bluuebunny/crossref_metadata_2025_split huggingface dataset:
AN IN VIVO INVESTIGATION OF THE NEGATIVE CHRONOTROPIC EFFECT OF CHOLIC ACID IN THE RAT
Authors: Joubert P. 
Published: June 2007

SUMMARY1. Experimental obstructive jaundice in the Wistar rat causes a significant decrease in heart rate.2. Intravenous administration of cholic acid in vivo elicits a dose‐dependent negative chronotropic effect.3. Atropine or vagotomy significantly reduces, but does not abolish, the negative chronotropic effect of cholic acid.4. Ganglion blockade and decerebration diminishes the negative chronotropic effect of cholic acid, but to a lesser extent than atropine or vagotomy.5. Sympathetic depletion by reserpine slightly potentiates the response to cholic acid.6. The effect of cholic acid injected cranially into the common carotid artery is less than when administered into the jugular vein.7. The haemolysis caused by cholic acid does not appear to be involved in the negative chronotropic effect.8. It is concluded that cholic acid causes both a direct as well as a vagally mediated negative chronotropic effect in the Wistar rat.
EFFECTS OF MONOSODIUM GLUTAMATE‐INDUCED OBESITY IN MICE ON CARBOHYDRATE METABOLISM IN INSULIN SECRETION
Authors: Cameron D. P. , Cutbush L. , Opat F. 
Published: June 2007

SUMMARY1. The syndrome of obesity induced by neonatal injection of monosodium glutamate (MSG) has been further studied in mice. In confirmation of previous studies stunting and decreased pituitary and gonadal weights were observed.2. After weaning food intake was consistendy less in MSG‐treated than control mice. Body lipid stores were significantly elevated in MSG‐treated mice by 2 weeks of age and increased progressively up to 4 months.3. Plasma glucose was comparable between MSG‐treated and control mice in the fed state whereas after an overnight fast MSG‐treated mice exhibited relative hypo‐glycaemia.4. Obese MSG‐treated mice did not exhibit resistance to exogenous insulin and disposed of an intravenous glucose load more rapidly than control mice.5. Hyperinsulinaemia was present inconsistently in both fed and fasted mice and in response to administered glucose.6. Neonatal administration of MSG provides a useful additional model for studying the role of the hypothalamus in obesity.
GAS CHROMATOGRAPHIC MEASUREMENT OF PLASMA LEVELS OF SODIUM VALPROATE: TENTATIVE THERAPEUTIC RANGE OF A NEW ANTICONVULSANT IN THE TREATMENT OF REFRACTORY EPILEPTICS
Authors: Vajda F. J. E. , Drummer O. H. , Morris P. M. , McNeil J. J. , Bladin P. F. 
Published: June 2007

SUMMARY1. A precise and rapid gas chromatographic method for the measurement of plasma sodium valproate concentrations is presented.2. The extraction is a single step procedure, and is reproducible and linear throughout the concentration range encountered.3. Clinical evaluation of the drug is presented in eighteen epileptics on the basis of the percentage of days on which subjects had seizures before and after sodium valproate therapy.4. A tentative therapeutic range for sodium valproate is presented on the basis of plasma levels and therapeutic effect.
INTERACTIONS BETWEEN PRAZOSIN, CLONIDINE AND DIRECT VASODILATORS IN THE ANAESTHETIZED RAT
Authors: Oates H. F. , Stoker L. M. , Stokes G. S. 
Published: June 2007

SUMMARY1. Prazosin, clonidine, hydrallazine and diazoxide were administered intravenously, alone or in various combinations, to anaesthetized rats.2. Prazosin and clonidine were equipotent. Their combined hypotensive effects in no instance exceeded the maximum effect attainable with either agent alone. The hypotensive effects of hydrallazine or diazoxide were, in contrast, additive to those of either prazosin or clonidine.3. Pressor responses to clonidine were antagonized by prazosin. Prazosin may prove useful in hypertensive crises provoked by clonidine.
MODIFICATION OF BRAIN BIOGENIC AMINES BY METS‐ENKEPHALIN AMIDE IN THE RAT
Authors: Laska F. J. , Fennessy M. R. 
Published: June 2007

