bluuebunny/crossref_metadata_2025 huggingface dataset:
Ascending tonic‐clonic seizure syndrome in a dog following inadvertent intrathecal use of ionic contrast agent
Authors: Finke Maureen D. , Meola Stacy D. , Mazzaferro Elisa M.
Published: July 2012

Objective

To describe the successful management of ascending tonic‐clonic seizure syndrome in a dog after inadvertent intrathecal administration of ionic contrast material.

Case Summary

A 7‐year‐old, 5.9 kg, male castrated Miniature Pinscher inadvertently received intrathecal ionic contrast material during a myelogram to investigate cervical pain. Ascending tonic‐clonic muscle spasms quickly progressed to generalized seizure activity that was resistant to anticonvulsant medications. The dog developed complete respiratory arrest, which necessitated mechanical ventilatory support for 26 hours. Pneumonia developed and was treated successfully. After resolution of seizure activity and resumption of voluntary respiration, the dog remained tetraparetic for 16 days and was not able to walk on his own for 20 days post contrast injection. Despite a prolonged recovery, the patient survived and recovered normal neurologic function.

New or Unique Information Provided

Intrathecal administration of ionic contrast material resulting in ascending tonic‐clonic seizure syndrome is rarely reported in the human and veterinary literature. No previous veterinary report has described successful treatment after prolonged respiratory arrest. In previous veterinary reports, patients recovered complete neurologic function within hours to days in contrast to this report in which the patient was tetraparetic for 16 days. This report demonstrates complete recovery from intrathecal ionic contrast administration is possible despite a high dose of contrast and a prolonged recovery.
Interactions between acetylcholine, 5‐hydroxytryptamine, nicotine and morphine on isolated rabbit atria
Authors: CHITTAL S. M. , DADKAR N. K. , AITONDÉ B. B.
Published: July 2012

The effects of 5‐hydroxytryptamine (5‐HT) and morphine on the responses to acetylcholine and nicotine of isolated rabbit atria were studied.

5‐Hydroxytryptamine (10 μg/ml.) and morphine (20 μg/ml.) blocked the negative chronotropic and inotropic actions of acetylcholine.

Nicotine (20 μg/ml.) produced stimulation of the atria, which was blocked by dichlorisoprenaline, morphine, 5‐HT, bretylium and hemicholinium. Hemicholinium block was reversed by choline.

In reserpinized preparations, nicotine produced inhibition of atria and this action was also blocked by atropine, 5‐HT and morphine. Inhibition induced by nicotine was potentiated by physostigmine.

5‐Hydroxytryptamine (20 μg/ml.) produced stimulation of atria. This was blocked by bretylium and reduced by hemicholinium. Hemicholinium block was reversed by choline.

It is concluded that 5‐HT in low concentrations acts as a weak agonist at the cholinoceptive receptors and therefore blocks the action of acetylcholine. Furthermore, nicotine and larger doses of 5‐HT have actions on ganglionic structures and liberate acetylcholine, which in turn releases catecholamines.
The distribution of tritium‐labelled prostaglandin E1 injected in amounts sufficient to produce central nervous effects in cats and chicks
Authors: HOLMES S. W. , HORTON E. W.
Published: July 2012

After injection of tritiated prostaglandin E1 into the lateral cerebral ventricle, the carotid and vertebral arteries and the aorta in cats, only a small proportion of the radioactivity was recovered from the central nervous system.

Similar results were obtained when the prostaglandin was given intravenously and intra‐arterially to chicks.

The results of this study confirm work in other species (Hansson & Samuelsson, 1965; Samuelsson, 1964, 1965) and suggest that prostaglandin E1 exerts its central pharmacological actions in small concentrations.
5‐Hydroxytryptamine metabolism in rat brain and liver homogenates
Authors: FELDSTEIN A. , WILLIAMSON O.
Published: July 2012

The metabolism of 5‐hydroxyindoleacetaldehyde derived from 5‐hydroxytryptamine incubated with tissue homogenates was studied as an indicator of aldehyde dehydrogenase and alcohol dehydrogenase activities.

In liver and brain from rats, there were indications of the presence of one or more aldehyde dehydrogenases which were stimulated by NAD+ to a greater extent than by NADP+.

In liver from rats, there were indications of the presence of one or more alcohol dehydrogenases, which were stimulated by NADH to a greater extent than by NADPH.

In brain from rats, there were indications of the presence of one or more alcohol dehydrogenases which were stimulated by NADPH to a greater extent than by NADH.
Effects of physostigmine on the afterdischarge and slow postsynaptic potentials of bullfrog sympathetic ganglia
Authors: KOKETSU K. , NISHI S. , NODA Y.
Published: July 2012

The effects of anticholinesterases (anti‐ChEs) (physostigmine, prostigmine and TEPP) on the afterdischarges and the extracellular and intracellular slow potentials of bullfrog sympathetic ganglia were studied.

The anti‐ChEs augmented the early afterdischarge, the late negative potential and the slow excitatory postsynaptic potential. This indicated that the nature of the early afterdischarge was cholinergic (muscarinic) and that the late negative potential or the slow excitatory postsynaptic potential generated the early afterdischarge.

Since the anti‐ChEs increased the positive potential, the depression of the early afterdischarge observed in the presence of an antiChE was explained to be caused by the increased inhibitory effect of the enhanced positive potential.

Prostigmine and tetraethyl pyrophosphate did not show any appreciable effects on the late afterdischarge, the late late negative potential nor the late slow excitatory postsynaptic potential. This indicated that the nature of the late afterdischarge was non‐cholinergic and that the late late negative potential or the late slow excitatory postsynaptic potential generated the late after‐discharge.

