bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Possible Reduction in the Renal Clearance of Ciprofloxacin by Fenbufen in Rats
Authors: Naora Kohji , Katagiri Yoshihiro , Ichikawa Nobuhiro , Hayashibara Masakazu , Iwamoto Kikuo 
Published: April 2011

Abstract
The change in plasma concentration-time profile, serum protein binding and renal and biliary clearances of ciprofloxacin caused by coadministration of fenbufen has been studied in rats administered an intravenous dose of ciprofloxacin (5 mg kg−1) alone or with fenbufen (10 mg kg−1). Coadministered fenbufen significantly prolonged the plasma elimination half-life of ciprofloxacin from 40.5 to 57.6 min and tended to reduce the total body clearance of this quinolone by about 20%. The extent of ciprofloxacin binding to rat serum protein was not affected by fenbufen, nor did it affect the biliary clearance of the quinolone. However, fenbufen tended to reduce renal clearance and significantly decreased the cumulative renal excretion of the quinolone during at least the first 3 h after drug administration. These results suggest a possible reduction of ciprofloxacin clearance owing to inhibition of renal excretion by fenbufen.
Pharmacokinetics of GM1 Ganglioside Following Parenteral Administration
Authors: Cornelli Umberto , Panucci Aldo , Zingali Gaetano , Kirschner Günter , Baggio Carlo , Cogo Roberto 
Published: April 2011

Abstract
The pharmacokinetic parameters of monosialotetrahexosylganglioside (GM1) have been determined in healthy volunteers at 3 dose levels: 100, 200, 300 mg. Each dose was administered to separate groups of 12 volunteers. GM1 levels were determined in plasma, urine, and faeces by a method based on the property of the cholera toxin β subunit to react specifically with GM1 ganglioside. A non-compartmental model was applied to determine standard pharmacokinetic parameters. The average AUC increased with dose (1002 ± 121.2, 1306 ± 146.1, 3155 ±121.6 μg mL−1 h after 100, 200, 300 mg, respectively). Plasma clearance was less than 3 mL min−1 and the distribution volume was close to the plasma volume (on average between 4.3 and 7.2 L). Mean residence time was about 43 h for all doses. GM1 was not detected in urine, while in faeces the amount of GM1 determined was similar to the baseline values obtained before dosing.
Renal Responses to Magnesium Lithospermate B
Authors: Yokozawa Takako , Lee Tae Woong , Chung Hae Young , Oura Hikokichi , Nonaka Gen-Ichiro , Nishioka Itsuo 
Published: April 2011

Abstract
Renal responses to magnesium lithospermate B isolated from Salviae miltiorrhizae radix were examined in normal rats. Urinary sodium, potassium, prostaglandin E2 and kallikrein excretion was significantly increased after magnesium lithospermate B administration, whereas excretion of urinary 6-keto-prostaglandin F1α and thromboxane B2 was unchanged. Rats administered with the drug also revealed a slight elevation of plasma renin activity and the levels of angiotensins I and II. Plasma aldosterone was decreased slightly. No significant changes were observed in angiotensin-converting enzyme or blood pressure.
Potentiating Effect of Daunorubicin on Vasocontractile Responses to KCl and BAY K 8644 in Rat Aorta
Authors: Wakabayashi Ichiro , Sakamoto Kunihiro , Kakishita Eizo 
Published: April 2011

Abstract
The effects of daunorubicin on vasocontraction by several agonists have been investigated on isolated aortic strips from rats. Pretreatment of the strips with daunorubicin (17.7 μM) potentiated the contractile response to low concentrations of KCl or to BAY K 8644 but not to phenylephrine or clonidine. The maximal contractile response to KCl was not affected by the pretreatment while that to BAY K 8644 was increased. The potentiated response to KCl could be eliminated by addition of nifedipine (1 μM) or use of a calcium-free solution. The maximal contractile response to BAY K 8644 was greatly increased by partial depolarization with KCl (10 mM, final concn) in the control solution but only slightly increased by the partial depolarization in the solution with daunorubicin. These results suggest that daunorubicin facilitates activation of the voltage-dependent calcium channel and increases the contractile responses to KCl and BAY K 8644 in rat aorta.
Distribution of griseofulvin in the rat: comparison of the oral and topical route of administration
Authors: Nimni Marcel E , Ertl Delia , Oakes Roger A 
Published: April 2011

