bluuebunny/crossref_metadata_2025_split huggingface dataset:
The effect of ascorbate on the acetylcholine release from guinea-pig ileal myenteric plexus
Authors: Hayashi Eiichi , Haga Yuko , Shinozuka Kazumasa , Takeda Mitsuhiro 
Published: April 2011

Abstract
The effect of ascorbate on the release of acetylcholine from the longitudinal muscle-myenteric plexus preparation of the guinea-pig isolated ileum has been investigated using a bioassay and an isotopic technique. Ascorbate at 5 mM increased the spontaneous output of acetylcholine and enhanced DMPP-induced output of acetylcholine, while iso-ascorbate, 5 mM, did not. Ascorbate did not influence either the spontaneous or the DMPP-induced release of acetylcholine from synaptosomes of the ileal myenteric plexus. These results suggest that ascorbate promotes acetylcholine release from intramural cholinergic nerves.
The effect of α-(3,5-di-t-butyl-4-hydroxybenzylidene)-γ-butyrolactone (KME-4), a new anti-inflammatory drug, on leucocyte migration in rat carrageenan pleurisy
Authors: Hidaka Takayoshi , Hosoe Kazunori , Katsumi Ikuo , Yamashita Toshiaki , Watanabe Kiyoshi 
Published: April 2011

Abstract
KME-4, α-(3,5-di-t-butyl-4-hydroxybenzylidene)-γ-butyrolactone was found to reduce the accumulation of leucocytes and exudate volume in the rat carrageenan pleurisy model. When administered orally 1 h before carrageenan, KME-4 (3–10 mg kg−1) induced a degree of inhibition of leucocyte migration almost equal to that of indomethacin (3–10 mg kg−1) in both 5 n and 24 h pleurisies. Furthermore, KME-4, when administered orally 5 h after the carrageenan, inhibited both monocyte numbers and exudate volume in a 24 h pleurisy and was more effective than indomethacin and BW755c which inhibited only monocyte migration. These results suggest that KME-4 has a differential anti-inflammatory activity. Dexamethasone (0.25 mg kg−1) showed strong inhibition of total cell numbers and exudate volume.
Measurement of hardness and strength of tablets and their relation to compaction performance of powders
Authors: Jetzer W E 
Published: April 2011

Abstract
Materials with different deformation properties were compressed into tablets at a range of pressures. The compacts were characterized in terms of indentation hardness which quantifies resistance to deformation and tensile strength quantifying resistance to fracture. A unifying description of these two competing mechanical responses is made using the evaluated single compaction parameters obtained with the equation proposed by Leuenberger. The compaction performance parameter and the bonding index make it possible to characterize the deformation and bonding behaviour of a substance under pressure. Furthermore, useful information is obtained for predicting when capping problems occur. It is evident that more than one index or parameter is necessary to describe the variety and complexity of the tableting properties.
Factors influencing cryoprotective activity and drug leakage from liposomes after freezing
Authors: Higgins J , Hodges N A , Olliff C J , Phillips A J 
Published: April 2011

Abstract
The effects of freezing and thawing conditions and cryoprotective additives on release of streptomycin from lecithin liposomes following freeze-thaw cycles have been investigated. Drug retention was maximized by slow cooling (approx. 1°C min−1). At temperatures between 0° and −20°C, the extent of drug loss was time-dependent indicating incomplete freezing; below −45°C this effect was abolished and the system was stable. Osmotic gradients across the liposome membrane during freezing were found to have little effect on drug loss. Marked cryoprotective activity was shown by dimethylsulphoxide, glycerol, alanine and glycinebetaine at concentrations of 3% w/v or less. At this concentration sucrose and mannitol had little activity.
The effects of peripherally administered monoaminergic drugs on ethanol diuresis in rats
Authors: Pohorecky L A 
Published: April 2011

