bluuebunny/crossref_metadata_2025_split huggingface dataset:
Characterization of the α1-adrenoceptors of the rat prostate gland
Authors: Couldwell Caroline , Jackson Andrea , O'Brien Helen , Chess-Williams Russell 
Published: April 2011

Abstract
The α1-adrenoceptor-mediated responses of the rat prostate to phenylephrine have been examined in-vitro. Phenylephrine induced concentration-dependent contractions of the isolated prostate gland which were antagonized by WB4101 (1–30 nm). Schild plot analysis of the antagonism yielded a straight line with a slope not significantly different from unity. The pKB value of 9·2 was similar to that obtained for WB4101 on the rat vas deferens (9·4) but was greater than that obtained on the rat spleen (8·4). Chloroethyl-clonidine depressed responses to phenylephrine of the rat spleen but not the prostate or the vas deferens. These results indicate that the rat prostate gland possesses a typical α1A-adrenoceptor similar to that found in the vas deferens.
The purely chronotropic effects of relaxin in the rat isolated heart
Authors: Thomas G Roger , Vandlen Richard 
Published: April 2011

Abstract
The endogenously occurring protein relaxin was evaluated for its cardiac effects in the rat isolated heart. Relaxin caused a dose-dependent tachycardia without positive inotropic effects in intact preparations and in preparations where the atria had been removed. It is concluded that relaxin acts on both the atrial and ventricular pacemakers to increase heart rate, but the precise mechanism of action remains unknown.
Partitioning and thermodynamics of dipyridamole in the n-octanol/buffer and liposome systems
Authors: Betageri G V , Dipali S R 
Published: April 2011

Abstract
The thermodynamics of partitioning (K) of dipyridamole has been determined in n-octanol/buffer and liposome-buffer systems at pH 7·4. Dimyristoylphosphatidylcholine (DMPC) and dipalmitoylphosphatidylcholine (DPPC) were used to prepare multilamellar liposomes. Partitioning of dipyridamole did not depend on the amount of n-octanol employed, however, partitioning was dependent upon the quantity of DMPC employed to prepare liposomes. Plots of log K vs 1/T were linear in the n-octanol and liposome systems. Partitioning was generally greater in liposomes than in the n-octanol/buffer system. Among liposomes, the partitioning was greater in DMPC liposomes at all temperatures. The values of enthalpy (ΔH) and entropy (ΔS) were positive in both the n-octanol and liposome systems. These values were lower in DMPC liposomes and were comparable in the n-octanol and DPPC liposomes. Thus, the interaction of dipyridamole depends on the rigidity of lipid bilayers and liposomes constitute a more selective partitioning system than the n-octanol/buffer system.
Anomalous parameter estimates in the one-compartment model with first-order absorption
Authors: Purves R D 
Published: April 2011

Abstract
A difficulty sometimes encountered in least-squares fitting of a one-compartment model with first-order absorption is that estimated values (ka and ke) of the rate constants of absorption and elimination are almost identical, are highly correlated and have very large standard deviations. This anomaly is explained by the existence of a class of data sets for which least-squares estimates of the rate constants are complex quantities. Such data sets may arise either from an unfortunate combination of random (e.g. assay) errors in the concentration values if ka and ke are sufficiently similar in magnitude, or from delayed absorption.
Sennoside-induced Secretion is Not Caused by Changes in Mucosal Permeability or Na+,K+-ATPase Activity
Authors: Leng-Peschlow Elke 
Published: April 2011

Abstract
The effect of sennosides (50 mg kg−1) on the rat colon in-situ was studied 6 h after oral treatment when the laxative effect was maximal. In a second experiment, rhein (4 × 10−3 m), an active sennoside metabolite, was administered into the lumen of the colon for 1 h. Both sennosides and rhein reduced net H2O and Na+ absorption or reversed it to net secretion. Paracellular permeability, as measured using erythritol as a small marker molecule, was increased 2- to 3-fold; permeability to a large molecule, PEG 1000, was unchanged. The activity of Na+, K+-ATPase in the colon mucosa was not affected. There was no damage of the epithelial cells as determined by lactic acid dehydrogenase release. These results indicate that neither inhibition of Na+, K+-ATPase nor damage of the colon epithelium are involved in the secretory effect of sennosides or rhein. The increased paracellular permeability of small molecules fits into the concept of stimulation of active chloride secretion by sennosides, which is electrochemically and osmotically balanced by an increase in Na+ and H2O flow via the paracellular pathway.
The Role of Cyclic AMP and Phosphodiesterase Activity in the Mechanism of Action of Tetramethylpyrazine on Human and Dog Cardiac and Dog Coronary Arterial Tissues
Authors: Lin Cheng-I , Wu Shiou-Ling , Tao Pao-Luh , Chen Hsing-Ming , Wei Jeng 
Published: April 2011