Physostigmine reversibly depressed the late afterdischarge, the late late negative potential and the late slow excitatory postsynaptic potential. The depressant action of physostigmine was not due to its anti‐ChE action.
Investigation of the spasmogenic effect of manganese on the guinea‐pig isolated ileum preparation
Authors: SCHNIEDEN H. , WESTON A. H.
Published: July 2012

The mechanism of the manganese‐induced spasm of the guinea‐pig ileum was investigated using agents known to modify nerve function. The spasm was reduced by cooling, tetrodotoxin, procaine, Botulinus toxin (Type A), hyoscine and pempidine. It was potentiated by mipafox.

In the presence of manganese, the release of acetylcholine from the ileum was greatly increased.

Tetrodotoxin prevented the manganese‐induced increase in acetylcholine output from the ileum but had no significant effect on the spontaneous acetylcholine output.

It is suggested that the manganese‐induced spasm of the ileum results from an action on intramural cholinergic nerves.
Studies of the effect of natural and synthetic polypeptide type ergot compounds on a peripheral vascular bed
Authors: AELLIG W. H. , BERDE B.
Published: July 2012

Six ergot alkaloids were tested for their effect on vascular resistance and for α‐adrenergic blocking activity on the innervated perfused hind limb of the dog. The results were compared with those obtained earlier for three compounds of the ergotamine group.

Ergostine, dihydroergostine, 1‐methylergostine and dihydroergocristine resembled ergotamine, dihydroergotamine and 1‐methylergotamine in eliciting vasoconstriction at low vascular resistance and vasodilatation at high vascular resistance. The changeover occurred at the following “inversion points”: ergostine and dihydroergostine as with ergotamine and dihydroergotamine at about 4 R.U.; 1‐methylergostine as with 1‐methylergotamine at about 2·3 R.U.; dihydroergocristine at about 1·9 R.U. [1 R.U. = 1 resistance unit = 1 mm Hg/ml. per min.]

1‐methyldihydroergocristine consistently elicited vasodilatation (for initial vascular resistances down to 1·3 R.U.) and 5′‐methylergoalanine always caused vasoconstriction (for initial values up to 5·8 R.U.).

Ergostine and 5′‐methylergoalanine had the most powerful vasoconstrictor effect, which was of the same order of magnitude as that of ergotamine. Dihydroergostine, like dihydroergotamine, was considerably less active. Both 1‐methylergostine and 1‐methylergotamine elicited only weak vasoconstriction. Moreover, when the initial vascular resistance exceeded the critical inversion value, they elicited only weak vasodilatation. Dihydroergocristine and 1‐methyldihydroergocristine had the least effect on vascular resistance.

The increase in vascular resistance by noradrenaline was inhibited in a dose‐dependent manner by all the ergot alkaloids investigated. Ergostine, 5′‐methylergoalanine and ergotamine had the greatest α‐adrenergic blocking activity and 1‐methylergostine, 1‐methyldihydroergocristine and 1‐methylergotamine the weakest. The activity of dihydroergostine, dihydroergocristine and dihydroergotamine fell between these two extremes.

No correlation was found between the qualitative effect of these ergot alkaloids on vascular resistance (inversion point) and (a) their quantitative effect on this parameter or (b) their α‐adrenergic blocking activity. Determination of the inversion point thus provides additional pharmacological information on the vasoactive properties of the ergot alkaloids.
Effects of reserpine on the disposition of sympathomimetic amines in vascular tissue
Authors: KALSNER S. , NICKERSON M.
Published: July 2012

The effects of reserpine pretreatment on the intrinsic inactivation of low concentrations of phenylephrine and noradrenaline in strips of rabbit thoracic aorta were assessed by measuring the rates of relaxation, after oil immersion to prevent loss of active amine by diffusion into the surrounding medium.

Reserpine pretreatment considerably augmented the amplitude of responses to low concentrations of phenylephrine, noradrenaline and nordefrine (Cobefrine).

Reserpine pretreatment did not reduce the overall rate of inactivation of either phenylephrine or noradrenaline, but it did appear to decrease the contribution of uptake and storage, measured as an increased effect of enzyme inhibition and a decreased effect of cocaine on the rate of inactivation.

The role of catechol‐O‐methyl transferase (COMT), but not that of monoamine oxidase (MAO), in terminating the action of noradrenaline was increased in strips from animals pretreated with reserpine. Thus it appears that interference with intraneuronal storage diverts active amine to inactivation by COMT in vascular tissue, rather than by MAO as has been previously suggested.

As in preparations not treated with reserpine, inhibition of MAO alone had little effect on the rate of inactivation of noradrenaline, and this enzyme appears to function predominantly as an alternate pathway of little importance as long as COMT activity is unimpaired. Enzymatic processes accounted for about 85 and 70% of the inactivation of a low concentration of noradrenaline in reserpine pretreated and untreated preparations, respectively.

Cocaine potentiated responses to noradrenaline and phenylephrine as effectively in reserpine pretreated as in untreated preparations, and inhibition of the pathways of enzymatic inactivation did not appreciably decrease the potentiation produced by this agent.

The present results cannot be explained by the hypothesis that interference with amine inactivation by nerve uptake and storage is responsible for the potentiation of responses to noradrenaline or phenylephrine by either reserpine or cocaine, and emphasize the unrealiability of potentiation as an index of interference with mechanisms involved in terminating the action of sympathomimetic amines.
The possible role of histamine in the cortisone induced gastric acid hypersecretion of the guinea‐pig
Authors: HEISLER S. , KOVACS EVA M.
Published: July 2012

The effects of cortisone treatment combined with agents influencing histamine metabolism were studied on the free and total acid output in pylorus ligated guinea‐pigs.

