Elevated serum levels of macrophage migration inhibitory factor and stem cell growth factor β in patients with idiopathic and systemic sclerosis associated pulmonary arterial hypertension.

Pulmonary arterial hypertension (PAH) can be idiopathic or secondary to autoimmune diseases, and it represents one of the most threatening complications of systemic sclerosis (SSc). Macrophage migration inhibitory factor (MIF) is a pleiotropic cytokine with proinflammatory functions that appears to be involved in the pathogenesis of hypoxia-induced PH. In SSc patients, high serum levels of MIF have been associated with the development of ulcers and PAH. Stem cell growth factor β (SCGF β) is a human growth factor that, together with MIF, is involved in the pathogenesis of chronic spinal cord injury. The aim of our study was to measure serum levels of MIF in patients with idiopathic and SSc-associated PAH. We enrolled 13 patients with idiopathic PAH and 15 with SSc-associated PAH. We also selected 14 SSc patients without PAH and 12 normal healthy controls, matched for sex and age. PAH was confirmed by right hearth catheterism (mPAP>25 mmHg). MIF and SCGF β levels were measured by ELISA. We found significantly higher circulating levels of MIF and of SCGF β in patients with idiopathic PAH (P=0.03 and P=0.004) and with PAH secondary to SSc (P=0.018 and P=0.023) compared to SSc patients without PAH. Higher levels of MIF were found in those patients with an higher New York Heart Association (NYHA) class (P=0.03). We can hypothesize that MIF and SCGF β are able to play a role in PAH, both idiopathic or secondary, and in the future they may be evaluated as useful biomarkers and prognostic factors for this serious vascular disease

Therapeutic Strategies in Pulmonary Arterial Hypertension

Pulmonary arterial hypertension (PAH) is a serious and life-threatening condition for which the prognosis remains poor. Treatment options include endothelial receptor antagonists, phosphodiesterase (PDE5) inhibitors and prostanoids. Despite all demonstrating good short-term efficacy, none of the currently available drug therapies are curative. Treatment with prostanoids is complex and requires careful monitoring and management through a specialist centre. Furthermore, clinical efficacy is dependent on adequate up-titration of the drug. Treatment should be individualised and modified according to clinical response, with the addition of other therapies if required. The importance of monitoring and modifying therapeutic regimes is discussed. There appears to be reluctance among patients and physicians to employ prostanoid therapy, though an aggressive first-line therapy may be appropriate in advanced cases

Echocardiography combined with cardiopulmonary exercise testing for the prediction of outcome in idiopathic pulmonary arterial hypertension

BACKGROUND: Right ventricular (RV) function is a major determinant of exercise intolerance and outcome in idiopathic pulmonary arterial hypertension (IPAH). The aim of the study was to evaluate the incremental prognostic value of echocardiography of the RV and cardiopulmonary exercise testing (CPET) on long-term prognosis in these patients. METHODS: One hundred-thirty treatment-naïve IPAH patients were enrolled and prospectively followed. Clinical worsening (CW) was defined by a reduction in 6-minute walk distance plus an increase in functional class, or non elective hospitalization for PAH, or death. Baseline evaluation included clinical, hemodynamic, echocardiographic and CPET variables. Cox regression modeling with c-statistic and bootstrapping validation methods were done. RESULTS: During a mean period of 528 ± 304 days, 54 patients experienced CW (53%). Among demographic, clinical and hemodynamic variables at catheterization, functional class and cardiac index were independent predictors of CW (Model-1). With addition of echocardiographic and CPET variables (Model-2), peak O2 pulse (peak VO2/heart rate) and RV fractional area change (RVFAC) independently improved the power of the prognostic model (AUC: 0.81 vs 0.66, respectively; p=0.005). Patients with low RVFAC and low O2 pulse (low RVFAC + low O2 pulse) and high RVFAC+low O2 pulse showed 99.8 and 29.4 increase in the hazard ratio, respectively (relative risk -RR- of 41.1 and 25.3, respectively), compared with high RVFAC+high O2 pulse (p=0.0001). CONCLUSIONS: Echocardiography combined with CPET provides relevant clinical and prognostic information. A combination of low RVFAC and low O2 pulse identifies patients at a particularly high risk of clinical deterioration

