bluuebunny/crossref_metadata_2025_split huggingface dataset:
Digoxin-specific Fab fragments impair renal function in the rabbit
Authors: Timsina M P , Hewick D S 
Published: April 2011

Abstract
A 2 mg kg−1 intravenous bolus dose of digoxin-specific Fab fragments produced a 28% reduction in creatinine clearance in rabbits after 24 h. Urine output was reduced, while plasma and urinary creatinine concentrations were unaffected and increased, respectively. By 5 days the creatinine clearance had returned to normal. The fractional excretion of Na+ was nearly halved, indicating that the tubular reabsorption of Na+ increased to compensate for the reduced glomerular filtration rate, suggesting that tubular (as opposed to glomerular) function was not impaired.
Effect of Cromakalim on the Smooth Muscle of the Cat Gastric Antrum
Authors: Kortezova N , Bayguinov O , Boev K , Papasova M 
Published: April 2011

Abstract
The effect of the K+-channel opener cromakalim (BRL 34915) on the electrical and contractile activity of the smooth muscle of the cat gastric antrum has been studied. Cromakalim induced a concentration-dependent inhibition of the contractions and shortening of the sustained partial repolarization phase of the plateau action potential. High concentrations of cromakalim produced hyperpolarization and shortening of the repolarization and depolarization phases of the plateau action potential. The K+-channel blockers 4-aminopyridine (10−2 m) and tetraethylammonium (10−2 m) decreased the effect of cromakalim on the phasic contractions, while glibenclamide (5 × 10−5 m) completely abolished it. We suggested that the inhibitory effect of cromakalim on the electrical and contractile activity of the gastric antrum smooth muscle is due to the cromakalim-induced increase of the outward K+-current through glibenclamide-dependent K+-channels.
Effect of Fenbufen on the Entry of New Quinolones, Norfloxacin and Ofloxacin, into the Central Nervous System in Rats
Authors: Ichikawa Nobuhiro , Naora Kohji , Hayashibara Masakazu , Katagiri Yoshihiro , Iwamoto Kikuo 
Published: April 2011

Abstract
The entry of two new quinolone antibacterial agents, norfloxacin and ofloxacin, into the central nervous system (CNS) of rats, and the effect of fenbufen on this was investigated. At various times after the administration of a bolus intravenous dose of norfloxacin or ofloxacin (10 mg kg−1) with or without fenbufen (20 mg kg−1), serum and cerebrospinal fluid (CSF) samples and whole brain were collected from the rats and the concentration of norfloxacin or ofloxacin in each sample was determined. Serum concentrations of both quinolones declined biexponentially with time and were significantly elevated by coadministration with fenbufen at the terminal phase. The fractions of these quinolones bound to serum protein were not altered by coadministration with fenbufen. Coadministered fenbufen raised the brain concentrations of both quinolones but did not affect their brain to serum unbound concentration ratios. In contrast, CSF to serum unbound concentration ratios as well as CSF concentrations of norfloxacin and ofloxacin were elevated by coadministration with fenbufen. Apparent diffusional clearances between blood and CSF of norfloxacin and ofloxacin estimated by the physiological model analysis increased by 1·9 and 2·6 times, respectively, after coadministration with fenbufen. These findings suggest that coadministered fenbufen may facilitate the entry of norfloxacin and ofloxacin into the CNS.
Enantioselective Pharmacokinetics of α-Fluoromethylhistidine in Rats and Its Comparison with Histidine
Authors: Sakurai Eiichi , Yamasaki Seiji , Iizuka Yukisumi , Hikichi Noboru , Maeyama Kazutaka , Watanabe Takehiko 
Published: April 2011

Abstract
The enantiomer-specific pharmacokinetics of histidine and its analogue, α-fluoromethylhistidine (FMH), were investigated in rats. After bolus intravenous administration of each enantiomer of histidine or FMH at a dose of 40·3 mg kg−1 as free base equivalents, the plasma concentrations of l-histidine, d-histidine, (S)-FMH and (R)-FMH decreased biexponentially with half-lives of 39·2, 20·8, 32·8 and 25·0 min, respectively, in the elimination phase. Although the concentration of l-histidine in the plasma was lower than that of d-histidine, there was no large difference in plasma concentration-time curves of the enantiomers of FMH. The apparent total clearance of l-histidine from rat plasma was about 4 times that of d-histidine or the enantiomers of FMH. l-Histidine was quickly transferred to the peripheral tissues where the concentrations also decrease biphasically. l-Histidine penetrated more rapidly into the brain than either its d-enantiomer or a compound closely related in structure such as FMH. However, the disappearance of l-histidine from the various brain regions was very rapid. In contrast, brain/plasma ratios of d-histidine and (S)-FMH increased continuously after injection of these compounds, indicating that d-histidine or (S)-FMH partitioned into the brain and was very slowly removed from the brain; (R)-FMH was not distributed to the brain. These results suggested stereoselectivity in disposition of histidine and FMH enantiomers in rats.
Selective Inhibition of Calcium Entry Induced by Benzylisoquinolines in Rat Smooth Muscle
Authors: Anselmi Elsa , Fayos Gloria , Blasco Rafael , Candenas Luz , Cortes Diego , D'Ocon Pilar 
Published: April 2011