It was found that reduction in the synthesis of histamine produced by the administration of α‐methylDOPA significantly inhibited the acid response to cortisone.

Enhancement of the oxidative deamination of histamine brought about by the administration of diamine oxidase or heparin inhibited cortisone induced acid hypersecretion significantly.

Inhibition of the oxidative deamination of histamine by aminoguanidine and iproniazid resulted in a significant increase of the cortisone induced acid hypersecretory response.

Inhibition of the methylation of histamine by chlorpromazine or 1, 4‐methylhistamine inhibited the cortisone induced hypersecretory response significantly.

Studies with labelled histamine indicated that cortisone increases the sequestration of histamine to the stomach.
The effects of atropine and dyflos on tremor and increase in whole brain acetylcholine produced by injection of oxotremorine in the rat
Authors: COX B. , POTKONJAK D.
Published: July 2012

Injection of oxotremorine in the rat results in tremor and an increase in brain acetylcholine. The effects of atropine and dyflos have been investigated on both these actions.

Atropine decreased brain acetylcholine concentration and inhibited oxotremorine‐tremor. It did this in doses which did not prevent the oxotremorine‐induced increase in whole brain acetylcholine.

Dyflos increased brain acetylcholine concentration, but it was without effect on oxotremorine tremor. Some mutual antagonism was observed between the actions of oxotremorine and dyflos on rat brain acetylcholine concentration.

These results do not support a causal relationship between the increase in whole brain acetylcholine and the tremor produced by oxotremorine.
The effect of morphine dependence on the vesicular content of adrenergic nerves in relation to arteriolar smooth muscle in the pancreas of the rat
Authors: GRAHAM J. D. P. , LEVER J. D. , SPRIGGS T. L. B.
Published: July 2012

. Sibling male Wistar rats were kept in groups of three under identical conditions. Two groups were made morphine dependent in 28 days and the third served as control. The state of dependence was established by recording the development of tolerance to the analgesic action of the drug and the effect of acute withdrawal of morphine and injection of nalorphine on one test group.

. Animals in the other test group and the control group were killed and specimens of pancreas collected and prepared for examination by electron microscopy. The adrenergic innervation of pancreatic arterioles was located and photographed and the effect of morphinization on the percentage of granular and agranular small vesicles in the axons determined.

. Morphinization produces a significant reduction in the granular or dense core vesicle population of these adrenergic axons.
Factors involved in maintenance of cardiac catecholamine content: relative importance of synthesis and re‐uptake
Authors: BHAGAT B. , FRIEDMAN EITAN
Published: July 2012

. When animals were exposed to a temperature of 4° C for 6 hr, endogenous catecholamines remained unaltered or reduced slightly depending upon the strain of rats used. In contrast, labelled noradrenaline declined rapidly, but the decline was inhibited when animals were pretreated with monoamine oxidase inhibitors.

. Increased sympathetic nervous activity associated with cold resulted in a four‐fold increase in rate of synthesis of noradrenaline.

. Reduction in endogenous and labelled catecholamine levels associated with cold was exaggerated by pretreatment with cocaine, imipramine or phenoxy‐benzamine—drugs known to inhibit the uptake of noradrenaline into the nerve terminal.

. Cocaine and imipramine in higher doses inhibited the release of both endogenous and labelled noradrenaline, suggesting a dual action: in small doses they increased the depletion of catecholamines by blocking the reincorporation, while in higher doses they inhibited the release of noradrenaline.

. It is concluded that, under normal conditions, the re‐uptake mechanism may not play a significant role in the maintenance of normal cardiac catecholamine levels and that such levels are maintained by synthesis alone. However, when the heart is subjected to high impulse nerve activity, synthesis is not sufficiently accelerated to compensate for impulse‐induced massive release and may require the support of an additional mechanism, such as the partial reincorporation of released transmitter. In fact, the re‐uptake mechanism is enhanced during high impulse activity.
Effects of chronic administration of (+)‐amphetamine on maze performance of the rat
Authors: BREDA J. B. , CARLINI E. A. , SADER N. F. A.
Published: July 2012

. The influence of (+)‐amphetamine, given 1 min after each training session, on the performance of 124 rats in a Lashley III maze was measured every 48 hr.

. The first three injections of the drug significantly improved the learning ability of naive rats.

. With prolonged treatment, (+)‐amphetamine strongly impaired the maze performance of these rats.

. The chronic administration of (+)‐amphetamine to previously trained rats produced the same adverse effect.

. Amylobarbitone sodium given to previously trained rats 30 min before the training sessions completely blocked the adverse effect of (+)‐amphetamine.

. (+)‐Amphetamine did not produce impairment of performance when given chronically 30 min before training sessions, to previously trained rats.
Antagonism by physostigmine of the “running fit” caused by levorphanol, a morphine congener, in mice
Authors: SHARKAWI MAHMOUD , GOLDSTEIN AVRAM
Published: July 2012

. Drugs of the morphine type cause a stereotyped “running fit” in the mouse.

. The intensity and duration of this response are related to the dose.

. Measurement of this phenomenon serves as a good method for the quantitative comparison of drugs of this type and for the study of their antagonists.

. Intracerebral injection of physostigmine antagonized the “running fit” induced by a wide range of doses of levorphanol.

. The results are consistent with the hypothesis that drugs of the morphine type act by retarding the release of acetylcholine at some central cholinergic synapses.
Kinin forming and destroying activities in human bile and mucous membranes of the biliary tract
Authors: NIELSEN H. M.
Published: July 2012

. Human bile and tissue homogenates from the mucous membranes of the biliary tract possess plasma kinin forming activity (kininogenases) and plasma kinin destroying activity (kininases) in varying degrees.

