Biomedical subjects
J Shook
Publications and source records attributed to J Shook.
Changes in opioid receptor selectivity following processing of peptide E: effect on gut motility.
Peptide E is a mu-selective opioid peptide derived from proenkephalin A which contains [Met5]-enkephalin at the amino end and [Leu5]-enkephalin at the carboxyl end. Peptide E is further processed both centrally and peripherally to a [Leu5]-enkephalin-containing fragment which was investigated to determine if processing leads to alterations in receptor selectivity. Peptide E-(15-25) inhibited electrically stimulated contractions in both the mouse vas deferens, longitudinal muscle, myenteric (IC50 = 459 nmol/L), and guinea pig ileum (IC50 = 2630 nmol/L), indicating a sixfold delta-receptor selectivity. When administered intracerebroventricularly to mice, peptide E-(15-25) also produced potent analgesia which was completely antagonized by naloxone pretreatment, but the peptide had no effect on intestinal transit as measured by the radiochromium geometric center method. This is consistent with earlier findings that intracerebroventricular delta-opioid-selective agents are analgesic but do not inhibit intestinal transit. In vitro radioligand binding assays were performed using male Sprague-Dawley rat whole brain homogenates. The IC50 for peptide E against [3H]naloxone was 1.8 nmol/L compared with the delta-opioid ligand, [3H] [D-Pen2, D-Pen5]-enkephalin of 38.8 nmol/L. The IC50 for peptide E-(15-25) against [3H]naloxone was 497 nmol/L, but for [3H] [D-Pen2, D-Pen5]-enkephalin it was 50.6 nmol/L. Therefore, peptide E loses mu-opioid receptor affinity (1.8-497 nmol/L) after proteolytic processing and the loss of the amino terminal tyrosine but maintains a high delta-opioid affinity (38.8-50.6 nmol/L). These studies demonstrate that enzymatic peptide processing of peptide E to peptide E-(15-25) leads to a shift from mu- to delta-receptor selectivity and a different spectrum of biological effects on gut motility.
Systemic administration of kainic acid differentially regulates the levels of prodynorphin and proenkephalin mRNA and peptides in the rat hippocampus.
The effects of systemic kainic acid (KA) administration on hippocampal levels of prodynorphin and proenkephalin mRNA, as well as opioid peptides derived from these precursors, were evaluated. A single subcutaneous injection of KA induced a range of seizure states, from mild wet dog shakes to generalized motor seizures. Northern blot analysis of hippocampal mRNA revealed an increase in both prodynorphin and proenkephalin mRNA levels which corresponded to the intensity of the convulsions. Conversely, hippocampal levels of immunoreactive dynorphin A (1-8) and [Met]5-enkephalin were decreased as a function of seizure frequency and intensity. The time course of KA-induced alterations in prodynorphin and proenkephalin mRNA and peptide levels was also investigated. Hippocampal prodynorphin mRNA levels rose at a dramatic rate. At 3 h following KA administration, mRNA levels were maximally elevated approximately 13-fold. The levels decreased over a 48 h period, eventually reaching control values. In contrast, proenkephalin mRNA levels increased more slowly. At 24 h, a maximal 24-fold increase was observed. At 72 h after injection, proenkephalin mRNA levels were still slightly elevated. In the same experiment, immunoreactive enkephalin peptide levels, although somewhat decreased at 3-12 h, began to increase between 12 and 24 h after injection, and were still rising at 72 h. In marked contrast, immunoreactive dynorphin peptide levels ranged from 40% to 80% of control values at all times tested.(ABSTRACT TRUNCATED AT 250 WORDS)
Dressing for success. Promoting independence among cognitively impaired elderly.
In demented persons, activities of daily living skills may deteriorate more quickly than their cognitive decline warrants because caregivers do not allow them to perform ADLs to the full extent of their abilities. Caregiver actions that promote independent behaviors were used with subjects in home and nursing home settings. Four of five home subjects showed decreased caregiver assistance and increased ability to dress more independently. Although nursing home subjects did not show a decrease in caregiver assistance, observation showed that some nursing home caregivers did incorporate behavioral strategies, suggesting potential clinical efficacy of the strategies.
Specialized ambulatory dementia clinic. Arkansas: diagnostic & treatment services for patients and families.
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Beneficial effects of psychiatric intervention on recovery after coronary artery bypass graft surgery.
