Neuroprotective strategies that limit secondary tissue loss and/or improve functional outcomes have been identified in multiple animal models of ischemic, hemorrhagic, traumatic and nontraumatic cerebral lesions. However, use of these potential interventions in human randomized controlled studies has generally given disappointing results. In this paper, we summarize the current status in terms of neuroprotective strategies, both in the immediate and later stages of acute brain injury in adults. We also review potential new strategies and highlight areas for future research. 相似文献
The liver may be injured during the course of many systemic diseases. The mechanisms of injury can be broadly divided into four pathways: vascular, toxic, immune, and hormonal. Vascular obstruction may be an early event but is also the late common pathway from all mechanisms. Despite the large number of possible initiating factors, the end results are few, including death of hepatocytes or cholangiocytes, leading to the stereotyped syndromes of acute liver failure, non-cirrhotic portal hypertension, or cirrhosis. This small number of outcomes is a reflection of the few anatomic patterns that can be generated by microvascular obstruction. Vascular obstruction may occur by thrombosis, inflammation, or congestive injury. The innate immunity pathway is activated by endotoxin and other agents, leading to inflammatory infiltration, release of cytokines and reactive oxygen species, and necrosis. The adaptive immune pathway involves the generation of antibodies and antigen-specific cell-mediated attack on hepatic cells. Hormonal effects are principally involved when overnutrition leads to hyperinsulinemia followed by hepatocellular necrosis. 相似文献
We used mixed methods to examine the association between setting-level factors and observed implementation of a social and emotional learning intervention (Responsive Classroom® approach; RC). In study 1 (N?=?33 3rd grade teachers after the first year of RC implementation), we identified relevant setting-level factors and uncovered the mechanisms through which they related to implementation. In study 2 (N?=?50 4th grade teachers after the second year of RC implementation), we validated our most salient Study 1 finding across multiple informants. Findings suggested that teachers perceived setting-level factors, particularly principal buy-in to the intervention and individualized coaching, as influential to their degree of implementation. Further, we found that intervention coaches’ perspectives of principal buy-in were more related to implementation than principals’ or teachers’ perspectives. Findings extend the application of setting theory to the field of implementation science and suggest that interventionists may want to consider particular accounts of school setting factors before determining the likelihood of schools achieving high levels of implementation. 相似文献
Incubation of human platelets, human neutrophils, or highly metastatic mouse lymphoma cells with sulfate-labeled extracellular matrix (ECM) results in heparanase-mediated release of labeled heparan sulfate cleavage fragments (0.5 less than Kav less than 0.85 on Sepharose 6B). This degradation was inhibited by native heparin both when brought about by intact cells or their released heparanase activity. Degradation of heparan sulfate in ECM may facilitate invasion of normal and malignant cells through basement membranes. The present study tested the heparanase inhibitory effect of nonanticoagulant species of heparin that might be of potential use in preventing heparanase mediated extravasation of bloodborne cells. For this purpose, we prepared various species of low-sulfated or low-mol-wt heparins, all of which exhibited less than 7% of the anticoagulant activity of native heparin. N-sulfate groups of heparin are necessary for its heparanase inhibitory activity but can be substituted by an acetyl group provided that the O-sulfate groups are retained. O-sulfate groups could be removed provided that the N positions were resulfated. Total desulfation of heparin abolished its heparanase inhibitory activity. Heparan sulfate was a 25-fold less potent heparanase inhibitor than native heparin. Efficiency of low-mol-wt heparins to inhibit degradation of heparan sulfate in ECM decreased with their main molecular size, and a synthetic pentasaccharide, representing the binding site to antithrombin III, was devoid of inhibitory activity. Similar results were obtained with heparanase activities released from platelets, neutrophils, and lymphoma cells. We propose that heparanase inhibiting nonanticoagulant heparins may interfere with dissemination of bloodborne tumor cells and development of experimental autoimmune diseases. 相似文献
The cytoprotective effects of prostaglandins have been utilized in the prevention of hepatitis B virus reactivation after liver transplantation. This pilot study evaluated the effects of oral prostaglandin E2 (PGE2) in chronic viral hepatitis B and C. Twenty patients with chronic hepatitis B and 20 patients with chronic hepatitis C received 4mgday–1 PGE2 for 6 months. The lymphocyte antiviral enzyme 2',5'-oligoadenylate synthetase (2',5'-OAS) and peripheral blood monocyte procoagulant activity (PCA) were measured before, during and after the treatment. Three of 20 hepatitis B and five of 20 hepatitis C patients withdrew from the study. Eight of 17 hepatitis B patients responded: in seven of these eight patients, serum alanine aminotransferase (ALT) levels normalized; loss of viral replication was sustained in all eight patients; and seroconversion from hepatitis Be antigen (HBeAg) to hepatitis Be antibody (HBeAb) positivity occurred in seven patients over the 48-week duration of this study. In 14 of the 15 hepatitis C patients, hepatitis C virus (HCV) RNA remained detectable and the serum ALT levels remained elevated. 2',5'-OAS levels and PCA values did not correlate with other markers of response to PGE2 therapy in either chronic hepatitis B or C. In summary, PGE2 was associated with sustained loss of viral replication in 47% of chronic hepatitis B patients; no beneficial effects were apparent in chronic hepatitis C. 相似文献
Central haemodynamics and regional blood flow were studied comprehensively in conscious New Zealand White rabbits before and during the development of chronic low output cardiac failure produced by administration of the anticancer agent adriamycin. After eight weeks of adriamycin treatment, cardiac index fell from 326(40 to 225(56) ml.min-1.kg-1. This was accompanied by an increase in heart rate and total peripheral resistance but no change in mean systemic blood pressure. Myocardial function was shown to be depressed by the measurement of Frank-Starling curves, the slopes of which were appreciably flatter in adriamycin treated rabbits. Regional blood flow (measured by the radioactive microsphere technique) was redistributed. There were decreases in renal, splenic, small gut, and skeletal muscle blood flow, whereas myocardial and cerebral blood flow were unchanged. There was an increase in total body exchangeable sodium, indicating some salt and water retention. Systemic toxic effects of adriamycin could be limited by treating the animals for eight weeks with adriamycin and then allowing a two week recovery period before haemodynamic study. This would appear to be the optimal dosage schedule. 相似文献
Nodular regenerative hyperplasia of the liver is an infrequent condition characterized by transformation of the hepatic parenchyma into nodules with only mild fibrosis. Little is known about the etiology except that there is usually an underlying chronic disease, such as Felly's syndrome, which antedates the development of clinical liver disease. It is poorly understood how the associated diseases contribute to the pathogenesis of nodular regenerative hyperplasia. Presented are four cases of nodular regenerative hyperplasia in which macroglobulinemia was also present. This new association suggests to us a hypothesis for the pathogenesis of nodular regenerative hyperplasia.
Histologic examination of the livers in these and other cases of nodular regenerative hyperplasia reveals widespread obliteration of the small portal veins. Postmortem angiography of one liver in the present series demonstrated that the nodules were well perfused and that the atrophic areas were poorly perfused with portal blood. This supports the view that atrophy of lobules results from a lack of portal blood supply and that nodules develop from lobules well supplied with portal blood. In each of the clinical conditions associated with nodular regenerative hyperplasia, including macroglobulinemia, inflammatory or thrombotic vascular lesions are found in many organs. Therefore, nodular regenerative hyperplasia may be the hepatic expression of a more widespread vascular disease. 相似文献