Síndrome de piel indurada en un paciente pediátrico: un desafío terapéutico. Presentación de un caso / Stiff skin syndrome in a pediatric patient: a therapeutic challenge. Clinical case

El síndrome de la piel indurada es un trastorno esclerosante crónico, infrecuente, que se presenta en la infancia, caracterizado por la induración progresiva de la piel. Esta afección puede provocar restricciones torácicas y dificultad respiratoria, limitaciones en la movilidad articular y trastornos en la marcha, con importante deterioro de la calidad de vida. Debido a que sus opciones terapéuticas son escasas y poco eficaces, es fundamental que el paciente inicie precozmente una terapia física para prevenir estas complicaciones y que se continúe estudiando esta enfermedad a fin de poder ofrecer a los pacientes más y mejores tratamientos. Se presenta el caso de una paciente de 9 años con síndrome de la piel indurada y su desafío terapéutico.

Stiff skin syndrome is a chronic, rare sclerosing disorder that occurs in childhood, characterized by progressive induration of the skin that can cause thoracic restrictions and respiratory distress, limitations in joint mobility and gait difficulties, with significant deterioration of the quality of life. Because their therapeutic options are scarce and ineffective it is essential to start an early physical therapy to prevent these complications and to continue studying this condition to be able to offer patients more and better treatments. We present the case of a 9-year-old patient with indurated skin syndrome and its therapeutic challenge.

Informe diário de evidências COVID-19: busca realizada em 14 de maio de 2020 / COVID-19 daily evidence report: search conducted on May 14, 2020

Essa é uma produção do Departamento de Ciência e Tecnologia (Decit) da Secretaria de Ciência, Tecnologia, Inovação e Insumos Estratégicos em Saúde (SCTIE) do Ministério da Saúde (Decit/SCTIE/MS), que tem como missão promover a ciência e tecnologia e o uso de evidências científicas para a tomada de decisão do SUS, tendo como principal atribuição o incentivo ao desenvolvimento de pesquisas em saúde no Brasil, de modo a direcionar os investimentos realizados em pesquisa pelo Governo Federal às necessidades de saúde pública. Informar sobre as principais evidências científicas descritas na literatura internacional sobre tratamento farmacológico para a COVID-19. Além de resumir cada estudo identificado, o informe apresenta também uma avaliação da qualidade metodológica e a quantidade de artigos publicados, de acordo com a sua classificação metodológica (revisões sistemáticas, ensaios clínicos randomizados, entre outros). Foram encontrados 15 artigos.

Polifarmácia e cognição em pacientes com idade avançada / Polypharmacy and cognition in elderly patients

Objetivo: Avaliar a prevalência da polifarmácia e da prescrição de medicações inapropriadas, bem como suas associações com a capacidade cognitiva e funcional do idoso. Métodos: Estudo observacional transversal, no qual foram analisadas as medicações prescritas em 141 prontuários para pacientes acima de 50 anos, em associação com testes que quantificaram a capacidade funcional e cognitiva deles. Resultados: Observou-se média de 4,41 medicamentos por paciente, sendo que 0,41 deles foram considerados inapropriado, segundo o critério de Beers. Verificou-se também relação estatisticamente significativa quanto ao número de medicações e testes que mediam a capacidade funcional e cognitiva dos idosos. Conclusão: O aumento da polifarmácia e da prescrição de medicações potencialmente inadequadas acarretou significativa piora da capacidade cognitiva e funcional do idoso

Objective: To evaluate the prevalence of polypharmacy and of the prescription of inappropriate medications, as well as their associations with the cognitive and functional capacity of the elderly. Methods: Cross-sectional observational study which analyzed the drugs prescribed in 141 medical records for patients over 50 years of age, associated with tests that quantified their functional and cognitive capacity. Results: An average of 4.41 medications per patient was observed, and 0.41 were considered inappropriate according to the Beers criteria. There was also a statistically significant relation regarding the number of medications and tests that measure the functional and cognitive capacity of the elderly. Conclusion: The increase in polypharmacy and in the prescription of potentially inappropriate medications led to a significant impairment of the cognitive and functional capacity of the elderly

Prescripción de fármacos bloqueadores del sistema renina angiotensina en pacientes con enfermedad renal crónica etapa 3 en atención primaria de salud / Prescription of renin-angiotensin-aldosterone system blockers in patients with stage 3 chronic kidney disease

Background: To reduce the progression of chronic kidney disease (CKD) and cardiovascular risk, the guidelines recommend the blockade of the renin-angiotensin-aldosterone system (RAAS) in patients with proteinuria. Aim: To assess the frequency of enalapril or losartan use in diabetics or hypertensive patients with stage 3 CKD. Material and Methods: Review of clinical records of patients with CKD in an urban primary care clinic. Results: We identified 408 subjects aged 40 to 98 years (66% women) with stage 3 CKD. Sixty six percent had only hypertension and 34% were diabetic with or without hypertension. Seventy four percent received RAAS blockers (52% used enalapril, 45% losartan and 2% both medications). RAAS blockers were used in 70% of hypertensive and 78% of diabetic patients. The prescription in hypertensive diabetics with microalbuminuria was lower than in those without microalbuminuria (72% vs 87%, p < 0.05), but the opposite occurred in pure hypertensive patients with and without microalbuminuria (88% vs 69%, p < 0.05). There were no significant differences in blood pressure levels, microalbuminuria or serum potassium levels between RAAS blocker users and non-users. No differences were observed either between enalapril and losartan users. Conclusions: The adherence to clinical guidelines is insufficient and users of the recommended drugs did not achieve the expected goals.

