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Biomedical subjects

M J Daly

Publications and source records attributed to M J Daly.

At least 145 records · Page 8Linked to original sources
PubMed1981

Some in vitro and in vivo actions of the new histamine H2-receptor antagonist, ranitidine.

1 Ranitidine has been investigated as an antagonist of the H2-receptor-mediated responses to histamine of guniea-pig atrium and rat uterus in vitro and as an inhibitor of gastric acid secretion in the rat. 2 Ranitidine competitively antagonized histamine-induced increases in contraction frequency of the guinea-pig isolated rat atrium. Ranitidine had a pA2 of 7.2 and was 7.9 and 4.5 times more potent than metiamide and cimetidine respectively. 3 Ranitidine competitively antagonized histamine-induced relaxations of the rat isolated uterine horn. Ranitidine had a pA2 of 6.95 and was 3.6 and 5.9 times more potent than metiamide and cimetidine respectively. 4 Ranitidine, even at high concentrations, did not affect responses of the guinea-pig isolated atrium or rat isolated uterus to (-)-isoprenaline. Similarly it was without effect on either histamine or bethanechol-induced contractions of guinea-pig isolated ileum. 5 Ranitidine inhibited histamine- and pentagastrin-induced gastric acid secretion in the perfused stomach preparation of the anaesthetized rat. Ranitidine was 5.2 and 7.0 times more potent on a molar basis than metiamide and cimetidine respectively, as an inhibitor of histamine-induced gastric acid secretion. 6 It is concluded that ranitidine is a potent, competitive and selective antagonist of histamine at H2-receptor sites and and effective inhibitor of gastric acid secretion in vivo.

Animals↗
PubMed1981

Antagonism of vasodepressor and gastric secretory responses to histamine by the H2-receptor antagonists, ranitidine and cimetidine, in the anaesthetized dog.

1 The new H2-receptor antagonist, ranitidine, has been compared with cimetidine as an inhibitor of gastric acid secretion in the anaesthetized dog. 2 Both ranitidine and cimetidine given intravenously inhibited histamine-induced gastric secretion in a dose-related manner. Ranitidine was 4.2 times more potent than cimetidine when given as an intravenous infusion and 9.6 times more potent as an intravenous bolus dose. 3 In a separate series of experiments, ranitidine was compared with cimetidine as an antagonist of vasodepressor responses to histamine. Mepyramine alone displaced the histamine dose-response curve to the right. After a maximally effective dose of mepyramine, further displacement could be achieved with ranitidine and cimetidine, ranitidine being 19.2 times more potent than cimetidine. 4 Ranitidine alone has no effect on vasodepressor response curves to histamine, acetylcholine or (-)-isoprenaline or on vasopressor response curves to phenylephrine. 5 These results indicate that displacement of the histamine dose-response curve after mepyramine blockade by ranitidine and cimetidine is due to selective H2-receptor antagonism.

Anesthesia↗
PubMed1981

Oestrogen metabolism in adult rat's brain.

In vitro incubation of pituitary, hypothalamus and cerebral cortex with [3H]oestrogens revealed that the oestrogens are actively metabolized by these tissues. The covalent binding of oestrone and oestradiol to acid precipitable proteins was observed. Pituitary from male rats exhibited higher covalent binding of oestrogens than females. The 2-hydroxylation was found to be greater than 16-hydroxylation. Furthermore, male pituitary exhibited higher 2-hydroxylation of oestrogens than females. No such sexual dimorphism was observed in 16-hydroxylation. C17-reduction was found to be greater than oxidation in these tissues. Furthermore, the C17-reduction in pituitary and hypothalamus from females was greater than males, which is in contradistinction to protein binding and 2-hydroxylation of oestrogens. In both male and female animals the pituitary was metabolically more active than hypothalamus and cortex. In addition, oestradiol was hydroxylated more than oestrone either at 2- or 16-positions. These results indicate that in central nervous system and pituitary the oestrogens are metabolized preferentially by 2-hydroxylation pathway and it is suggested that the in situ metabolism of oestrogens in neuroendocrine tissues may be important in the control of oestrogen effects on neuroendocrine function and sex behaviour.

Age Factors↗
PubMed1981

A review of the animal pharmacology of ranitidine--a new, selective histamine H2-antagonist.

