bluuebunny/crossref_metadata_2025_split huggingface dataset:
Binding of Organic Cations to Brush Border Membrane from Rat Small Intestine
Authors: Saitoh Hiroshi , Kawai Shinji , Iseki Ken , Miyazaki Katsumi , Arita Takaichi 
Published: April 2011

Abstract
The binding of six organic cations (chlorpromazine, promethazine, imipramine, diphenhydramine, methochlorpromazine and propantheline) to the brush border membrane isolated from rat small intestine has been investigated. The cations were bound to the membrane to varying extents, the order of binding being chlorpromazine &gt; promethazine &gt; methochlorpromazine &gt; imipramine &gt; propantheline &gt; diphenhydramine. There was no relation between binding and the chloroform-water partition coefficient. Chlorpromazine binding was significantly decreased in the presence of imipramine, methochlorpromazine and propantheline. Anionic compounds (indomethacin and xanthene-9-carboxylic acid) did not affect chlorpromazine binding. High and low affinity binding of the cations to the intestinal brush border membrane was demonstrated with Scatchard plots and Hill plots. Imipramine and methochlorpromazine inhibited chlorpromazine binding at both binding sites. From the results, it was suggested that the organic cations tested were specifically bound to common binding sites on the brush border membrane.
Application of difference spectroscopy to the determination of some pharmaceutically important nitro compounds
Authors: Hassan S M , El-Din M Sharaf , Belal F , Sultan M 
Published: April 2011

Abstract
A simple and selective spectrophotometric method for the determination of some pharmaceutically important nitro compounds has been developed. The suggested method depends upon the spectral changes induced by reduction using either Zn/HCl or Zn/NH4Cl. The different experimental parameters were studied and incorporated into the procedure. The mean percentage recovery ranged from 99 to 101. The proposed method was applied to the determination of the studied compounds in dosage forms, and the results obtained were compared favourably with those given with the compendial ones.
Uterine inhibitory effect of reticuline
Authors: Martin M L , Sagredo J A , Morais J M , Montero M J , Sanchez M T , Roman L San 
Published: April 2011

Abstract
Reticuline, the most abundant benzylisoquinoleic alkaloid of Laurobasidium lauri, exerts a uterine inhibitory effect mainly related to a decrease in the concentration of cytosolic calcium available for contraction.
The in-vitro percutaneous absorption of glycerol trioleate through hairless mouse skin
Authors: Moloney Stephen J 
Published: April 2011

Abstract
The chemical composition of the aqueous receptor fluid in one-chambered diffusion cells used for in-vitro percutaneous absorption studies has been shown to significantly affect the apparent extent of absorption of the triglyceride, glycerol trioleate. Using murine skin samples it was found that the addition of albumin to the receptor fluid resulted in an increase in the apparent extent of absorption, while the presence of the bacteriostatic agent thiomersal resulted in a decrease. The viability of the skin samples had no effect on absorption. It was determined that the chemical species in the receptor fluid was the free fatty acid. Albumin presumably bound the fatty acid, therey creating a sink which enabled the fatty acid to partition from the skin into the receptor fluid.
Effect of Butylated Hydroxyanisole on Hepatic Glucuronidation and Biliary Excretion of Drugs in Mice
Authors: Gregus Zoltan , Klaassen Curtis D 
Published: April 2011

Abstract
Inhibition of glucuronidation by depletion of UDP-glucuronic acid from liver impairs the hepatobiliary transport of glucuronidated xenobiotics. However, it is not known if enhancement of hepatic glucuronidation increases the biliary excretion of these compounds. Therefore, the effect of treatment with butylated hydroxyanisole (BHA), which increases hepatic glucuronidation capacity, on the biliary excretion of compounds undergoing glucuronidation was studied in mice. BHA-feeding (1% for 10 days) increased hepatic UDP-glucuronic acid content by 240% and enhanced hepatic UDP-glucuronosyltransferase activities (expressed per kg body weight) toward valproic acid, phenolphthalein, iopanoic acid and bilirubin 220, 180, 120 and 60%, respectively. BHA treatment did not influence the biliary excretion of unmetabolized cholephils, phenol-3,6-dibromphthalein disulphonate and phenolphthalein glucuronide, but enhanced that of phenolphthalein (+108%), iopanoic acid (+63%) and bilirubin (+33%) as glucuronides. However, these increases were apparent only in the initial phase of excretion. In contrast, BHA markedly decreased (−43%) the biliary excretion of valproic acid glucuronides. Simultaneously, BHA increased the urinary excretion of the glucuronides of phenolphthalein (+48%), iopanoic acid (+450%) and valproic acid (+150%). A shift in the distribution of iopanoic acid and valproic acid and metabolites from liver to kidney was also apparent in BHA-fed mice. Thus, enhanced glucuronidation does not facilitate the biliary excretion of all glucuronidated compounds and only transiently increases others. It is likely that this phenomenon is the result of the glucuronides readily entering the plasma and being excreted by the kidney.
Biochemical Characterization of a New Highly Cardioselective β-Adrenoceptor Antagonist
Authors: Gobbi Marco , Mennini Tiziana , Ratti Emiliangelo 
Published: April 2011

