A Case of Cutaneous Leukocytoclastic Vasculitis Associated with Granulocyte Colony-Stimulating Factor: An Unusual Presentation

Drug-induced vasculitis is an inflammation of small-sized blood vessel caused by the use of drugs. It accounts for approximately 10% of acute cutaneous vasculitis. Propylthiouracil, hydralazine, and allopurinol have been widely known as causative agents. The most common clinical feature of drug-induced vasculitis is palpable purpura on lower extremities. A 66-year-old Korean female presented with erythematous nodules on upper chest and back. She had been on medication for multiple myeloma. Laboratory results showed neutropenia. After a single injection of filgrastim (recombinant granulocyte colony-stimulating factor), she developed cutaneous lesions with concurrent increase in absolute neutrophil count. A skin biopsy revealed leukocytoclastic vasculitis. After discontinuation of filgrastim injection, her skin lesions disappeared spontaneously.

Hydralazine-associated adverse events: a report of two cases of hydralazine-induced ANCA vasculitis / Eventos adversos associados à hidralazina: um relatório de dois casos de vasculite associada ao ANCA induzida por hidralazina

Abstract Hydralazine is a direct-acting vasodilator, which has been used in treatment for hypertension (HTN) since the 1950s. While it is well known to cause drug-induced lupus (DIL), recent reports are indicating the emergence of the drug-induced anti-neutrophil cytoplasmic antibody (ANCA) associated vasculitis (DIV). Herein, we describe two patients (aged 57 and 87 years) who presented with severe acute kidney injury (AKI), proteinuria, and hematuria. Both were receiving hydralazine for the treatment of hypertension. ANCA serology was positive in both patients along with anti-histone antibodies (commonly seen in drug-induced vasculitis). Renal biopsy revealed classic crescentic (pauci-immune) glomerulonephritis in these patients and hydralazine was discontinued. During the hospital course, the 57-year-old patient required dialysis therapy and was treated with steroids and rituximab for the ANCA disease. Renal function improved and the patient was discharged (off dialysis) with a serum creatinine of 3.6 mg/dL (baseline = 0.9 mg/dL). At a follow-up of 2 years, the patient remained off dialysis with advanced chronic kidney disease (CKD) (stage IIIb). The 87-year-old patient had severe AKI with serum creatinine at 10.41 mg/dL (baseline = 2.27 mg/dL). The patient required hemodialysis and was treated with steroids, rituximab, and plasmapheresis. Unfortunately, the patient developed catheter-induced bacteremia and subsequently died of sepsis. Hydralazine can cause severe AKI resulting in CKD or death. Given this extremely unfavorable adverse-event profile and the widespread availability of alternative anti-hypertensive agents, the use of hydralazine should be carefully considered.

Resumo A hidralazina é um vasodilatador de ação direta, que vem sendo utilizado no tratamento da hipertensão arterial (HA) desde a década de 1950. Embora seja bem conhecido por causar lúpus induzido por drogas (LID), relatórios recentes estão indicando o surgimento da vasculite associada ao anticorpo citoplasmático anti-neutrófilo (ANCA), induzida por drogas (VID). Aqui, descrevemos dois pacientes (com idade entre 57 e 87 anos) que apresentaram lesão renal aguda grave (LRA), proteinúria e hematúria. Ambos estavam usando hidralazina para o tratamento da hipertensão. A sorologia para ANCA foi positiva em ambos os pacientes, juntamente com anticorpos anti-histona (comumente vistos na vasculite induzida por drogas). A biópsia renal revelou glomerulonefrite rapidamente progressiva clássica (pauci-imune) nestes pacientes e a hidralazina foi interrompida. Durante a internação hospitalar, o paciente de 57 anos necessitou de diálise e foi tratado com esteroides e rituximab para a doença do ANCA. A função renal melhorou e o paciente recebeu alta (fora da diálise) com creatinina sérica de 3,6 mg/dL (basal = 0,9 mg/dL). Em um seguimento de 2 anos, o paciente permaneceu fora da diálise com doença renal crônica avançada (DRC) (estágio IIIb). O paciente de 87 anos apresentava IRA grave com creatinina sérica em 10,41 mg/dL (valor basal de = 2,27 mg/dL). O paciente necessitou de hemodiálise e foi tratado com esteroides, rituximabe e plasmaferese. Infelizmente, o paciente desenvolveu bacteremia induzida por cateter e, posteriormente, evoluiu a óbito por sepse. A hidralazina pode causar IRA grave, resultando em DRC ou óbito. Dado este perfil de eventos adversos extremamente desfavorável e a disponibilidade generalizada de agentes anti-hipertensivos alternativos, o uso de hidralazina deve ser considerado com muita parcimônia.

