bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effect of Perfusion Flow Rate on the Tissue Uptake of Solutes After Dermal Application Using the Rat Isolated Perfused Hindlimb Preparation
Authors: Cross Sheree E , Wu Zhenyu , Roberts Michael S 
Published: April 2011

Abstract
The rat perfused hindlimb preparation was investigated as a model to study the dermal clearance and tissue distribution of three solutes with differing physicochemical properties ([3H]water, [3H]diazepam, and [14C]lignocaine). The dermal clearance of each solute increased and the depth of tissue preparation decreased with increasing perfusion flow rate. The half-life for solute efflux from tissues into perfusate, and the peak times for amount of solute in tissue were in the order water &gt; lignocaine &gt; diazepam. Topical iontophoresis, which has previously been shown to achieve similar clearances from topical sites to those seen following passive dermal application, resulted in a clearance of lignocaine in the perfused hindlimb comparable with that obtained in the preparation following passive absorption through exposed dermis. The distribution of capillary blood flow in the perfused hindlimb was quantified using 51Cr-labelled 15-μm microspheres, with greater increases in flow found in deeper muscle tissues with increasing perfusion flow rate compared with superficial layers. Microsphere studies in anaesthetized rats also demonstrate slight differences in the distribution of flow within the hindlimb compared with the perfused preparation. We conclude that the rat perfused hindlimb preparation successfully combines many of the advantages of in-vitro and in-vivo methods and has potential for routine use in the study of solute dermal absorption kinetics.
A Stable and Highly Potent Hexamethonium Derivative Which Modulates Muscarinic Receptors Allosterically in Guinea-pig Hearts
Authors: Bejeuhr G , Blaschke G , Holzgrabe U , Mohr K , Sürig U , Terfloth G 
Published: April 2011

Abstract
W84 (N, N,N′,N′-tetramethyl-N,N′-bis-(3-phthalimidopropyl)-N,N′-hexane-1,6-diyl-bis-ammomum dibromide) is a potent stabilizer of antagonist binding to muscarinic receptors; however, W84 hydrolyses in aqueous buffered medium. The synthesis of the stable derivative CHIN3/6 is presented containing a 2-phenyl-quinazolinone instead of the labile phthalimide substituent. This compound retarded [3H]N-methylscopolamine-dissociation in guinea-pig cardiac membranes with slightly higher potency than W84, the EC50 values amounting to 7·5 × 10−7and 13× 10−7 m, respectively. Molecular modelling revealed differences in the electron density of the substituents and in their molecular shape. It is suggested that the derivatives use partially different sites of attachment when occupying the allosteric binding site of the receptor protein.
Intestinal bacterial hydrolysis is indispensable to absorption of 18β-glycyrrhetic acid after oral administration of glycyrrhizin in rats
Authors: Akao Teruaki , Hayashi Tomoko , Kobashi Kyoichi , Kanaoka Matao , Kato Hiromi , Kobayashi Masashi , Takeda Shuichi , Oyama Tsutomu 
Published: April 2011

Abstract
Gnotobiote rats were prepared by infecting germ-free rats with Eubaclerium sp. strain GLH, a human intestinal bacterium capable of hydrolysing glycyrrhizin to 18β-glycyrrhetic acid. Their faeces and caecal contents showed glycyrrhizin-hydrolysing activities (31·7 and 31·3 pmol min−1 (mg protein)−1, respectively) similar to those (81·0 and 39·9 pmol min−1 (mg protein)−1, respectively) of conventional rats, although there was no detectable activity in germ-free rats. When glycyrrhizin (100 mg kg−1) was orally administered to conventional, germ-free and gnotobiote rats, no glycyrrhizin could be detected in plasma 4 or 17 h after the administration, using EIA and HPLC assays. Plasma 18β-glycyrrhetic acid was not detected 4 or 17 h after the administration of glycyrrhizin to germ-free rats nor could this compound be detected in caecal contents or in the faeces. However, 18β-glycyrrhetic acid (0·6–2·6 nmol mL−1) was detected in plasma of the conventional and the gnotobiote rats 4 and 17 h after the administration, and the caecal contents after 4 h and the cumulative faeces up to 17 h of the conventional and the gnotobiote rats contained considerable amounts of 18β-glycyrrhetic acid. These findings indicate that orally administered glycyrrhizin is poorly absorbed from the gut, but is hydrolysed to 18β-glycyrrhetic acid by intestinal bacteria such as E. sp. strain GLH, and the resulting 18β-glycyrrhetic acid is absorbed.
Interactions of opioids with caffeine: evaluation by ambulatory activity in mice
Authors: Kuribara Hisashi , Uchihashi Yoshitaka 
Published: April 2011