The animal pharmacology and metabolism of ranitidine have been reviewed. Experiments using guinea-pig isolated right atrium and ileum preparations have shown that ranitidine is a selective, potent, and competitive histamine H2-receptor antagonist. In the conscious dog gastric acid secretion induced by histamine, pentagastrin, bethanechol and food was inhibited by ranitidine at doses 4 to 12 times lower than equi-effective doses of cimetidine. Ranitidine inhibited the formation of aspirin-induced gastric lesions, both in the presence and absence of gastric acid. Unlike cimetidine, ranitidine neither possessed anti-androgenic activity, nor did it inhibit the mixed function oxygenase metabolizing enzyme system in the liver. Ranitidine has been recommended for clinical trial in the treatment of peptic ulcer disease.

Administration, Oral↗
PubMed1981

Radionuclide imaging of the biliary tract.

Cholescintigraphy with technetium-labeled biliary agents has great value in evaluation of the patient with suspected acute cholecystitis. Visualization of the gall bladder virtually excludes acute cholecystitis and obstruction of the cystic duct. Nonvisualization of the gall bladder, however, is not specific for acute cholecystitis and may also occur in some patients with chronic cholecystitis or pancreatitis. Interpretation of gall bladder nonvisualization, therefore, must be correlated with the clinical presentation. Biliary tract imaging is also useful in evaluation of some focal abnormalities within the liver, neonatal jaundice, detection of bile leaks or bile reflux, and biliary-enteric shunts. The role of technetium-labeled biliary agents in the evaluation of patients with jaundice is less clear. Excretion of tracer into the gut excludes complete biliary tract obstruction, but the test may be nonconclusive at higher serum bilirubin levels. If persistent common bile duct activity is observed with delayed excretion into the gut, the diagnosis of partial obstruction may be made, but this procedure will be inconclusive if the common bile duct is not visualized and/or significant hepatocellular disease is present. Ultrasonography and abdominal CT are the preferred tools for the diagnosis of biliary tract obstruction at present, but newer biliary tract agents which achieve better hepatic extraction and greater bile concentration at high serum bilirubin levels may improve the diagnostic efficacy of cholescintigraphy.

Biliary Tract↗
PubMed1980

Estrogen metabolism in neural tissues of six-day-old rats.

In vitro incubation of pituitary, hypothalamus and cerebral cortex from 6-day-old rats with [6,7-3H]estradiol revealed that estradiol is actively metabolized in these tissues. Pituitary was found to be more active than hypothalamus and cerebral cortex in metabolizing estradiol in these animals. Covalent binding of estradiol to acid-precipitable proteins was observed in all these tissues from both sexes. While there was no significant sex difference in protein binding of estradiol in any of the tissues tested, treatment with progesterone or estradiol valerate increased protein binding. 2- and 16-hydroxylation and 17 beta-oxidation were demonstrated in all the tissues tested. While there were no significant sex differences observed in 2,16-hydroxylation, 17 beta-oxidation appeared to be more in males. Progesterone treatment of males increased 2-hydroxylation of estradiol 4-fold in pituitary and doubled the levels in hypothalamus. 16-Hydroxylation and 17-oxidation were also elevated significantly in pituitary and hypothalamus by progesterone treatment. Estradiol valerate treatment, however, decreased 2-hydroxylation and 16-hydroxylation in pituitary and hypothalamus; 17-oxidation was increased in pituitary. These results suggest that the estradiol metabolism, and especially 2-hydroxyestradiol formation, can be increased by progesterone and thereby mediate antagonistic effect of progesterone on estrogen-mediated brain sexual differentiation.

Animals↗
PubMed1980

In vitro actions of ranitidine, a new histamine H2-receptor antagonist.

Ranitidine has been tested on isolated guinea-pig right atrium and rat uterine horn, tissues known to possess histamine H2-receptors; and on isolated guinea-pig ileum a tissue containing histamine H1-receptors. These experiments have shown ranitidine to be a potent competitive antagonist of histamine at H2-receptor sites in vitro. This action is selective since high concentrations of ranitidine do not affect beta-adrenoceptor, histamine H1-receptor and muscarinic receptor mediated responses.

Animals↗
PubMed1980

An improved apparatus for intragastric titration in the conscious dog.

