bluuebunny/crossref_metadata_2025_split huggingface dataset:
U-46619-induced Ischaemic Electrocardiographic Changes in Rats: Preventive Effects of Prostacyclin and Nitroglycerin
Authors: Yamamoto Taku , Kikuta Chie , Hosoki Kanoo 
Published: April 2011

Abstract
The anti-anginal effect of nitroglycerin and prostacyclin was examined using, as an index, the ischaemic electrocardiogram (ECG) change (ST elevation) induced by intracoronary arterial injection of 9,11-dideoxy-11α,9α-epoxymethano-PGF2α (U-46619), a stable thromboxane A2 agonist, in anaesthetized rats. The ST elevation induced by U-46619 (5–20 μg kg−1, i.c.a.) was dose-dependent and reproducible. U-46619-induced ST elevation was markedly prevented by the pretreatment of intravenous administration of prostacyclin (0·01 μg kg−1), and to a lesser extent by nitroglycerin (0·3 mg kg−1). Simultaneously, platelet count decreased significantly in the coronary arterial blood which indicated that platelet aggregation was enhanced by U-46619. The decrease of platelet count in coronary arterial blood at the time of ST elevation was significantly suppressed by prostacyclin (0·1 μg kg−1, i.v.), but not by nitroglycerin (0·3 mg kg−1, i.v.). These results suggest that the ST elevation induced by intracoronary arterial injection of U-46619 may be derived from spasm of coronary artery and platelet aggregation in the intracoronary artery in rats.
Metabolic Cage Isolation Reduces Antipyrine Clearance in Rats
Authors: Brunner Lane J , Dipiro Joseph T , Feldman Stuart 
Published: April 2011

Abstract
Rats are commonly isolated individually in cages during pharmacokinetic studies. However, isolation-induced changes in drug disposition are not commonly examined. Antipyrine is a marker of hepatic oxidative function and total body water. The purpose of the study was to investigate the effect of individual housing on antipyrine pharmacokinetics. Rats were individually housed in either standard polycarbonate boxes (n = 8) or metabolic cages (n = 10). On day 1 and day 9 rats were administered a single intravenous bolus injection of antipyrine 20 mg kg−1. Blood samples (100 μL) were obtained before and at 20, 40, 60, 90, 120, 180, 240, 300 and 360 min following the administration of the dose. Rats remained in their respective cages between evaluations. Serum antipyrine concentrations were determined by capillary electrophoresis. Pharmacokinetic parameters were estimated by model-independent methods. Antipyrine clearance was reduced by 383·4% in rats isolated in metabolic cages for eight days (P = 0·013) while the volume of distribution remained unchanged in both rat groups. These data suggest that the isolation of rats in metabolic cage systems may markedly alter the pharmacokinetics of xenobiotics, thus possibly masking experimental outcome.
Enantioselective Pharmacokinetics of Homochlorcyclizine: Disposition of (+)- and (–)-Homochlorcyclizine after Intravenous and Oral Administration of Racemic Homochlorcyclizine to Rats
Authors: Nishikata Mayumi , Nakai Aki , Fushida Hitomi , Miyake Keishiro , Arita Takaichi , Iseki Ken , Miyazaki Katsumi 
Published: April 2011

Abstract
Concentrations of homochlorcyclizine enantiomers in blood, urine, and tissues of the liver, lung, kidney, brain, heart, spleen, intestine and stomach of rats after drug administration were determined by high-performance liquid chromatography on a chiral stationary phase. After intravenous administration (10 mg kg−1), homochlorcyclizine was rapidly distributed in many tissues, with the highest concentration in lung. No differences were found between enantiomers in blood concentrations. After oral administration (50 mg kg−1), the concentrations of the (+)-isomer in nearly all tissues were higher than those of the (–)-isomer. The AUC0-x values of the (+)- and (–)-isomers differed significantly. The absorption of racemic homochlorcyclizine from rat small intestine was not enantioselective. These results suggested that the different concentrations between enantiomers after oral administration were not caused by enantioselective absorption or distribution but rather by preferential first-pass metabolism of the (–)-isomer in the liver. The enantioselectivity of metabolism was also demonstrated by in-vitro experiments.
Pharmacokinetics and brain distribution of zolpidem in the rat after acute and chronic administration
Authors: Trenque T , Bustany P , Lamiable D , Legros S , Choisy H 
Published: April 2011

