bluuebunny/crossref_metadata_2025_split huggingface dataset:
The therapeutic effect of sodium stibogluconate in BALB/c mice infected with Leishmania donovani is organ-dependent
Authors: Carter K C , Baillie A J , Alexander J , Dolan T F 
Published: April 2011

Abstract
A study of the antileishmanial efficacy of sodium stibogluconate was carried out in BALB/c mice. The drug was administered to Leishmania donovani-infected animals on days 7 and 8 post-infection in one of three forms; free (40–50 mg Sbv Kg−1), liposomal, or niosomal (6.4–8.0 mg Sbv Kg−1) drug. On day 14 post-infection counts of the number of parasites present in the liver, spleen and bone marrow of treated and control animals showed that although all three drug preparations significantly reduced parasite numbers in the liver (≃99% suppression) they had little effect on those residing in the spleen or bone marrow. The carrier forms of the drug were therefore significantly more effective than free drug in reducing liver parasite burdens. Increasing the concentration and the number of doses of free drug (maximum of 500 mg Sbv Kg−1), and reducing the size of the vesicles used to deliver the drug had a minimal effect on parasite numbers in the spleen and bone marrow. It is proposed that because of the resistance of spleen and bone marrow parasites to drug therapy, the BALB/c mouse infected with L. donovani provides an excellent model system for the study of drug delivery to these deeper tissue sites.
The effects of the selective κ-opioid agonist MR 2034 on the guinea-pig ileum
Authors: Coupar Ian M , Quinn Michael J 
Published: April 2011

Abstract
The effects of the selective κ-opioid agonist MR 2034 on the guinea-pig ileum were compared with those produced by the μ-agonist morphine. MR 2034 induced acute tolerance and inhibited electrically evoked contractions to the same extent as morphine. The slope of the concentration-effect curve to MR 2034 was not significantly different from that of morphine. However, MR 2034 and morphine may act at their respective receptors since naloxone was 6.57 times more effective at inhibiting responses to morphine than MR 2034. MR 2034, like morphine, induced acute dependence as revealed by naloxone-induced contractions of tissues that had been incubated with MR 2034 for 5 h. The functional properties of κ-opoid receptors are the same as μ-receptors in the guinea-pig ileum.
Influence of Relative Humidity on the Adhesive Properties of a Model Interactive System
Authors: Kulvanich Poj , Stewart P J 
Published: April 2011

Abstract
The influence of relative humidity on the adhesive properties of model drug-carrier interactive systems was investigated using the centrifuge method. The degree of adhesion was quantified by determining the S50 from the adhesion profile. High ambient humidity (greater than 40% r.h.) decreased the degree of interaction of three sulphonamide powders with model hydroxypropyl methylcellulose phthalate-coated glass bead carriers during blending. All drug-carrier interactive systems displayed decreases in the degree of adhesion during storage. The extent and rate of the decreases increased with relative humidity and was interactive system-dependent. Preconditioning the powders to varying moisture contents produced contrasting results during blending, with one system showing a decrease in adhesion as the relative humidity increased, while the other’s interactive capability increased. This increase was attributed to the enhancement of charging sites on the drug’s powders surface by the adsorbed moisture.
Influence of 5-Tridecylpyrazole-3-carboxylic Acid, a New Hypolipidaemic Agent, on Cholesteryl Ester Formation in Rabbit Intestinal Mucosa
Authors: Seki Kunio , Horie Shuichi , Watanabe Takafumi , Suga Tetuya 
Published: April 2011

Abstract
The comparative effects of 5-tridecylpyrazole-3-carboxylic acid (TDPC), β-sitosterol and melinamide on the esterification of cholesterol (CH) have been investigated in rabbit intestinal microsomes and cytosol in-vitro. The three agents did not show an effect on cholesteryl ester formation by cholesterol esterase (CEase). TDPC and β-sitosterol did not affect cholesteryl oleate formation from oleoyl CoA by microsomal acyl CoA: cholesterol acyltransferase (ACAT), whereas melinamide significantly inhibited cholesteryl oleate formation. TDPC significantly inhibited the incorporation of oleic acid into cholesteryl oleate, which is associated with acyl CoA synthetase (ACS) plus ACAT in mucosal microsomes, at a concentration of 20–100 μM. On the other hand, 5-tridecylpyrazole-3-carbinol (TDPC-OH) a congener of TDPC, and β-sitosterol did not show any effect. From these results, it is demonstrated that carboxylic moiety of TDPC is necessary to inhibit ACS in-vitro. According to the kinetic analytical results, it is suggested that TDPC acts as a competitive inhibitor of ACS. These results suggest that the inhibitory effect of TDPC on cholesteryl ester formation may be mediated by an inhibition of ACS activity. It is apparent from the data presented that there are substantial differences between TDPC, β-sitosterol and melinamide with respect to their action on cholesteryl ester formation in rabbit intestinal mucosa.
The Biphasic Effects of Centrally and Peripherally Administered Caffeine on Ethanol-induced Motor Incoordination in Mice
Authors: Dar M Saeed 
Published: April 2011