SUMMARY1.Gross changes in behaviour and whole brain levels of noradrenaline, dopamine, serotonin and 5‐hydroxyindoleacetic acid were examined in rats for 3 min following intracerebral injections of met5‐enkephalin amide or morphine.2. Both the enkephalin and morphine depressed respiration and induced a cataleptic‐like state, but only the enkephalin produced wet‐shake responses.3. All doses of met5 enkephalin amide (150, 200 and 600μg) and morphine (134 and 200 /Kg) increased the brain levels of 5‐hydroxyindoleacetic acid, whereas only the large doses modified the levels of noradrenaline and serotonin.4. The similarity of the effects of these two compounds indicates that morphine may act through an enkephalin‐like mechanism.
A STUDY OF THE INTERACTION OF PRACTOLOL WITH ACETYLCHOLINE, HISTAMINE, SEROTONIN AND BRADYKININ IN THE GUINEA‐PIG, AND WITH BEAN‐SPROUT JUICE IN THE MOUSE
Authors: Chang L. C. T. , Wong J. C. Y. , Roberts M. B. 
Published: June 2007

SUMMARY1. The interactions of practolol with acetylcholine, histamine, serotonin and bradykinin were studied on the trachea and lung of the guinea‐pig, an animal whose sensitivity to bronchoactive endogens is known to be similar to that of human asthmatic bronchi.2. Practolol, like propranolol, potentiated the action of the first three agonists mentioned above, but, unlike propranolol, it did not potentiate the bronchospastic effect of bradykinin.3. Practolol, in fact, antagonized the action of bradykinin, but this effect was unlike that produced by nonsteroidal anti‐inflammatory drugs.4. The possibility that β‐adrenoreceptor antagonists might show adverse interactions with certain foodstuffs was investigated, and is discussed.5. It is suggested that the feasibility of the continued use of practolol (or the newer cardioselective β‐blockers) in asthmatics necessarily depends on the type of allergic reaction involved, and so it is not possible to generalize. Any drug or food that might cause a bronchospastic effect synergistically in the presence of a β‐adrenoreceptor antagonist, even a cardioselective one, should be regarded with suspicion.
ASSESSMENT OF THE CORONARY VASODILATOR ACTION OF SK&F 24260 IN THE DOG
Authors: Narimatsu A. , Satoh K. , Taira N. 
Published: June 2007

SUMMARY1. The effects of SK&F 24260 administered intravenously or intraduodenally on the coronary sinus outflow, coronary arteriovenous oxygen difference (A‐V O2), myocardial oxygen consumption (MVO2), systemic blood pressure, heart rate and atrioventricular (AV) conduction time were examined in open‐chest dogs.2. SK&F 24260 in doses of 0.3–10 μg/kg, i.v., caused a dose‐dependent increase in coronary sinus outflow, but the increase was smaller with 30 μg/kg, i.v., than with 10μg/kg, i.v.3. SK&F 24260 (0.3–30μg/kg, i.v.) decreased A‐V O2 and MVO2 in a dose‐dependent manner.4. SK& F 24260 (0.3–30μg/kg, i.v.) decreased systemic blood pressure and heart rate, and increased AV conduction time.5. Intraduodenal administration of SK&F 24260 (1 mg/kg) produced almost the same effects on coronary sinus outflow, A‐V O2, MVO2, systemic blood pressure, heart rate and AV conduction time as did the intravenous administration of the compound (10μg/kg).6. The property of SK&F 24260 to increase the coronary blood flow and to moderately decrease MVO2, systemic blood pressure and heart rate indicates that this agent is a potential antianginal drug.
WARFARIN SODIUM: STEADY‐STATE PLASMA LEVELS AND PATIENT AGE
Authors: Hotraphinyo Kanda , Triggs E. J. , Maybloom B. , Maclaine‐Cross A. 
Published: June 2007

