Anabel Puig-Ramos

U-69593, a Kappa Opioid Receptor Agonist, Decreases Cocaine-Induced Behavioral Sensitization in Female Rats

This study was designed to investigate if the kappa opioid system regulates the locomotor response to cocaine in the female rat and to determine if the effect is dependent on estradiol treatment. Adult rats were ovariectomized (OVX) and half received an estradiol (OVX-EB) implant. After a week, rats were injected for 5 consecutive days with vehicle or with the kappa opioid receptor (KOPr) agonist U-69593 (0.16, 0.32, and 0.64 mg/kg) 15 min prior to cocaine injection (15 mg/kg). Following a 7-day drug-free period, rats were challenged with cocaine (Day 13). The locomotor response to cocaine was measured on Days 1, 5, and 13. U-69593 (0.32 mg/kg) decreased cocaine-induced locomotor activity in drug-naïve OVX rats and in those that received the OVX-EB implant. These results indicate that the acute effects of U-69593 are independent of estradiol treatment. Repeated exposure to U-69593 (0.32 mg/kg) prior to cocaine decreased the development of behavioral sensitization in OVX-EB-implanted rats. This decrease in cocaine-induced hyperlocomotion persisted after 1 week of cocaine withdrawal. These data indicate that the KOPr system participates in estradiol modulation of cocaine-induced behavioral sensitization in the female rat.

Estrogen receptors mediate estradiol's effect on sensitization and CPP to cocaine in female rats: role of contextual cues.

Preclinical studies show that estradiol enhances sensitization to cocaine in females by mechanisms not fully understood. These studies consistently show that ovariectomized (OVX) rats exhibit little or no sensitization to cocaine compared to OVX rats administered estradiol. In this study we varied the dose of cocaine (10, 15, and 30mg/kg), the length of cocaine treatment (from 5 to 10days) and the context of cocaine injections to determine if these factors play a role on estradiols effects on cocaine sensitization. Because OVX rats are hormonally compromised, they are not representative of the natural state of the animal, and thus the physiological context of these studies remains unclear. To address this issue, we blocked ERs in gonadally intact females by icv administration of the antiestrogen ICI-182,780. Varying the dose or length of exposure to cocaine does not alter estradiols effect on cocaine sensitization. In contrast, a highly context-dependent sensitization protocol results in robust sensitization even in OVX rats. Interestingly, using this protocol, sensitization in OVX rats diminished with time, suggesting that estradiol is necessary for the maintenance of cocaine sensitization. Blocking brain ERs with ICI completely abolishes the development and expression of cocaine sensitization in gonadally intact female rats, even when tested in a highly context-dependent sensitization protocol. Given these findings, we propose that activation of brain ERs is required for the development and maintenance of sensitization and CPP.

Incidence and Risk Factors for Developing Dengue-Associated Hemophagocytic Lymphohistiocytosis in Puerto Rico, 2008 - 2013

Background Hemophagocytic lymphohistiocytosis (HLH) is a rare, potentially fatal disorder characterized by fever, pancytopenia, hepatosplenomegaly, and increased serum ferritin. HLH is being increasingly reported as a complication of dengue, a common tropical acute febrile illness. Methodology/Principal Findings After a cluster of pediatric dengue-associated HLH patients was identified during the 2012–2013 dengue epidemic in Puerto Rico, active surveillance and a case-control investigation was conducted at four referral hospitals to determine the incidence of HLH in children and identify risk factors for HLH following dengue. Patients with dengue-associated HLH (cases) were matched by month of illness onset and admission hospital to dengue patients that did not develop HLH (controls). During 2008–2013, a total of 33 HLH patients were identified, of which 22 (67%) were associated with dengue and 1 died (dengue-associated HLH case-fatality rate: 4.5%). Two patients with dengue-associated HLH had illness onset in 2009, none had illness onset during the 2010 dengue epidemic, and 20 had illness onset during the 2012–2013 epidemic. Frequency of infection with either dengue virus (DENV)-1 or DENV-4 did not differ between cases and controls. Cases were younger than controls (median age: 1 vs. 13 years, p < 0.01), were hospitalized longer (18 vs. 5 days, p < 0.01), and were admitted more frequently to pediatric intensive care units (100% vs. 16%, p < 0.01). Cases had co-infection (18.2% vs. 4.5%, p = 0.04), recent influenza-like illness (54.5% vs. 25.0%, p = 0.01), and longer duration of fever (7 vs. 5 days; p < 0.01). Cases were more likely to have lymphadenopathy, hepatomegaly, splenomegaly, anemia, and elevated liver transaminases (p ≤ 0.02). Conclusions/Significance During this cluster of dengue-associated HLH cases that was temporally associated with the 2012–2013 epidemic, most patients with dengue-associated HLH were infants and had higher morbidity than dengue inpatients. Physicians throughout the tropics should be aware of HLH as a potential complication of dengue, particularly in patients with anemia and severe liver injury.

114: PRISM III VS. RACHS-1 AS PREDICTORS OF MORTALITY IN CHILDREN WHO UNDERWENT CARDIAC SURGERY

Crit Care Med 2015 • Volume 43 • Number 12 (Suppl.) PCICU within 7 days of initial discharge. Methods: We retrospectively reviewed an emergency response database that records all acute decompensations outside ICU, at a tertiary care academic pediatric hospital over a three-year period. All patients who were in PCICU, 7 or fewer days before the acute decompensation and readmitted to ICU were included in this study. Results: Fifty-six readmissions after acute decompensation in 50 patients were studied. Median age at readmission was 4.9 mo. 21(38%) events occurred in patients with single ventricle (SV) physiology, 24(42%) with biventricular physiology (BV) and 11(20%) with acquired heart disease (AHD). Hypoplastic left heart syndrome (post Norwood and systemic to pulmonary shunt) comprised more than half of SV cases; common atrioventricular canal or repaired anomalous pulmonary venous return were more than half of the BV cases, and dilated cardiomyopathy was the most likely AHD case. Cardiac surgery had occurred within 30 days of the readmission in 37(66%) cases. Echocardiographic and chest radiographic signs of worsening were present in 30% and 46% cases at readmission respectively. Interventions needed within 72 hr of ICU admission were: 1) ventilation (SV:28%, BV:33%, AHD:54%), 2) Hemodynamic support (SV:29%, BV:12.5%, AHD:27%). Mortality within 30 days of the readmission was 34% (SV: 43%, BV: 16%, AHD: 37%). Conclusions: Congenital heart disease patients are more likely to have ICU readmission after acute decompensation. Patients with single ventricle physiology and acquired heart disease are more likely to need ventilation and hemodynamic support after readmission and have higher 30-day mortality.