bluuebunny/crossref_metadata_2025_split huggingface dataset:
Inhibition by metrifonate and dichlorvos of cholinesterases in schistosomes
Authors: BUEDING E. , LIU C. L. , ROGERS S. H. 
Published: July 2012

Summary
No species differences between Schistosoma haematobium and Schistosoma mansoni were detected when the I50 of metrifonate for the acetylcholinesterases (AChE) and the cholinesterases (ChE) of these two trematodes were determined in isolated enzyme preparations or following exposure of the intact worms to this drug in vitro.
S. haematobium appeared to be more affected by AChE inhibition because, after administration of metrifonate to hamsters, a hepatic shift of the parasites was observed with a dose of metrifonate (150 mg (0·6 mmol) per kg) which produced no shift of S. mansoni, although AChE inhibition was comparable in both species.
Administration of a possible metabolite of metrifonate, dichlorvos, to hamsters resulted in a greater inhibition of AChE and ChE activities of S. haematobium than those of S. mansoni. Furthermore, when schistosomes were incubated with dichlorvos, inhibition of AChE activity of female S. haematobium was significantly greater (P<0·005) than that of both sexes of S. mansoni and of male S. haematobium.
The discrepancy between the lack of a significant chemotherapeutic effect of metrifonate in hamsters infected with S. haematobium and the clinical results obtained with this organophosphorus compound in human schistosomiasis haematobium is discussed, and the need to conduct similar studies in primates is pointed out.
Myocardial and circulatory effects of E. coli endotoxin; modification of responses to catecholamines
Authors: PARRATT J. R. 
Published: July 2012

Summary
The predominant acute effect of E. coli endotoxin in anaesthetized, ventilated cats was pulmonary hypertension resulting from a 8–12 fold increase in pulmonary vascular resistance. This was followed by decreases in left ventricular (LV) and systemic arterial pressures and in LV dP/dt max. Recovery occurred within 2–4 min and was dependent upon increased sympathetic drive; recovery did not occur in cats treated with the β‐adrenoceptor blocking drug alprenolol.
The pulmonary vasoconstriction was reduced in cats given compound 48/80 and evidence is presented that it results primarily from histamine release.
Over the 2–3 h period following endotoxin injection, systemic arterial pressure tended to decrease and heart rate and myocardial metabolic heat production to increase. Myocardial blood flow and LV dP/dt remained fairly stable until the terminal stages of shock.
The predominant delayed effects of E. coli endotoxin in cats were a markedly reduced stroke volume, an increase in peripheral vascular resistance and a severe metabolic acidosis (arterial base excess—20 mEq/litre). Arterial pO2 and pCO2 were not significantly affected. It is concluded that myocardial contractility is maintained at this time through the release of catecholamines and that endotoxin itself depresses contractility.
The effects of adrenaline and noradrenaline infusions on systolic and diastolic blood pressures, heart rate, cardiac output, myocardial blood flow and LV dP/dt max were markedly reduced in the period 2–3 h after endotoxin. In a few animals some recovery of the response to noradrenaline occurred and was associated with a general circulatory improvement and a reduced metabolic acidosis.
Pharmacological properties of centrally‐administered agents which interfere with neurotransmitter function: a comparison with the central depressant effects of ouabain
Authors: DOGGETT N. S. , SPENCER P. S. J. 
Published: July 2012

Summary
Centrally administered sodium diethyldithiocarbamate (DDC) produced hypothermia, central nervous depression and potentiation of the antinociceptive effect of morphine. These effects resemble those seen with centrally administered ouabain. Furthermore, the interactions of (+)‐amphetamine, desmethylimipramine and nialamide with DDC and ouabain were similar.
6‐Hydroxydopamine by the same route also produced central nervous depressant effects including hypothermia, decreased locomotor activity and catalepsy but not ptosis.
Both ouabain and chlorpromazine produced similar effects on behaviour and body temperature including selective abolition of a conditioned avoidance response.
Although centrally administered tetrabenazine produced ptosis, decreased locomotor activity and catalepsy, it had no significant effect on body temperature. However, the hypothermia produced by peripherally administered reserpine was reversed by centrally administered dibutyryl cyclic 3′,5′‐adenosine monophosphate.
Centrally administered cocaine and desmethylimipramine produced no depressant effects but an increased excitability and responsiveness were apparent in both cases.
Although the observed behavioural depression and hypothermia can occur independently both seem to involve an interference with dopaminergic systems.
Effect of 2‐diethylaminoethyl‐2,2‐diphenylvalerate hydrochloride (SKF 525‐A) on sulphacetamide distribution and excretion in rats
Authors: MARCHAND C. , NADEAU D. 
Published: July 2012

