Bloqueo del eje renina angiontensina aldosterona (RAAS) en la enfermedad renal diabética. Más allá del control de la hipertensión arterial / Renin angiotensin aldosterone system (RAAS) and its suppression in diabetic kidney disease. Control of arterial hypertension and beyond

La enfermedad renal diabética (ERD) es una comorbilidad con alta prevalencia a nivel mundial, siendo una de las complicaciones más frecuentes de la diabetes mellitus (DM). La ERD se relaciona con complicaciones cardiovasculares y progresión de la enfermedad renal crónica (ERC), por ello la identificación de factores modificables, como el control de la presión arterial, es uno de los pilares más importantes en el manejo integral. En esta revisión hacemos un recorrido sobre el papel de la hipertensión y el bloqueo del eje renina angiotensina aldosterona (RAAS) en el curso de la ERD y las estrategias terapéuticas orientadas a la reducción de la presión arterial (PA), el bloqueo RAAS y el impacto en resultados renales y cardiovasculares. El objetivo de este artículo es hacer una revisión de las intervenciones más importantes que actúan bloqueando el eje renina angiotensina aldosterona (RAAS) y determinar si estas medidas en los pacientes con ERD, solo tienen impacto en el control de la presión arterial o si también son estrategias de nefro y cardio-protección. Conclusión: La ERD es una de las complicaciones más frecuentes de la diabetes mellitus (DM). El control de la PA sigue siendo un pilar fundamental para lograr estos objetivos. Los bloqueadores del RAAS (iECAS y BRAs) son los antihipertensivos de elección con efecto terapéutico por el bloqueo RAAS y esto les permite tener además del control de la PA, efectos nefroprotectores y cardioprotectores importantes en pacientes con ERD, sobre todo cuando hay la presencia de albuminuria. Evaluamos que además de los inhibidores de la enzima convertidora de angiotensina (iECAs) y los bloqueadores del receptor de angiotensina (BRAs), vienen tomando importancia los antagonistas selectivos del receptor mineralocorticoide (ARM) como Finerenona.

Diabetic kidney disease (DKD) is a comorbidity with a high worldwide prevalence, and one of the most frequent complications of diabetes mellitus (DM). CKD is related to cardiovascular complications and the progression of chronic kidney disease (CKD), therefore the identification of modifiable factors, such as blood pressure control, is one of the most important pillars in comprehensive management. In this review, we will analyze the role of hypertension and the renin-angiotensin-aldosterone system (RAAS) and its suppression in the course of CKD, and therapeutic strategies aimed at reducing blood pressure (BP), RAAS blockade, and the impact on renal and cardiovascular outcomes. The objective of this article is to review the most important interventions that act by blocking the renin-angiotensin-aldosterone system (RAAS) and to determine if these measures in patients with CKD only have an impact on blood pressure control or if they are also nephron and cardio-protective strategies. Conclusion: DKD is one of the most frequent complications of diabetes mellitus (DM). BP control continues to be a fundamental pillar to achieve these objectives. RAAS blockers (iECAS and ARBs) are the first-line antihypertensive with a therapeutic effect due to RAAS blockade and this allows them to have, in addition to BP control, important nephroprotective and cardioprotective effects in patients with CKD, especially when there is albuminuria. We evaluated that in addition to angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs), selective mineralocorticoid receptor antagonists (MRA) such as Finerenone are gaining importance.

Determination of perindopril erbumine by oxidative coupling reaction using 2, 6-dichloroquinone-4-chlorimide

Abstract Perindopril erbumine (Perindopril tert-butylamine salt) is a potent angiotensin-converting enzyme (ACE) inhibitor. It is used to treat the patients with hypertension and heart failure problems. A sensitive, inexpensive and precise analytical technique has been developed for the estimation of perindopril in bulk and formulations. The procedure involves the development of colour by forming an oxidative coupling reaction between drug (PPE) and reagent such as 2, 6-dichloroquinone-4-chlorimide (DCQC). The formed colored species were measured at (max=520 nm. The developed method showed linearity within the concentration limits of 25-75 µg mL-1. The linear correlation coefficient (r) and molar absorptivity were found to be 0.9999 and 3.285 x 103 mol-1cm-1. % Recovery ± SD values were in the range of 99.69 - 100.51 (+ 0.42 - ( 0.41) (n=3) which indicates the accuracy of the developed method. The interference of other excipients that are commonly present in formulations is found to be negligible. Precision and accuracy of the proposed method were confirmed by student t-test and F-tests at 95% confidence limits with (n-1) degrees of freedom. The validity parameters of proposed method were calculated by ICH guidelines