Abstract
The aim of the present experiments was to explore the underlying cellular mechanisms responsible for the actions of tetramethylpyrazine (TMP) on atrial, ventricular and coronary arterial tissues. Transmembrane potentials of cardiac tissues were detected by means of the glass microelectrode technique and contractile tension by a force transducer. Tissue cyclic (c) AMP level was determined by protein binding assay. Results show that in human atrial and dog Purkinje fibres, high concentration of TMP (3 Mm) induced a persistent positive inotropic effect only in the presence of adrenaline. Also, 3 Mm TMP increased the cAMP level of the atrial muscle fibres, especially in the presence of adrenaline. Determination of the activity of cAMP-phosphodiesterase revealed that 0·3 and 3 Mm TMP inhibited the phosphodiesterase activity of dog coronary artery and human atrial tissues in a concentration-dependent manner. When compared at the lower concentration (0·3 Mm), the inhibitory effect of TMP was about 60% that of theophylline. The above findings indicate that the cardiovascular effects of TMP are related to the inhibition of phosphodiesterase activity and the subsequent elevation of the cAMP concentration.
Sex-related Differences in Rat Liver Microsomal Enzymes and Their Induction by Doxapram
Authors: Ozaki Masayasu , Ishikawa Masaaki , Takayanagi Yoshio , Sasaki Ken-Ichi 
Published: April 2011

Abstract
The effects of doxapram on the hepatic microsomal mono-oxygenase system of male and female rats were investigated. Male and female rats were administered doxapram (10–120 mg kg−1 day−1, i.p.) for 4 days. In female rats, administration of doxapram (20, 40, 60, 80, 100 and 120 mg kg−1) elevated the parameters in a dose-dependent manner while doxapram (100 and 120 mg kg−1) elevated the levels of cytochrome P450 and hexobarbitone hydroxylase in male rats. Doxapram (40 mg kg−1) caused induction of hepatic drug metabolism typified by an increase of hepatic microsomal cytochrome P450 content and activities of hexobarbitone hydroxylase, benzphetamine N-demethylase and ethylmorphine N-demethylase in female rats, but no change in male rats. These findings were supported by the results of SDS/polyacrylamide-gel electrophoresis. However, 7-ethoxycoumarin O-de-ethylase and arylhydrocarbon hydroxylase activities were significantly increased in male rats. NADPH-cytochrome c reductase and NADH-cytochrome c reductase activities, and cytochrome b5 content were unaffected in rats of both sexes. The sex-dependent cytochrome P450 species may be selectively sensitive to the action of doxapram.
Intestinal brush-border transport of the oral cephalosporin antibiotic, cefdinir, mediated by dipeptide and monocarboxylic acid transport systems in rabbits
Authors: Tsuji Akira , Tamai Ikumi , Nakanishi Masaru , Terasaki Tetsuya , Hamano Schoichiro 
Published: April 2011

Abstract
Intestinal absorption of the orally active cephalosporin, cefdinir, was investigated using brush-border membrane vesicles prepared from rabbit small intestine. The initial uptake of cefdinir was pH-dependent, with increased uptake at acidic pH, and was not influenced by either sodium gradient or membrane potential difference. Cefdinir uptake was saturable with an apparent Michaelis constant of 8·1 Mm. Initial uptake of cefdinir was inhibited by dipeptides (glycyl-l-proline and glycylsarcosine), β-lactam antibiotics (cephradine, cefixime and penicillin V), and monocarboxylic acids (acetic acid and l-lactic acid), whereas the uptake of cephradine and cefixime was not inhibited by monocarboxylic acids. Cefdinir significantly inhibited the initial uptake of cephradine, cefixime and [3H]acetic acid. From these results, it was suggested that cefdinir was transported across brush-border membranes by both dipeptide and monocarboxylic acid carriers.
Negative inotropic effect of pinacidil on the rat left atria
Authors: Doggrell Sheila A 
Published: April 2011

