Soluble urinary somatic angiotensin converting enzyme is overexpressed in patients with preeclampsia: a potential new marker for the disease?

OBJECTIVE: The aim of this study was to identify and quantify urinary Angiotensin-Converting-Enzyme (ACE) in hypertensive disorders of pregnancy. METHODS: Urine samples were analyzed by Western blot. Patients were classified into: normotensive pregnancy (N); preeclampsia and superimposed preeclampsia (PE+SPE); and gestational hypertension (GH). RESULTS: Somatic ACE protein expression was higher in PE+SPE compared to N and GH. There was a positive correlation between ACE and urinary protein to creatinine ratio, systolic and diastolic blood pressures. CONCLUSION: These results indicate ACE overexpression in the urine of preeclamptic patients and suggest that it may be a new marker for the disease.

Mechanisms of vascular dysfunction in the interleukin-10-deficient murine model of preeclampsia indicate nitric oxide dysregulation.

Preeclampsia is a pregnancy-specific hypertensive disorder characterized by proteinuria, and vascular injury in the second half of pregnancy. We hypothesized that endothelium-dependent vascular dysfunction is present in a murine model of preeclampsia based on administration of human preeclamptic sera to interleukin-10-/- mice and studied mechanisms that underlie vascular injury. Pregnant wild type and IL-10-/- mice were injected with either normotensive or severe preeclamptic patient sera (sPE) during gestation. A preeclampsia-like phenotype was confirmed by blood pressure measurements; assessment of albuminuria; measurement of angiogenic factors; demonstration of foot process effacement and endotheliosis in kidney sections; and by accumulation of glycogen in placentas from IL-10-/- mice injected with sPE sera (IL-10-/-sPE). Vasomotor function of isolated aortas was assessed. The IL-10-/-sPE murine model demonstrated significantly augmented aortic contractions to phenylephrine and both impaired endothelium-dependent and, to a lesser extent, endothelium-independent relaxation compared to wild type normotensive mice. Treatment of isolated aortas with indomethacin, a cyclooxygenase inhibitor, improved, but failed to normalize contraction to phenylephrine to that of wild type normotensive mice, suggesting the additional contribution from nitric oxide downregulation and effects of indomethacin-resistant vasoconstricting factors. In contrast, indomethacin normalized relaxation of aortas derived from IL-10-/-sPE mice. Thus, our results identify the role of IL-10 deficiency in dysregulation of the cyclooxygenase pathway and vascular dysfunction in the IL-10-/-sPE murine model of preeclampsia and point towards a possible contribution of nitric oxide dysregulation. These compounds and related mechanisms may serve both as diagnostic markers and therapeutic targets for preventive and treatment strategies in preeclampsia.

Phosphodiesterase Inhibition in the Treatment of Preeclampsia: What Is New?

PURPOSE OF REVIEW: The present study intends to review the possibility of using phosphodiesterase inhibitors as a treatment option for preeclampsia, addressing potential risks and benefits. RECENT FINDINGS: Preeclampsia is the most common hypertensive disorder of pregnancy, often responsible for severe maternal and fetal complications, which can lead to early pregnancy termination and death. Despite the numerous studies, its pathophysiology is still unclear, although it seems to involve a multiplicity of complex factors related to angiogenesis, ineffective vasodilation, oxidative stress, inflammatory cytokines, and endothelial dysfunction. It has been hypothetically suggested that the use of phosphodiesterase inhibitors is capable of improving placental and fetal perfusion, contributing to gestational scenario, by decreasing the symptomatology and severity of this syndrome. In this literature review, it has been found that most of the studies were conducted in animal models, and there is still lack of evidence supporting its use in clinical practice. Research in human indicates conflicting findings; randomized controlled trials were scarce and did not demonstrate any benefit in morbidity or mortality. Data regarding to pathophysiological and interventional research are described and commented in this review. The use of phosphodiesterase inhibitors in the treatment of preeclampsia is controversial and should not be encouraged taking into account recent data.

Immature platelet fraction in hypertensive pregnancy.

BACKGROUND: Imbalance in hemostatic mechanisms can occur during pregnancy with a tendency for hypercoagulability and increased thrombosis risk. Pregnant women with hypertensive disorder, especially preeclampsia, show alterations in platelet indexes. Immature platelet fraction (IPF) has been suggested as a sensitive index for monitoring changes in platelet production and destruction. OBJECTIVES: To evaluate the IPF in patients diagnosed with a gestational hypertensive disorder (GHD). PATIENTS AND METHODS: A cross-sectional study was conducted at an University Hospital to estimate maternal blood IPF index in 99 pregnant women, divided into three groups: normotensive pregnancy (NP), preeclampsia syndrome (PES), and non-proteinuric hypertensive pregnancy (nPHP). Following ethical approval and written informed consent, samples were collected from 33 NP, 34 PES, and 32 nPHP women. Platelet indexes were measured by fluorescent flow cytometry. RESULTS: IPF and mean platelet volume (MPV) counts in GHD were significantly higher than in NP (IPF: 3.8, 2.4-5.1%; 8.6, 5.8-10.6%; 7.3, 4.2-10.2%; p < 0.001 and MPV: 10.6 ± 0.9 fL; 12.1 ± 1.0 fL; 11.6 ± 1.0 fL; p < 0.001 for NP, PES, and nPHP, respectively). No difference was detected between PES and nPHP groups. The distribution of patients with an IPF above 6.1%for NP, PES, and nPHP was 9%, 65%, and 43.8%, respectively (p < 0.001). IPF as a test to differentiate GHD from the controls achieved an area under the curve of 0.83 on a receiver operating characteristics curve. CONCLUSION: A distinct profile in platelet indexes was detected in hypertensive pregnancies. It suggests that these markers could be used in daily routine as an additional tool in the management of pregnant women.