Abstract
Effective penetration of griseofulvin across the dermal barrier has been achieved using an anhydrous solvent system of benzyl alcohol (10%), acetone (40%), and isopropanol (50%). There were quantitative differences in the relative accumulation of griseofulvin in skin compared with internal organs, when the topical and oral routes of administration were compared. The topical route enhanced localized concentrations of griseofulvin at the site of application, and these persisted for several days. After daily topical application a steady state was reached at day 3, when the diffusion across the skin barrier and epidermal loss seemed to equal the total amount applied to the skin surface. The application of griseofulvin topically, required a much smaller amount of drug to achieve similar integumentary levels compared with the amount required orally.
The excitatory effect of dopamine on isolated canine tracheal smooth muscle
Authors: Shue Chung-Hung , Chen Ching-Ju 
Published: April 2011

Abstract
The effect of exogenous dopamine on canine tracheal smooth muscle has been studied in-vitro. Dopamine at concentrations over 10−5 M induced contractions of tracheal muscle strips and repeated exposures resulted in desensitization (tachyphylaxis) of the muscle. The sensitivity of the response varied dramatically among muscle strips. At lower concentrations, dopamine caused neither muscle relaxation nor inhibition of contractions evoked by 10−6 M acetylcholine. Both a dopaminergic antagonist, haloperidol (10−5 and 10−4 M), and an α-adrenoceptor antagonist, phentolamine (10−7 to 10−5 M), attenuated the contraction to 10−3 M dopamine. The β-adrenoceptor antagonist, propranolol (10−8 to 10−6 M), enhanced the contraction. However, the contraction could only be abolished by phentolamine at 10−4 M. Thus, in canine tracheal smooth muscle, the contractile response to dopamine is predominantly through the activity of α-adrenoceptors and the role of dopaminergic receptors is vague. It is suggested that the weakness of the dopamine-induced contraction results from an antagonism between α- and β-adrenoceptor effects and the dopamine tachyphylaxis may reflect a gradually decreased activation of the α-adrenoceptor mechanism in comparison with the β-adrenoceptor mechanism.
Cytotoxic drugs and the aquatic environment: estimation of bleomycin in river and water samples
Authors: Aherne G Wynne , Hardcastle Anthea , Nield Alan H 
Published: April 2011

Abstract
A radioimmunoassay has been used to determine levels of the anticancer drug bleomycin in sewage treatment works effluent, river and potable water samples. Samples were concentrated 100-fold by lyophilisation and a final limit of detection of 5 ng L−1 was achieved. Concentrations of immunoreactive bleomycin of between 11 and 19 ng L−1 were found in the effluents but a lower concentration range &lt; 5–17 ng L−1 was found in river and potable water samples. The risk to human health of ingesting water (in SE England) with such low levels of this cytotoxic drug appears to be minimal in relation to the normal chemotherapeutic doses administered (20–30 mg m−2).
Evaluation of In-vitro Percutaneous Absorption across Human Skin and in Animal Models
Authors: Přborský Jan , Mühlbachová Elfa 
Published: April 2011

Abstract
The in-vitro permeability characteristics of human skin have been examined and compared with results in laboratory animals using various types of penetration enhancers. The study was focused on evaluation of predictable validity of the data obtained in animals mostly used in permeation studies. The results in man using the same penetration enhancers were about 30% of the value in the rat. The least potent enhancer was dimethylsulphoxide and the maximum efficacy was observed with sodium laurylsulphate in the rat experiments while in man the results were approximately equal when using any of the studied enhancers. Comparison of the results of experiments performed with N-methyl-2-pyrrolidone in several laboratory animals and man showed that the skin permeability in man is approximately 4 times lower than with the rat. Man and guinea-pig were not significantly different in these experiments. There were no significant differences in laurocapram penetration enhancing effect in the concentration range 0.1 to 0.5%, but there was an optimum concentration of laurocapram of 1%. The results showed quantitative differences in percutaneous absorption in various animal species in comparison with man. These differences should be considered in selecting a suitable model for preclinical drug evaluation. The guinea-pig skin penetration seems to be most similar to that in man.
Erythrocytes as Carriers for L-Asparaginase. Methodological and Mouse In-vivo Studies
Authors: Kravtzoff R , Ropars C , Laguerre M , Muh J P , Chassaigne M 
Published: April 2011