Abstract
The effect of peripherally administered drugs that modify monoaminergic function, on ethanol (2.0 g kg−1, intragastrically)-induced changes in urine output has been examined in rats. The α-noradrenoceptor agonist, clonidine (0.05–0.15 mg kg−1) produced marked urine output and potentiated slightly the diuretic effect of ethanol. The α-noradrenoceptor antagonist, phentolamine (1–5 mg kg−1) dose-dependently decreased ethanol-induced diuresis. p-Chloroamphetamine (0.8–2.0 mg kg−1) produced significant diuresis and potentiated the diuresis produced by ethanol. Methysergide (1.25, 2.5 mg kg−1), a 5-hydroxytryptamine receptor antagonist, had no effect on urine output while it depressed the ethanol-induced increase in urine output. Apomorphine (0.8, 1.5 mg kg−1), a dopamine receptor agonist, did not modify urine output in either control or ethanol-treated animals, while the dopamine receptor antagonist, pimozide (0.75–3.0 mg kg−1), dose-dependently decreased ethanol-induced diuresis, but had no effect on urine output in control animals. Since our previous research indicates that the intraventricular administration of drugs that alter dopaminergic and 5-HT function does not alter ethanol-induced diuresis, the interaction of these types of agents with ethanol-induced diuresis in the present study suggests that the interaction was mediated peripherally.
Metabolism of cathinone to (−)-norephedrine and (−)-norpseudoephedrine
Authors: Brenneisen R , Geisshüsler S , Schorno X 
Published: April 2011

Abstract
S-(−)-Cathinone (S-(−)-α-aminopropiophenone) is the major active principle of khat leaves (Catha edulis), which are widely used in East Africa and the Arab peninsula as an amphetamine-like stimulant. After oral administration of synthesized cathinone (isomers, racemate), 22–52% was recovered in 24 h urine samples mainly as aminoalcohol metabolites. With GC/MS, HPLC and CD, the main metabolite of S-(−)-cathinone was identified as R/S-(−)-norephedrine and the main metabolite of R-(+)-cathinone as RR-(−)-norpseudoephedrine. Both aminoalcohols are formed by a stereospecific keto reduction.
Amineptine: its effect on the dopaminergic system of rats
Authors: Ponzio F , Achilli G , Garattini S , Perego C , Sacchetti G , Algeri S 
Published: April 2011

Abstract
3-Methoxytyramine formation was enhanced by amineptine (40 mg kg−1 i.p.) in the striatum and limbic area, indicating an increase in the concentration of dopamine in the extraneuronal space. Since dopamine turnover, determined as the rate of L-dopa accumulation, is reduced by the drug at short (10 min) times, the enhanced extraneuronal dopamine concentration seems mainly related to amineptine-induced inhibition of its uptake.
ATP causes postjunctional potentiation of noradrenergic contractions in the portal vein of guinea-pig and rat
Authors: Kennedy Charles , Burnstock Geoffrey 
Published: April 2011

Abstract
Superfusion of the portal vein of rat and guinea-pig with Krebs' solution maintained at 25°C greatly inhibits spontaneous contractions of the preparations and allows contractile responses to ATP and noradrenaline to be measured accurately. Under these conditions, continuous superfusion with ATP (10−5 M), a concentration which had no effect on either basal tension or spontaneous activity, caused a significant shift to the left of the concentration-response curve to exogeneous noradrenaline in both tissues. The mechanism of this potentiation induced by ATP may differ in the two tissues since in the rat portal vein potentiation appeared to be rapidly reversed by superfusing with ATP-free solution, whereas in the guinea-pig portal vein a further concentration-response curve to noradrenaline, in the absence of ATP, was still significantly shifted to the left compared with the control curve. However, potentiation in the rat portal vein may have had a longer duration than is suggested by the results since control concentration-response curves to noradrenaline in this tissue showed a progressive shift to the right which, although not significant, is likely to have affected the apparent time course of potentiation. It is concluded that ATP can potentiate contractions to exogeneous noradrenaline in the portal vein of rat and guinea-pig via an, as yet, unidentified postjunctional mechanism.
Eating caused by neuropeptide-Y injection in the paraventricular hypothalamus: response to (+)-fenfluramine and (+)-amphetamine in rats
Authors: Bendotti C , Garattini S , Samanin R 
Published: April 2011