A study on the knowledge and management practices on hypertension in pregnancy among midwives in the different public health centers of Cebu City / Philippine Journal of Obstetrics and Gynecology

ABSTRACT:BACKGROUND: The Millennium Development Goal (MDG) for 2015 has a target MMR of 52/100,000 live births but this goal been difficult to achieve. In the Philippines, 11 mothers die everyday from pregnancy related complications, a bulk contributed by Hypertension. Public health midwives sometimes attend to these obsterical emergencies often in the absence of a physician. this led to the BEmONC program, which addresses the rising morbidities from far-flung areas where resources are scarce, and helps train midwives in essential obsterical emergency care. The midwives are our allies in providing the best standard of care every mother and child rightfully deserves. Only thru periodic evaluation can we help strengthen BEmONC program, making it crucial to evaluate the midwives' knowledge and management practices in hypertension to help identify the setbacks that have impeded our progress in achieving the MDG.GENERAL OBJECTIVE: To access the knowledge and management practices of midwives in the management of hypertension in pregnancy in accourdance to the BEmONC protocol.STUDY DESIGN: Descriptive StudySTUDY SETTING: The 69 public health centers of Cebu CitySTUDY POPULATION: Public Health MidwivesMETHODOLOGY:This is descriptive study where a survey questionnaire was used and convenience sampling was done. Chi square and Fischer exact tests were employed to compare proportions. Descriptive statistics was used to summarize the data in proportion.RESULT: More than 70% of the midwives were knowledgeable regarding expected competencies, where BEmONC-trained midwives were 5-14x more likely to identity appropriate function. However, Only a dismal 22-36% will actually administer Magnesium Sulfate, which shows that knowledge is not translated into practice. Also, more than 70% were knowledgeable on the risk factors and danger signs of hypertension in pregnancy. It also showed that the midwives agreed to give antihypertensive medications- where Methyldopa was commonly given. Among those who agreed too give Methyldopa, majority were BEmONC-trained. A number also agreed to give hydralazine and diazepam in the setting of sever preeclampsia and eclampsia, where more non-BEmONC midwives agreed. Alarmlingly, only less than 50% will refer to a physician in the management og gestational hypertension and mild preeclampsia, and only 50%-60% agreed to facilitate hospital transport in the setting of severe preeclampsia and eclampsia.CONCLUSION: The BEmONC manual must be updated to keep up with current guidelines and ensure the conversation of knowledge into practice. The BEmONCcoverage of training must also be expanded so that all practicing midwives know the protocol. However, the DOH must further strengthen their role in the active surveillance of public health midwives and review the retention of their skills and regular practice of knowledge. Midwives must also be certified proficient, not merely trained. The must also be consulted to explore their problems in the implementation of current guidelines so we can better understand their situation as to why knowledge is not put into practice. By identifying deficiencies, we can improve and address setbacks that have impeded our progress towards achieving the Millennium Development Goal.

Anti-TNF-α and hydralazine drug-induced lupus

Drug-induced lupus is a rare drug reaction featuring the same symptoms as idiopathic lupus erythematosus. Recently, with the introduction of new medicines in clinical practice, an increase in the number of illness-triggering implicated drugs has been reported, with special emphasis on anti-TNF-α drugs. In the up-to-date list, almost one hundred medications have been associated with the occurrence of drug-induced lupus. The authors present two case reports of the illness induced respectively by hydralazine and infliximab, addressing the clinical and laboratorial characteristics, diagnosis, and treatment.

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.