Levels of angiotensin-converting enzyme 1 and 2 in serum and urine of children with Sickle Cell Disease / Níveis de enzima conversora da angiotensina 1 e 2 no soro e na urina de crianças com Doença Falciforme

Abstract Introduction: Sickle cell nephropathy begins in childhood and presents early increases in glomerular filtration, which, over the long term, can lead to chronic renal failure. Several diseases have increased circulating and urinary angiotensin-converting enzyme (ACE) activity, but there is little information about changes in ACEs activity in children with sickle cell disease (SCD). Objective: We examined circulating and urinary ACE 1 activity in children with SCD. Methods: This cross-sectional study compared children who were carriers of SCD with children who comprised a control group (CG). Serum and urinary activities of ACE were evaluated, as were biochemical factors, urinary album/creatinine rates, and estimated glomerular filtration rate. Results: Urinary ACE activity was significantly higher in patients with SCD than in healthy children (median 0.01; range 0.00-0.07 vs median 0.00; range 0.00-0.01 mU/mL·creatinine, p < 0.001. No significant difference in serum ACE activities between the SCD and CG groups was observed (median 32.25; range 16.2-59.3 vs median 40.9; range 18.0-53.4) mU/m`L·creatinine, p < 0.05. Conclusion: Our data revealed a high urinary ACE 1 activity, different than plasmatic level, in SCD patients suggesting a dissociation between the intrarenal and systemic RAAS. The increase of urinary ACE 1 activity in SCD patients suggests higher levels of Ang II with a predominance of classical RAAS axis, that can induce kidney damage.

Resumo Introdução: A nefropatia falciforme começa na infância e apresenta aumentos precoces na filtração glomerular, que, em longo prazo, podem levar à insuficiência renal crônica. Várias doenças têm aumentado a atividade da enzima conversora da angiotensina (ECA) urinária e circulante, mas há pouca informação sobre alterações na atividade das ECAs em crianças com doença falciforme (DF). Objetivo: Examinamos a atividade da ECA-1 circulante e urinária em crianças com DF. Métodos: Este estudo transversal comparou crianças que eram portadoras de DF com crianças que compunham um Grupo Controle (GC). As atividades séricas e urinárias da ECA foram avaliadas, assim como os fatores bioquímicos, a relação albumina/creatinina urinária e a taxa de filtração glomerular estimada. Resultados: A atividade urinária da ECA foi significativamente maior em pacientes com DF do que em crianças saudáveis (mediana 0,01; intervalo 0,00-0,07 vs mediana 0,00; intervalo 0,00-0,01 mU/mL·creatinina, p < 0,001. Não foi observada diferença significativa nas atividades séricas da ECA entre os grupos DF e GC (mediana 32,25; intervalo 16,2-59,3 vs mediana 40,9; intervalo 18,0-53,4) mU/mL·creatinina, p < 0,05. Conclusão: Nossos dados revelaram uma alta atividade urinária da ECA-1, diferente do nível plasmático, em pacientes com DF, sugerindo uma dissociação entre o Sistema Renina Angiotensina Aldosterona (SRAA) intra-renal e sistêmico. O aumento da atividade urinária da ECA-1 em pacientes com DF sugere níveis mais elevados de Ang II com predominância do eixo clássico do SRAA, que pode induzir lesão renal.

Interactions amongst inflammation, renin-angiotensin-aldosterone and kallikrein-kinin systems: suggestive approaches for COVID-19 therapy

Coronavirus disease 2019 (COVID-19) is a rapid-spread infectious disease caused by the SARS-CoV-2 virus, which can culminate in the renin-angiotensin-aldosterone (RAAS) and kallikrein-kinin (KKS) systems imbalance, and in serious consequences for infected patients. This scoping review of published research exploring the RAAS and KKS was undertaken in order to trace the history of the discovery of both systems and their multiple interactions, discuss some aspects of the viral-cell interaction, including inflammation and the system imbalance triggered by SARS-CoV-2 infection, and their consequent disorders. Furthermore, we correlate the effects of continued use of the RAAS blockers in chronic diseases therapies with the virulence and physiopathology of COVID-19. We also approach the RAAS and KKS-related proposed potential therapies for treatment of COVID-19. In this way, we reinforce the importance of exploring both systems and the application of their components or their blockers in the treatment of coronavirus disease.(AU)

Genomics and epidemiology of the P 1 SARS-CoV-2 lineage in Manaus, Brazil

Cases of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in Manaus, Brazil, resurged in late 2020 despite previously high levels of infection. Genome sequencing of viruses sampled in Manaus between November 2020 and January 2021 revealed the emergence and circulation of a novel SARS-CoV-2 variant of concern. Lineage P.1 acquired 17 mutations, including a trio in the spike protein (K417T, E484K, and N501Y) associated with increased binding to the human ACE2 (angiotensin-converting enzyme 2) receptor. Molecular clock analysis shows that P.1 emergence occurred around mid-November 2020 and was preceded by a period of faster molecular evolution. Using a two-category dynamical model that integrates genomic and mortality data, we estimate that P.1 may be 1.7- to 2.4-fold more transmissible and that previous (non-P.1) infection provides 54 to 79% of the protection against infection with P.1 that it provides against non-P.1 lineages. Enhanced global genomic surveillance of variants of concern, which may exhibit increased transmissibility and/or immune evasion, is critical to accelerate pandemic responsiveness.