Abstract
Cromakalim at 50 μm and pinacidil at 0·1–10 μm had no effect, but pinacidil at 0·1 Mm had a negative inotropic effect on the rat electrically-driven left atria without altering the positive inotropic responses to isoprenaline or phenylephrine alone. Glibenclamide had no effect but 4-aminopyridine, procaine (30 μm) and tetraethylammonium (3 Mm) augmented the cardiac stimulation response. The ability of pinacidil to attenuate the cardiac stimulation response was not altered by glibenclamide, 4-aminopyridine or procaine but was prevented by pretreatment with tetraethylammonium. Thus, on the rat left atria, pinacidil has a negative inotropic effect which is unrelated to the opening of ATP-sensitive potassium channels, but may be due to opening the inward rectifying potassium channels.
Spontaneous Formation of Small Sized Albumin/acacia Coacervate Particles
Authors: Burgess D J , Singh O N 
Published: April 2011

Abstract
Microgel coacervate particles form spontaneously on mixing aqueous solutions of oppositely charged albumin and acacia, under specific conditions of pH, ionic strength, and polyion concentration, close to but not at the optimum conditions for maximum coacervate yield. The mean particle diameter of these coacervate particles is approximately 6 μm when suspended in aqueous media, as determined by HIAC/Royco particle analysis. The geometric standard deviation of the particles falls in the range 1·2–1·9 μm. The particle size was not dependent on the method of emulsification of the coacervate in the equilibrium phase, or on the stirring speed applied during the manufacturing process. The microgel particles were stable on storage, for periods up to forty-six days, without the addition of a chemical cross-linking agent, or the application of heat. Stability was measured with respect to the change in particle size of samples stored at different temperatures. The non-cross-linked microcapsules were also shown to be stable on pH change, to pH values outside the coacervation pH range. At the optimum conditions for maximum coacervate yield the albumin/acacia system formed a very viscous coacervate phase, which was unsuitable for microcapsule preparation. The Theological properties of albumin/acacia and gelatin/acacia complex coacervates optimized for maximum coacervate yield were compared. The albumin/acacia coacervate was shown to be three orders of magnitude more viscous than the gelatin/acacia system.
The Redistribution of Bulk Aqueous Phase Phospholipids During Thermal Stressing of Phospholipid-stabilized Emulsions
Authors: Groves M J , Herman C J 
Published: April 2011

Abstract
The mechanism of the stabilization of triglyceride emulsions by phospholipids has been studied using an HPLC-FID method to determine phosphatidylcholine, lyso-phosphatidylcholine and phosphatidylethanolamine in the oil and aqueous phases of a model emulsion consisting of soybean oil 20 g, egg phospholipid 1·2 g, glycerol 2·25 g and water to 100 mL. It was shown that, on heat sterilization of the emulsions, the phospholipids rapidly relocate from the aqueous phase to the oil phase. It is suggested that the phospholipids concentrate in the oil/water meso phase, forming a cubic liquid crystalline phase, the bulk of which is converted to a lamellar phase on cooling, and that this organization of interfacial material accounts for the enhanced stability of phospholipid emulsions after heat sterilization.
Comparison of Depolarizing and Direct Current Systems on Iontophoretic Enhancement of Transport of Sodium Benzoate Through Human and Hairless Rat Skin
Authors: Numajiri Sachihiko , Sakurai Hidetomo , Sugibayashi Kenji , Morimoto Yasunori , Omiya Harumi , Takenaka Haruyuki , Akiyama Noriyoshi 
Published: April 2011

Abstract
A direct current (DC) system and a pulsed depolarization (PD) system were evaluated for their iontophoretic permeation of sodium benzoate, as a model drug, through hairless rat and human skin. Approximately the same initial permeation of sodium benzoate through the hairless rat skin was obtained at 0·1 mA for the DC device and at 3·0 mA for the PD device. Study of the drug’s permeation was performed using a two-chamber iontophoretic diffusion cell, over two cycles of three successive on-off experimental conditions [stage I (off) 0–4 h, II (on) 4–6 h, III (off) 6–10 h, saline washing 10–24 h, IV (off) 24–28 h, V (on) 28–30 h and VI (off) 30–34 h]. Skin permeation rate during stage IV of the iontophoresis as compared with the control group through hairless rat or human skin for the DC system was 2–4 times that in stage I, whereas in the same stage using the PD system it was almost the same as in stage I. Impedance of skin decreased during the application of either system (stage II); however, the value significantly recovered during stage III only in the case of the PD system use on human skin. Histological observation revealed no tissue alteration in the hairless rat skin after using either system. When the DC or PD system was applied to volunteers, the minimum current density producing pain was 0·016 or 2·7 mA cm−2, respectively. These results suggested that the PD system was more appropriate for iontophoresis application than the DC system from the point of view of skin permeability of the drug and effect on the skin.
Effects of Capsaicin on the Pharmacokinetics of Antipyrine, Theophylline and Quinine in Rats
Authors: Wanwimolruk S , Nyika S , Kepple M , Ferry D G , Clark C R 
Published: April 2011