Abstract
(+)-Fenfluramine and (+)-amphetamine have been compared for their ability to reduce food intake in food-deprived rats or eating caused by injecting neuropeptide-Y in the paraventricular hypothalamus of free feeding rats. (+)-Fenfluramine at doses ranging from 0&#x006d;̇625 to 5 mg kg−1 reduced eating caused by neuropeptide-Y more effectively than it did the food intake of food-deprived rats, whereas (+)-amphetamine (dose range 0&#x006d;̇625-2&#x006d;̇5 mg kg−1) reduced both types of eating to a similar extent. The results confirm that (+)-fenfluramine, although less potent than (+)-amphetamine in reducing eating by food-deprived rats, markedly reduces overeating caused by various endogenous substances or stress in free feeding rats. The physiological significance of the neuropeptide-Y-induced eating and its control by (+)-fenfluramine remains to be elucidated.
Influence of the new antihypertensive drug, SM-2470 (a quinazoline derivative), on cholesterol metabolism in rats
Authors: Seki Kunio , Watanabe Takafumi , Suga Tetsuya 
Published: April 2011

Abstract
The influence of SM-2470. (4-amino-2-{4-[bicyclo(2,2,2)oct-2-ene-5-carbonyl]-1-piperazinyl}-6,7 -dimethoxyquinazoline), a new antihypertensive agent, on cholesterol metabolism was investigated in hypercholesterolaemic rats, using the dual isotope method (cholesterol absorption) and the intestinal ligated loop method (cholesterol uptake). In the hypercholesterolaemic model, 1-30 mg kg−1 doses of SM-2470 significantly inhibited the elevation of the total serum cholesterol and very low and low density lipoproteins (VLDL + LDL)-cholesterol, without causing any change in the hepatic cholesterol level. In a dual isotope model experiment, SM-2470 (10, 30 mg kg−1) inhibited the intestinal absorption of cholesterol, but did not affect biliary excretion of sterol and/or bile acids, nor did it affect cholesterol movement from the liver to blood. In the intestinal ligated loop method, SM-2470 remarkably inhibited the mucosal uptake of cholesterol in a dose-dependent manner in 0dependent manner in5-2dependent manner in0 mg mL−1 of micellar solution. In addition, SM-2470 inhibited micellar formation in-vitro, which increased the distribution of large sized micelles as well as cholesterol absorption inhibitors. From these results, it can be assumed that a possible mechanism behind the hypocholesterolaemic effect of SM-2470 is the inhibition of cholesterol absorption related to the reduction of cholesterol solubilization, occurring in the gut micelles, similar to the action of plant sterol.
Selective agonists and antagonists for 5-hydroxytryptamine receptor subtypes, and interactions with yohimbine and FG 7142 using the elevated plus-maze test in the rat
Authors: Pellow Sharon , Johnston Amanda L , File Sandra E 
Published: April 2011

