bluuebunny/crossref_metadata_2025_split huggingface dataset:
Autonomic regulation involved in the ocular hypotensive action of (β-adrenergic blocking agents
Authors: Alkondon M , Ray A , Sen P 
Published: April 2011

Abstract
The effects of racemic propranolol and some related drugs on the intraocular pressure (IOP) were studied after topical application in rabbits. These drugs produced a significant reduction in IOP with the following order of potency: (−)-propranolol &gt; timolol &gt; (±)-propranolol &gt; sotalol &gt; (+)-propranolol &gt; pranolium. Pretreatment of rabbit eyes with atropine significantly antagonized the ocular hypotensive action of (±)-propranolol, timolol and pranolium. Both (±)-propranolol and timolol produced a significant increase in pupil diameter in the presence of a submydriatic dose of atropine. The activities of monoamine oxidase and carbonic anhydrase were unaffected by (±)-propranolol, timolol and pranolium in-vitro. It is concluded from the results that both cholinergic and adrenergic mechanisms may be involved in the ocular hypotensive effects of the drugs.
The effect of temperature on the plasto-elasticity of some pharmaceutical powders and on the tensile strengths of their tablets
Authors: Esezobo S , Pilpel N 
Published: April 2011

Abstract
Measurements have been made of the stress relaxation (SR) during, and of the elastic recovery (ER) after, compression of four directly compressible excipients, and of chloroquine diphosphate and of a paracetamol tablet formulation at temperatures between −10 and +65 °C and of the tensile strengths of the tablets produced. It was found that at a fixed packing fraction, the stress relaxation and tensile strength of all the materials increased and the ratio ER/SR decreased as the compression temperature was raised. Tensile strength was inversely proportional to ER/SR at all the temperatures studied. Values for the activation energies (Eo) of bonding between particles for all the materials were derived from plots of the log of tensile strength and of log SR/ER versus the reciprocal of the absolute temperature. The values of Eo obtained from the latter plots tended to be higher than from the former by a factor of between 1.5 and 4.5.
Characterization of in-vitro drug release and biological activity of methotrexate-bovine serum albumin conjugates
Authors: Halbert G W , Florence A T , Stuart J F B 
Published: April 2011

Abstract
Two series of methotrexate (MTX)-bovine serum albumin (BSA) conjugates have been prepared containing either 96 ± 16 mg (mean ± s.d.) or 32 ± 13 mg of MTX per gram of conjugate. The conjugates released MTX in-vitro in a biphasic manner, the release rate being dependent on the quantity of MTX in the conjugate and on the pH of the release medium. An initial rapid release over 6 h appears to be due to physically adsorbed MTX with the slower secondary release due to covalently bound drug. The conjugates retain a degree of antineoplastic activity in-vitro, but this might be related to the small fraction of MTX that is tightly physically bound.
Auranofin inhibits the active uptake of bile acid by rat ileum
Authors: Hardcastle J , Hardcastle P T , Kelleher D K 
Published: April 2011

Abstract
Auranofin in the mucosal fluid inhibited the active Na+-dependent absorption of taurocholic acid by everted sacs of rat ileum. It did not however, affect the passive uptake of taurocholic acid by sacs of mid-intestine. The inhibition by auranofin of active bile acid absorption could result from its previously demonstrated ability to inhibit Na+, K+-ATPase activity. A reduction in the reabsorption of bile acids by the ileum may contribute to the diarrhoea experienced by some patients taking auranofin.
Effect of moderate haemodilution with Fluosol-DA or normal saline on low-dose phenytoin and (±)-5-(4-hydroxyphenyl)-5-phenylhydantoin kinetics
Authors: Shrewsbury Robert P , Lewis Lee M , Oliver Sharon R 
Published: April 2011

Abstract
Phenytoin kinetics were determined in the rat following moderate (50%) blood exchange with either Fluosol-DA or normal saline. Rats received an intravenous phenytoin dose (10 mg kg−1) 0&#x006d;̇5, 24, 48, or 72 h after exchange and were compared with non-exchanged controls. Phenytoin t1/2 was not altered by exchange with either fluid. Its Cl and Vd were decreased and AUC increased 24, 48, and 72 h after saline exchange and 24 h after Fluosol-DA exchange. (±)-5-(4-Hydroxyphenyl)-5-phenylhydantoin (HPPH), a major metabolite of phenytoin, showed a decreased t1/2 and VHPPH 24, 48, and 72 h after exchange with either fluid; t1/2 was also reduced 0&#x006d;̇5 h after Fluosol-DA exchange. The decreased Vd and VHPPH may result from changes in cardiac output secondary to haemodilution, or may represent a redistribution in the microcirculation. Fluosol-DA appears to enhance phenytoin and HPPH metabolism 48 and 72 h after exchange.
Interactions of trimebutine with guinea-pig opioid receptors
Authors: Roman François , Pascaud Xavier , Taylor John E , Junien Jean-Louis 
Published: April 2011