The effects of perioperative psychiatric intervention were studied in 33 patients undergoing coronary artery bypass graft (CABG) surgery. All patients were evaluated preoperatively using the Mini-Mental State Exam and the Psychological Adjustment to Illness Scale-Self-Report. Participants in the study group (N = 16) had a structured psychiatric interview prior to surgery and were followed daily with supportive psychotherapy throughout their hospitalization. The number of medical complications was higher in the control group. No significant differences were found in neurologic or psychologic complications. The study group used significantly more oxycodone-acetaminophen (Percocet), but less morphine-sulfate or benzodiazepine on postoperative days 3, 4, and 6. The mean length of stay was 3 days shorter for patients in the study group. In the current era of escalating health care costs and high technology, clinical protocols and research studies that evaluate the cost effectiveness and efficacy of psychiatric intervention in medically ill patients should be pursued.
Precipitation of spinally mediated withdrawal signs by intrathecal administration of naloxone and the mu-receptor antagonist CTP in morphine-dependent mice.
We evaluated the ability of naloxone and the mu receptor antagonist CTP (D-Phe-Cys-Tyr-D-Trp-Lys-Thr-Pen-Thr-NH2) to precipitate withdrawal in morphine-dependent mice after intrathecal (i.t.) administration. The withdrawal syndromes elicited by naloxone and CTP given i.t. were compared to those of CTP or naloxone injected intracerebroventricularly (i.c.v.). When given i.t. or i.c.v., naloxone produced the classical syndrome of events including jumping, wet dog shakes, urination, defecation followed by diarrhea, and weight loss. There was no significant difference in the potency or efficacy of naloxone when it was given i.t. or i.c.v. The profile of withdrawal effects produced by i.t. CTP resembled that caused by i.c.v. CTP; both were different from that of naloxone. The withdrawal signs seen following both i.t. or i.c.v. CTP included wet dog shakes and defecation. Mice treated with i.t. CTP lost significantly less body weight than those treated with i.c.v. CTP. In addition, i.t. and i.c.v. CTP did not stimulate jumping behaviors or diarrhea. In contrast, while i.c.v. CTP resulted in increased incidence of urination, CTP given i.t. did not. These finding indicate that naloxone given spinally acts on mu receptors to precipitate wet dog shaking and defecation, but acts on other non-mu opioid receptors (i.e. delta and/or kappa) to cause jumping, urination, diarrhea and weight loss. The differential effects of CTP given i.c.v. or i.t. suggest that supraspinal mu receptors are more involved in gastrointestinal and urinary bladder function during dependence/withdrawal than their spinal counterparts.(ABSTRACT TRUNCATED AT 250 WORDS)
Spotting the borderline personality.
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The nucleus paragigantocellularis and opioid withdrawal-like behavior.
Participation of the nucleus paragigantocellularis (PGi) in mediation of opioid withdrawal was examined in conscious, unrestrained, non-opioid-dependent rats, using electrical stimulation of the PGi. A characteristic series of behaviors, which resembled those seen during naloxone-precipitated withdrawal from dependence on the opioid agonist, butorphanol, was elicited during 30 min of PGi stimulation. Thus, the behavioral syndrome has been termed opioid withdrawal-like. Simultaneous microdialysis measurement of glutamate within the locus ceruleus indicated a positive correlation between extracellular glutamate concentrations and behavioral responses. Behavioral responses were inhibited by 50% during reverse dialysis perfusion of the locus ceruleus with the glutamate receptor antagonist, kynurenic acid, without any effect on glutamate concentrations. Thus, increases in locus ceruleus glutamate partially mediate opioid withdrawal-like behavior. Intracerebroventricular (i.c.v.) injections of the opioid antagonist, naloxone, or of the mu-selective (beta-funaltrexamine) or the delta-selective (naltrindole) opioid antagonists decreased, but did not abolish, stimulation-induced behavioral responses. Similar i.c.v. injections of the kappa-selective antagonist, nor-binaltorphimine, had no effect on behavioral responses to PGi stimulation. Activation of the PGi by electrical stimulation can elicit behaviors similar to those observed during opioid withdrawal. Moreover, additional levels of complexity are evident in the neuropharmacology of PGi stimulation-induced opioid withdrawal-like behavior.
Cleft-foot closure: a simplified technique and review of the literature.
The purpose of this article is to present a simplified technique to close the cleft in the feet of children affected with congenital clefts. This technique evolved after several frustrating attempts to close the cleft with mediocre results by using triangular flaps. This report concerns nine children with 15 feet. We describe a simplified technique for cleft closure to narrow the feet. One of the children had an associated syndactyly of the foot, and two others had syndactyly of the hands. No other associated anomalies were present in these children. We operated on seven patients with a total of 42 operations. The feet with the clefts that were repaired by rectangular flaps maintained good cosmesis and function.