bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effect of 711389-S, a New Antiarrhythmic Agent, on Myocardial Energy Metabolism in Guinea-Pigs and Rats
Authors: Iwaki K , Ishii M , Shinosaki T , Ueda M , Yonetani Y 
Published: April 2011

Abstract
The effect of 711389-S, a new antiarrhythmic agent, on myocardial energy metabolism was investigated using anaesthetized guinea-pigs and rats. 711389-S elevated the adenylate energy charge and phosphorylation potential in normal guinea-pig myocardium. Large doses also increased the myocardial lactate content with ECG abnormalities. The close relationship between rate-pressure product and the myocardial energy state under 711389-S treatments showed the suppression of energy consumption due to a decrease of work output. In guinea-pigs with arrhythmic myocardia induced by intravenous infusion of ouabain, 711389-S prevented the loss of high-energy phosphate compounds and the acceleration of anaerobic glycolysis concomitant with the effective antiarrhythmic property. In ischaemic myocardium produced by ligation of the coronary artery in rats, 711389-S suppressed the decreases of creatine phosphate, NAD+ and adenylate energy charge. Moreover, this agent effectively blocked the incidence of ventricular arrhythmias at an early stage following the ligation. In all of these actions, 711389-S was more effective than disopyramide, which is in the same class of antiarrhythmics. 711389-S was concluded to be a favourable antiarrhythmic agent offering beneficial action against arrhythmic and ischaemic metabolic changes in the myocardium.
Inhibition of Glucose-induced Insulin Secretion by Calcium Channel Blocking Drugs In-vitro but not In-vivo in the Rat
Authors: Semple Colin G , Smith Maureen , Furman Brian L 
Published: April 2011

Abstract
The organic calcium channel blocking drugs darodipine, nicardipine, diltiazem and verapamil inhibited glucose-induced (8.3 mmol L−1) insulin secretion by rat isolated islets in a concentration-dependent manner. The IC50 values (μmol L−1) for nicardipine, diltiazem and verapamil were 0.0025, 1.94 and 3.6, respectively. There were no significant differences between the potencies of any one drug when compared at two different glucose concentrations (27.8 and 8.3 mmol L−1). Isolated islets were also responsive to the calcium channel activating drugs BAY K 8644 and CGP 28392, which enhanced glucose-induced insulin secretion and prevented the inhibitory effect of verapamil. BAY K 8644 was more potent than CGP 28392. In the anaesthetized rat, neither verapamil (1 mg kg−1 i.v. 10 min before glucose) nor nicardipine (0.2 mg kg−1 i.v.) modified the glucose or insulin response to intravenous glucose whilst producing marked cardiovascular effects. The plasma concentrations of nicardipine (3.9 × 10.8 M at 10 min post injection) were similar to those producing effects in-vitro whereas the plasma concentrations of verapamil (5 × 10−7 M) were lower. It thus appears that the islet B cell calcium channel is less sensitive to calcium channel blocking drugs in-vivo than in-vitro. Moreover, in-vivo, the cardiovascular system is more sensitive to these drugs than are the islet B cells, although the potencies of the calcium channel blocking drug in isolated islets are similar to those reported for cardiac muscle and vascular smooth muscle in-vitro.
Distribution of 7-hydroxymethotrexate in human blood
Authors: Slørdal Lars , Sager Georg , Huseby Nils-Erik , Aarbakke Jarle 
Published: April 2011

Abstract
We have examined the in-vitro distribution of 7-hydroxymethotrexate (7-OH-MTX), a cytotoxic metabolite of methotrexate (MTX), in human blood, and its protein binding in serum. The distribution of 7-OH-MTX (10−6 M) in fresh samples of whole blood was studied at 37 °C and pH 7.51 ± 0.05 (mean ± s.d.), and its protein binding was assessed by equilibrium dialysis of serum against Krebs Ringer phosphate buffer at 37 °C and pH 7.41 ± 0.07 (mean ± s.d.). 7-OH-MTX had a mean cell/plasma concentration ratio of 0.03 (range 0–0.27, n = 18). It was extensively bound in human serum, with a bound fraction of 90.4 ± 3.3% (mean ± s.d.) in healthy volunteers (n = 11), and significantly lower, 82.3 ± 4.0% (mean ± s.d.), in hypoalbuminaemic surgical patients (n = 7). The binding of 7-OH-MTX was correlated with serum albumin (HSA) concentrations (r = 0.72, P &lt; 0.0007, n = 18). Blood distribution data support the contention that 7-OH-MTX has a small volume of distribution, and HSA appears to be mainly responsible for the high degree of its protein binding in serum.
The guinea-pig trachea O-methylating system is more effective in modulating β2- than β1-adrenoceptor-mediated responses to isoprenaline
Authors: Proença J , Paiva M Q , Guimarāes S 
Published: April 2011

