bluuebunny/crossref_metadata_2025_split huggingface dataset:
Stimulation of brain dopamine autoreceptors by remoxipride administration in reserpine-treated male rats
Authors: Ahlenius Sven , Ericson Evalena , Wijkström Agneta 
Published: April 2011

Abstract
Male Sprague-Dawley rats were treated subcutaneously with reserpine (5 mg kg−1, — 18 h) and with the aromatic amino acid decarboxylase inhibitor, NSD-1015 (3-hydroxybenzylhydrazine) (100 mg kg−1 -30 min). Remoxipride 0 -8, 3 -2 or 12 -8 mg kg−1 was administered subcutaneously at -50 min. Immediately following decapitation (0 h), the ventral striatum and the anterior neocortex were dissected. Dopa and 5-hydroxytryptophan accumulation in these brain areas were analysed by HPLC with electrochemical detection. Reserpine produced a marked increase in striatal and neocortical dopa accumulation, in comparison with glucose vehicle + NSD-1015-treated controls, and this increase was dose-dependently antagonized by remoxipride treatment. Thus, together with demonstrated dopamine receptor antagonist actions in intact animals, remoxipride behaves as a mixed dopamine receptor agonist-antagonist. Such properties could contribute to the favourable endocrine and extrapyramidal side effect profile of remoxipride as an antipsychotic agent.
Inhibitory effect of CP-96,345, a non-peptide neurokinin-1-receptor antagonist, on neurogenic responses of guinea-pig isolated airway smooth muscle
Authors: Kamikawa Yuichiro , Shimo Yasuo 
Published: April 2011

Abstract
The actions of CP-96,345, a non-peptide neurokinin-1 receptor antagonist, on the responses evoked by electrical-field stimulation or by acetylcholine and substance P in guinea-pig tracheal and bronchial muscle strips were examined. Electrical-field stimulation evoked a biphasic response, consisting of a cholinergically-mediated fast contraction followed by non-adrenergically-mediated relaxation in tracheal muscle and by a non-cholinergically-mediated slow contraction in bronchial muscle. CP-96,345 (1–10 μM) caused a concentration-dependent and non-selective inhibition in the amplitude of these neurogenic responses, where non-cholinergic contractions were more profoundly inhibited. Submaximal contractions of tracheal and bronchial muscles evoked by exogenous substance P (01–3 μm) were partly inhibited by CP-96,345 (1–10 μm), but acetylcholine-induced contractions were hardly inhibited. The results indicate that in guinea-pig isolated airway smooth muscle, CP-96,345 can non-selectively inhibit neurogenic responses probably via neurokinin-1 receptor-dependent and independent mechanisms.
Histamine H3 agonist decreases arterial blood pressure in the guinea-pig
Authors: Kim L Ea , Javellaud J , Oudart N 
Published: April 2011

Abstract
Intravenous injection of an H3-agonist, (R)-α-methylhistamine, dose-dependently caused a transient fall in mean arterial pressure of guinea-pigs. This pressor response was not reduced by combined mepyramine/cimetidine (up to 1 mg kg−1), atropine or propranolol, but was attenuated by either a selective H3-antagonist, thioperamide, or a competitive inhibitor of nitric oxide synthesis, NG-monomethyl l-arginine. The reduction by the inhibitor of nitric oxide synthesis was reversed by l- but not d-arginine. Histamine activated the H3-sites since its depressor response (obtained with mepyramine and cimetidine) was similar to that of (R)-α-methylhistamine. Our data indicate that H3-sites could exist in the cardiovascular system of guinea-pigs and that their stimulation might be mediated through the l-arginine/nitric oxide pathway.
Design and In-vitro Evaluation of a Modified-release Oral Dosage Form of Nifedipine by Hybridization of Hydroxypropyl-β-cyclodextrin and Hydroxypropylcellulose
Authors: Wang Zheng , Horikawa Takashi , Hirayama Fumitoshi , Uekama Kaneto 
Published: April 2011