Factores moleculares implicados en insuficiencia cardiaca / Molecular factors involved in heart failure

La insuficiencia cardiaca se define como un síndrome caracterizado por la incapacidad de proveer las necesidades metabólicas del organismo, presentando disnea y fatiga. Hasta ahora, se ha descrito la participación de varias moléculas involucradas en los mecanismos de señalización intracelular que conducen a la insuficiencia cardiaca y estimulan la síntesis de algunas proteínas, como colágeno, la cual induce a una hipertrofia cardiaca(AU)

Heart failure is defined as a syndrome characterized by the inability to meet the metabolic needs of the organism, causing dyspnea and fatigue.Descriptions are available of the involvement of several molecules in cell signaling mechanisms which lead to heart failure and prompt the synthesis of some proteins, such as collagen, inducing cardiac hypertrophy(AU)

Informe diário de evidências COVID-19: busca referente aos dias 11, 12 e 13 de julho de 2020 / COVID-19 daily evidence report: search for July 11, 12 and 13, 2020

O Informe Diário de Evidências é uma produção do Ministério da Saúde que tem como objetivo acompanhar diariamente as publicações científicas sobre tratamento farmacológico e vacinas para a COVID-19. Dessa forma, são realizadas buscas estruturadas em bases de dados biomédicas, referentes ao dia anterior desse informe. Não são incluídos estudos pré-clínicos (in vitro, in vivo, in silico). A frequência dos estudos é demonstrada de acordo com a sua classificação metodológica (revisões sistemáticas, ensaios clínicos randomizados, coortes, entre outros). Para cada estudo é apresentado um resumo com avaliação da qualidade metodológica. Essa avaliação tem por finalidade identificar o grau de certeza/confiança ou o risco de viés de cada estudo. Para tal, são utilizadas ferramentas já validadas e consagradas na literatura científica, na área de saúde baseada em evidências. Cabe ressaltar que o documento tem caráter informativo e não representa uma recomendação oficial do Ministério da Saúde sobre a temática. Foram encontrados 14 artigos.

COVID-19, ACE -inhibitors and angiotensin receptor blockers: The need to differentiate between early infection and acute lung injury / COVID-19, y IECA -inhibidores y bloqueadores de los receptores de angiotensina: la necesidad de diferenciar entre una infección temprana y una lesión pulmonar aguda

SARS-CoV-2, along with SARS-CoV and MERS-CoV, forms part of the three highly pathogenic coronaviruses identified since the start of the millennium.1,2 While SARS-CoV was identified on 2003 and MERS-CoV on 2012, the initial reports of SARS-CoV-2 (the etiological agent of COVID-19) were first released at the end of December 2019.3,4 Now, after less than four months, the virus has distributed globally and has become the focus of extensive medical research, as the number of cases keeps rising.A significant part of the investigative effort has been directed to the search for an effective therapy or intervention that could stop the spread of the disease or be used to effectively treat infected patients. Likewise, potential predisposing factors to develop a more severe clinical presentation are progressively being identified. Some of the more relevant are older age and the presence of certain comorbidities, such as cerebrovascular and coronary heart disease, hypertension and diabetes.5­8 It is important to highlight that the last two are chronic conditions commonly treated with ACE-inhibitors and angiotensin II type-I receptor blockers.9­11 However, the evidence suggests that these medications can upregulate the expression of angiotensin converting enzyme 2 (ACE2), the cellular receptor for both SARS-CoV and SARS-CoV-2.11­16 Thus, a group of researchers hypothesized that ACE2-increasing drugs could raise the risk of infection and prompt a more severe clinical course or a fatal outcome in diabetic and hypertensive patients.