Abstract
Assuming that responses of the guinea-pig trachea to isoprenaline in the presence of atenolol (10 μmol L−1) are exclusively, or at least predominantly, (β2-adrenoceptor mediated and that responses to isoprenaline in the presence of ICI 118,551 (erythro-DL-1(7-methylindan-4-yloxyl)-3-isopropylaminobutan-2-ol) (1 nmol L−1) are exclusively, or at least predominantly (β1-adrenoceptor mediated, the influence of inhibition of COMT by U-0521 (dehydroxy-2-methyl propiophenone) (50 μmol L−1) has been compared in both conditions. U-0521 enhanced (β2-adrenoceptor mediated responses to isoprenaline 3-3-fold, while those mediated by (β1-adrenoceptors were enhanced only 2-2-fold. It is concluded that in guinea-pig trachea COMT activity is functionally more effective in modulating responses which are mediated by β2-adrenoceptors than responses mediated by β1-adrenoceptors.
The structure of phenindamine base and salts in the solute state
Authors: Branch S K , Casy A F , Hussain R , Upton C 
Published: April 2011

Abstract
High-field NMR (13C and 1H) studies of phenindamine are reported which establish structures of the free base and some of its salts in the solute condition. The base exists as a mixture of two isomers which differ in double bond position (9–9a or 4a–9a) while most salts are 9–9a isomers. The clinically employed tartrate (Thephorin) is exceptional in being a 4a–9a ene. Salts of both double bond type exist in solution as mixtures of protonated epimers of variable epimeric ratio, that of the tartrate in D2O being approximately 1:1.
Variation of Population Release Kinetics in Polydisperse Multiparticulate Systems (Microcapsules, Microspheres, Droplets, Cells) with Heterogeneity of One, Two or Three Parameters in the Population of Individuals
Authors: Donbrow Max , Hoffman Amnon , Benita Simon 
Published: April 2011

Abstract
Release kinetics of active substances from ensembles of microparticles such as microcapsules, cells, droplets and liposomes constituted of individual entities releasing their contents at constant rates may follow zero order, first order, sigmoid or biphasic equations. The release equation observed depends upon the statistical distribution of release-determining parameters among the population. Typical cases are presented in terms of the distribution of two parameters, payload (m∞ and time for complete payload release (t∞) which also define the release rate constant (k). Heterogeneity of the two parameters generally leads to first order ensemble behaviour, whereas heterogeneity of one parameter only may lead to different ensemble release equations, viz. zero order (m∞ heterogeneous) or first order (t∞ heterogeneous). Biphasic distribution can lead to an apparent ‘burst’ effect, with apparent change of kinetics. The presence of a third heterogeneous parameter, lag time, yields a sigmoid ensemble release curve. These conclusions are demonstrated by simulations or experimentally, and are also valid for linearized curves of microparticles following matrix kinetics.
The influence of binder film thickness on the mechanical properties of binder films in tension
Authors: Ononokpono Okon E , Spring M S 
Published: April 2011

Abstract
The physicomechanical properties of films of different thicknesses, made from methylcellulose and gelatinized maize starch, have been studied in tension. There was a linear relation between film thickness and tensile strength, toughness, elastic resilence and elongation at fracture. Young’s modulus increased with decreasing film thickness particularly with films with a thickness of less than 15 μM.
Lipid solubility of a series of drugs and its relevance to fatal poisoning
Authors: Cassidy S L , Lympany P A , Henry J A 
Published: April 2011

Abstract
For 11 commonly used drugs, the n-octanol/water partition coefficient (pH 7.4 temperature 37°C) and solubility in n-octanol were determined. The drugs tested were chlorpromazine, amitriptyline, trazodone, dextropropoxyphene, diltiazem, dibucaine, amethocaine, procaine, quinidine, acetylsalicylic acid and paracetamol. For eight of the drugs, the relative lipid saturation corresponding to a fatal plasma concentration was estimated from the two parameters determined above and the median fatal blood concentrations reported in the literature. For five of those eight drugs, the estimated relative saturation in the lipid phase fell within the range 0.001–0.004 which is close to relative saturation figures in aqueous and vapour phases already published for chemicals possessing a non-specific or physical mechanism of toxicity. Since this is determined largely by their lipid solubility, it is probable that accumulation in the lipid phase is an important determinant of the lethal toxicity of drugs and chemicals with a non-specific mechanism of toxicity.
Inhibition of the cataleptic effect of tetrahydrocannabinol by other constituents of Cannabis sativa L.
Authors: Formukong Evelyn A , Evans A Tudor , Evans Fred J 
Published: April 2011

