Determinação de adenosina deaminase, fator de necrose tumoral-alfa e interleucina-1 em gestantes portadoras de pré-eclâmpsia

Preeclampsia is a specific disorder of pregnancy, characterized by arterial hypertension and proteinuria detected after 20 weeks of gestation. This pathology is associated with hyperuricemia, higher levels of pro-inflammatory cytokines, enhanced leukocyte activation and oxidative stress. Adenosine deaminase (ADA) is an enzyme present in all human tissues and, it is involved with the maturation of the immune system. Although its function is not fully understood, ADA is considered an indicator of cellular inflammation and, its increased serum concentration is observed in inflammatory diseases, such as tuberculosis and rheumatoid arthritis. This study aimed to assess serum ADA levels in preeclamptic patients (PE) compared with normotensive pregnant (NT) and non-pregnant women (NP), and to correlate these values with TNF-α and IL-1β production. Ninety pregnant women were included: 60 were pre-eclamptic and 30 were normotensive matched for gestational age. As control group 20 healthy non-pregnant women matched with pregnant for age were included. Peripheral blood mononuclear cells (PMMC) obtained from the three groups studied were cultured with or without lipopolysaccharide (LPS) for 18h at 37oC, and TNF-α and IL-1β production was assessed in the supernatant of cultures by enzyme immunoassay (ELISA). ADA plasmatic concentration was determined by colorimetric method. The results show that ADA plasma levels were significantly higher in PE group compared with NT and NP groups. A positive correlation between ADA and uric acid levels was detected in preeclamptic women. There was no significant difference in relation to ADA levels when PE patients were classified in early and late-onset PE. The endogenous production of IL-1β and TNF-α by PBMC was significantly higher in PE group than in NT and NP women, showing the activation state of these cells in PE. LPS induced...(Complete abstract click electronic access below)

Efeitos da exposição pré-natal ao etanol e ao chumbo, isoladamente e em associação, sobre a pressão arterial e a reatividade da aorta de ratos recém-desmamados

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

High sodium intake during postnatal phases induces an increase in arterial blood pressure in adult rats

Coordenadoria de Aperfeiçoamento em Pesquisa (CAPES)

Effects of different inspired oxygen fractions on sildenafil-induced pulmonary anti-hypertensive effects in a sheep model of acute pulmonary embolism

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Effects of NAMPT polymorphisms and haplotypes on circulating visfatin/NAMPT levels in hypertensive disorders of pregnancy

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

The effect of non-antihypertensive doses of angiotensin converting enzyme inhibitor on myocardial necrosis and hypertrophy in young rats with renovascular hypertension

In renovascular hypertensive rats, low doses of angiotensin converting enzyme (ACE) inhibitors have been found to prevent myocardial hypertrophy independent of blood pressure level. This finding would suggest humoral rather than mechanical control of myocyte growth. The aim of this study was to examine the effect of nonantihypertensive doses of ACE inhibitor on myocardial hypertrophy and necrosis in hypertensive rats. Renovascular hypertension (RHT) was induced in four-week-old Wistar rats. Twenty-eight animals were treated for four weeks with three doses of ramipril (0.01, 0.1 or 1. 0 mg/kg/day, which are unable to lower blood pressure. Fourteen animals were not treated (RHT group). A sham operated, age/sex-matched group was used as control (n = 10). Myocardial histology was analysed in 3 microm thick sections of the ventricle stained with either haematoxylin-eosin, reticulin silver stain or Masson's trichrome. There was a significant correlation between systolic blood pressure and left ventricular to body weight ratio in both sets of animals: untreated plus controls and ramipril-treated rats. ACE inhibition prevented myocyte and perivascular necrosis and fibrosis in a dose-dependent manner. We conclude that myocardial hypertrophy in rats with renovascular hypertension is directly related to arterial pressure, and that this relationship is not affected by nonantihypertensive doses of ACE inhibitor. Myocardial necrosis/fibrosis and coronary artery damage induced by angiotensin II are prevented by ACE inhibitor in a dose-dependent manner, despite the presence of arterial hypertension.

