A survey of the content of BSc courses in pharmacology in UK universities--is it time for a core curriculum?

The 18 UK universities offering three--of four--year BSc pharmacology courses were surveyed by questionnaire to determine course content, laboratory-practical content and project or dissertation requirements. In this article David Dewhurst and Clive Page provide an overview of the study, which highlighted the fact that there is no core curriculum. There was considerable variation in course content [only a limited number of common topics were taught in depth (> 15 h timetabled time)] and the time spent doing 'wet' laboratory practicals varied considerably (range 0-145 h). A research project in the final year was the norm (although the time allocation varied considerably), but some universities used a library-based dissertation as an alternative.

Comparison of a computer simulation program and a traditional laboratory practical class for teaching the principles of intestinal absorption.

Here we describe an evaluation of the effectiveness, compared with a traditional laboratory, of an interactive computer-assisted learning (CAL) program, which simulates a series of experiments performed using isolated, everted sacs of rat small intestine. The program is aimed at undergraduate students of physiology and is designed to offer an alternative student-centered learning approach to the traditional laboratory-based practical class. The evaluative study compared two groups of second-year undergraduate students studying a module on epithelial transport: one group worked independently using the CAL program and associated learning materials, and the other group followed a conventional practical class approach, working in the laboratory under supervision. Knowledge gain of each group was measured by means of a test consisting of a range of question types (e.g., short-answer factual, calculation, interpretation) given to students before and after the module. Student attitude to both approaches was assessed by questionnaire, and the resource requirements were also compared. It was found that the knowledge gain of both groups of students was the same, that students had a positive attitude toward using CAL programs of this type, and that the cost of the conventional laboratory-based approach was five times greater. The potential for integrating CAL programs into the undergraduate curriculum is discussed.

A computer simulation for learning about the physiological response to exercise.

An interactive computer program written for IBM-compatible microcomputers, which simulates the physiological response to graded exercise in healthy individuals, is described. The program presents high-resolution graphic data (heart rate, pulmonary ventilation, oxygen consumption, and blood lactate concentration) in a form comparable to that of a chart recorder display. Data are derived from an empirical model that allows users to select certain parameters of the subject they wish to investigate, including sex, age, height, weight, and level of training. Measurements may be taken directly from the monitor screen by use of the cross-hair cursor facility provided. The program has been positively evaluated in use by undergraduate students and shown to be an effective teaching aid. The potential use of the software in light of these findings is discussed.

Automated analysis of prerecorded evoked electromyographic activity from rat muscle.

An automated microprocessor-based data acquisition and analysis system has been developed specifically to quantify electromyographic (EMG) activity induced by the convulsant agent catechol in the anaesthetized rat. The stimulus and EMG response are recorded on magnetic tape. On playback, the stimulus triggers a digital oscilloscope and, via interface circuitry, a BBC B microcomputer. The myoelectric activity is digitized by the oscilloscope before being transferred under computer control via a RS232 link to the microcomputer. This system overcomes the problems of dealing with signals of variable latency and allows quantification of latency, amplitude, area and frequency of occurrence of specific components within the signal. The captured data can be used to generate either signal or superimposed high resolution graphic reproductions of the original waveforms. Although this system has been designed for a specific application, it could easily be modified to allow analysis of any complex waveform.

Relative importance of estrogen and progesterone receptor assays as prognostic indicators in primary breast cancer: a short-term study.

This short-term study of the relative importance of estrogen and progesterone receptors shows that progesterone receptor correlates better than estrogen receptor with tumor recurrence regardless of lymph-node status. Life-table analysis has effectively identified only two groups of patients that may be classified by progesterone receptor status alone. Progesterone-receptor negativity correlated well with tumors of histological Grade III; estrogen-receptor positivity correlated with Grade I and II tumors. The earlier recurrence of Grade III breast tumors may explain why progesterone receptor is a better prognostic indicator than estrogen receptor in short-term studies.

Possible role of excitatory amino acids in the convulsant action of catechol.

The effects of several excitatory amino acid receptor antagonists on sensory-evoked electromyographic activity induced by catechol have been studied in urethane-anaesthetised rats. 2-Amino-5-phosphono-valearic acid (1.2 mumol/kg i.c.), cis-2,3-piperidine dicarboxylic acid (1.4 mumol/kg i.c.), gamma-D-glutamyl-glycine (2.0 mumol/kg i.c.), 2-amino-7-phosphono-heptanoic acid (230 mumol/kg i.v.) and MK-801 (5 mg/kg i.p.) all significantly decreased the frequency of occurrence of those components of the sensory evoked EMG dependent on supraspinal structures, but were without effect on the spinal component.

