bluuebunny/crossref_metadata_2025_split huggingface dataset:
Rat brain and serum lithium concentrations after acute injections of lithium carbonate and orotate
Authors: Kling Mitchel A , Manowitz Paul , Pollack Irwin W 
Published: April 2011

Abstract
Eight hours after intraperitoneal injections of 1·0, 2·0, and 4·0 m equiv Li kg−1, the serum and brain lithium concentrations of rats were significantly greater after lithium orotate than after lithium carbonate. While little serum lithium remained at 24 h after injection of 2·0 m equiv kg−1 lithium carbonate, two-thirds of the 2 h serum lithium concentration was present 24 h after lithium orotate. Furthermore, the 24 h brain concentration of lithium after lithium orotate was approximately three times greater than that after lithium carbonate. These data suggest the possibility that lower doses of lithium orotate than lithium carbonate may achieve therapeutic brain lithium concentrations and relatively stable serum concentrations.
Corticosterone concentrations in mice during ethanol drinking and withdrawal
Authors: Tabakoff Boris , Jaffe Randal C , Ritzmann Ronald F 
Published: April 2011

Abstract
Consumption of an ethanol-containing diet by mice resulted in a significant increase in circulating concentrations of corticosterone which was maintained for 8 days. There were no changes in the concentrations of plasma corticosterone binding globulin. Ethanol withdrawal symptoms followed the removal of ethanol from the diet and circulating corticosterone concentrations were further increased. There was no correlation between blood ethanol and glucocorticoid concentrations during the chronic ethanol treatment. Stress related to ethanol consumption may be of greater importance than the circulating ethanol concentrations in producing the elevation in plasma glucocorticoids.
Antidotal effects of dimethyl sulphoxide against paracetamol-, bromobenzene-, and thioacetamide-induced hepatotoxicity
Authors: Siegers C-P 
Published: April 2011

Abstract
In mice the hepatotoxic effects of paracetamol (0·5–1·0 g kg−1, orally) as evidenced by increased serum enzyme activities of the aminotransferases and sorbitol dehydrogenase were dose-dependently inhibited by simultaneous treatment with dimethyl sulphoxide (DMSO 0·25–1·0 g kg−1, i.p.). DMSO was also active against bromobenzene- and thioacetamide-induced hepatotoxicity, but failed to protect mice against carbon tetrachloride-induced liver damage. Hepatic glutathione depletion in mice amounting to 94% after paracetamol (0·5 g kg−1, orally) and to 60% after bromobenzene (0·25 ml kg−1, orally) was dose-dependently reduced by the simultaneous administration of DMSO (0·25–1·0 g kg−1, i.p.). This indicates less conjugation of the toxic metabolites of paracetamol and bromobenzene to liver glutathione (G-SH) in the presence of DMSO.
Effectiveness of pyridostigmine in reversing neuromuscular blockade produced by soman
Authors: Dirnhuber P , Green D M 
Published: April 2011

Abstract
The effects of pyridostigmine pretreatment on the neuromuscular blockade produced by soman in anaesthetized, atropinized animals have been studied on the soleus and anterior tibialis muscle (rhesus monkeys, cats and rabbits) and the gastrocnemius muscle (guinea-pigs and rats). Pyridostigmine pretreatment produced a complete recovery of neuromuscular function following blockade by soman; the rate of recovery was similar in all the species, suggesting a common mechanism of action. In the absence of pyridostigmine or if pyridostigmine was delayed until after blockade by soman, there was no recovery of neuromuscular function. Detailed studies in the guinea-pig showed that the recovery of neuromuscular function was related to the dose of soman and to the degree of carbamoylation of blood cholinesterase at the time of nerve agent challenge, i.e. to the dose of pyridostigmine and the time interval between the administration of pyridostigmine and soman. It is suggested that the effectiveness of pyridostigmine pretreatment is due to the carbamoylation of a portion of the tissue acetylcholinesterase, which protects it against irreversible inhibition by soman: after poisoning spontaneous decarbamoylation produces sufficient free acetylcholinesterase to restore normal function.
The relationship between cholinesterase inhibition in the chick biventer cervicis muscle and its sensitivity to exogenous acetylcholine
Authors: Green A L , Lord J A H , Marshall I G 
Published: April 2011