Intrauterine growth restricted rats exercised before and during pregnancy: maternal and perinatal repercussions

This study aimed at evaluating the effect of swimming before and during pregnancy on rats born with intrauterine growth restriction (IUGR) and their offspring. For this, nondiabetic and streptozotocin-induced severely diabetic (SD) pregnant rats were mated and generated offspring with appropriate (control, C) and small (IUGR) for pregnancy age, respectively. Following that, C and IUGR groups were further distributed into nonexercised control (C), exercised control (Cex), nonexercised IUGR (IUGR), and exercised IUGR (IUGRex). IUGR rats presented lower mating rate than control rats. Regardless of physical exercise IUGR rats presented decreased body weight from birth to lactation. At 90 days of life, IUGR rats presented glucose intolerance. Maternal organ weights were increased and relative adiposity of IUGRex rats was lower than Cex. IUGR and IUGRex offspring presented reduced body weight than C and Cex, respectively. IUGRex dams presented an increased rate of appropriate for pregnancy age newborns. IUGEex male and female offspring relative brain weight was increased compared with Cex. Therefore, swimming before and during pregnancy prevented glucose intolerance, reduced general adiposity, and increased maternal and offspring organ weight in rats, showing the benefit of physical exercise for IUGR rats.

Sodium nitrite prevents both reductions in circulating nitric oxide and hypertension in 7-day lead-treated rats

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Adrenomedullin induces pulmonary vasodilation but does not attenuate pulmonary hypertension in a sheep model of acute pulmonary embolism

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Análise de inflamassoma induzido por urato monossódico em monócitos de gestantes portadoras de pré-eclampsia

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Coupling between respiratory and sympathetic activities as a novel mechanism underpinning neurogenic hypertension

Enhanced sympathetic outflow to the heart and resistance vessels greatly contributes to the onset and maintenance of neurogenic hypertension. There is a consensus that the development of hypertension (clinical and experimental) is associated with an impairment of sympathetic reflex control by arterial baroreceptors. More recently, chronic peripheral chemoreflex activation, as observed in obstructive sleep apnea, has been proposed as another important risk factor for hypertension. In this review, we present and discuss recent experimental evidence showing that changes in the respiratory pattern, elicited by chronic intermittent hypoxia, play a key role in increasing sympathetic activity and arterial pressure in rats. This concept parallels results observed in other models of neurogenic hypertension, such as spontaneously hypertensive rats and rats with angiotensin II–salt-induced hypertension, pointing out alterations in the central coupling of respiratory and sympathetic activities as a novel mechanism underlying the development of neurogenic hypertension.

Resolution of tremor fluoxetine-induced in an elderly patient

Aim: To report a possible case of tremor fluoxetine-induced treated as Parkinson’s disease in an elderly female patient noncompliant with the pharmacotherapy, with uncontrolled hypertension and using fluoxetine to treat depression. Presentation of Case: Patient complained of sleepiness in the morning, agitation, anxiety, insomnia and mental confusion. Her greatest concern was about bilateral hand tremors which, in her view became, worse after biperiden was prescribed. Therefore, she stopped taking it. The initial medication was: omeprazole, losartan, biperiden, fluoxetine, atenolol + chlorthalidone, acetylsalicylic acid, atorvastatin and diazepam. Pharmacotherapeutic follow up was performed in order to check the necessity, safety and effectiveness of treatment. Discussion: During the analysis of pharmacotherapy, the patient showed uncontrolled blood pressure and had difficulty complying with the treatment. Thus, in view of the complaints expressed by the patient, our first hypothesis was a possible serotonin syndrome related to fluoxetine use. We proposed a change in the fluoxetine regime and discontinuation of biperiden. As tremors persisted, we suggested the replacement of fluoxetine by sertraline, since a possible tremor fluoxetine-induced could explain the complaint. This approach solved the drug-related problem identified. Conclusion: Tremors reported by the patient was identified as an iatrogenic event related to fluoxetine, which was solved by management of serotonin-reuptake inhibitors.