Diuretics are Similar to Losartan on Echocardiographic Target-Organ Damage in Stage I Hypertension. PREVER-Treatment Study / Diuréticos são Similares à Losartana na Avaliação Ecocardiográfica de Lesão a Órgãos-Alvo no Estágio I da Hipertensão. Estudo PREVER-Treatment

Abstract Blood pressure (BP)-lowering therapy improves left ventricular (LV) parameters of hypertensive target-organ damage in stage II hypertension, but whether there is a drug-class difference in echocardiographic parameters in stage I hypertension patients is less often studied. In the PREVER treatment study, where individuals with stage I hypertension were randomized for treatment with diuretics (chlorthalidone/amiloride) or losartan, 110 participants accepted to participate in a sub-study, where two-dimensional echocardiograms were performed at baseline and after 18 months of antihypertensive treatment. As in the general study, systolic BP reduction was similar with diuretics or with losartan. Echocardiographic parameters showed small but significant changes in both treatment groups, with a favorable LV remodeling with antihypertensive treatment for 18 months when target blood pressure was achieved either with chlorthalidone/amiloride or with losartan as the initial treatment strategy. In conclusion, even in stage I hypertension, blood pressure reduction is associated with improvement in echocardiographic parameters, either with diuretics or losartan as first-drug regimens.

Resumo A terapia de redução da pressão arterial (PA) melhora os parâmetros do ventrículo esquerdo (VE) na lesão a órgãos-alvo causada pela condição hipertensiva na hipertensão de estágio II; no entanto, se existem ou não diferenças relacionadas à classe de medicamentos nos parâmetros ecocardiográficos de pacientes com hipertensão estágio I é menos frequentemente estudado. No estudo PREVER-treatment, em que indivíduos com hipertensão estágio I foram randomizados para tratamento com diuréticos (clortalidona/amilorida) ou losartana, 110 participantes aceitaram participar de um subestudo, no qual foram realizados ecocardiogramas bidimensionais basais e após 18 meses de tratamento anti-hipertensivo. Como no estudo geral, a redução da PA sistólica foi semelhante com diuréticos ou com losartana. Os parâmetros ecocardiográficos mostraram pequenas mas significativas alterações em ambos os grupos de tratamento, com um remodelamento favorável do VE com tratamento anti-hipertensivo por 18 meses, quando a pressão arterial alvo foi atingida com clortalidona/amilorida ou com losartana como estratégia inicial de tratamento. Em conclusão, mesmo na hipertensão estágio I, a redução da pressão arterial está associada à melhora nos parâmetros ecocardiográficos tanto com o uso de diuréticos ou losartana como primeiro esquema de tratamento farmacológico.

Farmácia Popular Program: pharmaceutical market analysis of antihypertensive acting on the renin-angiotensin system medicines / Programa Farmácia Popular: análise do mercado farmacêutico de anti-hipertensivos do sistema renina-angiotensina

Abstract This paper aims to analyse changes in the retail pharmaceutical market following policy changes in the Farmácia Popular Program (FP), a medicines subsidy program in Brazil. The retrospective longitudinal analyses focus on therapeutic class of agents acting on the renin-angiotensin system. Data obtained from QuintilesIMS (formerly IMS Health) included private retail pharmacy sales volume (pharmaceutical units) and sales values from 2002 to 2013. Analyses evaluated changes in market share following key FP policy changes. The therapeutic class was selected due to its relevance to hypertension treatment. Market share was analysed by therapeutic sub-classes and by individual company. Losartan as a single product accounted for the highest market share among angiotensin II antagonists. National companies had higher sales volume during the study period, while multinational companies had higher sales value. Changes in pharmaceutical market share coincided with the inclusion of specific products in the list of medicines covered by FP and with increases in or exemption from patient copayment.

Resumo Este artigo visa analisar as mudanças no mercado de varejo farmacêutico, seguindo as alterações de diretiva no Programa Farmácia Popular (FP), que realiza subvenção de medicamentos no Brasil, em parceria pública privada. Foi realizada análise longitudinal retrospectiva dos medicamentos da classe terapêutica dos agentes que atuam sobre o sistema renina-angiotensina. Os dados obtidos do QuintilesIMS incluíram o varejo farmacêutico em termos do volume e valores de vendas de 2002 a 2013. Análises realizadas consideraram intervenções e reformas ocorridas no FP e seu impacto no mercado farmacêutico da classe terapêutica selecionada, devido a sua relevância para o tratamento da hipertensão. Também se examinou o comportamento do mercado tomando por base as empresas farmacêuticas produtoras. Losartan monodroga representou a maior fatia de mercado entre os antagonistas de angiotensina II. Empresas nacionais obtiveram maior volume de vendas durante o período de estudo, enquanto as empresas multinacionais exibiram maior valor de vendas. Mudanças no mercado farmacêutico coincidiram com a inclusão de produtos específicos na lista de medicamentos abrangidos pelo FP e com aumentos ou isenção de copagamento pelos pacientes.