Abstract
The effect of physostigmine has been studied on cholinesterase in homogenates of chick biventer cervicis muscles and on the contractile responses of the intact muscles to acetylcholine and carbachol. The concentration of physostigmine required to produce the maximum increase in sensitivity to acetylcholine almost completely inhibited the cholinesterase in muscle homogenates. This concentration of physostigmine had no effect on muscle contractures elicited by carbachol. By taking account of the combined effects of acetylcholine diffusion and enzymic hydrolysis, a quantitative theoretical relationship has been derived between the level of cholinesterase activity in cylindrical muscles and the fractional occupancy of the acetylcholine receptors in these muscles in the presence of different concentrations of exogenous acetylcholine. This theory attributes the thousand-fold increase in sensitivity to exogenous acetylcholine produced by anticholinesterases in chick biventer cervicis muscles largely to an alteration in acetylcholine concentration gradient within the muscle and accounts satisfactorily for the shift in the dose-response curve for acetylcholine which occurs after treatment of the muscles with various concentrations of physostigmine.
Pharmacological study of chicken airway smooth muscle
Authors: Chand N , Eyre P 
Published: April 2011

Abstract
Isolated chicken bronchus contracts to carbachol, PGF2α, histamine, 5-HT, bradykinin and phenylephrine. The bronchial strips from the horse plasma sensitized domestic fowl contracted to specific sensitizing antigen in vitro (Schultz-Dale anaphylactic reaction) and were 5 to 10 fold more reactive to PGF2α, histamine and 5-HT compared with the bronchi from normal chickens. Second antigen challenge was inactive or produced a weak response (desensitization). Allowing the bronchi to rest for 1 h resulted in partial recovery of anaphylactic response. Bronchi which had partially contracted submaximally to carbachol, antigen or PGF2α, relaxed to isoprenaline, adrenaline and PGE1 and E2.
The interaction of preservatives with polyhydroxyethylmethacrylate (polyHEMA)
Authors: Richardson N E , Davies D J G , Meakin B J , Norton D A 
Published: April 2011

Abstract
The interaction of the four most commonly used preservatives in contact lens solutions (chlorbutol, thiomersal, chlorhexidine gluconate and benzalkonium chloride) with polyhydroxyethylmethacrylate (polyHEMA), has been examined. Benzalkonium chloride and chlorhexidine gluconate show typical high affinity type isotherms. The interaction of benzalkonium chloride with polyHEMA from aqueous solution was reversible whereas that of chlorhexidine was only reversible in the presence of electrolyte or surfactant. Chlorbutol showed a typical reversible linear isotherm. Thiomersal does not interact with polyHEMA above pH 5·0. The extent of chlorhexidine—polyHEMA interactions is increased by the presence of formulatory adjuvants such as electrolyte and hydrophilic polymers. PolyHEMA lenses that apparently have been equilibrated with chlorhexidine gluconate will, on the addition of fresh preservative solution, bind further quantities of chlorhexidine above that which would be predicted from the sorption isotherm.
Bioavailability of griseofulvin from a novel capsule formulation
Authors: Fell J T , Calvert R T , Riley-Bentham P 
Published: April 2011

Abstract
The in vivo availability of griseofulvin from a novel formulation has been compared with the micronized powder. The formulation technique involves the conversion of the hydrophobic surface of the drug to a hydrophilic one by treatment with a film forming polymer. This enhances the wettability of the power, and increases its dissolution rate. The results of the in vivo study show the formulation technique has increased the rate and extent of bioavailability of griseofulvin when compared with the non-treated powder.
Direct effect of a nomifensine derivative on dopamine receptors
Authors: Poat Judith A , Woodruff G N , Watling K J 
Published: April 2011

Abstract
A study was made of the effects of nomifensine, 4′-hydroxynomifensine and 3′,4′-dihydroxynomifensine on dopamine receptors in rat striatum and nucleus accumbens, using the dopamine-sensitive adenylate cyclase assay. Nomifensine and its 4′-hydroxy metabolite were both inactive as dopaminergic agonists. 3′,4′-dihydroxynomifensine was, however, a potent agonist, being approximately 2 to 4 times less active than dopamine. The effects of dopamine and of 3′,4′-dihydroxynomifensine were blocked by Fluphenazine. It is concluded that the dopaminergic activity of 3′,4′-dihydroxynomifensine is dependent upon the presence of the two hydroxyl groups.
Further biochemical characterization of [3H]dihydroazapetine binding to α-adrenoceptor — related proteins from the rat vas deferens
Authors: Ruffolo Robert R , Turowski Bethany S , Patil P N 
Published: April 2011