Abstract
Tetrahydrocannabinol (THC) induced catalepsy in mice, whereas a cannabis oil (6.68% w/w THC), four cannabinoids and a synthetic mixture did not. Cannabinol (CBN) and olivetol inhibited THC-induced catalepsy in the mornings and the evenings, but cannabidiol (CBD) exhibited this effect only in the evenings. A combination of CBN and CBD inhibited THC-induced catalepsy equal to that of CBN alone in the mornings, but this inhibition was greater than that produced by CBN alone in the evenings.
Inhibition of thromboxane biosynthesis by 3-pyridinol carboxypentyl ethers substituted with a hydroxylated octyl chain
Authors: Conti S , Desideri N , Passaghe S , Castagnoli M N , Cerletti C , Stein M L 
Published: April 2011

Abstract
Racemic 6-[4-(3′-hydroxy-l′-octenyl)-3-pyridyloxy] hexanoic and 6-[4-(3′-hydroxyoctyl)-3-pyridyloxy] exanoic acids have been synthesized and their activity as inhibitors of the biosynthesis of thromboxane A2 in human serum has been studied, in comparison with isomers having the eight-carbon chain in the 2 position. Very high, selective activity was found for the new 4-substituted 3-pyridinol ethers, whereas the 2-substituted compounds showed no action.
Effect of sodium valproate on midazolam distribution
Authors: Calvo R , Suárez E , Rodríguez-Sasiaín J M , Aguilera L 
Published: April 2011

Abstract
The displacement of midazolam, a new water-soluble, short-acting benzodiazepine, from its plasma binding sites by sodium valproate, has been studied in man. An increase of its free fraction (ranging from 2.71 to 5.35%) in plasma from epileptic patients receiving sodium valproate was observed. A similar situation was created in rabbits by pretreatment with sodium valproate (600 mg kg−1 day−1) and posterior hypnosis with midazolam. Due to the interaction, sodium valproate-pretreated rabbits showed an increase in midazolam brain levels (130.91 μg g−1 in cortex vs 84.55 μg g−1 in control animals). Therefore, it seems likely that displacement of midazolam by sodium valproate in epileptic patients could lead to an increase of the midazolam response.
Repeated treatment with imipramine and amitriptyline reduced the immobility of rats in the swimming test by enhancing dopamine mechanisms in the nucleus accumbens
Authors: Cervo Luigi , Samanin Rosario 
Published: April 2011

Abstract
Bilateral injections of 1 μg sulpiride in the rat nucleus accumbens antagonized the effect of a seven-day treatment with 20 mg kg−1 day−1 imipramine or amitriptyline in the swimming test. The data suggest that dopamine mechanisms in the limbic regions of the rat brain are involved in the effect of repeated treatment with imipramine and amitriptyline in that test.
Vesicular Systems (Niosomes and Liposomes) for Delivery of Sodium Stibogluconate in Experimental Murine Visceral Leishmaniasis
Authors: Hunter C A , Dolan T F , Coombs G H , Baillie A J 
Published: April 2011

Abstract
Suppression of Leishmania donovani liver amastigotes by sodium stibogluconate has been determined in a murine model of experimental visceral leishmaniasis. Niosomal and liposomal drug formulations were equiactive and both increased drug efficacy by an order of magnitude compared with that of free drug. Niosomes containing 30 mol % cholesterol were prepared from three different non-ionic surfactants and no significant difference in activity was detected among the different drug-loaded niosomes. Both negatively charged and neutral vesicles were found to be equally effective. However, vesicle cholesterol content had a slight influence on the antiparasitic activity of the drug-loaded niosomes. Empty vesicles produced a dose-dependent parasite suppression for all vesicles studied. Studies of antimony distribution in the mouse using neutron activation analysis showed high liver levels after i.v. administration of the carrier forms of the drug.
Association of Liposome-entrapped [3H]Methotrexate with Thioglycollate-elicited Macrophages In-vitro
Authors: Foong W C , Green K L 
Published: April 2011

Abstract
The association of free or liposome-entrapped [3H]methotrexate ([3H]MTX) with thioglycollate-elicited macrophages was investigated in-vitro. [14C]Cholesteryl oleate was incorporated into the liposomes as a lipid marker. [3H]MTX association with the macrophages was 5 to 9-fold higher with liposome-entrapped [3H]MTX than with the free drug. Macrophage-liposome association was biphasic, temperature-dependent and saturable at high liposomal lipid concentration. A high liposome cholesterol (CH) content or the presence of 2,4-dinitrophenol or colchicine also reduced macrophage-liposome association.
Evaluation of Different Drugs in Two Models of Immediate Hypersensitivity
Authors: Ayala L E , Aleixandre M A , Mora L García 
Published: April 2011

