Accumulation of Mn, Co, Zn, Rb, Cd, Sn, Ba, Sr, and Pb in the otoliths and tissues of eel (Anguilla anguilla) following long-term exposure in an estuarine environment.

Aiming at increasing the resolution of otolith tracers, we investigated the possibility to use Mn, Co, Zn, Rb, Cd, Sn, Ba, Sr, and Pb otolith composition to retrieve the movements of eels (Anguilla anguilla) in the lower Gironde watershed. Caging experiments were designed to validate the site specific otolith signatures. Individually identified eels were reared in cages in three locations along the estuarine and river gradient. Three trials were set up for successive periods of 3 months and 6 months. Water Mn, Co, Zn, Rb, Cd, Sn, Ba, Sr, and Pb concentrations were monitored. The eel otolith composition corresponding to the experimental period was measured with an ICPMS coupled with a femtosecond laser. Liver Cd, Zn and Pb concentrations were measured. For each caging experiments, we tested the influence of individual weight gain, caging site and trial on elemental otolith concentrations. Mn, Co, Zn, Rb, Cd, Sn, Ba, Sr, and Pb were detected in eel otolith above the detection limits. Otolith Sr and Ba concentrations significantly discriminated the caging sites for one trial. Individual weight gain did not have a significant influence on otolith elemental concentrations. Co, Rb, Cd, Sn, Zn, Sr and Ba otolith concentrations were significantly influenced by the trials. Water elemental composition was only partly reflected by otolith elemental composition. The results showed that otolith composition had a more integrative value than water composition. Complex elemental seasonal variations and individual eel incorporation potential complicated the interpretation of otolith composition. Liver and otolith Cd and Zn concentrations did not show a statistically significant correlation.

Follow-up in train-the-trainer continuing medical education events.

BACKGROUND: The purpose of train-the-trainer (TTT) programs within the context of continuing medical education (CME) is to help facilitators acquire and/or enhance their skills at leading CME sessions. The provision of follow-up is one feature of successful CME workshops over which CME providers have some control. Follow-up is defined as any encounter between participants and workshop leaders, following an initial workshop or other development session, and is designed to enhance, maintain, reinforce, transfer, extend, or support the learning from the original workshop. In this article, we elaborate on the use of audio teleconferences to provide follow-up for a TTT workshop in Saskatchewan, a largely rural province in western Canada. METHODS: The teleconferences began 6 weeks after the workshop and were held at approximately 6-week intervals, with five conference calls in total. Each lasted about 45 minutes. Participants were interviewed to determine their view of the value of the teleconferences. RESULTS: Participants reported learning from the teleconferences and feeling more prepared to conduct CME sessions due to their participation in the teleconferences. Participants missed teleconferences only for extenuating circumstances (e.g., emergency deliveries). FINDINGS: We have found that audio teleconferences allow for and encourage professional discussion that is crucial to changing practices. They are an effective way to incorporate follow-up to TTT workshops when participants travel great distances to attend.

Using a Lego-based communications simulation to introduce medical students to patient-centered interviewing.

PURPOSE: Teaching patient-centered interviewing skills to medical students can be challenging. We have observed that 1st-year medical students, in particular, do not feel free to concentrate on the interviewing skills because they are preoccupied with complicated technical medical knowledge. The Lego simulation we use with our 1st-year students as part of a professional-skills course overcomes that difficulty. SUMMARY: The Lego activity is a role play analogous to a doctor-patient interview that uses identical sets of Legos for the "doctor" and for the "patients" and a small construction that represents a patient history. CONCLUSIONS: With a simple questionnaire, data were collected from students at different points during instruction. Results indicate that the Lego activity was very effective in helping students learn the importance of open-ended questioning. It also was rated as highly as the very dynamic interactive part of the instructional session. The effectiveness of the Lego activity may be due to the properties of analogies.

If students are not customers, what are they?