Abstract
Morphine (up to 10 mg kg−1), buprenorphine (up to 0·1 mg kg−1), pentazocine (30 mg kg−1) and caffeine (up to 10 mg kg−1), significantly increased mouse ambulation. The combination of morphine, buprenorphine and pentazocine with caffeine generally enhanced the effect. Dopamine D1- and D2-receptor bockade, depletion of stored dopamine, and inhibition of dopamine synthesis could reduce the ambulation increased by single administration of morphine, buprenorphine and caffeine, and by combined administration of morphine and buprenorphine with caffeine. Although naloxone (0·1–3 mg kg−1) itself did not change mouse ambulation, at 3 mg kg−1, it reduced the effect of caffeine. The repeated administration of morphine (10 mg kg−1) induced a sensitization to the ambulation-increasing effect, and was inhibited by the combination of caffeine (10 mg kg−1) in the repeated administration schedule. The repeated administration of caffeine (10 mg kg−1) with buprenorphine (0·3 mg kg−1) resulted in a decrease in the effect to the level of caffeine alone. The development of cross-sensitization to morphine (10 mg kg−1) by the repeated treatment with buprenorphine (0·3 mg kg−1) was inhibited by caffeine (10 mg kg−1). Our results suggest that the dopaminergic systems are involved in the enhanced interaction of opioids having agonistic action on μ- or σ-receptors with caffeine. However, it is also considered that, following the repeated administration, caffeine acts to reduce the sensitivity to the ambulation-increasing effect of opioids, probably inducing up-regulation of adenosinergic systems.
Effects of hypolipidaemics cetaben and clofibrate on mitochondrial and peroxisomal enzymes of rat liver
Authors: Schön Hans J , Grgurin Mario , Klune Gerhard , Prager Christiane , Marz Richard , Legenstein Elisabeth , Böck Peter , Kramar Robert 
Published: April 2011

Abstract
Clofibrate or cetaben was administered to male rats for 10 days. Peroxisomal and mitochondrial enzymes were assayed in liver subcellular fractions. Clofibrate affected the specific activities of both mitochondrial enzymes (glycerol-3-phosphate dehydrogenase and nicotinamide-linked isocitrate dehydrogenase) and peroxisomal enzymes (fatty acyl-CoA oxidase, glycerone phosphate acyltransferase, urate oxidase, and D-amino-acid oxidase). In contrast, cetaben raised only the peroxisomal enzymes, acyl-CoA oxidase, glyceronephosphate acyltransferase, D-amino-acid oxidase, catalase, and urate oxidase. Thus, the hypolipidaemic activity of these drugs may be. exclusively related to stimulated peroxisomal functioning, while mitochondria play only a minor role.
Aluminium β-Cyclodextrin Sulphate as a Stabilizer and Sustained-release Carrier for Basic Fibroblast Growth Factor
Authors: Fukunaga Kazuhiro , Hijikata Shigeki , Ishimura Kimihiro , Sonoda Ryouichi , Irie Tetsumi , Uekama Kaneto 
Published: April 2011