[Comparison between effects of intravenous labetalol and hydralazine on control of hypertension and maternal and neonatal outcomes in severe preeclamptic patients: a randomized clinical trial]

Severe preeclampsia and eclampsia are responsible for 25% of maternal mortality, especially in developing countries. Considering the importance of this complication, the present study aimed to compare between effects of labetalol and hydralazine on control of hypertension and the maternal and neonatal outcomes in severe preeclamptic patients. This clinical trial study was conducted on 190 severe preeclamptic patients classified into two groups [95 subjects in each group]. Two groups were randomly received hydralazine [5 mg intravenously, every 20 minutes, up to a maximum of five doses] or labetalol [at first 20 mg intravenously, and if not effective, 40, 80, 80, 80 mg respectively, every 20 minutes, up to a maximum of five doses]. In both groups, blood pressure and heart rate were recorded 20 minutes after drug administration. Blood pressure control, as well as the maternal and neonatal outcomes, compared between two groups. Maternal and neonatal outcomes were compared using chi-square, Fisher's exact, Mann-Whitney, and t tests. All significant differences were at p<0.05. Demographic characteristics and blood pressure control were similar in both groups, only five women in the hydralazine group and four women in labetalol group had persistent severe hypertension after maximum of five doses. Hypotension was not observed in both groups. Maternal tachycardia was similar in two groups. Others maternal and neonatal outcomes had no significant differences between two groups. According to the results of this study, the effect of labetalol and hydralazin is similar in the control of hypertension in severe preeclamptic patients and there isn't significant different in maternal and neonatal outcome in two groups

Antihypertensive drug procurement trends from 1995 to 2004: transition over a decade

To evaluate antihypertensive procurement trends in Bahrain from 1995 to 2004. Pharmacology and Therapeutics, Arabian Gulf University/Directorate of Material Management, Ministry of Health. A retrospective audit study based on the data from the Directorate of Material Management, Ministry of Health [MOH], Bahrain. A review of the annual antihypertensive drug procurement data from 1995 to 2004 was performed. The procurement rate of angiotensin converting enzyme inhibitors [ACEIs], diuretics and alpha-blockers, significantly increased while the rate of calcium channel blockers [CCBs], methyldopa and hydralazine declined during this decade. Beta-blockers were the top-ranked agents in both 1995 and 2004. Significant interclass changes were evident: increase in procurement of long-acting ACEIs, CCBs and indapamide associated with a decline in short-acting ACEIs, CCBs and thiazide and thiazide-like diuretics in 2004. Angiotensin-II receptor blocker [ARB] - valsartan was introduced in 1999. The procurement of fixed-dose combinations [FDCs] increased from 0.9% in 1995 to 3.4% in 2004, associated with a significant decline in Moduretic and Brinerdin and by introduction of Co-Diovan, Preterax and Bi-Preterax. High cost due to renin-angiotensin-aldosterone inhibitors [ACEIs and ARBs] accounted for approximately half of the total antihypertensive drugs budget. According to Ministry of Health budget, the annual drug budget for antihypertensive drugs increased from 6.7% in 1995 to 14.1% in 2004. During that decade, there was a rapid annual growth rate for diuretics, CCBs and FDCs. The antihypertensive procurement strategy has qualitatively improved; there is a shift towards selection of more rational long-acting antihypertensives and FDC products. Analysis of drug procurement trend should be a critical component of national drug policy

Comparison of the efficacy of nifedipine and hydralazine in hypertensive crisis in pregnancy

Intravenous hydralazine is a commonly administered arteriolar vasodilator that is effective for hypertensive emergencies associated with pregnancy. Oral nifedipine is an alternative in management of these patients. In this study the efficacy of nifedipine and hydralazine in pregnancy was compared in a group of Iranian patients. Fifty hypertensive pregnant women were enrolled in the study. A randomized clinical trial was performed, in which patients in two groups received intravenus hydralazine or oral nifedipine to achieve target blood pressure reduction. The primary outcomes measured were the time and doses required for desired blood pressure achievement. Secondary measures included urinary output and maternal and neonatal side effects. The time required for reduction in systolic and diastolic blood pressure was shorter for oral nifedipine group [24.0 +/- 10.0 min] than intravenus Hydralazine group [34.8 +/- 18.8 min] [P