Abstract
The possible biphasic effect of caffeine on acute ethanol-induced motor incoordination by rotorod evaluation was investigated in mice. Caffeine in various doses was administered intracerebro-ventricularly (i.e.v.) to mice implanted with permanent indwelling stainless steel guide cannulae and intraperitoneally (i.p.) to non-cannulated animals. A motor incoordinating test dose of ethanol, 2 g kg−1, was given i.p. in both cases. Caffeine &lt; 25 μg administered i.e.v., dose-dependently attenuated while 75 μg i.c.v. potentiated ethanol (i.p.)-induced motor incoordination. Similarly, caffeine &lt; 20 mg kg−1 given i.p., dose-dependently attenuated while 62.5 mg kg−1 potentiated ethanol (i.p.)-induced motor incoordination. The data obtained demonstrated that caffeine given either i.c.v. or i.p. exerted biphasic effects on ethanol-induced motor incoordination. The data also suggested that caffeine antagonized ethanol-induced motor incoordination when administered in appropriately low concentrations. At these low concentrations (&lt; 25 μg i.c.v.; &lt; 20 mg kg−1 i.p.) caffeine is well known to display high affinity for adenosine binding sites. Therefore, the present investigation lends further support to our earlier suggestion that adenosine may be involved in the motor impairing effect of ethanol.
Effects of an extract of feverfew on endothelial cell integrity and on cAMP in rabbit perfused aorta
Authors: Voyno-Yasenetskaya T A , Loesche W , Groenewegen W A , Heptinstall S , Repin V S , Till U 
Published: April 2011

Abstract
Extracts of feverfew inhibit platelet aggregation and secretion of granular contents from platelets and other cells. They also modify the interaction of platelets with collagen substrates: feverfew extracts inhibit both platelet spreading and formation of thrombus-like platelet aggregates on the collagen surface. We have now investigated the effect of an extract of feverfew on the vessel wall using rabbit aortas that were perfused with a physiological salt solution in-situ. Addition of feverfew extract to the perfusion medium protected the endothelial cell monolayer from perfusion-induced injury and led to a reversible increase in the cAMP content of aorta segments. The results indicate that feverfew may have a vasoprotective effect in addition to its effects on platelets.
Comparison of the In-vitro Receptor Selectivity of Substituted Benzamide Drugs for Brain Neurotransmitter Receptors
Authors: Chivers J K , Gommeren W , Leysen J E , Jenner P , Marsden C D 
Published: April 2011

Abstract
The in-vitro selectivity of a group of substituted benzamide drugs for brain neurotransmitter receptors was determined to assess the most appropriate drugs for use in human PET studies. All substituted benzamide drugs studied inhibited [3H]haloperidol and [3H]spiperone binding to rat striatal membranes. The most potent compounds were YM 09151-2, clebopride and raclopride. However, these substances also interacted in differing degrees with α-l, α-2, β-adrenergic, 5-HT-1, 5-HT-2, and opiate sites. Sulpiride, alizapride, SL 74205, TER 1546 and tiapride were specific for D-2 receptors, but these drugs were active only in the 10−7–10−6 M range. Raclopride, amisulpiride and sultopride showed a 100–1000 differentiation between action on dopamine sites compared with other neurotransmitter receptors. No such selectivity was observed for clebopride or YM 09151-2. Specific substituted benzamides such as alizapride, may be appropriate in high concentrations for defining the interaction of PET ligands with brain dopamine receptors. More potent, but selective, drugs such as raclopride and amisulpiride, may be effective in low concentrations as ligands for labelling dopamine receptor sites. However, the ability of these various substituted benzamide drugs to penetrate into brain and in-vivo to identify dopamine receptors in all brain areas must be assessed.
High speed photographic analysis of aerosols produced by metered dose inhalers
Authors: Dhand R , Malik S K , Balakrishnan M , Verma S R 
Published: April 2011