Abstract
Affinities of trimebutine (TMB) and N-desmethyl trimebutine (NDTMB) for mu, delta and kappa opioid receptor subtypes have been examined using specific 3H-ligands and guinea-pig membrane. TMB and NDTMB showed a relative higher affinity for the mu receptor subtype although they were, respectively, 30-and 48-fold less active than morphine. The receptor selectivity index for mu, delta and kappa were 100:12:14&#x006d;̇4 for TMB, 100:32:25 for NDTMB and 100:5:5 for morphine. The sodium shift ratio was 14 for TMB, 10 for NDTMB and 37 for morphine. These data show that (unlike morphine, a pure mu agonist) TMB and NDTMB can be classified as weak opioid agonists and confirm that peripheral opioid receptors mediate their gastrointestinal motility effects.
Effect of age on gastrointestinal and hepatic first-pass effects of levodopa in rats
Authors: Iwamoto Kikuo , Watanabe Jun , Yamada Mika , Atsumi Fumie , Matsushita Tomoko 
Published: April 2011

Abstract
Presystemic elimination of levodopa (20 mg kg−1) has been studied in 5- to 104-week-old male Wistar rats. The gastrointestinal and hepatic contribution to the overall first-pass effect was estimated separately after the drug had been administered intravenously, orally and intraportally. The contribution of the gut to the overall first-pass effect of this drug was greater than that of the liver in any age-group of the rats. Both the overall and intestinal first-pass effects of levodopa were greatest in 11-week-old rats and relatively small in both young (between weeks 5 and 7) and aged (between weeks 52 and 104) rats. In contrast, the hepatic first-pass effect did not show any significant age-dependent change. Age-related change in the jejunal blood flow could not explain the unique age-dependence in the intestinal first-pass metabolism of levodopa. However, the present age-dependence in the oral systemic availability of this drug between adult (11 weeks) and aged (52 to 104 weeks) rats was found to be similar to the tendency that has been reported between normal adult subjects and aged patients with Parkinson's disease.
The differential cytotoxicity of antiseptic agents
Authors: Blenkharn J I 
Published: April 2011

Abstract
The cytotoxicity of the antiseptic agents noxythiolin and chlorhexidine has been evaluated in-vitro using a range of tissue culture cell lines of differing degrees of neoplasticity. Noxythiolin appeared more cytotoxic than did chlorhexidine when tested against established neoplastic cell lines. By contrast, noxythiolin was not cytotoxic to normal control (non-neoplastic) cells. For chlorhexidine, the cytotoxic activity against control cells was similar to that observed for neoplastic cell lines. The results confirm an earlier observation of limited antitumour activity of noxythiolin solutions and, on the basis of differential cytotoxicity, confirm that noxythiolin is free from adverse effects against normal tissues and is safe for use as an antimicrobial agent applied to peritoneal surfaces and the healing wound.
Water distribution in creams prepared using cetostearyl alcohol and cetrimide
Authors: Rowe R C , Bray D 
Published: April 2011

Abstract
The water distribution in an antiseptic cream formulation prepared using cetostearyl alcohol and cetrimide has been studied using thermogravimetric analysis, differential scanning calorimetry, ultracentrifugation and scanning electron microscopy. In addition to a free water phase two types of interlamellarly fixed water were found, one associated with the liquid crystalline network around the oil droplets and one associated with the liquid crystalline network of the bulk. The latter was in equilibrium with the free water and can be classed as freely drainable.
The biliary excretion of acenocoumarol in the rat: stereochemical aspects
Authors: Thijssen H H W , Baars L G M 
Published: April 2011