Candesartan, rather than losartan, improves motor dysfunction in thioacetamide-induced chronic liver failure in rats

Minimal hepatic encephalopathy is more common than the acute syndrome. Losartan, the first angiotensin-II receptor blocker (ARB), and candesartan, another widely-used ARB, have protected against developing fibrogenesis, but there is no clear data about their curative antifibrotic effects. The current study was designed to examine their effects in an already-established model of hepatic fibrosis and also their effects on the associated motor dysfunction. Low-grade chronic liver failure (CLF) was induced in 3-month old Sprague-Dawley male rats using thioacetamide (TAA, 50 mg·kg−1·day−1) intraperitoneally for 2 weeks. The TAA-CLF rats were randomly divided into five groups (n=8) treated orally for 14 days (mg·kg−1·day−1) as follows: TAA (distilled water), losartan (5 and 10 mg/kg), and candesartan (0.1 and 0.3 mg/kg). Rats were tested for rotarod and open-field tests. Serum and hepatic biochemical markers, and hepatic histopathological changes were evaluated by H&E and Masson's staining. The TAA-CLF rats showed significant increases of hepatic malondialdehyde, hepatic expression of tumor necrosis factor-α (TNF-α), and serum ammonia, alanine aminotransferase, γ-glutamyl transferase, TNF-α, and malondialdehyde levels as well as significant decreases of hepatic and serum glutathione levels. All treatments significantly reversed these changes. The histopathological changes were moderate in losartan-5 and candesartan-0.1 groups and mild in losartan-10 and candesartan-0.3 groups. Only candesartan significantly improved TAA-induced motor dysfunction. In conclusion, therapeutic antifibrotic effects of losartan and candesartan in thioacetamide-induced hepatic fibrosis in rats are possibly through angiotensin-II receptor blocking, antioxidant, and anti-inflammatory activities. Improved motor dysfunction by candesartan could be attributed to better brain penetration and slower "off-rate" from angiotensin-II receptors. Clinical trials are recommended.

Renin-Angiotensin System Blockade Associated with Statin Improves Endothelial Function in Diabetics / Bloqueio do Sistema Renina-Angiotensina Associado a Estatina Melhora a Função Endotelial em Diabéticos

Abstract Background: Studies suggest that statins have pleiotropic effects, such as reduction in blood pressure, and improvement in endothelial function and vascular stiffness. Objective: To analyze if prior statin use influences the effect of renin-angiotensin-aldosterone system inhibitors on blood pressure, endothelial function, and vascular stiffness. Methods: Patients with diabetes and hypertension with office systolic blood pressure ≥ 130 mmHg and/or diastolic blood pressure ≥ 80 mmHg had their antihypertensive medications replaced by amlodipine during 6 weeks. They were then randomized to either benazepril or losartan for 12 additional weeks while continuing on amlodipine. Blood pressure (assessed with ambulatory blood pressure monitoring), endothelial function (brachial artery flow-mediated dilation), and vascular stiffness (pulse wave velocity) were evaluated before and after the combined treatment. In this study, a post hoc analysis was performed to compare patients who were or were not on statins (SU and NSU groups, respectively). Results: The SU group presented a greater reduction in the 24-hour systolic blood pressure (from 134 to 122 mmHg, p = 0.007), and in the brachial artery flow-mediated dilation (from 6.5 to 10.9%, p = 0.003) when compared with the NSU group (from 137 to 128 mmHg, p = 0.362, and from 7.5 to 8.3%, p = 0.820). There was no statistically significant difference in pulse wave velocity (SU group: from 9.95 to 9.90 m/s, p = 0.650; NSU group: from 10.65 to 11.05 m/s, p = 0.586). Conclusion: Combined use of statins, amlodipine, and renin-angiotensin-aldosterone system inhibitors improves the antihypertensive response and endothelial function in patients with hypertension and diabetes.

Resumo Fundamentos: Estudos sugerem que as estatinas possuem efeitos pleotrópicos, como melhora da função endotelial, da rigidez vascular e redução da pressão arterial. Objetivo: Analisar se o uso prévio de estatina influenciou o efeito sobre a pressão arterial, a função endotelial e a rigidez vascular de drogas inibidoras do sistema renina-angiotensina-aldosterona. Métodos: Pacientes hipertensos e diabéticos com pressão arterial de consultório sistólica ≥ 130 mmHg e/ou diastólica ≥ 80 mmHg tiveram suas medicações anti-hipertensivas substituídas por anlodipino durante 6 semanas. Em seguida, foram randomizados para associação de benazepril ou losartana por mais 12 semanas. Pressão arterial (através da monitorização ambulatorial da pressão arterial), função endotelial (dilatação mediada por fluxo da artéria braquial) e rigidez vascular (velocidade da onda de pulso) foram avaliados antes e após o tratamento combinado. Neste trabalho, uma análise post-hoc foi realizada para comparar pacientes que vinham (grupo CE) ou não (grupo SE) em uso de estatina. Resultados: O grupo CE apresentou maior redução na pressão arterial sistólica nas 24 horas (134 para 122 mmHg, p = 0,007) e na dilatação mediada por fluxo da artéria braquial (6,5 para 10,9%, p = 0,003) quando comparado com o grupo SE (137 para 128 mmHg, p = 0,362, e 7,5 para 8,3%, p = 0,820). Não houve diferença estatisticamente significante na velocidade de onda de pulso (grupo CE 9,95 para 9,90 m/s, p = 0,650 e grupo SE 10,65 para 11,05 m/s, p = 0,586). Conclusão: O uso combinado de estatinas, anlodipino e inibidores do sistema renina-angiotensina-aldosterona melhora a resposta anti-hipertensiva e a função endotelial em pacientes hipertensos e diabéticos.

