Browsing by Subject "Biomedical"
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Item Opioid and Nitric Oxide Interaction in the Control of Heart Rate(2002-12-01) Farias III, Martin; James Caffrey; Fred H. Downey; Patricia GwirtzFarias III, Martin, Opioid and Nitric Oxide Interaction in the Control of Heart Rate. Doctor of Philosophy (Biomedical Sciences), December 2002, 130 pp, 2 tables, 30 figures. Understanding of the role endogenous opioids play as modulators of parasympathetic function has increased. The endogenous opioid, methionine-enkephalin arginine phenylalanine (MEAP) attenuates vagal control of heart rate when delivered by microdialysis directly in the canine sinoatrial node. This effect was mimicked by the δ-2 agonist, deltorphin-II indicating involvement by a δ-opioid receptor. The nodal delivery of the δ-antagonist naltrindole abolished the effect of deltorphin-II, further supporting the delta character of the receptor. Although the findings suggested that the opioid receptor mediating vagolysis was delta in character, the exact subtype of δ-receptor remained in question. Selective agonist and antagonists for δ-1 and δ-2 opioid receptors were employed to determine which subtype of δ-receptor mediated MEAP vagolysis. In these experiments, vagolysis produced by the nodal delivery of MEAP was unaltered by the highly selective δ-1 antagonist BNTX but abolished by the δ-2 antagonist, naltriben. Nodal delivery of deltorphin-II attenuated vagal bradycardia similar to MEAP while δ-1 agonists, DPDPE and TAN-67 failed to interrupt vagal bradycardia. TAN-67 actually improved vagal transmission and this effect was reversed by BNTX. These data indicate that δ-2 opioid receptors in the sinoatrial node and vagolytic and support the presence of vagotonic δ-1-opioid receptors in the same location. Nitric Oxide/Opioid Interaction. The hypothesis that intranodal nitric oxide synthase (NOS) modulates vagal transmission and that MEAP attenuates vagal bradycardia via the interruption of the NOS-cGMP pathway was tested. The general (L-NAME) and neuronal (7-nitroindazole) NOS inhibitors each attenuated vagal bradycardia and both effects were reversed by adding excess of the NOS substrate, L-arginine. These findings suggested that nNOS was a necessary component of vagal bradycardia in the canine sinoatrial node. Various probes of the NOS-cGMP pathway (L-arginine, SNAP, cGMP, and IBMX) were employed to determine if MEAP interrupted this pathway to produce vagolysis. The delivery of MEAP into the sinoatrial node for sixty minutes exerted a consistent vagolytic effect during vagal simulations. When MEAP was combined with a NOS pathway components, the vagolytic effect was reversed after 15-45 minutes of treatment. These findings suggested that MEAP exerted its effect by interacting with the NOW-cGMP system. The site of convergence maybe cAMP since the phosphodiesterase inhibitor, IBMX (by allowing the accumulation of cAMP) reversed the vagolytic effect of MEAP. To rule out a postjunctional effect, MEAP and the NOS inhibitors were combined with the direct acting muscarinic agonist, methacholine. The bradycardia produced by methacholine was unaltered by MEAP or nNOS inhibitors. This suggested that the effect of NOS inhibitors and MEAP were prejunctional. In summary, the cumulative findings suggest that MEAP, by activating δ-2-opioid receptors, attenuated vagal bradycardia prejunctionally, through modulating the cAMP component of the NOS-cGMP pathway in the canine sinoatrial node.Item Osteopathic Focus in the Biomedical Sciences: A Survey of Biomedical Science Faculty at Osteopathic Medical Schools in the United States(2007-05-01) Ebert, Didi Elise; Rustin E. Reeves; Stuart Williams; Stuart WilliamsEbert, Didi E., Osteopathic Focus in the Biomedical Sciences: A Survey of Biomedical Science Faculty at Osteopathic Medical Schools in the United States. Master of Science (Clinical Research and Education), May, 2007, 73 pp., 6 tables, 2 figures, bibliography, 20 titles. The purpose of this study was to describe and evaluate the knowledge of osteopathic principles and osteopathic manipulative medicine (OMM) among biomedical science faculty at osteopathic medical schools (COMs) and