Abstract
Capsaicin is the active principal of capsicum fruits, such as hot peppers. The influence of 1-week pretreatment of capsaicin (25 mg kg−1) on the pharmacokinetics of antipyrine, theophylline and quinine was investigated in rats. The drugs were given as an intravenous bolus dose. The control rats received the vehicle solvent (polyethylene glycol) only. Clearance of antipyrine in the capsaicin-pretreated rats was significantly lower than that observed in the control rats (0·241 ± 0·029 vs 0·344 ± 0·034 L h−1 kg−1, P &lt; 0·05). This is consistent with a prolongation in the elimination half-life of antipyrine in animals pretreated with capsaicin (2·06 ± 0·30 vs 1·61 ± 0·27 h), as the volume of distribution was not significantly changed. In contrast, capsaicin pretreatment had no significant effect on the pharmacokinetics of theophylline and quinine.
The Effects of N-Benzoyl-β-alanine, a New Nephroprotective Drug, on the Distribution and Renal Excretion of Enprofylline in Rats
Authors: Wang Li , Hasegawa Takaaki , Nadai Masayuki , Nabeshima Toshitaka 
Published: April 2011

Abstract
The effects of the new nephroprotective drug N-benzoyl-β-alanine (BA) on the disposition and renal excretion of the bronchodilator enprofylline, which is actively secreted in urine, were investigated in rats. Enprofylline was administered intravenously at a dosage of 2·5 mg kg−1 under three different steady-state plasma BA concentrations (100,200 and 400 μg mL−1) which were achieved by constant infusion rates. Pharmacokinetic parameters for both total and unbound enprofylline were estimated by model-independent methods. The presence of BA (400 μg mL−1) increased the systemic clearance by 25% and the volume of distribution at steady-state by 90%. A significant increase in the dissociation constant, which is the protein binding parameter of enprofylline was observed in the presence of BA (400 μg mL−1), indicating that BA competitively inhibits the protein binding of enprofylline. However, BA significantly decreased the systemic clearance and volume of distribution for unbound enprofylline. These results suggest that BA, the organic anion transport inhibitor, inhibits renal excretion of enprofylline with a high affinity for renal tubular secretion, although the unbound concentration of enprofylline increases with administration of BA. We conclude that BA decreases the renal tubular secretion of enprofylline probably by reducing the affinity of the tubular transport system, and that these changes have marked effects on the pharmacokinetic behaviour of enprofylline.
Distribution of Free and Liposome-encapsulated Cefoxitin in Experimental Intra-abdominal Sepsis in Rats
Authors: Kresta A , Shek P N , Odumeru J , Bohnen J M A 
Published: April 2011

Abstract
The distributions of radiolabelled free cefoxitin (FC) and liposome-encapsulated cefoxitin (LC) were compared in an animal model of intra-abdominal sepsis. Intraperitoneally administered LC was initially retained in the peritoneal cavity with subsequent preferential drug targeting to the liver (14% injected LC) and spleen (6% injected LC) by 3 h post-injection. Differing patterns of liposomal drug and lipid retention indicated that drug release from the liposome complex occurred within the peritoneum, liver and spleen. Intraperitoneal FC was rapidly taken up into the systemic circulation, with peak recovery in the blood (9% injected FC) and liver (5% injected FC) at 1 h post-injection. FC was also rapidly eliminated; 7% of the injected drug was recovered in the kidney 1 h post-injection. A negligible amount of FC was recovered in the spleen and very little FC or LC was found in the lungs of treated animals. Unlike FC, LC was found to provide a sustained bactericidal drug level (&gt; 40 μg mL−1) in the peritoneal fluid for up to 5 h post-injection. LC also achieved significantly higher drug levels, compared with FC, within the liver at 3 and 5 h post-injection. Since severe intra-abdominal sepsis is often characterized by the presence of intraphagocytic bacteria in hepatic and splenic reticuloendothelial systems, the enhanced delivery of liposome-encapsulated anti-microbial agents, such as cefoxitin, to the liver and spleen may provide a more effective treatment for the septic condition.
Genetic Control of Drug-induced Recovery from Murine Visceral Leishmaniasis
Authors: Carter K C , Baillie A J , Alexander J 
Published: April 2011

