Search

The investigation reported in this paper studied the relationship between 31 variables from 80 subjects graduated in pharmacy. Variables included in the study were average grades taken from the examination held at age 16 (Ordinary “O” level), predicted and actual Advanced level scores usually 3 subjects taken at around age 18 and the complete pattern of university examinations. The average of O-level scores was not a useful predictor but the teachers' estimates of performance at A-level were. A-levels themselves correlated particularly well with early parts of the course and the average grade still showed a small but significant correlation through to the end. Undergraduate examinations throughout the 3 years were generally intercorrelated. It is argued that given the appropriate circumstances both teachers' estimates of A-level performance and actual A-level scores remain useful in selection and forecasting.

Cationic compounds used in the treatment of veterinary African trypanosomiasis have structural properties similar to those of pentamidine, which has been used in the therapy of human trypanosomiasis and infection with Pneumocystis carinii. We have compared the activities of these drugs and other antimicrobial agents in an immunosuppressed rat model of P. carinii pneumonia. Diminazene, imidocarb, amicarbalide, quinapyramine, and isometamidium showed efficacy greater than or equal to that of pentamidine in the therapy of P. carinii infection, whereas ethidium and methylglyoxal bis(guanylhydrazone) were only slightly active against the organism. Diminazene and pentamidine also exhibited comparable efficacy in P. carinii prophylaxis, alpha-Difluoromethylornithine (DFMO), a polyamine inhibitor, was ineffective therapy when used alone and did not improve the effectiveness of pentamidine or diminazene. Quinine, quinidine, quinacrine, chlorpromazine, spiramycin, Pentostam, Astiban, dehydroemetine, ampicillin, gentamicin, chloramphenicol, and spectinomycin also showed little or no activity against the organism. Thus, in this model anti-P. carinii activity appears to be a common property of veterinary cationic trypanocidal compounds. This should be important in studying structure-activity relationships and in developing new drugs for the treatment of P. carinii infection in humans.

The pharmacological actions of a diuretic drug, fenquizone have been investigated and its effects compared with well characterized diuretics in rats, mice and rabbits. Changes in sodium and potassium excretion and urine volume were similar in magnitude and duration to those of the thiazide diuretics over dose range 0·05–100 mg kg−1. Free water clearance in rabbits was decreased indicating an action at the cortical diluting site in the nephron and since free water reabsorption was relatively unaffected it appears unlikely to have actions at other sites. Calcium and phosphate excretion studies also suggested that the predominant effects are those occurring at the cortical diluting segment of the nephron. Additional parameters not affected by the drug were blood flow to the cortex and medulla of the kidney (and other major organs), plasma glucose concentration and plasma urate concentration.

Pneumocystis carinii pneumonia was induced in rats by the administration of corticosteroids, and histologic and quantitative techniques were compared in the evaluation of the severity of the disease and response to therapy. A highly significant correlation was found between the histologic score of the extent of alveolar involvement (the standard method of assessment) and the number of P. carinii cysts and nuclei in lung homogenates, lung weight, and lung weight/body weight ratio. Clear differences were noted between rats which responded well and rats which responded poorly to therapy by all techniques. Quantitation of P. carinii cysts and nuclei revealed a 10(4)-fold reduction in organism burden with successful treatment. Thus, these techniques should be helpful in the development of testing of new antimicrobial agents in the rat model of pneumocystosis.

SUMMARY Acute occlusion of the blood supply to the liver decreases inactivation of tritiated cortisol, corticosterone and aldosterone. In malnourished animals which had lost approx. 25% of their initial body weight, only cortisol inactivation was decreased.

The use of objective tests in the examination of pharmacy undergraduates in physiology is described, and examples are given. These tests have produced examinations of high reliability and discriminating power, and are at least as acceptable to the examinees as traditional essay-type questions.

Noradrenaline, 5-hydroxytryptamine and dopamine are present in the fruit of Musa sapientum, var. paradisiaca (Plantain), which forms a staple food of many inhabitants of West Africa. The amounts of 5-hydroxytryptamine and noradrenaline are highest when the fruit is ripe. An estimated daily intake of 10 mg. of 5-hydroxytryptamine by West Africans has little apparent effect on the normal functioning of the intestinal tract.

(1967). Examinations in Higher Education—A Review. Journal of Biological Education: Vol. 1, No. 2, pp. 139-151.

Zugabe von Glibenclamid bei Alloxan induzierten, stark zuckerkranken Ratten vermindert den Gehalt freier Fettsauren im Blutplasma. Kein entsprechend antilipolytischer Effekt wurde bei Wiederholung des Experimentes beobachtet, wenn Chlorpropamid und Tolbutamid hundertfach starker als Glibenclamid verabreicht wurde.

Glomerular filtration rate (GFR), cardiac output, regional blood flow and kidney weight were measured in alloxan and streptozotocin diabetic rats at different times after the administration of diabetogen. A high GFR was found together with increased kidney weight and reduced blood flow.

Es wurden die Wirkungen von Chlorpropamid, Glibenclamid und Tolbutamid auf die Nieren wasserbelasteter normaler und diabetischer Ratten untersucht.