. The common bile duct, especially its lower part, had high kininase activity.

. The liver possessed a high kininase activity, but no kinin forming activity.

. The inactive precursor of plasma kinin, kininogen, was not detected in the bile.

. Results from different pathological conditions are reported.

. The implications of the findings are discussed. Special importance is attached to the question of a formation of kininogenases in the liver and to the significance of a plasma kinin activity in the bile and the biliary tract.
Relationships between chemical structure and affinity for acetylcholine receptors
Authors: ABRAMSON F. B. , BARLOW R. B. , MUSTAFA M. G. , STEPHENSON R. P.
Published: July 2012

. Series of analogues of acetylcholine have been prepared in which the acetyl group was replaced by phenylacetyl, cyclohexylacetyl, diphenylacetyl, dicyclohexylacetyl, (±)‐phenylcyclohexylacetyl, benziloyl and (±)‐phenyl‐cyclohexylhydroxyacetyl groups and the trimethylammonium group was replaced by Me2EtN+, MeEt2N+, Et3N+,

Further series were prepared in which the acetoxyethyl group was replaced by ethoxyethyl, phenylethoxyethyl, cyclohexylethoxyethyl, diphenylethoxyethyl, and dicyclohexylethoxyethyl groups, and by n‐pentyl, 5‐phenylpentyl, 5‐cyclohexylpentyl and 5:5‐diphenylpentyl groups.

. The ethoxyethyl and n‐pentyl series contain some compounds which are agonists or partial agonists when tested on the isolated guinea‐pig ileum, but all the other compounds are antagonists.

. The affinity of the compounds for the postganglionic (“muscarine‐sensitive”) acetylcholine receptors has been measured in conditions in which the antagonists have been shown to be acting competitively. There were considerable differences between their affinities, the most active (log K, 9.8) having one million times the affinity of the least active (log K, 3.7).

. The changes in affinity as the onium group was modified were not entirely independent of changes in the rest of the molecule. Increasing the size of the onium group, as judged from conductivity measurements on simpler onium salts, increased affinity in the series containing one large group (phenyl or cyclohexyl) but, in the series with two large groups, affinity declined when the size was increased beyond ‐N+MeEt2.

. In general, the effects of changes in the rest of the molecule on affinity were bigger than the effects of changes in the onium group and there were bigger interactions. Affinity was increased to a greater extent by introducing one phenyl and one cyclohexyl group together than by introducing either two phenyl or two cyclohexyl groups; the increment was greater than the separate contributions made by one phenyl and one cyclohexyl group.

. The factors which influence the binding of molecules to receptors are discussed. There is no evidence that the separation between the onium group and the group in the receptor with which it interacts is greater in compounds with high affinity nor is there any evidence, from the study of the series which contain agonists and partial agonists, that ability to activate receptors depends upon the onium group being able to come close to this charged group in the receptors.
The action of eledoisin on the peristaltic reflex of guinea‐pig isolated ileum
Authors: BELESLIN D. B.
Published: July 2012

. Low concentrations of eledoisin, acting from the serosal surface of the guinea‐pig isolated ileum, had no effect on the peristaltic reflex, whereas in high concentrations it depressed or sometimes abolished this reflex.

. Eledoisin stimulated the peristaltic activity of the guinea‐pig ileum subjected to continuously raised intraluminal pressure. This stimulatory effect could be produced regularly when the interval between additions of eledoisin was at least 20 min. When added at shorter intervals, tachyphylaxis to eledoisin developed, but its ability to promote peristaltic activity was restored by the addition of an anticholinesterase to the bath fluid. During tachyphylaxis to eledoisin, nicotine and dimethylphenylpiperazinium were unable to restore peristalsis.

. When the peristaltic reflex had been abolished by ganglion‐blocking agents, morphine and morphine‐like substances, or adrenaline, eledoisin restored the reflex. Eledoisin was much more effective in overcoming the blocking effect of hexamethonium, tetraethylammonium and azamethonium than that of nicotine or dimethylphenylpiperazinium.

. Eledoisin did not antagonize the inhibitory effects of atropine, hyoscine and hyoscine butylbromide.

. It is suggested that the stimulant effect of eledoisin may be due to a direct action on the smooth muscle and a release of acetylcholine from postganglionic nerve endings, but an effect on the intestinal ganglion cells cannot be excluded.
Studies on the mode of action of hexobendine, a prospective anti‐anginal drug
Authors: McINNES LINDA , PARRATT J. R.
Published: July 2012

. In cats anaesthetized with pentobarbitone sodium, hexobendine (0.25 mg/kg) markedly increased myocardial blood flow (measured using a heat clearance technique) and usually decreased myocardial metabolic heat production, without influencing cardiac contractility or systemic arterial blood pressure. These effects lasted for about 45 min.

. Larger doses (0.5 and 1.0 mg/kg) decreased systemic arterial blood pressure and the rate of rise of the left ventricular pressure pulse (dp/dt), although left ventricular end‐diastolic pressure was usually increased. This is indicative of a decrease in myocardial contractility.

. In a concentration of 5 × 10−6g/ml., hexobendine protected isolated rabbit atria against the decrease in contractility that follows the removal of oxygen.