Abstract
To modify the release rate of nifedipine, a potent calcium channel antagonist, a double-layer tablet was designed, anticipating a more balanced oral bioavailability and a prolonged efficacy than the simple plain tablet. Amorphous nifedipine powders prepared by spray-drying with 2-hydroxypropyl-β-cyclodextrin (HP-β-CyD) and nonionic surfactant HCO-60 were employed as a fast-release portion to attain an initial rapid dissolution of nifedipine. Hydroxypropylcelluloses (HPCs) with different viscosity grades (type L, M, and H) were used for a slow-release portion to provide an appropriate sustained-release. Taking into account the physiological conditions of the gastrointestinal tract (pH and motility), an optimal formulation of the double-layer tablet was obtained by changing the mixing ratios of each component. For example, the tablet consisting of HP-β-CyD with 3% HCO-60/(HPC-L:HPC-M) in the weight ratio 1/2(1:1) provided a sufficient slow release of the drug over a wide pH region following an initial rapid dissolution. The release of nifedipine from the double-layer tablets was little affected by pH of the medium and rotation speed of paddle after accelerated storage conditions (60°C, 75% r.h.). The present results suggest that a combination of HP-β-CyD, HCO-60 and HPCs can serve as a modified-release carrier for poorly water-soluble nifedipine.
Use of Enzymatic Activity for Design of Orally Administered Enteric Dosing Forms
Authors: Nishihata Toshiaki , Yamamoto Ken , Ishizaka Mayumi 
Published: April 2011

Abstract
Liquid and semi-solid enteric dosage forms were prepared by entrapping drug with an appropriate partition coefficient in a lipid base vehicle which would then be released by the action of intestinal enzymes. Lipid ester derivatives such as glyceryl monocaprylate and polysorbate 80 were used as vehicles. These vehicles readily dissolved the poorly water-soluble compounds used in the study, itazigrel, indomethacin and the dye, sudan II, and were digested by lipase and esterase, releasing the test drugs with time profiles similar to those observed in dissolution studies. The vehicles released little or only a small amount of the drugs into aqueous medium in the absence of an appropriate enzyme. The enzyme-sensitive enteric vehicles when containing sudan II did not release the dye in the stomach of rats after oral administration, but released significant amounts of the dye in the small intestine.
KCl Contractions in the Rat Isolated Seminal Vesicle
Authors: Sharif Suleiman I 
Published: April 2011

Abstract
Potassium chloride (K+) produced dose-dependent contractions of the rat isolated seminal vesicle with no sign of tachyphylaxis. The contractile response was biphasic in nature and composed of an early rapid phasic contraction and a slowly developing, but more sustained, tonic response separated by a transient relaxation. Neither cocaine nor depletion of tissue catecholamines by reserpine influenced responses to K+. Moreover, guanethidine, phentolamine, phenoxybenzamine, atropine and physostigmine all failed to modify responses of the tissue to K+. Thus, the possibility of K+ acting via release of endogenous noradrenaline or acetylcholine is excluded. Calcium-free conditions with or without EGTA reduced both the components of K+-induced contraction. The rate of reduction of both responses was faster in the presence of EGTA with part of the tonic response being resistant even to calcium deprivation in the presence of EGTA. On the other hand, verapamil reduced both responses in a similar manner, whereas nifedipine produced dose-dependent rightward shifts of the concentration-response curves of both the phasic and tonic responses to K+. However, in the presence of nifedipine, the maximum response of only the phasic contraction was significantly lowered. It is concluded that both phases of KCl contraction in the rat seminal vesicle use extracellular Ca2+, of which some is tightly bound with high affinity, probably to plasma membranes. In addition, two subtypes of voltage-sensitive Ca2+ channels may exist, one of which is preferentially sensitive to nifedipine and both are sensitive to verapamil.
Effect of the Selective A1 Adenosine Antagonist 8-Cyclopentyl-1,3-dipropylxanthine on Acute Renal Dysfunction Induced by Escherichia coli Endotoxin in Rats
Authors: Knight R J , Bowmer C J , Yates M S 
Published: April 2011