The answers to questions about the relationship between faculty and students-including medical students-depend on an understanding of the nature of teaching and the underlying ethical principles of our society. The authors maintain that teaching is purposive, rational, communal, and moral. They assert that Western society is based on the values of liberal democracy and that the key ethical principles for the professions that are derived from those values are autonomy, standard of care, and respect for democratic institutions. There are three candidates for ethical models on which to base the relationship between students and faculty. Two of them (clientism and paternalism) the authors reject. The one that they favor (the fiduciary model) is based on mutual trust and respect, which both students and faculty have responsibilities to maintain. Using that model, the authors conclude that students are, in some aspects, customers of faculty. This student-centered approach is balanced by treating society and other faculty as customers as well. Pathologies in medical education attributed to clientism (such as an obsession with marks and overemphasis on memorization) existed well before medical students were purportedly being treated as customers; perhaps it is not the student who is "broken" but the system in which the student is made to function. Whether students are called customers, clients, knowledge workers, or simply students, faculty must involve them more in shaping their education and in dealing with enduring problems that profoundly affect their learning.

Pharmacological characterization of muscarinic receptors implicated in rabbit detrusor muscle contraction and activation of inositol phospholipid hydrolysis in rabbit detrusor and parotid gland.

In the present study, we evaluated the pharmacological characteristics of the functional muscarinic receptors implicated in rabbit detrusor contraction and coupled to inositol phospholipid turnover in rabbit detrusor and parotid gland. The selectivity of several muscarinic antagonists for detrusor vs. salivary gland muscarinic receptors was also examined. The affinities for the muscarinic m1-, m2- and m3-receptor subtypes were determined using membranes from human cloned receptors expressed in CHO-K1 cells using [3H]-N-methyl scopolamine as a radioligand. Anti-muscarinic activity was determined in isolated rabbit detrusor by measuring the displacement of the contractile response to carbachol, and in rabbit detrusor and rabbit parotid by measuring the displacement of inositol phospholipid hydrolysis (total inositol phosphate accumulation) to carbachol. A significant correlation was found between the potencies to antagonize carbachol-induced rabbit detrusor contraction (pK(B)) and the affinities (pKi) for the m3-receptor subtype (r = 0.93, P = 5 x 10(-6)). Lower, but significant, correlations [0.88 (P = 6.3 x 10(-5)), 0.72 (P = 4.6 x 10(-3))] were obtained with m1- or m2-receptor subtypes, respectively. Each muscarinic antagonist tested displayed similar potency to antagonize carbachol-stimulated inositol phospholipid hydrolysis in rabbit detrusor and parotid (r = 0.96, P = 8 x 10(-3)). A significant correlation was found between the potencies to antagonize carbachol-stimulated inositol phospholipid hydrolysis (pK(B)), determined in rabbit detrusor and rabbit parotid, and the affinities (pK(i)) for the m3-receptor subtype [r = 0.96 (P = 0.01), 0.99 (P = 5 x 10(-5)), respectively] and for the m1-receptor subtype [r = 0.98 (P = 3.5 x 10(-3)), 0.94 (P = 0.02), respectively] but not for the m2-receptor subtype [r = 0.33, 0.57, ns, respectively]. In each in vitro assay, methoctramine (preferential M2 selective antagonist) and pirenzepine (preferential M1 selective antagonist) were slightly potent. We suggest that the muscarinic receptor implicated in the response to carbachol in rabbit detrusor and parotid gland corresponds to the M3-subtype. None of the muscarinic antagonists studied in rabbit tissues displayed preferential affinity for the detrusor.

Mechanisms of the hypoglycemic effects of the alpha2-adrenoceptor antagonists SL84.0418 and deriglidole.