Abstract
The water-insoluble aluminium salt of β-cyclodextrin sulphate (Al · β-CyD-Sul) was used as a stabilizer and sustained-release carrier for recombinant human basic fibroblast growth factor (bFGF). An adsorbate of bFGF with Al · β-CyD-Sul was prepared by incubating the protein with a suspension of Al · β-CyD-Sul in water. The mitogenic activity of bFGF released from the adsorbate, as indicated by the proliferation of kidney cells of baby hamster (BHK-21), was almost comparable with that of the intact bFGF. Al-β-CyD-Sul significantly protected bFGF from proteolytic degradation by pepsin and α-chymotrypsin, compared with the water-soluble sodium salt. The in-vitro release of bFGF from the adsorbate was sustained in proportion to a rise in the ratio of Al · β-CyD-Sul to the protein in the adsorbate. Of the bFGF preparations evaluated, the adsorbate of bFGF with Al ·β-CyD-Sul, when given subcutaneously to the rat, showed the most prominent increase in the formation of granulation tissues, due to the stabilization and slow-release of the mitogen. The limited data presented here suggest that the adsorbate of bFGF with Al · β-CyD-Sul has a potent therapeutic efficacy for wound healing, and may be applicable to oral protein formulations for the treatment of intestinal mucosal erosions.
The Aggregation of Bovine Serum Albumin in Solution and in the Solid State
Authors: Jordan Geraldine M , Yoshioka Sumie , Terao Tadao 
Published: April 2011

Abstract
The aggregation of bovine serum albumin (BSA) in the solid state and in solution was studied to elucidate the effect of water mobility on the aggregation rate and mechanism. The results suggest that the freeze-dried BSA forms covalently-bonded aggregates via disulphide bonding during storage in the moistened solid state and in solution. The aggregation rate largely depended on the water content. The freeze-dried BSA to which a small amount of water was added (in the moistened state) was found to be more liable to aggregation than that in solution. The aggregation rate in the moistened solid state exhibited a maximum at a very low level of moisture. In contrast, the aggregation rate in solution increased with increasing ratio of water to protein (with decreasing protein concentration). The results suggest that the increased rate is related to the increase in water mobility, as measured by the spin-lattice relaxation time, T1, of water using 17O NMR, with increasing ratio of water to protein.
In-vitro Interaction between H2 Antagonists and Vecuronium
Authors: Mishra Y , Torda T , Ramzan I , Graham G 
Published: April 2011

Abstract
The interaction between histamine H2 antagonists and the neuromuscular blocking drug vecuronium was investigated in the rat phrenic nerve-hemidiaphragm preparation. Cimetidine alone, in the concentration range 800–4000 μm produced between 14 and 74% neuromuscular paralysis with an EC50 (mean ± s.e.) of 2900 ± 100 μm. Ranitidine augmented the indirectly-evoked muscle response at concentrations between 30 and 160 μm but at higher concentrations, between 300 and 1800 μm, produced neuromuscular paralysis. Famotidine produced negligible and statistically insignificant (0–5%) neuromuscular paralysis at concentrations between 0·3 and 300 μm. Cimetidine (800 μm) shifted the neuromuscular concentration-effect curve of vecuronium to the left in a parallel manner, while ranitidine (160 μm) shifted it to the right. The potentiation ratio was 1·90 ± 0·14 for cimetidine and 0·62 ± 005 for ranitidine. Famotidine (30 μm) did not alter the response to vecuronium. These data indicate that higher than clinically relevant concentrations of cimetidine and ranitidine produce neuromuscular paralysis and may potentiate the action of vecuronium. Low concentrations of ranitidine may antagonize the action of vecuronium. Famotidine, in contrast, lacks significant neuromuscular effects.
The Disposition of Thioperamide, a Histamine H3-Receptor Antagonist, in Rats
Authors: Sakurai Eiichi , Gunji Eri , Iizuka Yukisumi , Hikichi Noboru , Maeyama Kazutaka , Watanabe Takehiko 
Published: April 2011