Menores niveles circulantes del péptido vasoactivo y cardioprotector angiotensina-(1-9) en pacientes con hipertension arterial pulmonar / Lower circulating levels of angiotensin-(1-9), a vasoactive and cardio-protective peptide in patients with pulmonary artery hypertension

RESUMEN: Introducción: La vía clásica del sistema renina-angiotensina (SRA) está activado en pacientes con hipertensión arterial pulmonar (HAP). Previamente, hemos encontrado que en la disfunción ventricular post infarto al miocardio experimental la activación del eje clásico del SRA, dado por la enzima convertidora de angiotensina I (ECA) y angiotensina (Ang ) II se correlaciona negativamente con el eje paralelo del SRA dado por la ECA homóloga (ECA2) y el péptido vasoactivo y cardioprotector Ang-(1-9). Resultados preclínicos muestran la eficacia de la administración de Ang-(1-9) en el tratamiento del remodelamiento cardiovascular patológico. Hasta la fecha no existen antecedentes de los niveles circulantes de Ang-(1-9) en pacientes con hipertensión arterial pulmonar comparados con sujetos sanos. Objetivo: Determinar los niveles circulantes del péptido vasoactivo y cardiprotector Ang-(1-9) en pacientes con HAP y compararlos con sujetos sanos pareados por edad y sexo. Métodos: Estudio comparativo transversal en pacientes con HAP (grupo I, OMS) con presión de arteria pulmonar media (mPAP) ≥25 mmHg bajo tratamiento con furosemida (40%), espironolactona (53%), Acenocumarol/Warfarina (47%), Bosentan/Ambrisentan (27%), Sildenafil (80%), iloprost (7%) y digoxina (13%). Los sujetos controles correspondieron a sujetos asintomáticos sanos sin enfermedad cardiovascular, cardiopatía estructural ni pulmonar (n=14). En todos los pacientes se determinó mPAP, proBNP, resistencia vascular pulmonar (RVP, WU), presión capilar pulmonar (PCP, mmHg), gasto cardíaco (L/min), capacidad funcional por test de caminata 6 minutos (TC6M), cambio del área fraccional del ventrículo derecho VD (FAC, %). Se utilizó prueba t de Student y programa estadístico SPSS10.0. Un valor de p < 0,05 fue considerado como estadísticamente significativo. Resultados: Los pacientes ingresados al estudio mostraron: etiología de la HAP, idiopática (86,7%), VIH (13,3%), capacidad funcional I (6,2%), II (68,3) y III (25%) y promedio mPAP 51,3±1,9. Pacientes con HAP (grupo I, OMS) versus sujetos sanos mostraron disminución significativa de FAC, actividad plasmática de la ECA2 y niveles circulantes de Ang-(1-9). En la vía clásica del RAAS pacientes con HAP mostraron mayor actividad plasmática de ECA y niveles circulantes e Ag II. Correlaciones significativas se encontraron entre niveles de Ang-(1-9) y mPAP (r = -0.701, p < 0,001) y Ang-(1-9) vs FAC (r = 0.549, p < 0,01). Conclusiones: En pacientes con HAP (grupo I, OMS), los niveles circulantes de Ang-(1-9) están significativamente disminuidos y se asocian inversamente con la PAP, severidad del remodelamiento y disfunción del ventrículo derecho. El uso terapéutico de Ang-(1-9) como agente vasodilatador y cardioprotector podría ser relevante y potencialmente útil, desde una perspectiva clínica, en la HAP. Ang-(1-9) podría reducir la PAP y mejorar el remodelamiento vascular y del ventrículo derecho en la HAP. Por lo tanto, este péptido podría ser útil como blanco terapéutico en la HAP.

ABSTRACTS: Classic renin-angiotensis pathway (RAP) is activated in patients with pulmonary artery hypertension (PAH). We have previously shown that in patients with post myocardial infarction systolic dysfunction the activation of RAP mediated by angiotensin converting enzyme (ACE) and angiotensin II (Ang II) is inversely correlated with the parallel RAP axis mediated by homologous ACE (ACE2) and by the vasoactive and cardioprotective peptide Ang-(1-9). Pre clinical studies show that administration of Ang-(1-9) leads to a favorable ventricular remodelling. At present there is no information regarding levels of Ang-(1-9) in PAH patients compared to healthy subjects. Methods: 16 PAH patients (WHO group 1), with mean PA pressure > 25mmHg being treated with furosemide (40%), Bosentan/Ambrisentan (27%), Sildenafil (80%), iloprost (7%) were compared with healthy subjects (n=14). mPAP, pro BNP, pulmonary vascular resistance (Wu), pulmonary capillary pressure (PCP mmHg), cardiac output (L/min), functional capacity (6 min walking test) (6mWT), and changes in right ventricular fractional area (RV FA), were measured in all subjects. Results: In HAP subjects, the eiotology of PAH was unknown in 87%, or HIV (13%). Functional class was I (6.2 %), II (68.3%) or III (25%). Mean PAP was 51.3±1.9. Compared to healthy subjects, PAH patients had significantly lower RV FA, ACE2 and Ang-(19) levels. Also they had greater ACE plasma activity and AngII circulating levels. Significant correlations were found between Ang-(1-9) and mPAP (-0.701, p < 0,001) and between Ang-(1-9) and RV FA (r = 0.549, p < 0,01). Conclusion: group I PAH subjects, circulating levels of Ang-(1-9) are significantly lower than in healthy subjects and are inversely related to PAP, severity of ventricular remodeling and right ventricular dysfunction. The use of Ang-(1-9) as a vasodilator and cardioprotector agent could be clinically useful in PAH subjects.