SUMMARY1. Steady‐state plasma levels of warfarin were measured in thirty‐nine ambulatory patients attending a haematology clinic.2. Plasma concentrations, plasma clearance, and prothrombin ratio showed no significant differences when patients below 65 years of age were compared with those above 65 years. The mean daily maintenance dose of warfarin required was marginally greater for the younger patients but the difference was not statistically significant (P= 0.10).3. A significant relationship was found between the daily maintenance dose of warfarin required by all patients and their mean steady‐state plasma level (r = 0.5667, P< 0.001).4. For one elderly hospitalized patient it was apparent that there was a marked depression of the vitamin K‐dependent clotting factor synthesis by warfarin which was associated with a hypoprothrombinaemic response.
STUDY OF THE IN VITRO PHARMACOLOGICAL EFFECTS OF GRAM‐NEGATIVE ENDOTOXINS IN PARALLEL WITH TOXICITY TESTING IN NORMAL ADULT GUINEA‐PIGS
Authors: McLean A.J. 
Published: June 2007

SUMMARY1. Lipopolysaccharide extracts (endotoxins), obtained from E. coli organisms by heat, trichloracetic or phenol‐water extraction, were shown to be toxic to normal adult guinea‐pigs.2. These agents did not produce any detectable changes in the contractile properties of a range of standard guinea‐pig smooth muscle‐containing tissues; however, the heat‐extract of E. coli cells caused relaxation of isolated preparations of guinea‐pig ileum. This effect was not demonstrated by the trichloracetic acid or phenol‐water extracts.3. These agents did not produce any changes in the electrical properties of the smooth muscle membranes of guinea‐pig vas deferens studied by microelectrode techniques, or in the properties of rabbit and sheep mesenteric portal veins studied using sucrose gap techniques.4. There were no effects observed when isolated preparations of guinea‐pig atrium were exposed to endotoxins.5. No effects of endotoxin were detected on sympathetic adrenergic neuromuscular transmission in guinea‐pig vas deferens and portal vein, and there was no change in the responsiveness of the portal veins to noradrenaline.6. Endotoxin did not produce any changes in the responses of isolated preparations of ileum and atrium to histamine.7. It is concluded that the toxic effects of endotoxin in guinea‐pigs are likely to be independent of direct pharmacological effects on smooth and cardiac muscle or neuromuscular transmission. It is suggested that the toxic effects do not involve interactions with receptor mechanisms for a‐adrenoceptor agonists or histamine in this species.
THE EFFECT OF HEART RATE ON MYOCARDIAL OUABAIN UPTAKE AND ON THE SUSCEPTIBILITY TO OUABAIN CARDIOTOXICITY IN THE DOG
Authors: Lloyd Brian L. , Taylor Roger R. 
Published: June 2007

SUMMARY1. Tissue ouabain concentrations were estimated 30 min after intravenous 3H‐ouabain administration to sedated dogs, the heart rates of which were adjusted to range between 50 and 200 beats/min. Significant correlations were present between heart rate and ouabain content in left ventricle (r=0.93, P< 0.001), in right ventricle and left atrium. In contrast, no significant correlations were present between heart rate and ouabain content in liver, in renal cortex, skeletal muscle or plasma.2. To determine the functional effect of the greater myocardial ouabain uptake associated with higher heart rate, anaesthetized open‐chest dogs were studied. The heart rates of two groups were controlled at 199 ± 9 (s.d.) beats/min and 90 ± 14 beats/min during ouabain administration, and 30 min later, at a common heart rate, acetyl strophanthidin tolerance tests were performed.3. Acetyl strophanthidin infusion induced ventricular tachycardia significantly earlier, after a correspondingly lower dose in the fast heart rate group (P<0.01). Significant inverse correlations were present between the concentrations of ouabain in both left and right ventricular muscle and the duration of acetyl strophanthidin infusion.4. The results indicate that higher heart rate is associated with greater myocardial ouabain uptake and that this ouabain is functionally active.
RENOVASCULAR HYPERSENSITIVITY TO NORADRENALINE IN DIETARY‐INDUCED HYPERCHOLESTEROLAEMIA IN BABOONS
Authors: Bomzon L. , Kew M. C. , Rosendorff C. 
Published: June 2007

