Ex situ regeneration of liver remnants hypothermically preserved for 24 hours.

INTRODUCTION: After partial hepatectomy (PH), the liver remnant (LR) shows a regenerative response, always keeping a percent relationship with the host. This process has been well described in the literature, but several aspects still need to be understood. There are no studies on hepatic LR regeneration during hypothermic preservation. Thus, the objective of the present study was to analyze LR regeneration after PH under conditions of hypothermal preservation. MATERIALS AND METHODS: Twenty adult Wistar rats were divided into 4 experimental groups: PHS (70% PH); PHP (70% PH of an organ perfused and preserved for 24 hours); PWL (perfused whole liver preserved for 24 hours); and NPWL (nonperfused whole liver). The liver was perfused with 250 mL Celsior solution with a catheter connected to a 1.30-cm-high liquid column. Hepatic tissue samples were submitted to immunohistochemical analysis for the evaluation of protein Ki67 expression, related to the mechanism of cell proliferation, to analysis of micro-RNA expression (miR-21 and miR-16) by real-time polymerase chain reaction, and to analysis of mitochondrial function. Nonparametric statistical analysis was used (P < .05). RESULTS: Ki67 analysis revealed that the PHP group showed 17.41% cell proliferation in LR (P < .01) compared to PHS (42.22%), PWL (11.43%), and NPWL (11.98%). miR-16 expression (proapoptotic) was found to be higher in the NPWL group compared to all others (PHS, PHP, and PWL), with a statistically significant difference between the NPWL group and the PHS and PHP groups. CONCLUSION: The animals submitted to PHS and PHP presenting greater Ki67 expression showed low miR-16 expression, indicating a low apoptotic index. In summary, the LR showed ex situ regeneration even under hypothermal conditions. There are no similar data in the literature surveyed.

PP091. Prematurity and hypertensive disorders in pregnancy. A major public health problem.

INTRODUCTION: Around the world each year 10% to 15% of direct maternal deaths are associated with hypertensive disorders in pregnancy. Not only it can be devastating and life threatening for the mothers but also for the babies. Risks for the baby include poor growth and prematurity [1]. In low and middle income countries many public hospitals have limited access to neonatal intensive care, and so the mortality and morbidity is likely to be considerably higher than in settings where such facilities are available. Thus, the approach to the problem preeclampsia should include issues related to prematurity and its impact, since many of these babies develop definitive complications, constituting a major public health problem with social and economic repercussions. OBJECTIVES: To evaluate the prevalence of preterm births in a public hospital health of the city of São Paulo, checking its main causal conditions, focusing in particular on the importance of hypertensive disorders in its determinism. METHODS: This was a retrospective study of a consecutive series of preterm infants, defined as gestational age less than 37 weeks born at Maternity School Vila Nova Cachoeirinha, situated at the north of Sao Paulo City, in the period from 01/04 to 31/12/2011. The study population was classified according to three main groups of causal factors: spontaneous labor, premature rupture of membranes and elective preterm delivery. In this group was evaluated the specific participation of hypertensive disorders. RESULTS: The number of live births during the study period was 5302 babies. Among these 433 had gestational age less than 37 weeks, corresponding to a prematurity rate of 8.16%. Of all infants, 385 cases were included in the analysis. Regarding the causes of the onset of preterm labor found that 140 cases (36.4%) presented with spontaneous labor, 128 cases (33.2%) had premature rupture of membranes and 117 (30.4%) cases were born as a result of elective preterm delivery. In the latter group 88 cases (75.2%) had complications related to hypertensive disorders. Regarding the general population of premature infants, hypertension accounted for 22.8% of cases. CONCLUSION: We conclude that among the various obstetric problems, hypertensive disorders represent an important impact on preterm birth in our setting, considering that our institution is a reference to this type of care across the city of São Paulo. This knowledge is a fundamental tool to support the adoption of interventions that can detect groups at risk for hypertension in pregnancy, the promotion of follow-up to intercept severe cases and provide an efficient network of maternity care that may have neonatal intensive care units. This set of measures is essential to minimize the impact of this serious problem.

PP163. Are we using magnesium sulphate excessively for preeclamptic patients?

INTRODUCTION: There is now evidence that magnesium sulfate can prevent and control eclamptic seizures. For women with pre-eclampsia, magnesium sulfate reduces by more than one half the risk of eclampsia. After Magpie Trial [1] our clinical practice has been modified in terms of more liberal use of MgSO4, but the evidence regarding the benefit-to-risk ratio of MgSO4 prophylaxis in mild preeclampsia remains uncertain [2]. Thus we consider important to evaluate whether there are specific characteristics between patients who received the medicine that might signal risk and justify our decisions. OBJECTIVES: To identify in a group of hypertensive patients who used magnesium sulfate, clinical and/or laboratory characteristics that can be defined as specific risk factors and be useful to base clinical decisions. METHODS: The study was conducted at the Maternity School of Vila Nova Cachoeirinha, a public institution located in the north of the city of São Paulo (Baazil) between 01/07 and 31/12/2011. This is a retrospective study of a series of 103 pregnant women with hypertensive disorders, defined according to NHBPEP. We excluded patients admitted in labor. Patients were assigned into two groups according to the use of MgSO4. We compared clinical and laboratory characteristics between the two groups. RESULTS: Of 103 patients included, 31 (30.1%) received MgSO4. Among the outcomes analyzed, there were significant differences in the group that received MgSO4 in terms of blood pressure equal to or greater than 110mmHg, clinical symptoms (eg headache and visual disturbance) and at least some evidence of organ dysfunction (hepatic, renal, haematologic, or central nervous system) (Table 1). Table 1. Variables associated with theuse of magnesium sulfate. CONCLUSION: We can say that in our institution over the years was an increase in the use of magnesium sulfate. Our results support the hypothesis that about one in three patients treated at this institution receive the medication. Although our protocol admits that the decision may be based on subjective criteria, we identified some objective characteristics that supported their application, and that these criteria do not differ from the classic recommendations. We can also conclude that in our clinical experience we do not have identified a clear justification for support the routinely use of magnesium sulphate for all women with preeclampsia.

