5-HT3 Receptor-independent Inhibition of the Depolarization-induced 86Rb Efflux from Human Neuroblastoma Cells,TE671, by Ondansetron

The 5-HT₃-receptor antagonist, ondansetron, has been shown to have positive effects in selected in-vivo models of memory impairment and anxiety. The exact mechanisms underlying such bioactivities are unknown. In the present work, an ⁸⁶Rb efflux bioassay was used to show that ondansetron has a unique ability to block voltage-gated potassium channels in TE671 human neuroblastoma cells. This intrinsic potassium-channel-blocking (KCB) property is relatively weak (IC50 20 (M), but is not shared by other 5-HT₃-receptor ligands including zatosetron, MDL 72222, LY 278, 584, zacopride, 1-phenylbiguanide, and ICS 205–930 (tropisetron). Pre-incubation of the target neuroblastoma cells with several 5-HT-receptor ligands including 5-hydroxytryptamine, 8-OH-DPAT, ketanserin, 2-methyl-5-HT, as well as a number of potent 5-HT₃ agonists and antagonists and two selective neurotoxins, failed to abolish the KCB action of ondansetron. A preliminary structure-activity relationship analysis indicates that the KCB activity of ondansetron is almost entirely attributable to its structural nucleus, 2,3-dihyro-9-methyl-4(lH)-carbazolone. It is hypothesized that the KCB action of ondansetron is mediated through receptors other than 5-HT₃ receptors. The KCB activity of ondansetron may be a significant factor in the in-vivo cognition-enhancing activities of this compound, conceivably due to depolarization of the hippocampal synaptic membranes and a consequent augmentation of neurotransmission.     

Elevated levels of acute phase plasma proteins in major depression.

Levels of acute phase and other plasma proteins were measured in 21 men with major depression, 28 men with alcohol dependence, and 12 men who acted as controls. The depressed men had significantly elevated levels of the acute phase proteins, haptoglobin and alpha-1-antichymotrypsin, and of immunoglobulin G. The elevations in haptoglobin and alpha-1-antichymotrypsin were highly correlated with each other, and were correlated with the severity of depression and negatively correlated with the thyroid stimulating hormone response to thyrotropin. The alcoholic men had elevated haptoglobin levels, but significantly decreased levels of immunoglobulin G. These findings provide further evidence for an inflammatory response during depression.     

Effects of bromocriptine on hepatic cytochrome P-450 monooxygenase system

We have evaluated the in vitro effects of bromocriptine (Br), on the hepatic cytochrome P-450 monooxygenase system of rats pretreated with saline phenobarbitone (PB) and beta-naphthoflavone (BNF). Br inhibited ethoxyresorufin O-dealkylase (EROD) activity in liver microsomes of rats pretreated with saline and PB but not in BNF pretreated animals. Maximum inhibition of EROD activity by Br in the microsomes of saline and PB pretreated rats were 50%-60% of the control. In contrast, a dual effect was observed on aminopyrine N-demethylase activity (APD) by Br in microsomes of saline, PB and BNF pretreated rats. At a low concentration (25 microM), Br inhibited the activity of APD to a similar extent in all pretreatment groups; however, with higher concentrations of Br (50 microM to 300 microM), enhancement of APD activity was observed. Br (300 microM) increased the APD activity to 2-3 times the control level in microsomes of rats pretreated with saline, PB or BNF. Spectral studies revealed a Type II binding of Br to cytochrome P-450 from microsomes of saline and PB pretreated rats. A reverse type I binding was observed for BNF induced microsomes. In addition, Br also enhanced NADPH cytochrome c (P-450) reductase activity to a similar extent in all pretreatment groups. These results suggest that the inhibition of EROD activity may be due to direct binding by Br to certain isozymes of cytochrome P-450 and that the enhancing effect of Br on APD activity may be in part due to the activation of the NADPH cytochrome c reductase component of the cytochrome P-450 monooxygenase system.     

Pediatric resident performance. The reliability and validity of rating forms.

A large pediatric residency program conducted an extensive analysis of the reliability and validity of the rating forms used to evaluate the pediatric residents enrolled in the program. Analyses were conducted on groups of residents who took the Pediatric In-Training Program (PITE) from 1977 through 1981. An average of 7.1 faculty members rated each resident on a standard form. The data indicate that although the reliability of individual ratings is very low, several factors achieved acceptable levels of reliability when aggregated. The first-year rating of history-taking ability correlated significantly with the PITE but ratings for more advanced residents did not correlate with PITE scores, mostly because of ceiling effects.     

Advanced practice nurses in emergency care settings: A demographic profile.

