bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effects of Urapidil on Catecholamine Turnover and Release in the Central Nervous System of the Rat
Authors: Singer Ernst A , Cichini G , Valenta B , Kraupp O 
Published: April 2011

Abstract
The actions of urapidil, prazosin, idazoxan, and haloperidol on the turnover of noradrenaline in the hypothalamus and dopamine in the nucleus accumbens of the rat were investigated using changes in the ratios of 3-methoxy-4-hydroxyphenyl-glycol/noradrenaline (MHPG/NA) and 3,4-dihydroxyphenylacetic acid/dopamine (DOPAC/DA), respectively, as measures for drug-induced effects. Urapidil (2·5–30 mg kg−1 i.v.) increased the ratios of MHPG/NA and DOPAC/DA. Its effects on NA turnover were maximal at 60 min (160% of control at 30 mg kg−1), and on DA turnover at 30 min (138% of control at 30 mg kg−1). Prazosin (0·5–2·5 mg kg−1 i.v.) had no effect, but the high dose of 5 mg kg−1 i.v. significantly increased the ratio of MHPG/NA in the hypothalamus. Idazoxan (2–50 mg kg−1 i.v.) and haloperidol (0·02–0·5 mg kg−1 i.v.) selectively enhanced turnover of NA and DA, respectively. In experiments on field-stimulated overflow of tritium from slices of hypothalamus and nucleus accumbens labelled with [3H]NA or [3H]DA, respectively, urapidil (1 μmol L−1) facilitated the evoked responses in both regions. Prazosin (0·1 μmol L−1) had no effect in either of the two areas. Idazoxan (0·1 μmol L−1) increased stimulated overflow of [3H]NA from the hypothalamus but not of [3H]DA from the nucleus accumbens. Conversely, haloperidol (0·1 μmol L−1) greatly enhanced evoked overflow of [3H]DA but not of [3H]NA. From the present results it is concluded that urapidil has an antagonistic effect at central α2-adrenoceptors and also a weak antagonistic action at central dopamine D2-receptors.
Non-linear Intestinal Absorption Kinetics of Cefadroxil in the Rat
Authors: Sánchez-Picó Antonio , Peris-Ribera José-Esteban , Toledano Coral , Torres-Molina Francisca , Casabó Vicente-Germán , Martín-Villodre Adela , Plá-Delfina José M 
Published: April 2011

Abstract
Absorption of Cefadroxil in a selective intestinal absorption area (the proximal third of the small intestine) of the anaesthetized rat, at seven initial perfusion concentrations, ranging from 0·01 to 10·0 mg mL−1, is shown to be a non-linear transport mechanism. With the aid of computer-fitting procedures based on differential and integrated forms of Michaelis-Menten equation, Vm and Km values of 36·7–37·3 mg h−1 and 12·0–13·0 mg, respectively, were found. The statistical parameters were better than those obtained both for first-order and for combined Michaelis-Menten and first-order kinetics. There is no evidence for substantial passive diffusion processes. The results reported here, together with allometric considerations and literature data analysis, may help to explain some particular non-linear features of plasma level curves associated with the administration of fairly high oral doses of Cefadroxil to humans.
The transport of microspheres from the gastro-intestinal tract to inflammatory air pouches in the rat
Authors: Alpar H O , Field W N , Hyde R , Lewis D A 
Published: April 2011

Abstract
The distribution of latex microspheres (1·1 μ diam) has been investigated in-vivo, as a potential passive targeted system for the treatment of inflammation. Microspheres administered orally were found in the circulation and in inflamed tissues and exudates of inflammatory air pouches in rats. Oral absorption was also found in a rabbit. Particles administered directly into the circulation also penetrated into the air pouch tissues and fluids. The possibility of using microspheres as a passive targeted system for the treatment of inflammation is discussed.
Sustained release ophthalmic formulations of pilocarpine
Authors: Deshpande S G , Shirolkar Satish 
Published: April 2011

