Continued development of the Nimbus/University of Pittsburgh (UOP) axial flow left ventricular assist system

Nimbus and the University of Pittsburgh (UOP) have continued the development of a totally implanted axial flow blood pump under the National Institutes of Health (NIH) Innovative Ventricular Assist System (IVAS) program. This 62 cc device has an overall length of 84 mm and an outer diameter of 34.5 mm. The inner diameter of the blood pump is 12 mm. It is being designed to be a totally implanted permanent device. A key achievement during the past year was the completion of the Model 2 pump design. Ten of these pumps have been fabricated and are being used to conduct in vitro and in vivo experiments to evaluate the performance of different materials and hydraulic components. Efforts for optimizing the closed loop speed control have continued using mathematical modeling, computer simulations, and in vitro and in vivo testing. New hydraulic blade designs have been tested using computational fluid dynamics (CFD) and flow visualization. A second generation motor was designed with improved efficiency. To support the new motor, a new motor controller fabricated as a surface mount PC board has been completed. The program is now operating under a formal QA system.     

Preclinical evaluation of Seprafilm bioresorbable membrane

OBJECTIVE: To characterize Seprafilm bioresorbable membrane and assess its efficacy and safety in reducing adhesions. DESIGN: In vitro and animal studies designed to provide precise control of tissue trauma and closely approximate clinically relevant conditions in abdominal surgery. SETTING: Experimental laboratories, USA. SUBJECTS: Experimental animals, principally rats and rabbits. INTERVENTIONS: The rat cecal abrasion or sidewall injury model evaluated the efficacy of seprafilm in the presence of blood and irrigation solutions, in multiple layers, under ischemic conditions, and in adhesion reformation. A rabbit anastomosis model tested the effect of the membrane on wound healing, and a series of challenge tests determined its toxicology, immunogenicity, and biocompatibility. MAIN OUTCOME MEASURES: Incidence and severity of adhesions; mutagenicity; pyrogenicity; irritation effects; systemic toxicity. RESULTS: Seprafilm significantly reduced the number of cecal adhesions (p < 0.001) and the number of animals with severe adhesions (p < 0.001) when compared with nontreated controls, even in the presence of bleeding. The membrane also significantly decreased the number of animals with any adhesions (p < 0.001). Seprafilm maintains efficacy when used with excess irrigation solutions, when layered, and under ischemic conditions. Among rats tested for adhesion reformation, the treated group had a significantly larger proportion of adhesion-free animals than the untreated group, 72% versus 28%, (p = 0.007). Seprafilm did not impair wound healing in anastomosis and is nontoxic, nonmutagenic, nonimmunogenic, nonpyrogenic, nonirritating, and biocompatible. CONCLUSION: Preclinical studies have shown that Seprafilm is safe and effective in reducing postsurgical adhesions. Seprafilm meets the requirements of an ideal barrier and can be a useful adjuvant in abdominal and pelvic surgery.     

Translating between orthogonally oriented stimulus and response arrays in four-choice reaction tasks

The human mineralocorticoid receptor (MR) is a member of the steroid-thyroid hormone receptor superfamily, which includes receptors for retinoic acid, vitamin D, and other steroids, such as the glucocorticoids (which bind the glucocorticoid receptor, GR). MR and GR, the corticosteroid receptors, share significant homology and are activated by steroid binding, resulting in a conformational change, nuclear translocation, and DNA binding. Despite these similarities with GR, the MR remains less well characterized. However, protein components known to be present in the unliganded GR are also likely to be components of the heteromeric MR complex. In the current study, we investigated whether or not hsp70, hsp90, and the immunophilin FKBP-52 are present in the nonsteroid-bound MR complex, because these proteins are known to be present in the unliganded GR complex. The unliganded MR complex was assembled in vitro using reticulocyte lysate and in vivo using the baculovirus overexpression system and Spodoptera frugiperda (Sf9) cells. Western blot analysis revealed the presence of hsp70, hsp90, and FKBP-52 in the unliganded complexes, but hsp90 and FKBP-52 were not detected following exposure to aldosterone. Electrophoretic mobility shift analysis demonstrated that DNA binding of MR occurred only after treatment with aldosterone. These studies indicate that proteins associated with the unliganded GR are also present in the unliganded MR complex, and that hsp90 and FKBP-52 dissociate prior to DNA binding in a manner similar to that described for GR. Finally, the stoichiometric analysis of the proteins present within the heteromeric MR complex suggests a divergence between this receptor and the GR.     

NMDA receptor-mediated oscillatory activity in the neonatal rat spinal cord is serotonin dependent

The effect of serotonin (5-HT) receptor blockade on rhythmic network activity and on N-methyl--aspartate (NMDA) receptor-induced membrane voltage oscillations was examined using an in vitro neonatal rat spinal cord preparation. Pharmacologically induced rhythmic hindlimb activity, monitored via flexor and extensor electroneurograms or ventral root recordings, was abolished by 5-HT receptor antagonists. Intrinsic motoneuronal voltage oscillations, induced by NMDA in the presence of tetrodotoxin (TTX), either were abolished completely or transformed to long-lasting voltage shifts by 5-HT receptor antagonists. Conversely, 5-HT application facilitated the expression of NMDA-receptor-mediated rhythmic voltage oscillations. The results suggest that an interplay between 5-HT and NMDA receptor actions may be critical for the production of rhythmic motor behavior in the mammalian spinal cord, both at the network and single cell level.     

Altering conception of dairy cattle by gonadotropin-releasing hormone preceding luteolysis induced by prostaglandin F2 alpha

The objective of these experiments was to determine the effect on fertility of GnRH when used in conjunction with one or two injections of PGF2alpha. In Experiment 1, GnRH was administered 7 d before the second of two injections of PGF2alpha (14 d apart). The control group received two injections of PGF2alpha without GnRH. Conception was reduced from 63.5% for 74 controls to 48.7% for the 79 heifers and cows that had been treated with GnRH, but estrus detection and pregnancy rates were similar. In Experiment 2, 85 heifers and cows received GnRH at a random stage of the estrous cycle, followed in 7 d by PGF2alpha. Thirty to 32 h after PGF2alpha, a second dose of GnRH was given to induce ovulation of the preovulatory follicle, followed by one fixed-time insemination 18 to 19 h later (treatment designated as GnRH, PGF2alpha, and GnRH). Controls (n = 85) were given PGF2alpha and inseminated at estrus. Although conception rate was not different, one fixed-time insemination after the GnRH, PGF2alpha, and GnRH treatment tended (35.3%) to reduce fertility compared with effects of the control (47.1%). It is unclear how an injection of GnRH during the intervening week between two injections of PGF2alpha reduced fertility in Experiment 1. However, in Experiment 2, when GnRH was given 7 d before one injection of PGF2alpha and when ovulation was induced with a second GnRH injection, one fixed-time insemination seemed to produce acceptable fertility in dairy cows but probably less than that when inseminations were based on detected estrus.