Summary
Administration of 2‐diethylaminoethyl‐2,2‐diphenylvalerate hydrochloride (SKF 525‐A), 40 mg/kg, i.p., simultaneously or 40 min before sulphacetamide sodium, 100 mg/kg, i.p., was associated with a three‐fold increase in sulphacetamide plasma concentration of rats. This effect was no longer evident after 30 minutes.
The augmentation in sulphacetamide plasma concentration was associated with parallel increases in the muscle, kidney and brain tissue. The stomach was the only organ that contained less sulphacetamide.
When sulphacetamide was administered i.v., a similar phenomenon was observed but the differences were less marked.
Pretreatment with SKF 525‐A was associated with decreased excretion of sulphacetamide by the kidney.
It is concluded that SKF 525‐A may alter the distribution and excretion of drugs as well as inhibiting drug metabolizing enzymes.
Cellular and metabolic tolerance to an opioid narcotic in mouse brain
Authors: GOLDSTEIN A. , JUDSON BARBARA A. , SHEEHAN PATRICIA 
Published: July 2012

Summary
Running activity and brain levorphanol concentration were measured in nontolerant and tolerant mice given various doses of 3H‐levorphanol.
The principal factor responsible for tolerance in the mouse is a loss of sensitivity to the narcotic drug at the cellular level in brain; despite adequate brain concentrations, the pharmacological effects are diminished or absent.
There is also metabolic tolerance; a given dose establishes a lower brain concentration in tolerant than in non‐tolerant animals.
The two kinds of tolerance are distinguished here and the contribution of each is assessed.
Kinetics and bioavailability of two formulations of amiloride in man
Authors: SMITH A. J. , SMITH R. N. 
Published: July 2012

Summary
Two formulations of [14C]‐amiloride were compared in six oedema‐free subjects in single‐dose (20 mg) studies separated by a two‐week interval.
Calculation of the elimination rate constant (Ke), half‐life (T½) and apparent volume of distribution (Vd) from serum and urinary data showed no significant difference between the two formulations. The Vd values (350 to 380 litres) were greater than total body fluid volume suggesting extravascular sequestration of amiloride.
Serum and urinary amiloride levels were similar with both formulations. Pharmacokinetic parameters were similar to those of an earlier report based on one formulation.
The calculated amiloride concentration in the renal distal tubule (3 μm to 20 μm) was similar to, but higher than, reported in vitro concentrations of amiloride which reduced sodium transport in isolated membranes.
The effect of prolonged treatment with oxyfedrine on intracellular potentials and on other features of cardiac function in rabbits and guinea‐pigs
Authors: POLSTER P. , WILLIAMS E. M. VAUGHAN 
Published: July 2012

Summary
Previous work in acute experiments has shown that the main pharmacological action of oxyfedrine is stimulation of β‐adrenoceptors, yet there have been clinical reports that the drug is beneficial in the treatment of angina pectoris.
In the present experiments rabbits and guinea‐pigs were treated for several weeks with daily i.p. injections of oxyfedrine.
A daily dosage of 15 mg/kg oxyfedrine had no effect on growth rate for 4 weeks, but thereafter the growth rate of treated animals fell below that of controls.
The heart weights of the treated animals, expressed as a percentage of body weight, were significantly lower than those of controls.
Measurement of intracellular potentials in hearts taken from treated rabbits showed that the main effects were a reduction in the maximum rate of depolarization and a prolongation of the plateau of the action potential.
Guinea‐pigs treated for 6 weeks with 15 mg/kg oxyfedrine daily i.p. were protected to some extent from the toxic effect of ouabain infused intravenously.
Further evidence for a central hypotensive action of α‐methyldopa in both the rat and cat
Authors: FINCH L. , HAEUSLER G. 
Published: July 2012