Abstract
The bioavailability of drugs from conventional ophthalmic formulations is low. To optimize the therapy, sustained release ophthalmic dosage forms are warranted. Hydrogels such as sodium-carboxymethyl cellulose, hydroxypropylmethyl cellulose, Carbopol-940, Carbopol-941 and Lutrol-FC-127 increase the duration of action of various drugs. Gels containing pilocarpine were prepared and evaluated by measuring the intensity and duration of miotic response in albino rabbits. Carbopol-940 gels, being the best of those used, were studied further for the effect of its concentration and of additives (benzalkonium chloride, phenylmercuric nitrate, chlorbutol and disodium edetate), autoclaving at 121°C for 30 min and irradiation with gamma rays (2·5 Mrad), on the end product.
Comparative effects of ouabain on isolated papillary muscle from tree shrews, guinea-pigs and rats
Authors: Koga Takaki , Shiraki Yasuyuki , Sakai Kazushige 
Published: April 2011

Abstract
Inotropic effects of ouabain were investigated in the isolated papillary muscle preparations of the tree shrew (Tupaiaglis), guinea-pigs and rats. In the guinea-pig and shrew papillary muscles, ouabain at concentrations of 10−8 to 3 × 10−7 M caused a concentration-dependent positive inotropic response in a similar magnitude, while in the rat, ouabain at concentrations of 10−7 to 3 × 10−6 M elicited negative inotropic one. Either phentolamine or pindolol in a concentration sufficient to block the α- and β-adrenoceptors did not antagonize the positive inotropic effect of ouabain in the papillary muscle preparation of the shrews.
Nasal absorption of 17α-ethinyloestradiol in the rat
Authors: Bawarshi-Nassar R N , Hussain A , Crooks P A 
Published: April 2011

Abstract
The bioavailability of 17α-ethinyloestradiol was determined after intravenous, nasal, and intraduodenal, administration in the rat. The results showed that the bioavailability of nasally-administered and intraduodenally-administered drug was 80–85, and 15–25%, respectively, of that following intravenous administration. The study demonstrates that the nasal route for the administration of 17α-ethinyloestradiol is superior to the oral route in this species, and may thus provide an alternative for the administration of this drug at lower doses.
Inhibition of Na+, K+ -ATPase Activity by Phospholipase A2 and Several Lysophospholipids: Possible Role of Phospholipase A2 in Noradrenaline Release from Cerebral Cortical Synaptosomes
Authors: Nishikawa Takashige , Tomori Yuichi , Yamashita Sukehide , Shimizu Shin-Ichiro 
Published: April 2011

Abstract
p-Bromophenacyl bromide (PBPB), quinacrine and indomethacin, which inhibit phospholipase A2 (PLA2; EC 3.1.1.4) activity in several tissues, caused a dose-dependent inhibition of prelabelled [3H]noradrenaline ([3H]NA) release evoked by high concentrations of K+ from rat cerebral cortical synaptosomes. Release of prelabelled [3H]NA was caused by natural lysophosphatidic acid (LPA; 10−6-10−5 gmL−1) and lysophosphatidylcholine (LPC; 10−6-10−5 g mL−1) and synthetic LPA (6 × 10−6, 2 × 10−5 M) and LPC (6 × 10−6, 2 × 10−5 M), but not by natural lysophosphatidylserine (LPS; 10−5 g mL−1), lysophosphatidylethanolamine (LPE; 10−5 g mL−1) and lysophosphatidylinositol (LPI; 10−5 g mL−1). The release evoked by natural LPA and LPC could be inhibited only marginally by PBPB and quinacrine. Phosphatidic acid (PA)-specific and phosphatidylcholine (PC)-specific PLA2 activities from rat cerebral cortical synaptosomes were stimulated in incubation medium containing high concentrations of K+ or calcium ionophore A23187. Low concentrations of PLA2 (10−6–10−8 g mL−1, from bee venom) inhibited the synaptic membrane Na+, K+-ATPase activity in incubation media with intracellular levels of free Ca2+. Several lysophospholipids (LPLs), metabolites of the PLA2 type, also inhibited the synaptic membrane Na+, K+-ATPase activity in a dose-dependent manner. The minimum effective concentrations of natural LPA, LPC, LPS, LPI and LPE were 10−6, 4·7 × 10−6, 10−5,4·7 × 10−5 and 4·7 × 10−5 g mL−1, respectively. These results suggest that PLA2 and/or its metabolites, LPLs, especially LPA and LPC, may play partial roles in the depolarization and/or release of noradrenaline through their inhibitory action on the Na+, K+-ATPase activity in the brain.
Involvement of Sialic Acid in High-affinity Binding of Quaternary Ammonium Compounds by Brush Border Membrane from Rat Intestine
Authors: Saitoh Hiroshi , Ebina Mikiko , Fukuda Seiko , Iseki Ken , Miyazaki Katsumi , Arita Takaichi 
Published: April 2011