Abstract
The effect of the selective A1 adenosine antagonist, 8-cyclopentyl-1,3-dipropylxanthine (CPX), on Escherichia coli endotoxin-induced acute renal dysfunction was determined in anaesthetized rats. Bolus administration of endotoxin at doses of either 1 or 20 mg kg−1 evoked decreases in inulin clearance, renal blood flow, urine flow and excretion of sodium, potassium and chloride. The changes in renal function produced by 20 mg kg−1 endotoxin were more severe than those noted with 1 mg kg−1 toxin and, by contrast to this lower dose, renal function showed no signs of recovery. Intravenous administration of CPX (0·1 mg kg−1) elicited a statistically significant, although modest, attenuation of the decline in inulin clearance, renal blood flow, urine output and electrolyte excretion induced by 20 mg kg−1 endotoxin. By contrast, treatment with 0·1 mg kg−1 CPX resulted in statistically significant protection against the falls in excretory function evoked by 1 mg kg−1 endotoxin but not against the reductions in renal blood flow and inulin clearance produced by the lower dose of toxin. These results suggest that adenosine may play a role, albeit not a major one, in the pathophysiology of endotoxaemic acute renal failure.
A factorial design study on the physical stability of 3-in-1 admixtures
Authors: Li L C , Sampogna T P 
Published: April 2011

Abstract
The effects of dextrose concentration, the compounding method, and storage conditions, on the physical stability of 3-in-1 admixtures were investigated using a 2n factorial design. The main effect of these three variables on the weight percent of oil globules larger than 5 μm (by HIAC) was found to be statistically significant. However, the effects of interaction amongst these variables, except the two-way interaction between dextrose concentration and storage conditions, were found to be statistically insignificant. A higher dextrose concentration was shown to enhance the physical stability of the admixtures, while low-temperature storage (three days at 5 C) was more favourable for maintaining the physical stability of the admixtures with a low dextrose concentration. Although sequential pumping produced admixtures with a slightly lower final weight percentage of larger oil globules (&gt; 5 μm), the method of compounding has the least impact on the physical stability of the admixtures in comparison with the other two variables evaluated in this study. The storage of the admixtures at room temperature for one day was shown to have a greater adverse effect on admixtures with a low dextrose concentration.
Differences in the mode of cough augmentation by four angiotensin-converting enzyme inhibitors in guinea-pigs
Authors: Takahama K , Fuchikami J , Suzuki A , Tabata T , Kai H , Miyata T 
Published: April 2011

Abstract
The effects of four angiotensin-converting enzyme (ACE) inhibitors, captopril, enalapril, quinapril and alacepril, on the cough responses caused by citric acid and capsaicin inhalation were studied in normal and bronchitic guinea-pigs. After an oral dose of 10 mg kg−1, none of the ACE inhibitors had an effect on the citric acid-induced coughing response in normal guinea-pigs. Enalapril 10 mg kg−1 significantly increased the number of coughs caused by capsaicin inhalation. In bronchitic guinea-pigs, 10 mg kg−1 captopril and enalapril significantly increased the number of capsaicin-induced coughs. When administered daily for 8 days, captopril was the only ACE inhibitor which significantly increased the number of coughs due to citric acid inhalation. The present results indicate that the ACE inhibitors had different modes of cough augmentation.
Influence of heparin on the chemotactic activity of human thrombin
Authors: Morin A , Arvier M Marchand , Humbert J C , Doutremepuich F , Vigneron C 
Published: April 2011