Abstract
Within 24 h, 50% of a single dose of the acenocoumarol enantiomers was recovered in bile and 20% in urine of Wistar rats. The elimination products were mainly (&gt;90%) the 6- and 7-hydroxyacenocoumarol as conjugates in the bile but free in the urine. Only R-acenocoumarol, free and conjugated, was excreted in bile. There were no gross differences between the enantiomers in metabolic pattern or in the amount of metabolites formed. A significant difference was observed for the biliary excretion of the 7-hydroxy metabolite; the ratio of free and conjugated 7-hydroxyacenocoumarol was three times higher for the S-than for the R-isomer. An unknown third metabolite was recovered in bile in higher amounts with the S- than with the R-acenocoumarol. Only traces of this metabolite were recovered from urine. The data show an extensive biliary excretion of acenocoumarol and demonstrate stereoselective mechanisms in the excretion processes.
Stereoselective blockade of central [3H]5-hydroxytryptamine binding to multiple sites (5-HT1A, 5-HT1B and 5-HT1C) by mianserin and propranolol
Authors: Alexander Beverley S , Wood Martyn D 
Published: April 2011

Abstract
The interaction of the enantiomers of mianserin and propranolol with the binding of [3H]5-hydroxytryptamine ([3H]5-HT) to the 5-HT1A, 5-HT1B and 5-HT1C sites, and with the binding of [3H]ketanserin to the 5-HT2 site, has been evaluated in rat brain membranes. A stereoselective interaction at the 5-HT1A, 5-HT1B and 5-HT1C sites was demonstrated for both compounds, with (-)-mianserin being a more potent displacer than (-)–mianserin and (-)-propranolol being more potent than (+)-propranolol. Only mianserin interacted in a stereoselective manner with the 5-HT2 site, (+)-mianserin being the more potent isomer. The stereoselective association of mianserin and propranolol with the 5-HT1A, 5-HT1B and 5-HT1C sites may prove useful in the characterization of these sites.
Gastric ulcerogenicity of non-steroidal anti-inflammatory drugs in mice with mucosa sensitized by cholinomimetic treatment
Authors: Rainsford K D 
Published: April 2011

Abstract
A novel technique is described for the assay of acute gastric irritancy of non-steroidal anti-inflammatory drugs (NSAIDs) in mice in which (a) the gastric mucosa is sensitized to the irritant actions of the drugs by coadministration of bethanechol chloride to increase acid and pepsin production, and (b) the area and number of haemorrhagic lesions in the glandular mucosa is measured quantitatively by visual image analysis. The technique has been used to assess the acute gastric irritancy of 20 NSAIDs in mice. In relation to published values for their acute and chronic anti-inflammatory activities, drugs with low relative gastric irritancy (e.g. carprofen, chloroquine, diclofenac, fenbufen, tenoxicam, tilomisole) were differentiated from the drugs of higher relative irritancy.
A quantitative assessment of the reactivity of the fatty alcohols with cetrimide using immersion calorimetry
Authors: Rowe R C 
Published: April 2011

Abstract
The reactivity of the fatty alcohols with cetrimide has been quantitatively assessed using immersion calorimetry. In all cases the reaction was endothermic i.e. it had a positive enthalpy. For the n-alcohols the reactivity, as evaluated by the rate of enthalpy change, decreased with increasing chain length although branching on the tetradecanol and hexadecanol resulted in a higher reactivity. Adding 1-octadecanol to 1-hexadecanol resulted in an increased reactivity rising to a maximum for mixtures containing 20–40% w/w 1-octadecanol. The results have been interpreted in terms of the polymorphic form of the alcohol.
The effect of digoxin dosage on the digoxin—quinidine interaction in the bile duct-cannulated rat
Authors: Hewick D S , Ostenfeld T 
Published: April 2011

Abstract
Pretreating anaesthetized bile duct-cannulated rats with 9 mg kg−1 quinidine significantly decreased the cumulative biliary excretion of digoxin and its metabolites after 10 or 100 μg kg−1 [3H]digoxin, although the effect was more marked in animals receiving the high dose of digoxin. In contrast, however, although quinidine pretreatment raised plasma radioactivity levels by 50–80% in animals given the higher dose of digoxin, no significant effect on circulating plasma levels was observed in rats receiving 10 μg kg−1 digoxin. Generally, quinidine had no statistically significant effect on other aspects of digoxin disposition, although with both digoxin doses there were trends towards a reduction in the direct intestinal secretion and urinary excretion of digoxin-derived radioactivity with an increase in tissue levels of radioactivity (apart from the small intestine wall where concentrations were reduced). The radioactivity in the bile after 100 or 10 μg kg−1 digoxin comprised about 25 and 33% of digoxin and digoxigenin bis-digitoxoside, respectively, as well as appreciable amounts of the mono-digitoxoside and a highly polar component. This metabolite profile was unaffected by quinidine. The influence of cardiac glycoside dosage shown by the present work indicates that the digoxin—quinidine interaction and possibly analogous interactions involving other cardiac glycosides, may not always be readily detectable from plasma concentration data.
Identification of 15-Hydroperoxyabietic Acid as a Contact Allergen in Portuguese Colophony
Authors: Karlberg Ann-Therése , Bohlinder Karin , Boman Anders , Hacksell Uli , Hermansson JÖrgen , Jacobsson Sven , Nilsson J Lars G 
Published: April 2011