Abstract
As one approach to clarify the absorption mechanisms of quaternary ammonium compounds (QACs), their binding characteristics have been studied using brush border membrane vesicles isolated from rat small intestine and liposomes composed of phospholipid and GM3 ganglioside. The binding of propantheline was significantly decreased when the vesicles were pretreated with neuraminidase. Propantheline and methochlorpromazine bound to the liposomes, the binding for the latter drug being significantly greater than that for propantheline. When GM3, isolated from rat small intestine, was incorporated into the liposomes their binding capacity for both drugs increased significantly. It is suggested that the binding of QACs to the lipid layer and sialic acid play a role in the high binding of drugs to the intestinal brush border membrane. Furthermore, a sensitive and reproducible high-performance liquid chromatographic method for sialic acid has been developed.
Assignment of the C-5 configuration of penicilloic acids
Authors: Bird A E , Cutmore E A 
Published: April 2011

Abstract
Penicilloates prepared by the method of Munro et al (1978) were examined by nuclear magnetic resonance spectroscopy and optical rotation to assign the configuration at C-5. The configuration was 5S for carbenicillin and ticarcillin penicilloates and 5R for the other seven penicilloates examined. The chemical shift and coupling constants of 5-H and 6-H showed consistent differences between the isomers and the optical rotation of the 5R- isomers is consistently more positive than that of the corresponding 5S-isomer.
Solute adsorption and concentration-dependent permeability in certain polymer films
Authors: Okor R S 
Published: April 2011

Abstract
Certain parameters (solute adsorption, permeability and swellability) of films of a cationic acrylatemethacrylate copolymer have been determined as functions of the solute (sulphacetamide sodium) concentrations. Both permeability coefficients and the free (unadsorbed fraction of solute increased almost proportionately during increase in solute concentration 1–5%, above 5%, further increase in the fraction of free solute was slight, while the permeability coefficients decreased slightly. The solute also reduced film swellability but the observed concentration-dependent permeability related more to the adsorption phenomenon.
The Effect of Gelatin Grade and Concentration on the Migration of Solutes Into and Through Glycerogelatin Gels
Authors: Gebre-Mariam Tsige , Armstrong N Anthony , Brain Keith R , James Kenneth C 
Published: April 2011

Abstract
The diffusion of 4-hydroxybenzoic acid and phenobarbitone through glycerogelatin gels was found to be independent of the type of gelatin used. Three types of gelatin, two acid-processed and one alkali-processed were studied, and the bulk viscosities of gels prepared from them was seen to vary considerably. However, the microviscosities of the gels, as measured by ESR, showed no significant differences. Thus microviscosity was the factor governing diffusion. Gelatin concentration in aqueous solutions without glycerol influenced microviscosity and hence diffusion. This is believed to be caused by dissolution of water-soluble fractions of the gelatin. Interstices in the gelatin matrix, though reduced in size when gelatin concentration is raised, are still too large to act as physical barriers to diffusing molecules. It is suggested that hydrated gelatin forms the matrix of glycerogelatin mixtures and that the interstitial fluid, through which migration occurs, consists almost entirely of glycerol and water.
Vascular Smooth Muscle Function in Rats with Acute Renal Failure
Authors: Douglas S A , Bowmer C J , Yates M S 
Published: April 2011