Abstract
The pharmacokinetics of zolpidem were studied after single dose, administered for either 7 or 28 days to rats. Thirty minutes after the last dose, animals were killed and the brain removed. The highest concentrations in plasma, which were observed at the first sampling time (0·5 h) were 2341±540 (day 0), 1956 ± 325 (day 7) and 2908 ± 1369 ng mL−1 (day 28). Corresponding AUC values of 1742 ± 488, 1583 ± 422 and 2683 ± 1249 ng mL−1 h were found. MRT increased significantly from 0·46 ± 0·06 h on day 0 to 0·67 ± 0·02 h on day 28. The cerebral levels showed no significant change during the chronic administration (766 ± 285, 685 ± 171 and 887 ± 264 ng g−1, respectively). No modification of the principal kinetic parameters was detected up to the 28th day of treatment.
Pharmacokinetic behaviour in polymorphonuclear leucocytes of N,N-dimethylcarbamoylmethyl α,2-dimethyl-5H-[1]benzopyrano[2,3-b]-pyridine-7-acetate (Y-23023), a new prodrug type of antiinflammatory agent, and indomethacin after oral administrations in rats
Authors: Yamada Ichimaro , Nagamatsu Yuko , Imayoshi Tomonori , Shibata Masahiro , Tsuji Akira 
Published: April 2011

Abstract
N,N-Dimethylcarbamoylmethyl α,2-dimethyl-5H-[1]-benzopyrano[2,3-b]pyridine-7-acetate (Y-23023) is a prodrug developed as a new non-steroidal anti-inflammatory drug (NSAID). Y-23023 is rapidly hydrolysed to an active metabolite, α,2-dimethyl-5H-[1]benzopyrano[2,3-b]pyridine-7-acetic acid (M1) following its absorption and then exhibits a strong anti-inflammatory activity. We have examined the pharmacokinetic behaviour in polymorphonuclear leucocytes (PMNs) of M1 and of indomethacin after oral administration to rats of Y-23023 and indomethacin, respectively. Y-23023 was rapidly absorbed, producing a mean Cmax (1·13 μg mL−1) of M1 after 1 h in plasma. Indomethacin was less rapidly absorbed, producing a mean Cmax (3·38 μg mL−1) after 3 h in plasma. The mean AUC of M1 and indomethacin in plasma were 5·45 μg h mL−1 and 22·49 μg h mL−1, respectively. The mean tmax, Cmax and AUC of M1 in PMNs were 1 h, 11·1 ng (41 pmol)/108 cells and 58·6 ng (164 pmol) h/108 cells, respectively. The same parameters for indomethacin in the PMNs were 3 h, 15·4 ng (57 pmol)/108 cells and 95·2 ng (266 pmol) h/108 cells, respectively. The PMNs/plasma ratio of M1 was about 2·8 times that of indomethacin. These results indicate that the association of M1, an active metabolite of Y-23023, from blood to the PMNs is greater than that of indomethacin.
The Influence of Cosolvents on the In-vitro Percutaneous Penetration of Diclofenac Sodium From a Gel System
Authors: Ho Hsiu-O , Huang Feng-Chin , Sokoloski Theodore D , Sheu Ming-Thau 
Published: April 2011

Abstract
The influence of cosolvents on the in-vitro percutaneous penetration of diclofenac sodium from a gel system was studied using a simplex lattice experimental design. Gel formulations were prepared by gelling the vehicle mixture of water, alcohol and propylene glycol with Carbomer 940. The synthetic membrane Durapore and hairless mouse skin were employed as barriers in a Franz-type diffusion cell. It was found that the penetration through the synthetic membrane was well described by the Higuchi model. There existed a better inverse relationship between the penetration rate and the drug solubility in the respective vehicle. It appeared to be a membrane-controlled mechanism when using hairless mouse skin as the barrier. The penetration rates in steady-state for nine formulations were fitted to a polynomial equation based on this simplex lattice method. A three-dimensional plot was constructed in this simplex surface studied. The maximal penetration rate was found to be from the vehicle containing water and ethanol in an exact volume ratio of 3:1 and the minimal penetration rate was observed from the vehicle containing water only.
Nasal Absorption of Desmopressin in Rats and Sheep. Effect of a Bioadhesive Microsphere Delivery System
Authors: Critchley H , Davis S S , Farraj N F , Illum L 
Published: April 2011

