Apelin decreases myocardial injury and improves right ventricular function in monocrotaline-induced pulmonary hypertension

Falcao-Pires I, Goncalves N, Henriques-Coelho T, Moreira-Goncalves D, Roncon-Albuquerque R Jr, Leite-Moreira AF. Apelin decreases myocardial injury and improves right ventricular function in monocrotaline-induced pulmonary hypertension. Am J Physiol Heart Circ Physiol 296: H2007-H2014, 2009. First published April 3, 2009; doi: 10.1152/ajpheart.00089.2009.-We investigated the endogenous production of apelin and the cardiac and pulmonary effects of its chronic administration in monocrotaline (MCT)-induced pulmonary hypertension (PH). Male Wistar rats were injected with MCT (60 mg/kg sc) or vehicle (day 0). One week later, these animals were randomly treated during 17 days with pyroglutamylated apelin-13 (Pyr-AP13; 200 mu g.kg(-1).day(-1) ip) or a similar volume of saline, resulting in four groups: sham (n = 11), sham-AP (n = 11), MCT (n = 16), and MCT-AP (n = 13). On day 25, right ventricular (RV) and left ventricular (LV) hemodynamic and morphometric parameters were assessed. Tissue and plasma samples were collected for histological and molecular analysis. When compared with sham, the MCT group presented a significant increase of RV mass (166 +/- 38%), diameter of cardiomyocyte (40 +/- 10%), myocardial fibrosis (95 +/- 20%), peak systolic pressure (99 +/- 22%), peak rate of ventricular pressure rise (dP/dt(max); 74 +/- 24%), peak rate of ventricular pressure decline (dP/dt(min); 73 +/- 19%), and time constant tau (55 +/- 16%). In these animals, RV expression of apelin (-73 +/- 10%) and its receptor APJ (-61 +/- 20%) was downregulated, whereas mRNA expression of type B natriuretic peptide (9,606 +/- 713%), angiotensinogen (191 +/- 147%), endothelin-1 (RV, 497 +/- 156%; and LV, 799 +/- 309%), plasmatic levels of apelin (104 +/- 48%), and angiotensin 1-7 (161 +/- 151%) were increased. Chronic treatment with Pyr-AP13 significantly attenuated or normalized these changes, preventing apelin-APJ mRNA downregulation and PH-induced neurohumoral activation of several vasoconstrictors, which exacerbates apelin-APJ vasodilator effects. Therefore, apelin delayed the progression of RV hypertrophy and diastolic dysfunction. Together, these observations suggest that the apelin-APJ system may play an important role in the pathophysiology of PH, representing a potential therapeutic target since it significantly attenuates RV overload and PH-induced neurohumoral activation

Influence of P53 on the radiotherapy response of hepatocellular carcinoma

Hepatocellular carcinoma (HCC) is one of the most common cancers worldwide, and it has a poor prognosis and few therapeutic options. Radiotherapy is one of the most effective forms of cancer treatment, and P53 protein is one of the key molecules determining how a cell responds to radiotherapy. The aim of this study was to determine the therapeutic efficacy of iodine-131 in three human HCC cell lines

Tuberculosis screening in patients receiving biological therapy

AIM: Biological therapies are a risk factor for tuberculosis (TB). Portuguese recommendations recommend universal baseline screening for TB before starting biologics (2006) and annually thereafter if screened negative (2012 update). The gain with re-screening remains unknown. We aimed to i)identify the risk of latent TB infection at baseline screening among patients candidates to initiate biologics ii)present follow-up results for patients receiving different biological therapies and analyse intolerance or toxicity related to preventive therapy, conversions of immunodiagnostic tests under biological therapy and development of active TB. METHODS: Patients screened for TB at a reference centre before starting biological therapy between 2008-2012 were identified. Medical files were retrospectively reviewed. Demographic data, screening and follow-up results and information on biological therapy were collected. EXCLUSION CRITERIA: unavailable information on initiation of biological therapy. RESULTS: 183 patients were included in the study, with 115 starting biological therapy. The baseline screening was positive in 52(45,2%) patients - 50(96,2%) were proposed for preventive treatment (2 had abnormal liver enzymes). Mild hepatotoxicity occurred in 4(8%) patients without need to interrupt TB prophylaxis. No cases of active TB occurred during follow-up in patients with positive baseline screening. Among the 63(54,8%) patients who screened negative, 2(3,2%) developed active TB (under infliximab and adalimumab) more than one year after initiation of biologics. 26(41,3%) patients were re-screened at the TB centre. 5(19,2%) had tuberculin skin test (TST) conversion and one concomitantly undetermined IGRA. No IGRA conversions were observed. The follow-up period was 4,0 years. TB baseline screening's negative predictive value (NPV) was 96,8% (95%CI: 89,0% to 99.5%). A low rate of re-screening was observed. CONCLUSION: The rate of latent TB at baseline screening was higher than expected. Preventive treatment was well tolerated. No patients with positive baseline screening developed active TB. Efforts should be made to raise awareness concerning the risk of TB exposure, specially considering that the active TB cases were compatible with new infection. The rate of re-screening suggests a low awareness regarding current recommendations Nation-wide studies are necessary to evaluate the efficacy of the re-screening strategy and to clarify what risk groups most benefit from it

