The alteration of neuronal activities of the cuneiform nucleus in non-hypovolemic and hypovolemic hypotensive conditions / Alterações da atividade neuronal no núcleo cuneiforme em condições hipovolêmicas e não hipovolêmicas

Abstract Background: The cuneiform nucleus is located in the center of the circuit that mediates autonomic responses to stress. Hemorrhagic hypotension leads to chemoreceptor anoxia, which consequently results in the reduction of baroreceptor discharge and stimulation of the chemoreceptor. Objective: Using the single-unit recording technique, the neuronal activities of the cuneiform nucleus were investigated in hypotensive states induced by hemorrhage and administration of an anti-hypertensive drug (hydralazine). Methods: Thirty male rats were divided into the control, hemorrhage, and hydralazine groups. The femoral artery was cannulated for the recording of cardiovascular responses, including systolic blood pressure, mean arterial pressure, and heart rate. Hydralazine was administered via tail vein. The single-unit recording was performed from the cuneiform nucleus. Results: The maximal systolic blood pressure and the mean arterial pressure significantly decreased and heart rate significantly increased after the application of hydralazine as well as the following hemorrhage compared to the control group. Hypotension significantly increased the firing rate of the cuneiform nucleus in both the hemorrhage and hydralazine groups compared to the control group. Conclusions: The present data indicate that the cuneiform nucleus activities following hypotension may play a crucial role in blood vessels and vasomotor tone.

RESUMO Antecedentes: O núcleo cuneiforme está localizado no centro do circuito que media as respostas autonômicas ao estresse. A hipotensão hemorrágica leva à anóxia dos quimiorreceptores, que, consequentemente, resulta na redução da descarga dos barorreceptores e estimulação do quimiorreceptor. Objetivo: Utilizando a técnica de registro em unidade única, as atividades neuronais do núcleo cuneiforme foram investigadas em estados de hipotensão induzida por hemorragia e administração de um anti-hipertensivo (hidralazina). Métodos: Trinta ratos machos foram divididos nos grupos controle, hemorragia e hidralazina. A artéria femoral foi canulada, para o registro de respostas cardiovasculares, incluindo pressão arterial sistólica, pressão arterial média e frequência cardíaca. A hidralazina foi administrada na veia da cauda. O registro de unidade única foi realizado a partir do núcleo cuneiforme. Resultados: A pressão arterial sistólica máxima e a pressão arterial média diminuíram significativamente, e a frequência cardíaca aumentou significativamente após a aplicação de hidralazina, bem como a hemorragia seguinte, em comparação com o grupo controle. A hipotensão aumentou significativamente a taxa de disparo da população do núcleo cuneiforme em ambos os grupos de hemorragia e hidralazina, em comparação com o grupo de controle. Conclusões: Os presentes dados indicam que as atividades do núcleo cuneiforme após hipotensão podem desempenhar um papel crucial nos vasos sanguíneos e no tônus vasomotor.

Synthesis and antileishmanial activity of naphthoquinone-based hybrids / Síntesis y actividad antileishmania de híbridos naftoquinónicos / Síntese e atividade antileishmania de híbridos naftoquinónicos

SUMMARY Introduction: Leishmaniasis is a disease caused by protozoa of the genus Leishmania and is considered endemic in 98 countries. Treatment with pentavalent antimonials has a high toxicity, which motivates the search for effective and less toxic drugs. α- and β-lapachones have shown different biological activities, including antiprotozoa. In recent studies, the isonicotinoylhydrazone and phthalazinylhydrazone groups were considered innovative in the development of antileishmania drugs. Molecular hybridization is a strategy for the rational development of new prototypes, where the main compound is produced through the appropriate binding of pharmacophoric subunits. Aims: To synthesize four hybrids of α- and β-lapachones, together with the isonicotinoylhydrazone and phthalazinylhydrazone groups and to determine the antileishmania activity against the promastigotic forms of L. amazonensis, L. infantum and L. major. Results: β-lapachone derivatives were more active against all tested leishmania species. βACIL (IC50 0.044μM) and βHDZ (IC50 0.023μM) showed 15-fold higher activity than amphotericin B. The high selectivity index exhibited by the compounds indicates greater safety for vertebrate host cells. Conclusion: The results of this work show that the hybrids βACIL and (3HDZ are promising molecules for the development of new antileishmania drugs.

