Effect of constant administration of a gonadotropin-releasing hormone agonist on reproductive activity in mares: induction of ovulation during seasonal anestrus

The potential of a gonadotropin-releasing hormone (GnRH) agonist (goserelin acetate), delivered constantly for 28 days via a subcutaneous depot, to induce ovulation in seasonally anestrous mares, was investigated. Two experiments were conducted, in which a range of doses (30 to 240 micrograms/mare/d) was examined. Mares were selected on the basis of lack of substantial follicular development (follicle diameter < 20 mm determined ultrasonically) and low serum concentrations of luteinizing hormone (LH) and progesterone. Constant administration of the GnRH agonist-induced ovulation in anestrous mares, but a dose-response relation was not observed. Furthermore, with identical doses tested in consecutive or alternate years, considerable variation was observed in the ovulatory response. In general, ovulation in all treated mares was accompanied by increased circulating concentrations of LH and a decrease in follicle-stimulating hormone values. Ovulation was preceded by an increase in estradiol and LH concentrations. In mares in which ovulation did not occur, concentration of LH increased during agonist treatment, whereas that of follicle-stimulating hormone either increased or did not change. It was concluded that constant administration of GnRH agonists may induce ovulation in mares during seasonal anestrus; however, percentage of mares ovulating and the lack of reproducibility of effect indicate that this approach is inappropriate for use as a reliable method to manipulate breeding activity in commercial broodmares.     

The concept of synergism in radiobiology]

We have demonstrated previously that pemphigus vulgaris (PV)-IgG induces activation of phospholipase C (PLC), production of inositol 1,4,5-trisphosphate, and a rapid transient increase in [Ca2+]i in cultured human keratinocytes, leading to secretion of plasminogen activator and cell-cell detachment in cell culture. In the current study, to examine the involvement of protein kinase C (PKC) in the mechanism of blister formation in PV, we studied the PV-IgG-induced translocation of PKC isozymes from the cytosol to the particulate/cytoskeleton (p/c) fractions and the activation of PKC in human keratinocytes. Cells cultured in Eagle's minimum essential medium were incubated with PV-IgGs for 30 s, 1 min, 5 min, or 30 min. PV-IgG binding to the cell surface antigen (desmoglein III) induced translocation of PKC-alpha from the cytosol to the p/c fractions within 30 s, with a peak at 1 min that lasted at least 30 min. PKC-delta also was translocated within 1 min and reached a peak at 5 min but was reduced to basal levels at 30 min. Alternatively, PKC-eta translocation to the p/c fraction was induced slowly, taking more than 5 min, and was reduced to approximately half-maximum at 30 min, whereas PKC-zeta translocation reached a maximum at 30 s, rapidly returning to baseline by 5 min after PV-IgG stimulation. The total PKC activity in the p/c fraction also was increased after PV-IgG exposure, peaked at 1 min, and was sustained for at least 30 min. These findings suggest that a unique activation profile of PKC isomers may be involved in mediating the intracellular signaling events induced by PV-IgG binding to desmoglein III in cultured human keratinocytes.     

Chest radiographic data acquisition and quality assurance in multicenter studies

Dorsal fusion with the internal fixator has become the standard treatment of instabilities and deformities of the thoracolumbar spine. With our new device, the modular spine fixator (MSF), which has been specially designed for short-distance instrumentations, we have increasingly been treating unstable injuries of the thoracolumbar spine by one-level stabilization. Prerequisite is an accurate evaluation of the indication, including CT and MRI to assess the involvement of the intervertebral disc and the ligamental structures. The operative technique differs in some details from the procedure in more-multi-level instrumentations, especially concerning the application of the pedicle screws. The instrumentation is always combined with posterior allogenic bone grafting. Since the beginning of 1993 we also perform anterior autogenic transpedicular bone grafting. Between January 1991 and July 1995, 57 one-level stabilizations with the MSF were performed. Of the 57 patients operated on 39, 27 men and 12 women, with an average age of 41 years, have had a clinical and radiographic follow-up examination so far, on average, 27 months after the accident. Seventeen patients were completely free of pain and 17 patients (were only) sensitive to weather changes or had minor pain during great physical stress. Five patients had pain even during slight physical stress or at rest. The preoperatively measured Cobb angle was 15.1 degrees on average, after the operation 5.2 degrees, and at the time of the follow-up examination amounted to 8.1 degrees. The patients' range of motion was normal. Only five minor complications have been seen. No implant fatigue failure has been noted in this series. We derive from these results that, for correct indications, one-level stabilization can be performed successfully and should be firmly established in the operative treatment of unstable fractures of the thoracolumbar spine.     

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.     

Mechanism of cardiovascular actions of the chromogranin A fragment catestatin in vivo

Catestatin (bovine chromogranin A(344-364); RSMRLSFRARGYGFRGPGLQL), reduces catecholamine secretion from chromaffin cells in vitro. We investigated the effects of this peptide on catecholamine release and blood pressure in vivo. Intravenous catestatin reduced pressor responses to activation of sympathetic outflow by electrical stimulation in rats, and the catestatin effect persisted even after adrenergic (alpha plus beta) blockade. Catestatin did not alter plasma norepinephrine levels, but increased plasma epinephrine 11-fold. Catestatin also blunted pressor responses to exogenous neuropeptide Y agonists. A control peptide (chromogranin A(141-160)) did not alter pressor or catecholamine responses to electrical stimulation. Pretreatment with a histamine H1 receptor antagonist blocked both the vasodepressor response to catestatin and the elevation in plasma epinephrine. Catestatin elevated endogenous circulating histamine 21-fold, and exogenous histamine mimicked both the epinephrine elevation and the vasodepressor actions of catestatin. We conclude that catestatin is a potent vasodilator in vivo whose actions appear to be mediated, at least in part, by histamine release and action at H1 receptors.