bluuebunny/crossref_metadata_2025_split huggingface dataset:
The influence of pH on the cardiac depressant action of tobramycin
Authors: Name C F , Vettore O , Antonio A 
Published: April 2011

Abstract
Tobramycin, like other aminoglycoside antibiotics, is a basic compound which causes a reduction of cardiac contractile force and inhibits the inotropic action of calcium. Its antagonistic action towards calcium had been analysed at different pH values of the solution bathing the rat left atrium. The isometric tension of the electrically driven atrium (4 Hz, 2 ms, supramaximal voltage) in response to cumulative increase in the bath calcium concentration (2·0 to 32·0 mM) was measured in the absence and in the presence of 20 × 10−5 M tobramycin. The increase in pH from 6·6 to 8·2, which decreased the ionization of tobramycin, reduced the cardiac depression. Similar experiments were carried with other cardiac depressants. Thus, the effect of methoxyverapamil (3·5 × 10−7 M), also a basic compound, was increased at higher values of pH; the acidic pentobarbitone (4 × 10−5 M) was less effective at more alkaline pH; the cardiac depression of the non-electrolyte ethanol (2 × 10−4 M) was practically the same over the pH range studied. The time for equilibrium of the antagonism was small for tobramycin, moreover, its antagonism could only be fully reversed by an increase in extracellular calcium. These results suggest a competitive type of antagonism, between the ionized fraction of tobramycin and calcium, for superficial sites of the sarcolemma. The effect of methoxyverapamil, pentobarbitone and ethanol seems to occur at a more internal site of the cardiac cell since the unionized form of the drug is the most active.
In-vitro evaluation of filaricidal activity of GABA and 1,3-dipalmitoyl-2-(4-aminobutyryl)glycerol HCl: a diglyceride prodrug
Authors: Deverre Jean R , Loiseau Philippe , Couvreur Patrick , Letourneux Yves , Gayral Philippe , Benoit Jean P 
Published: April 2011

Abstract
A diglyceride ester of γ-aminobutyric acid (GABA) has been synthesized and its filaricidal activity compared with GABA, and progabide in-vitro, on infective larvae and microfilariae of Molinema dessetae, a rodent filaria. GABA induced paralysis in infective larvae but was inactive on microfilariae. There were interactions between the culture medium and GABA. The ester drug at 0·1 mmol L−1 (1,3-dipalmitoyl-2-(4-aminobutyryl)glycerol HCl) was as active as progabide on infective larvae and hundredfold more potent than GABA. Its microfilaricidal activity at 1 mmol L−1 was lower than that progabide at 0·1 mmol L−1 but a delayed effect was observed. The data confirm filariae sensitivity to GABA derivatives.
Effect of lithium chloride on the neurotransmitter release from adrenergic nerve terminals of guinea-pig atria
Authors: Mantelli L , Ledda F 
Published: April 2011

Abstract
Lithium chloride at 1 and 10 mM produced a dose-dependent inhibition of the cardiac response to field stimulation of the adrenergic nerve terminals, without affecting myocardial contractility in electrically stimulated guinea-pig atria. This effect was calcium-independent and was also present in preparations super-fused with 10 mM myoinositol. Moreover, 10 mM lithium chloride reduced the positive inotropic effect of tyramine. These results indicate that lithium reduces the evoked release of noradrenaline from the adrenergic nerve endings, probably lowering the content of releasable neurotransmitter.
Rilmenidine Differs From Clonidine in that it Lacks Histamine-like Activity
Authors: Li C G , Rand M J 
Published: April 2011