Abstract
15-Hydroperoxyabietic acid (15-HPA) has been isolated from Portuguese colophony of the gum rosin type and identified as its methyl ester. The structure of the compound was elucidated using UV, IR, NMR and mass spectrometry. 15-HPA methyl ester was found to be an elicitor when tested in colophony-sensitized guinea-pigs. The sensitizing capacity was verified in the same species and 15-HPA methyl ester was considered to be a strong allergen. The eliciting potential was also verified in patients with known allergy to colophony. The Portuguese gum rosin investigated contained approximately 1% of 15-HPA. Based on its allergenicity and the amounts isolated, we conclude that 15-HPA is a main contact allergen in Portuguese gum rosin.
Evidence for a functional cholinergic deficit in human colonic tissue resected for constipation
Authors: Burleigh D E 
Published: April 2011

Abstract
There is evidence to suggest an abnormality of the colonic myenteric plexus in severe chronic constipation. The present study investigates whether this abnormality involves functional changes in the cholinergic innervation of human colon. Human taenia coli muscle strips (taenia), previously incubated with [3H]choline to radiolabel neuronal stores of acetylcholine, were subjected to electrical field stimulation (1 Hz or 10 Hz, 1 ms, 480 pulses at 200 mA). The stimulation evoked release of tritiated material, shown previously to accurately represent neural [3H] acetylcholine release, was depressed in tissue from constipated compared with non-constipated patients. Evoked release of tritiated material was reduced by storage of the taenia at 4 °C or by increasing the frequency of stimulation, but increased by stimulation during incubation with [3H]choline. The results indicate that reduced activity of cholinergic nerves may occur within the bowel wall of colon removed for severe chronic constipation.
Effects of zinc sulphate on gastric mucosal blood flow and gastric emptying of the rat
Authors: Lloris J M , Esplugues J V , Sarria B , Calvo M A , Marti-Cabrera M , Marti-Bonmati E , Esplugues J 
Published: April 2011

Abstract
Zinc sulphate (50 mg kg−1 p.o.) did not modify basal gastric mucosal blood flow, as measured by [3H]aniline clearance, but inhibited its reduction by noradrenaline (3.5 μg kg−1 min-1). Zinc sulphate also influenced gastric emptying of phenol red but its effects depended upon the dose; 30 mg kg−1 caused no variation whereas 80 mg kg−1 induced a significant delay. The nature of both actions is discussed and their implications in the development and prevention of gastric ulceration have been analysed.
Solubilization of Vitamin K1 by Bile Salts and Phosphatidylcholine-Bile Salts Mixed Micelles
Authors: Nagata Mariko , Yotsuyanagi Toshihisa , Ikeda Ken 
Published: April 2011

Abstract
The solubilization of vitamin K1 by bile salts (sodium deoxycholate, sodium cholate and their corresponding glycine conjugates) and phosphatidylcholine (egg)-bile salt mixed micelles has been investigated. The solubilization curves were not always linear with increasing bile salts, but the vitamin was appreciably solubilized in the region below their CMCs. In the bile salt solutions (20 mM, phosphate buffered saline, pH 7.5, ions strength 0.2), the solubilized vitamin ranged from 0.3 to 0.9 mM. With increasing phosphatidylcholine, the amount of vitamin solubilized was dramatically increased; at the molar ratio of 1:1 (both 20 mM), the amount of vitamin solubilized was about 25–30 times more than by the corresponding bile salts alone. There is a possibility that exogeneous phospholipid given orally as liposomal forms assists the solubilization of vitamin K1, in the intestine. This characteristic is suggested as being responsible, in part, for the enhanced recovery of blood coagulation after oral administration of liposomal vitamin K1 to warfarin-treated rabbits.
Age-dependent pulmonary first-pass elimination of propranolol in rats
Authors: Iwamoto Kikuo , Watanabe Jun , Aoyama Yoko 
Published: April 2011