Abstract
The effects of some 5-HT receptor ligands were investigated on measures of anxiety in an elevated plus-maze test in the rat. Quipazine (2 and 4 mg kg−1), a non-specific 5-HT agonist and ritanserin (0&#x006d;̇25-10 mg kg−1), a 5-HT2 receptor antagonist displayed anxiogenic profiles by reducing both of the measures of anxiety used in this test. Two 5-HT1A receptor ligands, buspirone (4 and 8 mg kg−1) and ipsapirone (2.5-10 mg kg−1) and the 5-HT1 agonist, RU 24969 (0&#x006d;̇1875-1&#x006d;̇5 mg kg−1) significantly reduced only the percentage of time spent on the open arms. (-)-Propranolol (5 and 10 mg kg−1), a 5-HT1 receptor antagonist significantly reduced only the percentage of entries made onto the open arms. Metergoline (4 mg kg−1), a non-specific 5-HT antagonist displayed anxiolytic effects in this test by increasing both measures of anxiety. The 5-HT1A receptor agonist, 8-OH-DPAT (0&#x006d;̇0625-0dependent manner in25 mg kg−1) had no effect on either of the measures of anxiety. The results from the non-specific ligands (quipazine and metergoline) are consistent with the theory that a reduction in 5-HT function reduces anxiety. However, in spite of their more selective effects on 5-HT receptors the results in this test from the more specific ligands are not consistent with a strong involvement of any single receptor subtype. The interaction studies with yohimbine and FG 7142 (β-carboline-3-carboxylate methylamide) provided no clear evidence for a major role of 5-HT pathways in the mediation of their anxiogenic effects.
Effects of three new anthracyclines and doxorubicin on the rat isolated heart
Authors: Chen Zheng Min , Colombo Tina , Conforti Laura , Donelli Maria Grazia , Fiedorowicz Roza J , Marchi Stefano , Paolini Angela , Riva Emma , Zuanetti Giulio , Latini Roberto 
Published: April 2011

Abstract
The acute cardiac toxicity of three second-generation anthracycline analogues and doxorubicin was compared in a model of the rat isolated Langendorff perfused heart. The drugs, doxorubicin (DX), 4-epi-doxorubicin (4′EDX), 4-demethoxy-daunorubicin (4DMDR) and 4′-deoxy-doxorubicin (4′dxDX) were infused for 40 min at a concentration of 26 μM into the isolated hearts. All four compounds significantly reduced cardiac work and its first derivative. The time to 50% decrease in work (TW50) was respectively 36, 23, 9 and 7 min for DX, 4′EDX, 4′dxDx and 4DMDR. The three anthracycline derivatives, but not DX, significantly increased coronary resistance. Heart rate was reduced by all compounds compared with baseline, but not compared with controls. Rhythm disturbances were seen with all five hearts perfused with 4DMDR, which stopped beating before 40 min; 2/5 hearts in the 4′EDX group and 1/5 hearts in the 4′dxDX group also stopped before the end of perfusion. All the compounds reached concentrations in the myocardium 8 to 50 times higher than in the perfusing medium. The more cardiotoxic the compound, the higher was its myocardial concentration; a significant correlation was found for all four agents. Noradrenaline was never measurable in the perfusate of control and DX hearts; perfusion with the three anthracycline derivatives caused some release, but the pattern was not clearcut and the maximum concentrations attained in the perfusate were relatively low (&lt; 1&#x006d;̇6 times 10−9 M). In conclusion, in the rat isolated perfused heart, the early cardiotoxicity induced by equimolar concentrations of the three anthracycline compounds was greater than that induced by DX and was directly related to drug accumulation in the myocardium. Catecholamines do not seem to have a major role in the development of toxicity in this model.
The effects of the calcium channel agonist, Bay K-8644, on guinea-pig ileum and rat uterine horn
Authors: Conte-Camerino Diana , Lograno Marcello D , de Luca Annamaria , Persichella Michele , Franconi Flavia 
Published: April 2011

Abstract
Bay K-8644 (methyl 1,4-dihydro-2,6-dimethyl-3-nitro-4-(2-trifluoromethylphenyl)pyridine-5-carboxylate) concentration-dependently caused contractions of the partly depolarized ileum, but at higher concentrations (10−6 to 10−5 M) produced relaxation. 10−8 to 4 times 10−7M nifedipine antagonized while 10−9 and 4 times 10−9 M potentiated Bay K-8644. On the partly depolarized uterus, Bay K-8644 (10−9 to 10−6 M) had only a spasmogenic effect whereas nifedipine (4 times 10−9 to 10−7 M) was spasmolytic. Verapamil and diltiazem (each at 10−4 M) both reduced the maximal response to Bay K-8644, while other spasmolytics were ineffective. Thus, Bay K-8644 activates ileum and uterus by opening voltage-operated Ca2+ channels, but its relaxant action at high concentration and its potentiation by nifedipine is not seen in both organs. Such differences probably depend on the concentration of the compounds used and the polarization state of the cell membranes.
Monolayer studies on poly(isobutylcyanoacrylate)-ampicillin association
Authors: Baszkin A , Couvreur P , Deyme M , Henry-Michelland S , Albrecht G 
Published: April 2011