Abstract
The effect of the calcium antagonists, verapamil, nicardipine and diltiazem, the two cromones, disodium cromoglycate and SM-857 (11-oxo-11 H-pyrido[2,1-b]quinazoline-2-carboxylic acid), and the anthelmintic, diethylcarbamazine citrate, have been compared on the ovalbumin (OA)-induced contraction of the isolated trachea and longitudinal muscle-myenteric plexus (LM-MP) from sensitized guinea-pigs. The calcium antagonists prevented the OA-induced contractions in LM-MP and to a lesser degree the OA-induced contractions in trachea. Similar doses of SM-857 protected both tissues but neither cromoglycate (10−5M) nor diethylcarbamazine (10−5M) affected these contractions. The OA-induced contraction in trachea had a tonic phase that was not present in the LM-MP response. Only the calcium antagonists succeeded in relaxing this OA tonic component, diltiazem being the more potent. These results unmask different mechanisms of drug action on immediate hypersensitivity and specific sensibilities, depending on the kind of tissue.
Contractile activity of calcitonin gene-related peptide on pulmonary tissues
Authors: Hamel R , Ford-Hutchinson A W 
Published: April 2011

Abstract
Rat calcitonin gene-related peptide was shown to be a very potent contractile agent on guinea-pig trachea, contractions being observed at 10 pM and maximal contractions (32–36% of the methacholine maximum) being observed between 0.3 and 13.3 nM. The response was largely inhibited (88%) by pretreatment with indomethacin indicating that the effect was mediated through the secondary generation of cyclooxygenase products.
Kinetic mechanism for the intestinal absorption of ofloxacin
Authors: Prieto J G , Barrio J P , Alvarez A I , Gómez G 
Published: April 2011

Abstract
The absorptive behaviour of ofloxacin, a quinolone antibacterial agent, was studied following recirculation in small intestine of both male and female rats, at initial doses ranging from 0.125 to 5 mg mL−1. A saturable Michaelis-Menten process is suggested to explain the intestinal absorption. No significant differences were found in the absorption parameters per metabolic weight unit.
β-Adrenoceptor stimulating effects of phenylephrine and noradrenaline in the rat pulmonary vascular bed
Authors: Uma S , Tuncer M 
Published: April 2011

Abstract
The effects of phenylephrine and noradrenaline have been investigated on the perfusion pressure of the rat isolated lung. Both drugs (0.3–30 μg) produced a dose-dependent decrease in perfusion pressure elevated by 20 mM KCl, which was reversed to a dose-dependent increase after addition of propranolol (1 × 10−7 M) to the perfusion fluid. Increments due to both agonists in the presence of propranolol were antagonized by prazosin (1 × 10−6 M). Propranolol, but not prazosin, elevated the basal perfusion pressure. The results indicate that phenylephrine and noradrenaline are more effective in stimulating β-adrenoceptors than α-adrenoceptors in the rat pulmonary vascular bed and that β-adrenoceptors may regulate the vascular tone of the rat pulmonary circulation.
High doses of L-naloxone but neither D-naloxone nor β-funaltrexamine prevent hyperthermia-induced seizures in rat pups
Authors: Laorden M L , Miralles F S , Puig M M 
Published: April 2011

Abstract
The effects of the non-specific opiate antagonist L-naloxone and the inactive isomer D-naloxone, as well as the specific mu receptor antagonist β-funaltrexamine, have been examined on hyperthermia-induced seizures in unrestrained 15 days old rats. Saline-injected animals exposed to an ambient temperature of 40°C showed a gradual increase in body temperature reaching a maximum of 42±0.1°C at 50 min exposure. At this time all the pups had seizures and died. Similar results were obtained when the animals were pretreated with different doses of D-naloxone and β-funaltrexamine. Rats pretreated with L-naloxone also showed an increase in rectal temperature; but the temperature was lower than in saline-injected animals. Only high doses of L-naloxone prevented seizures and deaths. These data indicate that endogenous opioid peptides may play a role in seizures induced by hyperthermia and that receptors other than mu receptors could be involved in hyperthermia-induced seizures.
Proteoglycan biosynthesis as a determinant of patella damage in the murine antigen-induced arthritis model
Authors: Steward A , Rising T J , Bottomley K M K , Haddrell L 
Published: April 2011