Human fetal malformations associated with the use of an angiotensin II receptor antagonist: Case Report / Malformações fetais associadas ao uso de antagonista dos receptores de angiotensina II: Relato de Caso

Introduction: The potential risks related to drug exposure during pregnancy represent a vast chapter in modern obstetrics and data regarding the safety of antihypertensive drugs during pregnancy are relatively scarce. Case report: A 37-year-old patient discovered her fifth pregnancy at our hospital after 26 weeks and 4 days of gestation. She reported a history of hypertension and was currently being treated with Losartan. Hospitalization was recommended for the patient and further evaluation of fetal vitality was performed. On the fourth day an ultrasound was performed, resulting in a severe oligohydramnios, fetal centralization and abnormal ductus venosus. After 36 hours, the newborn died. Pathologic evaluation: At autopsy, the skullcap had large fontanels and deficient ossification. The kidneys were slightly enlarged. A microscopic examination detected underdevelopment of the tubules and the presence of some dilated lumens. Immunohistochemical detection of epithelial membrane antigen was positive. Immunoreactivity of CD 15 was also assayed to characterize the proximal tubules, and lumen collapse was observed in some regions. Discussion: Angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor antagonists (ARAs) are among the most widely prescribed drugs for hypertension. They are often used by hypertensive women who are considering become pregnant. While their fetal toxicity in the second or third trimesters has been documented, their teratogenic effect during the first trimester has only recently been demonstrated. Conclusion: Constant awareness by physicians and patients should be encouraged, particularly in regard to the prescription of antihypertensive drugs in women of childbearing age who are or intend to become pregnant. .

Introdução: Os riscos relacionados à exposição de drogas durante a gestação representam um vasto capítulo na obstetrícia moderna e dados sobre a segurança de drogas anti-hipertensivas são relativamente escassos. Relato do caso: Paciente de 37 anos, hipertensa crônica, descobriu a gravidez com 26 semanas e 4 dias de gestação. Estava em uso regular de Losartana. Durante avaliação fetal ultrassonográfica, foi relatada a presença de grave oligoâmnio associado ao quadro de centralização fetal com alteração de ducto venoso, e, após 36 horas, verificou-se óbito neonatal. Necrópsia: Observou-se calota craniana com fontanelas amplas e ossificação deficiente. Rins levemente aumentados de volume e, à microscopia, hipodesenvolvimento de túbulos com presença de lúmen dilatado. Imunohistoquímica com expressão em túbulos distais de antígeno epitelial de membrana. Imunoperoxidade com expressão em túbulos proximais de CD 15 em células epiteliais e colapso de alguns lúmens fora observado. Discussão: Inibidores da conversão de angiotensina e antagonistas de receptor de angiotensina estão entre as drogas mais prescritas para hipertensão. Estas drogas são frequentemente prescritas para mulheres em idade fértil e que pretendem engravidar. Enquanto a toxicidade fetal destas, nos segundo e terceiro trimestres, já é conhecida, seus efeitos durante o primeiro trimestre foi apenas recentemente demostrado. Conclusão: A conscientização por parte de médicos e pacientes deve ser realizada de rotina, principalmente no que diz respeito à prescrição e utilização de drogas potencialmente teratogênicas ou fetotóxicas. Este cuidado deve ser redobrado para pacientes que estão ...

Short-term add-on therapy with angiotensin receptor blocker for end-stage inotrope-dependent heart failure patients: B-type natriuretic peptide reduction in a randomized clinical trial

OBJECTIVE: We aimed to evaluate angiotensin receptor blocker add-on therapy in patients with low cardiac output during decompensated heart failure. METHODS: We selected patients with decompensated heart failure, low cardiac output, dobutamine dependence, and an ejection fraction <0.45 who were receiving an angiotensin-converting enzyme inhibitor. The patients were randomized to losartan or placebo and underwent invasive hemodynamic and B-type natriuretic peptide measurements at baseline and on the seventh day after intervention. ClinicalTrials.gov: NCT01857999. RESULTS: We studied 10 patients in the losartan group and 11 patients in the placebo group. The patient characteristics were as follows: age 52.7 years, ejection fraction 21.3%, dobutamine infusion 8.5 mcg/kg.min, indexed systemic vascular resistance 1918.0 dynes.sec/cm5.m2, cardiac index 2.8 L/min.m2, and B-type natriuretic peptide 1,403 pg/mL. After 7 days of intervention, there was a 37.4% reduction in the B-type natriuretic peptide levels in the losartan group compared with an 11.9% increase in the placebo group (mean difference, -49.1%; 95% confidence interval: -88.1 to -9.8%, p = 0.018). No significant difference was observed in the hemodynamic measurements. CONCLUSION: Short-term add-on therapy with losartan reduced B-type natriuretic peptide levels in patients hospitalized for decompensated severe heart failure and low cardiac output with inotrope dependence. .