Abstract
The nasal absorption of desmopressin was studied in two animal models, the rat and the sheep. The bioavailability after nasal administration was found to be 13 times higher in the rat model. This discrepancy is suggested to be due to the impaired mucociliary clearance mechanism in the rat model and possibly differences in enzymatic degradation and elimination rates of the drug. The effect of the addition of L-α-lysophosphatidylcholine (LPC) to the formulations as an absorption enhancer was most pronounced in the sheep model. The use of the bioadhesive starch microsphere delivery system, especially in combination with LPC, had a profound effect on the absorption of desmopressin in sheep, with bioavailabilities reaching nearly 10% compared with 1·2% for a simple nasal solution of desmopressin.
Constipation Evoked by 5-HT3-Receptor Antagonism: Evidence for Heterogeneous Efficacy among Different Antagonists in Guinea-pigs
Authors: Sanger G J , Wardle K A 
Published: April 2011

Abstract
The abilities of selective 5-HT3-receptor antagonists to evoke constipation were examined in conscious guinea-pigs and in preparations of guinea-pig isolated colon. Compared with vehicle-treated guinea-pigs, acute doses of granisetron (0·1, 1 and 10 mg kg−1, i.p.) and tropisetron (10 mg kg−1, i.p., but not 1 and 0.1 mg kg−1, i.p.) significantly (P &lt; 0·05) reduced the total number of faecal pellets excreted during a 12-h observation period. By contrast, BRL 46470 (0·1–10 mg kg−1, i.p.) had no significant effect on the incidence of defecation. Mid-to-distal lengths of guinea-pig isolated colon spontaneously expelled faecal pellets. Granisetron (0·1 and 1 μm) and tropisetron (1 μm) reduced or prevented the rate at which they were spontaneously expelled. Morphine (0·1 μm) and clonidine (10 nm) also slowed faecal pellet transit time. Naloxone (0·1 μm) had no effects alone, but reversed the actions of granisetron, morphine and clonidine. BRL 46470 (1 μm) had no significant effect on the transit of faecal pellets in guinea-pig isolated colon. In segments of guinea-pig isolated colon which did not contain faecal pellets, granisetron, tropisetron and BRL 46470 antagonized the ability of 5-HT to evoke cholinergically-mediated contractions of the longitudinal muscle. The respective pA2 values and slopes of the Schild plots were 8·5 ± 0·05, slope 1·06 ± 0·03; 8·5 ± 0·1, slope 0·91 ± 0·04; and 7·9 ± 0·1, slope 0·93 ± 0·05. Our experiments suggest that not all 5-HT3-receptor antagonists are the same. In particular, BRL 46470 does not prevent defecation or faecal pellet expulsion in guinea-pig colon, even though this compound is an effective 5-HT3-receptor antagonist in the same tissue. For the 5-HT3-receptor antagonists which did cause constipation, the effects can be at least partly attributed to an indirect opioid-dependent action within the colonic enteric nervous system.
The Release of Macromolecules from Fatty Acid Matrices: Complete Factorial Study of Factors Affecting Release
Authors: Kaewvichit S , Tucker I G 
Published: April 2011

Abstract
A replicated complete factorial design to study the main effects and interactions of four factors: bovine serum albumin (BSA) particle size (Factor A); stearic acid particle size (Factor B); BSA loading (Factor C); and compression force (Factor D), on the release of BSA from compressed stearic acid pellets was performed in isotonic phosphate buffer pH 7·4 at 37°C. Samples were withdrawn over 64 h. Analysis of variance of the percentage released at 64 h showed that A, B, and C., but not D, affected the release and the interactions AB, BC, ABC were highly significant. At low loading (5%), the surface release depended on BSA particle size. The release increased when BSA particle size was large. At high loading (20%), more release was shown when stearic acid particle size was large. More release with increasing BSA particle size occurred only when stearic acid particle size was small. It is proposed that release is due to the interconnected pore networks created, not only by BSA particles, but also by the void space between stearic acid particles. These void spaces vary according to particle size-dependent arrangements of stearic acid and BSA particles. An increase in the pellet thickness was observed probably due to the relaxation of compacted stearic acid particles.
Biodegradable Controlled Antibiotic Release Devices for Osteomyelitis: Optimization of Release Properties
Authors: Zhang Xichen , Wyss Urs P , Pichora David , Goosen Mattheus F A 
Published: April 2011