Isolated spontaneously beating atria from streptozocin diabetic rats were compared with those from controls. Diabetic atria were found to have reduced rates, increased forces of contraction and reduced sensitivity to the inotropic effects of noradrenaline, isoprenaline, tyramine and calcium. Positive chronotropic responses to tyramine were also reduced but those to noradrenaline and isoprenaline were increased suggesting that tyramine releasable stores of noradrenaline were reduced. Elevation of glucose concentration in the medium from 5·6 to 27 min resulted in a decrease of inotropic sensitivity to the agents used in both control and diabetic rat atria. Resting contractile force of control rat atria was reduced by the inclusion of either 22 niM 2-deoxyglucose, 10−3 i.u. insulin ml−1 or 5 mM acetate in the medium. The rate was also reduced by medium containing 2-deoxyglucose but increased by insulin. 2-Deoxyglucose also reduced inotropic but increased chronotropic sensitivity to isoprenaline. Possible mechanisms responsible for the changes observed are discussed.

Rat superior mesenteric vascular bed was isolated, perfused by the artery with Krebs solution and the perfusion pressure monitored. Dose-response curves to noradrenaline and KCl administered as bolus doses were obtained. A 1 hr continuous infusion of either piretanide (10 micrograms ml-1) frusemide (40 micrograms ml-1) or bumetanide (2 micrograms ml-1) decreased the sensitivity of the preparation to noradrenaline but not to KCl. This effect was antagonized by flurbiprofen (12 micrograms ml-1) pretreatment. A 1 hr continuous infusion of prostaglandin (PG)E2 increased the sensitivity of the preparation to both noradrenaline and KCl. PGI2 (5 ng bolus) or diuretic perfusion antagonized the responses to noradrenaline but not those to KCl. PGI2 and diuretics in combination further decreased the responsiveness of the preparation to noradrenaline. KCl responses were unaffected by either PGI2 or diuretics, alone or combined. The results suggest that the loop diuretics decrease the responsiveness of the isolated rat superior mesenteric vascular bed preparation to noradrenaline, possibly by increasing the level of PGI2, an effect which may be an important factor in the cardiovascular activity of the diuretics.

1. Frusemide, in doses which were maximal or supramaximal in respect of its natriuretic, diuretic and kaliuretic properties, produced a dose dependent, transient hyperglycaemic response in the mouse.2. Bilateral nephrectomy resulted in a complete abolition of the hyperglycaemic response.3. The hyperglycaemic response was accompanied by a decrease in liver glycogen and was significantly attenuated by adrenalectomy, adrenal demedullation and pretreatment with dihydroergotamine (DHE).4. In the nephrectomized mouse frusemide treatment produced a marked reduction in intravenous glucose tolerance and a reduction in the plasma concentration of immunoreactive insulin following glucose administration. The drug had no detectable effect upon insulin sensitivity.5. Hydrochlorothiazide exerted no detectable effect on mouse blood sugar.6. Ethacrynic acid hyperglycaemia was obtainable after intraperitoneal or intramuscular injection, but not after intravenous injection. Intravenously administered ethacrynic acid exerted no effect upon intravenous glucose tolerance or insulin sensitivity in the nephrectomized mouse.

SUMMARY Using a radioactive isotope technique, water turnover (biological half-life of tritium, T½) has been determined in a number of endocrine deficient states in rats. Water turnover was decreased after adrenalectomy but restored to normal in animals kept on 0·9% NaCl solution. A number of glucocorticoid hormones (cortisone, hydrocortisone, prednisolone and dexamethasone) were also able to restore water turnover to normal in adrenalectomized rats. Water turnover was also decreased in rats which had been thyroidectomized 3–5 days previously, but in chronically thyroidectomized animals or those in which hypothyroidism had been produced by propylthiouracil treatment, no significant change in water turnover could be detected. Propylthiouracil-treated animals kept on 0·5% NaCl solution had an increased water turnover. Water turnover was increased in hypophysectomized animals.

L'administration de grandes doses de l'acide Ethacrynic par injection i.p. aux souris produit l'hyperglycemie. Les investigations preliminaires indiquent un role important pour la medulle surrenale dans la production de la reponse hyperglycemique.

Treatment of mice for 14 days with ethacrynic acid or frusemide (100 mg/kg daily orally) increased the fasting blood sugar and liver glycogen. Oral glucose tolerance was altered so that blood sugar concentrations in drug-treated groups were significantly above control values. The failure of the drugs to affect intravenous glucose tolerance and sensitivity to insulin or to tolbutamide suggested that the decrease in the oral glucose tolerance was attributable to some effect of the drug treatments on the rate of absorption of glucose from the gastrointestinal tract. Treatment with hydrochlorothiazide (100 mg/kg daily orally) exerted no effect on blood sugar, liver glycogen or glucose tolerance.

Inhibitors of folic acid synthesis were compared alone and in different combinations in the therapy of pneumocystosis in immunosuppressed rats. Sulfonamides (sulfamethoxazole, sulfadiazine, and sulfadoxine) and sulfones (dapsone) used alone were very active against Pneumocystis carinii, as judged by histologic examination of the lungs and by organism quantitation. Improved efficacy could not be demonstrated by the addition of an inhibitor of dihydrofolate reductase to the regimen. Dihydrofolate reductase inhibitors (trimethoprim, diaveridine, and pyrimethamine) used alone were ineffective against P. carinii. All drugs were well tolerated except pyrimethamine, which caused bone marrow depression; folinic acid ameliorated this adverse reaction but did not interfere with P. carinii treatment. These data have potential clinical implications but need to be interpreted with caution and in light of other systems of P. carinii drug evaluation.