Abstract
Vascular smooth muscle function in rats with glycerol-induced acute renal failure (ARF) was investigated by recording both the contractile responses of portal vein segments and the relaxant responses of aortic ring preparations. The portal veins from rats with ARF showed depressed contractile responses to the (α1-agonist methoxamine, the α2-agonist B-HT 920 and to the calcium agonist BAY K 8644 when compared with controls. Both isoprenaline and nitroprusside produced 100% reversal of KCl induced tone in control aortic rings but in rings from rats with ARF complete reversal of tone could not be obtained with either dilator drug. It is suggested that a defect in mitochondrial function and hence energy supply may account for the diminished ability of vascular preparations from rats with ARF to constrict and relax.
Interactions of Apomorphine and a Novel Neuroleptic Dibenzodioxazocine Derivative, as Evidenced by Changes of Somato-autonomic Reflexes and Spontaneous Sympathetic Activity in Cats
Authors: Dóda Margit 
Published: April 2011

Abstract
The apomorphine-antagonistic effects of EGYT-2509, a novel neuroleptic compound, has been studied by two different methods suitable for investigating the dopaminergic modulation of sympathetic output. (1) In cats lightly anaesthetized with urethane (600 mg kg−1 i.p.), blood pressure (BP) reflexes evoked by electrical stimulation of the sciatic nerve were inhibited by apomorphine (0·2 mg kg−1 i.v.) at low frequencies of stimuli (2–8 Hz), while the BP reflexes were facilitated by apomorphine at higher frequencies of stimulation; the evoked contractions of the nictitating membrane were depressed in the entire range of frequencies applied. EGYT-2509 (1·5 mg kg−1 i.v.) antagonized both the inhibition and facilitation of pressor reflexes induced by apomorphine. EGYT-2509, given alone, in doses exceeding 1·5 mg kg −1 either did not influence or inhibited the responses of nictitating membrane and of BP; the inhibition could be antagonized by haloperidol. The apomorphine-induced sustained hypotension was inhibited by EGYT-2509 (18·5 mg kg−1): after EGYT-2509, higher doses of apomorphine (0·7 vs 0·2 mg kg−1) were required for the effect. Sustained hypotension could be elicited by EGYT-2509, too; after apomorphine, smaller doses of EGYT-2509 (8·5 vs 18·5 mg kg−1) were enough to decrease BP. (2) In cats anaesthetized with chloralose and urethane (50 and 400 mg kg−1 i.p., respectively), apomorphine (0·2 mg kg−1) inhibited the spontaneous activity of the postganglionic renal sympathetic nerve. EGYT-2509 (&lt;1 mg kg−1) and chlorpromazine (0·2-0·5 mg kg−1) failed to antagonize the apomorphine-induced inhibition. Haloperidol (0·4 mg kg−1), however, restored the renal nerve activity. All three compounds, EGYT-2509, chlorpromazine and haloperidol, themselves, inhibited the sympathetic discharges. The results indicate that EGYT-2509, in addition to its potent anti-apomorphine activity, possesses some apomorphine-like features, too.
Repeated Administration of Antidepressants Enhances Agonist Affinity for Mesolimbic D2-Receptors
Authors: Klimek Violetta , Maj Jerzy 
Published: April 2011

