Diagnostic branched tree as an assessment and feedback tool in undergraduate pharmacology education.

BACKGROUND: Multiple-choice, true-false, completion, matching, oral presentation type questions have been used as an evaluation criterion in medical education for many years. Although not as old as other question types, performance evaluation and portfolio-like assessment types, can be called alternative evaluation, have been used for a considerable time. While summative assessment maintains its importance in medical education, the value of formative assessment is gradually increasing. In this research, the use of Diagnostic Branched Tree (DBT), which is used both as a diagnostic and feedback tool, in pharmacology education was examined. METHODS: The study was conducted on 165 students (112 DBT, 53 non-DBT) on the 3rd year of undergraduate medical education. 16 DBTs prepared by the researchers were used as data collection tool. Year 3 first committee was elected for implementation. DBTs were prepared according to the pharmacology learning objectives within the committee. Descriptive statistics, correlation and comparison analyzes were used in the analysis of the data. RESULTS: DBTs with the most wrong exits are DBTs entitled phase studies, metabolism, types of antagonism, dose-response relationship, affinity and intrinsic activity, G-protein coupled receptors, receptor types, penicillins and cephalosporins. When each question in the DBTs is examined separately, it is seen that most of the students could not answer the questions correctly regarding phase studies, drugs that cause cytochrome enzyme inhibition, elimination kinetics, chemical antagonism definition, gradual and quantal dose response curves, intrinsic activity and inverse agonist definitions, important characteristics of endogenous ligands, changes in the cell as a result of G-protein activation, ionotropic receptor examples, mechanism of action of beta-lactamase inhibitors, excretion mechanism of penicillins, differences of cephalosporins according to generations. As a result of the correlation analysis, the correlation value calculated between the DBT total score and the pharmacology total score in the committee exam. The comparisons showed that the average score of the pharmacology questions in the committee exam of the students who participated in the DBT activity was higher than the students who did not participate. CONCLUSIONS: The study concluded that DBTs are a candidate for an effective diagnostic and feedback tool. Although this result was supported by research at different educational levels, support could not be shown in medical education due to the lack of DBT research in medical education. Future research on DBTs in medical education may strengthen or refute our research results. In our study, receiving feedback with DBT had a positive effect on the success of the pharmacology education.

Crucial role of nitric oxide synthases system in endothelium-dependent hyperpolarization in mice.

The endothelium plays an important role in maintaining vascular homeostasis by synthesizing and releasing several relaxing factors, such as prostacyclin, nitric oxide (NO), and endothelium-derived hyperpolarizing factor (EDHF). We have previously demonstrated in animals and humans that endothelium-derived hydrogen peroxide (H(2)O(2)) is an EDHF that is produced in part by endothelial NO synthase (eNOS). In this study, we show that genetic disruption of all three NOS isoforms (neuronal [nNOS], inducible [iNOS], and endothelial [eNOS]) abolishes EDHF responses in mice. The contribution of the NOS system to EDHF-mediated responses was examined in eNOS(-/-), n/eNOS(-/-), and n/i/eNOS(-/-) mice. EDHF-mediated relaxation and hyperpolarization in response to acetylcholine of mesenteric arteries were progressively reduced as the number of disrupted NOS genes increased, whereas vascular smooth muscle function was preserved. Loss of eNOS expression alone was compensated for by other NOS genes, and endothelial cell production of H(2)O(2) and EDHF-mediated responses were completely absent in n/i/eNOS(-/-) mice, even after antihypertensive treatment with hydralazine. NOS uncoupling was not involved, as modulation of tetrahydrobiopterin (BH(4)) synthesis had no effect on EDHF-mediated relaxation, and the BH(4)/dihydrobiopterin (BH(2)) ratio was comparable in mesenteric arteries and the aorta. These results provide the first evidence that EDHF-mediated responses are dependent on the NOSs system in mouse mesenteric arteries.

Short-term and long-term FK506 treatment alters the vascular reactivity of renal and mesenteric vascular beds.

