Mónica Acevedo

Administration of growth hormone to patients with advanced cardiac heart failure: effects upon left ventricular function, exercise capacity, and neurohormonal status

Experimental and clinical studies have shown that the administration of recombinant human growth hormone can improve deteriorated left ventricular function and hemodynamics in patients with heart failure. Herein, we compared the effects of growth hormone versus placebo upon resting left ventricular ejection fraction, exercise capacity and neurohormonal status in patients with advanced heart failure. Nineteen patients with advanced cardiac heart failure (ejection fraction <30%) were studied at baseline and after 8 weeks of treatment with growth hormone (0.03 U/kg per day) or placebo. Primary end points were resting left ventricular ejection fraction, peak oxygen consumption and neurohormonal status, including plasma norepinephrine levels and insulin like growth factor-1 and its binding protein-3. Results are presented as median and interquartile ranges. Patients receiving growth hormone had a significant increase in insulin growth factor-1 plasma levels (median difference growth hormone=83 ng/ml [57-170] versus placebo=-6 ng/ml [-23-6], P<0.05) and its binding protein-3. However, no significant increase in left ventricular ejection fraction after growth hormone treatment (ejection fraction pre=16% [13-18] and post=17% [14-27]) was noticed when compared to placebo (ejection fraction pre=20% [15-24] and post=20% [15-26]). Also, no significant effect of growth hormone treatment was seen on peak oxygen consumption or norepinephrine plasma levels. Although the administration of growth hormone to patients with advanced cardiac heart failure was associated with a significant increase in insulin growth factor-1, there were no significant changes in ejection fraction, exercise capacity and/or neurohormonal status.

Enalapril restores depressed circulating insulin-like growth factor 1 in patients with chronic heart failure

BACKGROUND Congestive heart failure (CHF) is characterized by increased activity of the renin-angiotensin system. Recent experimental studies have shown that infusion of angiotensin II results in depressed plasma levels of insulin-like growth factor 1 (IGF-1) and weight loss. We have previously reported that stable patients with CHF have decreased activity of the growth hormone (GH)-IGF1 axis. We have hypothesized, therefore, that angiotensin-converting enzyme (ACE) inhibition therapy should restore GH-IGF1 activity in CHF patients. METHODS AND RESULTS Nine patients with stable CHF who were taking digitalis and diuretics, New York Heart Association functional class III were studied before and after 8 weeks of therapy with Enalapril (10 mg twice daily). We measured IGF1 levels, radionuclide left ventricular ejection fraction (EF) and peak oxygen consumption (PVO2). We found that 7 of 9 patients had abnormally low levels of IGF1 (0.2-0.5 mU/ml). IGF1 levels reverted to normal after Enalapril therapy (0.36 +/- 0.03 to 0.8 +/- 0.14 mU/ml, P = .004). This was associated with a significant increase in EF (27.4 +/- 1.1 to 31.4 +/- 0.9%) and PVO2 (14.8 +/- 1.2 to 18.6 +/- 1.5 ml/kg/min) values (P < .05). CONCLUSION Chronic ACE inhibition therapy restored previously reduced IGF1 plasma levels in patients with CHF, most likely by reducing angiotensin II activity.

Effects of glucose-insulin-potassium solution on myocardial salvage and left ventricular function after primary angioplasty.

ObjectiveTo evaluate the effects of glucose-insulin-potassium (GIK) therapy on infarct size and left ventricular function when used as an adjuvant therapy to primary angioplasty. DesignProspective, randomized, double-blind, placebo-controlled study. SettingCardiac intensive care unit at a university hospital. PatientsThirty-seven patients with acute myocardial infarction for whom primary angioplasty was indicated. InterventionsEligible patients were randomized by a blinded pharmacist to GIK solution (30% glucose in water with insulin 50 U/L, and KCl 40 mM/L) vs. placebo at 1.5 mL/kg/hr for 24 hrs. Measurements and Main ResultsTc 99m sestamibi myocardial scintigraphy was performed at admission and at 3 months. Primary end points were the changes in left ventricular ejection fraction (LVEF) and the size of salvaged myocardium. Baseline clinical characteristics were similar in both groups. At the 3-month follow-up, a significant overall decrease in infarct size (37 ± 16% vs. 12 ± 10%, p < .005) and an increase in LVEF (34 ± 13% vs. 49 ± 9%, p = .005) were observed. Patients randomized to GIK solution experienced a significant increase in their LVEF at 3 months (39 ± 12 to 51 ± 13, p = .002). Patients who received placebo had no significant differences between baseline and 3-month measurements (44 ± 13 vs. 49 ± 14, p = NS). There was a trend toward an increase in myocardial salvage in the GIK group, which did not reach statistical significance. When patients from both groups were compared directly, differences in LVEF improvement were no longer significant. ConclusionsGIK solution did not improve LVEF or decrease the infarct size among patients undergoing primary angioplasty.

