bluuebunny/crossref_metadata_2025_split huggingface dataset:
Prediction of drug loss from PVC infusion bags
Authors: Atkinson H C , Duffull S B 
Published: April 2011

Abstract
PVC: water partition coefficients for a series of 13 drugs have been calculated from literature data and a high degree of correlation with octanol: water partition coefficients demonstrated. The resulting model, log PPVC= −0.35 + 0.69 log P, (r2 = 0.88) has been prospectively tested with 10 drugs. All the test drugs were within the 95% confidence intervals associated with predicted log PPVC values consistent with a valid model. In practice, predicted log PPVC values may be used to estimate drug loss from the aqueous phase of PVC bags at equilibrium. Equations are described which enable calculation of likely drug loss from 100, 500 and 1000 mL PVC bags. It is recommended that this approach is used to identify drugs which are unlikely to be significantly absorbed into PVC.
Effect of Physical and Chemical Properties on Drug Release From Selected Thermosoftening Vehicles
Authors: Kopcha Michael , Lordi Nicholas G 
Published: April 2011

Abstract
The release profile of several drugs, (chlorpheniramine maleate, salicylic acid, hydrochlorothiazide, p-hydroxy benzoic acid, sulphafurazole, anhydrous theophylline) and the marker (D&C yellow No. 10) was detailed to determine the effect of physical and chemical properties on release from selected thermosoftening matrices (Gelucire 50/02 and 50/13). At a concentration of drug or marker of 2·5% w/w, hydrochlorothiazide showed the slowest release from G50/02, due to its low aqueous solubility, while theophylline showed the highest release owing to its low mol. wt and moderate aqueous solubility. Release reflected two of the selection criteria, aqueous solubility and mol. wt, set forth for the drug/markers used in the study. The hydrophobic matrix, G50/02, offered no enhancement in drug release and functioned in a manner commensurate with other hydrophobic matrices. No hydrogen bonding was noted between any of the drugs or markers and the matrix. As drug or marker concentration increased from 2·5 to 15% w/w, potential hydrogen bonding was noted between p-hydroxy benzoic acid and the matrix. Theophylline no longer had the highest release being replaced by chlorpheniramine maleate and D&C yellow No. 10. With Gelucire excipient G50/13, chlorpheniramine maleate showed the highest release; it dissolved within the matrix at experimental temperature and lowered the matrix melting point. The matrix swelled upon exposure to the dissolution medium and it was from this swollen layer that release occurred. Sulphafurazole, hydrochlorothiazide, salicylic acid and p-hydroxy benzoic acid exerted a similar effect to chlorpheniramine maleate on the matrix. No hydrogen bonding was observed between the drugs and matrix. As drug or marker concentration was further increased, chlorpheniramine maleate and D&C yellow No. 10 demonstrated the highest release; all other drugs formed a cluster. Apparent diffusion coefficients for G50/02 and G50/13 matrices were in agreement with published data confirming the predictive ability of the experimental design and postulated mechanistic models of release from hydrophilic and lipophilic matrices.
The Effect of Moderate Haemodilution with Fluosol-DA or Hespan on the Nonmicrosomal Acetylation of Sulphadimidine in the Rat
Authors: Shrewsbury Robert P , Hong Donald D , White Lisa G , Gordon Teressa R 
Published: April 2011

Abstract
The effects of Fluosol-DA (Fluosol) and Hespan haemodilution on the nonmicrosomal acetylation of sulphadimidine were studied in male rats. Fluosol increased the acetylsulphadimidine percent excreted in urine, the metabolic formation rate constant (kf), and the formation clearance (CLF) for 72 h after haemodilution without any significant changes in the sulphadimidine apparent volume of distribution (Vd) or total body clearance (CL). Hespan haemodilution increased the acetylsulphadimidine percent excreted in urine only at 48 h while significantly decreasing the sulphadimidine clearance, urinary excretion rate constant (ku), and renal clearance (CLR) for 72 h. The enhanced N-acetyltransferase activity after Fluosol haemodilution may have therapeutic consequences for concomitantly given drugs metabolized by this enzyme.
Effects of Opioid and α2-Adrenoceptor Agonists on the Isolated Ileum of Morphine-dependent Guinea-pigs During Withdrawal and After Clonidine Treatment
Authors: Colado M I , Martin M I 
Published: April 2011