Abstract
Controlled antibiotic release films, melt-extruded cylinders, and suspension-extruded/coated cylinders were manufactured from biodegradable poly(d, l-lactide) (PDLLA) and poly(d, l-lactide-co-∈-caprolactone). These devices have potential application in the treatment of osteomyelitis. The in-vitro release properties of the devices were examined with drug loadings varying from 16 to 50%. Gentamicin sulphate films and melt-extruded gentamicin/PDLLA cylinders demonstrated a large initial burst and incomplete release. The films and melt-extruded cylinders made from poly(d, l-lactide-co-∈-caprolactone), low mol. wt poly(d, l-lactide), and a mixture of d, l-lactic acid oligomer and high mol. wt poly(d, l-lactide), did not remain intact during the entire release period. While this is undesirable, these materials do have the advantage of not requiring a processing temperature of greater than 110°C. Antibiotic release from high mol. wt PDLLA-coated gentamicin/PDLLA cylinders, with 40 and 50% loading, was very rapid. The antibiotic could only diffuse out through the open ends of the cylinder. Coated gentamicin sulphate cylinders with 20 and 30% drug loading gave the most promising properties in terms of a small initial burst, and a gradual and sustained release. The release rate and duration from the coated cylinders could be adjusted by cutting the cylinder into different lengths; the time required for 90% of the entrapped gentamicin to be released into water from 30% loaded PDLLA-coated cylinders 0·2, 0·4, 0·7 and 1 cm in length was 1000, 1700, 2300, and 2800 h, respectively. This offers a convenient method to adjust the release to meet the specific antibiotic requirement of different patients. Cephazolin and benzylpenicillin were found to be unsuitable for sustained release longer than 300 h due to the hydrolytic instability of the drugs in water.
Effect of caffeine and nicotine on avoidance learning in mice: lack of interaction
Authors: Sansone Mario , Battaglia Mario , Castellano Claudio 
Published: April 2011

Abstract
Tested alone, nicotine (0·25 or 0·5 mg kg−1) improved shuttle-box avoidance learning in mice of the CD-1 strain. Caffeine had no effect at doses of 2·5 and 5 mg kg−1 and impaired performance at a dose of 10 mg kg−1. Combinations of the two drugs did not increase avoidance responses more than nicotine alone, nor was nicotine able to attenuate performance depression induced by the highest dose of caffeine. Lack of drug interaction in the avoidance test contrasts with the occurrence of interactive effects of the two drugs in a locomotor activity test. When given in combination, caffeine and nicotine increased locomotor activity at doses ineffective by themselves. The results seem to indicate no advantage in combining caffeine and nicotine to improve active avoidance learning.
Effect of Preservatives on Systemic Delivery of Insulin by Ocular Instillation in Rabbits
Authors: Sasaki Hitoshi , Tei Choyu , Yamamura Kenzo , Nishida Koyo , Nakamura Junzo 
Published: April 2011

Abstract
The effects of absorption promoters and ophthalmic preservatives on the systemic absorption of insulin through the ocular route were investigated in albino rabbits. Insulin absorption was evaluated by its hypoglycaemic response. Although ocular instillation of insulin alone did not decrease the serum glucose concentration, instillation of insulin with absorption promoters such as EDTA and saponin decreased it. The promoting effect depended on the concentration of the absorption promoters. Of ophthalmic preservatives investigated (benzalkonium chloride, paraben, 2-phenylethanol, benzyl alcohol and sorbic acid), benzal-konium, chloride and paraben showed promoting effects. The promoting effect for benzalkonium chloride was reversible and dependent on concentration of both benzalkonium chloride and insulin in the formulation.
Alterations of In-vitro 5-HT Receptor Pharmacology as a Function of Multiple Treatment with 5-Hydroxytryptamine or 8-Hydroxy-2-(di-N-propylamino) Tetralin in Rat Isolated Aorta, Uterus and Fundus, and Guinea-pig Isolated Trachea
Authors: Helton David R , Colbert Walter E 
Published: April 2011

Abstract
The effects of single and multiple (5, 10, or 15 days) administration of the 5-HT1A agonist 8-hydroxy-2-(di-N-propylamino) tetralin (8-OH-DPAT) (3 mg kg−1, i.p.) or 5-HT (3 mg kg−1, i.p.) in-vivo on the response of selected isolated smooth muscles to 5-HT in-vitro were investigated. Single dosing with 8-OH-DPAT did not alter the responses of the isolated tissues (rat aorta, uterus or fundus, or guinea-pig trachea) to 5-HT, while multiple dosing with 8-OH-DPAT produced rightward shifts and a suppression of the maximum response of all these tissues to 5-HT, with the exception of the rat stomach fundus. Multiple administration of 5-HT had no effect on the in-vitro response of the tissues to 5-HT. These data indicate that multiple administration of 8-OH-DPAT desensitizes or down-regulates the peripheral 5-HT2 receptors found on the rat aorta and uterus, and guinea-pig trachea.
Aescin formation in calli and embryoids from cotyledon and stem explants of Aesculus hippocastanum L.
Authors: Profumo Paola , Caviglia Anna Maria , Gastaldo Paola 
Published: April 2011