Abstract
Studies have shown an increased responsiveness of the dopaminergic system after repeated administration of a variety of antidepressant drugs. In the present study, the effect of repeated administration (twice daily for 14 days) of imipramine and mianserin on the affinity of dopamine D2-receptors for quinpirole, a D2-agonist, and on the quinpirole-induced locomotor hyperactivity was examined in rats. Repeated doses of imipramine and mianserin increased the affinity of quinpirole for [3H]spiperone binding sites in membranes prepared from the limbic system but not the striatum. The locomotor hyperactivity induced by quinpirole was enhanced by chronic treatment with both antidepressants. The data indicate that the enhanced responsiveness of the dopaminergic system in rats, observed after chronic treatment with antidepressants, may result from an increased affinity of agonists at D2-receptors in the mesolimbic system.
High resolution electron microscopy study of sulphathiazole crystals
Authors: Luklinska Z H , Solanke O O , Summers M P 
Published: April 2011

Abstract
A high resolution electron microscopy study was undertaken on samples of sulphathiazole obtained by recrystallization at 0°C, 30°C and 70°C. Low magnification electron microscopy study of the crystals showed featureless morphology yet the resolved lattice images showed imperfections such as dislocations, lattice irregularities and regions of discontinuity.
Pharmacokinetic study of tempo carboxylic acid, a nitroxyl MRI contrast media, in control and streptozocin diabetic rats
Authors: Michel A , Fernandez J P , Subra G , Pull L , Bonnet P A 
Published: April 2011

Abstract
The pharmacokinetics of tempo carboxylic acid (TCA), a nitroxyl contrast medium have been evaluated in control and streptozocin-diabetic rats. Previous magnetic resonance imaging (MRI) studies in diabetic rats showed prolongation of contrast visualization in the renal cavities after injection of TCA. Diabetes induced only slight alterations to the pharmacokinetic parameters. Rate constants and half lives were unchanged after four months of diabetes. A significant decrease of the apparent total body clearance and volume of distribution was observed while the area under the curve was increased. These alterations are not sufficient to explain MRI abnormalities which have to be elucidated.
The protective mechanisms of paracetamol against ethanol-induced gastric mucosal damage in rats
Authors: Poon Y K , Cho C H , Ogle C W 
Published: April 2011

Abstract
The protective mechanisms of paracetamol against ethanol-induced gastric mucosal damage have been examined. The antiulcer action of subcutaneously (s.c.)-injected paracetamol, 250 mg kg−1, was attenuated by either subdiaphragmatic vagotomy or s.c. injection of N-ethylmaleimide, 10 mg kg−1. This attenuation was not seen in rats given paracetamol by the oral route (p.o.). Indomethacin pretreatment, 5 mg kg−1, did not influence the lesion-preventing action of paracetamol given s.c. or p.o. The findings suggest that the antiulcer effect of s.c.-administered paracetamol results from an action involving the vagal nerve and tissue sulfhydryls, but not prostaglandins. On the other hand, the protective mechanism of paracetamol p.o. is independent of the vagal system or tissue sulfhydryls and prostaglandins. It seems that paracetamol given p.o. exerts its antiulcer effect by acting directly on the mucosal cell to strengthen mucosal integrity.
Effects of metabolic inhibitors and incubation temperature on the saturable uptake of propranolol by isolated rat lung tissue
Authors: Iwamoto Kikuo , Watanabe Jun , Yonekawa Hina 
Published: April 2011

