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.     

Self-limited autoimmune disease related to transient donor B cell activation in mice neonatally injected with semi-allogeneic F1 cells.

BALB/c mice injected at birth with 10(8) semi-allogeneic (C57BL/6 x BALB.IgHb)F1 spleen cells develop a lupus-like syndrome in which autoantibodies bear exclusively the donor allotype. We have analyzed the evolution of donor B cell chimerism and the autoimmune manifestations during the first year of life in these mice. Anti-DNA, -histone, and -cardiolipin IgG antibodies as well as circulating immune complexes appeared in the second week of life, reached the highest values around the sixth week, and then progressively dropped to normal values after the sixth month in most mice. The kinetics of the evolution of the autoimmune manifestations, as well as the kinetics of serum donor Ig allotype, were parallel to the kinetics of donor B cell chimerism, which was particularly prominent in the spleens in early weeks of life, and progressively decreased after remission of the autoimmune syndrome. Membrane-proliferative glomerulonephritis, which was followed as the more representative histological abnormality in this model, was particularly evident after 10 weeks of life, but disappeared by the end of the follow-up. Interestingly, when mice with a self-limited disease were re-injected with 10(8) F1 spleen cells i.v., a flare in the serological manifestations was observed. In these re-injected mice a predominance of anti-DNA, IgG1 antibodies bearing exclusively the donor allotype was also observed, as in the early weeks of life.(ABSTRACT TRUNCATED AT 250 WORDS)     

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.