Influence of ACE polymorphism on echocardiographic data of patients with heart failure / Influência do polimorfismo da ECA nos dados ecocardiográficos de pacientes com insuficiência cardíaca

Background: Angiotensin converting enzyme (ACE) polymorphism has been associated with different clinical and echocardiographic parameters in patients with heart failure (HF). However, no studies have been investigated such association with HF caused by Chagas disease. Objectives: To perform a genetic study to evaluate the frequency of ACE polymorphism in patients with HF caused by Chagas disease attending a university hospital in the central-west region and its association with echocardiographic findings. Methods: Descriptive study of ACE polymorphism (I/D) and echocardiographic data of 103 patients with HF caused by Chagas disease. Echocardiographic parameters were compared between the genotypes using the ANOVA test. Results: Genotypic distribution of the ACE polymorphism was 16.5% DD, 57.3% DI and 26.2% II. There was no statistically significant difference in the distribution of genotypes between men and women. The echocardiographic findings were: left ventricular ejection fraction: 43.8 ± 14.8 (DD) vs. 42.3 ± 11.6 (ID) vs. 44.9 ± 13.0 (II), p = 0.664; left ventricular diastolic diameter: 59.2 ± 9.7 (DD) vs. 60.3 ± 7.6 (ID) vs. 59.7 ± 78.1 (II), p = 0.879; left ventricular systolic diameter: 48.6 ± 12.8 (DD) vs. 50.6 ± 9.7 (ID) vs. 49.3 ± 11.9 (II), p = 0.753; and left atrial volume: 44.9 ± 10.1 (DD) vs. 40.9 ± 9.6 (ID) vs. 38.2 ± 7.8 (II), p = 0.068. Significant correlation coefficients were found for gender, age, ethnicity, heart rate and dyslipidemia. Conclusion: ACE polymorphism was not associated with echocardiographic findings in patients with HF caused by Chagas disease

Novas angiotensinas e suas implicações fisiológicas / Novel angiotensin peptides and their physiological implications

Introdução: O sistema renina-angiotensina (SRA) é a maior rede regulatória da pressão arterial, do balanço hidroeletrolítico e da homeostase do organismo. Desde que o papel do SRA na regulação da função cardiovascular foi descrito, os componentes do eixo endócrino do sistema, em especial a angiotensina II - na regulação e fisiologia cardiovascular e renal, têm sido foco de pesquisa. Os achados das últimas décadas, no entanto, mostraram que o sistema é muito mais complexo e intricado do que se imaginava. Objetivo: Apresentar, através de uma revisão da literatura, alguns dos novos elementos que compõem o SRA e suas implicações fisiológicas, atualizando o leitor sobre o estado da arte. Material de Métodos:Revisão bibliográfica abordando as principais publicações, indexadas pelo PubMed, relacionadas aos novos peptídeos do SRA. Resultados: Dentre os novos componentes do SRA, encontram-se a angiotensina­(1-9), um nonapeptídeo que promove vasodilatação, ação anti-hipertrófica em cardiomiócitos e ação anti-hipertensiva. A Angiotensina-(1-7), por sua vez, apesar de se diferenciar da Ang II apenas pela ausência de um único aminoácido, é responsável por efeitos fisiológicos opostos aos observados com a Ang II. A Angiotensina A, outro peptídeo biologicamente ativo, é formado a partir da descarboxilação do aspartato, desempenhando efeitos semelhantes à Ang II. A Alamandina, também derivada de uma descarboxilação, é um heptapeptídeo vasodilatador, anti-hipertensivo e cardioprotetor. Conclusão: Os achados envolvendo as novas angiotensinas permitem o entendimento do sistema como uma extensa rede composta de vias e eixos alternativos, muitos dos quais, ainda sem esclarecimento científico. O enfoque em novas vias de formação de produtos com funções biológicas poderá ser útil para o desenvolvimento de novas estratégias terapêuticas e, descobertas no campo da fisiologia e fisiopatologia de uma série de condições.

