Gary C. Rosenfeld

Advancing educators and education by defining the components and evidence associated with educational scholarship

Objective  This study aimed to establish documentation standards for medical education activities, beyond educational research, for academic promotion consistent with principles of excellence and scholarship.

Pirenzepine (LS 519): A weak inhibitor of acid secretion by isolated rat parietal cells

Carbamylcholine-stimulated potentiation of dibutyryl cyclic AMP-induced acid secretion by isolated rat parietal cells was specifically inhibited by the muscarinic cholinergic antagonist pirenzepine at an IC50 of 1.1 microM. In contrast to the weak inhibition by pirenzepine, the potentiation was inhibited by atropine at an IC50 of 4.6 nM. In vivo, pirenzepine is one-tenth as potent as atropine as an inhibitor of acid secretion. The weak activity of pirenzepine shown in this study suggests that its in vivo inhibitory activity is likely due to an interaction with a site involved in the regulation of gastric acid secretion which has higher-affinity muscarinic receptors for pirenzepine than those associated with parietal cells.

Isolated rat gastric parietal cells: Cholinergic response and pharmacology

Abstract Isolated, partially purified or enriched rat gastric muscosal parietal cells were shown to respond to carbamycholine (EC 50 = 2 μ M) and other muscarinic cholinergic agonists as measured by an increased accumulation of 14 C-aminopyrine, an indirect measure of acid secretion. The secretory response to carbamylcholine was shown to be inhibited stereoselectively and reversibly by nanomolar concentrations of muscarinic cholinergic antagonists. Non-muscarinic antagonists, including cimetidine, were either ineffective or very weak inhibitors. The affinity constants calculated for cholinergic antagonist inhibition of 14 C-aminopyrine accumulation induced by carbamylcholine were similar to those previously calculated from direct binding studies on purified parietal cell particulate fractions using 3 H-QNB (1). These studies support the existence of specific parietal cell muscarinic cholinergic receptors with which the natural secretagogue acetylcholine interacts to regulate gastric acid secretion.

Neurotransmitter mediation of morphine hypothermia in rats.

Abstract Subcutaneous (sc) injections of morphine (10 mg/kg) caused transient falls in body temperature of rats. The hypothermic responses to morphine were inhibited by the prior intracerebroventricular (icv) administration of methysergide or phentolamine. Methysergide treatment also prevented hypothermic responses to icv 5-hydroxytryptamine (5-HT), but not responses to icv norepinephrine or dopamine. Phentolamine inhibited responses to icv norepinephrine and dopamine, but not to 5-HT. Haloperidol, which inhibited responses to icv dopamine, did not alter the hypothermia induced by sc or icv morphine. The results indicate that both 5-HT and norepinephrine participate as central mediators of morphine-induced hypothermia.

Histamine H2-receptors in the gastric mucosa: Role in acid secretion

Abstract Currently, two major hypotheses dominate thinking about the role of histamine in the regulation of gastric acid secretion. Code has proposed that histamine is the final common mediator of secretagogue action on the parietal cell while Konturek and Grossman have suggested a multi-receptor control of the secretory process. Experimental results derived from the use of recently synthesized histamine H2-receptor antagonists have been used by both groups to support their hypotheses. Paradoxically, these hypotheses depend on the presumed specificity of the H2-antagonists in blocking histamine mediated acid secretion while the apparent lack of such secretagogue specificity of the H2-antagonists is an important basis for the development of the hypotheses. Our review will analyze the experimental evidence which implicates the histamine H2-receptor in the control of hydrogen ion secretion as well as evidence for and against receptor specificity in the gastric mucosa of histamine H2-receptor antagonists.

Histamine stimulation of rat gastric parietal cell adenylyl cyclase: modulation by guanine nucleotides.

Abstract Histamine activation of adenylyl cyclase activity in sonicated enriched rat gastric parietal cells showed a time, temperature, and concentration dependence upon guanine diphosphoimide (Gpp(NH)p). Enzyme activation was first order with Gpp(NH)p alone or Gpp(NH)p plus histamine. The K a for Gpp(NH)p was ~2 μ m and was not influenced by histamine. GTP and GDP were inactive alone or with histamine and were competitive with Gpp(NH)p, showing apparent K i s of near 0.4 and 0.3 μ m , respectively. In the presence of Gpp(NH)p, parietal cell adenylyl cyclase was activated by histamine with an EC 50 of 24 μ m , the most potent in a series of histamine analogs, further substantiating an H 2 -receptor classification for this response. H 2 -Receptor antagonists were competitive inhibitors with submicromolar K i s. Preincubation of parietal cells with histamine and Gpp(NH)p resulted in adenylyl cyclase activity up to 15 times the basal level. The activated state was retained after washing the cells free of histamine and Gpp(NH)p and was not reversed by the subsequent addition of either histamine, cimetidine, or GTP. The other gastric acid secretagogues, pentagastrin and carbamylcholine, were without effect upon histamine activation or the activated state of adenylyl cyclase. These results describe a level of control of histamine-sensitive adenylyl cyclase that requires consideration in the activation of the parietal cell H 2 -receptor system by histamine to modulate acid secretion.

A Problem-Based Learning Approach to Incorporating Nutrition into the Medical Curriculum

Abstract Problem Based Learning (PBL) provides a unique opportunity for medical students to learn nutrition principles in the context of evidence-based clinical cases. At the University of Texas Medical School at Houston (UTMSH), PBL is a major component during the second year of the four year undergraduate medical curriculum. A recent review of forty-two clinical cases has shown that over half of the cases include nutrition-specific objectives related to diagnosis, therapy, prognosis, or disease prevention. Thus, these PBL cases provide students the opportunity to study a broad range of nutrition topics in a clinically relevant context. The students’ nutrition knowledge is evaluated using clinically-oriented, multiple-choice questions. In order for students to develop fully their competency in clinical nutrition topics, they are also provided a foundation in basic nutrition principles. This report describes a comprehensive approach through a case-based curriculum to help prepare students in their pre-clinical years for the nutritional care of patients in their clerkships, residency, and as practicing physicians.

Low attendance by basic science educators at medical education meetings.

Background: Recently, concern has been expressed about the perception that few basic science educators (BSE) attend national and regional medical education meetings. Purpose: This study was designed to analyze the issues affecting BSE decisions about whether to attend medical education meetings. Method: An online survey was created and submitted to basic science course directors at the 128 U.S. allopathic medical schools. Results: Responses from 486 BSE suggest that because of the pressure to obtain research funding and achieve academic promotion, participation in medical education meetings is not a high priority with most BSE. Conclusions: BSE attendance at medical education meetings can be improved, but it will require joint efforts by the BSE home institution and medical education organizations.

Regulation of gastric acid secretion

Despite the fact that increased gastric acid secretion is not diagnostic for peptic ulcer disease, it is generally believed that where there is no acid there is no ulcer. Thus, there remains a strong medical interest in the understanding of the cellular regulation of gastric acid secretion by the major secretagogues, histamine, gastrin and acetylcholine and therapy designed to interfere with this regulation. Released as a result of various physiological stimuli, including food, these paracrine, endocrine, and neurohumoral agents act by both direct and indirect pathways to effect the production and secretion of hydrogen ions from parietal cells located in the lower portion of the oxyntic glands in the fundic stomach. Recently, the study of gastric acid secretion has been advanced by the advent of methods to isolate gastric oxyntic glands and gastric parietal cells. These preparations have allowed the formulation of new concepts to explain in vivo and in vitro physiological and pharmacological data derived from studies on the interactions of hormones that regulate the acid secretory process14,17,20.