to assess their attitudes towards the integration of osteopathic principles and OMM concepts into the biomedical science curriculum and biomedical science research. A cross-sectional survey was administered to biomedical science research. A cross-sectional survey was administered to biomedical science faculty at COMs within the United States. Descriptive statistics were used to characterize data, and means were compared between health science center faculty and non-health science center faculty and between anatomy faculty and non-anatomy faculty. The survey response rate was 29%. Overall, survey respondents demonstrated positive attitudes and high levels of knowledge regarding osteopathic principles and less positive attitudes toward OMM. Significant differences were noted between faculty at health science centers versus faculty at non-health science centers and between anatomy faculty and non-anatomy faculty. Data from this survey may be useful in designing strategies to increase the integration of osteopathic principles into the biomedical science curriculum.Item Sexually Dimorphic Anxiety-Like Interoceptive Discriminative Stimuli(1997-12-01) Jung, Marianna E.; Walls, Cleatus; Downey, H. Fred; Forster, MichaelJung, Marianna E., Sexually Dimorphic Anxiety-Like Interoceptive Discriminative Stimuli. Doctor of Philosophy (Biomedical Sciences), December 1997, 150 pp, introduction, 2 chapters, discussion, bibliography, 109 titles. This study compared gender differences in the anxiogenic stimuli induced by either a GABA-A antagonist, pentylenetetrazol (PTZ) or by a 5-HT1b/2 agonist, m-chlorophenylpiperazine (m-CPP) before and during ethanol withdrawal (EW). Rats were trained to discriminate either PTZ (16mg/kg, IP) or m-CPP (1.2 mg/kg, IP) from saline in a two lever choice task for food reward. Male and female rats were gonadectomized or sham-operated, and ovariectomized (OVX) female rats were tested during replacement treatment with 17β estradiol (2.5 mg, 21 day release, sc). The dose-response for the discrimination of the interoceptive stimulus (IDS) produced by PTZ (0-16 mg/kg) or m-CPP (0 to 1.2 mg/kg) was measured under all hormonal conditions. For m-CPP trained rats, latency to first lever-press response was also tested. Results: sham and estradiol-replaced female rats had higher ED50s for discrimination of the PTZ or m-CPP IDS than intact males or OVX rats. There is a dose-related impairment of operant responding after mCPP injection. Sham and estradiol replaced OVX rats showed an increased delay to the initiation of response after m-CPP injection as compared to sham or castrated male rats or OVX rats that showed no effect at the doses tested. Rats then received a chronic ethanol diet (6.5%) for 10 days. At twelve hours of ethanol withdrawl, they were tested for lever selection after saline injection. Fewer sham female and estradiol-replaced female rats responded on the drug lever during acute EW as compared to sham male, castrated or OVX rats. In general, the anxiogenic drug lever selection of OVX rats resembled that of male rats but was restored toward that of sham female rats by estradiol replacement. Castration did not alter the response of male rats to either PTZ or mCPP. Serum β –estradiol concentrations were determined by radioimmunoassay for sham, OVX, and estradiol-replaced female rats. The concentration was significantly higher in hormone-replaced female rats than in OVX. The estradiol concentration in sham female rats showed a cyclic pattern over 4 consecutive days, but this pattern did not correlate with any difference in IDS. Blood ethanol concentration (BEC) was determined using head space gas chromatography. BEC was higher in intact female rats than in intact male rats after ethanol injection (2 g/kg, ip), but did not differ during EW. Conclusions: females produce less anxiogenic IDS in response to either GABA inhibition or 5-HT1b/2 activation, but are more impaired by m-CPP in their ability to initiate operant responses than male rats. In addition, fewer intact females developed a spontaneous IDS during EW than males which is not the result of lower BEC. Estrogen appears to play a trophic role in altering responsiveness to anxiogenic stimuli.