INTRODUCTION: Very little is known about clinical nurse specialists and nurse practitioners (advance practice nurses [APNs]) who practice in emergency care settings. The Advanced Practice Committee of the ENA sought to determine a profile of these individuals. METHODS: Surveys were distributed to all registrants at 2 ENA conferences and posted on the ENA Web site. This survey asked 17 questions concerning the demographic characteristics of the APN respondents (eg, education, experience, certification, state recognition, and practice area). The survey was completed by 166 APNs. RESULTS: APNs had considerable experience as ED registered nurses before becoming an APN. They obtained their APN education at the master's degree or post-master's degree level. State recognition was required for 89.2% of the APNs. The majority of APNs (61.4%) obtained their certification through the American Nurses Credentialing Center. Nurse practitioners were predominantly family nurse practitioners (43%), and clinical nurse specialists were either critical care clinical nurse specialists (8.9%) or had other certifications (5.9%). APNs provided services in both the main emergency department and the fast track (45.7%) and were relatively new to their role as an APN. DISCUSSION: Consistent with current educational and certification requirements, the vast majority of APNs held a master's degree. Although relatively new to their role as APNs in emergency care, they were nonetheless very experienced as ED registered nurses. The majority of APNs were certified, even though that is not required for practice in all states. Continued research is needed to identify the most effective utilization of APNs, document their contributions to patient care outcomes, and develop strategies to meet their educational and practice needs.     

Presence of circulating suppressive factor for muscarinic acetylcholine receptor in senile dementia

Alzheimer's disease is one of the main causes of senile dementia. Although its pathogenesis is not clear, some evidence has revealed that the activity of acetylcholine receptor in the brains of these patients is decreased. In the present study, possible circulating factors, affecting the muscarinic acetylcholine receptor of the synaptic vesicle from the rat brain, were evaluated in the serum of 95 senile subjects (34 males and 61 females, mean +/- SD age of 77.5 +/- 8.6 years). The cognitive function of these subjects was assessed by their Mini-Mental State scores, and they subjects were divided into non-dementic-subjects with a score of 21 or more, or subjects with dementia with a score of 20 or less. The latter were further divided into senile dementia with Alzheimer type (SDAT) and vascular type dementia (VS) using Hatchinski's ischemic score. The mean suppression rate by the serum from the SDAT patients on the binding of tritiated quinuclidinyl benzilate (3H-QNB), an antagonist for muscarinic acetylcholine receptor, to the rat synaptic membrane, was 18.1 +/- 7.2% of the control value, which was significantly greater than that of the non-dementic subjects, (4.7 +/- 3.8%). However, that in the VD group (8.4 +/- 6.8%), was not significantly different from the control value. Moreover the suppression rate of the serum on 3H-QNB binding showed significant positive correlated with score for the Mini-Mental State (r = 0.480, p less than 0.01) in the SDAT group. These data support the hypothesis that circulating suppression factors may participate in the pathogenesis of SDAT.     

The Alcohol Beverage Warning Label: When Did Knowledge Increase?

This article presents data on the awareness of the alcohol beverage warning label among a sample of 5,169 inner city African-American gravidas seeking prenatal care. While the label law was implemented in November 1989, a significant increase in knowledge of the label did not occur until March 1990. Women who predominantly consumed wine coolers and beer, and those under age 30 were more likely to know about the label than their counterparts.     

Coordinated diagnostic approach for adult obstructive lung disease in primary care.

AIMS: To present an age-stratified approach to the diagnosis of obstructive lung disease based on asthma and COPD guidelines and epidemiology. METHODS: Asthma guidelines emphasize the role of the history and physical examination, with pulmonary function used primarily to confirm the diagnosis. COPD guidelines begin with symptoms and risk exposure, presenting spirometry as the primary diagnostic maneuver. Data from the National Health Interview Survey and the Third National Health and Nutrition Examination Survey illustrate relationships in prevalence of asthma and COPD in nationally representative samples. RESULTS: Asthma prevalence in adults declines with age from 5-10% at age 20-40 to 4-8% above age 60. COPD is uncommon in adults under age 40 but increases with age, surpassing asthma in older adults. CONCLUSIONS: These trends suggest that asthma screening is most useful in adults up to age 40, after which COPD screening and differential diagnosis are of comparable or greater utility.     

Physiological evaluation of gait disturbances post stroke.

A large proportion of stroke survivors have to deal with problems in mobility. Proper evaluations must be undertaken to understand the sensorimotor impairments underlying locomotor disorders post stroke, so that evidence-based interventions can be developed. The current electrophysiological, biomechanical, and imagery evaluations that provide insight into locomotor dysfunction post stroke, as well as their advantages and limitations, are reviewed in this paper. In particular, electrophysiological evaluations focus on the contrast of electromyographic patterns and integrity of spinal reflex pathways during perturbed and unperturbed locomotion between persons with stroke and healthy individuals. At a behavioral level, biomechanical evaluations that include temporal distance factors, kinematic and kinetic analyses, as well as the mechanical energy and metabolic cost, are useful when combined with electrophysiological measures for the interpretation of gait disturbances that are related to the control of the central nervous system or secondary to biomechanical constraints. Finally, current methods in imaging and transcranial magnetic stimulation can provide further insight into cortical control of locomotion and the integrity of the corticospinal pathways.