Abstract
Studies were carried out to determine whether rilmenidine, a recently introduced antihypertensive agent with a similar mechanism of action of Clonidine, possesses histamine-like activity on tissues responding to histamine H2-receptor agonists. In guinea-pig isolated atria, both histamine and Clonidine caused concentration-dependent positive chronotropic effects which were blocked by the histamine H2-receptor antagonist Cimetidine (5 μM);.in contrast, rilmenidine produced a concentration-dependent negative chronotropic effect which was not altered by Cimetidine. In stilboestrol-treated rat isolated uterus contracted by KC1, histamine and Clonidine produces concentration-dependent relaxations which were blocked by Cimetidine (5 μM); rilmenidine also produced relaxation, but this was not affected by Cimetidine (5 μM). These findings suggest that rilmenidine, unlike Clonidine, does not activate histamine H2-receptors in either guinea-pig atria or rat uterus.
A new approach to prostate cancer
Authors: Ito Yoshikazu Z , Nakazato Yoichi , Petrow Vladimir 
Published: April 2011

Abstract
Growth of androgen-dependent human prostatic adenocarcinoma implanted in the nude mouse (Honda tumour), is inhibited by 6-methyleneprogesterone. This steroid is a potent inhibitor of both rat and human prostatic 5α-reductase in-vitro. In-vivo, at the studied dose level, it reduces metabolic conversion of testosterone to dihydrotestosterone with minimal effects upon circulating LH and testosterone. These data support the hypothesis that dihydrotestosterone and not testosterone is the main trophic androgen of the human prostatic neoplasm.
Effect of reserpine pretreatment on brown fat iodothyronine 5′-deiodinase of mouse
Authors: Muraki Takamura , Tsukahara Fujiko , Oike Nobuko , Nomoto Teruko 
Published: April 2011

Abstract
The effect of pretreatment with reserpine (1 mg kg−1 i.p. daily for 7 days) on the regulation of iodothyronine 5′-deiodinase (5′D) in mouse brown adipose tissue (BAT) has been examined. 5′D activity of BAT homogenate was assessed by the in-vitro formation of 3,5,3′-triiodothyronine from thyroxine and 3,3′-diiodothyronine from 3,3′,5′-triiodothyronine in the presence of 20 mM dithiothreitol. Reserpine treatment decreased the stimulation of BAT 5′D induced by acute cold exposure (4°C, 2h) without a significant decrease in the basal 5′D activity, whereas stimulation of BAT 5′D elicited by noradrenaline (0.4 and 0.8 mg kg−1 s.c. 2 h previously) was not augmented after reserpine treatment. Although both noradrenaline and acute cold exposure increase BAT 5′D through α1-adrenoceptors, our results show that chronic reserpine treatment prevents the effect of cold, but does not induce α1-adrenoceptor supersensitivity in BAT.
Calculation of Punch Displacement and Work of Powder Compaction on a Rotary Tablet Press
Authors: Oates R J , Mitchell A G 
Published: April 2011

Abstract
To calculate the work of compaction during tableting it is necessary to have accurate values of force and punch displacement. The direct measurement of punch displacement on a rotary press is both costly and complicated but calculated displacements will be in considerable error unless deflections in the press during compression are taken into account. By analysing the physical restraints imposed on the punches during tablet compression, an expression for punch displacement was derived. From preliminary measurements made on the tablet press of machine deflections and punch displacement under static conditions, the terms of this expression were evaluated for dynamic conditions. This analytic solution was then used to determine the true punch displacement and work of compaction from direct measurements of vertical force and turret position.
Influence of capsaicin-sensitive fibres on experimentally-induced colitis in rats
Authors: Evangelista Stefano , Meli Alberto 
Published: April 2011

Abstract
Systemic capsaicin pretreatment worsens trinitrobenzene sulphonic acid-induced colitis but has no effect on colitis induced by ethanol or acetic acid. The influence of capsaicin-sensitive fibres on experimentally-induced colitis seems to depend upon the type of ulcerogenic stimuli in relation to its chronic nature.
Postnatal effects of maternal nicotine exposure on the striatal dopaminergic system in rats
Authors: Fung Yiu K 
Published: April 2011