Summary
α‐Methyldopa (300 mg/kg i.p.) produced a fall in blood pressure in conscious genetic hypertensive rats. Pretreatment with intraventricular 6‐hydroxydopamine prevented this hypotensive effect of α‐methyldopa, whilst intravenous 6‐hydroxydopamine reduced but did not prevent the hypotension.
The hypotensive effect of α‐methyldopa was prevented or reversed by intraventricular injection of phentolamine (200 μg/rat).
Pressor responses obtained by stimulation of the entire sympathetic outflow in the Gillespie & Muir preparation, were unaffected by pretreatment with α‐methyldopa (300 mg/kg i.p.).
Vasoconstrictor responses to periarterial nerve stimulation of the isolated renal artery preparation of the rat were markedly reduced by pretreatment with α‐methyldopa. Furthermore, α‐methylnoradrenaline was found to have one‐eighth the vasoconstrictor potency of noradrenaline in this particular artery preparation.
Pressor responses obtained by stimulation of the posterior hypothalamus or midbrain reticular formation in the rat anaesthetized with urethane were markedly reduced by pretreatment with α‐methyldopa. FLA‐63, a selective dopamine‐β‐hydroxylase inhibitor, prevented the reduction of the pressor responses to hypothalamic stimulation produced by α‐methyldopa.
Stimulation of the posterior hypothalamus in the anaesthetized cat caused both an increase in sympathetic nerve activity and a rise in blood pressure. These responses were markedly reduced 3–4 h after the injection of α‐methyldopa (100 mg/kg i.v.).
These results strongly suggest that the central actions of α‐methyldopa are important for its hypotensive effect, although a possible peripheral effect cannot be excluded.
Effect of centrally acting drugs on the uptake of γ‐aminobutyric acid (GABA) by slices of rat cerebral cortex
Authors: HARRIS M. , HOPKIN JUDY M. , NEAL M. J. 
Published: July 2012

Summary
The effects of centrally acting drugs on the uptake of 3H‐γ‐aminobutyric acid (GABA) by slices of rat cerebral cortex have been studied.
Many centrally acting drugs at concentrations of 0·1–1·0 mm significantly inhibited the uptake of 3H‐GABA by cortical slices, but the only classes of drugs in which all members consistently produced inhibition of uptake were the phenothiazines, tricyclic antidepressants, and butyrophenones.
The receptor blocking drugs; phentolamine, propranolol, thymoxamine, mepyramine, and diphenhydramine at concentrations of 0–5–1 mm also significantly reduced the uptake of 3H‐GABA. However, atropine, hexamethonium and (+)‐tubocurarine had little effect on the uptake of 3H‐GABA by cortical slices.
Centrally acting drugs, which did not significantly inhibit 3H‐GABA uptake, included barbiturates, local anaesthetics, hallucinogens, monoamine oxidase inhibitors, anticonvulsants, and convulsants (except picrotoxin).
Chlorpromazine, prochlorperazine, l‐2,4,diaminobutyric acid, desmethylimipramine, and iprindole inhibited the uptake of 3H‐GABA by 50% (IC50) at concentrations of 30–100 μm. The most potent inhibitor of 3H‐GABA uptake was p‐chloromercuriphenylsulphonate (IC50 = 18 μM).
With the exception of l‐2,4,diaminobutyric acid, an outstanding characteristic of these drugs was their complete lack of specificity. Thus at the IC50 for GABA, p‐chloromercuriphenylsulphonate, chlorpromazine, prochlorperazine, iprindole, desmethylimipramine, apomorphine and diphenylhydramine also inhibited the uptake of radioactive glycine, alanine, noradrenaline, and 5‐hydroxytryptamine. The uptake of the latter two compounds was often inhibited to a greater extent than GABA, glycine and alanine.
Kinetic analysis indicated that the inhibition of 3H‐GABA by p‐chloromercuriphenylsulphonate, chlorpromazine, and desmethylimipramine was non‐competitive. l‐2,4,Diaminobutyric acid reduced the uptake of 3H‐GABA by a ‘mixed’ type of inhibition.
The present results do not support the suggestion that some centrally acting drugs may produce their effects by reducing the uptake of GABA in the brain after its release from inhibitory nerve terminals. Conceivably, the design of compounds which interfere effectively with the mechanisms of GABA operated synapses may lead to the introduction of whole new groups of centrally acting drugs.
The effect of immunosympathectomy and of 6‐hydroxydopamine on the responses of the rat anococcygeus to nerve stimulation and to some drugs
Authors: GIBSON A. , GILLESPIE J. S. 
Published: July 2012

Summary
The rat anococcygeus muscle possesses a dense motor adrenergic innervation and also a powerful inhibitory innervation whose transmitter is unknown. The possibility that the adrenergic nerves released both noradrenaline and the unknown inhibitory transmitter was investigated by destroying the adrenergic nerves either by immunosympathectomy or by 6‐hydroxydopamine.
Immunosympathectomy was only partially effective in destroying the adrenergic neurones to the anococcygeus. 6‐Hydroxydopamine destroyed the terminal adrenergic varicosities abolishing almost completely the motor response. Neither treatment affected the inhibitory response.
6‐Hydroxydopamine induced a specific hypersensitivity of the muscle to noradrenaline which was not shared with carbachol.
The maximum tension response of the anococcygeus muscle was greater in the male than in the female probably because the muscle is bigger.
Effects of salicylates on blood changes in mycoplasma arthritis in rats
Authors: EISEN V. , LOVEDAY C. 
Published: July 2012