Abstract
Surface pressure-area isotherms (π-A) of poly(isobutylcyanoacrylate) monolayers with or without glucose and dextran as polymerization adjuvants used in the preparation of nanoparticles have been derived from measurements made at the air-water interface with the subphase pH at 2&#x006d;̇7, 5&#x006d;̇5 or 8&#x006d;̇8. The isotherms were characteristic of the expanded type of polymer monolayer curves, yielding unusually low limiting area values compared with those of other known poly(acrylate) derivatives. This behaviour may be explained by the folding of polar moieties of the polymer groups in the water subphase. Ampicillin incorporated during preparation of nanoparticles had a negligible effect on the general behaviour of adjuvant-free monolayers, but a significant one on the adjuvant-loaded polymer monolayer system which showed an increase in surface area throughout the compression cycle, as compared with the surface area of the adjuvant-free polymer system although the collapse pressure was practically the same at 67 mN m−1.
Comparison of albumin and casein microspheres as a carrier for doxorubicin
Authors: Chen Yan , Willmott N , Anderson J , Florence A T 
Published: April 2011

Abstract
Doxorubicin (Adriamycin)-loaded casein and albumin microspheres, with diameters between 14 and 38 μm (50% weight average) were prepared by glutaraldehyde stabilization of the aqueous phase (containing protein and drug) of a water in oil emulsion. Physical properties, drug loading characteristics and release rates from microspheres in-vitro have been compared and correlated with effects on tumour growth when injected intratumourally in rats. Compared with albumin, the surface charge of the casein system was more negative and the microspheres exhibited a slower release of drug in-vitro. Both observations could be explained by the lower drug content of the casein system. There was evidence for the formation of a doxorubicin complex in the microspheres, the significance of which is not yet known. Casein microspheres containing 11 μg of doxorubicin had a similar inhibitory effect on tumour growth (growth delay = 20&#x006d;̇7 days) to 85 μg of drug incorporated into albumin microspheres (growth delay = 18&#x006d;̇6 days). The absence of a simple dose-response relationship shows that carrier matrix can influence potency of incorporated drug. The results are consistent with release rate of the drug from microspheres (obversely, rate of drug delivery to the tumour), being a determinant of potency in these systems.
The stereoselectivity of the ‘single drug binding site’ of human α1-acid glycoprotein (orosomucoid)
Authors: Brunner F , Müller W E 
Published: April 2011