Abstract
The biochemical effects of continuous prenatal exposure to nicotine (1·5 mg kg−1 day−1) have been examined in 14 day old male and female rat pups. The ability of striatal tissue slices from the nicotine-exposed pups to synthesize [3H]dopamine from [3H]tyrosine was enhanced. However, the ability of (+)-amphetamine to stimulate formation and release of [3H]dopamine from [3H]tyrosine was not affected. Furthermore, prenatal exposure to nicotine increased the rate of striatal dopamine turnover in the male, but not the female nicotine-exposed pups.
Effect of Structural Variations of Non-ionic Surfactants on Micellar Properties and Solubilization: Surfactants with Semi-polar Hydrophobes
Authors: Attwood D , Elworthy P H , Lawrence M J 
Published: April 2011

Abstract
Novel non-ionic surfactants have been synthesized in which a polar group (either an ether or a keto group) has been introduced into the hydrocarbon chain of an octadecylpolyoxyethylene glycol monoether (C15En) with an oxyethylene chain length, n, of 17–18 units. Light scattering studies have indicated aggregation numbers for these semi-polar surfactants in aqueous solution of between 55–65% of that of an unsubstituted octadecylpolyoxyethylene glycol monoether, C18E22. The solubilizing capacities of the semi-polar surfactant micelles for test compounds which were mainly solubilized at the polyoxyethylene/core interface were lower than those of C18E22 whilst solubilizates which exhibited a reasonable degree of solubility in both the interface and the micellar core showed an increased solubilization.
Time Course of Verapamil Interaction with Morphine Effects on Physiological Parameters in Rats
Authors: Puppa Andrea Della , Ford-Rice Felicia , Snyder Frederick R , Cone Edward , London Edythe D 
Published: April 2011

Abstract
The effects of subcutaneous doses of morphine and verapamil on respiratory and cardiovascular parameters have been assessed in conscious rats. Verapamil (10 mg kg−1) was injected simultaneously with morphine (16 mg kg−1) or at 10, 30, or 60 min before morphine administration. Morphine induced respiratory depression, as indicated by marked hypercapnia, hypoxia and acidosis, and caused marked tachycardia. Although morphine produced only a minor and inconsistent (but statistically significant, P&lt;0·01) reduction of mean arterial blood pressure, morphine potentiated verapamil-induced hypotension. Verapamil suppressed morphine-induced hypercapnia only when injected simultaneously with morphine. Verapamil alone did not affect arterial blood gases or pH, but decreased heart rate and mean arterial blood pressure. Verapamil attenuated and delayed the maximum positive chronotropic effects of morphine at all times tested. Antagonism by verapamil of respiratory depression and tachycardia produced by morphine was unrelated to morphine levels in plasma. Thus, the explanation of verapamil-morphine interactions on respiration and cardiovascular function is not pharmacokinetic.
Pharmacokinetics of Cyanamide in Dog and Rat
Authors: Obach R , Colom H , Arso J , Peraire C , Prun̂onosa J 
Published: April 2011

Abstract
A pharmacokinetic study of cyanamide, an inhibitor of aldehyde dehydrogenase (E.C. 1.2.1.3) has been made in the beagle dog and Sprague-Dawley rat. Cyanamide plasma levels were determined by a sensitive high performance liquid chromatographic assay, specific for cyanamide. In the dog, i.v. administration of cyanamide at 1, 2 and 4 mg kg−1, produced a dose-dependent pharmacokinetic behaviour. Statistically significant changes were observed in plasma clearance values (12·6 to 19·7 mL kg−1 min−1), half life values (39 to 61 min) and mean residence times (50 to 79 min). Peak plasma concentrations, after oral administration of 4 mg kg−1 were achieved at 30 min and oral bioavailability was about 65%. In the rat after i.v. or oral administration, cyanamide (2 mg kg−1) had a half life of 30 min, a total plasma clearance of 117 mL kg−1 min−1 and a mean residence time of 26 min. Oral bioavailability was about 69%.
Ergometrine and 5-hydroxytryptamine binding sites in rat brain and myometrium
Authors: Hollingsworth M , Dascombe M J , Price D , Acton L 
Published: April 2011