Pancreatic hemangioma manifesting as variceal gastroesophageal bleeding during pregnancy: case report

There are only 10 reported cases of pancreatic hemangiomas in adults, only one of them causing digestive bleeding. We present a case of variceal bleeding and portal hypertension caused by a pancreatic hemangioma. The patient had 19 year-old and was received at her 16th week of pregnancy. She had massive hematemesis, controlled after variceal band ligation. Her image exams revealed a cystic lesion of 164 cm³ in the pancreas tail and signs of portal hypertension. Two months after, the ultrassonographic exam documented the lesion growth, achieving 200 cm³ at that time. The patient was submitted to distal pancreatectomy, and the histopathological analysis revealed a pancreatic hemangioma of 11 x 9 x 8 cm. Therefore, we report the second case of digestive bleeding caused by a pancreatic hemangioma, which had a well documented growth during the pregnancy. Additionally, we review the previous reports of pancreatic hemangiomas and discuss the hypothesis of hormonal infl uence on the natural history of these tumors.

Effects of Matrix Metalloproteinase (MMP)-2 Polymorphisms on Responsiveness to Antihypertensive Therapy of Women with Hypertensive Disorders of Pregnancy

Imbalanced matrix metalloproteinase (MMP) expression, including MMP-2, has been demonstrated in pre-eclampsia. However, little is known about the effect of polymorphisms in MMP-2 gene on hypertensive disorders of pregnancy. We examined whether two functional MMP-2 polymorphisms (g.-1306C>T and g.-735C>T) are associated with pre-eclampsia and/or gestational hypertension and whether these polymorphisms affect therapeutic responses in women with these conditions. We studied 216 healthy pregnant women (HP), 185 patients with gestational hypertension (GH) and 216 patients with pre-eclampsia (PE). They were stratified as responsive or non-responsive to antihypertensive therapy according to clinical and laboratorial parameters of therapeutic responsiveness. Genomic DNA was extracted from whole blood and genotypes for g-1306C>T and g.-735C>T polymorphisms were determined by real-time PCR using Taqman allele discrimination assays. Haplotype frequencies were inferred using the PHASE 2.1 program. The distributions of MMP-2 genotypes and haplotypes were similar in HP, GH and PE patients (p > 0.05). In addition, we found no significant differences in MMP-2 genotype or haplotype frequencies when GH or PE patients were classified as responsive or non-responsive to antihypertensive therapy (p > 0.05). Our results suggest that MMP-2 polymorphisms do not affect the susceptibility to hypertensive disorders of pregnancy. In parallel, MMP-2 polymorphisms apparently do not affect the responsiveness to antihypertensive therapy of women with these hypertensive disorders of pregnancy.

eNOS Tag SNP Haplotypes in Hypertensive Disorders of Pregnancy

Haplotypes formed by polymorphisms (T-786C, rs2070744; a variable number of tandem repeats in intron 4, and Glu298Asp, rs1799983) of the eNOS gene were associated previously with gestational hypertension (GH) and preeclampsia (PE). However, no study has explored the Tag SNPs rs743506 and rs7830 in these disorders. The aim of the current study was to compare the distribution of the genotypes and haplotypes formed by the five eNOS polymorphisms mentioned among healthy pregnant (HP, n = 122), GH (n = 138), and PE (n = 157). The haplotype formed by "C b G G C" was more frequent in HP compared to GH and PE (p = 0.0071), which is supported by previous findings that demonstrated the association of the combination "C b G" with a higher level of nitrite (NO marker). Our results suggest a protective effect of the haplotype "C b G G C" against the development of hypertensive disorders of pregnancy.