The effects of the alpha2-adrenoceptor antagonist SL84.0418 and its two enantiomers, (+) deriglidole and (-)SL86.0714 on glucose and insulin levels were examined in mice and in neonatal streptozotocin-induced diabetic rats. It was recently demonstrated in mouse pancreatic beta-cells that both deriglidole and SL86.0714 inhibit ATP-sensitive K+ channel with similar potency whereas alpha2-adrenoceptors are blocked only by deriglidole. In the present study, we showed, in vivo in mice, that SL84.0418 and deriglidole potently reduced glycemia and antagonized diazoxide-induced hyperglycemia, whereas SL86.0714 and tolbutamide were markedly less potent. In diabetic rats, SL84.0418 and deriglidole (10 mg/kg i.p.) fully normalized glucose tolerance whereas SL86.0714 and tolbutamide only slightly improved it. Five min after deriglidole administration in mice a marked and short lasting rise in insulin levels was observed, followed by a progressive reduction of glycemia. In diabetic rats, insulin and norepinephrine levels rose 15 min after deriglidole administration. Sympathetic outflow blockade by chlorisondamine, beta-adrenoceptor blockade by propranolol or their combination markedly reduced deriglidole-induced rise in insulin levels in a similar manner. Furthermore, in chlorisondamine-treated animals norepinephrine levels were strongly lowered and not modified by deriglidole and propranolol administration. However, in spite of sympathetic outflow and beta-adrenoceptor blockade, a moderate rise in insulinemia was still observed after deriglidole administration. Taken together these data demonstrate that deriglidole is the enantiomer that mediates the antihyperglycemic and insulin secretory effects of SL84.0418. Our study suggests that the major part of deriglidole effects is the consequence of the blockade of prejunctional alpha2-adrenoceptors that have reinforced the release of catecholamines in adrenergic nerve endings and indirectly activated postjunctional beta-adrenoceptors to further potentiate insulin secretion. However, it is also suggested that another undefined mechanism is involved in deriglidole potentiation of insulin secretion.

Involvement of alpha 2-adrenoceptors in metabolic and hormonal responses to a mixed meal in beagle dogs.

The effects of alpha 2-adrenoceptor blockade or activation on glucose, insulin, free fatty acids (FFA), and glycerol responses to a mixed meal were studied in the beagle dog. The alpha 2-adrenoceptor antagonist deriglidole (1 mg/kg po), administered 45 min before feeding, significantly reduced glycemia and increased insulin, FFA, and glycerol levels. Although the alpha 2-adrenoceptor agonist UK-14.304 (3 micrograms/kg sc), administered 15 min before feeding, had no effect per se, it completely blocked meal-induced insulin release, thus promoting a mild increase in glycemia, and prolonged the meal-induced FFA decrease. Deriglidole antagonized the reduction of insulin secretion and the hyperglycemia induced by UK-14.304. The meal-induced fall in FFA levels was still observed after deriglidole treatment and was markedly amplified when UK-14.304 was administered with deriglidole. These results suggest that, in the dog, insulin release and lipolysis are very sensitive to alpha 2-adrenoceptor stimulation. It is also suggested that the meal-evoked decrease in lipid mobilization results from an increase in alpha 2-adrenoceptor stimulation rather than from an increase in insulin secretion.

Inhibition of insulin release induced by galanin in the dog is not exclusively mediated by activation of ATP-sensitive K+ channels.

Exogenous galanin (9 pmol/min during 20 min i.a.) decreased insulin levels in the plasma sampled from the pancreatic vein of the blood-perfused pancreas of dogs in which ganglionic transmission and beta-adrenoceptors had been blocked. This effect was not modified by idazoxan (1 mg/kg followed by 0.02 mg/kg/min i.v.) but was partially reduced (50%) by glibenclamide (1 mg/kg followed by 0.02 mg/kg/min i.v.). This dose of glibenclamide blocked entirely the hypoinsulinemic activity of diazoxide, an activator of pancreatic ATP-modulated K+ channels, whereas the dose of idazoxan prevented the effect of the alpha 2-adrenoceptor agonist UK-14,304. Therefore, in dogs, the decrease in insulin secretion produced by exogenous galanin is only partially mediated by activation of glibenclamide-sensitive ATP-gated K+ channels and is independent of alpha 2-adrenoceptor stimulation.

Adrenergic and nonadrenergic cotransmitters inhibit insulin secretion during sympathetic stimulation in dogs.