Abstract
An HPLC method using an ovomucoid-conjugated column has been developed for measurement of thioperamide, a histamine H3 antagonist, with a minimum quantitation limit of 0·05 μg mL−1 The assay was used to study the disposition of thioperamide in rats. After bolus intravenous administration of thioperamide (10 mg kg−1), the plasma concentration decreased monoexponentially with a half-life of 26·9 min. The apparent total body clearance of thioperamide from rat plasma was 74·6 mL min−1 kg−1. Although thioperamide was quickly transferred to various tissues, its concentrations in peripheral tissues were higher than that in the brain. However, the brain regional tissue/plasma ratios of thioperamide increased continuously after its injection.
Adaptogenic and Cardioprotective Action of Galleria mellonella Extract in Rats and Frogs
Authors: Rachkov A K , Spiridonov N A , Kondrashova M N 
Published: April 2011

Abstract
Pharmacological and metabolic effects of Galleria mellonella larvae extract used in Russian folk medicine to treat cardiovascular and senile diseases were studied. It was shown that the extract possesses adaptogenic, cardiotropic, cardioprotective, and hypocoagulant properties. The extract possesses low toxicity and does not cause significant changes in biochemical parameters in the blood serum of laboratory animals. Increase in catecholamine content in the heart and aortic tissues and their decrease in adrenal glands are unfavourable effects of high doses of the extract.
Enzymatic Hydrolysis of Zenarestat 1-O-Acylglucuronide
Authors: Tanaka Yoshio , Suzuki Akira 
Published: April 2011

Abstract
Zenarestat, (3-(4-bromo-2-fluorobenzyl)-7-chloro-2,4-dioxo-1,2,3,4-tetrahydroquinazolin-1-y1) acetic acid, an aldose reductase inhibitor is metabolized mainly to the glucuronide in rat and man. The glucuronide was purified from urine of volunteers after ingestion of zenarestat. The structure of the glucuronide was confirmed by LC-MS and NMR as 1-O-acyl-β-glucuronide. This compound was unstable at physiological pH, being converted to its structural isomers and the aglycone with half-life of 25 min at pH 7·4 and 37°C in aqueous solution. Enzymatic hydrolysis of the glucuronide was studied in urine, blood and tissues. β-Glucuronidase in human urine contributed little to the hydrolysis of the glucuronide, while in rat urine at pH 6, it was degraded by β-glucuronidase and the formation of zenarestat was clearly faster than its formation in buffer at pH 6. In both rat and human blood, these reactions were accelerated by albumin, although rat red blood cells may also contribute. The rate of degradation was not affected by red blood cell membrane, haemoglobin, globulin, esterases or β-glucuronidase. Arylesterase in rat liver, arylesterase and acetylcholinesterase in the kidney, and β-glucuronidase in both tissues may contribute. Thus, enzymatic degradation of zenarestat 1-O-acyl-β-glucuronide is dependent not only on pH and temperature but also on species and the type of tissue or body fluid.
Purine- and Nucleotide-mediated Relaxation of Rabbit Thoracic Aorta: Common and Different Sites of Action
Authors: Chinellato A , Ragazzi E , Pandolfo L , Froldi G , Caparrotta L , Fassina G 
Published: April 2011

Abstract
The mechanisms of the relaxant effect of purines and pyrimidines in New Zealand rabbit isolated aorta were investigated at endothelial and smooth muscle cell levels. Endothelium-mediated relaxation by ATP was only partially inhibited by the P2-purinoceptor antagonist suramin (0·1 Mm). The pyrimidine UTP produced vasodilation by acting at the endothelial level and relaxation was not antagonized by suramin (0·1 Mm). This effect was not mediated by P2 purinoceptors, indicating that UTP, like ATP to a certain extent, produces relaxation via an endothelium nucleotide (N) pyrimidinoceptor. ATP, ADP, AMP, adenosine, 5′-N-ethylcarboxamidoadenosine (NECA) and inosine were all active as relaxants on smooth muscle. The NECA relaxant effect was not antagonized by P1-purinoceptor antagonists 3,7-dimethyl-1-propargylxanthine (50 μm) or 1,3-dipropyl-8-(2-amino-4-chlorophenyl)xanthine (5 μm), excluding a P1-mediated effect. P2-related activity was excluded because adenosine-mediated relaxation was not antagonized by suramin (0·1 Mm). UTP was ineffective as a relaxant at smooth muscle level, thus excluding the presence of muscular nucleotide (N) pyrimidinoceptor and suggesting a P3 purinoceptor. The rank order of potency of this muscle purinoceptor was NECA &gt; adenosine &gt; ATP ≅ ADP ≅ AMP ≅ inosine.
Disposition of Nifurtimox and Metabolite Activity Against Trypanosoma cruzi using Rat Isolated Perfused Liver
Authors: González-Martin Guillermo , Paulos Claudío , Guevara Alfredo , Ponce Graciela 
Published: April 2011

