Influence of antihypertensive drugs on aortic and coronary effects of Ang-(1-7) in pressure-overloaded rats

This study investigated the influence of antihypertensive drugs, such as angiotensin-converting enzyme inhibitors (ACEIs), AT1 receptor blockers (ARBs), voltage-gated L-type calcium channel blockers, and mineralocorticoid receptor antagonists (MRAs), on the effects of angiotensin-(1-7) [Ang-(1-7)] on aorta and coronary arteries from pressure-overloaded rats. Pressure overload was induced by abdominal aortic banding (AB). To evaluate the role of antihypertensive drugs on the effect of Ang-(1-7), AB male Wistar rats weighing 250–300 g were treated with vehicle or low doses (5 mg·kg-1·day-1, gavage) of losartan, captopril, amlodipine, or spironolactone. Isolated aortic rings and isolated perfused hearts under constant flow were used to evaluate the effect of Ang-(1-7) in thoracic aorta and coronary arteries, respectively. Ang-(1-7) induced a significant relaxation in the aorta of sham animals, but this effect was reduced in the aortas of AB rats. Chronic treatments with losartan, captopril or amlodipine, but not with spironolactone, restored the Ang-(1-7)-induced aorta relaxation in AB rats. The coronary vasodilatation evoked by Ang-(1-7) in sham rats was blunted in hypertrophic rats. Only the treatment with losartan restored the coronary vasodilatory effect of Ang-(1-7) in AB rat hearts. These data support a beneficial vascular effect of an association of Ang-(1-7) and some antihypertensive drugs. Thus, this association may have potential as a new therapeutic strategy for cardiovascular diseases.

Evaluación del seguimiento de 29 niños chilenos con la enfermedad de la orina olor a jarabe de arce clásica / Follow up evaluation of 29 chilean children with classical maple syrup urine disease

Introduction: Maple Syrup Urine Disease (MSUD) is caused by a defect of the ketoacid dehydrogenase enzyme complex of the branched amino acids Valine, Isoleucine and Leucine (VIL). The treatment consists of a leucine-restricted diet. Objective: To evaluate the long-term follow-up in children with MSUD. Methodology: 29 records were reviewed of patients with MSUD, of which 24 were clinically identified (> 5th day of life), 4 cases by MSUD family history and one by neonatal screening (< 5th day of life). Leucine (Leu) levels were measured at diagnosis (Biotronic 2000) and during follow-up (mass spectrometry). The number of decompensation events, Total Intellectual Quotient (TIQ, Bayley and Wechsler scale) and nutritional status were also measured. STATA statistical software version 9.2 was applied (p≤0.05). Results: Mean age at diagnosis was 14 days old. In all cases the diagnosis was confirmed by elevated levels of Leu and alloisoleucin. When comparing the TIQ of 19 cases over 3 years old with their age at diagnosis, it was observed that those cases screened by the 5th day of life had a TIQ 84.6 ± 13, while those diagnosed later had a TIQ 73 ± 17 (p≤0.05). In assessing the number of hospitalizations that occurred during follow-up, we determined that the 5 cases screened early never had a metabolic crisis and had a higher TIQ than those who had had one or more decompensation (92 and 74, respectively, p≤0.05). An inverse correlation was observed between the Leu+Isoleucine value and TIQ. Conclusion: The diagnosis before the 5th day of life and a good metabolic control during follow-up, enables children with MSUD to have normal cognitive development.

La enfermedad de la orina olor a jarabe de arce (EOJA) se produce por un defecto del complejo enzimático deshidrogenasa de los cetoácidos de los aminoácidos ramificados: Valina, Isoleucina, Leucina (VIL). El tratamiento es una dieta restringida en leucina (Leu). Objetivo: evaluar el seguimiento a largo plazo en niños con EOJA. Metodología: Se revisaron 29 fichas de pacientes EOJA, 24 fueron pesquisados por clínica (> 5to día de vida) y 4 casos por antecedentes familiares con EOJA y 1 por pesquisa neonatal (< 5to día de vida). Se midió nivel de Leu al diagnóstico (Biotronic 2000) y durante el seguimiento (Espectrometría de masa), número de descompensaciones, Coeficiente Intelectual Total (CIT) (Escalas de Bayley y Wechsler) y estado nutricional. Se aplicó programa estadístico STATA versión 9.2 (p≤0.05). Resultados: La edad de diagnóstico fue a los 14 días de edad. En todos se confirmó el diagnóstico por los niveles elevados de Leu y presencia de alloisoleucina. Al comparar el CIT de los 19 casos mayores de 3 años con la edad de diagnóstico, se observó que aquellos casos pesquisados antes del 5to día tenían un CIT de 84,6±13, a diferencia de los diagnosticados posteriormente que tenían un CIT=73±17 (p≤0.05). Al evaluar el número de descompensaciones ocurridas durante el seguimiento, se determinó que los 5 casos nunca habían tenido una crisis metabólica, tuvieron un CI mayor que aquellos que habían tenido una o más descompensaciones (92 y 74 respectivamente) (p≤0.05). Cuando se correlacionó el valor de Leu+Iso de seguimiento con el CIT, se observó una correlación inversamente proporcional. Conclusión: el diagnóstico antes de los 5to día de vida y un buen control metabólico durante el seguimiento, permite que los niños con EOJA tengan un desarrollo cognitivo normal.

