The monoamine uptake blocking agents, imipramine HC1 (5 mg/kg i.v.) and desipramine HC1 (4.8 mg/kg i.v.), and the monoamine oxidase inhibitor, pargyline HC1 (30 mg/kg i.v.) antagonized bulbospinal inhibition (BSI) of the monosynaptic reflex (MSR) in unanaesthetized cats decerebrated at the mid-collicular level. The effect of imipramine was quantitatively more on BSI of the quadriceps (QUAD)-MSR compared to that on BSI of the posterior biceps-semitendinosus (PBST)-MSR. Imipramine's action on this inhibition was also quantitatively greater compared to that of the equimolar dose of desipramine. Pretreatment of the animals with the tryptophan hydroxylase inhibitor, DL-p-chlorophenylalanine (p-CPA) (300 mg/kg i.p. for 3 consecutive days) completely eliminated the blocking action of imipramine. However, pretreatment of the animals with the tyrosine hydroxylase inhibitor, DL-α-methyl-p-tyrosine methyl ester HC1 (α-MPT) (126 mg/kg i.p. given 16 and 4 hours before the recording ) had no effect on imipramine's action. These findings strongly suggest that a 5-hydroxytryptamine (5-HT, serotonin) system antagonizes BSI of the MSR. They do not support the proposal of Clineschmidt and Anderson (1970) that the bulbospinal inhibitory pathway involves a 5-HT interneurone in the spinal cord. Imipramine HC1 (5 mg/kg i.v.) and pargyline HC1 (30 mg/kg i.v.) blocked recurrent inhibition (RI) of the MSR evoked by stimulation of a dorsal root. Imipramine blocked RI of the QUAD-MSR but had no effect on RI of the PBST-MSR. Pretreatment of the animals with either p-CPA or α-MPT prevented the blocking action of imipramine on RI. Application of a 'cold block' which potentiated RI of the QUAD-MSR also eliminated the blocking action of imipramine on this inhibition. These observations suggest that a supraspinal monoaminergic system which involves 5-HT and noradrenaline links has a tonic inhibitory effect on RI of the QUAD-MSR. / Pharmaceutical Sciences, Faculty of / Graduate

Note:

Background: Postprandial symptoms in irritable bowel syndrome (IBS) have been associated with increased bowel contractility. Aim: To compare ileocolonic and colonic responses to feeding in health and IBS. Methods: We prospectively analyzed data from separate research trials in 122 IBS patients and 41 healthy volunteers. Ileocolonic transit (ICT) was evaluated before (colonic filling [CF]3h) and immediately after (CF4h) a standard lunch at 3 h 45 min, and 2 h thereafter. The colonic geometric center (GC) was calculated 2 h (GC6h) after lunch ingested at 4 h (GC4h) and directly after (GC8h) a standard dinner ingested at 7 h 45 min. Results: ICT immediately after eating was higher in IBS diarrhea predominant (IBS-D) patients than in the healthy cohort (23.1 ± 2.4 vs. 17.5 ± 2.8%, P = 0.059). ICT 2 h after lunch was similar between groups (P = 0.55). There was significant overall group differences in colonic transit 2 h post-lunch (P = 0.045), particularly in the IBS constipation predominant (IBS-C; GC6-GC4, Δ0.29 ± 0.08) patients versus healthy volunteers (Δ0.56 ± 0.12 GC units). Conclusions: After feeding, ICT is increased in IBS-D, whereas colonic transit is blunted in IBS-C.

No description available.

No description available.

No description available.

No description available.

Thesis (Ph. D.)--University of Chicago, Committee on Neurobiology, March 1999. / Includes bibliographical references. Also available on the Internet.

Thesis (Ph. D.)--University of Texas at Austin, 2000. / Vita. Includes bibliographical references (leaves 119-126). Available also in a digital version from Dissertation Abstracts.

Background: One population prone to aspiration pneumonia and impaired cough is the postoperative patient. Postoperative pneumonia is the third most common complication among surgical patients after urinary tract and wound infections (Wren, Martin, Yoon, & Bech, 2010). A patient who has their surgical course complicated by aspiration pneumonia has increased morbidity, increased length of hospital stay and places greater demands on the health system. Mortality rates are cited as high as 70% (Wren, et al., 2010). Despite the prevalence of postoperative pneumonia and the high morbidity and mortality rates, little is known about the effect of anaesthesia on swallowing and airway protection. This study investigated the effect of clinical doses of fentanyl on suppressed cough reflex in healthy participants. Materials and Methods: After receiving ethical approval, 14 young, healthy participants gave informed written consent and completed the study protocol. Each participant received a total of 2 mcg/kg of fentanyl in four doses administered at five-minute intervals. Fentanyl effect site concentrations (ESC) were estimated using a standard pharmacokinetic model. During the administration period, suppressed cough response testing (SCR) with nebulised citric acid was performed after each fentanyl dose. Citric acid was presented in increments of 0.2M from each participant’s baseline cough response until a present-strong response was achieved. During the post-administration period, SCR was compared with reducing effect site concentrations to determine the time course for resolution of cough suppression. Results: Suppressed cough threshold increased and decreased in parallel with modeled fentanyl effect site concentrations. Mean citric acid concentration increased from 0.5M at baseline to 0.6M after 0.5 mcg/kg of fentanyl, 0.7 M after 1 mcg/kg of fentanyl, 0.9M after 1.5 mcg/kg of fentanyl and 1.2M after 2 mcg/kg of fentanyl. Predicted effect site concentrations after final doses of fentanyl (2 mcg/kg) were 1.89 ng/mL (1.81-1.96), well within the range seen clinically in the postoperative period. After the final dose of fentanyl, participants had on average 3.4 increments of change in their cough response (at increments of 0.2M). Conclusion: SCR testing with citric acid is sensitive enough to mirror changes in fentanyl ESC in healthy, young participants. The degree of reflex suppression seen has been associated with an 8-fold increase in aspiration risk in the general medical patient with dysphagia (Miles, Moore, McFarlane, Lee, Allen, Huckabee, 2013). Further research into the application of SCR in the postoperative period may help clinical decisions regarding safety to commence oral intake.