Razón cintura estatura como predictor de riesgo cardiometabólico en niños y adolescentes

Resumen: En ninos, la obesidad general y visceral se asocian con mayor riesgo cardiometabolico. El aumento en la prevalencia del sindrome metabolico (SM) en ninos y adolescentes empeora el riesgo cardiovascular. Nece-sitamos contar con nuevos marcadores que permitan predecir el SM en ninos. Objetivo: Comparar indice de masa corporal (zIMC) con razon cintura estatura (RCE) como pre-dictores de SM en ninos chilenos. Metodo: Estudio transversal en 618 escolares, edad 10.8± 1.9 anos, 51.6 % mujeres, 190 eutroficos, 174 sobrepeso, 254 obesos, estrato socioeconomico medio y medio bajo, area urbana de Santiago. Determinamos peso, talla, circunferencia de cintura, presion arterial, perfil lipidico y glicemia. Diagnostico de SM basado en la presencia de ≥ 3 criterios de Cook. El SM se modelo en funcion de RCE y z score IMC , con mo-delos de regresion logistica. Se usaron curvas ROC para comparar RCE y zIMC como predictores de SM. Punto de corte segun indice de YOUDEN. Resultados: La prevalencia de SM fue 15.37 %. Promedio de z IMC + 1.22± 0.90 y de RCE 0.52±0.07. Punto de corte optimo para SM: RCE 0.55 (sensibili-dad 72%, especificidad 70%) y zIMC: 1.76 (sensibi-lidad 71%, especificidad 74%).

Comparison of Lipoprotein-Associated Phospholipase A2 and High Sensitive C-Reactive Protein as Determinants of Metabolic Syndrome in Subjects without Coronary Heart Disease: In Search of the Best Predictor

High sensitivity C-reactive protein (hsCRP) is a marker of metabolic syndrome (MS) and cardiovascular (CV) disease. Lipoprotein-associated phospholipase A2 (Lp-PLA2) also predicts CV disease. There are no reports comparing these markers as predictors of MS. Methods. Cross-sectional study comparing Lp-PLA2 and hsCRP as predictors of MS in asymptomatic subjects was carried out; 152 subjects without known atherosclerosis participated. Data were collected on demographics, cardiovascular risk factors, anthropometric and biochemical measurements, and hsCRP and Lp-PLA2 activity levels. A logistic regression analysis was performed with each biomarker and receiver operating characteristic (ROC) curves were constructed for MS. Results. Mean age was 46 ± 11 years, and 38% of the subjects had MS. Mean Lp-PLA2 activity was 185 ± 48 nmol/mL/min, and mean hsCRP was 2.1 ± 2.2 mg/L. Subjects with MS had significantly higher levels of Lp-PLA2 (P = 0.03) and hsCRP (P < 0.0001) than those without MS. ROC curves showed that both markers predicted MS. Conclusion. Lp-PLA2 and hsCRP are elevated in subjects with MS. Both biomarkers were independent and significant predictors for MS, emphasizing the role of inflammation in MS. Further research is necessary to determine if inflammation predicts a higher risk for CV events in MS subjects.

Use of Endovascular Stents in Atherosclerotic Renovascular Stenosis: Blood Pressure and Renal Function Changes in Hypertensive Patients

Atherosclerotic renal artery stenosis may result in hypertension and ischemic nephropathy. Renal artery endovascular stenting has emerged as current therapy; however, the percentage of patients who benefit from this procedure is still not well established. The authors studied 116 hypertensive patients with atherosclerotic renovascular stenosis who underwent successful renal artery stenting for the first time. At 1 year, there was a significant overall decrease in blood pressure in the group after stenting; however, there was no change in renal function. Also, no significant change in the number of antihypertensive drugs was noted. Blood pressure improved in 55% of the patients, worsened in 14%, and remained unchanged in 31%. Renal function improved in 16% of the patients, worsened in 30%, and remained stable in 54%. In relation to blood pressure control, patients with resistant or difficult‐to‐control hypertension showed the most improvement in blood pressure control after stenting.

Role of BK human polyomavirus in cancer

Human polyomaviruses (HPyV), which are small DNA viruses classified into the polyomaviridae family, are widely distributed in human populations. Thirteen distinct HPyVs have been described to date. Some of these viruses have been found in human tumors, suggesting an etiological relationship with cancer. In particular, convincing evidence of an oncogenic role has emerged for a specific HPyV, the Merkel cell polyomavirus (MCPyV). This HPyV has been linked to rare skin cancer, Merkel cell carcinoma (MCC). This finding may be just the tip of the iceberg, as HPyV infections are ubiquitous in humans. Many authors have conjectured that additional associations between HPyV infections and neoplastic diseases will likely be discovered. In 2012, the International Agency for Research on Cancer (IARC) evaluated the carcinogenicity of the BK virus (BKPyV), reporting that BKPyV is “possibly carcinogenic to humans.” This review explores the BKPyV infection from a historical point of view, including biological aspects related to viral entry, tropism, epidemiology and mechanisms potentially involved in BKPyV-mediated human carcinogenesis. In order to clarify the role of this virus in human cancer, more epidemiological and basic research is strongly warranted.