Effects of a BLT receptor antagonist on local and remote reperfusion injuries after transient ischemia of the superior mesenteric artery in rats.

Reperfusion of ischemic vascular beds may lead to recruitment and activation of leukocytes, release of mediators of the inflammatory process and further injury to the affected vascular bed and to remote sites. Neutrophils appear to play a major role in the pathophysiology of reperfusion injury. Amongst inflammatory mediators shown to activate neutrophils and induce their recruitment in vivo, much interest has been placed on the role of leukotriene (LT)B(4). Here, we have assessed the effects of the BLT receptor antagonist (+)-1-(3S, 4R)-[3-(4-phenyl-benzyl)-4-hydroxy-chroman-7-yl]-cyclopentane carboxylic acid (CP 105,696) in a model of neutrophil-dependent ischemia and reperfusion injury in the rat. The superior mesenteric artery was isolated and ischemia was induced by its total occlusion for 30 min. After 30 min of reperfusion, injury was assessed by evaluating the extravasation of Evans blue, an index of vascular permeability, and the levels of myeloperoxidase, an index of neutrophil accumulation, in the intestine, mesentery and lung. The neutrophil-dependence of the local (intestine and mesentery) and remote (lung) injury was confirmed by using fucoidin, a selectin blocker, and WT-3, an anti-CD18 monoclonal antibody. Post-ischemic treatment with CP 105,696 dose-dependently inhibited vascular permeability and neutrophil accumulation in the intestine and mesentery. CP 105,696 also blocked the vascular permeability changes, but not neutrophil accumulation, in the lungs after reperfusion injury. Virtually identical results were obtained with another BLT receptor antagonist, 1-(5-ethyl-2-hydroxy-4-(6-methyl-6-(1H-tetrazol-5-yl)-heptoxy++ +)-phenyl )ethanone (LY255283). Our results suggest that post-ischemic treatment with BLT receptor antagonists may inhibit local and remote ischemia and reperfusion injury by blocking both the accumulation and/or activation of neutrophils.

Scorpion venom-induced neutrophilia is inhibited by a PAF receptor antagonist in the rat.

A dramatic blood neutrophilia is an important feature of the severe envenoming caused by the Brazilian scorpion Tityus serrulatus and may contribute to the development of lung injury in children. We examined the effects of an intravenous injection of T. serrulatus scorpion venom (TsV) on the total number of leukocytes and neutrophils in the blood of anesthetized rats. Injection of TsV (250 microg/kg) induces a significant leukocytosis 2 and 3 h after its injection, explained by an increase in the number of neutrophils. The release of catecholamines and action on adrenoceptors is responsible for most of the systemic manifestations of TsV. However, pretreatment with the beta-adrenoceptor antagonists metoprolol and propranolol or the alpha1-adrenoceptor antagonist prazosin (0.25 mg/kg) did not prevent TsV-induced neutrophilia. Blood neutrophilia induced by TsV occurred simultaneously with a significant reduction of mature neutrophils in bone marrow. Pretreatment with the platelet-activating factor (PAF) receptor antagonists UK-74505 or WEB-2086 prevented TsV-induced increase in blood neutrophils and reduction in the number of neutrophils in the bone marrow. It is concluded that scorpion venom induces blood neutrophilia in rats, explained by a PAF receptor-dependent mobilization of neutrophils from the bone marrow.

Effects of the PAF receptor antagonist UK74505 on local and remote reperfusion injuries following ischaemia of the superior mesenteric artery in the rat.

The effects of the long lasting and potent PAF receptor antagonist UK74505 were assessed on the local and remote injuries following ischaemia and reperfusion (I/R) of the superior mesenteric artery (SMA) in rats. In a severe model of ischaemia (120 min) and reperfusion (120) injury, in addition to the local and remote increases in vascular permeability and neutrophil accumulation, there was significant tissue haemorrhage, blood neutropenia, systemic hypotension and elevated local and systemic TNF-alpha levels. Post-ischaemic treatment with the selectin blocker fucoidin (10 mg kg(-1)) prevented neutrophil accumulation in tissue and, in consequence, all the local and systemic injuries following severe I/R. Treatment with an optimal dose of UK74505 (1 mg kg(-1)) also reversed local and remote neutrophil accumulation, increases in vascular permeability and intestinal haemorrhage. UK74505 partially inhibited blood neutropenia and reperfusion-induced hypotension. Interestingly, both fucoidin and UK74505 prevented the local, but not systemic, increases of TNF-alpha levels following severe I/R injury, demonstrating an important role of migrating cells for the local production of TNF-alpha. However, the results do not support a role for PAF as an intermediate molecule in the production of systemic TNF-alpha. The beneficial effects of UK74505 and other PAF receptor antagonists in models of I/R injury in animals and the safety of UK74505 use in man warrant further investigations of the use of this drug as preventive measure for I/R injury in humans.