Abstract
P0160 (1-phenyl-3-(2-(3-(2-cyanophenoxy)-2-hydroxypropyl)amino) ethylhydantoin HCl) is an aryloxypropanolamine which contains a ureido group as part of the hydantoin ring. This molecule was synthesized to obtain a more cardioselective β-adrenoceptor blocker. Preliminary data have shown that it is as potent as propranolol and four times more cardioselective than atenolol in pharmacological tests in-vitro and in the conscious rat. In the present study we evaluated the interaction of P0160 with β-adrenoceptors by radioreceptor binding studies and by measuring adenylate cylase activity coupled to β-adrenoceptors. The data indicate that P0160 binds with nanomolar affinity to β-adrenoceptors labelled with [3H]DHA in the rat heart, but with micromolar affinity in the rat lung. Its binding is stereospecific, the S-(−)isomer being 200 times more active than the R-(+) form. P0160′s selectivity between cardiac β1- and β2-receptors was 1388, about 60 times that for metoprolol. Analysis of the thermodynamic characteristics of P0160′s interaction with rat heart β-adrenoceptors indicated antagonist properties of the same order of magnitude as propranolol, as confirmed by adenylate cyclase studies. These data indicate that P0160 is a potent, specific and selective β1-adrenoceptor antagonist, and give a molecular explanation for the cardioselective activity found in pharmacological tests.
The Use of a Perfluorochemical Emulsion as a Vascular Perfusate in Drug Absorption
Authors: Takahashi Hideaki , Nishikawa Masahiko , Hayashi Masahiro , Awazu Shoji 
Published: April 2011

Abstract
In-vitro simultaneous luminal and vascular perfusion using the perfluorochemical emulsion, FC-43 emulsion, as a vascular perfusate, was examined for drug absorption in rat jejunum. The intestinal membrane in this system was found to retain its normal barrier functions for drug transport, as evident from the following: (i) stable absorption clearance of tritiated water and salicylic acid at steady-state, (ii) agreement of this clearance with that by in-situ single-pass luminal perfusion, (iii) active transport of D-glucose and its inhibition by phloridzin and (iv) normal glutamate pyruvate transaminase activity in the intestinal mucosa. FC-43 emulsion gave a more normal absorption site blood flow than the usual vascular perfusate containing erythrocytes and albumin in Krebs-Henseleit bicarbonate buffer solution. Consequently, this emulsion was useful for examining the contribution of blood flow resistance toward drug absorption. The rate-limiting steps of absorption of tritiated water, antipyrine and salicylic acid were examined by perfusion using FC-43 emulsion. The absorption of tritiated water was almost completely blood flow-limited and its absorption clearance may possibly be an approximated absorption site blood flow. The contribution of blood flow resistance to total resistance for antipyrine absorption exceeded that for salicylic acid absorption.
Increase in Mouse Brain Regional Noradrenaline Turnover after L-Dopa Administration
Authors: Gibson Candace J 
Published: April 2011

Abstract
Noradrenaline (NA) and its major metabolite, 3-methyl-4-hydroxyphenylethylene glycol (MHPG) were measured by HPLC with electrochemical detection in five mouse brain regions after L-dopa treatment. Noradrenaline concentration increased significantly, by 30–40%, in the three terminal regions of the locus coeruleus; cortex, hippocampus and cerebellum, but did not change in hypothalamus and brainstem. In mice whose central NA levels had been depleted by prior treatment with the neurotoxin, DSP-4, remaining NA neurons in these terminal regions were still able to respond with an increase in NA after L-dopa loading. The NA metabolite, MHPG, increased several-fold in all five regions in both saline and DSP-4-pretreated mice. Thus, L-dopa may be a useful precursor of NA in specific brain regions, particularly when NA is depleted.
The Response of the Intestinal Mucosa to Prostaglandin E2 during Withdrawal from Morphine
Authors: Coupar Ian M , Hardcastle Jacqueline , Hardcastle Peter T 
Published: April 2011