. Hexobendine did not antagonize the systemic and myocardial effects of infusions of adrenaline and noradrenaline, nor (except in concentrations of 10−5g/ml.) the increase in contractility induced by these catecholamines on isolated rabbit atria.
Comparative study of the effect of three antibiotics on renal function
Authors: CALDWELL A. D. S. , MARTIN A. J. , TRIGGER D. J.
Published: July 2012

. Therapeutic doses of colistin sulphomethate sodium B.P. (Colomycin), pento‐N sulphomethylpolymyxin B sodium (Thiosporin) and ampicillin B.P. (Penbritin) as well as normal saline have been given to volunteers with normal kidney function.

. A blind crossover technique was used and the effects of the compounds on blood levels and clearances of urea and creatinine studied.

. All four treatments resulted in some changes in the parameters measured but were reversible. The most marked changes were found with pento‐N sulphomethylpolymyxin B sodium and were also associated with severe side‐effects.

. In contrast to penicillins it is established that the process of tubular secretion sensitive to probenecid block plays no part in the renal excretion of polymyxins.
The kinetics of elimination of salicylic acid and the formation of gentisic acid
Authors: BOREHAM D. R. , MARTIN B. K.
Published: July 2012

. A method for the estimation of gentisic acid in urine has been devised which is based on thin‐layer chromatography and fluorimetry.

. In man the urinary excretion of gentisic acid accounted for 0.6% of a 0.32 g dose of aspirin and 1.1% of a 1.28 g dose. The increase in the percentage of the dose excreted as gentisic acid provides further evidence that the elimination of salicylic acid cannot be entirely described by first order kinetics.

. Equations are presented which describe the amount of gentisic acid formed from various doses of salicylic acid in a model system, when elimination proceeds partly by simultaneous first order and zero order kinetics. The close argeement of the experimental and theoretical results indicates that the model provides an acceptable interpretation of salicylic acid elimination in man.
Studies on the mode of action of vasopressin on the isolated proximal colon of the guinea‐pig
Authors: BOTTING J. H. , TURMER A. D.
Published: July 2012

. Contractions of guinea‐pig isolated proximal colon produced by vasopressin are not affected by methyloxytocin (a compound that blocks pressor effects of vasopressin).

. Vasopressin contractions are inhibited by replacement of sodium with mannitol or sucrose, elevation of potassium or magnesium concentrations, the presence of the metabolic inhibitors sodium azide and triethyl tin or tetrodotoxin in the bathing fluid. Contractions produced by histamine or choline esters are comparatively insensitive to these procedures.

. Contractions of rat isolated uterus following vasopressin, oxytocin and methacholine are equally affected by replacement of sodium, increase of potassium or magnesium or addition of sodium azide.

. Neither vasopressin contractions nor contractions caused by transmural stimulation were consistently affected by morphine (10−6g/ml.) or hyoscine (10−7g/ml.) although both were reduced by anoxia or cooling the tissue. Morphine did not reduce the output of acetylcholine from stimulated colon.

. It is concluded that the action of vasopressin on proximal colon is unlike its action on other smooth muscle and is mediated by nervous tissue.
Capacitance changes in frog skin caused by theophylline and antidiuretic hormone
Authors: CUTHBERT A. W. , PAINTER ELISABETH
Published: July 2012

. Impedance loci for frog skins have been calculated by computer analysis from voltage transients developed across the tissues.

. Attention has been paid to simultaneous changes in conductance and capacitance of skins treated either with antidiuretic hormone (ADH) or with theophylline. These drugs always caused an increase in conductance and usually the skin capacitance also increased. However, changes in conductance were not correlated with capacitance changes.

. Changes in capacitance caused by the drugs may represent pore formation in the barrier to water flow, since both drugs increase hydro‐osmotic flow in epithelia. If this interpretation is correct, then 0.14% of the membrane area forms water‐permeable pores in response to a maximal dose of ADH. This value is somewhat less than the value obtained previously (0.3%) by graphical analysis.

. A theoretical account is given of the relative accuracy of the computer method and the graphical method for voltage transient analysis.
Uptake of antimony potassium tartrate by mouse liver slices
Authors: SMITH S. E.
Published: July 2012

. The uptake of 124Sb‐antimony potassium tartrate by isolated mouse liver slices has been measured and found to establish high tissue: medium concentration ratios.

. Uptake was not influenced by oxygen lack, potassium, ouabain, dinitrophenol or sodium arsenate. It was inhibited by dimercaprol and reduced at low temperature. No evidence was found of counter‐transport. After subcellular fractionation, most of the radioactivity was recovered from particulate fractions.

. Kinetic studies of uptake from media containing different concentrations of antimony suggest that uptake is due partly to diffusion and partly to a saturable binding mechanism, probably involving chelation by non‐diffusible thiol groups. Saturation studies suggest that only a small proportion of thiol groups bind antimony, the remainder undergoing catalytic oxidation.
Effect of β‐haloalkylamines and ephedrine on noradrenaline release from the intact spleen of the cat
Authors: KIRPEKAR S. M. , WAKADE A. R.
Published: July 2012

The effects of β‐haloalkylamines, phenoxybenzamine (PBZ), N‐α‐naphthyl‐methyl‐N‐ethyl‐β‐bromoethylamine (SY28), N‐cyclohexyl‐methyl‐N‐ethyl‐β‐chloroethylamine (GD131) and ephedrine on noradrenaline (NA) output following nerve stimulation were studied in the intact spleen of the cat. Postganglionic sympathetic nerves were stimulated at frequencies of 10 and 30 Hz for a total of 210 stimuli.

PBZ and SY28 (10 mg/kg) increased the transmitter output at 10 Hz by nearly 5–10 times.

Administration of GD131 (10 mg/kg) had no effect on output at either frequency. Phentolamine (3 mg/kg) given after GD131 increased NA output at 10 Hz.