An Angiotensin Receptor Blocker Prevents Arrhythmogenic Left Atrial Remodeling in a Rat Post Myocardial Infarction Induced Heart Failure Model

This study investigated the role of angiotensin II receptor blocker in atrial remodeling in rats with atrial fibrillation (AF) induced by a myocardial infarction (MI). MIs were induced by a ligation of the left anterior descending coronary artery. Two days after, the rats in the losartan group were given losartan (10 mg/kg/day for 10 weeks). Ten weeks later, echocardiography and AF induction studies were conducted. Ejection fraction was significantly lower in the MI rats. Fibrosis analysis revealed much increased left atrial fibrosis in the MI group than sham (2.22 +/- 0.66% vs 0.25 +/- 0.08%, P = 0.001) and suppression in the losartan group (0.90 +/- 0.27%, P 0.001) compared with the MI group. AF inducibility was higher in the MI group than sham (39.4 +/- 43.0% vs 2.0 +/- 6.3%, P = 0.005) and significantly lower in losartan group (12.0 +/- 31.6%, P = 0.029) compared with the MI. The left atrial endothelial nitric oxide synthase (NOS) and sarco/endoplasmic reticulum Ca(2+)-ATPase levels were lower in the MI group and higher in the losartan group significantly. The atrial inducible NOS and sodium-calcium exchanger levels were higher in the MI and lower in the losartan group significantly. Losartan disrupts collagen fiber formation and prevents the alteration of the tissue eNOS and iNOS levels, which prevent subsequent AF induction.

Dissociação da resposta anti-hipertensiva e metabólica à losartana e espironolactona em ratos com síndrome metabólica experimental / Dissociation of antihypertensive and metabolic response to losartan and spironolactone in experimental rats with metabolic sindrome

INTRODUÇÃO: O tratamento da hipertensão arterial (HA) em indivíduos com síndrome metabólica (SM) é um desafio, uma vez que terapias não medicamentosas são de difícil implementação e o tratamento farmacológico ideal não está totalmente estabelecido. OBJETIVO: Avaliar o bloqueio do sistema renina angiotensina aldosterona (SRAA) na pressão arterial (PA), na função e na morfologia renais em modelo experimental de SM induzida por dieta hiperlipídica. MÉTODOS: Ratos Wistar receberam ração hiperlipídica a partir da quarta semana de vida, por 20 semanas. Os grupos tratados receberam Losartana ou Espironolactona a partir da oitava semana de vida. Avaliou-se semanalmente o peso corporal e a PA de cauda por pletismografia. Ao final do experimento, foram realizados testes de tolerância oral à glicose, perfil lipídico, clearance de creatinina, medida direta da PA, análise morfométrica renal. RESULTADOS: A administração de dieta hiperlipídica se associou ao desenvolvimento de SM, caracterizada por acúmulo central de gordura, hipertensão arterial, hiperglicemia e hipertrigliceridemia. Nesse modelo não foram observadas alterações da histomorfometria renal. O bloqueio do receptor AT1 da angiotensina II (Ang II) preveniu o desenvolvimento da HA. O bloqueio mineralocorticoide não apresentou eficácia anti-hipertensiva, porém, associou-se à redução da gordura abdominal. CONCLUSÃO: A dissociação da resposta anti-hipertensiva aos bloqueios dos receptores da Ang II e mineralocorticoide indica a participação da Ang II na gênese da HA associada à obesidade. A redução da obesidade central com a Espironolactona sugere a presença de efeito adipogênico mineralocorticoide.

INTRODUCTION: The treatment of arterial hypertension (AH) in patients with metabolic syndrome (MS) is a challenge, since non drug therapies are difficult to implement and optimal pharmacological treatment is not fully established. OBJECTIVE: To assess the blockade of the rennin angiotensin aldosterone system (RAAS) in blood pressure (BP) in renal function and morphology in an experimental model of MS induced by high fat diet. METHODS: Wistar rats were fed on high fat diet from the fourth week of life, for 20 weeks. The groups received Losartan or Spironolactone from the eighth week of life. We weekly evaluated the body weight and BP by tail plethysmography. At the end of the experiment oral glucose tolerance, lipid profile, creatinine clearance tests, and the direct measurement of BP were performed. A morphometric kidney analysis was performed. RESULTS: The administration of high-fat diet was associated with the development of MS, characterized by central fat accumulation, hypertension, hyperglycemia and hypertriglyceridemia. In this model there were no changes in renal histomorphometry. The blockade of angiotensin II (Ang II) receptor AT1 prevented the development of hypertension. The mineralocorticoid blockage did not have antihypertensive efficacy but was associated with reduction of abdominal fat. CONCLUSION: The dissociation of the antihypertensive response to the blockades of Ang II receptors and mineralocorticoid indicates the involvement of Ang II in the pathogenesis of hypertension associated with obesity. Reduction of central obesity with Spironolactone suggests the presence of mineralocorticoid adipogenic effect.