Abstract
Experiments were designed to determine whether the diarrhoea characteristic of morphine withdrawal results from an enhanced sensitivity of the intestinal mucosa to PGE2. Rats (250–300 g) were made morphine-dependent by subcutaneous injection of an emulsion releasing 300 mg morphine HCl over 48 h. In-vivo, the transintestinal potential difference (PD) responses to PGE2 (4.6–46 μg kg−1 i.v.), which reflect increased Cl secretion, were significantly larger in withdrawn (morphine emulsion, 10 mg kg−1 naloxone s.c.) compared with non-dependent animals (emulsion only, naloxone s.c, P &lt; 0.05). Muscle-stripped intestinal sheets from dependent animals incubated with naloxone (10−5 mol L−1) in-vitro did not demonstrate a greater electrical response (PD, short circuit current) to PGE2 (1.4 × 10−6 mol L−1) than sheets taken from non-dependent animals. In-vitro preparations from animals withdrawn in-vivo did not respond differently from tissue taken from non-dependent animals (naloxone 10 mg kg−1 s.c, 10−4 mol L−1 in medium, in both groups). This occurred in whole sheets of intestine as well as sheets without attached muscle. Jejunal fluid absorption in-vivo was lower in withdrawn animals than in non-dependent animals. However, the responses to intra-arterial infusion of PGE2 were similar in both groups with 2 μg min−1 inhibiting absorption and 4 μg min−1 inducing secretion. In-vivo, PGE2-induced Cl secretion appears to be enhanced during withdrawal although net fluid transport is not altered, suggesting different effects of the withdrawal process on the electrogenic Cl secretory and neutral NaCl absorptive mechanisms.
Inhibitory Effect of Glycyrrhetinic Acid Derivatives on Arachidonic Acid-induced Mouse Ear Oedema
Authors: Inoue Hideo , Mori Takeo , Shibata Shoji , Koshihara Yasuko 
Published: April 2011

Abstract
The inhibitory effects of glycyrrhetinic acid and its derivatives were examined on arachidonic acid (AA)-induced ear oedema in mice. Of the compounds, dihemiphthalate derivatives of 18β-olean-12-ene-3β, 30-diol (IId, IId′), 18β-olean-9(11)12-diene-3β, 30-diol (IIIa, IIIa′) and olean-11,13(18)-diene-3β, 30-diol (IVa, IVa′) showed a strong inhibition of ear oedema on both topical (ID50, 1.9, 2.8 and 1.7 mg/ear, respectively) and oral (ID50, 90, 130 and 88 mg kg−1, respectively) administration. Topical ID50 values were approximately the same potency as nordihydroguaiaretic acid (ID50, 2.1 mg/ear). Given topically these compounds were also capable of inhibiting PGE2 and LTC4 formation at an early stage of AA-induced ear oedema. However, glycyrrhetinic acid (Ia) and deoxoglycyrrhetol (IIa), the fundamental skeletons of the derivatives, showed no detectable inhibition of oedema at a dose of 1 mg/ear (topical) or 200 mg kg−1 (oral). The most effective time for the topical administration of the compound IId against ear oedema was 0–30 min before AA application; this is different from dexamethasone which requires a time lag for reaction. The results suggest that the inhibitory effect of the hemiphthalate compounds (IId, IId′, IIIa, IIIa′, IVa and IVa′) is a direct action, and does not involve the anti-inflammatory action of steroids mediated by the secondary formation of a reactive protein.
Pharmacokinetic evaluation of local drug delivery: the intratesticular and intrarenal administration of acenocoumarol in the rat
Authors: Daemen M J A P , Vervoort-Peters H T M , Thijssen H H W 
Published: April 2011

Abstract
According to theory, the regional increase in drug concentration during target organ directed drug delivery as compared with systemic drug delivery is related to the quotient of the clearance of the drug and the blood flow of the target organ. We investigated the steady-state pharmacokinetic disposition of S-acenocoumarol in plasma, liver, testis, and kidney following its administration (constant rate infusion by an osmotic minipump) directly into the testis or the kidney of rats. The effects of clearance induction (phenobarbitone treatment) on the disposition of the drug were also investigated. The results confirm the theory of target-directed drug delivery.
Binding studies on two functional cardioselective antimuscarinic compounds
Authors: Choo L K , Mitchelson F 
Published: April 2011