Introdution: The renin-angiotensin system (RAS) is the major regulatory system of arterial blood pressure, hydroelectrolytic balance, and body homeostasis. Since the role of the RAS in the cardiovascular function has been described, much of the research in this area has focused on the role of its endocrine axis components, mainly angiotensin II (Ang II), in the cardiovascular and renal physiology. Over the last decades, the findings have shown that the system is much more intricate than thought. Objective:To present, upon a literature review, some of the new elements about the RAS and its physiological implications, updating the reader about the state of the art. Methods Material: Bibliographic review addressing the main PubMed publications related of the novels angiotensin-peptides. Results: Among the novel RAS components, angiotensin­(1-9) is a nonapeptide that exerts antihypertrophy effects in cardiomyocytes, and vasodilatory and anti-hypertensive actions. Angiotensin-(1-7), which differs from Ang II due to the absence of only one aminoacid, is responsible for physiological effects opposite to those of Ang II. Angiotensin A, another biologically active peptide, is synthesized through aspartate decarboxylation, and exerts effects similar to those of Ang II. Alamandine, also formed through decarboxylation, is a heptapeptide showing vasodilatory, antihypertensive, and cardioprotective effects. Conclusion: The discovery of novel angiotensins sheds more light on the view that the RAS is an extensive regulatory system with pathways and alternative axis, much of which without scientific knowledge. Scientific efforts envisioning novel formation pathways of biologically active products may be useful for development of innovative therapeutic strategies and discoveries in the field of several physiological and pathological conditions.

Proteinuria persistente en pacientes pediátricos, caracterización histopatológica y su influencia en la progresión de la enfermedad renal crónica / Persistent proteinuria in pediatric patients, histopathological characterization and its influence on chronic kidney disease progression / Proteinúria persistente em pacientes pediátricos, caracterização histopatológica e sua influência na progressão da doença renal crónica

Objetivo: describir los hallazgos histopatológicos y la progresión a enfermedad renal crónica de los pacientes sometidos a biopsia renal en un hospital de referencia de la ciudad de Medellín entre 2005 y 2014. Metodología: estudio descriptivo retrospectivo. Se revisaron historias clínicas de pacientes menores de 18 años con diagnóstico de proteinuria persistente, a quienes se les realizó biopsia renal durante el período 2005-2014 en el Hospital Pablo Tobón Uribe. Se analizaron variables sociodemográficas, clínicas, histológicas y de laboratorio. Resultados: se incluyeron 71 pacientes. La edad promedio del diagnóstico de proteinuria persistente fue 10.07 años. El 69.1% y 20.6% de los pacientes presentaron hematuria e hipertensión arterial respectivamente. La glomerulonefritis por IgA fue el hallazgo histológico más frecuente (21.13%), seguido de la nefropatía lúpica (18.31%). Del total de pacientes, 69.0% recibieron inhibidores de la enzima convertidora de angiotensina y el 15.9% presentaron deterioro de la función renal al cuarto año de seguimiento. Conclusiones: la prevalencia de glomerulopatías en niños con proteinuria persistente fue alta. Se sugiere la realización de la biopsia renal con el fin de detectar tempranamente glomerulopatías primarias o secundarias asociadas para así instaurar un tratamiento oportuno que controle o retarde el deterioro de la función renal.

Objective: To describe the histopathological findings and their progression of chronic kidney disease in pediatric patients who underwent kidney biopsy due to persistent proteinuria during 2005-2015 at a high-complexity hospital in Medellin, Colombia. Methods: A retrospective, cohort study was carried out; the medical records of children under 18 with diagnosis of persistent proteinuria were reviewed. Sociodemographic, clinical, and histopathological variables were analyzed. Results: A total of 71 patients were included. The mean age at the diagnosis of persistent proteinuria was 10.07 years old. 69.1% and 20.6% of the patients had hematuria and hypertension, respectively. Overall, the predominant pathological diagnosis in the current study was IgA nephropathy (21.13%) followed by lupus nephropathy (18.31%). 69.0% of the patients received angiotensin-converting enzyme inhibitors. At the last follow-up, 15.9% presented impaired renal function. Conclusion: In our cohort, the prevalence of glomerulopathies in children with persistent proteinuria was high. We recommended performing kidney biopsy in children with persistent proteinuria. This allows early detection of primary or secondary glomerulopathies to retard progression of renal damage.