RESUMEN Introducción: Leishmaniasis es una enfermedad causada por protozoos del género Leishmania y se considera endémica en 98 países. El tratamiento con antimoniales pentavalentes tiene una alta toxicidad, lo que motiva la búsqueda de fármacos eficaces y menos tóxico. α- y β-lapachones han mostrado diferentes actividades biológicas, incluido los antiprotozoarios. En estudios recientes, los grupos isonicotinoilhidra-zona y ftalazinilhidrazona se consideraron innovadores en el desarrollo de fármacos antileishmania. La hibridación molecular es una estrategia para el desarrollo racional de nuevos prototipos, donde el compuesto principal se produce a través de la unión apropiada de subunidades farmacofóricas. Objetivos: Sintetizar cuatro híbridos de α- y β-lapachones, junto con los grupos isonicotinoilhidrazona y ftalazinilhidrazona y determinar la actividad antileishmania frente a las formas promastigotas de L. amazonensis, L. infantum y L. major. Resultados: Los derivados de β-lapachone fueron más activos contra todas las especies de leishmania probadas. La βACIL (CI50 0,044μM) y βHDZ (CI50 0,023μM) mostraron actividad 15 veces mayor que la anfotericina B. El alto índice de selectividad que presentan los compuestos indica una mayor seguridad para las células huésped del vertebrado. Conclusión: Los resultados de este trabajo demuestran que los híbridos (ACIL y (HDZ son moléculas prometodoras para el desarrollo de nuevos fármacos antileishmania.

RESUMO Introdução: A leishmaniose é uma doença causada por protozoários do género Leishmania e é considerada endémica em 98 países. O tratamento com antimoniais pentavalentes apresenta alta toxicidade, o que motiva a pesquisa por medicamentos eficazes e menos tóxicos. α- e β-lapachones tém mostrado diferentes atividades biológicas, incluindo antiprotozoários. Em estudos recentes, os grupos isonicotinoilhi-drazona e ftalazinilhidrazona foram considerados inovadores no desenvolvimento de drogas antileishmania. A hibridização molecular é uma estratégia para o desenvolvimento racional de novos protótipos, onde o composto principal é produzido através da ligação apropriada de subunidades farmacofóricas. Objetivos: Sintetizar quatro híbridos de α- e β-lapachones, juntamente com os grupos isonicotinoil-hidra-zona e ftalazinilhidrazona e determinar a atividade antileishmania contra as formas promastigóticas de L. amazonensis, L. infantum e L. major. Resultados: Os derivados de β-lapachona foram mais ativos contra todas as espécies de leishmania testadas. BACIL (IC50 0,044 μM) e βHDZ (IC50 0,023 μM) apresentaram atividade 15 vezes maior do que a anfotericina B. O alto índice de seletividade dos compostos indica maior segurança para células hospedeiras de vertebrados. Conclusaõ: Os resultados deste trabalho mostram que os híbridos βACIL e βHDZ são moléculas promissoras para o desenvolvimento de novos fármacos antileishmania.

Inhibición de la hipertrofia ventricular izquierda, normalización de la respuesta contráctil cardíaca y estrés oxidativo en hipertensión experimental / Inhibition of Left Ventricular Hypertrophy, Normalization of the Contractile Response and Oxidative Stress in Experimental Hypertension