Sites and mechanisms of action of catechol (1,2-dihydroxybenzene) in the rat olfactory cortex slice.

Synaptic transmission in the isolated olfactory cortex slice from the rat was monitored by recording the surface field potentials evoked on lateral olfactory tract (LOT) stimulation. Catechol (approximately 0.05 to 2 mM) caused a concentration-dependent, partially reversible increase in the amplitudes of all field potentials. In a series of conditioning experiments, catechol (1 mM) potentiated postsynaptic inhibition by a mechanism which was at least partially picrotoxin-insensitive. When the relationship between the stimulus input and evoked output was investigated in picrotoxin-treated slices, for a given tract action potential amplitude, catechol (0.25 and 0.5 mM) increased the amplitude of the field potential known as the N-wave; in contrast, for a given N-wave amplitude, the latency of the population spike was increased. Catechol (1 mM) increased the K+-evoked release of endogenous aspartate by a tetrodotoxin-insensitive mechanism whereas the release of glutamate and gamma-aminobutyric acid (GABA) was unaffected. Catechol (1 mM) had no effect on submaximal depolarizations evoked by L-aspartate, L-glutamate or GABA. It is concluded that catechol potentiates excitatory transmission at the LOT-superficial pyramidal cell synapse, possibly by increasing evoked transmitter release. Other synaptic actions of catechol may be consequent upon this increased excitatory input but the results do not exclude the possibility of separate and distinct actions on polysynaptic transmission.

Non involvement of gamma-aminobutyric acid in catechol-induced seizures.

The effects of certain anticonvulsant agents, namely, valproate, diazepam and phenobarbitone were investigated on catechol-induced spontaneous and evoked convulsions, in anaesthetized rats and mice. Valproate and diazepam significantly reduced the intensity of spontaneous convulsions and the frequency of occurrence of the longer-latency components (M2 and M3) of the evoked muscle response. Phenobarbitone significantly reduced spontaneous convulsions and the M3 component of the evoked muscle response. None of the drugs affected the short latency M1 component indicating a supra-spinal site of action of these drugs. Agents which modify gamma-aminobutyric acid (GABA)-mediated transmission were without effect on the frequency of occurrence of M1, M2 or M3. The results suggest that the convulsant action of catechol is not dependent on antagonism of GABA-mediated inhibition.

The value of 6-phosphogluconate dehydrogenase (6-PGDH) activity as a marker of tumour cellularity and prognostic indicator in primary breast cancer.

The value of 6-phosphogluconate dehydrogenase (6-PGDH) activity as a cytosolic marker of tumour cellularity has been assessed, together with its use as a prognostic indicator for primary breast cancer in 87 patients over 4 years. 6-PGDH activity shows a good correlation with histologically-assessed tumour cellularity in a sample of 114 patients (correlation coefficient = 0.83). Patients whose primary breast tumour had a high 6-PGDH activity showed poor relapse-free survival times when compared to those with low 6-PGDH activities (Log Rank chi 2 = 6.87, P less than 0.01). This compared with a Log Rank chi 2 of 2.22, P less than 0.20 for oestrogen positive and negative patients. These results suggest that 6-PGDH activity is a better prognostic indicator in primary breast cancer than oestrogen receptor status.

Some characteristics of the long-latency component of the evoked muscle response induced by administration of catechol to the anaesthetized rat: a neurophysiological and neuropharmacological investigation.

Administration of catechol to rats anaesthetized with urethane produces a central excitatory state during which an EMG consisting of three temporally distinct components (M1, M2 and M3) can be recorded from forelimb and hindlimb muscles to electrical stimulation of cutaneous afferents. The probability of occurrence of all three components was measured in flexor and extensor muscles of fore- and hindlimb and showed that the long latency component (M3) occurred less frequently in hindlimb muscles than forelimb and that its probability of occurrence in hindlimb extensors was significantly reduced as compared to flexors. A possible reflex pathway for this long latency component of the EMG is suggested. Phenobarbitone (5 mg kg-1 i.v.) had no significant effect on the probability of occurrence of M1, M2 or M3. These results suggest that the long latency component (M3) is not due to activation of a spino-bulbo-spinal reflex as has been previously suggested. Cholinoceptor blocking drugs were found to reduce significantly the probability of occurrence of M2 and M3 and anticholinesterases to increase the probability of M2. None of the drugs was found to affect the short latency M1 component of the EMG. These results are discussed in relation to the possible reflex pathways of all three components of the EMG.