Abstract
L-Asparaginase has been encapsulated in Swiss mouse or human erythrocytes by hypotonic haemolysis followed by isotonic resealing and reannealing. The details of incorporation and properties of carrier erythrocytes are presented. When L-asparaginase loaded into 51Cr-labelled erythrocytes, was infused intravenously, the same half-life was found for asparaginase and 51Cr. In addition, L-asparaginase loaded into erythrocytes was much more effective in eliminating plasma asparagine compared with the same dose of free L-asparaginase injected in solution, during a sustained period (14 days).
Influence of the Endothelium on Vascular Responses of Aortae from Endotoxic Rats
Authors: Wakabayashi Ichiro , Hatake Katsuhiko , Kakishita Eizo , Hishida Shigeru 
Published: April 2011

Abstract
Intraperitoneal injection of endotoxin diminished the in-vitro contractile response of rat aorta to phenylephrine or clonidine, whether the intimal layer was disrupted or not. The relaxing responses to acetylcholine and sodium nitroprusside in aorta precontracted with 10−6 M phenylephrine were similar between control and endotoxic groups. However, when the precontractile force following phenylephrine was adjusted to an equivalent level, the relaxing responses to acetylcholine and sodium nitroprusside were diminished in the endotoxic aorta compared with the controls. There was no significant difference between the two groups in the increase in cyclic GMP levels induced by acetylcholine or by sodium nitroprusside. These results suggest that aortae from endotoxic rats show decreased responsiveness to α-adrenoceptor stimulation not because of enhancement of the endothelium-derived relaxing factor but because of abnormality in the vascular smooth muscle which is not specific for subtypes of the α-adrenoceptor.
Role of Presynaptic Purinoceptors and Cyclic AMP on the Noradrenaline Release in Cat Cerebral Arteries
Authors: Rivilla Fernando , Güemes Magdalena , Sanchez-Ferrer Carlos F , Ibañez Carmen , Salaices Mercedes , Marin Jesus 
Published: April 2011

Abstract
Field electrical stimulation (ES), K+ (50 mM) or ionophore X-537A (0.01 mM) induced tritium release from cat cerebral arteries preincubated with [3H]noradrenaline (NA). Adenosine and AMP (0.5 mM) did not modify tritium release caused by ionophore X-537A, but these agents and ATP (0.5 mM) significantly reduced that elicited by ES and K+; this reduction was antagonized by 1-methyl-3-isobutylxanthine (MIX; 0.05 mM). Inosine (0.5 mM) and the agonist of purinergic A2-receptors, 5′ N-ethylcarboxamide adenosine (NECA; 0.5 mM) had no effect, but the agonist of purinergic A1-receptors L-N6-phenylisopropyl adenosine (L-PIA; 0.1 mM) diminished tritium efflux caused by ES and K+. The adenosine inhibition of ES-induced radioactivity release was not affected by indomethacin (0.05 mM). MIX (0.05 mM) increased tritum release evoked by ES and K+. Agents that increase intracellular cyclic (c)AMP levels, such as dibutyryl cAMP (0.5 mM), the phosphodiesterase inhibitor Ro 20–1724 (01 mM), and the activators of adenylate cyclase, forskolin (0.005 mM) and NaF (2 mM) reduced tritium secretion elicited by ES and K+. However, the intracellular increase of cyclic GMP (cGMP) caused by 8-Br-cGMP did not affect this secretion. Dipyridamole (0.05 mM) and the adenosine deaminase inhibitor erythro-9-2-hydroxy-3 nonyl adenosine (EHNA; 0.1 mM) also produced inhibition of tritium secretion elicited by ES and K4. Dipyridamole reduced both the uptake of [3H]NA and [3H]adenosine. These results indicate that in these vessels: (1) presynaptic inhibition of exocytotic NA release induced by adenosine, ATP, and AMP is mainly mediated by purinoceptors of the A1-subtype, without participation of prostaglandins; (2) the nonexocytotic release is not presynaptically modulated; (3) intracellular increases of cAMP, but not of cGMP, reduced NA release; and (4) the effects of dipyridamole and EHNA appear to be mediated by augmentation of intracellular levels of adenosine by preventing its neuronal uptake and its adenosine deaminase inactivation, respectively.
The Pharmacokinetics and Pharmacodynamics of a New Thromboxane Synthetase Inhibitor, 6-(1-Imidazolylmethyl)-5,6,7,8-tetrahydronaphthalene-2-carboxylic acid (DP-1904) in Man after Repeated Oral Doses
Authors: Tanaka Makoto , Ono Kenji , Hakusui Hideo , Takegoshi Toshio , Shiozawa Tomoo , Suzuki Tomoyoshi , Nii Shigenori , Shibata Hisao 
Published: April 2011