An apparatus for automatic intragastric titration with on-line display of results has been described. The apparatus has been validated by titration of exogenous acid injected into the test meal in a reservoir and in vivo by assessing the secretory response of a dog with a gastric fistula to a test meal. A titration display unit provides a record of the secretory response both as a digital printout and a bar chart display. Cimetidine (2 mg kg-1h-1) significantly reduced the secretory response to a test meal.

Animals↗
PubMed1980

Inhibition of gastric acid secretion in the dog by the H2-receptor antagonists, ranitidine, cimetidine, and metiamide.

The new H2-receptor antagonist, ranitidine, has been compared with cimetidine and metiamide as an inhibitor of gastric acid secretion in the dog. All three compounds were effective both intravenously or by mouth in inhibiting secretion induced by histamine, pentagastrin, or bethanechol. This inhibition was mainly attributable to a reduction in the volume of secretion, although there was also a significant reduction in the concentration of acid secreted. Metiamide was slightly less active than cimetidine, but ranitidine was four to nine times more potent than cimetidine, depending on the secretagogue used. The antisecretory activity of ranitidine does not result from a limitation in blood flow to the gastric mucosa.

Animals↗
PubMed1980

Cardiac effects of beta-adrenergic receptor antagonists: beta-moderators versus beta-blockers.

Two adrenergic receptor antagonists, acebutolol and propranolol, were observed to depress rabbit heart contractile force and adrenaline-stimulated adenylate cyclase activity at 1 X 10-(5) to 1 X 10-(3) M and 1 X 10-(6) to 1 X 10-(3) M concentrations, respectively. Acebutolol depressed sarcoplasmic reticular and mitochondrial calcium uptake at 5 X 10-(3) to 10-(2) M concentrations. On the other hand, propranolol was found to decrease calcium uptake activities of sarcoplasmic reticular and mitochondrial fractions at 1 X 10-(4) to 1 X 10-(2) M and 1 X 10-(3) to 1 X 10-(2) M concentrations, respectively. On the basis of these results with calcium transport systems, it is proposed that beta-antagonists with a mild depressant effect, such as acebutolol, may be called beta-moderators, whereas those with a strong effect, such as propranolol, may be called beta-blockers.

Acebutolol↗
PubMed1980

Effects of dl-erythro-1-phenoxy-3-[(3,4-dimethoxyphenethyl)-amino]-butan-2-ol (PS-6) on rat heart sarcolemma.

Effects of dl-erythro-1-phenoxy-3-[(3,4-dimethoxyphenethyl)-amino]-butan-2-ol (PS-6) on ATPase and calcium binding activities of rat heart sarcolemma as well as adenylate cyclase of both sarcolemma and heart washed particles were studied under in vitro conditions. PS-6 at concentrations of 10(-7) mol/l or higher inhibited Na+-K+ ATPase and calcium binding activities significantly. The inhibition of calcium binding activity was dependent upon the concentration of calcium in the incubation medium with greater percentage inhibition seen at lower concentrations. While basal adenylate cyclase activity was not affected by 10(-7)--10(-4) mol/l, isoprenaline stimulated adenylate cyclase activity was inhibited by 10(-6) mol/l or higher concentrations of PS-6. At 10(-3) mol/l PS-6 a more generalized inhibitory effect was seen, with all parameters studied being inhibited. These results suggest that sarcolemma is one of the sites for the cardiac actions of PS-6.

Adenosine Triphosphatases↗
PubMed1980

Quantitative measurement of skin perfusion with xenon-133.

Quantitative assessment of skin perfusion has value in both medical and surgical therapeutic decision-making. We have adapted a technique using intradermal xenon-133 dissolved in saline for use with a gamma camera interfaced to a mini-computer. It allows rapid evaluation of several sites simultaneously. The monoexponential washout rate of the injected tracer during the first 6 min is entered into the Schmidt--Kety equation to provide blood-flow rates in ml/min per 100 g. Reproducibility of the method in normal subjects is satisfactory. An important experimental variable is ambient temperature, since perfusion rates in normal limbs at low temperatures can approach those levels found in ischemic limbs. The intradermal technique has practical advantages over other methods for study of limb or skin perfusion.

Adult↗