Abstract
The binding of [3H]dihydroazapetine, a reversible blocker of the α-adrenoceptor, has been characterized in a membrane preparation from the rat vas deferens. Binding is rapid, reversible and shows evidence of saturation. Postganglionic sympathetic denervation of the tissue does not decrease binding to the subcellular fraction. Drugs known to act on the α-adrenoceptor are specific inhibitors of [3H]dihydroazapetine binding while those acting on other receptors are without effect. Scatchard plot analysis suggests that two specific binding components are present, one of which has a similar dissociation constant for [3H]dihydro-azapetine to that determined pharmacologically. [3H]Dihydroazapetine binding is lowest in the physiological pH range and tends to decrease with increasing temperature in the range of 25 to 60°. Calcium, magnesium, sodium and potassium inhibit binding of [3H]dihydroazapetine with the divalent ions being approximately 100 times more potent. Studies with group selective reagents indicate that a disulphide bridge, and sulphydryl and carbonyl groups, are at or near the binding site and are necessary for binding. The site is protein possibly with involvement of phospholipids. Specific binding of [3H]dihydroazapetine is inhibited by low concentrations of local anaesthetics suggesting that the binding site of the antagonist may be related to the ‘calcium mobilization’ site of the α-adrenoceptor.
The influence of methysergide on 5-hydroxytryptamine-induced changes in regional distribution of blood flow
Authors: Forsyth Ralph P , Saxena Pramod R 
Published: April 2011

Abstract
Systemic and regional haemodynamic variables were measured at the baseline and after saline or 5-HT infusions (5 μg kg−1 min−1, i.v.) or methysergide injections (0–5 mg kg−1, i.V.). Cardiac output and its complete distribution were measured by the radioactive microsphere (15 μm diam.) technique. Although 5-HT did not change the systemic variables, methysergide caused a moderate increase in systolic and mean blood pressure and heart rate. 5-HT caused a substantial increase in gastric and a moderate increase in cerebral and myocardial blood flow at the expense of that to the lungs (arteriovenous shunt + bronchial flows), kidneys and skin. While methysergide was able to reduce the vascular responses to 5-HT in stomach, skin, kidneys, heart, lungs and brain, the drug itself, like 5-HT, decreased the number of microspheres reaching the lungs. Since a large number of 15 μm microspheres can escape through the arteriovenous anastomoses to lodge in the lungs it seems likely that both 5-HT and methysergide can reduce the ‘non-nutrient’ flow through these anastomoses.
The use of 13C-nmr spectroscopy for the detection and identification of metabolites of carbon-13 labelled amitriptyline
Authors: Hawkins D R , Midgley I 
Published: April 2011

Abstract
The antidepressant drug amitriptyline and two of its metabolites, nortriptyline and desmethylnortriptyline, each containing two 13C atoms, have been used to determine the sensitivity and selectivity of 13C-nmr spectroscopy for the detection of unchanged amitriptyline and N-desmethyl metabolites in the urine of animals dosed orally with the labelled drug. The resonance signals from the 13C atoms detected in the 13C-nmr spectrum of the entire extract from a control 12 h rat urine sample to which 1 mg of each labelled compound had been added were easily detected, using an instrument accumulation time of 1 h. The 13C-nmr spectrum of an extract of hydrolysed urine from a dog that had received an oral dose of [13Q]amitriptyline (30 mg) exhibited signals that could be assigned to metabolites resulting from N-dealkylation and N-oxidation, as well as those bearing the intact amitriptyline side-chain. These assignments were confirmed by analysis of the same extract by g.c.-ms and h.p.l.c.
Acidic in vivo metabolites of cannabinol isolated from rat faeces
Authors: Yisak Wolde-Ab , Widman Martanne , Agurell Stig 
Published: April 2011

Abstract
Six acidic metabolites were isolated from rat faeces and identified by gas chromatography-mass spectrometry and proton magnetic resonance. Cannabinol-7-oic acid was the most abundant acidic metabolite isolated. Others present in decreasing order of prominence were 1″-hydroxy-, 4”-hydroxy-, 3″-hydroxycannabinol-7-oic acid, cannabinol-3”-one-7-oic acid and 2″-hydroxycannabinol-7-oic acid.
Comparison between spontaneously beating atria from control and streptozocin-diabetic rats
Authors: Foy J M , Lucas P D 
Published: April 2011