Abstract
The design of pressurized metered dose inhalers (MDI) used to assess asthma is variable. We have examined the aerosol spray flumes generated by four commercially available MDI products using high speed video photography. For this purpose a moulded jacket was designed which could hold the inhaler in an immovable position during actuation. Fresh inhalers were fitted in the jacket after thorough shaking and three successive actuations 30 s apart were filmed with a high speed video camera (200 frames s−1). The aerosol, ejected at high velocity into calm room air, was seen to have a ‘jet’ phase followed by a ‘cloud’ phase as a result of particle dispersion. Filming was continued till the flume could no longer be visualized on the TV monitor. High speed photography was used to record flumes seen on the video monitor, to enable characterization of flume appearance, dimensions and mean velocity.
Excitatory P1-purinoceptors on pre- and post-ganglionic cholinergic nerve terminals in the chick oesophagus
Authors: Mishra S K , Raviprakash V 
Published: April 2011

Abstract
The mechanism of action of ATP and the purinoceptors involved have been investigated on the chick oesophagus. The susceptibility of the excitatory responses to ATP/adenosine to tetrodotoxin indicates that their action is neurally mediated. Blockade of ATP/adenosine responses by atropine suggests the involvement of endogenous acetylcholine. ATP action depends on breakdown to AMP/adenosine, since theophylline blocks ATP/adenosine responses. The inhibition of ATP responses by pentolinium implies the involvement of preganglionic fibres.
Enhancement of capsaicin-induced contraction of guinea-pig tracheal smooth muscle by vanadate
Authors: Nayler Ross A 
Published: April 2011

Abstract
Contractions of guinea-pig isolated tracheal smooth muscle by submaximal capsaicin (0.1 μM) were enhanced by 43% (P &lt; 0.01) after vanadate (10 μM for 10 min) preincubation. Contractile responses to acetylcholine (0.1–100 μM), histamine (1–100 μM) or substance P (0.01–1 μM) were, in contrast, not affected by prior vanadate exposure. It is suggested that tachykinin release from capsaicin-sensitive afferent nerve endings within the airways was enhanced by vanadate while airway smooth muscle reactivity remained unchanged.
Chronic antidepressant treatment increases the apomorphine-induced elevation of plasma corticosterone in rats
Authors: Kourkoubas Anthony , Pitoulis Spyros , Spyraki Christina 
Published: April 2011

Abstract
Plasma corticosterone concentrations in response to subcutaneous administration of apomorphine (25 and 200 μg kg−1) have been assessed in rats treated acutely (2 days) or repeatedly (15 days) with saline, clomipramine, electroshock and clomipramine + electroshock. Chronic, but not acute, antidepressant treatment decreased the corticosterone level which remained unchanged in control and in rats acutely treated with apomorphine. Chronic antidepressant treatment significantly increased the corticosterone response to apomorphine. Neuroendocrine evidence is provided for an increased responsiveness of dopamine receptors which are thought to mediate the apomorphine effect on corticosterone secretion following chronic antidepressant treatment.
Hydroxylation of Debrisoquine Using Perfused Liver Isolated from Sprague Dawley and DA Rats: Comparison With In-vivo Results
Authors: Vincent-Viry M , Deshayes S , Mothe O , Siest G , Galteau M M 
Published: April 2011

Abstract
The hydroxylation of debrisoquine was investigated in Sprague-Dawley (SD) and Dark-Agouti (DA) rats. Female and male rats were phenotyped in-vivo with debrisoquine six times during their growth. The ratios debrisoquine/4-hydroxydebrisoquine of the female DA rats increased until the 15th week and then decreased; but the values of the metabolic ratios never exceeded 2. Female DA rats cannot be considered as genetically deficient for hydroxylation of debrisoquine in regard to the metabolic ratio, but the percentage of debrisoquine excretion is up to ten fold higher than that in the other strains. Therefore SD and DA rat livers were perfused for 2 h when the clearance of debrisoquine was significantly lower in the female DA group than in the other groups. 4-Hydroxydebrisoquine in the perfusate increased with time, but the amount after 120 min was 12 fold lower in the female DA rat group than in the female SD rat group. The results of the male DA group fell between. This study confirms that female DA rats present a lower debrisoquine 4-hydroxylating capacity than other rats but shows that urinary metabolic ratio is not sufficient to assess the deficiency of debrisoquine hydroxylation.
Effect of Chlorpromazine on the Permeability of β-Lactam Antibiotics Across Rat Intestinal Brush Border Membrane Vesicles
Authors: Iseki Ken , Sugawara Mitsuru , Saitoh Hiroshi , Miyazaki Katsumi , Arita Takaichi 
Published: April 2011