Safety and efficacy of hyderalzine in hypertensive disorders of pregnancy

To find out safety and efficacy of IV bolus hydralazine in reducing blood pressure in severe hypertension during pregnancy. All pregnant patients with systolic blood pressure 160 or above and diastolic blood pressure 109 mmHg with eclampsia and hypertensive emergencies were included. The initial dose of hydralazine was 5 mg IV bolus then repeated 1mg at 20 minutes interval. Outcome measures to start treatment were, systolic and diastolic blood pressure, time required for achieving the desired BP level, total dose needed, side effects of drugs, maternal and fetal outcome in terms of safety and efficacy. One hundred and ten patients with eclampsia and hypertensive emergencies were included in the study. The mean + SD [range] of maternal age was 26.70 + 6.70[18 -45 years]. Blood pressure before starting therapy was systolic 165.5 + 16.65, and diastolic blood pressure was 115.45 + 8.25mmHg. After starting therapy, a significant difference [P=< 0.001] was observed with fall in systolic blood pressure 131.2 + 9.49 and in diastolic blood pressure 93.68+6.30mmHg. In 94[85.5%] patients, IV bolus hydralazine took 60 minutes, however, in 3[2.7%] > 180 minutes time was required to control the blood pressure. Total dose of drug required was <6mg in 40[38.4%] patients, 6 to 14mg in 44[40%] and in 17[15.5%] women 15 to 20 mg of dose was needed to control the blood pressure. Only 9[8.18%] needed dose between 21 to 30 mg IV bolus hydralazine. Hydralazine is safe and effective in controlling the blood pressure in severe hypertension during pregnancy and after delivery

O que acrescentar após inibidor da enzima conversora da angiotensina, betabloqueador e espironolactona na insuficiência cardíaca sintomática? / What to add after angiotensin-converting enzyme inhibitor, beta-blockers and spironolactone in the treatment of heart failure?

O tratamento padrão para a insuficiência cardíaca é aquele no qual o paciente apresenta aderência adequada tanto às medidas não-farmacológicas como às drogas comprovadamente eficazes e com impacto positivo no controle da doença. Existem pacientes, porém, que, mesmo otimizados, ainda persistem sintomáticos e refratários ao tratamento padrão. Para esse subgrupo de pacientes, deve-se atentar para o controle de co-morbidades associadas, como anemia, insuficiência renal e hipertensão pulmonar. Outras alternativas terapêuticas também têm sido benéficas na melhora do desempenho cardíaco e da capacidade física de pacientes refratários ao tratamento clínico padrão. A associação de duas classes diferentes de diuréticos e a adição de bloqueadores do receptor da angiotensina ou de nitrato e hidralazina ao esquema padrão com inibidor da enzima conversora da angiotensina, betabloqueadora e espironolactona têm demonstrado benefícios adicionais na redução da congestão pulmonar e na melhoria da classe funcional e da qualidade de vida.

Congenital mesoblastic nephroma: a case report

Congenital mesoblastic nephroma [CMN] is a rare renal tumor. It can be detected antenatally especially with judicious use of ultrasonography. A premature female neonate 28 weeks' gestation, complicated by polyhydramnios, was born to a 28-year-old woman. An abdominal mass was detected antenatally. At the end of the first week of life, the newborn had hypertension that was controlled by hydralazine. Ultrasonography and CT scan showed a right-sided renal heterogeneous solid mass. Right nephrectomy was performed and the histology showed CMN

Persistent hypertension and progressive renal injury induced by salt overload after short term nitric oxide inhibition

INTRODUCTION: Administration of the NO inhibitor Nwð-nitro-L-arginine methyl ester (NAME) and a high-salt diet (HS) promotes severe albuminuria and renal injury, which regresses upon discontinuation of treatments. OBJECTIVE: We investigated whether these changes reappear after reinstitution of HS, and whether they are prevented by treatment with the antilymphocyte agent mycophenolate mofetil (MMF) or the AT-1 receptor blocker losartan (L). Adult male Munich-Wistar rats received NAME and HS. A control Group (C) received only HS. After 20 days, rats receiving HS and NAME exhibited severe hypertension and albuminuria. After a 30-day recovery period, hypertension was attenuated and albuminuria had virtually disappeared. MATERIAL AND METHODS: Rats were then distributed among the following groups: HS, receiving HS; NS, receiving a normal salt (NS) diet; HS-MMF, receiving HS and MMF; HS-LOS, receiving HS and L; HS-HDZ, receiving HS and hydralazine (HDZ). Sixty days later, NS rats showed only slight albuminuria and renal damage or inflammation. In contrast, HS rats developed severe hypertension, marked glomerulosclerosis with interstitial expansion and renal infiltration by macrophages and angiotensin II-positive cells. The group treated with losartan had lowered blood pressure and a lack of albuminuria or renal injury. MMF provided similar protection without altering blood pressure, suggesting a nonhemodynamic effect, a hypothesis reinforced by the finding that HDZ lowered blood pressure without preventing renal injury. RESULTS: These results indicate that treatment with HS and NAME predisposes to the development of hypertension and renal injury upon salt overload, characterizing a new model of chronic nephropathy. CONCLUSION: The response to MMF or L, but not HDZ, suggests a key role for inflammatory rather than hemodynamic factors.

