bluuebunny/crossref_metadata_2025_split huggingface dataset:
Fab-bound Colchicine Appears to Adopt Fab Fragment Disposition in Rats
Authors: Sabouraud Alain E , Urtizberea Michel , Benmoussa Kamel , Cano Nathalie J , Scherrmann Jean-Michel G 
Published: April 2011

Abstract
The disposition of colchicine-specific Fab fragments and the effect of Fab fragment administration on the disposition of colchicine were studied in anaesthetized bile duct-cannulated rats. One group of rats (n = 6) received a 125I-Fab dose of 38 mg kg−1 i.v. The plasma disposition was characterized by a volume of distribution of 179 ± 48 mL kg−1, total body clearance of 1·02 ±0·07 mL min−1 kg−1, t½α of 0·17 ± 0·03 h and t½α of 1·3 ± 0·3 h. Fab fragments were in part excreted by the renal route (15·6 ± 6% of the Fab dose), while biliary excretion was a minor route (&lt; 2% of the Fab dose). Two other groups of rats received 15 μg kg−1 colchicine (n = 6) or 15 μg kg−1 colchicine plus 38 mg kg−1 colchicine-specific Fab fragments (n = 6) by intravenous infusion. Pharmacokinetics of colchicine was markedly altered in the Fab-colchicine-treated rats. In this group, distribution volume and total body clearance of colchicine were decreased by factors of 22 and 10, respectively, compared with the values in the colchicine-treated group and were very similar to those of Fab fragments. An 80% reduction of cumulative biliary excretion of colchicine was observed in Fab-colchicine-treated rats (P &lt; 0·01). The fraction of colchicine dose excreted by the urinary route was 38 ± 6·9 and 9 ± 0·7% respectively in Fab-colchicine- and colchicine-treated groups (P &lt; 0·01). These data show that during Fab treatment, colchicine followed the elimination kinetics of Fab fragments. This study supports the view that Fab fragments could be of benefit in acute colchicine poisoning by neutralizing colchicine in the vascular compartment and imposing its elimination kinetics on colchicine.
The Effect of Lipopolysaccharide on the Disposition of Xanthines in Rats
Authors: Wang Li , Hasegawa Takaaki , Nadai Masayuki , Muraoka Isao , Nabeshima Toshitaka , Kato Nobuo 
Published: April 2011

Abstract
The effect of lipopolysaccharide (LPS) isolated from Klebsiella pneumoniae O3 on the pharmacokinetic behaviour and metabolism of the xanthines, theophylline and 1-methyl-3-propylxanthine (MPX), which are mainly metabolized by the liver, was investigated in rats. LPS was infused at 0·25 mg kg−1 over a period of 20–30 min, 2 h before the administration of theophylline (10 mg kg−1) or MPX (2·5 mg kg−1). Concentrations of both xanthines in plasma and concentrations of the parent drug and metabolites in urine were measured by HPLC. Model-independent methods were applied to estimate the pharmacokinetic parameters for both xanthines. No significant changes in the pharmacokinetic parameters or metabolism of theophylline were observed in rats pretreated with LPS. However, the total body clearance and volume of distribution of MPX were significantly increased by pretreatments with LPS. Significant decreases in the binding capacity and number of binding sites on the albumin molecule were observed in the presence of LPS. Changes occurring in the protein binding behaviour as a result of the introduction of LPS is a primary factor which not only increases the volume of distribution but also increases total body clearance. These results indicate that LPS has no effect on the pharmacokinetics and metabolic pathway of theophylline although it changes the disposition of MPX due to decreases in the extent of the protein binding of MPX which is highly bound to protein.
Effect of Staurosporine Derivatives on Protein Kinase Activity and Vinblastine Accumulation in Mouse Leukaemia P388/ADR Cells
Authors: Miyamoto Ken-Ichi , Inoko Kohsei , Ikeda Kyoko , Wakusawa Shinya , Kajita Shinji , Hasegawa Takaaki , Takagi Kenzo , Koyama Masao 
Published: April 2011