Abstract
The pharmacokinetics of DP-1904, a new potent and selective thromboxane synthetase inhibitor, and its effects on ex-vivo prostanoid formation have been studied in groups of Japanese normal male volunteers, who received repeated oral doses of 200 mg every 12 h for 4 doses, or 400 mg every 24 h for 2 doses, or 200 mg every 12 h for 14 doses. The drug was well tolerated by all subjects without evidence of adverse reactions. Repeated administration showed no significant changes in half-lives, tmax values, cmax values and AUC values. DP-1904 did not exhibit time-dependent kinetics. Its plasma levels were lower than the quantifiable level (50 ng mL−1) at 12 h after each dose. These data suggest no significant accumulation of DP-1904 in normal volunteers. DP-1904 reduced the serum thromboxane B2 by about 80% during the medication, the serum concentrations returning to about 44, 75 and 20% of the predrug control values at 36 h after the last 200 mg doses and 48 h after the last 400 mg dose.
Interspecies Pharmacokinetic Scaling of Some Iodinated Organic Acids
Authors: Lázníček Milan , Lázníčková Alice , Štětovská Marie , Květina Jaroslav 
Published: April 2011

Abstract
We have investigated the possibility of interspecies scaling of relationships between the structure and total plasma clearance in a group of nine organic acids (iododerivatives of benzoic, phenylacetic and hippuric acids) in rabbits, rats and mice. The intercompound comparison established the dependence of total plasma clearance predominantly on the molecular structure in all the animals under study, but the dependence on drug lipophilicity was also meaningful. For interspecies scaling of total plasma clearance, the use of a biological clock with an effective renal plasma flow as the unit seemed most suitable and is probably connected with the principal role of the kidney in the elimination of the compounds under study.
Paracetamol potentiates stress-induced gastric ulceration in rats
Authors: Cho C H , Ogle C W 
Published: April 2011

Abstract
The effect of paracetamol on gastric ulcers produced by restraint at 4°C for 2 h (stress) was studied in rats. Paracetamol treatment s.c or p.o., with a dose as high as 250 mg kg−1, did not produce any haemorrhagic lesions in the glandular mucosa. Oral administration with 250 mg kg−1, however, significantly reduced the mast cell count in the gastric glandular mucosa and potentiated haemorrhagic ulceration but not mast cell degranulation caused by stress. The potentiating action was maximum when paracetamol was given between 15 and 30 min before stress. Ranitidine, astemizole, dimethylsulphoxide, sucralfate and verapamil did not protect against the adverse action of paracetamol on stress-evoked lesions. This study suggests that paracetamol worsens stress-induced stomach ulceration by an action which appears not to be due to histamine release, free radical production or intracellular calcium disturbance in the gastric mucosa.
Effect of phospholipid emulsifiers on physicochemical properties of intravenous fat emulsions and/or drug carrier emulsions
Authors: Ishii Fumiyoshi , Sasaki Ichiro , Ogata Hiroyasu 
Published: April 2011

Abstract
The physicochemical properties of soybean oil emulsions stabilized with purified egg lecithins (phosphatides) of various concentrations have been examined. The zeta potential of the emulsion droplets and the mean particle size of oil droplets in 10% (w/w) o/w-type emulsion decreased with increasing emulsifier concentration and then levelled off at more than 1.2% (w/w). In rheological measurements, at the initial stage, the viscosity of 10% (w/w) o/w-type emulsion gradually increased with increasing purified egg lecithin concentration, at the next stage, a plateau was reached at about 1.0–1.4% (w/w), and at the final stage, the viscosity curve showed a dramatic increase. These results indicate that emulsions stabilized by purified egg lecithin at more than 1.2% (w/w) are likely to be sufficiently stable.
Inhibitory action of calcitonin gene-related peptide (CGRP) in the mouse colon
Authors: Cadieux Alain , Pomerleau François , St-Pierre Serge , Fournier Alain 
Published: April 2011