INTRODUÇÃO: A administração de Nômega-nitro-L-arginina metiléster (NAME), um inibidor da produção de NO, com dieta rica em sal (HS) promove albuminúria e dano renal graves, reversíveis ao interromperem-se os tratamentos. OBJETIVO: Investigamos se tais alterações recrudescem ao reinstituir-se a HS e se são prevenidas pelo micofenolato mofetil (MMF), um agente antilinfócito, ou losartan, um bloqueador do receptor AT-1. MATERIAL E MÉTODOS: Ratos Münich-Wistar machos adultos receberam NAME e HS. Um grupo controle (C) recebeu apenas HS. Após 20 dias, os ratos que receberam HS e NAME exibiam hipertensão e albuminúria graves. Após recuperação de 30 dias, a hipertensão atenuou-se e a albuminúria praticamente desapareceu. Formaram-se então os grupos: HS, recebendo HS; NS, recebendo dieta normal em sal (NS); HS-MMF, recebendo HS e MMF; HS-LOS, recebendo HS e losartan; HS-HDZ, recebendo HS e hidralazina. Após sessenta dias os ratos NS tinham albuminúria e dano/inflamação renal apenas discretos. Já os ratos HS desenvolveram hipertensão e glomerulosclerose acentuadas, expansão intersticial e infiltração renal por macrófagos e células positivas para angiotensina II. Losartan baixou a pressão arterial e preveniu albuminúria e lesão renal. MMF proporcionou proteção semelhante sem alteração pressórica, sugerindo a ação de mecanismos não hemodinâmicos, hipótese reforçada pelo achado de que a HDZ baixou a pressão arterial sem prevenir a nefropatia. RESULTADOS: Esses resultados indicam que o tratamento com HS e NAME predispõe ao desenvolvimento de hipertensão e lesão renal induzidos por excesso de sal, caracterizando um novo modelo de nefropatia crônica. CONCLUSÃO: A resposta ao MMF ou losartan, mas não à hidralazina, sugere o predomínio de fatores inflamatórios.

Effect of Hydralazine on demethylation status and expression of APC gene, proliferation and apoptosis of human cervical cancer cell lines / 中华病理学杂志

<p><b>OBJECTIVE</b>To investigate the correlation between methylation status and gene expression of APC (adenomatous polyposis coli) gene in HeLa, CaSki and SiHa cell lines of cervical carcinoma, and explore the effect of hydralazine on the transcription regulation of the 5'CpG island demethylation of APC gene and the proliferation and apoptosis of the cell lines.</p><p><b>METHODS</b>Methylation status and the expression of APC gene were analyzed using methylated specific PCR, RT-PCR and FQ-PCR methods. The expression of beta-catenin protein which correlates closely with APC was detected by SP method after treatment with Hydralazine. MTT and FCM assays were used to observe the changes of proliferation activity and apoptosis of the cells after Hydralazine treatment.</p><p><b>RESULTS</b>(1) APC gene was methylated or hemimethylated respectively in HeLa and CaSki cell lines, at the same time, APC gene was not methylated in SiHa cell. (2) After having been treated by 40 micromol/L Hydralazine for 72 hours, growth inhibitory ratios of HeLa, CaSki and SiHa cell lines were (52.12 +/- 3.78)%, (44.31 +/- 2.59)% and (47.73 +/- 4.73)% respectively, on the contrary, normal cell HECV's growth inhibitory ratio was only (27.18 +/- 0.79)%. APC gene in HeLa and CaSki cell lines which were treated by 40 micromol/L Hydralazine for 72 hours was demethylated and expressed positively, the expression of APC mRNA in HeLa, CaSki and SiHa cell lines increased to 10.35, 11.40 and 0.73 times respectively. (3) Hydralazine, when used at the concentration of 40 micromol/L for 72 hours, induced S phase and G2/M phase arrest and apoptosis in HeLa and CaSki cells. beta-catenin protein can be expressed in cell membrane after treatment with Hydralazine.</p><p><b>CONCLUSION</b>APC gene methylation plays an important role in the carcinogenesis of cervical cells and can re-express after the treatment with Hydralazine which also could inhibit the growth of the cervical cancer cells.</p>