Abstract
Inhibition by staurosporine derivatives of cyclic AMP-dependent protein kinase (A-kinase) and protein kinase C (C-kinase), and drug resistance has been investigated. The substitution of an acetyl or an ethoxycarbonyl group for the amine N-ethoxycarbonyl-7-oxostaurosporine moiety on the tetrahydropyran ring of staurosporine decreased inhibition of both protein kinases, but increased selectivity for C-kinase by further modification of the lactam moiety to the imide (NA-382). The activities of SF-2370 on protein kinases were decreased by decarboxylation and hydroxyalkylation. These staurosporine derivatives enhanced accumulation of vinblastine in adriamycin-resistant P388 (P388/ADR) cells in a dose-dependent manner. The potency for the drug accumulation of these compounds was correlated with their inhibitory activity on the drug efflux, but was not correlated with their activity on protein kinases. Staurosporine and NA-382, with high potency for vinblastine accumulation, inhibited the photolabelling of [3H]azidopine on 140 kDa P-glycoprotein in the plasma membrane. The tetrahydrofuran compounds and NA-357, which had low potency for the drug accumulation, hardly interacted with azidopine on P-glycoprotein. Most of these compounds were highly cytotoxic by themselves, and only NA-382 was less cytotoxic among them and completely reversed the vinblastine-resistance of P388/ADR cells at a non-cytotoxic concentration. These results suggest that staurosporine derivatives can enhance drug accumulation and inhibit drug resistance through their direct action on the P-glycoprotein.
Stimulation of Enterocyte Protein Kinase C by Laxatives In-vitro
Authors: Beubler Eckhard , Schirgi-Degen Andrea 
Published: April 2011

Abstract
To elucidate the role of protein kinase C in the mechanism of action of stimulatory laxatives, experiments were performed with preparations of rat lysed enterocytes. The phorbol ester 4-β-phorbol 12-myristate 13-acetate (PMA) concentration-dependently (2–200 μg mL−1) stimulated the activity of protein kinase C in this preparation. Ricinoleic acid, the active principle of castor oil, deacetylbisacodyl, the active principle of bisacodyl, and deoxycholic acid exerted the same effect, although less efficiently. This reflects their potency for inducing intestinal fluid secretion and prostaglandin release, effects that are also induced more potently by PMA. Accordingly, the potency of the three C18 fatty acids, ricinoleic acid, stearic acid and oleic acid on protein kinase C activity in-vitro, on prostaglandin E2 release and on net fluid secretion in-vivo runs in parallel. It is therefore concluded that stimulatory laxatives activate protein kinase C., leading to prostaglandin E2 release, thus resulting in net fluid secretion.
Sorption of isosorbide dinitrate to central venous catheters
Authors: De Muynck C , Vandenbossche G M R , Colardyn F , Remon J P 
Published: April 2011

Abstract
As several studies demonstrated the sorption of isosorbide dinitrate (ISDN) to intravenous delivery systems, a study on the sorption of ISDN to several central venous catheters was performed. Fourteen different catheters were perfused during a 2 h period, under simulated infusion conditions, with ISDN (250 μg mL−1) in 0·9% (w/v) sodium chloride. The drug loss to a polyethylene and a silicone catheter was 0·2 and 6·1%, respectively. The sorption to a polyvinylchloride heparin-coated thermodilution catheter was 1–6·9% depending on the length of the catheter. The drug loss to polyurethane catheters of different composition varied between 3·8 and 28·9%. For polyurethane catheters composed of cycloaliphatic polyurethanes an inverse relation was shown between Shore A hardness and sorption.
Measuring the Uptake of Azone into Excised Human Stratum Corneum from Thin Polymer Films
Authors: Schückler Fritz , Lee Geoffrey 
Published: April 2011

