Carvedilol protects ischemic cardiac mitochondria by preventing oxidative stress.

Ischemia negatively affects mitochondrial function by inducing the mitochondrial permeability transition (MPT). The MPT is triggered by oxidative stress, which occurs in mitochondria during ischemia as a result of diminished antioxidant defenses and increased reactive oxygen species production. It causes mitochondrial dysfunction and can ultimately lead to cell death. Therefore, drugs able to minimize mitochondrial damage induced by ischemia may prove to be clinically effective. We analyzed the effect of carvedilol, a beta-blocker with antioxidant properties, on mitochondrial dysfunction. Carvedilol decreased levels of TBARS (thiobarbituric acid reactive substances), an indicator of oxidative stress, which is consistent with its antioxidant properties. Regarding cell death by apoptosis, although ischemia did increase caspase-8-like activity, there were no changes in caspase-3-like activity, which is activated downstream of caspase-8; this may indicate that the apoptotic cascade is not activated by 60 minutes of ischemia. We conclude that carvedilol protects ischemic mitochondria by preventing oxidative mitochondrial damage, and, by so doing, it may also inhibit the formation of the MPT pore.     

A flow visualization study of an anatomic coronary artery anastomosis model with an implant.

Flow Streamlining Devices is a new tool in Coronary Artery Bypass Grafting (CABG). They aim in: a) Performing a sutureless anastomosis to reduce thrombosis at the veno-arterial junction, and b) Providing a hemodynamically efficient scaffolding to reduce secondary flow disturbances. Thrombosis and flow disturbances are factors that have been reported as contributing factors to the development of intimal hyperplasia (IH) and failure of the graft. By reducing thrombosis and flow disturbances, it is expected that IH will be inhibited and the lifetime of the graft extended. To evaluate the hemodynamic benefits of such an implant, two models were designed and fabricated. One simulated the geometry of the conventional anastomosis without an implant, and the other simulated an anastomosis with a flow streamlining implant. Identical flow conditions relevant to a coronary anastomosis were imposed on both models and flow visualization was performed with dye injection and a digital camera. Results showed reduction of disturbances in the presence of the implant. This reduction seems to be favorable to hemodynamic streamlining which may create conditions that may inhibit the initialization of IH. However, the compliance and geometric mismatch between the anastomosis and the implant created a disturbance at the rigid compliant wall interface, which should be eliminated prior to clinical applications.     

Drug information course for pharmacy staff development.

An interactive course in drug information skills developed for pharmacists at a not-for-profit, tertiary-care hospital is described. Faculty members from the area school of pharmacy developed, taught, and evaluated the program. Before the course was developed, pharmacy staff members were asked to rate their drug information skills; the pharmacists' responses indicated their belief that they were not proficient enough in the skills needed in daily practice. The course content and format were refined after 11 pharmacists completed a pilot program. A handbook was developed that contained objectives, session outlines, and literature for each of the six topics chosen for the course. Although the handbook was the primary teaching aid, wall charts and computer demonstrations were also used. Sessions were structured for the needs of adult students by using a small-group discussion format that emphasized the practical relevance of the information and encouraged participants to share personal experiences. Each session was offered on two separate days to facilitate attendance. Those who completed the course received credit for 12 contact hours of continuing education. Of 16 pharmacists enrolled in the course, 11 completed it. An interactive course in drug information skills, developed to meet the needs of hospital pharmacists, was well accepted because it incorporated personal experiences, small-group activities, and flexible scheduling.     

Effective high-capacity gutless adenoviral vectors mediate transgene expression in human glioma cells.

Glioblastoma multiforme (GBM) is the most common subtype of primary malignant brain tumor. Although serotype 5 adenoviral vectors (Ads) have been used successfully in clinical trials for GBM, the capacity of Ads to infect human glioma cells and the expression of adenoviral receptors in GBM cells have been challenged. In this report, we studied the expression of three molecules that have been shown to mediate adenoviral entry into cells, i.e., coxsackie and adenovirus receptor (CAR), integrin alphavbeta3 (INT), and major histocompatibility complex class I (MHCI), in rodent glioma cell lines and low-passage primary cultures and cell lines from human GBM. We correlated levels of expression of CAR, INT, and MHCI with transduction efficiency elicited by several high-capacity helper-dependent adenoviral vectors (HC-Ads). Expression levels of adenoviral receptors were variable among the different GBM cells studied. HC-Ad-mediated therapeutic gene expression was efficient, ranging between 20 and 80% of the total target cells expressing the encoded transgenes. Our results show no correlation between the levels of CAR, INT, or MHCI molecules and the levels of transgene expression or the number of GBM cells transduced. We conclude that expression levels of adenoviral receptors do not predict their transduction efficiency or biological function.     

Involvement of IL-1beta in acute stress-induced worsening of cerebral ischaemia in rats.

Stress is known to be one of the risk factors of stroke. Most of the knowledge on the effects of stress on cerebrovascular disease in humans is restricted to catecholamines and glucocorticoids effects on blood pressure and/or development of atherosclerosis. However, few experimental studies have examined the possible mechanisms by which stress may affect stroke outcome. We have used an acute stress protocol consisting of the exposure of male Fischer rats to an acute, single exposure immobilisation protocol (6 h) prior to permanent middle cerebral artery occlusion (MCAO), and we have found that stress worsens behavioural and neurological outcomes and increased infarct size after MCAO. The possible regulatory role of the TNFalpha and IL-1beta was studied by looking at the release of these cytokines in brain. The results of the present study showed an increase in IL-1beta release in cerebral cortex after exposure to acute stress. Brain levels of IL-1beta are also higher in previously stressed MCAO rats than in MCAO animals without stress. Pharmacological blockade of IL-1beta with an antibody anti-IL-1beta led to a decrease in the infarct size as well as in neurological and behavioural deficits after MCAO. In summary, our results indicate that IL-1beta, but not TNFalpha, accounts at least partly for the worsening of MCAO consequences in brain of rats exposed to acute stress.