Abstract
The effect and mechanism of action of calcitonin gene- related peptide (CGRP) have been investigated on the mouse distal colon. CGRP caused a concentration-dependent relaxation which was not blocked by classical pharmacological antagonists. The response pattern was characterized by a relatively rapid onset and long sustained duration. The results suggest that CGRP itself may contribute to regulating the muscular tone of the mouse colon.
Cyclosporin A treatment enhances angiotensin converting enzyme activity in lung and serum of rats
Authors: Erman A , Chen-Gal B , Zabludowski J , Rosenfeld J B 
Published: April 2011

Abstract
Nephrotoxicity and arterial hypertension are the most common side effects of treatment with cyclosporin A (CSA). Its effects on angiotensin converting enzyme (ACE) activity in the renal cortex, lung and serum of nephrotoxic rats have been investigated. Wistar rats were treated with CSA (20 mg kg−1 day−1 i.p.) or vehicle (olive oil containing 10% ethanol) for 14 days. On day 15, the rats were killed and ACE activity determined by radiometric assay using [3H]hippuryl-glycyl-glycine as substrate. CSA treatment resulted in a decrease in creatinine clearance, urine flow and body weight and a significant increase in serum and lung ACE activities (436 ± 9 vs 391 ± 7 nmol mL−1 min−1, P &lt; 0.001; 184 ± 8 vs 142 ± 10 nmol mg−1 min−1 P &lt; 0.01, respectively). In contrast, renal cortex ACE activity was reduced in the CSA-treated rats (0.35 ± 0.02 vs 0.51 ± 0.02 nmol mg−1 min−1, P &lt; 0.01). ACE activities in the renal cortex and serum were not affected by treatment with gentamicin (80 mg kg−1 day−1) for 11 days. In rats treated simultaneously with CSA and captopril (50 mg kg−1 day−1) ACE activity in the serum, lung and renal cortex was inhibited by 95, 93 and 92%, respectively. These changes in ACE activity were associated with a decreased systolic blood pressure in the rats receiving CSA and captopril. Therefore, ACE activity in the serum and lung of CSA-treated rats was increased, while its activity in the renal cortex was reduced. This increased activity may support the suggestion that CSA induces hypertension through an angiotensin II-dependent mechanism and/or an increased degradation of vasodilatory kinins.
The Effect of Solubilized Water on the Size and Shape of Lecithin Micelles in an Apolar Solvent
Authors: Evans Richard M , Attwood David , Chatham Sarah M , Farr Stephen J 
Published: April 2011

Abstract
The changes in the size and shape of the micelles of soya lecithin in trichlorotrifluoroethane following the solubilization of increasing quantities of water have been examined by dynamic and static light scattering and viscometric techniques. Micelles in systems with water/lecithin molar ratios, R, of less than 2.6 were oblate and exhibited no significant changes in asymmetry or aggregation number with changes in the amount of solubilized water. Spherical micelles were evident in systems with R = 2.6 whereas prolate micelles were present in solutions of higher water content (3.5 ≤ R ≤ 5.2). An increase of R in these systems caused a decrease in the axial ratio and an increase in the aggregation number of the micelle.
Moisture Adsorption-desorption Effect on the Structure of Inclusion Complex of 6-Chloro-2-pyridylmethyl Nitrate and β-Cyclodextrin
Authors: Kitamura Satoshi , Koda Shigetaka , Yasuda Tsutomu 
Published: April 2011

Abstract
A new anti-anginal drug, 6-chloro-2-pyridylmethyl nitrate (FR46171), was found to form a complex with β-cyclodextrin (β-CyD), molecular ratio 1:1. The FR46171/β-CyD complex thus prepared showed a moisture adsorption-desorption hysteresis characteristic of hydrophilic polymers. The moisture adsorption-desorption isotherm and differential scanning calorimetry indicated that the moisture adsorbed FR46171/β-CyD complex includes 13–15 mol of water while the moisture desorbed complex includes 5 mol of water. X-ray diffraction patterns of these samples confirmed their different structures. The scanning electron photomicrographs and the surface areas (BET) suggested that the moisture adsorption-desorption hysteresis observed in FR46171/β-CyD complex can be attributed to reversible hydrogen bonding between water molecules and hydroxyl groups.