Introducción y objetivos: La hipertrofia ventricular izquierda secundaria a hipertensión arterial se ha interpretado como un mecanismo de protección para reducir el estrés parietal y prevenir la insuficiencia cardíaca. Sin embargo, paradójicamente, su presencia se acompaña de un incremento de la morbimortalidad cardiovascular. El presente estudio se llevó a cabo con el propósito de evaluar si el tratamiento antihipertensivo crónico inhibe el desarrollo de hipertrofia ventricular izquierda y revierte el deterioro de la respuesta betaadrenérgica cardíaca y su posible relación con cambios en el metabolismo oxidativo del miocardio. Material y métodos: Ratas macho espontáneamente hipertensas (REH, 2 meses de edad) se distribuyeron en grupos (n grupo = 18) grupo según (mg/kg, v.o.): losartán 30 (L), hidralazina 11 (H), rosuvastatina 10 (R), carvedilol 20 (C), agua (control tratamiento). Control hipertensión: 18 ratas normotensas (Wistar-Kyoto, WKY). Periódicamente se registraron la presión arterial sistólica (PAS) (pletismografía, en animales despiertos) y el peso corporal (PC). Luego de 16 meses se practicó eutanasia. El 50% de los corazones se montaron en preparación de Langendorff para medir contractilidad preestímulo y posestímulo betaadrenérgico [isoproterenol (Iso): 10-9M, 10-7M, 10-5M]. En los corazones restantes se registró el peso del ventrículo izquierdo (PVI), que se normalizó por el PC. Se cuantificó la expresión inmunohistoquímica de tiorredoxina 1(Trx-1), peroxirredoxina 2 (Prx-2) y glutarredoxina 3 (Grx-3) (indicadores antioxidantes). Resultados: Peso corporal: similar en todos los grupos. PAS (mm Hg): 154 ± 3 (L), 137 ± 1 (H), 190 ± 3 (R)**, 206 ± 3 (REH)*, 183 ± 1 (C)**, 141 ± 1 (WKY) (*p < 0,05 vs. L, H, WKY; **p < 0,05 vs. L, H, WKY, REH). El PVI/PC de REH y R fue mayor (p < 0,05) respecto de L, H, C y WKY. En C no se observó correlación entre hipertensión e hipertrofia ventricular izquierda. Grupos REH, R y C: mostraron depresión de contractilidad basal vs. L, H y WKY. Respuesta a Iso 10-5 M: similar en WKY y L; disminuida en C, H, R y REH. Expresión de Trx-1, Prx-2 y Grx-3: aumentó en C, H, R y L (1,5-2 veces promedio; p < 0,01 vs. REH y WKY). Conclusiones: El tratamiento con losartán, hidralazina y carvedilol previno el desarrollo de hipertrofia ventricular izquierda. El losartán normalizó la respuesta al isoproterenol en REH. Factores adicionales participarían en el desarrollo de hipertrofia ventricular izquierda con deterioro de la respuesta inotrópica a la estimulación betaadrenérgica en hipertensión. El aumento en la expresión de tiorredoxinas por tratamientos antihipertensivos sugiere un beneficio asociado, aumentando la respuesta antioxidante frente al estrés oxidativo en hipertensión.

Background and objectives: Left ventricular hypertrophy secondary to hypertension has been perceived as a protective mechanism to reduce wall stress and prevent heart failure. However, its presence is paradoxically associated with increased cardiovascular morbidity and mortality The aim of this study was to evaluate whether chronic antihypertensive treatment inhibits the development of left ventricular hypertrophy and normalize the reverting impaired cardiac beta-adrenergic response, and its possible association with changes in myocardial oxidative metabolism. Methods: Spontaneously hypertensive male rats (SHR, 2 months old) were divided into groups (n grupo = 18) according to (mg/ group kg, p.o): losartan 30 (L), hydralazine-11 (H), rosuvastatin 10 (R), carvedilol 20 (C), and water (control treatment). The control hypertension group consisted of 18 normotensive rats (Wistar-Kyoto, WKY). Systolic blood pressure (SBP) (plethysmography in awake animals) and body weight (BW) were measured periodically. The animals were sacrificed at 16 months and 50% of the hearts were mounted in a Langendorff system to measure contractility before and after beta-adrenergic stimulation [isoproterenol (Iso): 10-9 M, 10-7 M, and 10-5 M]. In the remaining hearts left ventricular weight (LVW) was measured and normalized by B W. Immunohistochemical expression of thioredoxin 1 (Trx-1), peroxyredoxin 2 (Prx-2) and glutaredoxin 3 (Grx-3) (antioxidant indicators) was quantified. Results: Body weight was similar in all groups. Systolic blood pressure (mm Hg) was 154 ± 3 (L), 137 ± 1 (H), 190 ± 3 (R)**, 206 ± 3 (SHR)*, 183 ± 1 (C)**, and 141 ± 1 (WKY) (* p < 0.05 vs. L, H, WKY, ** p < 0.05 vs. L, H, WKY, SHR). LVW/BW was higher in SHR and R (p < 0.05) compared with L, H, C and WKY. In C, there was no correlation between hypertension and left ventricular hypertrophy. SHR, R and C evidenced baseline contractile depression vs. L, H and WKY. The response to 10-5 M Iso was similar in WKY and L, and reduced in C, H, R and SHR. The expression of Trx-1, Prx-2 and Grx-3 increased in C, H, R and L (average increase: 1.5-2 times; p < 0.01 vs. SHR and WKY). Conclusions: Treatment with losartan, hydralazine, and carvedilol prevented the development of left ventricular hypertrophy. Losartan normalized the response to isoproterenol in SHR. Additional factors might participate in the development of left ventricular hypertrophy with impaired inotropic response to beta-adrenergic stimulation in hypertension. The increased ex-pression of thioredoxins as a result of antihypertensive treatment suggests an additional benefit, increasing the antioxidant response against oxidative stress in hypertension.