Abstract
Functional studies suggest that ergometrine is a partial agonist involving 5-hydroxytryptamine (5-HT) receptors in rat uterus. Ergometrine displaced [3H]5-HT from specific binding sites in rat brain, but did not displace [3H]5-HT at functionally important concentrations in rat myometrium. These binding studies indicate that the agonist and antagonist actions of ergometrine in rat uterus arise from its initial interaction with binding sites other than those for 5-HT.
Age-dependence of the effects of pinacidil on rat aorta
Authors: Wanstall Janet C , O'Donnell Stella R , Zeng Xiang-Ping 
Published: April 2011

Abstract
The effect of the K+ channel opening drug, pinacidil, has been examined on aortic ring preparations from young (2 months) and aged (&gt; 24 months) rats. The potency (neg log IC50) values for pinacidil in relaxing K+ (20 mM)-contracted preparations were in the range expected for its K+ channel opening (hyperpolarizing) effects but were not significantly different between young (6·34) and aged (6·31) rats. Thus, ageing does not affect the drug’s potency as a K+ channel opening drug. The more marked depression of the maximum response to noradrenaline by pinacidil (10 μM) in aged rats (85% reduction) compared with young rats (43% reduction), reflected a reduced α-adrenoceptor reserve for noradrenaline in preparations from aged rats. Pinacidil, in concentrations greater than 10 μM, was able to relax preparations contracted with 80 mM K+ suggesting that it may have a second mechanism which does not involve hyperpolarization. It was more potent in producing this effect on the preparations from aged rats.
β-Adrenoceptor antagonist activities and binding affinities of timolol enantiomers in rat atria
Authors: Karhuvaara Sakari , Kaila Timo , Huupponen Risto 
Published: April 2011

Abstract
S-Timolol is an effective anti-glaucoma drug, but has potentially hazardous side effects. Recently, R-timolol, also, has been reported to be effective in lowering elevated intraocular pressure. In the present study, the β-adrenoceptor antagonist activities and binding of RK- and S-enantiomers of timolol have been examined on rat atrial preparations. The β-antagonistic activities were investigated using spontaneously beating rat heart atria. Both timolol enantiomers inhibited (-)-isoprenaline-induced chronotropic action competitively. S-Timolol was about 54 times more potent than R-timolol. The apparent binding affinities of timolol enantiomers to β1 and β2-adrenoceptors were determined by a radioligand binding assay using (-)-[125I]iodocyanopindolol (ICYP) as a marker and CGP 20712 A as a β1- and ICI 118,551 as a β2-adrenoceptor antagonist. Both enantiomers of timolol inhibited ICYP binding in nanomolar concentrations with Hill coefficients near unity. Neither enantiomer showed selectivity between β1- and β2-adrenoceptors, but R-timolol was approximately 30 times less active than S-timolol. It is concluded that R-timolol is a relatively potent non-selective β-adrenoceptor blocking agent, but may possibly exert a more localized β-adrenoceptor action in the eye than S-timolol, thus improving the safety of ocular timolol therapy.
Disposition of alfentanil in patients receiving a renal transplant
Authors: Bower S , Sear J W 
Published: April 2011