Abstract
Chemoattractant properties of human thrombin have been studied, by polymorphonuclear leucocyte migration under agarose gel, in the presence of various sulphated macromolecules such as standard heparins, low molecular weight heparins, CY216, K2165, PK10169 and pentosane polysulphate. These compounds did not attract polymorphonuclear leucocytes within the range of concentrations used, whilst thrombin alone is a cytotaxin for these cells. Addition of heparins to thrombin led to an increase in the chemoattractant activity of this enzyme for at least one of the doses studied. Augmentation of the chemoattractant activity of thrombin by heparins was shown at concentrations equivalent to those found in-vivo after administration of therapeutic doses of heparin. Pentosane polysulphate, at the studied concentrations, did not lead to a significant rise in the chemoattractant activity of thrombin.
A new antimicrobial quinolone (AM-1155) analysed in hair as an index of drug exposure and as a time-marker
Authors: Uematsu T , Kusajima H , Umemura K , Ishida R , Ohkubo H , Nakashima M 
Published: April 2011

Abstract
Scalp hair samples were obtained at one-month intervals for up to four months after the administration from each of twelve healthy male volunteers participating in a phase I study of a new antimicrobial quinolone, AM-1155, (±)-1-cyclopropyl-6-fluoro-1, 4-dihydro-8-methoxy-7-(cis-3,5-dimethyl-1-piperazinyl)-4-oxo-3-quinoline carboxylic acid. After hair was sectioned into 1 cm lengths from the scalp end, corresponding portions from five pieces of hair were dissolved in 1 m NaOH and assessed for AM-1155 by HPLC. In all subjects who had taken a single dose (600 mg, n = 6) or repeated doses (300 mg twice daily for 6·5 days, n = 6), the drug was detected in hair. The hair portions containing the drug were shown in most subjects to move outwards month by month at the rate of about 1 cm month−1. A single hair, which was obtained from each subject of the repeated-dose study 3 months after the completion of administration, was cut into 2·5-mm lengths from the scalp side and analysed for AM-1155. The drug was shown to be contained in 4 to 6 consecutive 2·5-mm lengths, showing that there was no large axial diffusion of the drug along the hair shaft even after 3 months. These findings indicate the utility of measuring this quinolone derivative in hair as an index of drug exposure and, furthermore, as a time marker for analysing other drugs in hair.
A Chloroform Extract of the Herb Feverfew Blocks Voltage-dependent Potassium Currents Recorded from Single Smooth Muscle Cells
Authors: Barsby R W J , Knight D W , McFadzean I 
Published: April 2011

Abstract
We have studied the effects of a chloroform extract of fresh leaves from the herb feverfew (Tanacetum parthenium) on potassium currents in smooth muscle. The currents were recorded from single cells dissociated from the rat anococcygeus and the rabbit ear artery using the whole-cell patch-clamp technique. When applied to cells isolated from the rat anococcygeus, the extract reduced the inactivating voltage-dependent potassium current in a concentration-related manner, with an IC50 value (the concentration that reduced the current by 50%) of 56 μg mL−1. Complete block of the current occurred at 1 mg mL−1. In addition to reducing the peak current, feverfew decreased the time to peak of the current and increased the rate of decay of the current. These effects can be explained by the feverfew extract blocking open potassium channels. In single cells isolated from rabbit ear artery the feverfew extract again reduced the voltage-dependent potassium current, whilst at the same time having no effect on the spontaneous transient outward currents which arise as a consequence of activation of calcium-dependent potassium channels. These results suggest that chloroform extracts of feverfew leaf contain an as yet unidentified substance capable of producing a selective, open-channel block of voltage-dependent potassium channels.
Flumazenil and lignocaine-induced toxicity: is the inverse agonist type activity circadian-time dependent?
Authors: Bruguerolle Bernard , Emperaire Nicolle 
Published: April 2011