Abstract
The extent of uptake of Azone into excised human stratum corneum from thin polymer films has been measured using a sandwich model. With poly(dimethyl)siloxane, an Azone loading of the stratum corneum of 6–7% w/w was achieved. With Eudragit NE30D, a loading of less than 1% was reached. The extent of uptake into the stratum corneum and acceptor layers of the sandwich model depended on the Azone content of the films. The resulting enhanced uptake and flux of diazepam through the stratum corneum membrane into a polymeric acceptor layer corresponded closely to the amounts of Azone taken up and their known enhancing effects. The uptake of diazepam from the poly(dimethyl)siloxane films was ten times larger than that from Eudragit NE30D films. The extent of uptake is, therefore, controlled by the rate of release from the polymer and partitioning at the interface.
Dissimilarity in the mechanisms of action of KRN2391, nicorandil and cromakalim in canine renal artery
Authors: Kasai Hideo , Fukata Yuzo , Harada Katsuhiko , Fukushima Hideaki , Ogawa Nobuyuki 
Published: April 2011

Abstract
In the present study, we examined the mode of action of KRN2391 (N-cyano-N′-(2-nitroxyethyl)-3-pyridinecarboximida-mide monomethanesulphonate) in isolated canine renal artery compared with those of nicorandil and cromakalim. KRN2391 (10−8-3 × 10−5 m), nicorandil (10−7-3 × 10−4 m) and cromakalim (10−8-3 × 10−5 m) relaxed renal arteries contracted by 25 Mm KCl in a concentration-dependent manner. KRN2391-induced relaxation was inhibited by methylene blue (10−5 m) and glibenclamide (10−6 m). Nicorandil-induced relaxation was inhibited by methylene blue, but not by glibenclamide. The concentration-relaxation curve for cromakalim displayed a rightward parallel shift in the presence of glibenclamide. In the control observation, KRN2391 and nicorandil also produced full relaxation, but cromakalim did not. The present results suggest that KRN2391 acts as both a nitrate and a potassium channel opener, and nicorandil acts only as a nitrate and only in canine renal artery.
Percutaneous Permeation of Basic Compounds Through Shed Snake Skin as a Model Membrane
Authors: Takahashi Koichi , Tamagawa Satoko , Katagi Toyoshi , Rytting J Howard , Nishihata Toshiaki , Mizuno Nobuyasu 
Published: April 2011

Abstract
Relationships between the in-vitro permeability of basic compounds through shed snake skin as a suitable model membrane for human stratum corneum and their physicochemical properties were investigated. Compounds with low pKa values were selected to compare the permeabilities of non-ionized forms of the compounds. Steady-state penetration was achieved immediately without a lag time for all compounds. Flux rate and permeability coefficient were calculated from the steady-state penetration data and relationships between these parameters and the physicochemical properties were investigated. The results showed that permeability may be controlled by the lipophilicity and the molecular size of the compounds. Equations were developed to predict the permeability from the molecular weights and the partition coefficients of basic compounds.
Mechanisms of Action of Dopamine in the Peripheral Nervous System of Chicks and Rats
Authors: Lot Theodore Y 
Published: April 2011

Abstract
The effects and mechanisms of action of dopamine on the lower oesophagus and expansor secundariorum muscle (ESM) of chicks and on the bladder of rat have been examined. Dopamine contracted the lower oesophagus in a concentration-related fashion but failed to contract the muscle from chicks pretreated with reserpine or p-chlorophenylalanine. Contraction of the ESM by dopamine was antagonized by prazosin but not by propranolol. Supersensitivity of the ESM to dopamine observed 3 or 28 days after surgical denervation of the muscle was comparable. Dopamine did not exert any agonist effect on the rat bladder but depressed responses to stimulation of non-adrenergic, non-cholinergic (NANC) nerves in the bladder. These findings indicate that dopamine contracts the upper oesophagus of chicks by releasing 5-hydroxytryptamine, activates α-adrenergic receptors causing contraction of the ESM but depresses NANC neurotransmission in the bladder.
Comparison of the effects of loperamide and loperamide oxide on absorptive processes in rat small intestine
Authors: Hardcastle Jacqueline , Hardcastle P T , Goldhill J 
Published: April 2011