Workplace health promotion programs in different areas of Europe

Background Aging of the workforce challenges European countries. Keeping aged workers healthy and productive, through health promotion, is a key goal of European labour policy. The aim of the present study was to collect experiences of workplace health promotion for older workers (WHPOW) conducted in 10 representative countries of Central Europe, Eastern Europe and the Mediterranean. Methods A literature review of activities of WHPOW was conducted through a comprehensive search of major scientific databases and on the website of the major European Agencies on worker health promotion. The search was restricted to papers published in English from 2000 to 2015. Companies were asked for additional documentation about WHPOW programmes in a survey conducted with SurveyMonkey. Results A total of 756 initiatives regarding WHPOW were identified. 134 of these were guidelines, regulations, or review studies. The remaining 622 activities were intervention studies performed or promoted in the workplace and targeted at older workers or at the aging of the workforce. Most of the programs were carried out in Central Europe (295, 47.4%), less in East Europe (193, 31.0%) and in Mediterranean countries (134, 21.6%). Conclusion Our study shows that there are only a limited number of WHPOW actions throughout the 10 selected European Countries. While in Central Europe widespread interest in issues of aging workforce has resulted in national policies to encourage WHPO, not all the countries of Eastern Europe are equally well equipped. Lastly, in Southern Europe health promotion activities are largely inadequate compared to needs

Venous endotelin-1 (ET-1) and brain natriuretic peptide (BNP) plasma levels during 6-month bosentan treatment for pulmonary arterial hypertension

Objective: Bosentan, an endothelin (ET) ETA-ETB receptors antagonist, is an effective therapy for idiopathic pulmonary arterial hypertension (PAH) and for PAH related to connective tissue disease (CTD). The aim of this study was to evaluate the behaviour of ET-1 and brain natriuretic peptide (BNP) venous plasma levels during a 6-month dual ET-1 receptor blockade and the potential influence of baseline ET-1 venous plasma levels on the clinical efficacy of bosentan. Setting and patients: Twenty-five patients with PAH (idiopathic n = 16, CTD n = 9) in WHO functional class II-III were included in this study. After initial evaluation, patients' WHO class, 6-minute walking-test (6MWT), ET-1 and BNP venous plasma levels were assessed at baseline and after 6-month bosentan therapy. To evaluate whether the ET-1 levels could influence the clinical response to bosentan, data were analyzed for the whole population which was stratified according to high and low ET-1 plasma levels (on the basis of the baseline median value of ET-1 plasma: Gr.1 18.7 pg/ml). Results: Study population included patients with moderate-severe PAH. After 6-month of treatment we observed a significant increase in 6MWT distance (from 435 ± 85) m to 467 ± 77 m, p > 0.001) and an improvement in WHO class (from 2.4 ± 0.5 to 2 ± 0.6 p > 0.01), with a significant decrease in BNP (from 87 ± 33 pg/ml to 67 ± 41 pg/ml, p = 0.006) and a trend towards lower ET-1 plasma levels (from 17.7 ± 5 pg/ml to 16 ± 6 pg/ml, p = ns). Improvement in effort tolerance (Δ distance) was not correlated to modification in ET-1 (ΔET-1) and BNP (ΔBNP) plasma levels, while we found a significant correlation between ΔET-1 and ΔBNP (r = 0.63, p = 0.0006). Analyzing the subpopulation, Gr.2 patients were older (Gr.1: 41 ± 10 years vs Gr.2: 50 ± 9 years, p = 0.04), had less effort capacity (6MWT distance, Gr.1: 469 ± 76 m, vs Gr.2: 398 ± 82 m, p = 0.03), and showed a trend towards higher BNP values (Gr.1: 82 ± 41 pg/ml vs Gr.2: 92 ± 23 pg/ml, p = 0.051), but no significant differences in pulmonary hemodynamics. After the 6-month treatment both groups showed a significant improvement in 6MWT (Gr.1: + 32 ± 24 m, Gr.2: + 32 ± 21 m p = 0.05) without differences between groups. WHO class had a trend towards lower class (Gr.1: - 0.5 ± 0.5, Gr.2: - 0.3 ± 0.4 p = 0.15) in both groups. BNP plasma levels showed a significant decrease only in Gr.2 (Gr.1: - 6 ± 41 pg/ml, Gr.2: - 34 ± 19 pg/ml p = 0.02); similarly ET-1 plasma levels showed a trend towards a decrease only in Gr.2 (Gr.1: 0.2 ± 4.6 pg/ml, Gr.2: - 3.8 ± 6.6 pg/ml p = 0.09). Conclusions: Our data confirm that bosentan is an effective therapy for patients with PAH. Its clinical efficacy (effort tolerance and NYHA) seems to be independent from baseline venous ET1 plasma levels. Bosentan therapy seems to elicit different patterns in ET-1 and BNP plasma levels, with decrease of the peptides only in patients with higher activation of the systemic endothelin system. Further studies are warranted to explore the potential impact of baseline ET-1 levels on the long-term effects (clinical worsening) of bosentan therapy. © 2008 Elsevier B.V. All rights reserved