Señalización de la angiotensina II, a través de la producción de radicales libres en estructuras del sistema nervioso: papel en el estres agudo y crónico / Angiotensin II signaling, through the production of free radicals in structures of the nervous system: role in acute and chronic stress

Existen evidencias que apoyan la participación de las especies reactivas de oxígeno en las cascadas de señalización y transducción intracelular de la angiotensina II. La ANG II es importante en el mantenimiento de la homeostasis corporal, regulando la presión arterial y el metabolismo de fluidos y electrolitos. Se sabe que en la periferia, la ANG II es capaz de estimular a la NAD(P)H oxidasa con la subsiguiente producción de ERO. El anión superóxido es metabolizado secuencialmente por las enzimas antioxidantes como la superóxido dismutasa, la catalasa y la glutatión peroxidasa. A su vez, las especies reactivas de oxígeno son capaces de activar a las proteínas kinasas activadas por mitógenos, las cuales se encuentran asociadas al crecimiento y la diferenciación celular. Se evaluó la posible participación de las especies reactivas de oxígeno en el mecanismo de señalización intracelular mediado por el receptorAT1en el hipotálamo, el órgano subfornicaly médula suprarrenal de la rata. Nuestros resultados demostraron que la estimulación del tejido nervioso con ANG II in vitroincrementó la actividad de la enzimas antioxidante. Al evaluar el papel del receptor AT1, la NAD(P)H oxidasa, el anión superóxido y la proteína kinasa C; así como la activación de las ERK1/2 en la señalización de la ANG II en el hipotálamo, OSF y MSR, demostramos que el bloqueo del receptor AT1con losartán, la interferencia del ensamblaje de la NAD(P)H oxidasa con apocinina, el secuestro de anión superóxido empleando un mimético de la SOD, tempol,y la inhibición de la PKC con cheleritrina, bloquearon completamente el efecto que produce la ANG II sobre las enzimas antioxidantes in vitro.Igualmente, la activación de la ERK1/2 inducida por la ANG II fue reducida por APO y LOS a nivel hipotalámico. Adicionalmente, el bloqueo del receptor AT2hipotalámico con PD123319, no bloqueo sino que mas bien potenció la respuesta de las enzimas antioxidantes y la activación de las ERK1/2 inducida por la ANG II, lo que desenmascaró el efecto contra regulatorio del receptor AT2sobre la acción de la ANG II mediada por el receptor AT1. Se sabe que durante el estrés el sistema renina angiotensina circulante y cerebral se encuentra estimulado, por lo tanto el incremento de la ANG II endógena debería desencadenar vías de señalización similares a las reportadas in vitro. Efectivamente, nuestros hallazgos demostraron que tanto,el estrés agudo inducido por la inmovilización forzada,como el estrés crónico en ratas espontáneamente hipertensas incrementaron la actividad de las enzimas antioxidantes en las tres estructuras cerebrales estudiadas. Este efecto es mediado por la vía del receptor AT1, la estimulación de la NAD(P)H oxidasa y la producción de anión superóxido ya que el tratamiento in vivo con LOS, APO y TEM fue capaz de bloquear completamente el incremento de la actividad de las enzimas antioxidantes inducidas por el estrés y por ende por la ANG II endógena.A nivel de la MSR demostramos, por primera vez, que la estimulación del receptor AT2 esta asociada a la estimulación de la NAD(P)H oxidasa, ya que la APOy el PD 123319 fueron capaces de bloquear el incremento de la actividad de las enzimas antioxidantes inducida por la ANG II. Demostrando así, que el receptor AT1en la MSR contrarregula la acción de la ANG II a través del receptor AT2.En conclusión, nuestros resultados indican que a nivel del sistema nervioso las especies reactivas de oxígeno participan en la cascada de señalización intracelular de la ANG II, y ejercen un importante papel en la respuesta al estrés y la hipertensión.

[Studying the effect of the combination of angiotensin II receptor blockers [losartan] with glucocorticoids in the treatment of rheumatoid arthritis after inducing it in rats]

Rheumatoid arthritis is a chronic disease that lead to disability, and all drugs used to treat it have many side effects, the objective of this study is to investigate the effect of angiotensin receptor blockers [losartan], and their combination with glucocorticoids in the treatment of rheumatoid arthritis, after inducing this disease in rats. We studied this effect in male Wistar rats injected with complete freund's adjuvant [CFA] to induce this disease. And we investigated the effect of losartan, and its combination with dexamethasone in low dose, we compared too this effect with the effect of dexamethasone in low and high doses, the drugs were administrated On day 12[th] of the injection of CFA till the end of the experiment [day 28[th]], and at the end of the experiment, ankle joints from all groups were isolated for histological study. losartan reduced only the infiltration of inflammatory cells to the synovium, but it didn't reduce synovial hyperplasia and the destruction of the cartilage, but the combination of losartan with low dose of dexamethasone reduced all these parameters, and the efficacy of this combination was equal to the efficacy obtained by dexamethasone in high dose. The combination of losartan with low dose of glucocorticids leads to a significant efficacy in the treatment of rheumatoid arthritis, and so, with lower side effects of glucocorticoids.