Inhibición de la hipertrofia ventricular izquierda, normalización de la respuesta contráctil cardíaca y estrés oxidativo en hipertensión experimental / Inhibition of Left Ventricular Hypertrophy, Normalization of the Contractile Response and Oxidative Stress in Experimental Hypertension

Introducción y objetivos: La hipertrofia ventricular izquierda secundaria a hipertensión arterial se ha interpretado como un mecanismo de protección para reducir el estrés parietal y prevenir la insuficiencia cardíaca. Sin embargo, paradójicamente, su presencia se acompaña de un incremento de la morbimortalidad cardiovascular. El presente estudio se llevó a cabo con el propósito de evaluar si el tratamiento antihipertensivo crónico inhibe el desarrollo de hipertrofia ventricular izquierda y revierte el deterioro de la respuesta betaadrenérgica cardíaca y su posible relación con cambios en el metabolismo oxidativo del miocardio. Material y métodos: Ratas macho espontáneamente hipertensas (REH, 2 meses de edad) se distribuyeron en grupos (n grupo = 18) grupo según (mg/kg, v.o.): losartán 30 (L), hidralazina 11 (H), rosuvastatina 10 (R), carvedilol 20 (C), agua (control tratamiento). Control hipertensión: 18 ratas normotensas (Wistar-Kyoto, WKY). Periódicamente se registraron la presión arterial sistólica (PAS) (pletismografía, en animales despiertos) y el peso corporal (PC). Luego de 16 meses se practicó eutanasia. El 50% de los corazones se montaron en preparación de Langendorff para medir contractilidad preestímulo y posestímulo betaadrenérgico [isoproterenol (Iso): 10-9M, 10-7M, 10-5M]. En los corazones restantes se registró el peso del ventrículo izquierdo (PVI), que se normalizó por el PC. Se cuantificó la expresión inmunohistoquímica de tiorredoxina 1(Trx-1), peroxirredoxina 2 (Prx-2) y glutarredoxina 3 (Grx-3) (indicadores antioxidantes). Resultados: Peso corporal: similar en todos los grupos. PAS (mm Hg): 154 ± 3 (L), 137 ± 1 (H), 190 ± 3 (R)**, 206 ± 3 (REH)*, 183 ± 1 (C)**, 141 ± 1 (WKY) (*p < 0,05 vs. L, H, WKY; **p < 0,05 vs. L, H, WKY, REH). El PVI/PC de REH y R fue mayor (p < 0,05) respecto de L, H, C y WKY. En C no se observó correlación entre hipertensión e hipertrofia ventricular izquierda. Grupos REH, R y C: mostraron depresión de contractilidad basal vs. L, H y WKY. Respuesta a Iso 10-5 M: similar en WKY y L; disminuida en C, H, R y REH. Expresión de Trx-1, Prx-2 y Grx-3: aumentó en C, H, R y L (1,5-2 veces promedio; p < 0,01 vs. REH y WKY). Conclusiones: El tratamiento con losartán, hidralazina y carvedilol previno el desarrollo de hipertrofia ventricular izquierda. El losartán normalizó la respuesta al isoproterenol en REH. Factores adicionales participarían en el desarrollo de hipertrofia ventricular izquierda con deterioro de la respuesta inotrópica a la estimulación betaadrenérgica en hipertensión. El aumento en la expresión de tiorredoxinas por tratamientos antihipertensivos sugiere un beneficio asociado, aumentando la respuesta antioxidante frente al estrés oxidativo en hipertensión.(AU)