Actualización en el manejo agudo de errores congénitos del metabolismo / Update on acute management of inborn errors of metabolism

Inborn metabolic disorders are genetic diseases which are uncommon each one, but together they are not. They are characterized by an enzimatic defect that blocks a metabolic pathway, producing specific signs and symptoms. The current article pretends be an updated guideline for their acute management which is based on: 1) Inmediate life support, hydroelectrolyte balance and sample procurement, 2) Avoiding the production of toxic endogenous metabolites and anabolism promotion, 3) The supplementation of substrates and 4) The removal of toxic substances. Their prompt suspicious, identification and treatment starting will be crucial for neurological prognosis and prevention of death.

Los errores congénitos del metabolismo son enfermedades genéticas poco frecuentes pero que en conjunto no lo son. Se caracterizan por un defecto enzimático que bloquea una vía metabólica produciendo manifestaciones clínicas características. El objetivo del presente artículo es presentar una guía actualizada para su manejo agudo, el cual consiste en: 1) Medidas inmediatas de soporte vital, manejo hidroelectrolítico y obtención de muestras críticas; 2) Evitar la producción endógena de metabolitos tóxicos y favorecer el anabolismo; 3) Suplementación de sustratos y 4) Remoción de sustancias tóxicas. Su pronta sospecha, identificación e inicio de tratamiento, resulta fundamental para mejorar el pronóstico neurológico y evitar la muerte.

Estudio sobre dilución de tres tipos leche en polvo en familias pertenecientes a niveles socioeconómico: ABC1, C2 y C3 de Santiago / Study on dilution of three types of powderer milk in families belonging to socioeconomic groups: ABC1, C2 and C3 in Santiago

Introduction: The liquid and powdered forms of cow milk are comparable when the reconstitution of the powdered milk is adequately done. Objective: To evaluate the dilution of three types of powdered milk: whole, low-fat and non-fat, in three socioeconomic groups (SEG): upper (ABC1), upper-middle (C2) and lower-middle (C3) in Santiago. Methodology: There were 1050 surveys performed in 350 homes in each SEG representing 300,000 homes. The dilution of powdered milk was compared using the norms established by the Ministry of Health and the Food Health Regulations. Results: Of the total, 4.4% were SEG ABC1, 17,6% C2 and 78% C3. The age distribution was 24.2 % in < 15 years old, 50% in those between 15 and 60 years old and 25,3% in > 60 years old. It was observed that adequate dilution diminishes as age increases, showing that between 1 to 2 years of age and 2 to 5 years of age, 51.2% and 45.9% from ABC1 and 36.9% and 18.7% from C3 decrease, respectively. Evaluating the entire population, it was observed that 77.4% of ABC1, 89.6% from C2 and 78.2% from C3 dilute milk deficiently. Establishing differences between groups, it was observed that C2 dilute 2.6 times more deficiently than ABC1. However there were no differences between SEC ABC1 and C3, both diluting deficiently in the same proportion. Conclusion: As age increases, the percentage of deficient dilution increases, independent of age group, type of milk and SEC.

Introducción: La leche de vaca líquida y la polvo son comparables cuando la reconstitución de la leche en polvo se hace adecuadamente. Objetivo: Evaluar la dilución de tres tipos leche en polvo: entera, semidescremada y descremada, en niveles socioeconómico (NSE): alto (ABC1), medio alto (C2) y medio bajo (C3) de Santiago. Metodología: Se aplicaron 1050 encuestas, en 350 hogares por NSE, lo que representan a 300.000 hogares. La dilución de la leche en polvo se comparó con las normas establecidas por el Ministerio de Salud y Reglamento Sanitario de Alimentos. Resultados: Del total, el 4,4% era NSE ABC1, el 17,6% NSE C2 y el 78% NSE C3. La distribución etárea fue de: 24,2% < 15 años, 50% entre 15 y 60 años y 25,3% > 60 años. Se detectó que la dilución adecuada, va disminuyendo en la medida que aumenta la edad, observándose que el grupo de 1 a 2 años el 51,2% y 45,9% del NSE ABC1 y NSE C3 lo hace adecuadamente y entre los 2 y 5 años desciende a un 36,9% y 18,7% respectivamente. Al evaluar toda la población, se observó que el 77,4% del NSE ABC1, el 89,6% del C2 y el 78,2% C3, diluye deficientemente la leche. Al establecer diferencias entre grupos, se observó que el NSE C2 diluye 2,6 veces más deficiente que el NSE ABC1. Sin embargo entre el NSE ABC1 y C3 no hubo diferencias entre ellos, ya ambos lo hacen deficientemente en la misma proporción. Conclusión: En la medida que aumenta la edad, aumenta el porcentaje de dilución deficiente, independiente del grupo etáreo, tipo de leche y NSE.