Abstract
The present study was undertaken to investigate the effect of clonidine administration to opiate-dependent guinea-pigs after morphine withdrawal on subsequent twitch responses of the longitudinal muscle-myenteric plexus preparations to electrical field stimulation. The results indicate that clonidine, administered immediately after morphine removal, causes tolerance to the inhibition exerted by opioid and α2-adrenoceptor agonists on the electrically-evoked twitches. Such a finding suggests that the mechanism of action of clonidine involves not only its well-known effects on locus coeruleus neurons but also that it has specific actions on the myenteric plexus. This work shows the existence of interactions between opioid and α-adrenoceptor on the cholinergic neurons present in the isolated ileum.
Contractile Response of Human Omental Arteries to Endothelin
Authors: Vila J M , De Aguilera E Martín , Irurzun A , Aldasoro M , Flor B , Lluch S 
Published: April 2011

Abstract
The effects of endothelin have been studied in isolated arterial segments (0·8–1 mm in external diam.) of human omental arteries obtained during the course of abdominal operations (15 patients, 7 men and 8 women). Paired segments, one normal and the other de-endothelized, were mounted for isometric recording of tension in organ baths. Endothelin produced concentration-dependent contractions with an EC50 value of 5·4 × 10−9 m. Removal of endothelium did not affect significantly endothelin-induced contractions (EC50, 6·7 × 10−9 m). Removal of extracellular calcium or addition of the calcium channel blocker nicardipine (10−6 m) diminished but did not abolish responses to endothelin. These results indicate that endothelin exerts powerful contractile effects on human isolated omental arteries which are independent of the presence of an intact endothelial cell layer; this contraction cannot be explained solely by voltage-dependent calcium channels.
Further Characterization of the Protective Effect of 8-Cyclopentyl-1,3-dipropylxanthine on Glycerol-induced Acute Renal Failure in the Rat
Authors: Panjehshahin M R , Munsey T S , Collis M G , Bowmer C J , Yates M S 
Published: April 2011

Abstract
In the rat, treatment with the alkylxanthine 8-cyclopentyl-1,3-dipropylxanthine (CPX) at a dose of 0·1 mg kg−1 antagonizes adenosine-induced falls in renal blood flow and reduces the severity of glycerol-induced acute renal failure. Treatment of glycerol-injected rats with 0·03 mg kg−1 of CPX resulted in no significant improvements in a range of indices of renal function. However, treatment with 0·1 or 0·3 mg kg−1 doses of CPX did significantly ameliorate acute renal failure although there were no significant differences in the degree of protection of renal function afforded by these two doses. In glycerol-injected rats, 0·1 or 0·3 mg kg−1 CPX administered either as a single dose or repeated doses every 12 h for two days did not inhibit renal phosphodiesterase. Thus the beneficial effects of CPX can be produced by doses that have no effect on renal phosphodiesterase activity whereas 0·1 mg kg−1 of CPX has been shown previously to antagonize the actions of adenosine. The findings provide further evidence that the beneficial effect of CPX in glycerol-induced acute renal failure is a consequence of adenosine antagonism and not phosphodiesterase inhibition.
Improved transdermal delivery of prostaglandin E1 through hairless mouse skin: combined use of carboxymethyl-ethyl-β-cyclodextrin and penetration enhancers
Authors: Uekama Kaneto , Adachi Hirotoshi , Irie Tetsumi , Yano Tadanori , Saita Masaru , Noda Kanji 
Published: April 2011