Background and objectives: Left ventricular hypertrophy secondary to hypertension has been perceived as a protective mechanism to reduce wall stress and prevent heart failure. However, its presence is paradoxically associated with increased cardiovascular morbidity and mortality The aim of this study was to evaluate whether chronic antihypertensive treatment inhibits the development of left ventricular hypertrophy and normalize the reverting impaired cardiac beta-adrenergic response, and its possible association with changes in myocardial oxidative metabolism. Methods: Spontaneously hypertensive male rats (SHR, 2 months old) were divided into groups (n grupo = 18) according to (mg/ group kg, p.o): losartan 30 (L), hydralazine-11 (H), rosuvastatin 10 (R), carvedilol 20 (C), and water (control treatment). The control hypertension group consisted of 18 normotensive rats (Wistar-Kyoto, WKY). Systolic blood pressure (SBP) (plethysmography in awake animals) and body weight (BW) were measured periodically. The animals were sacrificed at 16 months and 50% of the hearts were mounted in a Langendorff system to measure contractility before and after beta-adrenergic stimulation [isoproterenol (Iso): 10-9 M, 10-7 M, and 10-5 M]. In the remaining hearts left ventricular weight (LVW) was measured and normalized by B W. Immunohistochemical expression of thioredoxin 1 (Trx-1), peroxyredoxin 2 (Prx-2) and glutaredoxin 3 (Grx-3) (antioxidant indicators) was quantified. Results: Body weight was similar in all groups. Systolic blood pressure (mm Hg) was 154 ± 3 (L), 137 ± 1 (H), 190 ± 3 (R)**, 206 ± 3 (SHR)*, 183 ± 1 (C)**, and 141 ± 1 (WKY) (* p < 0.05 vs. L, H, WKY, ** p < 0.05 vs. L, H, WKY, SHR). LVW/BW was higher in SHR and R (p < 0.05) compared with L, H, C and WKY. In C, there was no correlation between hypertension and left ventricular hypertrophy. SHR, R and C evidenced baseline contractile depression vs. L, H and WKY. The response to 10-5 M Iso was similar in WKY and L, and reduced in C, H, R and SHR. The expression of Trx-1, Prx-2 and Grx-3 increased in C, H, R and L (average increase: 1.5-2 times; p < 0.01 vs. SHR and WKY). Conclusions: Treatment with losartan, hydralazine, and carvedilol prevented the development of left ventricular hypertrophy. Losartan normalized the response to isoproterenol in SHR. Additional factors might participate in the development of left ventricular hypertrophy with impaired inotropic response to beta-adrenergic stimulation in hypertension. The increased ex-pression of thioredoxins as a result of antihypertensive treatment suggests an additional benefit, increasing the antioxidant response against oxidative stress in hypertension.(AU)

Hipertrofia miocárdica induzida por consumo elevado de sal na dieta: avaliação do sistema renina-angiotensina e do efeito da N-acetilcisteína / Cardiac hypertrophy induced by high salt diet: renin-angiotensin system and N-acetylcysteine effect

As doenças cardiovasculares são a maior causa de morte no mundo e entre essas doenças, a hipertrofia cardíaca (HC) tem se destacado especialmente por ser um fator de risco de insuficiência cardíaca. A HC é um fenômeno que acompanha a hipertensão arterial e no qual se observa aumento de proteínas estruturais e contráteis dos cardiomiócitos, havendo muitas vezes concomitantemente aumento do colágeno intersticial. Fatores independentes da pressão arterial também podem contribuir para o desenvolvimento da hipertrofia cardíaca. Dentre estes fatores, a sobrecarga de sal na dieta tem se destacado. Diversos estudos comprovam o efeito hipertrófico do sal. Em modelos animais onde se estudou sobrecarga de sal, não foi detectado aumento da atividade de renina plasmática, sugerindo que o sistema renina-angiotensina aldosterona (SRA) circulante pode não estar envolvido no desenvolvimento da hipertrofia cardíaca. Apesar de alguns estudos tentarem elucidar o papel do sal no desenvolvimento da hipertrofia ventricular esquerda, os mecanismos pelo qual o sal atua ainda não estão totalmente esclarecidos. Neste contexto, o objetivo do presente estudo é observar os fenômenos que ocorrem no ventrículo esquerdo em resposta a sobrecarga de sal na dieta na tentativa de elucidar sua fisiopatologia. Para tanto, ratos Wistar machos foram divididos em cinco grupos de acordo com a dieta (normossódica 1,26% e hipersódica 8% de NaCl) e com o tratamento (losartan, cloridrato de hidralazina ou N-acetilcisteína). Foi avaliada a evolução ponderal, pressão arterial caudal, medida do diâmetro transverso do cardiomiócito, fibrose intersticial, expressão gênica e proteica dos componentes do SRA, dosagem de aldosterona sérica e cardíaca, dosagem de TBARS cardíaco, concentração de angiotensina II e estado conformacional dos receptores AT1 e AT2. Os principais resultados observados foram: o aumento do consumo de ração (com elevada concentração de NaCl) do grupo HS+NAC e consequente aumento na...