Abstract
Nifurtimox disposition was investigated using the rat isolated perfused-liver method after administration of 25 μg mL−1 nifurtimox, and its disappearance was monitored by analysing the perfusate sample at various times. Biliary excretion was also measured. The drug concentration profile underwent a biexponential decline over the 2-h study period, with a terminal half-life of 62·76 ± 17·56 min. Nifurtimox is a high clearance compound (15·23±5·53 mL min−1). The extraction ratio was 0·621 ±0·159. Biliary excretion accounted for 0·05% of the dose, the remainder consisting of highly polar metabolites. By 2 h, a minimal fraction of unchanged nifurtimox was recovered from the perfusate. Nifurtimox activity against Trypanosoma cruzi (clone CA-1) during the perfusion was also determined. Epimastigotes isolated from continuous culture were exposed to the samples of perfusate at different perfusion times in a microtitre plate. After an incubation time of 72 h at 27°C, the parasite number in each well was counted under a microscope. From 0 to 75 min after the perfusion, the anti-trypanosomal activity decreased, but an increase in activity was observed at the later times. These findings show that active metabolites are formed during the perfusion.
Direct drug transport from the rat nasal cavity to the cerebrospinal fluid: the relation to the dissociation of the drug
Authors: Sakane Toshiyasu , Akizuki Motohiro , Yamashita Shinji , Sezaki Hitoshi , Nadai Tanekazu 
Published: April 2011

Abstract
We aimed to clarify the relationship between drug dissociation (sulphisomidine) and its direct transport from the nasal cavity to the cerebrospinal fluid (CSF). Rat nasal cavities were perfused in a single pass system with buffers (pH 5·5, 6·5, 7·4, 8·7 and 9·4). Plasma and CSF were collected and the concentration of sulphisomidine was measured. Nasal clearance increased with the increase in the un-ionized fraction of the drug. The ratio of the drug concentration in CSF to that in the nasal perfusion fluid (the index of the degree of the drug transport from the nasal cavity to CSF), was changed in accordance with the un-ionized fraction of drug. These results show that both the nasal absorption and the drug transport conform to the pH partition theory.
Vasorelaxing effect in rat thoracic aorta caused by laurotetanine isolated from Litsea cubeba Persoon
Authors: Chen Wen-Ying , Ko Feng-Nien , Wu Yang-Chang , Lu Sheng-Teh , Teng Che-Ming 
Published: April 2011

Abstract
The pharmacological effects of laurotetanine on rat isolated thoracic aorta were examined. The contraction of aortic rings caused by high potassium (60 Mm) and cumulative concentrations of calcium (0†03–3 Mm) was inhibited by 3–50 μm laurotetanine in a dose-dependent manner with an IC50 value of 19·8 ± 3·6 μm (n = 6) in a 1 Mm Ca2+ medium. The phenylephrine (3 μm)-induced contraction was also inhibited by laurotetanine. Its effect was more marked on the tonic contraction than on the phasic contraction and was not easily washed-out. On addition of laurotetanine during the tonic contraction, relaxation could also be observed. This relaxing effect was not antagonized by indomethacin (20 μm) and was still seen in denuded aorta or in the presence of nifedipine (1 μm). The caffeine (20 Mm)-induced contraction was not affected by laurotetanine. cAMP and cGMP levels of aorta were not changed by laurotetanine. It is concluded that laurotetanine relaxed the rat thoracic aorta mainly by suppressing the Ca2+ influx through both voltage- and receptor-operated calcium channels.
Effects of epidermal growth factor dosage forms on dermal wound strength in mice
Authors: Çelebi N , Erden N , Gönül B , Koz M 
Published: April 2011