Abstract
The mechanism of relaxant activity of six benzylisoquinolines was examined in order to determine the minimal structural requirements that enable these compounds to have either a non-specific action like papaverine or an inhibitory activity on calcium entry via potential-operated channels. All the alkaloids tested totally or partially relaxed KCl-depolarized rat uterus and inhibited oxytocin-induced rhythmic contractions. Only glaucine and laudanosine inhibited K+-induced uterine contractions more than oxytocin-induced uterine contractions. In Ca+-free medium, sustained contractions induced by oxytocin or vanadate were relaxed by the alkaloids tested except for glaucine and laudanosine indicating no inhibitory effect on intracellular calcium release. Those alkaloids containing an unsaturated heterocyclic ring (papaverine, papaverinol, papaveraldine, N-methylpapaverine and dehydropapaverine) exhibited a more specific activity than those with a tetrahydroisoquinoline ring.
Postoperative course of plasma protein binding of lignocaine, ropivacaine and bupivacaine in sheep
Authors: Rutten Albert J , Mather Laurence E , Plummer John L , Henning Elke C 
Published: April 2011

Abstract
The plasma protein binding of the 2,6-xylidide local anaesthetic agents lignocaine, ropivacaine and bupivacaine enantiomers was determined by equilibrium dialysis in plasma obtained from chronically catheterized sheep before and up to 21 days after surgery. Three concentrations (1, 5 and 10 mg L−1), were used for each agent. Concentration-dependent binding was evident for each agent throughout the study period. R(+)-Bupivacaine was more extensively bound than S(–)-bupivacaine at the higher concentrations. Compared with pre-surgery, binding of each agent was less on the first postoperative day but did not differ significantly from days 8 to 21.
The cytoprotective effect of zinc l-carnosine on ethanol-induced gastric gland damage in rabbits
Authors: Cho C H , Hui W M , Chen B W , Luk C T , Lam S K 
Published: April 2011

Abstract
The effects of zinc l-carnosine on the damaging actions of ethanol were examined in rabbit isolated gastric glands. Ethanol (8%, v/v) incubation produced a 50% viability of the gland populations and released a significant amount (38%) of the total lactate dehydrogenase (an index of membrane injury) of the glands. Zinc l-carnosine pre-incubation for 15 min markedly prevented these actions of ethanol; however, l-carnosine by itself did not have these effects. These findings indicate that zinc ion but not carnosine in the zinc l-carnosine molecule possesses cytoprotective action against ethanol-induced gastric gland damage in rabbits.
Effects of the Mucoadhesive Polymer Polycarbophil on the Intestinal Absorption of a Peptide Drug in the Rat
Authors: Lehr Claus-Michael , Bouwstra Joke A , Kok Wouter , De Boer Albertus G , Tukker Joseph J , Verhoef J Coos , Breimer Douwe D , Junginger Hans E 
Published: April 2011

Abstract
The absorption across rat intestinal tissue of the model peptide drug 9-desglycinamide, 8-arginine vasopressin from bioadhesive formulations was studied in-vitro, in a chronically isolated internal loop in-situ and after intraduodenal administration in-vivo. A controlled-release bioadhesive drug delivery system was tested, consisting of microspheres of poly(2-hydroxyethyl methacrylate) with a mucoadhesive Polycarbophil-coating, as well as a fast-release formulation consisting of an aqueous solution of the peptide in a suspension of Polycarbophil particles. Using the controlled-release system, a slight improvement of peptide absorption was found in-vitro in comparison with a non-adhesive control system, but not in-situ or in-vivo. In contrast, bioavailability was significantly increased in all three models from the Polycarbophil suspension in comparison with a solution of the drug in saline. The effect appeared to be dose-dependent, indicative of intrinsic penetration-enhancing properties of the mucoadhesive polymer. A prolongation of the absorption phase in-vitro and in the chronically isolated loop in-situ suggested that the polymer was able to protect the peptide from proteolytic degradation. This could be confirmed by degradation studies in-vitro. The duration of the penetration enhancing/enzyme inhibiting effect was diminished with increasing complexity of the test model, in the same way as was previously found for the bioadhesive effect. This interrelationship suggests that the observed improvement in peptide absorption and the mucoadhesive properties of this polymer are associated. The development of a fast-release oral dosage form for peptide drugs on the basis of Polycarbophil appears to be possible.
In-vitro Evaluation of 5-Lipoxygenase and Cyclo-oxygenase Inhibitors using Bovine Neutrophils and Platelets and HPLC
Authors: Dannhardt Gerd , Lehr Matthias 
Published: April 2011