O sistema renina-angiotensina na doença periodontal induzida experimentalmente em ratos / The renin-angiotensin system in experimentally-induced periodontal disease in rats

A doença periodontal (DP) compreende um grupo de lesões que afetam os tecidos periodontais de proteção (gengivite) e suporte (periodontite), envolvendo a participação de células residentes, células estruturais e mediadores inflamatórios. Pesquisa recente do nosso laboratório mostrou a existência de um Sistema Renina-Angiotensina (SRA) local no tecido gengival de ratos e sugeriu que o SRA possa ter participação na DP. Portanto, o objetivo deste trabalho foi avaliar a se o SRA está envolvido na iniciação e na progressão da DP induzida experimentalmente em ratos. Para tanto, foi utilizado modelo de indução da DP por colocação de ligadura, por 7 e 14 dias, ao redor do primeiro molar inferior de ratos e tratamento destes animais com drogas que afetam o SRA [losartan (50 mg/Kg/dia), alisquireno (30 mg/Kg/dia) ou enalapril (10 mg/Kg/dia)]. Foram realizadas técnicas de análise da perda óssea alveolar, reação em cadeia da polimerase (PCR) quantitativa e imunoistoquímica. Após a coleta, os dados foram devidamente analisados por meio de gráficos e tabelas, sendo utilizada ANOVA a 2 e 3 critérios e adotado nível de significância de 5%. Em nível protéico, houve aumento significativo da maioria dos componentes do SRA (p<0,05) na DP. A renina apresentou aumento nos tratamentos com losartan, alisquireno e enalapril tanto nos animais sham (cirurgia fictícia de indução da DP) quanto nos animais com DP, aos 7 e 14 dias, e não apresentou marcação no grupo controle (água), demonstrando efeito dependente dos tratamentos farmacológicos. Na DP houve aumento dos componentes AT1 (aos 7 e 14 dias), AT2 (aos 7 dias) e enzima conversora da angiotensina (ECA; aos 7 e 14 dias) nos grupos tratados com losartan, alisquireno e enalapril. Também houve aumento de imunomarcação nos animais com DP para AT2 (aos 14 dias) e ECA (aos 14 dias) em animais do grupo controle. Em relação à expressão gênica, houve aumento da expressão de RNAm nos animais com DP para o...

Periodontal disease (PD) comprises a group of lesions that affect protection (gingivitis) and support periodontal tissues (periodontitis) involving the participation of resident and structural cells as well as inflammatory mediators. Recent research in our laboratory showed the existence of a local gingival renin-angiotensin system (RAS), and suggested that it might participate in PD. Therefore, the aim of this study was to evaluate whether the RAS is involved in the initiation and progression of the experimentally-induced PD in rats. For this purpose, a model of ligature placement, for 7 and 14 days, around the lower first molar in rats, and the treatment of such animals with drugs that affect the RAS [losartan (50 mg/Kg/day), aliskiren (30 mg/Kg/day) or enalapril (10 mg/Kg/day)] were employed. The following techniques were performed: alveolar bone loss analysis, quantitative real-time polymerase chain reaction and immunohistochemistry. Data were collected, organized in tables and graphs, and submitted to 2 and 3 way ANOVA with significance level established at 5%. In the protein level, there was a significant increase in the majority of the RAS components in PD. Immunolocalization for renin increased when animals were treated with losartan, aliskiren or enalapril, for 7 and 14 days, in both sham (fictitious surgery for PD induction) and PD animals, whereas the control group (water) had no staining, demonstrating a drug-related effect. In animals with PD treated with losartan, aliskiren or enalapril there was an increase in staining for AT1 (at 7 and 14 days), AT2 (at 7 days) and angiotensin-converting enzyme (ACE; at 7 and 14 days). There was also increased staining in PD animals for AT2 (at 14 days) and ACE (at 14 days) in the control group. As far as genic expression, there was an increase in mRNA expression for AT2 in control animals with PD (at 7 and 14 days), and in the animals treated with losartan or enalapril (at 7 days)...

How to avoid discontinuation of antihypertensive treatment: The experience in São Paulo, Brazil

OBJECTIVES: To evaluate the importance of providing guidelines to patients via active telephone calls for blood pressure control and for preventing the discontinuation of treatment among hypertensive patients. INTRODUCTION: Many reasons exist for non-adherence to medical regimens, and one of the strategies employed to improve treatment compliance is the use of active telephone calls. METHODS: Hypertensive patients (n=354) who could receive telephone calls to remind them of their medical appointments and receive instruction about hypertension were distributed into two groups: a) "uncomplicated" - hypertensive patients with no other concurrent diseases and b) "complicated" - severe hypertensive patients (mean diastolic >110 mmHg with or without medication) or patients with comorbidities. All patients, except those excluded (n=44), were open-block randomized to follow two treatment regimens ("traditional" or "current") and to receive or not receive telephone calls ("phone calls" and "no phone calls" groups, respectively). RESULTS: Significantly fewer patients in the "phone calls" group discontinued treatment compared to those in the "no phone calls" group (4 vs. 30; p<0.0094). There was no difference in the percentage of patients with controlled blood pressure in the "phone calls" group and "no phone calls" group or in the "traditional" and "current" groups. The percentage of patients with controlled blood pressure (<140/90 mmHg) was increased at the end of the treatment (74 percent), reaching 80 percent in the "uncomplicated" group and 67 percent in the "complicated" group (p<0.000001). CONCLUSION: Guidance to patients via active telephone calls is an efficient strategy for preventing the discontinuation of antihypertensive treatment.