Abstract
The disposition of alfentanil has been investigated in 10 anaesthetized patients with chronic renal failure undergoing kidney transplantation and compared with eight age matched anaesthetized patients with normal renal function. Plasma samples were collected to 660 min following intravenous administration of alfentanil 3–5 mg (50 μg kg−1). Drug concentrations were measured by RIA; and alfentanil binding to plasma proteins by equilibrium dialysis against 0·1 M phosphate buffer, pH 7·4. Alfentanil binding to plasma proteins was 87·6% (s.d. 2·0) in the patients with chronic renal failure, and 89·7% (1·2) in patients with normal renal function (P = 0·025). There was no correlation between alfentanil binding and plasma albumin, total plasma proteins, plasma urea or plasma creatinine concentrations. In both groups, the drug concentration-time profile decayed in a curvilinear manner; in the chronic renal failure patients, restoration of function did not influence the decay profile. Elimination half life, mean residence time and apparent volume of distribution at steady state were not different in the two groups of patients (mean values: 142·4 and 120·2 min; 128·5 and 136·0 min; and 40·5 and 27·6 L, respectively in chronic renal failure patients and patients with normal renal function). Total drug clearance and Vd area were significantly increased in the chronic renal failure patients: 341·9 vs 211·8 mL min−1; and 69·3 and 35·5 L. There were no differences in intrinsic clearance or apparent volume of distribution at steady state for unbound drug between the two patient groups.
In-vivo Radiolabelled Oxiracetam Binding to Rat Brain
Authors: Mennini Tiziana , Taddei Carlo , Cagnotto Alfredo , Ponzio Franca 
Published: April 2011

Abstract
The in-vivo binding of [3H]oxiracetam has been studied in brain areas of rats examined 30 min after i.c.v. injection. Soluble radioactivity accounted for more than 90% of total radioactivity in all the structures considered and was not affected by co-injection with a 1000-fold excess of unlabelled oxiracetam. Both total and bound radioactivity showed a marked regional distribution, with highest concentrations in the septum, followed by the hippocampus; the cerebral cortex, striatum and cerebellum had the lower concentrations of radioactivity. Computer-assisted quantitative autoradiography with [14C]oxiracetam confirms these findings. Analysis of [3H]oxiracetam bound to membranes indicated that, after co-injection with a 1000-fold excess of unlabelled oxiracetam, there was a significant reduction of binding only in the septum, hippocampus and cerebral cortex. These results suggest that in those cerebral structures oxiracetam binds to saturable sites.
Halothane, Isoflurane and Enflurane Potentiate the Effect of Noradrenaline on Ventricular Automaticity in the Rat Heart: Evidence of the Involvement of Both α- and β-Adrenoceptors
Authors: Cárceles M D , Laorden M L , Hernandez J , Miralles F S , Campos M 
Published: April 2011

Abstract
Direct evidence has been sought as to what extent the sensitization of heart to the arrhythmogenic action of sympathomimetic drugs in the presence of the inhalatory anaesthetics, halothane, isoflurane and enflurane, is mediated by either α- or β- adrenoceptors. For this purpose, the effects of isoprenaline, noradrenaline and phenylephrine on ventricular automaticity induced by local injury have been studied in the isolated right ventricle of the rat. Isoprenaline was more potent in increasing ventricular automaticity than either phenylephrine or noradrenaline. The anaesthetic potentiated the effects of noradrenaline, as well as that of higher concentrations of phenylephrine, but not those of isoprenaline. These results support the contention that increases in ventricular automaticity induced by sympathomimetic drugs are mainly mediated by adrenoceptors of the β-type. However, the simultaneous activation of both α- and β-adrenoceptors seems to be necessary for the effect of the anaesthetics in sensitizing the heart to sympathomimetic drugs.
The vascular relaxant effects of guanabenz are not mediated by α2-adrenoceptors in rat aortic rings
Authors: Soares-da-Silva P , Villanueva M M 
Published: April 2011

