuir a amplificar la respuesta inflamatoria y daño vascular de los pacientes con Síndrome Metabólico. En estos pacientes también se ha encontrado aumentada la agregación plaquetar con respecto a los controles, asociada a niveles disminuidos de adiponectina. También se muestra que la adiponectina regula el sistema CD40/CD40L en monocitos, células endoteliales y plaquetas. Esta adipoquina disminuye la expresión de CD40/CD40L en monocitos y células endoteliales. Y en las plaquetas, principal fuente de CD40L, la adiponectina disminuye la agregación y la liberación plaquetar de CD40L y P-selectina. Estos hallazgos suponene nuevos efectos antiinflamatorios y antitrombóticos de la adiponectina y sugieren que la hipoadinectinemia podría contribuir en parte a la inflamación y estado protrombótico que se encuentran en el Síndrome Metabólico