Abstract
The effect of chlorpromazine on the membrane permeability of β-lactam antibiotics (benzylpenicillin, ampicillin, cephradine and cephalexin) and actively transported substances (glycylglycine and D-glucose) has been studied using rat intestinal brush border membrane vesicles. Except for cephalexin, the initial uptakes at 25°C of these antibiotics were significantly enhanced in the presence of chlorpromazine. In contrast, the transport of glycylglycine and D-glucose was significantly inhibited. These results suggest that the two groups, drugs and actively transported substances, have a different permeation process. The effect of chlorpromazine concentration on membrane lipid fluidity, as assessed by the fluorescence polarization of 1,6-diphenyl-1,3,5-hexatriene (DPH) and 1-anilino-8-naphthalene sulphonate (ANS), was also examined. The fluorescence polarization of ANS decreased with increasing concentration of chlorpromazine, while that of DPH increased suggesting an increase of membrane surface fluidity might affect the permeation of β-lactam antibiotics and actively transported substances in a different manner.
Studies In The Guinea-pig With ICI 185,282: A Thromboxane A2 Receptor Antagonist
Authors: Birch J , Brown E , Calnan C , Jessup C L , Jessup R , Wayne M 
Published: April 2011

Abstract
The effects of ICI 185,282 (5(Z)-7-([2,4,5-cis]-4-O-hydroxyphenyl-2-trifluoromethyl-1,3-dioxan-5-yl)heptenoic acid) have been studied on guinea-pig platelets and pulmonary smooth muscle in-vitro and in-vivo. When tested on guinea-pig lung parenchyma in-vitro, ICI 185,282 (1 × 10−7 M) produced a significant shift in U-46619 response curves (concentration ratio of 13.3); the antagonist (1 × 10−5 M) did not modify histamine responses. When tested on guinea-pig trachea in-vitro ICI 185,282 (1 × 10−7 M) caused significant inhibition of U-46619 and PGD2 responses (concentration ratios of 8.3 and 14.1, respectively); the antagonist (1 × 10−5 M) proved less effective against contractions of PGF2α, LTD4 and histamine (concentration ratios of 7.0, 1.5 and 1.6). When added to guinea-pig platelet rich plasma in-vitro, ICI 185,282 (× 10−6, 1 × 10−5 M) caused concentration-dependent parallel shifts to the right of U-46619 aggregation curves, yielding concentration ratios of 13.6 and 141.9, respectively. In-vitro, addition of ICI 185,282 (× 10−5 M) to indomethacin-treated pulmonary smooth muscle did not modify resting tone, neither did it induce aggregation or swelling in platelet-rich plasma preparations. When administered orally to guinea-pigs ICI 185,282 (0.1, 0.5 mg kg−1) caused a significant inhibition of U-46619-induced platelet aggregation ex-vivo which persisted ≥8 h. In-vivo, a single oral dose of ICI 185,282 (1 mg kg−1) inhibited bronchospasm induced by U-46619, PGD2, PGF2α, arachidonic acid, LTD4 and PAF; responses to histamine were unaffected. When dosed intravenously to lightly anaesthetized spontaneously breathing guinea-pigs ICI 185,282 (25 mg kg−1) failed to modify Cdyn and Raw. We conclude that ICI 185,282 is a potent, selective, orally active antagonist, which expresses activity at platelet and pulmonary TXA2 receptors.
The local modulation of vascular permeability by endothelial cell derived products
Authors: Chander C L , Moore A R , Dfsa F M , Howat D , Willoughby D A 
Published: April 2011

Abstract
Endothelin has been shown to suppress increased vascular permeability in the rat at doses of 0.01 pmol. The agonists used were nitric oxide and nitroprusside, which have the same activity as endothelial-derived relaxing factor. Histamine, 5-hydroxytryptamine, platelet activating factor and carrageenan were the other agonists used. It is proposed that endothelin and EDRF act as local hormones produced by endothelial cells to control local vascular permeability.
Rate and Extent of Absorption of Clonidine from a Transdermal Therapeutic System
Authors: Toon S , Hopkins K J , Aarons L , Rowland M 
Published: April 2011

Abstract
The in-vivo performance of a clonidine transdermal therapeutic system (TTS 3·5 cm2, 2·5 mg) was assessed in 12 healthy normal volunteers. Particular attention was paid to the rate and extent of absorption of clonidine from the TTS dosage form by reference to a 2 h i.v. infusion of clonidine. The absolute bioavailability of clonidine from the TTS dosage form was found to be approximately 60% with clonidine being released from the TTS at a relatively reproducible and consistent rate of 4·32 μg h−1 over a 7-day period.
In-vivo Effects of (E)-2-(3′,4′-dimethoxyphenyl)-3-fluoroallylamine (MDL 72145) on Amine Oxidase Activities in the Rat. Selective Inhibition of Semicarbazide-sensitive Amine Oxidase in Vascular and Brown Adipose Tissues
Authors: Elliott Jonathan , Callingham Brian A , Barrand Margery A 
Published: April 2011