The aims of this study were to investigate the role of endothelin-1 in FK506-induced hypertension and vascular dysfunction of rats treated with the drug for 8 (short-term) or 30 (long-term) days and to measure malondialdehyde levels in the kidneys. Kidney and mesentery of rats were perfused. In the short-term treated groups, there was no significant change in systolic blood pressure. The response to noradrenaline only in renal vascular beds was significantly increased by FK506 and this increase was prevented by Bosentan. FK506 had no significant effect on sodium nitroprusside-induced vasodilation in comparison with solvent in both vascular beds. Bosentan failed to prevent these responses. In the long-term treated groups, at the end of the treatment with FK506, there was a significant increase in blood pressure, but no change in the response to noradrenaline in either kidneys or mesentery. The increase in blood pressure was prevented by bosentan treatment. FK506 increased malondialdehyde levels in the kidneys of the rats from only the long-term treated groups. Bosentan did not change this increase. Our results indicated that endothelin-1 plays a key role in the FK506-induced change in vascular reactivity to noradrenaline in renal vascular beds and drug-induced hypertension in the rats. There was no relationship between oxidative stress and FK506-induced hypertension.

The role of endothelin in FK506-induced vascular reactivity changes in rat perfused kidney.

Tacrolimus (FK506) is an immunosuppressant agent that is widely used in transplanted patients. The aim of this study was to investigate the role of endothelin in the acute effects of FK506 on the vascular reactivity in perfused isolated rat renal and mesenteric vasculature. Left kidney/mesentery of male Wistar rats (230-300 g) were perfused by a constant flow and perfusion pressure was recorded. The responses to noradrenaline and sodium nitroprusside were obtained both in the absence and presence of FK506 (10(-7) M) or polyoxyethylene hydrogenated castor oil 60 (HCO-60 and solvent of the drug at equivalent concentrations). FK506 significantly increased the noradrenaline-induced vasoconstrictor responses in renal, but not in mesenteric vascular beds. Bosentan (10(-5) M), a nonselective endothelin ET-1 receptor antagonist given by perfusion, reversed the increase in noradrenaline responses in the kidney. Sodium nitroprusside-induced vasodilator responses in both renal and mesenteric vascular beds were significantly decreased by FK506. However, in renal vasculature, there was no significant difference between the inhibitory effects of FK506 and HCO-60, although the effect of the solvent was not significantly different from that of the control. While in the mesenteric bed, the solvent significantly inhibited nitroprusside-induced vasodilation, similar to that of FK506. The effect of FK506 on vasodilation in both vascular beds was not reversed by bosentan. Our results indicated that FK506 increased the reactivity of the renal vascular bed to noradrenaline through endothelin ET-1 receptor activation. The mechanism of impaired vasodilation due to FK506 appears to be due to its solvent action and is independent of endothelin release.

Mechanism of action of the cisapride-induced vasodilatation in renal vasculature of rat.

BACKGROUND & OBJECTIVES: Cisapride is a prokinetic agent with cholinomimetic and 5-HT4 receptor agonistic properties. It has been proposed that cisapride-induced hypotension is partly mediated by cholinergic system. The aim of this study was to investigate the mechanism of cisapride-induced dilatation in the rat isolated perfused kidney. METHODS: Left kidneys of Wistar rats were isolated and perfused via renal artery and the perfusion pressure was recorded. Cisapride given as bolus injections (10(-10)-3x10(-5) mol/l) produced dose-dependent dilatations. Perfusion of antagonists or inhibitors was started 30min before the onset of phenylephrine perfusion. RESULTS: 4-Diphenylacetoxy-N-methylpiperidine methiodide (4-DAMP; blocker of M1, and M3 muscarinic receptors; 10(-7) mol/l) inhibited the responses to the lower doses of cisapride while, dextran (10(-7) mol/l), glibenclamide (inhibitor of ATP-sensitive potassium channels; 10(-5) mol/l) and capsaicin (for neuromediator depletion; 10(-6) mol/l) inhibited those to the higher doses. Dilatations induced by most of the doses of cisapride were inhibited by atropine (non-selective muscarinic receptor antagonist; 10(-7) mol/l), methylene blue (inhibitor of soluble guanylate cyclase; 10(-5) mol/l), 1H-[1,2,4] oxadiazolo-[4,3-a] Quinoxalin-1-One (ODQ; inhibitor of soluble guanylate cyclase; 10(-5) mol/l), and NG-nitro-L-arginine (L-NOARG; NO synthase inhibitor; 10(-4) mol/l). Inhibition induced by L-NOARG was reversed by L-arginine (10(-3) mol/l). The dilatation induced by cisapride was not affected by GR113808 (5-HT4 receptor antagonist; 10(-7) mol/l) and indomethacin (cyclooxygenase inhibitor; 10(-5) mol/l). INTERPRETATION & CONCLUSION: The findings indicated that cisapride caused vasodilatation through the release of nitric oxide (NO) as a result of the release of a substance acting on muscarinic receptors, in the renal vascular bed of the rat. The role of 5-HT4 receptors and prostanoids seemed unlikely.