Abstract
We have investigated the possible influence of time of day on the activity of flumazenil on lignocaine-induced toxicity in mice. The circadian pattern of the period of latency for convulsions and the induced mortality for lignocaine alone and for lignocaine plus flumazenil was not statistically significant (cosinor or analysis of variance) but the influence of flumazenil on lignocaine-induced toxicity was circadian-time dependent (F = 27·8, P = 00001).
Pharmacokinetics and Absolute Bioavailability of Cyclosporin Following Intravenous and Abomasal Administration to Sheep
Authors: Charles Bruce G , Filippich Lucio J , Pass Michael A 
Published: April 2011

Abstract
Cyclosporin A pharmacokinetics were studied following intravenous and abomasal dosing in an open, crossover study in healthy, merino ewes. Five different doses of cyclosporin A were dispersed in milk and administered into the abomasum through a surgically inserted fistula which simulates oral administration. Cyclosporin A was well tolerated. Whole blood concentrations of cyclosporin A were measured by HPLC and mean clearance (0·45 ± 0·05 L h−1 kg−1), distribution volume (4·4 ± 2·0 L kg−1), mean residence time (9·6 ± 4·1 h) and half-life (12·1 ± 3·1 h) were calculated. Negligible cyclosporin A was excreted in urine or bile. Area under the curve increased proportionally with doses up to 26·3 mg kg−1, but was curvilinear above this dose. Abomasal bioavailability at 6·4 mg kg−1 was 0·26 ± 0·09, and mean absorption time was 4·7 ± 11·1 h. Considerable pharmacokinetic variability was observed, particularly after abomasal administration. Cyclosporin A pharmacokinetics in sheep lie within the values reported in man after renal, bone marrow and cardiac transplantation.
Impact of free magnolol excretions in asthmatic patients who responded well to Saiboku-To, a Chinese herbal medicine
Authors: Homma Masato , Oka Kitaro , Kobayashi Hitoshi , Niitsuma Tomoyuki , Yamamoto Shinobu , Itoh Hisao , Takahashi Noriyuki 
Published: April 2011

Abstract
Saiboku-To, a mixture of ten different herbal extracts, has been used in Japan and Czechoslovakia for corticosteroid-dependent severe asthma to reduce the maintenance doses of corticosteroid. Magnolol has been considered to be an active component of Saiboku-To as an inhibitor of 11β-hydroxysteroid dehydrogenase and T-lymphocyte proliferation resulting in corticosteroid-sparing. To investigate the relationship between magnolol and the clinical effects of Saiboku-To, urinary magnolol excretion was compared in responders and non-responders under long-term Saiboku-To treatment. The clinical outcome of the Saiboku-To treatment was evaluated in nine asthmatic patients at 52 weeks after the onset of the treatment, using individual fluctuation of asthmatic points obtained from the patients' diary cards. Three patients whose clinical conditions were improved by the treatment were termed responders and six others were termed non-responders. The difference in the amounts of the total magnolol excreted were not significant; however, free (or non-conjugated) amounts of magnolol excreted in the responders were 7 times those in the non-responders (P &lt; 0·05). These results suggest that the magnolol might be responsible for the therapeutic effect of Saiboku-To, indicating practical bioavailability in the responders.
Effects of Different Agents on the Contractile Response Elicited by Extracellular Calcium after Depletion of Internal Calcium Stores in Rat Isolated Aorta
Authors: Noguera M Antonia , D’Ocon M Pilar 
Published: April 2011