Ephedrine (0·5 mg/kg) caused no changes in catecholamine output, while higher doses of ephedrine (10–20 mg/kg) increased the amount released at 10 Hz.

Perfusion of the spleen with Krebs‐bicarbonate solution containing either SY28, GD131 or ephedrine (10 μg/ml) increased the recovery of infused NA by 80–90%.

It is concluded that presynaptic as well as postsynaptic events determine the overflow of NA following stimulation of sympathetic nerves of the spleen.
The inactivation of noradrenaline and isoprenaline in dogs
Authors: GRYGLEWSKI R. , VANE J. R.
Published: July 2012

The removal of infused noradrenaline and isoprenaline from the circulation of the dog has been studied, using the blood‐bathed organ technique.

Both catecholamines were removed in peripheral vascular beds; in all organs studied, noradrenaline was removed to a greater degree than isoprenaline.

The hind legs removed an average of 60% of the noradrenaline passing through, but only 34% of the isoprenaline. With noradrenaline, the degree of removal decreased as the concentration increased, but with isoprenaline, the degree of removal increased with concentration.

After phenoxybenzamine, the proportion of isoprenaline removed was unchanged, whereas that of noradrenaline was decreased. The change in removal with the concentration of noradrenaline was also abolished.

The results are consistent with the concept that a small fraction of infused noradrenaline is removed from the circulation by Uptake1 and that this is blocked by phenoxybenzamine. Isoprenaline, and the rest of the noradrenaline, are removed by another process (Uptake2?) followed by intracellular metabolism. This inactivation process is unaffected by phenoxybenzamine in concentrations sufficient to give α‐adrenoceptor blockade.

After isoprenaline infusions, a substance sometimes appeared in the circulation which contracted the blood‐bathed organs.

The systemic pressure response to vaso‐active hormones is not a reliable indicator of the concentration of hormone in the arterial circulation.
Some central effects in mice of compounds related to nicotine
Authors: BARLOW R. B. , OLIVERIO A. , SATTA M. , THOMPSON G. M.
Published: July 2012

Some hydroxy‐, amino‐, and methoxy‐ phenylalkyltrimethylammonium compounds, β‐pyridylmethyl‐ dimethylamine and pyrrolidine, and β‐pyridyl>‐ethyltrimethylammonium, were tested on avoidance learning in mice and their effects were compared with those of (–)‐nicotine.

The o‐ and m‐ hydroxybenzyl‐, o‐hydroxyphenethyl‐ and m‐hydroxyphenylpropyl‐ trimethylammonium compounds improved performance; (–)‐nicotine, in one‐quarter of the dose, had similar effects. The m‐ and p‐hydroxyphenethyl‐, o‐hydroxyphenylpropyl‐ and o‐ and p‐ aminobenzyl, and o‐, m‐, and p‐ aminophenethyl‐trimethylammonium compounds impaired performance.

(−)‐Nicotine and m‐hydroxyphenylpropyltrimethylammonium appeared also to enhance memory consolidating processes.

The central actions of some of the compounds suggest that the possibility that they can penetrate into the central nervous system should not be ruled out even though they are quaternary salts.

No correlation was found between the effects of the compounds on avoidance learning and on the frog rectus muscle. Though the differences may be due to differences in access to the central nervous system, it is also possible that the receptors associated with learning processes are different from those in the frog rectus and possibly more specialized.
The relationship between functional vasodilatation in adipose tissue and prostaglandin
Authors: BOWERY N. G. , LEWIS G. P. , MATTHEWS J.
Published: July 2012

. Earlier it had been found that during fat mobilization there was an increased blood flow in the adipose tissue and the tissue contained a vasodilator substance.

. Extract of an activated fat pad contained 3 to 25 times as much activity as the contralateral resting fat pad.

. The following findings suggest that the vasodilator substance is prostaglandin E2:

It caused contractions of the guinea‐pig ileum which were not reduced by mepyramine, but were reduced by atropine.

It caused a prolonged vasodilator response when injected close‐arterially to the epigastric fat pad.

It was eluted from a silicic acid column by a solvent system which is known to elute prostaglandins of the E series but not those of the F series.

Its indices of discrimination were similar to those of prostaglandin E's when assayed on three different pharmacological preparations.

On thin‐layer chromatography it behaved more like prostaglandin E2 than E1.

. Neither prostaglandin E1 nor prostaglandin E2 inhibited the release of free fatty acids from the rabbit epigastric fat pad by ACTH1–24.

. It seems likely that prostaglandin E2 is responsible for the vasodilatation accompanying fat mobilization from adipose tissue.
Removal of 5‐hydroxytryptamine in the pulmonary circulation of rat isolated lungs
Authors: ALABASTER VALERIE A. , BAKHLE Y. S.
Published: July 2012

. Rat isolated lungs perfused via the pulmonary artery with Krebs solution removed 92% of the 5‐hydroxytryptamine (5‐HT) infused through it. This degree of removal was independent of concentration in the range from 5 to 100 g/ml.

. The removal of 5‐HT by the lungs was inhibited by amitriptyline and desmethylimipramine (10−6–10−5m).

. The monoamine oxidase inhibitors, mebanazine and iproniazid (10−6–10−5m), inhibited the initial removal slightly, but their main effect was to preserve the 5‐HT taken up and this 5‐HT slowly reappeared in the effluent from the lungs. Tranylcypromine (5 × 10−7–10−6m) showed a combination of amitriptyline‐like and mebanazine‐like effects on the 5‐HT removal in rat lung.