Abstract
Mucosal loperamide inhibited the absorption of glycine by everted sacs of rat small intestine over 10-, 30- or 60-min incubation periods, but loperamide oxide was without effect. In stripped intestinal sheets, loperamide inhibited the rise in short-circuit current associated with Na+-linked glucose absorption, but this effect was not observed with loperamide oxide. It is concluded that although there is evidence that loperamide oxide is converted to loperamide in the intestinal lumen, the rate at which free loperamide appears is not sufficient to inhibit absorptive processes.
Influence of a Bacterial Lipopolysaccharide on the Pharmacokinetics of Tobramycin in Rats
Authors: Nadai Masayuki , Hasegawa Tataaki , Kato Katsuyoshi , Wang Li , Nabeshima Toshitaka , Kato Nobuo 
Published: April 2011

Abstract
The effects of Klebsiella pneumoniae O3 lipopolysaccharide on the renal handling and distribution characteristics of the aminoglycoside tobramycin were investigated in rats. Tobramycin (2 mg kg−1) and inulin (100 mg kg−1) were administered intravenously 2 h after administration of 50,250 or 500 μg kg−1 lipopolysaccharide. Lipopolysaccharide delayed the disappearance of tobramycin from plasma in a dose-dependent manner. A dose-dependent decrease in systemic clearance of tobramycin was observed, although the elimination rate constant and fraction of urinary recovery of unchanged drug were not significantly different in any group. Lipopolysaccharide significantly decreased the central compartment volume of distribution of tobramycin, but did not influence the steady-state volume of distribution. A dose-related increase in the ratio of the rate constant of transfer to the peripheral compartment to the rate constant of transfer from peripheral compartment to central compartment was observed. The glomerular filtration rate was significantly decreased by pretreatment with 250 μg kg−1 lipopolysaccharide and the clearance ratio was decreased by 20%, indicating that lipopolysaccharide increases the tubular reabsorption of tobramycin. Our findings suggest that K. pneumoniae O3 lipopolysaccharide modifies the glomerular filtration rate and tubular reabsorption without change in the terminal half-life and that drug distribution characteristics from the rapidly-distributing compartment to the peripheral compartment were altered without expansion of the extracellular fluid volume.
Albumin microspheres as a drug delivery system for dexamethasone: pharmaceutical and pharmacokinetic aspects
Authors: Dilova Valia , Shishkova Valentina 
Published: April 2011

Abstract
Four types of albumin microspheres containing dexamethasone prepared by varying cross-linking time—30, 60, 120 and 180 min—were tested to examine the influence of heat cross-linking degree on the in-vitro drug release. Release rate of dexamethasone associated with the microspheres was slower for samples with a longer time of high temperature denaturation. Encapsulation in neat-stabilized albumin microspheres for 60 min at 100°C significantly retards the in-vivo release of dexamethasone and hence retards absorption from the injection site.
Subcutaneous Absorption Kinetics and Local Tissue Distribution of Interferon and Other Solutes
Authors: Cross Sheree E , Roberts Michael S 
Published: April 2011