Pneumonia em doentes idosos e com menor gravidade internados: há alguma especificidade?

info:eu-repo/semantics/publishedVersio

Potencial hidrogeniônico de antimicrobianos, segundo os fatores ambientais temperatura e luminosidade

The objective of this experimental study was to measure the pH of antibiotics administered by intravenous infusion - ceftriaxone sodium, vancomycin hydrochloride, metrodinazole, penicillin G potassium and amikacin sulfate - after reconstitution with sterile water and dilution with NaCl 0.9% or dextrose 5% in water, according to temperature and luminosity of the environment. The results showed that variation in the drugs' pH was less than 1.0 value and that some antibiotics remained acidic after dilution and maintained this chemical profile in all situations studied, suggesting that the studied environmental factors did not change the solutions' acid base characteristic. Some pH values measured characterize risk for the development of chemical phlebitis and infiltration, and it is important for clinical practice to emphasize the profile of intravenous solutions of antibiotics, considering method of dilution, and time to infusion.El objetivo de este estudio experimental fue medir el pH de los antibióticos de administración intravenosa ceftriaxona sódica, clorhidrato de vancomicina, metronidazol, penicilina G potásica y sulfato de amikacina, después de reconstitución con agua destilada y dilución con NaCl a 0,9%, o suero glucosado a 5%, considerando la influencia de la temperatura y luminosidad ambientales, así como el tiempo de exposición, en el comportamiento químico de esos fármacos. Los resultados demostraron variaciones que no ultrapasaron 1,0 (valor de pH) y que algunos antimicrobianos, eminentemente ácidos después de la dilución, mantuvieron ese comportamiento en todas las situaciones estudiadas, no sugiriendo la influencia de factores ambientales en el comportamiento químico de las soluciones. Considerando que algunos valores de pH encontrados pueden contribuir para el desarrollo de flebitis química e infiltración, es importante enfatizar que para la práctica clínica en salud, existe la necesidad de conocer las características de las soluciones de infusión intravenosa, considerando el tipo de dilución y el tiempo de infusión.O objetivo deste estudo experimental foi medir o pH dos antibióticos de administração intravenosa ceftriaxona sódica, cloridrato de vancomicina, metronidazol, penicilina G potássica e sulfato de amicacina, após reconstituição com água destilada e diluição com NaCl 0,9%, ou soro glicosado 5%, considerando a influência da temperatura e luminosidade ambientais, assim como do tempo de exposição, no comportamento químico desses fármacos. Os resultados demonstraram variações que não ultrapassaram 1,0 valor de pH e que alguns antimicrobianos, eminentemente ácidos após a diluição, mantiveram esse comportamento em todas as situações estudadas, não sugerindo a influência de fatores ambientais no comportamento químico das soluções. Como alguns valores de pH encontrados podem contribuir para o desenvolvimento de flebite química e infiltração, é importante enfatizar para a prática clínica em saúde, a necessidade de conhecer as características das soluções de infusão intravenosa, considerando tipo de diluição e tempo de infusão.Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Universidade Federal de São Paulo (UNIFESP) Departamento de EnfermagemUNIFESP, Depto. de EnfermagemCNPq: 476295/2004-1CNPq: 502382/2007-4SciEL

Discrimination of water quality monitoring sites in River Vouga using a mixed-effect state space model

The surface water quality monitoring is an important concern of public organizations due to its relevance to the public health. Statistical methods are taken as consistent and essential tools in the monitoring procedures in order to prevent and identify environmental problems. This work presents the study case of the hydrological basin of the river Vouga, in Portugal. The main goal is discriminate the water monitoring sites using the monthly dissolved oxygen concentration dataset between January 2002 and May 2013. This is achieved through the extraction of trend and seasonal components in a linear mixed-effect state space model. The parameters estimation is performed with both maximum likelihood method and distribution-free estimators in a two-step procedure. The application of the Kalman smoother algorithm allows to obtain predictions of the structural components as trend and seasonality. The water monitoring sites are discriminated through the structural components by a hierarchical agglomerative clustering procedure. This procedure identified different homogenous groups relatively to the trend and seasonality components and some characteristics of the hydrological basin are presented in order to support the results