Pneumonia da comunidade: diagnóstico e manejo inicial / Community pneumonia: diagnosis and initial management

A Pneumonia é a principal causa de morte por doença infecciosa em países subdesenvolvidos.¹ No Brasil, a pneumonia adquirida na comunidade é uma das principais causas de internação por doença. Afeta principalmente homens, com taxas de hospitalização mais elevadas em menores de 5 e maiores de 80 anos.²

Pneumonia is the first cause of death in underdeveloped countries.¹ In Brazil, Community-Acquired Pneumonia is one of the main causes of hospitalization due to disease. It affects mostly males, with higher hospital admission rates in those with less than 5 and more than 80 years old.²

Angiotensin Converting Enzyme 90 kDa isoform: Biomarker for diagnosis of preeclampsia?

Preeclampsia (PE), one of the leading gestational hypertensive diseases, is characterized by increased blood pressure (⩾140/90mmHg) and pathological proteinuria after 20weeks gestation. It is a complex, multifactorial syndrome with an unestablished etiology and cure. The search continues for a biomarker that could assist in the early prediction or diagnosis of PE, reducing the rate of maternal and fetal mortality. Based on the findings of Casarini et al. that suggest the 90kDa isoform of the Angiotensin Converting Enzyme (ACE) as a possible marker of hypertension, we hypothesized that this isoform may be present in pregnant women with PE, since they present a transient and spontaneous model of systemic arterial hypertension in pregnancy. We believe, therefore, that pregnant women with pure PE (PPE) express the ACE 90kDa isoform in urine, as well as having elevated isoform enzymatic activity, during pregnancy only. Postpartum, with the normalization of blood pressure, the protein isoform would no longer be expressed. Pregnant women with superimposed preeclampsia (SPE) would present the ACE 90kDa isoform both during and after the gestation period, and its enzymatic activity would remain high as they are chronically hypertensive. It is expected that normotensive pregnant women do not present this isoform in their urine as elevated blood pressure levels do not occur. Both normotensive and PPE affected pregnant women with a family history of hypertension, will possibly express the ACE 90kDa isoform before pregnancy and may become hypertensive, only after some years, through the influence of environmental factors and/or other diseases. If our hypothesis is confirmed, it will allow differentiation of PPE and SPE sooner than 12weeks postpartum, which is currently the estimated period for confirmation of the specific diagnosis. Furthermore, it could be an early biomarker for predicting the disease, enabling the physician to choose the best clinical management. In addition, it would minimize the use of other methods as the biological sample for obtaining the marker is urine, a practical and effective test with good reproducibility. Finally, test results would enable a greater understanding of the mechanisms involved in gestational hypertension.

Arterite de Takayasu diagnosticada durante o puerpério em mulher com doença hipertensiva gestacional: relato de caso / Takayasu Arteritis diagnosed during puerperium in a woman with pregnancy-induced hypertension: Case report

Objetivos: Descrever um caso de Arterite de Takayasu diagnosticada durante o puerpério precoce, demonstrando a importância da aferição adequada da pressão arterial para o diagnóstico da doença hipertensiva gestacional.Descrição do caso: Uma mulher de 40 anos, em sua quarta gestação, com idade gestacional de 36 semanas e três dias, foi hospitalizada por gestação de alto risco devido a hipertensão arterial sistêmica crônica. Durante a internação observou-se diferença nos níveis tensionais e assimetria de pulsos entre os membros superiores. No pós-parto a paciente foi submetida à ecografia de carótidas com Doppler, que demonstrou oclusão de artéria carótida comum esquerda e de artéria subclávia esquerda, levando ao diagnóstico de Arterite de Takayasu.Conclusões: O diagnóstico precoce da Arterite de Takayasu é difícil, pois as manifestações iniciais são inespecíficas e os sintomas discretos. Entretanto, um exame físico cuidadoso pode evidenciar sinais que suscitem suspeitas e justifiquem investigação adicional, podendo prevenir um desfecho negativo, especialmente no período gestacional.

Aims: To describe a case of Takayasu arteritis diagnosed during the early postpartum period, demonstrating the importance of proper blood pressure measurement for the diagnosis of gestational hypertension.Case description: A 40 year old woman in her fourth pregnancy, with gestational age of 36 weeks and three days, was hospitalized for highrisk pregnancy due to chronic hypertension. During hospitalization, difference in blood pressure levels and pulse asymmetry between the upper limbs were observed. In the postpartum the patient underwent carotid Doppler ultrasound, which showed occlusion of the left common carotid artery and left subclavian artery, leading to the diagnosis of Takayasu arteritis. Conclusions: Early diagnosis of Takayasu arteritis is difficult because initial manifestations are nonspecific and symptoms are mild. However, a careful physical examination may reveal signs that raise suspicion and warrant further investigation, which may prevent a negative outcome, especially during pregnancy.