Efetividade do tratamento de gestantes hipertensas / Perinatal outcome in the different clinical forms of hypertension during pregnancy

OBJETIVO: Comparar as intercorrências clínicas materno-fetais e a efetividade do tratamento entre grupos das síndromes hipertensivas na gestação (SHG). MÉTODOS: Foram revisados 200 prontuários de gestantes com SHG, sendo avaliados as intercorrências fetais, a classificação da síndrome hipertensiva e o uso de anti-hipertensivos. RESULTADOS: Entre as intercorrências maternas, 85 (42,5 por cento) das pacientes foram classificadas no grupo controle; 32 (16 por cento) apresentaram hipertensão gestacional (HG); 67 (33,5 por cento) PE; 6 (3 por cento) hipertensão crônica; e 10 (5 por cento) pré-eclâmpsia sobreposta a hipertensão crônica (PSHC). Os menores valores para a idade gestacional, peso dos recém-nascidos e para o índice de Apgar foram observados nos grupos de pacientes com PE e PSHC. A utilização do tratamento não alterou os parâmetros perinatais em relação aos grupos com HG. O grupo de pacientes com PE apresentou a menor idade gestacional e o menor índice de Apgar quando comparado ao grupo controle. CONCLUSÃO: A introdução da terapia anti-hipertensiva durante a gestação foi de fundamental importância para o atendimento à gestante com SHG, embora tenha proporcionado poucos avanços em relação à prevenção das intercorrências perinatais, pois não houve alteração dos parâmetros gestacionais nos casos em que se comparou a utilização do tratamento. A medicação utilizada pouco interfere no fluxo sangüíneo materno-fetal, e conseqüentemente, nas condições de nascimento da criança.

OBJECTIVE: To compare the maternal-fetal clinical intercurrences and the effectiveness of treatment in the different clinical forms of hypertensive syndromes during pregnancy (HSP). METHODS: Medical records of 200 pregnant women with HSP were reviewed to appraise fetal intercurrences, classification of the hypertensive syndrome and use of antihypertensives. RESULTS: Of the 200 patients analyzed, 85 (42.5 percent) were controls; 32 (16 percent) presented gestational hypertension (GH), 67 (33.5 percent) had Pre-eclampsia (PE), 6 (3 percent) had chronic hypertension and 10 (5 percent) cases had PE superimposed chronic hypertension (PSCH). The lowest values for gestational age, weights of the newborn and for the Apgar index were observed in the patients with PE and PSCH. Treatment did not alter the Apgar index in relation to control and non-treated GH patients. Patients with PE presented the lowest gestational age and the smallest Apgar index when compared to controls. CONCLUSION: Introduction of an antihypertensive therapy during gestation was of fundamental importance for health improvement and pressure control of the pregnant woman with HSP. Nevertheless, it has been of little help for prevention of perinatal intercurrences. This was substantiated by the absence of improvement in the gestational conditions between the treated group when compared to the non-treated. Medication did not significantly improve the maternal-fetal blood flow and consequently in the birth condition of the child.

Kinetics and mechanisms of cholesterol esterase inhibition by cardiovascular drugs in vitro.

Cardiovascular drugs such as lovastatin, simvastatin, amlodipine besylate, nifedipine, and hydralazine hydrochloride inhibit cholesterol esterase (CEase) in vitro. In the present paper, an attempt was made to determine kinetically the reaction mechanism for CEase inhibition by these drugs. The inhibition constant, Ki, for the mixed-type inhibition of CEase by these drugs in the presence of triton-X-100 or taurochloate were measured. Moreover, the pKi values were correlated with the molecular weights of these drugs. In conclusion, the fact that these drugs lower cholesterol levels in the plasma low-density lipoprotein may be partially due to the CEase inhibition by these drugs.