Cardiovascular diseases are the leading cause of death worldwide and among these diseases, the cardiac hypertrophy (CH) has been highlighted, especially as an important risk factor for developing heart failure. The CH is a phenomenon that accompanies hypertension and in which there is increased structural and contractile proteins in cardiomyocytes, with often concomitant increase of interstitial collagen. Blood pressure independent risk factors can also contribute to the development of cardiac hypertrophy. Among these factors, the high salt intake has been outstanding. Several studies confirm the hypertrophic effect of salt. In animal models submitted to salt overload, no increase in plasma renin activity was observed, suggesting that the renin-angiotensin (RAS) circulating system may not be involved in the development of cardiac hypertrophy. Although some studies attempting to elucidate the role of salt in the development of left ventricular hypertrophy, the mechanisms by which salt acts are not yet fully understood. In this context, the objective of this study is to observe the phenomena occurring in the left ventricle in response to dietary salt overload in an attempt to elucidate its pathophysiology.Male Wistar rats were divided into five groups according to their diet (1.26% and 8% NaCl) and treatment (losartan, hydralazine or N-acetylcysteine). We evaluated the body weight, tail-cuff blood pressure, the transverse diameter of the cardiomyocyte, interstitial fibrosis, gene and protein expression of RAAS components, serum and cardiac aldosterone dosage, cardiac TBARS, angiotensin II concentration and binding of conformation-specific anti-AT1 and anti-AT2 antibodies. The main results were: increased food intake (with high NaCl content) in the HS + NAC group and consequent increase in blood pressure and body weight; developing blood pressure-independent CH in the HS + HZ group partial or total prevention of such hypertrophy by treatment with losartan and...

Floating tablets of hydralazine hydrochloride: optimization and evaluation

Hydralazine hydrochloride has a half-life of 2 to 4 hours with an oral bioavailability of 26-50%. Since hydralazine has a demethylating effect on various suppressor genes, it can be used in various types of cancer to support chemotherapy. The purpose of this study was to optimize and evaluate floating tablets of hydralazine hydrochloride designed to prolong the gastric residence time and to provide controlled release of the drug for 14 h. The floating tablets of hydralazine hydrochloride were prepared by the wet granulation method. Semi-synthetic polymers of hydroxy propyl methyl cellulose (HPMC K100M) and ethyl cellulose were used as the release retarding agents. A 2² factorial design was applied to systematically optimize the drug release profile. The concentrations of HPMC K100M and ethyl cellulose were optimized to provide controlled release of hydralazine for 14h. Non-Fickian diffusion release transport was confirmed as the release mechanism for the optimized formulation and the predicted values agreed well with the experimental values. Drug excipient compatibility studies were investigated by FTIR, DSC and XRD. These data indicate that there were no chemical interactions between the drug and the polymer. In vivo X-ray imaging showed floating tablet performance in rabbits.