Objetivo: descrever os descobrimentos histopatológicos e a progressão a doença renal crónica dos pacientes submetidos a biopsia renal num hospital de referência da cidade de Medellín entre 2005 e 2014. Metodologia: estudo descritivo retrospectivo. Se revisaram histórias clínicas de pacientes menores de 18 anos com diagnóstico de proteinuria persistente, a quem se lhes realizou biopsia renal durante o período 2005-2014 no Hospital Pablo Tobón Uribe. Se analisaram variáveis sócio-demográficas, clínicas, histológicas e de laboratório. Resultados: se incluíram 71 pacientes. A idade média do diagnóstico de proteinúria persistente foi de 10.07 anos. 69.1% e 20.6% dos pacientes apresentaram hematúria e hipertensão arterial respectivamente. A glomerulonefrite por IgA foi a descoberta histológico mais frequente (21.13%), seguido da nefropatia lúpico (18.31%). Do total de pacientes, 69.0% receberam inibidores da enzima convertedora de angiotensina e 15.9% apresentaram deterioro da função renal ao quarto ano de seguimento. Conclusões: a prevalência de glomerulopatias em crianças com proteinúria persistente foi alta. Se sugere a realização da biopsia renal com o fim de detectar precocemente glomerulopatias primárias ou secundárias associadas para assim instaurar um tratamento oportuno que controle ou retarde o deterioro da função renal.

Solid lipid nanoparticles of irbesartan: preparation, characterization, optimization and pharmacokinetic studies

ABSTRACT Irbesartan is an antihypertensive with limited bioavailability and solid lipid nanoparticles (SLN) is one of the approaches to improve bioavailability. Solid lipid nanoparticles were prepared using glyceryl monostearate by solvent emulsification method followed by probe sonication. Irbesartan loaded SLNs were characterized and optimized by parameters like particle size, zeta potential, surface morphology entrapment efficiency and in vitro release. The optimized formulation was then further evaluated for the pharmacokinetic studies in Wistar rats. Irbesartan-loaded SLN of particle size 523.7 nm and 73.8% entrapment efficiency showed good bioavailability in Wistar rats and also showed optimum stability in the studies. The SLN prepared using glyceryl monostearate by solvent emulsification method leads to improve bioavailability of the drug.

Espironolactona aumenta los niveles circulantes de angiotensina-(1-9) y revierte el remodelado cardíaco en la hipertensión arterial experimental / Spironolactone increases circulating levels of angiotensin-(1-9) and reverts cardiac remodeling in experimental hypertension

Previamente hemos demostrado que la eficacia de enalapril, candesartán y de fasudil -inhibidor de la vía RhoA/ROCK,- en el tratamiento del remodelado cardíaco en la hipertensión (HTA) e infarto al miocardio está mediada por aumento en los niveles circulantes del péptido vasoactivo angiotensina [Ang]-(1-9). Sin embargo, no hay información disponible si el antagonista del receptor de mineralocorticoide, espironolactona (espiro) disminuye el remodelado cardíaco aumentando los niveles circulantes de Ang-(1-9). El objetivo de este trabajo fue determinar si espironolac-tona disminuye el remodelado cardíaco aumentando los niveles circulantes de Ang-(1-9) en la hipertensión arterial experimental. Métodos. Estudio comparativo de 3 grupos experimentales. Se utilizaron ratas Sprague Dawley macho (150 ± 10 grs) unifrectomizadas tratadas con desoxi-corticosterona (DOCA, 60mg/Kg 2 veces sem, im) por 6 semanas. Como controles (Sham) se usaron ratas unifrectomizadas. A partir de la 3° semana las ratas DOCA con HTA> 140 mmHg fueron randomizadas a recibir vehículo o espiro (100 mg/kg día, gavage) por 3 sem. Al finalizar el tratamiento se determinó la presión arterial sistólica (PAS), masa corporal, peso del corazón (PC) y masa cardíaca relativa al largo de la tibia (MCR, mg ventrículos/LT*100). El grado de hipertrofia car-diomiocitaria se determinó midiendo el área y perímetro de los cardiomiocitos y la fibrosis por el contenido de colágeno en cortes teñidos con rojo picrosirio. Resultados (promedio ± ES): Conclusión: Espironolactona disminuye la PAS y aumenta los niveles circulantes de Ang-(1-9). Este aumento en los niveles circulantes de Ang-(1-9) se asocia con una disminución significativa de la hipertrofia y la fibrosis cardiaca hipertensiva. Este nuevo efecto de espironolactona en los niveles circulantes de Ang-(1-9), - péptido vasoactivo de la vía paralela del sistema renina-angiotensina-aldosterona,- podría contribuir al efecto antihipertensivo y disminución del daño cardiaco en la hipertensión y remodelamiento cardiovascular y renal patológico. Estos hallazgos pueden tener relevancia terapéutica en términos que Ang-(1-9) podría disminuir el daño cardiovascular patológico.