SUMMARY1. Using the xenon‐133 washout technique, the renovascular response to intra‐renal infusions of 3 and 30 μ/min noradrenaline in four baboons with dietary‐induced hypercholesterolaemia was measured.2. The degree of reduction in cortical blood flow rate during an intrarenal infusion of 3μmol/min. noradrenaline in the four hypercholesterolaemic baboons was not significantly different from that in normocholesterolaemic baboons. However, a significant difference in the degree of reduction in cortical blood flow rate was found with the 30μmol/min noradrenaline infusion (P < 0.05).3. The mean arterial blood pressure of the four animals was significantly higher (P< 0.001) than the mean blood pressure in baboons used in this laboratory for other experiments.4. These results have shown that baboons with dietary‐induced hypercholesterolaemia have an enhanced renovascular sensitivity to exogenous noradrenaline. However, the possibility that this enhanced sensitivity was due to the associated hypertension cannot be excluded.
CLINICAL DOSE‐RESPONSE STUDIES WITH GUANFACINE (BS 100‐141), A NEW ANTIHYPERTENSIVE AGENT
Authors: MacCarthy P. , Isaac P. , Frost G. , Freeman A. , Stokes G. 
Published: June 2007

SUMMARY1. Blood pressure, pulse rate, salivary flow and the degree of sedation were recorded at intervals following oral administration of single doses of guanfacine, a clonidine‐like agent, to hypertensive patients.2. Between 2 and 10 h after administration of guanfacine (3 mg or S mg), there were dose‐related decreases in lying and standing blood pressure, together with significant reductions in pulse rate and salivary flow.3. It is concluded that guanfacine lowers blood pressure in hypertensive patients and is probably suitable for twice daily administration, but produces xerostomia and sedation.
THE EFFECTS OF ADRENALECTOMY ON THE CARDIOVASCULAR RESPONSES TO A'‐TETRAHYDROCANNABINOL IN RATS
Authors: Li D. M. F. , Chung J. P. C. 
Published: June 2007

SUMMARY1. In urethane anaesthetized sham‐operated rats, intravenous administration of Δ1‐THC (1 mg/kg) caused an immediate and prolonged fall in blood pressure, with a concomitant reduction in pulse rate.2. In rats which had been adrenalectomized 24 h previously, Δ1‐THC (1 mg/kg, i.v.) also caused a depressor response, but it was significantly shorter in duration than that observed in sham‐operated animals. The durations of the cardiac slowing effect were similar in both groups of rats.3. Hydrocortisone pretreatment (25 μg/kg> i‐v), given 45 min before Δ1‐THC, restored the duration of the depressor response to Δ1‐THC in adrenalectomized rats, but it did not have any effect on the bradycardia induced by Δ‐THC.4. Hydrocortisone did not produce any significant effect on the hypotensive action of Δ1‐THC in sham‐operated rats, but the cardiac slowing effect was markedly potentiated.5. These results suggest a lack of correlation between the hypotensive and cardiac slowing actions of the drug and that a certein level of adrenal steroids is necessary for the maintenance of the depressor response to Δ1‐THC.
THE EFFECT OF VARIOUS DRUGS ON ADENOSINE TRIPHOSPHATE CONTENT AND HISTAMINE RELEASE FROM RAT PERITONEAL CELL SUSPENSIONS RICH IN MAST CELLS
Authors: Day R. O. , Wade D.N. 
Published: June 2007

SUMMARY1. Iopanoic acid and iophenoxic acid were potent inhibitors of compound 48/80‐induced histamine release from rat peritoneal cell suspensions rich in mast cells and caused a parallel dose‐related reduction in ATP content of these cells.2. Lignocaine was less potent and ouabain and probenecid were ineffective in inhibiting histamine release and reducing cellular ATP content.3. Various drugs can inhibit 48/80‐induced histamine release from rat peritoneal cells and this activity may result from depletion of cellular ATP. It is apparent that little structural specificity is required for activity in this cell system.
PERIPHERAL MUSCLE EFFECTS OF LEVODOPA IN THE ANAESTHETIZED CAT
Authors: Bowman W. C. , Nott M. W. 
Published: June 2007