Abstract
Isolated spontaneously beating atria from streptozocin diabetic rats were compared with those from controls. Diabetic atria were found to have reduced rates, increased forces of contraction and reduced sensitivity to the inotropic effects of noradrenaline, isoprenaline, tyramine and calcium. Positive chronotropic responses to tyramine were also reduced but those to noradrenaline and isoprenaline were increased suggesting that tyramine releasable stores of noradrenaline were reduced. Elevation of glucose concentration in the medium from 5·6 to 27 min resulted in a decrease of inotropic sensitivity to the agents used in both control and diabetic rat atria. Resting contractile force of control rat atria was reduced by the inclusion of either 22 niM 2-deoxyglucose, 10−3 i.u. insulin ml−1 or 5 mM acetate in the medium. The rate was also reduced by medium containing 2-deoxyglucose but increased by insulin. 2-Deoxyglucose also reduced inotropic but increased chronotropic sensitivity to isoprenaline. Possible mechanisms responsible for the changes observed are discussed.
Time-dependent deformation of some direct compression excipients
Authors: Rees J E , Rue P J 
Published: April 2011

Abstract
Three techniques were used to compare the time-dependent deformation of microfine cellulose (Elcema G250), anhydrous lactose, dicalcium phosphate dihydrate (Emcompress), modified starch (Sta-Rx 1500) and sodium chloride. (1) In stress-relaxation experiments using a reciprocating tablet machine, none of the materials behaved as a Maxwell body in contrast to recent published work (David & Augsburger, 1977). Possible reasons for this disagreement are discussed. (2) Heckel plots showed that increasing the time for which a material was under compression (contact times of 0·17 and 10 s) had no effect on dicalcium phosphate compacts but increased the consolidation of other materials in the rank order sodium chloride &lt; lactose &lt; cellulose &lt; starch. (3) Deformation tests on preformed compacts were carried out in diametral compression by loading compacts to 75% of their breaking force at four different strain rates between 0·05 and 6·5 mm min−1. The deformation of Sta-Rx compacts was time-dependent. Sodium chloride compacts exhibited brittle behaviour in the diametral compression test and in the 10 s contact time experiment. This was apparently due to work-hardening, following the extensive plastic deformation of crystals during compaction as indicated by the stress relaxation results.
Phospholipase inactivation induced by an amino-piperazine derivative: a study at the lipid — water interface
Authors: Defrise-Quertain F , Chatelain P , Ruysschaert J M 
Published: April 2011

Abstract
1-Amino-4-octylpiperazine, AP 22, an antiviral agent causes lipid accumulation in nervous tissue cultures. A physicochemical membrane model was used to demonstrate the formation of a lipid-AP 22 complex hindering phospholipase A2 action. A well defined amphiphilic balance seems essential to explain the mode of action of the drug. The hydrophilic group prevents enzyme-substrate complex formation whereas the hydrophobic group allows the penetration in the lipid layer and determines the stability of the drug-lipid complex. This stability of the drug-lipid association has a direct influence on phospholipase A2 activity but does not affect phospholipase C activity. No inactivation of phospholipase A2 due to a drug-enzyme interaction could be detected.
The indirect sympathomimetic activity of etilefrine — a comparison with tyramine and ephedrine using [3H]noradrenaline
Authors: Frost B R , Halloran T N , Frewin D B , Gerke D C , Downey J A 
Published: April 2011

Abstract
The indirect sympathomimetic activity of etilefrine has been examined using the ventral caudal artery of the rat. This vessel has a rich sympathetic innervation and lends itself to studies on [3H]noradrenaline efflux from these sites. Etilefrine possessed significant indirect activity on the artery and this action, although less than that of tyramine, was equivalent to that caused by ephedrine. Pretreatment of the vessels with a mixture of iproniazid, doca, cocaine and U0521 (3′,4′-dihydroxy-2-methyl propiophenone) significantly enhanced[3H]-noradrenaline efflux from the artery.
The absorption of aliphatic carbamates from the rat colon
Authors: Wood S G , Upshall D G , Bridges J W 
Published: April 2011

Abstract
The colonic absorption of a series of aliphatic carbamates has been studied using an in situ preparation in the rat. The absorption process appeared to be passive and no metabolism by the colon membrane was detected. A linear correlation between the logarithms of the absorption rate constants and apparent partition coefficients was found. The absorption rates were not affected by concurrent water flux.
The effect of some formulation and process variables on the surface roughness of film-coated tablets
Authors: Rowe R C 
Published: April 2011