. Experiments with 3H‐5‐HT showed that although under normal conditions only 10% of the radioactivity appeared in the lung effluent as 5‐HT within the first 5 min, the rest of radioactivity administered could be recovered in the effluent over 50 min as a metabolite, probably 5‐hydroxyindoleacetic acid.

. The following amines were without effect on the removal of 5‐HT by rat lungs: noradrenaline (6 × 10−7m), normetanephrine (5 × 10−6m), metaraminol (10−6m), reserpine (10−6–10−5m) and phenoxybenzamine (10−5m).

. We conclude that the removal of 5‐HT by rat lungs involves a process of uptake and metabolism rather than one of uptake and storage, but this process is not the catecholamine Uptake2. The cells involved in this process might be either capillary endothelial cells or septal cells.
The pharmacological basis of coronary and systemic vasodilator actions of diazepam (Valium)
Authors: ABEL R. M. , REIS R. L. , STAROSCIK R. N.
Published: July 2012

The effects of α and β‐adrenoceptor blockade, depletion of catecholamine stores, vagotomy, atropine, and ganglionic blockade on diazepam‐induced vasodilatation were investigated in forty‐six anaesthetized dogs.

Coronary blood flow was measured by timed collections of coronary venous efflux from fibrillating, decompressed ventricles; coronary and systemic vascular resistances were determined during total cardiopulmonary bypass under conditions of normothermia and constant aortic (coronary artery) pressure.

No significant alteration in the vasodilatation produced by diazepam was observed following either vagotomy or α‐adrenoceptor blockade; partial inhibition of vasodilatation occurred after β‐adrenoceptor blockade or catecholamine depletion, and nearly total inhibition was observed after small doses of atropine or ganglion‐blocking agents.

The results suggest that diazepam may act as a specific ganglion‐stimulant, causing active sympathetic and cholinergic vasodilatation.
Modification by ouabain of the electrical and mechanical effects of acetylcholine in isolated rabbit atria
Authors: KAJIMOTO N. , TODA N.
Published: July 2012

Left atrial preparations isolated from rabbits were stimulated electrically at frequencies between 6 and 240/min. Tension‐frequency curves were obtained from control preparations and preparations treated with ouabain and acetylcholine. Transmembrane potentials were recorded from single cells of the left atrium stimulated at different frequencies.

The tension‐frequency curve was moved downwards by acetylcholine (10−6 g/ml). Ouabain (10−6 g/ml) caused characteristic alterations in the tension‐frequency relationship, enhancing the contractile tension at low but not high frequencies. The negative inotropic effect of acetylcholine was reduced by treatment with ouabain.

Action potential durations were significantly influenced by alterations in frequency of contraction. The 10% duration increased with frequency within the range between 6 and 60/min but decreased at frequencies higher than 120/min. The 50% duration increased with frequency between 6 and 120/min but decreased at frequencies higher than 180/min. The dependence of the 50% duration upon frequency paralleled that of contractile tension. The 90% duration, the overshoot and the resting potential were not affected by frequency of contraction.

Acetylcholine (10−6 g/ml) shifted the 10%, 50% and 90% duration‐frequency curves downwards, but did not significantly alter the overshoot and the resting potential. Ouabain (10−6 g/ml) shifted the duration‐frequency curves downwards and also reduced the size of the overshoot and the resting potential. Treatment of atrial preparations with 10−6 g/ml ouabain potentiated the membrane effects of acetylcholine.

The inhibition by ouabain of the negative inotropic effect of acetylcholine did not appear to be due to antagonism at the receptor level, but to interference with the mechanisms responsible for the mechanical events.
Induction of hypovolaemia by thirst‐inducing doses of renin or angiotensin II
Authors: HAEFELI LISETTE , PETERS G.
Published: July 2012

Intravenous injection of five Goldblatt units (Gbl.U) of renin, or intravenous infusion of 2·5 μg of angiotensin into nephrectomized rats decreased plasma volume by 22 ± 2% (calculated from the increase of the haematocrit) or by 14 ± 2% (calculated from the increase in protein concentration) within 2 minutes. Fifteen minutes and 60 min after injection or infusion, the plasma volume (calculated from both parameters) was still 10% lower than initially.

The initial discrepancy between haematocrit values and plasma protein concentration was neither due to mobilization of red blood cells (r.b.c.) from the spleen, nor to an increase in r.b.c. volume.

The observed decrease in plasma volume was large enough to explain the drinking response to renin and angiotensin. Renin may thus induce or aggravate hypovolaemia rather than signalling its occurrence to hypothalamic receptors.
Maturation of convulsogenic activity induced by leptazol in the albino rat
Authors: DE CASRILEVITZ MIRA , ENGELHARDT E. , ESBÉARARD C. A.
Published: July 2012

Maturation of the excitatory and inhibitory neuromechanisms at various levels of the central nervous system was demonstrated by the convulsogenic activity induced by leptazol in the developing albino rat.

The somatomotor end points considered (myoclonic jerk, myoclonic seizure, tonic seizure and catalepsy) were not observed in all age groups. Tonic seizure was seen at birth, myoclonic jerks at 2 weeks of age, myoclonic seizure and catalepsy at 3 weeks of age.

The convulsive sequences described presented three different patterns, defining three age groups: the infant pattern (infant group: newborn‐1 week old animals); the transitional pattern (transitional group: 2 week old animals); and the adult pattern (adult group: 3 week old—adult animals).

Effective doses were determined for the three types of convulsive sequence: MJ50 for the myoclonic major sequence (maximal end point: myoclonic jerk), MS50 for the myoclonic major sequence (maximal end point: myoclonic seizure) and the TS50 for the myoclonic‐tonic‐clonic sequence (maximal end point: tonic seizure).