Abstract
The incorporation of 35SO4 into cartilage proteoglycan has been employed as a measure of patella damage in the murine antigen-induced arthritis model. In a preliminary set of experiments, where both the proteoglycan concentration and 35SO4 incorporation were determined in control and arthritic patella over a 2 day to 6 day week period, the arthritic joint contained significantly higher levels of radioactivity compared with the controls. A subsequent study over an extended period of 10 weeks confirmed the earlier results, and indicated that the 6 week samples showed the greatest difference (71%) in 35SO4 incorporation between the arthritic and control patella.
Non-ionic Surfactant Effects on Hairless Mouse Skin Permeability Characteristics
Authors: Walters Kenneth A , Walker Michael , Olejnik Orest 
Published: April 2011

Abstract
The influence of a range of polyethoxylated non-ionic surfactants upon the transport of methyl nicotinate across hairless mouse skin in-vitro was investigated using standard two-compartment diffusion cells. Those surfactants having a linear alkyl chain greater than C8 and an ethylene oxide chain length of less than E14 caused significant increases in the flux of methyl nicotinate. Surfactants having branched or aromatic moieties in the hydrophobic portion were ineffective. Maximum enhancement of flux was obtained using polyoxyethylene (10) lauryl ether (Brij 36T). Two possible modes of surfactant action are proposed. Initially the surfactant may penetrate into the intercellular regions of the stratum corneum, increase fluidity and eventually solubilise and extract lipid components. Secondly, penetration of the surfactant into the intracellular matrix followed by interaction and binding with the keratin filaments may result in a disruption of order within the corneocyte. The structural specificity required for the latter mechanism may explain, to some extent, the maximum activity obtained with the C12 surfactant.
Effects of Methylene Blue on the Uptake, Release and Metabolism of Noradrenaline in Mesenteric Arterial Vessels
Authors: Soares-da-Silva P , Caramona M M 
Published: April 2011

Abstract
Methylene blue (3, 10 and 30 μM) increased the spontaneous outflow of endogenous dopamine and noradrenaline from sympathetic nerves supplying the dog mesenteric artery and drastically reduced the formation of endogenous dihydroxyphenylglycol (DOPEG). In addition, it decreased the accumulation of [3H]noradrenaline in the tissue, reduced the formation of [3H]DOPEG and [3H]normetanephrine, without altering the formation of [3H]dihydroxymandelic acid. In tissue homogenates of the same blood vessel, methylene blue 30 and 100 μM produced a significant reduction in the deamination of 5-hydroxytryptamine (5-HT), β-phenylethylamine (β-PEA) and tyramine. Methylene blue increased the accumulation of [3H]isoprenaline in the tissue, and markedly reduced the formation of [3H]O-methylisoprenaline ([3H]OMI). These results show that methylene blue alters the storage and disposition of the adrenergic transmitter.
Pharmacological Modulation of Platelet Activating Factor (PAF)-induced Bronchoconstriction and Hypertension in Anaesthetized Guinea-pigs
Authors: Iwama Takehisa , Shikada Ken-Ichi , Tanaka Sakuya 
Published: April 2011

Abstract
The effect of PAF has been examined in anaesthetized guinea-pigs. Intravenous (i.v.) administration of PAF (10 ng kg−1) did not modify the respiratory response but decreased the arterial blood pressure. A high dose of PAF (200 ng kg−1) caused marked bronchoconstriction and concomitant hypertension. The cyclooxygenase inhibitors aspirin (5 mg kg−1) and indomethacin (5 mg kg−1) and the thromboxane A2 (TXA2) receptor antagonist BM-13.177 (1 mg kg−1) failed to inhibit the peak bronchoconstrictive response but significantly inhibited the prolonged response following peak response. These inhibitors also attenuated PAF-induced hypertension. On the other hand, the lipoxygenase inhibitors phenidone (10 mg kg−1) and NDGA (5 mg kg−1) and the leukotriene (LT) receptor antagonist FPL-55712 (2 mg kg−1) affected neither bronchoconstriction nor hypertension induced by PAF. However, when aspirin was given in combination with NDGA, phenidone or FPL-55712, the peak and the following prolonged bronchoconstriction were significantly inhibited. The suppression of PAF-induced hypertension by aspirin was not further inhibited by the combination of these inhibitors. These results indicate that in anaesthetized guinea-pigs PAF-induced bronchoconstriction is composed of a dual response, a direct action (peak response) and an indirect action (prolonged response). The latter may be produced by the generation of TXA2 and lipoxygenase products, while PAF-induced hypertension is indirectly mediated by the generation of TXA2.