Abstract
The subcutaneous absorption and consequent tissue distribution of interferon g was studied in an anaesthetized rat model. Interferon g showed a biphasic disappearance profile from a solution in a subcutaneous absorption cell. Both the initial rapid distribution phase and slower removal phase followed first order kinetics. The steady-state clearance of interferon g from the cell was 1·41 ± 0·38 × 10−3 mL min−1, and the absorption half-life (t½) was 3·8 ± 1·1 h (n = 4). Noradrenaline did not significantly alter either the clearance or absorption of interferon g (1·18 ± 0·44 × 10−3 mL min−1 P &gt; 0·05, absorption t½ 4·96 ± 1·9 h, P &gt; 0·05). Given that the clearance of smaller solutes, such as tritiated water, is significantly reduced when noradrenaline is coadministered, it is suggested that interferon g is removed via the lymphatic system rather than by the local blood supply. The amount of interferon g recovered in the plasma, urine and muscle is minimal relative to other solutes where the recovery is almost complete.
Renal Tubular Excretion of the N4-Acetyl Metabolites of Sulphasomidine and Sulphadimethoxine in the Dog
Authors: Boom Sandra P A , Wouterse Alfons C , Vree Tom B , Van Ginneken Cees A M , Russel Frans G M 
Published: April 2011

Abstract
To investigate whether dogs are able to excrete acetylated drugs by active transport, the plasma kinetics and renal excretion of the N4-acetyl metabolites of sulphasomidine and sulphadimethoxine were studied in the beagle dog after a rapid intravenous bolus injection. Two doses of N4-acetylsulphasomidine (1050 and 105 mg) and one dose of N4-acetylsulphadimethoxine (472 mg) were administered on separate occasions. The renal clearance (CLR) was as follows: N4-acetylsulphasomidine (1050 mg) 34 mL min−1; N4-acetylsulphasomidine (105 mg) 28 mL min−1; and N4-acetylsulphadimethoxine (472 mg) 24 mL min−1. CLR was higher than expected on the basis of the measured glomerular filtration rate, indicating that the N4-acetyl metabolites may be excreted by the renal tubules by active tubular transport. Saturation of the excretion process of N4-acetylsulphasomidine occurred with a transport maximum of 930 ± 190 μg min−1 and a Michaelis-Menten constant of 37 ± 10 μg mL−1. It may be concluded that the dog renal organic anion transport system is able to secrete acetylated sulphonamides.
Characterization of the Analgesic Effects of Paracetamol and Caffeine Combinations in the Pain-induced Functional Impairment Model in the Rat
Authors: Granados-Soto Vinicio , López-Muñoz Francisco J , Castañeda-Hernández Gilberto , Salazar Luis A , Villarreal Julian E , Flores-Murrieta Francisco J 
Published: April 2011

Abstract
The analgesic activities of paracetamol (100, 178, 316 and 562 mg kg−1), caffeine (10,18, 32 and 56 mg kg−1) and combinations of these doses were tested on a pain-induced functional impairment model in the rat. Dysfunction of the right hind limb was induced by an intra-articular injection of 30% uric acid in the knee. Drugs were given orally and the recovery of functionality over time was considered as an expression of analgesia. Paracetamol alone induced a dose-dependent analgesic effect whereas caffeine alone did not show any activity at the assayed doses. Combinations of 316 mg kg−1 paracetamol with either 10, 18, 32 or 56 mg kg−1 caffeine yielded analgesic effects significantly greater than that of paracetamol alone. The highest potentiation was observed with a paracetamol-caffeine mixture of 316–32 mg kg−1. Caffeine coadministration, however, did not significantly change paracetamol plasma levels. No potentiation was obtained with other combinations. Paracetamol plasma levels and analgesic effect observed with administration of 316 mg kg−1 paracetamol alone or 316–32 mg kg−1 of paracetamol-caffeine were fitted to the sigmoidal Emax model according to the Hill equation. The curves obtained were parallel, but that of the combination was shifted to the left. It is concluded that caffeine is able to potentiate the analgesic effect of paracetamol by a pharmacodynamic mechanism, but this only occurs at certain dose combinations.
New Pyrazolylhydrazone Derivatives as Inhibitors of Platelet Aggregation
Authors: Da Silveira Ivna Alana Freitas Brasileiro , Paulo Luiz Gonçalves , De Miranda Ana Luisa Palhares , Rocha Simone Oliveira , Freitas Antonio Carlos Carreira , Barreiro Eliezer Jesus 
Published: April 2011