Abstract
The effect of some formulation and process variables on the surface appearance of film-coated tablets has been examined by measuring the arithmetic mean roughness, Ra, values across the faces of tablets before and after they were coated with hydroxypropyl methyl-cellulose. For all tablet cores except those that were very porous, film coating resulted in an increasing surface roughness; for very porous cores a decrease was found. Tablets with rough surfaces were produced by coating with low molecular weight grades of the polymer; increaseing the polymer molecular weight resulted in a smoother finish with a minimum roughness at intermediate molecular weight grades. Increasing the polymer concentration above 2% w/v caused an increase in roughness as did increasing film thickness to 140 μm. There was a minimum in roughness at film thicknesses of 20 μm. The addition of pigment in low concentrations (0–25% v/v) caused a marginal increase in surface roughness but at concentrations above the critical pigment volume concentration, the surfaces were very rough. The results illustrate the potential of the method in the optimization of film formulations and process conditions during product development.
Lithium-6 stable isotope determination by atomic absorption spectroscopy and its application to pharmacokinetic studies in man
Authors: Birch N J , Robinson Delia , Inie R A , Hullin R P 
Published: April 2011

Abstract
No useful radioisotope of lithium exists to assist in. the study of its biochemical pharmacology. A simple method has been developed for the determination of the stable isotope 6Li by atomic absorption spectroscopy (AAS). The technique is applicable in any laboratory equipped with simple AAS apparatus. Analysis of total lithium content (E) by flame emission spectroscopy is followed by separate determination (A6 and A7) of atomic absorption by the sample of the light emitted by separate hollow cathode lamps manufactured from the isotopes 6Li and 7Li. The standard curve of absorption ratio (A6/A7) against isotopic ratio (6Li/7Li) at any concentration (E) is an exponential which may be solved using a simple programmable calculator. Application of this method to the study of the pharmacokinetics of 6Li adminstered to 4 normal volunteers previously loaded with 7Li suggests that the rate of appearance of lithium in blood is unaffected by the previous state of lithium loading.
Sustained release of sulphadiazine
Authors: Wise Donald L , McCormick Gerald J , Willet Gloria P , Anderson Lynne C , Howes John F 
Published: April 2011

Abstract
An implantable system was developed which released sulphadiazine in mice over an extended period of time efficacious against infective challenges by Plasmodium berghei. The most successful preparation was a copolymer of L(+)-lactic acid + (±)-lactic acid (90 and 10% by weight, respectively) with a molecular weight of 150 000, with which sulphadiazine was mixed at 33.3% of the total weight, in a formulation as beads of 1.5 mm diameter. This preparation released sulphadiazine at a nearly constant rate over three months as measured by the appearance in urine of mice of radioactivity from [35S] sulphadiazine in transplanted material. When implanted in mice, the beads gave effective protection against repetitive (weekly) infective challenges with P. berghei by implanted beads at dosages equivalent to 57 mg kg−1 sulphadiazine and greater over 21 weeks.
Dopamine antagonistic effects of a series of analogues of oxiperomide and spiroxatrine measured behaviourally in the rodent
Authors: Costall Brenda , Naylor Robert J 
Published: April 2011

Abstract
The activity spectra of oxiperomide, spiroxatrine and analogues were determined in two experimental models of abnormal peri-oral movements (induced by intrastriatal dopamine and subcutaneously administered 2-(NN-dipropyl)amino-5,6-dihydroxy-1,2,3,4-tetrahydronaphthalene (NN-diPr-5,6-diOHATN) in the guinea-pig), and in a stereotypy test (induced by subcutaneous apomorphine in the guinea-pig); the ability of the test compounds to induce catalepsy or catatonia in the rat was also determined. The parent compounds oxiperomide and spiroxatrine possessed optimal activity in all tests, although responses to the series of compounds allowed clear differentiation between an ability to antagonize the peri-oral movements (dopamine- or NN-di Pr-5,6-diOHATN induced) and an ability to antagonize apomorphine stereotypy. However, all compounds that antagonized the abnormal peri-oral movements also caused catalepsy/catatonia. The results are considered in terms of the selection of suitable agent(s) for the treatment of peri-oral dyskinesias.