Abstract
The influence of host genetic background on the response of Leishmania donovani-infected mice to chemotherapy was studied using the H-2d and H-2b haplotypes on a BALB or a B10 genetic background. Animals were treated with free or liposomal sodium stibogluconate and parasite burdens in the liver, spleen and bone marrow were assessed. In all the mouse strains and their congenic derivatives examined, the liver responded best to therapy regardless of drug formulation, whilst the spleen and the bone marrow respectively were increasingly less responsive to chemotherapy. Treatment with free drug was more effective in congenic mice carrying the H-2b haplotype than in those carrying the H-2d haplotype and in mice carrying the same H-2 haplotype, animals from a BALB background were better responders than those from a B10 genetic background. Liposomal drug was more effective than free drug treatment in all four mouse strains and produced a similar significant suppression (&gt; 99%, P &lt; 0·001) in liver parasite burdens to that obtained using a six times greater free drug dose. This liposomal drug dose was more effective than free drug in reducing bone marrow parasite burdens in all four mouse strains and equally (BALB/c mice) or more effective (P &lt; 0·01, BALB/B, B10 and B10.D2 strains) in reducing spleen parasite numbers. Liposomal drug, particularly in the B10 genetic background, effectively negated the H-2 dependent influences apparent using free sodium stibogluconate. These results are discussed in relation to the genetic factors which are known to control the course of L. donovani infection in mice.
Influence of Chinoin-170, a Novel Antitussive, on the Mucociliary Activity in Respiratory Airways of Rats, Rabbits, Guinea-pigs and Man
Authors: Saano Veijo , Minker Emil , Joki Susanna , Virta Pasi , Nuutinen Juhani , Korbonits Dezsö 
Published: April 2011

Abstract
Chinoin-170 (Ch-170; 3,7-dihydro-1,3-dimethyl-7-[(5-methyl-1,2,4-oxadiazol-3-yl)methyl]1H-purine-2,6-dione) is a new antitussive with bronchodilating activity. Its effects on the ciliary beating frequency (CBF) and mucociliary clearance were studied. In tracheal explants of rats, Ch-170 dose-dependently at concentrations 2 and 5 mg mL−1 depressed CBF by 24 and 33%, respectively. In human mucosal explants, however, no effects were seen at concentrations up to 5 mg mL−1. In anaesthetized guinea-pigs, an intravenous 50 mg kg−1 dose of Ch-170 caused no changes, and 100 mg kg−1 increased the CBF by 15%. Intravenous Ch-170 dose-dependently increased by 93 (50 mg kg−1), 179 (70 mg kg−1) and 253% (100 mg kg−1) the tracheobronchial mucociliary clearance in rabbits. The effect, studied using 99mTc-labelled red blood cells as a marker, was of similar quantity to that brought about by administering 16, 25 and 40 mg kg−1 doses of bromhexine. It is concluded that unlike many older antitussives, Ch-170 in-vitro only slightly decreases the CBF in rats and has no adverse effects on the CBF in human mucosal explants at concentrations up to 5 mg mL−1. In-vivo, Ch-170 does not significantly alter the CBF in guinea-pigs, but dose-dependently increases the mucociliary clearance in rabbits. The increase is most probably a result of changes in the production and the properties of respiratory mucus.
Antisecretory Activities of Orally Administered Loperamide and Loperamide Oxide on Intestinal Secretion in Rats
Authors: Beubler Eckhard , Badhri Pramila , Schirgi-Degen Andrea 
Published: April 2011

Abstract
In-vivo experiments in the rat jejunum have been performed to compare the antisecretory effect of orally administered loperamide with the effect of its pro-drug, loperamide oxide. Both loperamide and loperamide oxide, administered orally, reduced the secretory effect of prostaglandin E2 (32 ng min−1, intra-arterially) in the jejunum and the colon. Differences between the two drugs as to time course and dose response can be seen. Loperamide oxide shows its antisecretory effect in the jejunum, and at a dose of 2 mg kg−1 also shows its effect in the colon 1 h after administration. The effect was maximal after 2 h and decreased after 4 h. A dose-response relationship was demonstrated at 2 h in the jejunum and the colon. In comparison, the effect of loperamide started later, and a good dose-response relationship was not observed in the jejunum or in the colon, higher doses always appearing less effective than lower doses.