Abstract
Aescin in calli and embryoids obtained from both cotyledon and stem explants of Aesculus hippocastanum were investigated by HPLC. Determinations were carried out on tissues cultured in agarized medium supplemented with growth substances (2,4-dichlorophenoxyacetic acid; kinetin; 1-naphthaleneacetic acid). The results indicate that aescin was produced in all the analysed samples. The amount of active principle present in some samples was higher than that found in horse-chestnut seeds.
Further Studies on the Ex-vivo Effects of Procarbazine and Monomethylhydrazine on Rat Semicarbazide-sensitive Amine Oxidase and Monoamine Oxidase Activities
Authors: Holt Andrew , Callingham Brian A 
Published: April 2011

Abstract
Following administration of the anticancer agent, procarbazine, or one of its metabolites, monomethylhydrazine, to rats, activities of monoamine oxidases A and B (MAO A and MAO B) and of semicarbazidesensitive amine oxidase (SSAO) were measured ex-vivo.
Both compounds were found to be potent inhibitors of SSAO in tissue homogenates, exhibiting ID50 values in most tissues of approximately 8 mgkg−1 (procarbazine) and 0.08 mg kg−1 (monomethylhydrazine). Concurrent dose-dependent inhibition of MAO activities did not occur. However, in liver, potentiation of MAO B activity, to 140% of that in controls, was apparent following monomethyl-hydrazine and this effect was independent of the drug dose. Both compounds produced a dose-dependent potentiation of MAO A in brown adipose tissue, the elevation being more pronounced following monomethylhydrazine, with activity rising to 350% of that in control homogenates. In a parallel in-vitro study, monomethylhydrazine was without effect on MAO A in brown adipose tissue homogenates. By perfusing the SSAO substrate, benzylamine, through the isolated mesenteric arterial bed of the rat, it was found that pretreatment of animals with procarbazine or monomethylhydrazine reduced metabolism of this amine by a similar degree as had been determined ex-vivo in blood vessel homogenates.
The results presented suggest that these compounds would be suitable for use as selective inhibitors in pharmacological examinations of SSAO function in isolated tissues and organs.
Analysis of the Mechanisms Underlying the Contractile Response Induced by the Hydroalcoholic Extract of Phyllanthus urinaria in the Guinea-pig Urinary Bladder In-vitro
Authors: Dias Marcos A , Campos Alexandre H , Filho Valdir Cechinel , Yunes Rosendo A , Calixto Joao B 
Published: April 2011

Abstract
The hydroalcoholic extract of Phyllanthus urinaria (Euphorbiaceae), substance P and substance P methyl ester all caused graded contractions in the guinea-pig urinary bladder. Responses to hydroalcoholic extract and substance P were markedly inhibited in calcium-free Krebs solution, this effect being reversed by reintroduction of calcium in the medium.
The contraction in response to hydroalcoholic extract was unaffected by atropine, propranolol, prazosin, yohimbine, tetrodotoxin, w-conotoxin, nicardipine, HOE 140, guanethidine, staurosporine, phorbol ester or indomethacin, excluding the involvement of nervous mediated responses, or action via cholinergic, adrenergic, kinins, cyclo-oxygenase metabolites, protein kinase C or activation of L or N-type calcium channels. The selective NK1 tachykinin antagonist (FK 888), but not NK2 (SR 48968) antagonized substance P-induced contraction, but both drugs failed to effect Phyllanthus urinaria-induced contraction. Prolonged desensitization of guinea pig urinary bladder with capsaicin (10 μM) or preincubation of guinea-pig urinary bladder with capsazepine did not affect contraction caused by hydroalcoholic extract. Ruthenium red almost completely abolished capsaicin-induced contraction, but had no effect on hydroalcoholic extract-mediated contraction. Substance P and the hydroalcoholic extract caused marked potentiation of the twitch response in the preparations field stimulated. The facilitatory effect of substance P, but not that of hydroalcoholic extract, was prevented by the NK1 (FK 888), but not by NK2 (SR 48968) antagonist.
We concluded that contraction induced by hydroalcoholic extract of Phyllanthus urinaria in the guinea pig urinary bladder involves direct action on smooth muscle and relies on the mobilization of extracellular calcium influx unrelated to activation of L- and N-type calcium channels or activation of protein kinase C mechanisms. In addition contraction caused by the hydroalcoholic extract of Phyllanthus urinaria in guinea-pig urinary bladder does not involve the activation of tachykinin or vanilloid receptors.