O cloridrato de hidralazina apresenta meia-vida de 2 a 4 horas, com biodisponibilidade oral de 26-50%. Uma vez que a hidralazina possui efeito desmetilante em vários genes supressores, ela pode ser utilizada para diversos tipos de câncer, em apoio à quimioterapia. O objetivo deste estudo foi o de avaliar e otimizar comprimidos flutuantes de cloridrato de hidralazina, planejados para prolongar o tempo de residência gástrica e proporcionar liberação controlada do fármaco por 14 h. Os comprimidos flutuantes de cloridrato de hidralazina foram preparados pelo método de granulação úmida. Polímeros semi-sintéticos de hidroxipropiletil celulose (HPMCK100M) e acetato de celulose foram utilizados como agente de retardamento de liberação. Aplicou-se planejamento fatorial 2² para otimizar sistematicamente o perfil de liberação do fármaco. As concentrações de HPMCK100M e de etilcelulose foram otimizadas para se obter liberação controlada de hidralazina durante 14 h. O transporte de liberação de difusão não-Fickiana foi confirmado como o mecanismo de liberação para a formulação otimizada e os valores previstos estiveram de acordo com os valores experimentais. Estudos de compatibilidade entre fármaco e excipiente foram realizados por FTIR, DSC e DRX. Estes dados indicaram que não havia interação química entre o fármaco e o polímero. Imagens de raios-X in vivo mostraram o desempenho dos comprimidos flutuantes em coelhos.

Estados hipertensivos del embarazo en adolescentes, hospital maternidad Enrique C. Sotomayor, año 2004 / Hypertensive states of pregnancy in adolescents at the maternity hospital Enrique C. Sotomayor in 2004

Estudio realizado en el hospital-maternidad “Enrique C. Sotomayor” en pacientes adolescentes que se diagnosticó hipertensión arterial, año 2004. Tipo de estudio: retrospectivo descriptivo. Objetivo: conocer la incidencia y resultantes materno-neonatales que nos lleve a controlar esta patología. Metodología: análisis de historias clínicas en pacientes adolescentes e hijos de las mismas, atendidos en el hospital-maternidad, año 2004. Resultados: hubo 146 casos (10,6 de embarazadas), con predominio de preeclampsia severa; promedio de edad: 16 años; la desproporción cefalopélvica y distocias de presentación fueron los defectos más comunes; al 96 se le realizó cesárea, las presiones arteriales se normalizaron 8 horas posparto. Neonatos: fue en 85 aptos para la edad gestacional; y fallecieron el 4. Conclusiones: a pesar de la gran cantidad de casos, se ha logrado controlarlos en casi su totalidad con rápido diagnóstico y eficaz terapéutica a través de cesáreas e hidralazinaStudy carried out at the maternity hospital “Enrique G. Sotomayor” in adolescent patients who were diagnosed arterial hypertension in 2004.

Study type: retrospective and descriptive. Objective: identify the incidence and maternal-neonatal results which could help us control this pathology. Methodology: analyses of clinical history in adolescent patients and their children attended at the maternity hospital in the year 2004. Results: there were 146 cases (10.6 of pregnant women), in whom severe preeclampsia was predominant; average age: 16 years old; cephalopelvic disproportion and presentation dystocias were the most common defects (96). They had a cesarean section. Arterial pressures were normalized 8 hours after delivery. Neonates: 85 were appropriate for gestational age; and 4 passed away. Conclusions: despite the big amount of cases, almost all of them were under control through fast diagnosis and efficient therapy of cesarean section and hydralazine.

Uso da hidralazina intravenosa para o tratamento da crise hipertensiva / Use of intravenous hydralazine in treatment of hypertensive crisis

Purpose­To evaluate the efficacy and safety of intravenous hidralazine in arterial hypertension. Patients and Methods­12 patients, meanage 45,33 15,82,8 men and 4 women all of them with systolic (S) arterialpressure (AP) 180 and or diastolic (D) 126 mmHg with symptoms like headache, incaracteristic toraxic pain and others but without an hypertensive emergency neither acute manifestation of hypertensive encephalopathy through fundi examination were studied. The AP was taked 10 minutes after rest (inicial) and 5, 15, 30 and 60 min (final) after intravenous administration of hidralazine-HCL (5mg) which was repeated when at least 20% AP reduction was not achieved. Results­ The inicial and final SAP, DAPand heart rate (HR) wre 208 ± 19,4 and 176 ± 17,2 (p < 0.0001), 133 ± 11,3 and 112 ± 11,5 (p< 0.001) and 72 ± 12,9 and 80 ± 15,5 (NS), respectively. Side effects related to the drug were observed in 3 (25%) patients. One had symptomatic ortostatic hypotension, the second had precordial pain with ST-T changes compatible with myocardial ischemia and the third presented a torax and abdominal cutaneous erithema, but all of them reversible. Conclusion­ Intravenous hydralazineHC1 is an alternative when rapid arterial pressurereduction is needed