Atherogenic Dyslipidemia in Latin America: Prevalence, causes and treatment: Expert’s position paper made by The Latin American Academy for the Study of Lipids (ALALIP) Endorsed by the Inter-American Society of Cardiology (IASC), the South American Society of Cardiology (SSC), the Pan-American College of Endothelium (PACE), and the International Atherosclerosis Society (IAS)

La dislipidemia aterogenica (DA) es una entidad poco reconocida en las guias de practica clinica actuales. Debido a las frecuentes alteraciones lipidicas asociadas a esta anomalia metabolica en America Latina (AL), hemos organizado un grupo de expertos que ha adoptado el nombre de Asociacion Latinoamericana para el Estudio de Lipidos (ALALIP), para generar un documento en el que se analice la prevalencia en AL del perfil lipidico relacionado con esta afeccion y ofrecer recomendaciones practicas para su optimo diagnostico y tratamiento. Metodologia: Se selecciono un grupo de expertos regionales y, utilizando una metodologia Delphi modificada, se realizo una revision bibliografica exhaustiva, con enfasis en estudios o revisiones que tuvieran implicaciones para AL. Posteriormente se desarrollo una serie de preguntas clave sobre la epidemiologia, la fisiopatologia, el diagnostico y el tratamiento de la DA, que fueron discutidas por el grupo de expertos. Como convencion, las recomendaciones que tuvieron un 100% de aceptacion fueron consideradas unanimes; aquellas con al menos el 80% como para el consenso, y de desacuerdo, aquellas con menos del 80%. Resultados: Aunque no existe un estudio global sobre los factores de riesgo que se haya realizado sobre la base de una muestra representativa de toda la poblacion de AL, el analisis sistematico de las encuestas nacionales de salud y los estudios de cohortes regionales evidencian la alta prevalencia de las anormalidades lipidicas que definen la DA. La prevalencia de niveles bajos de colesterol de lipoproteinas de alta densidad (HDL-C) oscila entre el 34.1% (estudio CESCAS I) y el 53.3% (estudio LASO), con diferentes frecuencias entre hombres y mujeres y el punto de corte seleccionado. La prevalencia de trigliceridos elevados (TRG) varia de 25.5% (estudio LASO) a 31.2% (Encuesta Nacional de Salud de Chile) siendo siempre mas prevalente en..

GENDER DIFFERENCES IN CARDIOVASCULAR RISK BY TWO DIFFERENT SCORES: A FIVE YEARS FOLLOW UP ANALYSIS OF A 1500-PATIENT DATABASE

We have previously shown that Framingham traditional risk score is not correlated with the presence of CAD in the female population. This may be attributed to the fact that traditional scores underscore risk in women. We sought to evaluate gender differences in all cause mortality between Global

Crosslinking and mass spectrometry suggest that the isolated NTD domain dimer of Moloney murine leukemia virus integrase adopts a parallel arrangement in solution

BackgroundRetroviral integrases (INs) catalyze the integration of viral DNA in the chromosomal DNA of the infected cell. This reaction requires the multimerization of IN to coordinate a nucleophilic attack of the 3’ ends of viral DNA at two staggered phosphodiester bonds on the recipient DNA. Several models indicate that a tetramer of IN would be required for two-end concerted integration. Complementation assays have shown that the N-terminal domain (NTD) of integrase is essential for concerted integration, contributing to the formation of a multimer through protein-protein interaction. The isolated NTD of Mo-MLV integrase behave as a dimer in solution however the structure of the dimer in solution is not known.ResultsIn this work, crosslinking and mass spectrometry were used to identify regions involved in the dimerization of the isolated Mo-MLV NTD. The distances between the crosslinked lysines within the monomer are in agreement with the structure of the NTD monomer found in 3NNQ. The intermolecular crosslinked peptides corresponding to Lys 20-Lys 31, Lys 24-Lys 24 and Lys 68-Lys 88 were identified. The 3D coordinates of 3NNQ were used to derive a theoretical structure of the NTD dimer with the suite 3D-Dock, based on shape and electrostatics complementarity, and filtered with the distance restraints determined in the crosslinking experiments.ConclusionsThe crosslinking results are consistent with the monomeric structure of NTD in 3NNQ, but for the dimer, in our model both polypeptides are oriented in parallel with each other and the contacting areas between the monomers would involve the interactions between helices 1 and helices 3 and 4.