Abstract
The effects of several metabolic inhibitors (50 μM) on the initial uptake rate of propranolol (0·5 to 500 #mUg mL−1) by the minced lungs (0·4g) isolated from 7-week-old rats has been investigated in oxygenated, pH 7·4 Krebs-Ringer bicarbonate buffer solution (20 mL) containing 3% BSA at 37°C for 5 min. The effect of the incubation temperature was also examined. Metabolism of propranolol was almost insignificant (i.e. less than 1·3% of the initial load). The overall initial uptake rate was considered to be a combination of apparent linear transport and saturable processes. For the control uptake rate, the linear transport rate constant was 1·26 ± 0·16 g−1 mL−1 min−1, while Vmax and Km' of the capacity limited uptake process were estimated as 0·727 ± 0·074 mg g−1 min−1 and 24·8 ± 2·71 μg mL−1, respectively. No metabolic inhibitor tested had an effect on the linear transport rate of propranolol but 2,4-dinitrophenol and potassium cyanide inhibited saturable uptake rate (i.e. Vmax) of propranolol significantly (P&lt;0·01) while ouabain, phloridine and iodoacetic acid did not do so significantly. Reduction of the incubation temperature to 15°C decreased and at 25°C tended to decrease, both linear transport and saturable uptake rates.
The effect of Miglyol 812 oil on the oral absorption of propranolol in the rat
Authors: Woolfrey S G , Palin K J , Davis S S 
Published: April 2011

Abstract
This work has examined the effect of Miglyol 812 oil and its composite fatty acids on the oral absorption of propranolol with reference to its intravenous (i.v.) pharmacokinetics. Propranolol hydrochloride, spiked with 4-3 H labelled compound, was administered i.v. or orally to male Wistar rats and blood concentrations of parent material determined by liquid scintillation counting after extraction into toluene. An i.v. dose-linearity study indicated dose-independent pharmacokinetics for propranolol at 1–2 mg kg−1, with a mean Cls, Vss, MRTi.v. and t0·5β of 0·076 L min−1 kg−1, 4·74 L kg−1, 57·81 min and 47·10 min, respectively. At 5 mg kg−1, there was evidence of non-linearity with MRTi.v. increased by about 250%, Vss by 170% and t0·5β by 230% compared with the lower doses. After oral administration of propranolol (10 mg kg−1) in aqueous solution, with or without Tween 80 (6%), the mean absorption time (MAT) and terminal half-life were approximately 55 min and 86 min, respectively. The MAT for propranolol administered in a 50% octanoic and lauric acid (1:1 by weight) oil-in-water emulsion, stabilized with 6% Tween 80 (129·90 min), was significantly longer compared with that for a 50% Miglyol 812 oil-in-water emulsion containing the same surfactant (16·55 min). The terminal half-life of propranolol administered in the fatty acid formulation (128·96 min), unlike that for the Miglyol emulsion (54·37 min), was significantly longer compared with that observed after i.v. administration (t0·5β = 47 min). The fraction available for propranolol was independent of formulation with mean values between about 16 and 24%. These results show that the absorption of propranolol in the fatty acid formulation was decreased possibly due to a reduced rate of gastric emptying.
The Inotropic Effect of 4−Aminopyridine and pH Changes in Rabbit Papillary Muscle
Authors: Shahid M , Rodger I W 
Published: April 2011

Abstract
The effects of 4-aminopyridine (4AP), and pH changes have been examined on tension responses and cyclic nucleotide levels in rabbit isolated right ventricular papillary muscles. 4AP augmented papillary muscle contractions in a concentration-dependent manner. However, this positive inotropic action was largely due to an increase in extracellular pH produced by 4AP, rather than an intrinsic activity of the drug. Increases in extracellular pH (from 5 to 9) produced graded and reproducible increases in contractile force which were not blocked by propranolol (1 ± 10−7M) but were inhibited by verapamil in a concentration-dependent manner. The positive inotropic effects of Ca2+ were enhanced and depressed by alkaline and acidic pH, respectively. Neither 4AP nor alkaline pH significantly changed cyclic AMP concentration in rabbit papillary muscles. The cyclic GMP content, however, was increased by 4AP only and this effect was blocked by atropine. The results suggest that the positive inotropic effect associated with a rise in pH from neutrality may be due to facilitation of translocation of membrane Ca2+ and/or to increase the release of Ca2+ from sources within the cell. They also illustrate that a major component of the inotropic effect of 4AP is a result of an increase in extracellular pH.