Abstract
Inhibition of 5-lipoxygenase has been determined by monitoring the formation of leukotriene B4 and 5-hydroxyeicosatetraenoic acid in bovine polymorphonuclear leucocytes. For evaluating the inhibition of cyclo-oxygenase two different test systems are presented: the first uses 12-hydroxyheptadecatrienoic acid produced by bovine platelets as an indicator of the cyclo-oxygenase activity; the second test system monitors the prostaglandin E2 formation by bovine platelets. All arachidonic acid metabolites are quantified by reverse-phase HPLC with UV-detection.
A Comparative Study on Desipramine Pharmacokinetics in the Rat Brain after Administration of Desipramine or Imipramine
Authors: Daniel Wladyslawa , Melzacka Miroslawa 
Published: April 2011

Abstract
Chronic intraperitoneal administration of desipramine led to an extensive cumulation of the drug in brain and blood compared with that after a single dose treatment, while chronic treatment with desipramine by the oral route produced a brain concentration comparable with its level after a single oral dose. Comparison of the present results with the corresponding data of published imipramine pharmacokinetics indicated that the cumulation of desipramine in the rat brain was nearly the same when rats received desipramine or imipramine twice a day for two weeks at a dose of 10 mg kg−1 orally, or imipramine, twice a day for two weeks at a dose of 10 mg kg−1 intraperitoneally. It is suggested that these three experimental paradigms may be used as models for differentiation of the pharmacological effects of imipramine and desipramine in-vivo.
Elimination of non-reactive and weakly reactive human α1-acid glycoprotein after induction of the acute phase response in rats
Authors: Parivar Kourosh , Tolentino Lorna , Taylor Glyn , øie Svein 
Published: April 2011

Abstract
The disposition of concanavalin A (Con A)-non-reactive and Con A-reactive human α1-acid glycoprotein (AAG) was studied in normal male rats and in acute phase response-activated male rats. Activation of the acute phase response was made using a subcutaneous administration of ethynyloestradiol in sesame oil. This technique increased the endogenous AAG concentration 7-fold. In control rats the two forms of human AAG showed identical kinetics with an average clearance of 5·4 mL h−1 kg−1, terminal half-life of 13·5 h and a volume of distribution (steady state) of 91 mL kg−1. In the acute phase response-activated animals, both the clearance and volume of distribution were larger: the average clearance of the Con A-non-reactive AAG was 10·2 mL h−1 kg−1, the volume of distribution (steady state) 152 mL kg−1 and the terminal half-life 11·7 h. The Con A-reactive AAG had a clearance of 14·7 mL h−1 kg−1, a volume of distribution (steady state) of 262 mL kg−1 and a half-life of 15·8 h. The results indicate that not only does activation of the acute phase response alter the kinetics of AAG but that the change is different for the different types of AAG.
In-vitro assessment of a matrix system of levobunolol
Authors: Ghosh Tapash K , Gokhale Rajeev D , Chiao Charles S 
Published: April 2011

Abstract
In order to study the feasibility of systemic delivery of levobunolol transdermally, a matrix-type delivery system was fabricated using a silicone elastomer. The relationship between loading dose and skin permeation rate was evaluated in-vitro using hairless mouse skin mounted on the stirred receptor compartment of the Keshary–Chien glass diffusion cell maintained at 37°C. The concentration of levobunolol in the receptor compartment was determined by HPLC. A similar study without using the skin was carried out to determine the effect of loading dose on the release of levobunolol from discs. It was observed that the release of drug from disc followed a matrix-diffusion controlled (Q) vs square root of time relationship at different loading doses. In contrast, the results of skin permeation of levobunolol from transdermal discs containing different loading doses showed a linear Q vs time relationship indicating a constant zero order skin permeation rate at each loading dose. Skin permeation of levobunolol appeared to reach a plateau at a 5% (w/w) loading dose in the disc indicating the attainment of equilibrium concentration of levobunolol in the skin.
Improvement of Large Intestinal Absorption of Insulin by Chemical Modification with Palmitic Acid in Rats
Authors: Hashizume Minoru , Douen Takayuki , Murakami Masahiro , Yamamoto Akira , Takada Kanji , Muranishi Shozo 
Published: April 2011