Summary
The polyarthritis produced in rats by i.v. inoculation with Mycoplasma arthritidis was made more severe by salicylates.
The infection increased the erythrocyte sedimentation rate (ESR), serum lysozyme, counts of total white blood corpuscles, polymorphonuclear cells and lymphocytes, haemolytic serum complement (CH 50) and its component C3. Salicylates enhanced the rise in ESR, CH 50 and C3, but suppressed the rise in lymphocytes and even induced a fall.
Salicylates did not interfere with the development and action of metabolic inhibition antibodies against M. arthritidis, and did not promote the growth of M. arthritidis.
Rats treated with salicylate during the first infection acquired the same immunity to reinfection as did infected controls.
Salicylates did not render rats susceptible to M. fermentans which is nonpathogenic to rats, but may be involved in human rheumatoid arthritis.
Inhibition of functional vasodilatation and prostaglandin formation in rabbit adipose tissue by indomethacin and aspirin
Authors: BOWERY BARBARA , LEWIS G. P. 
Published: July 2012

Summary
The epigastric adipose depot of rabbits has been used to examine the effect of indomethacin, aspirin and nicotinic acid on the free fatty acid release and blood flow in fat tissue.
The prostaglandin formation which occurs in adipose tissue during lipolysis is prevented by indomethacin and aspirin. The corresponding functional vasodilatation which occurs after infusions of lipolytic substances is also abolished by these two anti‐inflammatory compounds.
This finding is consistent with the theory that prostaglandin E2 is the mediator of functional vasodilatation in adipose tissue.
Nicotinic acid sometimes inhibits the release of free fatty acids from adipose tissue by preventing activation of the tissue lipase. In those experiments in which this inhibition occurred, the vasodilatation was also prevented.
This finding is consistent with the view that the prostaglandin E2 which mediates the functional vasodilatation, originates in the triglycerides of the fat tissue.
The dependence of paracetamol absorption on the rate of gastric emptying
Authors: HEADING R. C. , NIMMO J. , PRESCOTT L. F. , TOTHILL P. 
Published: July 2012

Summary
The rate of gastric emptying was measured directly in 14 convalescent hospital patients and paracetamol absorption was studied following an oral dose of 1·5 g.
Rapid gastric emptying was associated with the early appearance of high peak plasma paracetamol concentrations whereas peak concentrations were low and occurred late when gastric emptying was slow.
There was a significant correlation between the rate of gastric emptying and the 0·4 and 0·24 h urinary excretion of paracetamol and its metabolites.
In five patients with abnormally slow gastric emptying the mean maximum plasma concentration and 0·4 and 0·24 h urinary excretion of paracetamol were significantly lower than in seven patients with normal gastric emptying rates while the time taken to reach maximum plasma concentrations was longer.
Individual differences in the rate of gastric emptying may contribute to variable absorption of many drugs.
A histochemical study of extraneuronal accumulation of noradrenaline in the guinea‐pig trachea
Authors: O'DONNELL STELLA R. , SAAR NILI 
Published: July 2012

Summary
Accumulation of noradrenaline in extraneuronal tissue of the guinea‐pig trachea has been studied by the use of the fluorescence histochemical technique of Falck and Hillarp.
After incubation in solutions of noradrenaline, fluorescence developed in cellular structures (tracheal smooth muscle, vascular smooth muscle and endothelium, fibroblasts and chondroblasts), in the intercellular matrix of the cartilage and throughout the loose connective tissue of the adventitia and submucosa.
The effect of various experimental procedures on the development of this fluorescence has been examined i.e. incubation with noradrenaline at reduced temperature (0° C), removal of fluorescence by washing with Krebs solution at 37° C or 0° C, incubation with phenoxybenzamine (10−4m) or metanephrine (10−4m).
From these observations it has been concluded that noradrenaline accumulates in the trachea:
(a) in cellular structures where it is firmly bound, i.e. not easily removed by washing at 0° C, and where the accumulation is prevented by phenoxybenzamine, metanephrine or cold.
(b) in the intercellular matrix of the cartilage where it is also firmly bound, but where the accumulation is not prevented by phenoxybenzamine, metanephrine or cold. This probably represents binding to sulphated mucopolysaccharides.
(c) in the adventitia and submucosa where it is loosely bound and easily removed by washing.
Some implications of these findings in pharmacological experiments with guinea‐pig trachea are discussed.
On the pharmacology and biochemistry of the amine‐uptake mechanism in human blood platelets
Authors: CAMPBELL I. C. , TODRICK A. 
Published: July 2012