A pharmacological investigation of the electrically evoked convulsive activity induced by administration of catechol in the anaesthetized rat.

1 The response evoked by electrical stimulation at the wrist has been recorded from muscles of the forelimb of anaesthetized rats induced to convulse by administration of catechol.2 This response can be divided into three temporally distinct components, the characteristics of which have been described.3 The probability of occurrence of the two early components of the response has been measured before and after administration of various drugs. The results show that the first component is not affected by cholinoceptor or adrenoceptor blocking drugs or anticholinesterase agents. The probability of occurrence of the second component is significantly reduced by cholinoceptor blocking drugs and increased by physostigmine.4 The implications of these results in explaining the convulsant actions of catechol are discussed.

The permeability of the secretin stimulated exocrine pancreas to non-electrolytes.

1. A method of measuring the permeability of the pancreas by determining the apparent reflexion coefficient (sigmaA) is described, in the isolated pancreas secreting maximally under the influence of secretin. The principle is to add a non-electrolyte to the perfusate which will create an osmotic gradient (RTsigmadeltaC) counter to that of active transport and reduce the secretion rate. This is compared with the effect of an equal concentration (0.1 M) of sucrose (RTdeltaC; sigma = 1). The apparent reflection coefficient is obtained by dividing the percentage reduction in the secretion rate due to the test molecule with that due to sucrose. 2. Sucrose when added to the perfusate inhibits pancreatic secretion. For every 10 mM increase in sucrose concentration, the secretion rate was inhibited by 7.1%. It has been estimated that an osmotic gradient of 131 m-osmole/kg water will cause zero flow rate. This is a measure of the pressure required to counteract the local osmotic gradient set up by active transport, it is equivalent to about 3.4 atm. 3. Non-electrolytes with molecular volumes greater than about 85 cm3 mole-1 are relatively impermeable, below this value they enter the pancreatic juice with increasing ease as the molecular volume decreases. 4. SigmaA for a number of compounds has been measured: urea 0.17; ethanediol 0.27; thiourea 0.51; glycerol 0.69; creatinine 0.81; erythritol 0.91; arabinose 0.96; xylose 0.98; sorbitol 0.98. 5. The addition of non-electrolytes to the perfusate had effects on pancreatic secretion which were a function of sigmaA. For molecules with sigmaA lying between 0.81 and 1.0 an osmotic load of 0.1 M increased both the concentration of sodium plus potassium and the concentration of chloride plus bicarbonate by about 50 m-mole/l. Whereas the cation change is almost exclusively one of sodium that of the anions was preferentially an increase in chloride. For compounds with sigmaA lying between 0 and 0.81 the concentration of sodium plus potassium was proportional to sigmaA. 6. A number of compounds have been described which inhibit pancreatic secretion, other than by an osmotic effect. These include acetaldehyde, thioglycerol, nicotinamide, ribose, dihydroxyacetone, and glyceraldehyde. 7. It is concluded that the pancreas is more permeable than the gall-bladder of rabbit, fish and bullfrog, the proximal tubule of the kidney of rat and the small intestine of bullfrog, but is probably similar to that of small intestine of guinea-pig and man.

A pharmacological study of the spontaneous convulsive activity induced by 1,2-dihydroxybenzene (catechol) in the anaesthetized mouse.

1. The convulsive activity induced by catechol has been examined in anaesthetized mice either by determining the CD50 for the convulsions in drug-treated and control animals, or by studying the effects of various drugs on the total whole body activity. 2. The results indicate that catecholamines play no part in the mechanism of action of catechol. Drugs which alter cerebral catecholamine levels had no effect on the convulsions, nor did the alpha- and beta-adrenoceptor blocking drugs. 3. 5-Hydroxytryptamine (5-HT) could possibly be important, though results with drugs which either change brain 5-HT levels, or block 5-HT receptors were inconsistent. 4. gamma-Aminobutyric acid also appears not to be involved in the mechanism of action of catechol. 5. The results strongly suggest that catechol primarily activates a central cholinergic system, in that muscarinic and nicotinic receptor blocking drugs inhibit, and anticholinesterases potentiate the convulsions.