Abstract
The intestinal absorption of 125I-labelled palmitoyl insulin was examined following administration into in-situ closed large intestinal loops of rats. When mono- and dipalmitoyl insulins (Palins-1 and Palins-2, respectively) were administered in polyoxyethylene hydrogenated castor oil (HCO 60) micellar system into intestinal loops, a marked increase in plasma radioactivity and a corresponding disappearance of residual radioactivity in the intestinal lumen were observed in the following rank order: Palins-2 &gt; Palins-1 &gt; native insulin. In addition, the derivatives were more stable than native insulin in the mucosal tissue homogenates of the large intestine. These results suggest that chemical modification of insulin with palmitic acid may not only increase the lipophilicity of insulin but also reduce its degradation, resulting in the increased transfer of insulin across the large intestinal mucous membrane. The linoleic acid-HCO 60 mixed micelles system did not have a significant effect on the large intestinal absorption of radioactivity associated with the lipophilic insulin analogues.
Interspecies Differences and Scaling for the Pharmacokinetics of Xanthine Derivatives
Authors: Tsunekawa Yoshimi , Hasegawa Takaaki , Nadai Masayuki , Takagi Kenzo , Nabeshima Toshitaka 
Published: April 2011

Abstract
Pharmacokinetic characteristics of the new xanthine bronchodilators, enprofylline and 1-methyl-3-propylxanthine (MPX), were investigated in mice, rats, guinea-pigs, rabbits and dogs. The possibility of an interspecies pharmacokinetic scale was also evaluated. The concentration of these two drugs in plasma and urine was determined by HPLC. Pharmacokinetic parameters were calculated using model-independent methods. The disappearance curves of the two drugs from plasma varied markedly among animal species. Interspecies differences in the plasma protein binding of each drug were observed for all animals in the study. Differences in the biotransformation of enprofylline and MPX were also confirmed among the various animal species: enprofylline is mainly excreted in an unchanged form in urine while MPX follows a non-renal route of elimination. In all animals, the renal clearance for enprofylline was greater than the glomerular filtration rate, indicating active tubular secretion. Significant allometric relationships were seen between the values of total body clearance and steady state volume of distribution for both total and unbound enprofylline and species body weight, but similar correlations could not be recognized for MPX. Renal clearance of enprofylline was also closely correlated with species body weight, suggesting no interspecies difference with relation to affinity and/or capacity for the active tubular secretion mechanism of enprofylline. Our findings suggest that xanthine derivatives, including enprofylline, are mainly eliminated via the kidney, and an estimate of the basic pharmacokinetics in man can be obtained from data in experimental animals.
Atrial natriuretic peptide inhibits the spontaneous contractions of rabbit isolated ileum
Authors: Blandizzi C , Agen C , Natale G , Del Tacca M 
Published: April 2011

Abstract
The present study investigates the effects of atriopeptin II on spontaneous phasic contractions of rabbit isolated ileum. Atriopeptin II caused a significant and concentration-dependent decrease in ileum motor activity. This effect was mimicked by 8-Br-cGMP and it was not affected by pretreatment with tetrodotoxin. Verapamil significantly decreased ileum contractions; however, in the presence of this calcium blocker, atriopeptin II further reduced ileal motility. These findings demonstrate that atriopeptin II depresses the motility of rabbit ileum through a cGMP-dependent mechanism and suggest that neither ileal neural networks nor extracellular calcium are involved in this effect.
Disposition of asarone after intravenous administration to rabbits assessed using HPLC
Authors: Tsai T H , Chen C M , Chen C-F 
Published: April 2011