SUMMARY1. Levodopa, dopamine, noradrenaline and adrenaline (in increasing order of potency) depressed the tension and degree of fusion of incomplete tetanic contractions of the slow‐contracting soleus muscle in chloralose‐anaesthetized cats.2. The effects of all compounds were antagonized by propranolol (50‐20 μg/kg), but not practolol (1.0‐5.0 mg/kg). This indicates that effects are mediated by β2‐adrenoceptor stimulation.3. The effect of levodopa, but not of the catecholamines, was antagonized by prior administration of the dopa decarboxylase inhibitor benserazide. This indicates that levodopa itself is inactive, whereas its decarboxylated metabolites are active.4. The depressant action of β‐adrenoceptor agonists on incomplete tetanic contractions of the cat soleus muscle, which are exerted directly on the muscle fibres, is a model for effects exerted on slow‐contracting units of human muscles; the latter effects probably underlie the tremor observed after β‐adrenoceptor agonist administration.5. These results therefore suggest that levodopa, via its decarboxylated metabolites, dopamine, noradrenaline and adrenaline, may produce or exacerbate tremor in man. Thus in Parkinsonian patients, any centrally induced relief of tremor that levodopa may produce may be masked by tremorogenic effects of such metabolites exerted in the periphery.
ACTION OF OCTOPAMINE AGONISTS AND STEREO ISOMERS AT A SPECIFIC OCTOPAMINE RECEPTOR
Authors: Dougan D. F. H. , Wade D. N. 
Published: June 2007

SUMMARY1. (±)‐Octopamine, (±)‐N‐methyl octopamine and (‐)‐α‐methyl octopamine increase the amplitude of contraction of the spontaneously beating ventricle of the mollusc Tapes watlingi through action on a specific octopamine receptor.2. Unlike the excitatory responses to dopamine, noradrenaline or serotonin, the excitatory response of the ventricle to agonists at the octopamine receptor is attenuated by metoclopramide.3. Compounds with potent agonist activity at the octopamine receptor all have a single phenolic hydroxyl in the para position of the benzene ring and a β‐hydroxyl group in the phenethylamine side chain. O‐Methylation of the para phenolic group or removal of the /3‐hydroxyl group results in complete loss of agonist activity. Bulky substituents but not a single methyl group on the amino groups impair agonist activity.4. The octopamine receptor is stereo‐selective, (‐)‐octopamine is more than twenty times more active than (+)‐octopamine.5. The weak octopamine‐like activity of (‐)‐N‐methyl and a‐methyl meta octopamine indicates that the stereo‐selective receptor has a relative rather than an absolute requirement for a single phenolic hydroxyl in the para position of the benzene ring.6. These data indicate the presence of a specific, stereo‐selective receptor for octopamine in the ventricle of the mollusc Tapes watlingi.7. The stereo‐selectivity and structural specificity of the octopamine receptor differentiates it from receptors for dopamine and serotonin also present in the ventricle.
BRAIN BIOGENIC AMINES AND INTRAVENOUS SELF‐ADMINSTRATION OF COCAINE IN RATS
Authors: Ross J. W. , Laska F. J. , Fennessy M. R. 
Published: June 2007

SUMMARY1. The possible involvement of noradrenaline, dopamine, serotonin and 5‐hydroxyindoleacetic acid in the behavioural reinforcement produced by intravenous cocaine has been investigated.2. Rats, in Skinner boxes, were allowed to self‐administer cocaine through a chronically implanted jugular vein cannula. A consistent response rate in the order of one self‐administration every 10 min was observed with a dose of 3.0 mg/kg cocaine hydrochloride per response.3. Another group of rats was cannulated and injected with a range of one to six such doses of cocaine at 10 min intervals on the basis of the responding rate, established by rats in the Skinner box. At times of 2, 5 and 8 min after each dose of cocaine, the rats were decapitated and brain concentrations of noradrenaline, dopamine, serotonin and 5‐hydroxyindoleacetic acid were determined.4. The brain levels of noradrenaline exhibited a cyclic pattern of rise and fall after each dose of cocaine, which corresponded in its time base with the time interval between responses established by the rats in the Skinner box.
THE CONTRACTION INDUCED BY CALCIUM IONS IN ISOLATED GUINEA‐PIG VAS DEFERENS
Authors: Sugjmoto J. , Furumichi A. , Murakami M. 
Published: June 2007