Abstract
The stereoselective binding of six pairs of basic, one pair of acidic drug enantiomers, and one pair of diastereomers to human α1-acid glycoprotein was investigated by means of competition experiments against [3H]propranolol- or [14C]nicardipine-labelled binding sites using equilibrium dialysis to separate free from bound marker ligand. The affinity constants (Ka) for association of [3H]propranolol and [14C]nicardipine with α1-AGP were 1&#x006d;̇ 2 ± 0&#x006d;̇6 times 105M−1 and 3&#x006d;̇4 ± 1&#x006d;̇4 times 105M−1, respectively, and control binding amounted to 57 ± 7 and 91 ± 2%, respectively. The following selectivity factors, calculated as the ratio of the higher over the lower enantiomer concentrations displacing 15% of control radiomarker binding (IC15***-value), were obtained against propranolol and nicardipine: (-)-/(+) propranolol: 1&#x006d;̇9 and 1&#x006d;̇7.; (+)-/(-)-disopyramide: ***2&#x006d;̇8 and 1&#x006d;̇4; (+)-/(-)-verapamil: 1&#x006d;̇6 and 1&#x006d;̇9; (+)-(S)-/(-)-(R)-202-791, a dihydropyridine derivative: 2&#x006d;̇6 and 2&#x006d;̇0; (-)-/(+)-asocainol: 1&#x006d;̇7 and 3&#x006d;̇0; (+)-/(-)-tilidine: 1&#x006d;̇1 and ã2; (-)-(S)-/(+)-(R)- warfarin: 1&#x006d;̇6 and 2&#x006d;̇4; (±)-cis/(±)-trans-trans-tilidine: 1&#x006d;̇7 and 1&#x006d;̇8. When the calculation of radioligand-free fractions is also taken into account, it is apparent that only the tilidine isomers show no selectivity at propranolol-marked, and the disopyramide isomers at nicardipine-marked α1-AGP-binding sites, in all other cases, a weak selectivity is detectable, which is, however, far below the values obtained for most neurotransmitter receptors. It is concluded that the single drug binding site of α1-AGP is only slightly stereoselective and that the stereoselective binding of the drugs investigated is probably of no clinical consequence.
Investigation into the effects in-vitro of the 5-hydroxytryptamine reuptake inhibitor, alaproclate, on carbachol-stimulated inositol phospholipid breakdown in the rat cerebral cortex
Authors: Fowler Christopher J , Thorell Gun , Ögren Sven-Ove 
Published: April 2011

Abstract
The effect of alaproclate in carbachol-stimulated inositol phospholipid (PI) breakdown in rat cerebral cortical miniprisms has been investigated. Carbachol-stimulated PI breakdown was greatly enhanced by increasing the assay potassium concentration from 5&#x006d;̇88 to 18&#x006d;̇2 mM. Alaproclate, on the other hand, did not influence carbachol-stimulated PI breakdown over the concentration range tested (0-100 μM) at either assay [K+]. The elution pattern of the inositol phosphates from the Dowex-1 columns was also unaffected by alaproclate both in the absence and presence of carbachol. Thus, the potentiation by alaproclate of tremor and salivation induced by the muscarinic agonist oxotremorine in-vivo reported previously is not seen when muscarinic function is measured in-vitro using carbachol-stimulated PI breakdown.
Effect of vanadate on cooling-induced tension changes in K-depolarized smooth muscles from guinea-pigs
Authors: Sunano Satoru , Shimada Tomoko , Kato Satoru , Shimamura Keiichi 
Published: April 2011

Abstract
Sodium vanadate reversed cooling-induced relaxation of K-depolarized taenia coli of guinea-pigs but failed to reverse it in the portal vein and uterus. It potentiated cooling-induced contraction of K-depolarized vas deferens and ureter. These effects were not mediated by the inhibition of Na,K-ATPase, but by the inhibition of the Ca-pump.
Diazepam facilitates reflex bradycardia in conscious rats
Authors: Yang C P , Chou L S , Liu H J , Lin M T 
Published: April 2011

Abstract
The effects of diazepam on cardiovascular function were assessed in conscious rats. Intravenous administration of diazepam (1-30 mg kg−1) produced a dose-dependent decrease in both the mean arterial pressure and the heart rate. Also, reflex bradycardia was produced in rats by intravenous infusion of adrenaline (1&#x006d;̇25-2&#x006d;̇5 μg kg−1). Intravenous pretreatment of the rats with diazepam, although causing no change in the adrenaline-induced pressor effect, did enhance the adrenaline-induced reflex bradycardia. However, the diazepam enhancement of adrenaline-induced reflex bradycardia was antagonized by pretreatment of rats with an intravenous dose of picrotoxin (an agent blocks chloride channels by binding to sites associated with the benzodiazepine-GABA-chloride channel macromolecular complex). The data indicate that diazepam acts through the benzodiazepine-GABA-chloride channel macromolecular complex within the central nervous system to facilitate reflex bradycardia mediated through baroreceptor reflexes in response to an acute increase in arterial pressure.