The correlation of the convulsive patterns with the dose and latency variations suggests that: (a) the neuromechanisms responsible for the tonic seizure and clonic seizure, located at brainstem and spinal cord levels, function at birth and reach maturity at 3 weeks of age; (b) the neuromechanisms responsible for the myoclonic manifestations and for catalepsy, located at the striato‐thalamocortical level, start functioning at 2–3 weeks of age, indicating the later maturation of the more cephalic structures.
Effects of the muscarinic agonist McN‐A‐343 on responses to sympathetic nerve stimulation in the rabbit ear artery
Authors: RAND M. J. , VARMA B.
Published: July 2012

Observations were made on the effects of 4‐(m‐chlorophenylcarbamoyloxy)‐2‐butynyltrimethylammonium chloride (McN‐A‐343) on responses of isolated segments of the central artery of the rabbit's ear to sympathetic nerve stimulation and noradrenaline.

With low frequencies of nerve stimulation (2–5 Hz), McN‐A‐343 caused a decrease in responses to sympathetic nerve stimulation. This effect of McN‐A‐343 was abolished by dexamphetamine or atropine. In the presence of atropine, McN‐A‐343 caused an increase in responses to sympathetic nerve stimulation.

With high frequencies of nerve stimulation (10–20 Hz), McN‐A‐343 caused an increase in responses. This effect was not qualitatively changed in the presence of atropine.

When McN‐A‐343 had an inhibitory effect on responses to sympathetic nerve stimulation, responses to noradrenaline were unaffected.

It is suggested that McN‐A‐343 acts on muscarinic receptors through which noradrenaline release may be inhibited; it may also act on the cholinergic stage in adrenergic transmission postulated by Burn & Rand (1959).
Turning behaviour as an index of the action of amphetamines and ephedrines on central dopamine‐containing neurones
Authors: CHRISTIE JANICE E. , CROW T. J.
Published: July 2012

Rats lesioned unilaterally in the substantia nigra show no obvious abnormalities after recovery from the operation but rotate towards the lesioned side after administration of drugs of the amphetamine and ephedrine groups.

(+)‐Amphetamine and (–)‐amphetamine are equally potent in producing turning behaviour but (+)‐methylamphetamine is considerably more effective.

(–)‐Ephedrine (with a β‐OH group on the ethylamine side chain) induces turning but only in doses approximately 20 times greater than (+)‐methylamphetamine.

(+)‐Norpseudoephedrine was the most effective of the ephedrine isomers tested followed by (–)‐ephedrine and (+)‐pseudoephedrine.

Turning produced by (–)‐ephedrine and (+)‐methylamphetamine is not reduced by FLA63 (50 mg/kg) 4 h previously, but is almost completely inhibited by α‐methyl‐p‐tyrosine (150 mg/kg) 12 h previously.

Reserpine pretreatment potentiates turning produced by (–)‐ephedrine.

Chlorpromazine (5 mg/kg) completely blocks turning induced by (+)‐methylamphetamine although it concurrently increases exploratory activity. The level of exploratory activity after the (+)‐methylamphetamine‐chlorpromazine combination is more than 3 times that attained after saline alone.
Effect of β‐adrenoceptor blocking compounds (propranolol, practolol and LB 46) on isoprenaline induced changes in regional blood flow in the rat
Authors: DEBRECZENI L. , FENYVESI T.
Published: July 2012

The effects of three β‐adrenoceptor blocking agents on isoprenaline induced changes in systemic and regional blood flow have been investigated in rats anaesthetized with pentobarbitone. The blood flow to the principal vascular beds was measured by the 86Rb fractionation method.

Isoprenaline infusion at a rate of 0.3 (μg/kg)/min intravenously caused an increase in cardiac output and a decrease in peripheral resistance which affected different vascular fields unevenly. The coronary and carcass fractions of cardiac output increased while the cutaneous, renal and splenic fractions decreased.

Pretreatment with propranolol (2 mg/kg intravenously) blocked all isoprenaline effects. Practolol (8 mg/kg intravenously) lessened the effect on cardiac output but did not prevent the vascular effects except those on the coronary circulation. LB 46 (0.2 mg/kg) had less marked β‐adrenoceptor blocking activity than propranolol (2.0 mg/kg).
Effects of progesterone on cardiovascular responses to amines and to sympathetic stimulation in the pithed rat
Authors: FOZARD J. R.
Published: July 2012

Blood pressure and heart rate responses to adrenaline, noradrenaline, tyramine, 5‐hydroxytryptamine and stimulation of the spinal sympathetic outflow were measured in pithed rats pretreated either with progesterone (20 mg/kg daily for 14 days) or the vehicle solution of ethyl oleate.

Pretreatment with progesterone increased the durations but not the magnitudes of the blood pressure and heart rate responses to adrenaline and that phase of the response to sympathetic stimulation attributable to amine release from the adrenal medulla.

Responses to noradrenaline, tyramine, 5‐hydroxytryptamine and that phase of the response to sympathetic stimulation associated with amine release from the sympathetic nerves were not significantly different in the two groups.

Pyrogallol (5 mg/kg) increased the duration but not the magnitude of responses to adrenaline, noradrenaline and sympathetic stimulation in both experimental groups. The increases in duration were consistently less in animals pretreated with progesterone than in controls.

Pretreatment with progesterone did not affect the total amount of radioactivity nor the proportion of catechol to non‐catechol metabolites excreted in the urine during a period of 7.25 h following an intraperitoneal injection of (±) isoprenaline‐7–3H.

It is concluded that the effects of progesterone may result from a localized decrease in catechol O‐methyl transferase activity within the cardiovascular system.