We have previously demonstrated that the efficacy of enalapril, candesartan and fasudil,- RhoA / ROCK inhibitor-, in the treatment of cardiac remodeling in hypertension (HT) and myocardial infarction is mediated by an increase in circulating levels of the vasoactive peptide angiotensin (Ang) -(1-9). However, it is not known whether the mineralocorticoid receptor antagonist, spironolactone (spiro) decreases cardiac remodeling by increasing the circulating levels of Ang- (1-9). The aim of this study was to determine whether spironolactone decreases cardiac remodeling by increasing circulating levels of Ang-(1-9) in experimental hypertension. Methods. Comparative study of 3 experimental groups. Unifirectomized male Sprague Dawley rats (150 ± 10 grams) were treated with deoxycorticos-terone (DOCA, 60 mg / kg 2 times a week, im) for 6 weeks. Unifirectomized rats were used as controls (Sham). At 3rd week after surgery, DOCA rats with HTA> 140 mmHg were randomized to receive vehicle or spironolactone (Spiro, 100 mg / kg day, gavage) for 3 weeks. At the end of treatment, systolic blood pressure (SBP), body mass (BM), heart weight (HW) and relative cardiac mass to the tibia length (MCR, mg ventricles / LT * 100) were determined. The degree of cardiomyocyte hypertrophy was determined by measuring the area and perimeter of cardiomyocytes and fibrosis by collagen content in sections stained with picrosirius red. Results (mean ± ES): Conclusion: Spironolactone decreases systolic blood pressure and increases circulating levels of Ang-(1-9). This increase in circulating levels of Ang- (1-9) was associated with a significant decrease in hypertrophy and hypertensive cardiac fibrosis. This new effect of spironolactone on the circulating levels of Ang- (1-9) - vasoactive peptide of the parallel pathway of the re-nin-angiotensin-aldosterone system - could contribute to the antihypertensive effect and decrease of cardiac damage in HT and cardiovascular remodeling and renal disease. These findings may have therapeutic relevance supporting that Ang-(1-9) may decreases pathologic cardiovascular damage.

Deformação miocárdica radial por meio do speckle tracking bidimensional em suínos com hipertensão pulmonar induzida e tratados com angiotensina-(1-7) / Evaluation of myocardial radial deformation by bidimensional speckle tracking in pigs with pulmonary hypertension treated with angiotensin- (1-7)

A hipertensão arterial pulmonar (HAP) é uma doença complexa, caracterizada por disfunção endotelial, que resulta em remodelamento vascular pulmonar e elevação da pressão arterial pulmonar, com consequente insuficiência cardíaca direita. O speckle tracking bidimensional (2D-STE) é uma das mais recentes ferramentas da ecocardiografia, o qual tem sido empregado para avaliação mais precoce da função ventricular e do efeito da HAP sobre a função dos ventrículos esquerdo e direito. O objetivo deste estudo foi avaliar a deformação (St e StR) miocárdica radial do VE em modelo experimental de suínos com HAP induzida e tratados com angiotensina-(1-7), a fim de verificar as possibilidades desse novo fármaco nas respostas clínica e hemodinâmica, pois apresenta efeitos anti-inflamatório e vasodilatador, bem como ações antiproliferativas no sistema cardiovascular. Neste estudo, foi possível observar que os animais tratados com Ang-(1-7) apresentaram St e StR radiais maiores que o grupo placebo aos 60 dias de experimento, demonstrando uma melhora na função sistólica do miocárdio pelo aumento da deformação miocárdica (16,06±7,50 - placebo; 25,14±14,91 - Ang-(1-7)) e StR (1,28±0,51 - placebo; 1,51±0,58 - Ang-(1-7)). Essa melhora na função sistólica pode ser atribuída aos efeitos do fármaco, que reduziram também o desenvolvimento da hipertensão pulmonar. Diante dos resultados, acredita-se que a Ang-(1-7) possa ser um medicamento promissor para tratamento da HAP.(AU)

Pulmonary arterial hypertension (PAH) is a complex disease characterized by endothelial dysfunction resulting in pulmonary vascular remodeling, increased pulmonary arterial pressure, with subsequent right heart failure. The two-dimensional speckle tracking (2D-STE) is one of the newer tools used for early assessment of ventricular function. The aim of this study was to evaluate the radial myocardial deformation (St and StR) of LV in experimental pigs with induced PAH and treated with Ang- (1-7), checking the possibilities of this new drug in clinical and hemodynamic response, since it has anti-inflammatory effects and antiproliferative actions on the cardiovascular system. In this study we observed that animals treated with Ang (1-7) had radial St and StR higher than the placebo group at 60 days of the experiment demonstrating an improvement in systolic function of the myocardium by increased myocardial deformation (16.06±7.50 - placebo; 25.14±14.91 - Ang (1-7)) and StR (1.28±0.51 - placebo; 1.51±0.58 - Ang (1-7)). This improvement in systolic function can be attributed to drug effects while also reducing the development of pulmonary hypertension. Based on the results it is believed that Ang (1-7) may be a promising drug for the treatment of PAH.(AU)