SUMMARY1. When isolated guinea‐pig vas deferens was pretreated with 0.01% sodium edetate in an isotonic sucrose medium and then transferred to an edetate‐free sucrose medium, the addition of CaCl2 (1.1 to 35.2 mmol/1) induced a contraction.2. The contraction was greatest when the CaCl2 was added soon after pretreat‐ment with edetate, and decreased with increasing time, almost disappearing after 1h.3. When KC1 (1.4 to 22.4 mmol/1) was added in place of CaCl2, the contraction was lowest soon after pretreatment with edetate, and increased with time; after 1 h, the effect was 80.7% of that observed in a preparation that had not been pretreated with edetate.
THROMBOXANE B2 INHIBITS PROSTAGLANDIN E2 INACTIVATION BY THE RAT ISOLATED PERFUSED LUNG
Authors: Boura A. L. A. , Murphy R. D. 
Published: June 2007

SUMMARY1. The effect of thromboxane B2 (T×B2) on inactivation of prostaglandin E2 (PGE2) by the rat isolated perfused lung has been studied.2. TxB2 when infused in low concentrations (100 ng/ml) into the pulmonary artery reduced PGE2 inactivation approximately two‐fold.3. The rat isolated fundus strip was contracted by higher concentrations of TxB2 (1.0 Mg/ml) in the presence of hyoscine, mepyramine, methysergide, phenoxy‐benzamine and propranolol. The size of contraction was reduced by indomethacin in concentrations known to inhibit prostaglandin synthetase.4. Thus, in circumstances in which T×B2 and PGE2 are released concomitantly by the lung, low concentrations of TxB2 may augment PGE2 release by reducing its inactivation.
AGONISTIC AND ANTAGONISTIC ACTIONS OF 3,4‐DmYDROXY‐SUBSTITUTED PHENOXYPROPANOLAMINES DM GUINEA‐PIG ATRIA AND TRACHEA
Authors: Keh G. S. , Raper C. , Dowd H. 
Published: June 2007

SUMMARY1. Racemic mixtures of noradrenaline, adrenaline, isoprenaline, N‐r‐butylnor‐adrenaline and their corresponding derivatives containing an oxymethylene (OM) link between the phenyl ring and ethanolamine side‐chain have been tested for their effects on β‐adrenoceptors in isolated guinea‐pig atrial and tracheal preparations.2.In atrial and in spontaneously contracted tracheal preparations both the parent catecholamines and their corresponding OM‐derivatives had a similar order of potency as 0‐receptor agonists.3.In carbachol‐stimulated tracheal preparations the OM‐derivatives were shown to have partial agonistic actions.4.As in other phenylethanolamines and phenoxypropanolamines, both the agonistic and antagonistic potency of the OM‐derivatives increased with increasing amine substitution.
ALTERATIONS EM LEVELS OF VASCULAR HISTAMINE IN THE DOCA‐HYPERTENSIVE RAT
Authors: Holcslaw T. L. , Imhoff L. 
Published: June 2007

SUMMARY1. Histamine was detected in the abdominal aorta and the femoral arteries of normotensive and also DOCA‐hypertensive rats.2. Levels of total histamine (mast cell and non‐mast cell histamine) were significantly reduced in both abdominal aorta and the femoral artery of the DOCA‐hypertensive rats, relative to the normotensive controls.3. It is suggested that the diminished level of vascular histamine may be related to the development and/or maintenance of the hypertensive state and is also related to the reduced magnitude of active reflex vasodilatation.