Abstract
The effect of topically administered epidermal growth factor (EGF) dosage forms was investigated on skin wound healing in mice. Two EGF dosage forms were prepared containing 100 ng mL−1 EGF. The solution dosage form was prepared in 0·9% w/v NaCl. A bioadhesive gel form was prepared in 0·2% Carbopol 940 polymer. The two dosage forms were applied on the skin incision wounds of mice at the rate of 5 μL twice a day for 7 and 15 days. The wound tear strength was tested for skin wound healing at the 7th and 15th days of treatment and compared with controls. The results indicate that the wound tear strength of mice were significantly higher at the 15th day of treatment in the gel-treated group compared with the solution-treated mice and controls (P &lt; 0·001).
Modification of the Dissolution Behaviour of a Water-insoluble Drug, Naftazone, for Zero-order Release Matrix Preparation
Authors: Giunchedi Paolo , Maggi Lauretta , La Manna Aldo , Conte Ubaldo 
Published: April 2011

Abstract
The preparation of hydrophilic matrix tablets able to release naftazone, a water-insoluble drug, into an aqueous medium at a constant rate (zero-order dissolution) is described. Enhancement of dissolution rate of the drug was achieved using cross-linked carmellose sodium, β-cyclodextrin or hydroxypropyl-β-cyclodextrin. Hypromellose was used as a water-gelling polymer. Tablets could be prepared that released naftazone at a constant rate over 16 h.
Plasma Levels of Peptide YY Correlate with Cisplatin-induced Emesis in Dogs
Authors: Perry Marc R , Rhee John , Smith William L 
Published: April 2011

Abstract
The effect of cisplatin on plasma peptide YY (PYY) and 5-hydroxytryptamine (5-HT) concentrations was determined in conscious dogs (n = 6 per group) pretreated with either saline, or the 5-HT3-receptor antagonists ondansetron or granisetron. Cisplatin (30 mg kg−1, i.v.) caused emesis (18·8 ± 2·9 episodes; 75–284 min) and significantly increased the mean area under the curve (AUC) over a 6-h period of plasma PYY concentrations (7·4 ± 1·8 to 11·5 ± 3·7 ng) in all saline-pretreated dogs, whereas the mean AUC of plasma 5-HT concentrations did not significantly increase (34·7 ± 7·4 vs 35·6 ± 12·3 pM h). The concentrations of PYY correlated closely with the incidence of emesis (r = 0·99). In animals pretreated (36 min) with ondansetron (0·316 mg kg−1, i.v.) or granisetron (0·316 mg kg−1, i.v.), the number of cisplatin-induced emetic episodes was significantly (P &lt; 0·005) decreased compared with control. In animals receiving cisplatin and pretreated with ondansetron, PYY concentrations were not significantly altered, whereas the mean AUC of plasma concentrations of 5-HT over 6 h increased (35·6 ± 12·3 to 82·3 ± 34·6 Pm h; P &lt; 0·05). In animals receiving cisplatin and pretreated with granisetron, plasma concentrations of 5-HT were not significantly altered, whereas the mean AUC of plasma PYY concentrations were significantly reduced compared with control (6·2 ± 1·7 vs 11·5 ± 3·7 ng h). Furthermore, in animals receiving ondansetron without cisplatin treatment, there was no change in the mean AUC of 5-HT or PYY concentrations, whereas the mean AUC of plasma 5-HT concentrations increased significantly (34·7 ± 7·4 to 68·6 ± 37·2 Pm h; P &lt; 0·05) in animals treated with granisetron alone. These studies indicate that plasma concentrations of PYY, and not 5-HT, correlate with cisplatin-induced emesis in dogs. Peptide YY may be an important mediator in cancer chemotherapy-induced emesis and other types of emesis.