Aldose Reductase Inhibitor Ameliorates Renal Vascular Endothelial Growth Factor Expression in Streptozotocin-Induced Diabetic Rats

PURPOSE: The vascular endothelial growth factor (VEGF) expression of podocyte is one of the well-known major factors in development of diabetic nephropathy. In this study, we investigated the effects of aldose reductase inhibitor, fidarestat on diabetic nephropathy, and renal VEGF expression in a type 1 diabetic rat model. MATERIALS AND METHODS: Twenty four Sprague-Dawley male rats which were performed intraperitoneal injection of streptozotocin and normal six rats were divided into four groups including a normal control group, untreated diabetic control group, aldose reductase (AR) inhibitor (fidarestat, 16 mg.kg(-1).day(-1)) treated diabetic group, and angiotensin receptor blocker (losartan, 20 mg.kg(-1).day(-1)) treated diabetic group. We checked body weights and blood glucose levels monthly and measured urine albumin-creatinine ratio (ACR) at 8 and 32 weeks. We extracted the kidney to examine the renal morphology and VEGF expressions. RESULTS: The ACR decreased in fidarestat and losartan treated diabetic rat groups than in untreated diabetic group (24.79 +/- 11.12, 16.11 +/- 9.95, and 84.85 +/- 91.19, p < 0.05). The renal VEGF messenger RNA (mRNA) and protein expression were significantly decreased in the fidarestat and losartan treated diabetic rat groups than in the diabetic control group. CONCLUSION: We suggested that aldose reductase inhibitor may have preventive effect on diabetic nephropathy by reducing renal VEGF overexpression.

Cálculo del impacto económico para Chile del uso de losartán en diabéticos tipo 2 con nefropatía diabética, basado en resultados del estudio RENAAL / Economic impact of Losartan use in type 2 diabetic patients with nephropathy

Background: The study RENAAL (Reduction of Endpoints in NIDDM with the Angiotensin II Antagonist Losartan) demonstrated that Losartan was more effective lo reduce the progression of kidney disease in diabetic patients with proteinuria and a reduction in glomerular filtration rate. Aim: To perform a cost benefit analysis of Losartan use from provider and payer points of view. Material and methods: Published data of the RENAAL study was analyzed. The costs of the use or not use of Losartan in patients with diabetic nephropathy were compared in terms of total costs of the disease including medications, hospital admissions for myocardial infarction, cerebrovascular accidents and congestive cardiac failure and the costs of chronic hemodialysis. Results: The reduction in antihypertensive medication use, hospital admissions, and the delay in dialysis requirement from a mean of 65 to 79 months induced by Losartan use, results in net savings of $7,576,135 per patient, at 3.5 years of intervention. The figure does not change using different sensitivity scenarios. Conclusions: The eventual use of Losartan in type 2 diabetic patients results in important savings.

Ação do lisinopril e do losartan na função endotelial após infarto agudo do miocárdio. Estudo experimental em ratos / Action of lisinopril and losartan in endothelial function after acute myocardialinfarction. Experimental study in rats.

JUSTIFICATIVA E OBJETIVOS: O presente estudo teve como objetivo estudar a influência do lisinopril e do losartan na função endotelial em ratos com infarto experimental do miocárdio. MÉTODO: Ratos Wistar machos, peso entre 350 e 400 g, divididos em quatro grupos (n igual 10): G1 igual ratos controle sem infarto, G2 igual ratos com infarto, G3 igual ratos com infarto e tratados com lisinopril (20 mg/kg/dia) e G4 igual ratos com infarto e tratados com losartan (30 mg/kg/dia). Os fármacos foram administrados via gavagem dois dias antes do infarto e continuado por mais sete dias. Os ratos foram anestesiados com éter para a ligadura da coronária descendente anterior. Após nove dias os animais foram anestesiados, o coração excisado e verificado a extensão do infarto. Utilizou-se para este fim a coloração pelo método do cloreto de trifeniltetrazólio a 1%, se considerando infarto grande quando excedia 40% da área do ventrículo esquerdo. A função endotelial foi verificada através de curva de concen­tração efeito com acetilcolina em segmento proximal da aorta torácica. Foram utilizados os testes estatísticos de ANOVA e de Duncan, sendo considerado significativo o valor de p menor que 0,05. RESULTADOS: Os resultados obtidos para a função en­dotelial para o relaxamento máximo foram: G 1 igual 78,24% mais ou menos 3,57%; G2 igual 14,04% mais ou menos 5,20%, G3 igual 48,94% mais ou menos 9,29% e G4 igual 26,98% mais ou menos 7,80%. Houve diferença estatístíca significatíva para entre os G3 e G4. CONCLUSÃO: Ocorreu disfunção endotelial em ratos na fase recente do infarto do miocárdio e o tratamento com lisinopril e losartan melhoraram esta disfunção endotelial.