Abstract
A simple and sensitive high-performance liquid chromatography (HPLC) method for the determination of asarone in rabbit plasma has been developed. Up to 0·1 mL of plasma containing asarone was deproteinated by acetonitrile, which contained an internal standard (indomethacin). The supernatant was injected into a Nucleosil 7C18 column using acetonitrile-water-triethylamine (55:45:0·1 v/v, pH 5·4–5·5, adjusted with orthophosphoric acid) as the mobile phase and UV detection at 257 nm, followed by UV spectrum identification (between 200 and 380 nm) with a photodiode array detector. The method is rapid, easily reproduced, selective and sensitive. It was applied to pharmacokinetic studies of asarone in rabbit, after 5, 10, or 20 mg kg−1 intravenous administration. Rapid distribution followed by a slower elimination phase was observed from the plasma concentration–time curve. The plasma disposition at each dose fitted well to a two-compartment open model and the terminal disposition became much slower as the dose was increased, suggesting a nonlinear dose-dependent plasma asarone disposition.
Transfer of Heparin Across the Human Perfused Placental Lobule
Authors: Bajoria Rekha , Contractor Soli F 
Published: April 2011

Abstract
A system of dual perfusion of an isolated lobule of term human placenta was used as a model to study the transfer of heparin from maternal to foetal circulation. The metabolic viability of the system was assessed by measuring β-HCG and alkaline phosphatase levels in both maternal and foetal perfusates. Creatinine and antipyrine were used as markers to determine juxtaposition of the maternal and foetal circulations. Results of this study indicate that following administration of a single bolus dose of heparin into the maternal circulation, its concentration declined slowly from 99·01 ±2·98 at 15 min to 97·23 ±4·12% and transfer of heparin in the foetal circulation was linear and increased from 0·10% ±0·05% at 15 min to 0·46 ±0·19% over a period of 120 min. The maternal (MAUC) and foetal (FAUC) concentration-time integrals were found to be 70160 ± 1332 and 340 ± 30 int. units min mL−1, respectively. Placental permeability of heparin and creatinine, calculated as the ratio of foetal concentration to the integral maternal–foetal concentration difference, was 8·65 × 10−5 ± 0·80 × 10−5 and 0·033 ±0006 mL min−1 g−1 of perfused placental weight, respectively. These data suggest that heparin was transferred from the maternal to the foetal circulation in small quantities.
Semicarbazide-sensitive Amine Oxidase from the Smooth Muscles of Dog Aorta and Trachea: Activation by the MAO-A Inhibitor Clorgyline
Authors: Yu Peter H , Fang Chiung-Yao , Yang Chuen-Mao 
Published: April 2011

Abstract
Semicarbazide-sensitive amine oxidase (SSAO) has been identified in the dog trachea and aorta smooth muscles. The dog SSAO is blocked by hydrazine inhibitors. SSAOs from several different vascular smooth muscle sources, such as the rat and bovine aorta, and human umbilical artery, as well as the bovine plasma, are insensitive to the MAO-A inhibitor clorgyline; the dog SSAO on the other hand is significantly activated by clorgyline. Two methods, i.e. radioenzymatic and fluoroemetric methods, have been applied to substantiate this clorgyline-induced activation. The activation was detected with respect to the deamination of different substrates, such as benzylamine, β-phenylethylamine and longer carbon chain aliphatic amines, but not with respect to methylamine. The clorgyline effect is reversible, non-competitive and time-independent; it depends on electrostatic and hydrophobic interactions between clorgyline and hydrophobic regions of the dog SSAO enzyme.
Contractile Responses of Chicken Rectum to Stimulation of Remak's Nerve or Purinoceptors: Effect of Suramin
Authors: Bartlet A L 
Published: April 2011

Abstract
Stimulation of Remak's nerve produced a rapid contraction of the rectal muscle which was resistant to blockade by hyoscine, followed by a slow contractile response which was cholinergic. With hyoscine (1 μm) in the Tyrode solution, the non-cholinergic contractile response to nerve stimulation was compared with the responses to adenosine triphosphate (ATP) and α,β-methylene adenosine triphosphate (α,β-Me ATP). In the presence of suramin (300 μm), the contractile response to ATP was increased by about 100%, whereas that to nerve stimulation was inhibited by approximately 17%. Suramin (60 μm) also discriminated between the contractile responses to ATP and nerve stimulation, only the former being potentiated by the drug. It seems probable that suramin potentiated the action of ATP in the rectum through inhibition of ectonucleotidase activity. If so, the potentiation should not extend to α,β-Me ATP, as this analogue of ATP is resistant to inactivation by the enzyme. Suramin inhibited the contractile response to α,β-Me ATP. Thus the neurotransmitter which mediated the hyoscine-resistant contractile response to stimulation of Remak's nerve was dissimilar to ATP, in that it was not potentiated by suramin and presumably was not inactivated by ectonucleotidase activity.