Human Herpesvirus 8 and Pulmonary Hypertension

El presente trabajo de investigación tuvo como objetivo evaluar el nivel de conocimiento sobre salud bucal y su relación con la prevalencia de gingivitis en embarazadas que acuden al servicio de gineco-obstericia del Hospital Camaná. Las técnicas usadas fueron el cuestionario y observación clínica; se aplicó un formulario de conocimiento en salud bucal a 100 gestantes que asistieron a dicho hospital en los meses de Junio y Julio. Para determinar la afectación de gingivitis se aplicó una ficha de observación, previa evaluación clínica, en donde se indicó el índice gingival de Löe y Silness de cada individuo. Los resultados indican que la mayor parte de gestantes presentaron un conocimiento regular en salud bucal con 63% y en cuanto a la prevalencia de gingivitis encontrada en el grupo evaluado de un 49% con inflamación leve, seguido por una inflamación severa con 25%. Se concluyó gracias a la prueba de chi cuadrado que la Gingivitis y el nivel de conocimiento sobre salud bucal presentaron relación estadística significativa (P<0.05) por lo que se rechaza la hipótesis nula y se aprueba la alterna. Finalmente se insta a implementar programas y charlas de salud bucal dirigidas a gestantes para lograr una cultura preventiva óptima. Palabras clave: Nivel conocimiento, salud bucal, gingivitis, gestantes

Human Herpesvirus 8 and Pulmonary Hypertension

Human herpesvirus 8 (HHV-8) antibodies were detected in 1 of 33 patients with pulmonary hypertension (including in 1 of 16 with idiopathic pulmonary arterial hypertension), 5 of 29 with cystic fibrosis, and 3 of 13 with interstitial lung disease. No relationship between HHV-8 infection and pulmonary hypertension was found

Low grade endotoxemia and oxidative stress in offspring of patients with early myocardial infarction

Background and aims: Offspring of patients with early myocardial infarction are at higher cardiovascular risk, but the underlying physio-pathological mechanism is unclear. NADPH oxidase-type 2 (NOX-2) plays a pivotal role as mediator of oxidative stress and could be involved in activating platelets in these patients. Furthermore, altered intestinal permeability and serum lipopolysaccharide (LPS) could be a trigger to promote NOX-2 activation and platelet aggregation. This study aims to evaluate the behavior of low grade endotoxemia, oxidative stress and platelet activation in offspring of patients with early myocardial infarction. Methods: We enrolled, in a cross-sectional study, 46 offspring of patients with early myocardial infarction and 86 healthy subjects (HS). LPS levels and gut permeability (assessed by zonulin), oxidative stress (assessed by serum NOX-2-derived peptide (sNOX2-dp) release, hydrogen peroxide (H2O2) production and isoprostanes), serum nitric oxide (NO) bioavailability and platelet activation (by serum thromboxane B2 (TXB2) and soluble P-Selectin (sP-Selectin)) were analyzed. Results: Compared to HS, offspring of patients with early myocardial infarction had higher values of LPS, zonulin, serum isoprostanes, sNOX2-dp H2O2, TXB2, p-selectin and lower NO bioavailability. Logistic regression analysis showed that the variables associated with offspring of patients with early myocardial infarction were LPS, TXB2 and isoprostanes. The multiple linear regression analysis confirmed that serum NOX-2, isoprostanes, p-selectin and H2O2 levels were significantly associated to LPS. Furthermore, serum LPS, isoprostanes and TXB2 levels were significantly associated with sNOX-2-dp. Conclusions: Offspring of patients with early myocardial infarction have a low grade endotoxemia that could generate oxidative stress and platelet activation increasing their cardiovascular risk. Future studies are needed to understand the role of dysbiosis in this population