Vascular and biochemical responses to pancreatic sympathetic nerve stimulation were investigated in the blood-perfused pancreas of anesthetized dogs. During sympathetic nerve stimulation, pancreatic perfusion pressure and norepinephrine release increased, whereas insulin secretion decreased. The latter effect did not occur after pretreatment with the alpha 2-adrenoceptor antagonist idazoxan. However, after beta-adrenoceptor blockade with propranolol, neither single administration of idazoxan nor the alpha 1-adrenoceptor antagonist prazosin or glibenclamide, a blocker of ATP-modulated K+ channels, affected the decrease in insulin secretion induced by sympathetic nerve stimulation. In contrast, the combination of glibenclamide with idazoxan markedly antagonised the decrease in insulin release evoked by the latter procedure. After depletion of catecholamines with syrosingopine, the stimulation-induced inhibition of insulin secretion remained unchanged even though no increases in pancreas perfusion pressure or norepinephrine release were observed. In this preparation, glibenclamide inhibited the decrease in insulin release by 50%. In animals pretreated with the neuronal blocking agent bretylium, all of the responses to sympathetic nerve stimulation were abolished. These results indicate that the inhibitory effects exerted by the sympathetic nervous system on insulin secretion are mediated not only by the classical neurotransmitter norepinephrine acting on alpha 2-adrenoceptors but also by a nonadrenergic cotransmitter that can maintain transmission under conditions of catecholamine deficiency. The postulated nonadrenergic cotransmitter(s) acts, at least partly, via the opening of ATP-modulated K+ channels blockable by glibenclamide, and its release can be prevented by the neuronal blocking agent bretylium.

The beta 1-adrenoceptor antagonist, betaxolol, is not released from the heart of the anaesthetized dog during sympathetic nerve stimulation.

1. We investigated the hypothesis that the beta 1-adrenoceptor antagonist, betaxolol, can be accumulated by cardiac sympathetic nerve endings and then released together with noradrenaline during accelerans nerve stimulation. 2. Dogs were chronically treated with betaxolol (1 mg kg-1 daily, s.c.) for 7 days. Twenty four hours after the last dose, there was a significant retention of betaxolol in the heart of these dogs treated chronically with the beta 1-adrenoceptor antagonist. However, during in vivo accelerans nerve stimulation, the concentration of betaxolol in the coronary sinus was not modified, whereas the noradrenaline concentration increased significantly. 3. Chronic betaxolol treatment antagonized the tachycardia induced by electrical stimulation of the cardiac accelerator nerves or by intravenous isoprenaline. However, the tachycardia induced by nerve stimulation was not antagonized to a greater extent than that induced by isoprenaline. 4. These findings are discussed in relation to a similar in vivo study in dogs treated with propranolol, in which the drug was found to be released into the coronary circulation during stimulation of the accelerans nerve.

Day-night rhythm of 5-methoxytryptamine biosynthesis in the pineal gland of the golden hamster (Mesocricetus auratus).

5-Methoxytryptamine is a potent agonist of presynaptic 5-hydroxytryptamine autoreceptors modulating serotonin release in the central nervous system. This methoxyindole can be synthesized in the pineal gland, but its presence in vivo is still controversial, probably because of rapid catabolism by monoamine oxidase. An improved high-pressure liquid chromatography method, with coulometric detection, has been developed for the simultaneous measurement of melatonin, 5-methoxytryptamine, 5-methoxytryptophol and 5-methoxyindolacetic acid. We have demonstrated a day-night rhythmicity in the amount of 5-methoxytryptamine in the pineal gland of golden hamsters (Mesocricetus auratus) maintained under a long photoperiod (14 h light: 10 h darkness) and pretreated with the monoamine oxidase inhibitor pargyline. Levels of 5-methoxytryptamine were highest at 16.30 h and lowest at 00.30 h. The rhythm for 5-methoxytryptamine appears to be the same as for serotonin (opposite in phase to that of melatonin). The identification of 5-methoxytryptamine has been confirmed by analysis with gas chromatography-mass spectrometry.