Abstract
Vecuronium and himbacine are antimuscarinic compounds which in functional studies exhibited a ca 6- and 10-fold higher potency at cardiac muscarininc receptors than at ileal muscarininc receptors. However in binding studies both compounds failed to differentiate between [3H](−)-QNB binding sites in guinea-pig atrial and ileal muscle homogenates. In the latter experiments, the dissociation constants of vecuronium in atria and ileum and that of himbacine in ileum were lower than the values determined functionally. The basis for the lack of cardioselectivity in binding studies is not known. These compounds add to the list of functional cardioselective muscarinic receptor antagonists that failed to display selectivity in binding studies with [3H](−)-QNB.
Flavonoids, leucocyte migration and eicosanoids
Authors: Mascolo N , Pinto A , Capasso F 
Published: April 2011

Abstract
Quercetin reduced the concentration of prostaglandin E2 (PGE2) and leukotriene B4 (LTB4) in the pleural exudate induced in rats by 1% carrageenan given intrapleurally. Leucocyte migration in the exudate was also reduced by the flavonoid. Inhibition of eicosanoids and leucocytes in the exudate was dose-related. Quercetin also reduced LTB4 synthesis in cells stimulated with ionophore A23187, either ex-vivo or in-vitro. A similar, though less active, mode of action was found with quercitrin, while apigenin and luteolin reduced leucocyte accumulation and PGE2 formation, but not LTB4–formation.
Naltrexone and the behavioural action of clonidine in normotensive and spontaneously hypertensive rats
Authors: van den Buuse M , Henneveld H , de Jong W 
Published: April 2011

Abstract
The present experiments were aimed at the behavioural effects of clonidine and the possible involvement of opiate systems therein. Previous work had shown that opiate antagonists could block the effects of clonidine on blood pressure. In the open-field, clonidine treatment induced a decrease in ambulation and rearing activity. This effect was similar in normotensive Wistar and Wistar-Kyoto rats and in spontaneously hypertensive rats. In neither strain did naltrexone pretreatment influence the behavioural action of clonidine, however. These results do not lend support to the proposed interaction between opiate systems and the central effects of clonidine.
Zacopride: anxiolytic profile in rodent and primate models of anxiety
Authors: Costall B , Domeney A M , Gerrard P A , Kelly M E , Naylor R J 
Published: April 2011

Abstract
Zacopride, a substituted benzamide derivative, was compared with diazepam in three models of experimental or provoked anxiety. The drug’s action (i) in reducing aversion to a brightly lit environment was assessed in mice using a two compartment black and white test box system, (ii) in disinhibiting a suppressed behaviour was measured in the rat social interaction test under high light/unfamiliar conditions and (iii) in antagonizing a defensive response in the marmoset was assessed using the threat of a human presence. Both zacopride and diazepam enhanced exploratory behaviour and social interaction in the mouse and rat models and antagonized the defensive response in the marmoset, zacopride being 100 times more potent than diazepam. It is concluded that the 5-HT3 receptor antagonist, zacopride, alters rodent and primate behaviour in a manner consistent with that of an anxiolytic agent.
Anticholinesterase activity of prolactin: correlation with analgesia
Authors: Ramaswamy S , Regunathan S , Bapna J S 
Published: April 2011

Abstract
The possible inhibitory effect of prolactin on serum cholinesterase activity has been examined. Prolactin given to mice inhibited the enzyme’s activity in a dose-related fashion. This inhibition was not reversed by naloxone. A significant correlation was observed between the anticholinesterase and analgesic activity of prolactin. The findings suggest that prolactin may exert its cholinomimetic activity by inhibition of cholinesterase. A significant contribution by the cholinergic activity, which was independent of the opioid system, was indicated in the analgesic effect.
Rate-controlled Absorption Enhancement of Rectally Administered Cefazolin in Rats by a Glyceride Mixture (MGK)
Authors: van Hoogdalem Ewoud J , Stijnen Anna M , de Boer Albertus G , Breimer Douwe D 
Published: April 2011