Abstract
A series of 5-pyrazolylhydrazone derivatives was designed to be mixed hybrid isosteres of both BW755C and CBS-1108, which belong to the class of dual cyclo-oxygenase and 5-lipoxygenase inhibitors. Some derivatives of this series inhibit the in-vitro platelet aggregation of citrated platelet-rich rabbit plasma induced by ADP (5 μm), collagen (5 μg mL−1) and arachidonic acid (100 μm). The structure-activity relationships of this class of compounds were determined from these results. When ADP is used as the aggregation inducer, the presence of free oxygenated substituents at the p-position in the phenyl subunit of the hydrazone moiety favours inhibitory activity; p-methoxyformylbenzene-5-(1-phenyl-3-methyl-4-nitropyrazolyl)hydrazone (100 μm), which has a methoxy group at this position was the most active with 62·8% inhibition of aggregation. In contrast, substitution in the aryl ring does not affect the aggregation induced by collagen, whereas the non-substituted compound, formylbenzene-5-(1-phenyl-3-methyl-4-nitropyrazolyl)hydrazone, showed similar activity to those of substituted derivatives. In the arachidonic acid assays, the presence of an aryl ring linked to the hydrazone moiety, with an adequate electronic density at the ring due to the nature of its substitutents, is an important structural requirement for inhibitory activity.
Function of the SOS Process in Repair of DNA Damage Induced by Modern 4-Quinolones
Authors: Howard B M A , Pinney R J , Smith J T 
Published: April 2011

Abstract
The recA13 mutant of Escherichia coli strain K-12, which lacks recombination and SOS error-prone DNA repair is hypersensitive to nalidixic acid and to the newer 4-quinolones ciprofloxacin, norfloxacin and ofloxacin. However, whereas recombination-proficient but SOS repair-deficient strains, such as those carrying the lexA3 or recA430 alleles are no more sensitive to nalidixic than the lexA+ recA+ parent, they are more sensitive to the newer quinolones, although not as sensitive as the recA13 derivative. Nalidixic acid possesses only bactericidal mechanism A (which requires RNA and protein synthesis and is only effective on actively dividing cells), whereas the newer 4-quinolones exhibit additional mechanisms B (which does not require RNA and protein synthesis and is effective on bacteria unable to multiply) and C (which requires RNA and protein synthesis but does not depend on cell division). Results obtained with bacteria suspended in phosphate-buffered saline, which inhibits mechanism A, and with bacteria suspended in nutrient broth plus rifampicin, which inhibits mechanisms A and C, showed that the lexA3 mutant was still more sensitive than the lexA+ parent under these conditions. The results suggest that, unlike bactericidal mechanism A, DNA damage that results from bactericidal mechanisms B and C of the newer 4-quinolones is subject to SOS error-prone (mutagenic) repair.
K+ -Channel blockers and coronary vasoconstriction in guinea-pig perfused hearts in-vitro
Authors: Gwilt M , Orme J , Rourke J D , Henderson C G 
Published: April 2011

Abstract
Glibenclamide, glipizide and phentolamine, three drugs which have been reported to block ATP-dependent potassium channels, increased the coronary perfusion pressure in guinea-pig isolated hearts perfused at constant flow. Blockers of other types of potassium channels, 4-aminopyridine and UK-66,914, did not significantly increase perfusion pressure. Exposing hearts to a single concentration of 3 μm glibenclamide caused a greater degree of vasoconstriction than when this was preceded by lower concentrations. The 3 μm glibenclamide-induced vasoconstriction was reduced by prazosin(1 μm), mepyramine(0·1 μm) and ranitidine (10 μm) but not by a combination of mepyramine and ranitidine or by ritanserin (001 μm). These results suggest that a component of the vasoconstriction induced by glibenclamide may result indirectly from the release of vasoactive mediators.