Abstract
One hour after MDL 72145 ((E)-2-(3′,4′-dimethoxyphenyl)-3-fluoroallylamine) (2·5 mg kg−1) was given by intraperitoneal injection, the semicarbazide-sensitive amine oxidase (SSAO) activity of rat aorta and brown adipose tissue measured in-vitro was reduced by more than 95% of its control value, whereas the monoamine oxidase (MAO-A) activity remained virtually unaffected. The action of this drug on amine oxidases in the liver at this dose was less selective. The in-vitro effect of MDL 72145 on the soluble enzyme diamine oxidase from rat intestine was 100 fold less potent than that of semicarbazide but about equipotent with semicarbazide on sheep plasma amine oxidase. Overall MDL 72145 was selectively more active against membrane bound SSAO enzymes that deaminate primary monoamines. Although MDL 72145 does inhibit MAO-B activity these results suggest that this compound may be used to study the effect of selective inhibition of SSAO activity on the pharmacological responses of appropriate preparations invitro.
The Effect of Diphenylamine-2-carboxylate on C1− Channel Conductance and on Excitability Characteristics of Rat Skeletal Muscle
Authors: Camerino Diana Conte , de Luca Annamaria , Mambrini Mercede 
Published: April 2011

Abstract
The effect of diphenylamine-2-carboxylate (DPC), a blocker of the C1− conductive pathway in C1− transporting epithelia, has been evaluated in-vitro on the electrophysiological variables of rat extensor digitorum longus muscle fibres. DPC (5–240 μM) caused a dose-related increase of membrane resistance which was attributed entirely to a fall in C1− channel conductance (IC50, 120 μM), since potassium conductance was not affected by the treatment. DPC also modified fibre excitability. A significant dose-dependent increase was observed in the latency of the action potential and in the excitability of the membrane. DPC was less potent on striated fibres than anthracene-9-carboxylic acid, another specific blocker of C1− channel conductance. Moreover DPC was less potent on skeletal muscle than on C1− transporting epithelia. Morphological differences in the C1− channels or of the drug binding sites may account for the differences between tissues.
The effects of B-HT 920 and St 91 on venous haemodynamics in cats
Authors: Widdop Robert E 
Published: April 2011

Abstract
The present study reports the effects of 2-amino-6-allyl-5,6,7,8-tetrahydro-4H-thiazolo-[4,5-d]azepin dihydrochloride (B-HT 920) and 2-(2,6-diethylphenylimino)-2-imidazolidine hydrochloride (St 91) in autoperfused cat hindquarters since we have previously shown that clonidine lowered blood pressure, heart rate and vena cava blood flow (VCBF) but not hindquarters perfusion pressure, indicating a selective venodilator action of this drug (Bentley et al 1986). It was found that intravenous (i.v.) and intracisternal (i.c.m.) administration of B-HT 920 caused essentially identical effects to those of Clonidine. St 91, given i.c.m. lowered blood pressure and VCBF but not perfusion pressure, while i.v. St 91 had little effect on these variables. Thus, parallel changes in blood pressure and VCBF occurred using both drugs, suggesting that these centrally-acting clonidine-like drugs also caused selective venodilatation.
QSAR study on species differences in microsomal N-oxygenation of N,N-dimethylalkylamines
Authors: Devínsky Ferdinand , Gorrod John W 
Published: April 2011

Abstract
The metabolic N-oxygenation of nine long chain N,N-dimethylalkylamines and tri-n-butylamine has been studied using hepatic microsomal homogenates from mice, dogs and guinea-pigs. The relative oxidizability of amines (ROA) was correlated with structure, lipophilicity and nucleophilicity parameters of substrates and corresponding amine oxides formed in this biological reaction. The highest conversion of amines to N-oxides was found with male guinea-pig, followed by dog (male, female) and the lowest amount of amine oxides has been produced with male mice microsomal homogenates. The analyses were carried out by GLC and the results quantified using QSAR methodology. ROA is parabolically dependent upon structure and physicochemical properties of the substrates and products which was proved by the high statistical significance of the regression equations. The biological N-oxygenation of these amines is controlled by lipophilicity, stereochemistry and electronic effects.