Abstract
Noradrenaline, 1 μm, induced a sustained contractile response in rat isolated aorta in the presence and in the absence of extracellular Ca2+. After depleting the noradrenaline-sensitive intracellular Ca2+ stores, an increase in the basal tone of the aorta was observed during the incubation period in the presence of Ca2+ and in the absence of the agonist. We have tested the possible pathways through which Ca2+ enters the cell to refill the previously depleted Ca2+ pools, a process that is accompanied by an increase in tension. The magnitude of this increase does not depend on the presence of Mg2+ in the extracellular medium nor on the temperature, suggesting that it is mediated by an event that does not depend on intracellular energy or Ca2+, Mg2+-ATPase. It is inhibited in a concentration-dependent manner by an unspecific relaxing compound, caffeine, and an organic Ca2+ entry blocker, verapamil, but not by an inorganic Ca2+ entry blocker, lanthanum. Caffeine (10 Mm) and verapamil (10−5 m) completely inhibited the increase in the resting tone, but only verapamil abolished the refilling of the noradrenaline-sensitive Ca2+ pools, indicating that the extracellular Ca2+ enters the cell through voltage-operated Ca2+ channels. Caffeine inhibited the increase in the resting tone without blocking the refilling process of the stores at 37°C, but at 25°C a partial inhibition of the repletion of internal Ca2+ pools was observed. These results confirm previous work that showed a temperature-dependent activity of caffeine.
Ca2+-Channel Blockade in Rat Thoracic Aorta by Crychine Isolated from Cryptocarya chinensis Hemsl
Authors: Ko Feng-Nien , Wu Yang-Chang , Lu Sheng-Teh , Teng Che-Ming 
Published: April 2011

Abstract
The pharmacological effects of crychine, isolated from Cryptocarya chinensis Hemsl, on rat thoracic aorta were examined. In the high-K+ medium (60 Mm), Ca2+ (0·03–3 Mm)-induced vasoconstriction was inhibited by crychine in a concentration-dependent manner (10–100 μg mL−1). Increasing the incubation time from 5 to 30 min did not cause more pronounced inhibitory effect on KCl-induced contraction. The tonic contractions elicited by KCl (60 Mm) and Bay K 8644 (0·1 μm) were also relaxed by the addition of crychine and were more marked in the 1·9 Mm than in the 5 Mm Ca2+ medium. The noradrenaline concentration-response curves were antagonized non-competitively by crychine (10–100 μg mL−1). At the plateau of noradrenaline-induced tonic contraction, the addition of crychine also caused relaxation. This relaxing effect of crychine was not antagonized by indomethacin (20 μm) or methylene blue (50 μm), and was still present in denuded aorta or in the presence of nifedipine (2 μm). Caffeine (10 Mm)-induced contraction and cAMP or cGMP levels were not affected by crychine. It is concluded that crychine relaxes the rat thoracic aorta mainly by suppressing the Ca2+ influx through both voltage- and receptor-operated calcium channels.
Dual Inhibition of Platelet-activating Factor and Arachidonic Acid Metabolism by Ajmaline and Effect on Carrageenan-induced Rat Paw Oedema
Authors: Saeed Sheikh Arshad , Simjee Rukhsana Usman , Mahmood Farah , Rahman Nurun Nahar 
Published: April 2011

Abstract
The effects of ajmaline on human platelet aggregation, arachidonate metabolism and platelet activating factor (PAF)-induced lethality in rabbits were examined. Platelet aggregation induced by several stimuli (ADP, collagen, and PAF) was inhibited by increasing concentrations of ajmaline. The potency of ajmaline was higher when PAF was employed as stimulating agent in comparison with other agonists (IC50 70, 270 and 380 μm for PAF, ADP and collagen, respectively) whereas ajmaline had no effect against arachidonic acid-induced aggregation. In contrast however, ajmaline inhibited arachidonate metabolism by platelet homogenates. The formation of both thromboxane A2 and 12-hydroxy-eicosatetraenoic acid was inhibited by ajmaline with comparable potencies. Pretreatment of rabbits with ajmaline (50 mg kg−1) completely abolished the lethal effects of PAF (11 μg kg−1) given intravenously (P &lt; 0·001). In addition, ajmaline at doses ranging from 50 to 100 mg kg−1 inhibited carrageenan-induced rat paw oedema (P &lt; 0·001). In this test ajmaline was three times more potent than aspirin. In the light of these results we conclude that ajmaline, a known anti-arrhythmic agent is a PAF antagonist and a dual inhibitor of platelet cyclo-oxygenase and lipoxygenase enzymes with anti-inflammatory properties.