Summary
The uptake of 5‐hydroxytryptamine (5‐HT) by human blood platelets in vitro has been studied with the object of identifying the biochemical mechanisms involved.
Drugs active in adrenergic systems are only moderate inhibitors of uptake, although prenylamine is as active as the less potent tricyclic anti‐depressive drugs; phenoxybenzamine is almost inactive as a competitive inhibitor but is effective if pre‐incubated with the platelets beforehand. This parallels its pharmacological pattern of action.
Inhibitors of oxidative phosphorylation do not inhibit 5‐HT uptake, but iodoacetate inhibits, if pre‐incubated with the platelets; p‐chloromercuribenzoate does also, when the platelets are suspended in synthetic medium, but not in plasma.
Ouabain causes significant inhibition at 10−7m; by 10−6m it achieves its maximal effect, namely 40% inhibition; in K+‐deficient medium, uptake falls to 30% of normal; the K+‐dependent fraction of the uptake includes the ouabain‐sensitive component. Mg++ has no effect.
A drug not possessing the imipramine structure, which has been tried in the treatment of depressive illness, 4‐phenyl bicyclo (2,2,2) octan‐1‐amine, is a highly potent inhibitor of 5‐HT uptake.
An analysis of the learning deficit following hyoscine administration to man
Authors: CROW T. J. , GROVE‐WHITE I. G. 
Published: July 2012

Summary
Twelve volunteer subjects completed a free‐recall word learning test, a number‐colour association test, and a scanning task after the following treatments: saline 1 ml, hyoscine 0·4 mg, or atropine 0·6 mg, administered by intravenous injection.
Performance on all three tests was not significantly impaired after atropine.
Performance on the two learning tests but not on the scanning task, was significantly impaired after hyoscine.
Analysis of the results of the free‐recall word learning test indicates that impairment of learning following hyoscine does not affect recall over intervals of a few seconds, but affects that portion of the learning curve which has been attributed to long‐term (or secondary) rather than short‐term (or primary) memory.
The results suggest that hyoscine 0·4 mg may impair learning processes, without significantly depressing other psychological functions, and that the impairment of learning following hyposcine does not affect recall over intervals memory.
Presynaptic and postsynaptic effects of the venom of the Australian tiger snake at the neuromuscular junction
Authors: DATYNER M. E. , GAGE P. W. 
Published: July 2012

Summary
Crude venom (TSV) from the Australian tiger snake (Notechis scutatus scutatus) has both presynaptic and postsynaptic effects at the neuromuscular junctions of toads.
TSV (50 μg/ml) rapidly blocked indirectly elicited muscle twitches without affecting the compound action potential in the sciatic nerve or twitches elicited by direct stimulation.
Low concentrations of the venom (1–10 μg/ml) reduced the amplitude of miniature endplate potentials (m.e.p.ps) and inhibited the depolarization of muscle fibres normally caused by carbachol. It was concluded that a fraction of the venom binds to acetylcholine receptors.
The frequency of m.e.p.ps was at first increased by TSV at a concentration of 1 μg/ml. Occasional, high frequency ‘bursts’ of m.e.p.ps were recorded in some preparations. The mean frequency of m.e.p.ps appeared to fall after several hours in the venom.
The quantal content of endplate potentials (e.p.ps) was reduced by the venom. With low concentrations (1 μg/ml), an initial increase in quantal content was often seen. When the quantal content was markedly depressed there was no parallel reduction in the amplitude of nerve terminal spikes recorded extracellularly, though a later fall in size and slowing of time course was often seen.
There was evidence that TSV eventually changed the normal Poisson characteristics of the spontaneous release of quanta and this may be correlated with electronmicroscopic changes in nerve terminals.
Tiger snake antivenene counteracted the postsynaptic, but not the presynaptic effects of TSV when they had developed.
Gastric mucosal blood flow during pentagastrin‐ and histamine‐stimulated acid secretion in the rat
Authors: MAIN I. H. M. , WHITTLE B. J. R. 
Published: July 2012

Summary
Gastric mucosal blood flow was studied in the rat by means of a [14C]‐aniline clearance technique.
There was a significant correlation between clearance and stimulated acid secretion.
No significant difference was found in the relationship between clearance and acid secretion during submaximal stimulation with either pentagastrin or histamine.
Estimates of mucosal blood flow per unit acid secretion by [14C]‐aniline clearance in the rat were similar to those reported with aminopyrine clearance in the dog and cat.