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Biomedical subjects

R W Wells

Publications and source records attributed to R W Wells.

12 recordsLinked to original sources

Divergent changes to muscarinic and serotonergic signalling following colitis.

BACKGROUND: The altered motility of the inflamed intestine derives in part from changes to the contractility of the intestinal smooth muscle cell. While modifications to the muscarinic receptor system are identified, changes to 5-hydroxytryptamine (5-HT; serotonin) receptors that also mediate contraction are less well studied. METHODS: In the trinitrobenzene sulphonic acid model of rat colitis, we used receptor antagonists to identify changes in receptor utilisation that accompany the selective reversal of the impaired contractile response to acetylcholine (ACh) and 5-HT during colitis (day 4 (D4)) and following resolution of inflammation (day 36 (D36)). RESULTS: In isolated circular smooth muscle cells, challenged with ACh, the muscarinic 3 receptor (M3R) antagonists 4-DAMP and pF-HSD each showed a 50% decrease in antagonism on D4 while the M2R antagonist methoctramine more than doubled its potency, showing a decreased role of M3R and an increased role of M2R, respectively. These changes were fully reversed by D36. In contrast, the 5-HT2 receptor (5-HT2R) antagonist ketanserin was sharply decreased in effectiveness on D4, with a further decrease by D36, when the contribution of 5-HT(2A)R was only 22% of control. There were no changes in response to the 5-HT4R antagonist SDZ-205-557 at any time. Western blotting identified decreased expression of 5-HT(2A)R on D36 versus controls, further supporting the conclusion that the persistence of the impaired response to 5-HT was due to decreased expression of the excitatory 5-HT(2A)R. CONCLUSIONS: Thus the lasting decrease in receptor expression and resulting impairment of the contractile response will compromise the capacity for an appropriate response to 5-HT, which may contribute to the intestinal dysfunction seen in post-enteritis syndromes.

Acetylcholine↗

Persistent and selective effects of inflammation on smooth muscle cell contractility in rat colitis.

Intestinal inflammation affects smooth muscle contractility contributing to altered motility, but changes to the individual smooth muscle cells are not well described. We used video microscopy to study the contractility of circular smooth muscle cells (CSMC) isolated from the rat mid-descending colon throughout the course of TNBS-induced colitis, measuring their shortening response to carbachol (CCh), 5-HT, histamine or high K(+). In control CSMC, CCh caused a maximal shortening response of 28 (2%), similar to that for 5-HT of 27 (1%), but by day 4 of colitis, these responses were decreased by 35% and 37%, respectively. By day 36, all aspects of cholinergic contraction returned to control levels, while 5-HT-induced contraction remained significantly attenuated. In contrast, the contractile responses to histamine remained similar at all time points. K(+)-induced contraction was impaired only on day 4, and the maximal response remained substantially greater than CCh or 5-HT. Colitis caused a 121% increase in CSMC length by day 2 that persisted through day 36, independent evidence for phenotypic change. We conclude that impaired CSMC contractility at both the receptor and non-receptor levels contribute to altered smooth muscle function during colitis. Persistent changes in contractile response remained detectable after resolution of inflammation, and similar events may occur in post-enteritis syndromes seen in humans.

Animals↗

Effects of acid-induced esophagitis on esophageal smooth muscle.

Acid-induced esophagitis is associated with sustained longitudinal smooth muscle (LSM) contraction and consequent esophageal shortening. In addition, LSM strips from opossums with esophagitis are hyper-responsive, while the circular smooth muscle (CSM) contractility is impaired. To determine the origin of these changes, studies were performed on esophageal smooth muscle cells isolated from opossum esophagi perfused intraluminally on 3 consecutive days with either saline (control; n = 8) or HCl (n = 9). CSM and LSM cells, obtained by enzymatic digestion, were exposed to various concentrations of carbachol (CCh) and fixed. CCh induced concentration-dependent contraction of both LSM and CSM cells. CCh-induced LSM cell contraction was not different between control and esophagitis animals; however, there was marked attenuation in the CCh-induced contraction of CSM cells from esophagitis animals. Morphological studies revealed significant hypertrophy of the CSM cells. These findings suggest that impaired CSM contractility can be attributed at least in part to alterations to the CSM cell itself. In contrast, hyper-contractility demonstrated in LSM strips is likely related to factors in the surrounding tissue.

Animals↗

Will nursing administration programs survive in the 21st century?

Why are graduate nursing administration (MSN/A) program enrollments declining? Do these programs truly meet the needs of potential students? Will they help them to be effective and innovative partners on the healthcare management team? The authors explore reasons for the decline in MSN/A enrollments, potential negative outcomes, and currently available alternative educational choices. They then suggest MSN/A program redesign and other courses of actions. Nurse administrators and nurse educators must be aware of these trends and have equal input into the creation of a viable MSN/A program that will be able to survive in the 21st century.

Curriculum↗

Making planned and unplanned role transitions.

Changes in organizations mean planned and unplanned role transitions for nurse administrators and managers. Keeping abreast of trends engaging in activities that promote professional growth, assessing work habits, maintaining job interviewing skills, and reviewing and updating resumes are essential to prepare for role changes. When unplanned changes occur because one is fired or a position is abolished, one has to organize personal needs, cope with the job loss, look for a job, and assume a new role. The authors discuss strategies that can be used personally or with others to facilitate job change.

Adaptation, Psychological↗

Revisioning the recruitment of talented professionals.

As organizations restructure and redesign, hiring appropriate staff members becomes even more crucial for their success. Skill sets become more complex, fit becomes more significant, and fast-paced organizations do not have the time or resources for extensive grooming or training of in-house or newly hired personnel. The authors examine how talented professionals can be recruited and hired in a timely manner while using fewer in-house organizational resources.

Clinical Competence↗