Abstract
The present experiments show that the α2-adrenoceptor agonist guanabenz produced a concentration-dependent relaxation in 5-hydroxytryptamine- and noradrenaline-preconstricted rat aortic rings, but not when tone was raised by high potassium in the medium. Similar findings were made for pinacidil. In 5-hydroxytryptamine-preconstricted preparations the relaxant effect of guanabenz was not affected by yohimbine, propranolol or by removal of the endothelium. In noradrenaline-preconstricted rings the relaxant effects of guanabenz and pinacidil were significantly antagonized by tetraethylammonium. The results suggest that guanabenz might act in the muscle tissue by opening potassium channels or antagonism of calcium mobilization from intracellular stores.
On the Use of Diazepam and Pro-diazepam (2-Benzoyl-4-chloro-N-methyl-N-lysylglycin anilide), as Adjunct Antidotes in the Treatment of Organophosphorus Intoxication in the Guinea-pig
Authors: Karlsson Britt , Lindgren Björn , Millquist Eric , Sandberg Maria , Sellström Åke 
Published: April 2011

Abstract
Diazepam and pro-diazepam (2-benzoyl-4-chloro-N-methyl-N-lysylglycin anilide) have been used as adjunct antidotes to pyridostigmine and atropine against the organophosphate, soman, in the guinea-pig. Both added significant protection to the pyridostigmine/atropine treatment. Animals pretreated with diazepam, 60 min before soman, were “better” protected than animals given an equimolar dose of pro-diazepam therapeutically 1 min after soman. A pretreatment with diazepam for three days further increased the protection. A therapeutic dose of pro-diazepam, 1 min after soman, gave no further protection, to the three day diazepam pretreatment. The serum concentrations of diazepam (given i.p.) and desmethyldiazepam (given i.m.) were determined by GLC after diazepam (i.p.) and pro-diazepam (i.m.) were given. The protection, relative to the control, provided by the diazepam pretreatment (60 min before and for three days before soman) correlated linearly, r = 0.9898, with the serum values of diazepam achieved at these times. Our data suggest that diazepam as adjunct to pyridostigmine and atropine administered as pretreatment gives a “safer” protection, than an equimolar dose of pro-diazepam given therapeutically.
Further Studies on the Metabolism of Methylamine by Semicarbazide-sensitive Amine Oxidase Activities in Human Plasma, Umbilical Artery and Rat Aorta
Authors: Lyles Geoffrey A , Holt Andrew , Marshall C M Susan 
Published: April 2011

Abstract
An ion exchange radiochemical assay has been developed to study the deamination of [l4C]methyIamine (MA) in homogenates of rat aorta and human umbilical artery, as well as in samples of human plasma. MA metabolism was found to be inhibited almost completely by 1 mM semicarbazide, but virtually unaffected by 0.1 mM clorgyline, suggesting that MA is a substrate for the semicarbazide-sensitive amine oxidase (SSAO) activities which also metabolize benzylamine (BZ) in these sources. Mean Km values for MA metabolism by aorta, umbilical artery and plasma were 182, 832 and 516 μM, respectively, with corresponding Vmax values in aorta and umbilical artery of 100 and 590 nmol (mg prot.)−1 h−1, and in plasma of 48 nmol (mL serum)−1 h−1. Kinetic constants determined for [14C]BZ metabolism in plasma (by an organic solvent extraction assay) and in umbilical artery (by the ion exchange assay) yielded mean Km values of 225 μM (plasma), 222 μM (umbilical artery), and Vmax values of 28 nmol (mL serum)−1 h−1 (plasma) and 377 nmol (mg prot.)−1 h−1 (umbilical artery). The deamination of [14C]MA was inhibited competitively by unlabelled BZ, with Ki values in umbilical artery and plasma of 220 and 172 μM, respectively. Also, metabolite formation from mixtures of [14C]BZ (200 μM) and [14C]MA (800 μM) was extremely close to that predicted for a single enzyme capable of metabolizing two alternative substrates in a competitive fashion. β-Aminopropionitrile was found to be a reversible, competitive inhibitor (Ki of 165 μM) of [14C]MA metabolism in umbilical artery, inhibitory properties characteristic of those found previously for the effects of β-aminopropionitrile upon BZ-metabolizing SSAO activities in other tissues. The possibility that vascular and plasma SSAO activities may be involved in the endogenous turnover of the biogenic amine MA is discussed.