Abstract
Plasma levels of propranolol after 2.5 mg kg−1 given i.v. and i.a. have been compared in 3- to 4-week-old rats to evaluate the effect of age on pulmonary first-pass elimination of the drug. In 5- to 52-week-old rats, the area under the plasma concentration-time curve (AUC) after an intra-arterial dose was always larger than that after the i.v. dose. The plasma elimination half-lives after both routes of administration were almost identical, but tended to increase with age between weeks 7 and 104. First-pass pulmonary clearance and extraction ratio tended to decrease with age between weeks 7 and 52.
Determination of rat cerebrospinal fluid concentrations of adenosine, inosine, hypoxanthine, xanthine and uric acid by high performance liquid chromatography
Authors: Walter Gary A , Phillis John W , O'Reagan Michael H 
Published: April 2011

Abstract
Isocratic reverse-phase high performance liquid chromatography techniques were developed to resolve and quantitate the purine nucleosides adenosine (Ado) and inosine (Ino) and their metabolites hypoxanthine (Hyp), xanthine (Xan), and uric acid (UA) in the cerebrospinal fluid of the rat. The moving phase composition for resolving hypoxanthine, xanthine and uric acid was a 0.22 M, pH 5.8 phosphate buffer. The moving phase composition for resolving adenosine and inosine was a 0.22 M, pH 6.8 phosphate buffer, 7% methanol (v/v) and 2.5 mM tetrabutylammonium phosphate. The observed cerebrospinal fluid concentrations in the rat were: Ado = 35 ± 9 nM (s.e.m.), Ino = 359 ± 85 nM, Hyp = 243 ± 77 nM, Xan = 1340 ± 423 nM and UA = 6130 ± 678 nM.
The emetic activity of centrally administered cisplatin in cats and its antagonism by zacopride
Authors: Smith William L , Callaham Esther M , Alphin Reevis S 
Published: April 2011

Abstract
Cisplatin administered by either the intravenous (i.v.) or intra-cerebroventricular (i.c.v.) route produced emesis in cats. The average time to onset of emesis was decreased significantly (4.0 min versus 100.6 min) when cisplatin was administered i.c.v. Zacopride administered either i.c.v. (0.02 mg) or i.v. (0.1 mg kg−1) completely blocked the emesis due to cisplatin given by either route. Their data show that cisplatin possesses a central emetic component and that this is blocked by zacopride.
The Dissolution Rate and Bioavailability of Hydrochlorothiazide in Pellet Formulations
Authors: Herman J , Remon J P , Lefebvre R , Bogaert M , Klinger G H , Schwartz J B 
Published: April 2011

Abstract
The influence of non-active ingredients in the manufacture of pellets on in-vitro dissolution rate and on bioavailability of hydrochlorothiazide has been studied. Pellets were formulated using either microcrystalline cellulose or microcrystalline cellulose-carboxymethylcellulose sodium blends as matrix, and hydrochlorothiazide as the active ingredient. In-vitro drug release from the different pellet formulations was retarded in comparison to a conventional tablet formulation and was dependent on the nature of the non-active ingredient and, for the microcrystalline cellulose-carboxymethylcellulose sodium blend, of the dissolution medium. In-vivo bioavailability of both pellet formulations was low compared with that of the conventional tablet and the plasma concentration-time profiles did not suggest slow release.
Evaluation of Reconstituted Sendai Virus Envelopes as Intra-articular Drug Vectors: Effects on Normal and Experimentally Arthritic Rabbit Knee Joints
Authors: Earl Rupert T , Hunneyball Ian M , Billett E Ellen , Mayer R John 
Published: April 2011

Abstract
Fusogenic vesicles reconstituted from the envelopes of Sendai virus particles were injected into rabbit knee joints (both normal and experimentally arthritic) to evaluate the in-vivo biocompatibility of these putative drug carriers. The reconstituted Sendai virus envelopes (RSVE) were &gt; 80% retained within the arthritic knee joints after 24 h and studies with 125I- and fluoroscein-labelled RSVE both showed association of the vesicles with the synovia of arthritic and healthy joints. However, RSVE were found to cause inflammation after intra-articular injection, as judged by joint swelling and histological assessment, and these effects were exacerbated by successive administrations. RSVE-entrapped methotrexate, whether free or conjugated to human serum albumin, was ineffective in preventing the irritancy of RSVE or in reducing the chronic inflammation in joints affected by an experimentally induced arthritis.
Gastric emptying of large single unit dosage forms
Authors: Davis S S , Norring-Christensen F , Khosla R , Feely L C 
Published: April 2011

Abstract
The gastrointestinal transit of two single unit dosage forms has been followed in healthy subjects under different feeding conditions. Transit was affected by the size of the meal administered. When two tablets were given concurrently they often emptied from the stomach at or about the same time, but in a number of cases the two units were seen to empty at widely different times.