Abstract
The enhancing effect of the medium chain glyceride preparation MGK on the rectal absorption of the cephalosporin antibiotic cefazolin sodium was evaluated in relation to the rate of delivery. Cefazolin sodium proved to be absorbed to a small extent (15 to 27%) after rectal administration without MGK. Bolus administration with MGK enhanced rate and extent of cefazolin sodium absorption, resulting in a bioavailability of 57 ± 26%. Linear infusion of 3 mg cefazolin sodium with MGK in 32 min produced complete absorption of the antibiotic (102 ± 7%), but absorption occurred slower in comparison with bolus delivery. The rate of administration proved to be an important variable of the absorption enhancing effect of MGK.
Glycogenolysis in the Rat Isolated Perfused Liver as a Measure of Chemically Induced Liver Toxicity
Authors: Nishihata Toshiaki , Ikawa Chie , Saitoh Yukiko , Sakai Kiyoshi 
Published: April 2011

Abstract
The relationship between chemically induced glycogenolysis and decreased thiol content in the rat isolated, perfused liver has been examined. Chemicals such as 2,4-dinitrophenol (DNP), diethyl maleate, alchohols and anti-inflammatory agents (except for sodium salicylate) accelerated glycogenolysis. Protein thiol loss correlated well with a marked increased rate of glucose release. Non-protein thiol loss, without significant loss of protein thiol, caused by a slight increase in the rate of glycogenolysis compared with controls. Since it has been reported that protein thiol loss rather than non-protein thiol loss is correlated to liver cell injury, a marked glucose release from the perfused liver may be a convenient measure of hepatic toxicity for a variety of chemicals.
Particulate contamination in solutions of antibiotics packed as dry powders in vials
Authors: Alexander D M , Veltman A M 
Published: April 2011

Abstract
The particulate contamination in 12 formulations of antibiotic solutions in vials packed as dry powders from five South African sources has been analysed quantitatively using a HIAC PC 320 light blockage particle analyser linked to a CMB 60 sensor. Results showed that the level of particulate contamination fell well within the limits set by the USP XXIst Edition for Small Volume Parenterals although four formulations contained some particles ≥50 μm. There was no apparent difference between the quality of the same antibiotics from different sources or between vials of the same antibiotics packed in different strengths.
The effect of moisture on the cohesive properties of microcrystalline celluloses
Authors: Heng Paul W S , Staniforth John N 
Published: April 2011

Abstract
A comparative evaluation of two microcrystalline celluloses, Avicel PH101 and Emcocel, revealed some differences in their cohesive properties at different moisture contents. A new method of sandwich rheometry was used to evaluate the cohesive properties of different powder masses. The force required to cause shear failure of a rough-surfaced blade in a powder bed was recorded. Avicel PH101 was found to be more cohesive than Emcocel at moisture contents less than 30 wt%, whereas at higher moisture contents the cohesive behaviour was comparable.
Presynaptic changes promoted by alloxan diabetes in the cat isolated heart
Authors: Ladosky E M P , Fonteles M C 
Published: April 2011

Abstract
Adrenergic presynaptic functions were evaluated in the cat isolated perfused heart preparation. The sympathetic nerve endings were labelled with [3H]noradrenaline ([3H]NA) and the effect of electric neural stimulation was determined in the presence of drugs which inhibit neuronal or extraneuronal uptake, or which antagonize α-adrenoceptors. [3H]NA overflow was measured in control and diabetic cats and was significantly increased by electric neural stimulation on both conditions. Perfusion with 0.1 μM phentolamine increased transmitter overflow in control hearts but failed to do so on organs obtained from alloxan-treated cats. The data provide evidence that in alloxan diabetic cats there is an abnormality of the adrenergic synapse.
Intracerebroventricularly administered bradykinin augments carrageenan-induced paw oedema in rats
Authors: Bhattacharya S K , Rao P J R Mohan , Das Neeta , Gupta G Das 
Published: April 2011

Abstract
Intracerebroventricular (i.e.v.) administered bradykinin (2.5 and 5.0 μg/rat) was found to augment carrageenan-induced acute paw oedema throughout the 4 h post-carrageenan observation period. The effect was statistically significant with the higher dose. The pro-inflammatory effect of i.c.v. bradykinin was antagonized following pretreatment with hemicholinium and atropine ethoiodide administered i.c.v., drugs that reduce central cholinergic activity. Similarly, central administration of drugs that inhibit the synthesis of eicosanoids, hydrocortisone, diclofenac and paracetamol, also attenuated the pro-inflammatory effect of bradykinin. The findings indicate that the inflammation-promoting effect of centrally administered bradykinin involves the central prostaglandin and cholinergic neurotransmitter systems.