HMG-CoA reductase inhibitors inhibit endothelial exocytosis and decrease myocardial infarct size

Three-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors protect the vasculature from inflammation and atherosclerosis by cholesterol dependent and cholesterol independent mechanisms. We hypothesized that HMG-CoA reductase inhibitors decrease exocytosis of Weibel-Palade bodies, endothelial cell granules whose contents promote thrombosis and vascular inflammation. We pretreated human aortic endothelial cells with simvastatin for 24 hours, then stimulated the cells with thrombin, and measured the amount of vWF released into the media. We then measured the effect of simvastatin on myocardial infarction in mice. Simvastatin decreased thrombin-stimulated Weibel-Palade body exocytosis by 89%. Simvastatin inhibited exocytosis in part by increasing synthesis of nitric oxide (NO), which S-nitrosylated N-ethylmaleimide sensitive factor (NSF), a critical regulator of exocytosis. Simvastatin treatment attenuated myocardial infarct size by 58% in wild-type but not eNOS knockout mice. Furthermore, simvastatin decreased endothelial exocytosis and neutrophil infiltration into ischemic-reperfused myocardium, which was mediated in part by P-selectin contained in Weibel-Palade bodies. However, simvastatin did not affect exocytosis and inflammation in myocardial infarcts of eNOS knockout mice. Inhibition of endothelial exocytosis is a novel mechanism by which HMG-CoA reductase inhibitors may reduce vascular inflammation, inhibit thrombosis, and protect the ischemic myocardium. These findings may explain part of the pleiotropic effects of statin therapy for patients with cardiovascular disease.     

Lower respiratory tract infections among american Indian and Alaska Native children and the general population of U.S. Children

BACKGROUND AND OBJECTIVE: Lower respiratory tract infections (LRTIs) cause substantial childhood morbidity. This study characterizes and compares LRTI-associated morbidity among American Indian/Alaska Native (AI/AN) children and the general population of U.S. children. METHODS: Hospitalization and outpatient records with a diagnosis indicating LRTIs were evaluated for children aged younger than 5 years during 1990-2001. RESULTS: For 1999-2001, the LRTI-associated hospitalization rate was significantly higher for AI/AN children than for U.S. children (116.1 versus 63.2/1000, respectively), with the disparity being greater for infants than for 1- to 4-year-old children. Also the rate of LRTI-associated outpatient visits among AI/AN infants was higher than that for all U.S. infants (737.7 versus 207.2/1000, respectively). LRTI hospitalization and outpatient visit rates were highest in the Alaska and Southwest Indian Health Service regions. During 1990-2001, the LRTI hospitalization rate among AI/AN infants in the Alaska region and among the general U.S. infant population increased. Bronchiolitis-associated hospitalization rates increased for AI/AN and U.S. infants, whereas the pneumonia-associated hospitalization rate decreased among AI/AN infants and remained stable among U.S. infants. CONCLUSIONS: LRTIs continue to be an important cause of morbidity in children, especially among AI/AN infants in the Alaska and Southwest regions. Strategies to reduce LRTI hospitalizations and outpatient visits are warranted for all infants, but the greatest potential impact would be among AI/AN infants.     

Dextran or polyethylene glycol added to curosurf for treatment of meconium lung injury in rats

BACKGROUND: In experimental lung injuries, improvement of lung function after treatment with surfactant/polymer mixtures may depend on both type of polymer and the specific surfactant. In vitro studies suggest that dextran is more effective when mixed with Curosurf, and polyethylene glycol (PEG) is more effective when mixed with Survanta. We therefore wanted to find out whether these results held true in an animal model of acute lung injury. OBJECTIVE: To compare the response to therapy of PEG vs. dextran when added to Curosurf after meconium lung injury. METHODS: Lung injury was produced by intratracheal instillation of meconium (30 and 4 ml/kg). One hour after injury, Curosurf (35 mg/ml) with or without 5% dextran (68 kDa) or 5% PEG (10 kDa) was given. Arterial blood gases and peak inspiratory pressures were measured for 3 h after treatment while animals were supported by volume-regulated ventilation. Then animals were sacrificed and pressure volume relationships, lung wet/dry weights, and histology were assessed. RESULTS: Initially, improved PaO2 and inspiratory pressure occurred for both Curosurf/PEG and Curosurf/dextran groups compared with Curosurf, but at three hours, peak inspiratory pressure and PaO2 remained significantly improved for the Curosurf/dextran but not for Curosurf/PEG groups when compared with Curosurf alone. Total lung capacity at the end of the experiment was also significantly increased in the Curosurf/dextran group, but not the Curosurf/PEG group when compared with Curosurf. CONCLUSION: Under these experimental conditions, Curosurf/dextran mixtures provided a better therapeutic response than Curosurf/PEG or Curosurf.     

Language development in preschool-age children adopted from China.

This study examined the language development of 55 preschool-age children adopted from China who had resided in their permanent homes for approximately 2 years or longer. Slightly over 5% of the children scored below average on 2 or more measures from a battery of standardized speech-language tests normed on monolingual English speakers. However, the vast majority scored within or well above the average range on 2 or more measures. Contrary to other reports on the language development of internationally adopted children, the results suggest that "second first language" acquisition proceeds rapidly in the majority of preschool-age children adopted as infants and toddlers. For the children in the sample who scored below average, results indicated that they were among the children who had been exposed to English for the least amount of time. The results of this study demonstrate both the robustness of the language system in the majority of adopted children from China as well as slower growth in a small subset of lower performers in the 1st years after adoption.     

Sexual abuse of vulnerable young and old women: a comparative analysis of circumstances and outcomes

Aggregated data from 125 substantiated Adult Protective Services cases of sexually abused women were collected during a 5-year period. Women older than 59 years represented 63% of the cases. Regardless of age, the most common types of abuse involved sexualized kissing and fondling and unwelcome sexual interest in the women's body. Most identified perpetrators were older males. Family members were most likely to abuse women living in the community, whereas women living in facilities usually experienced abuse by another resident. Perpetrators were prosecuted and convicted in six cases. About 12% of the women continued to be at risk of further sexual abuse.