Abstract
The optimal prescription of transdermal preparations of prostaglandin E1 (PGE1) for treatment of peripheral vascular diseases has been investigated. The chemical stability of PGE1 in fatty alcohol/propylene glycol (FAPG) ointment was markedly improved by carboxymethyl-ethyl-β-cyclodextrin (CME-β-CyD). Application of a PGE1 ointment containing the penetration enhancer, 1-dodecylazacycloheptane-2-one (Azone) or 1-[2-(decylthio)ethyl]azacyclopentane-2-one (HPE-101), onto the skin of hairless mice showed the increase of blood flow in the skin due to the vasodilating action of PGE1. In particular, the ointment containing a PGE1-CME-β-CyD complex supplemented with HPE-101 showed the most prominent increase of the blood flow. Compared with other ointments, this ointment was found to show significantly greater transfer of HPE-101 into in-vitro preparations of the skin of hairless mice. Transfer of PGE1 into the skin was thought to be facilitated by this increased transfer of HPE-101. These results suggest that a combination of CME-β-CyD and HPE-101 is useful for designing PGE1 ointments for topical application with good chemical stability and percutaneous permeability.
Toloxatone pharmacokinetics in the plasma and cerebrospinal fluid of the rabbit
Authors: Vistelle R , Lamiable D , Zinsou M , Leon A , Wiczewski M 
Published: April 2011

Abstract
The pharmacokinetics of toloxatone (5 and 10 mg kg−1, i.v.) was studied in anaesthetized rabbits. There was a biexponential decline in plasma concentration with time. No differences were observed in the pharmacokinetic parameters with the increase of the dose. The terminal half-life was short (47·4 ± 2·8 and 41·5 ± 4·2 min for 5 and 10 mg kg−1, respectively). The total clearance was 79 ± 18 mL min−1 after a dose of 5 mg kg−1 and 106 ± 40 mL min−1 after a dose of 10 mg kg−1. The volume of distribution was 5·8 ± 2·8 (5 mg kg−1) and 5·4 ± 1·8 L (10 mg kg−1). The average percentage of toloxatone bound to plasma protein was 30% and was not affected by concentrations within the investigated range. In cerebrospinal fluid (CSF), the highest concentrations of toloxatone were obtained within 15 min after the end of the injection. The CSF level of toloxatone was equal to that of plasma unbound toloxatone and declined at a rate similar to toloxatone in plasma. These results suggest that the toloxatone passage through the blood-brain barrier may be completed by passive diffusion. In addition, the unbound plasma concentration would accurately reflect the toloxatone concentration in CSF and could be a useful tool for drug monitoring.
Contractions induced by phenylephrine and noradrenaline are differently affected by endothelium-dependent relaxation in rat aorta
Authors: Auguet M , Tricoche R , Braquet P 
Published: April 2011

Abstract
In rings of rat aorta precontracted with phenylephrine (10 μm) or noradrenaline (10 μm), addition of carbachol (10 μm) produced an endothelium-dependent relaxation. However, regardless of the concentration of agonist tested, both the intensity and duration of the relaxation were significantly less when noradrenaline, rather than phenylephrine, was used as the precontracting agent. The different responses observed do not appear to be related to destruction of endothelium-derived relaxing factor by autoxidation of noradrenaline since neither EDTA (30 μm) nor superoxide dismutase (30 units mL−1) improved the relaxation to carbachol. In addition, in endothelium-free rings, the noradrenaline (1 μm)-induced contraction was less sensitive than the phenylephrine (1 μm)-induced contraction to sodium nitroprusside (0·1 μm) or to 8-Br-cGMP (300 μm). With phenylephrine-, but not noradrenaline-, induced contraction, the relaxation triggered by carbachol was significantly reduced by pretreatment of the aortic rings with chloroethylclonidine (50 μm), which inactivates a subpopulation of α1-adrenoceptors. Thus, the results confirm that both alkylation sensitive and resistant α1-adrenoceptors exist in rat aorta and indicate that EDRF may discriminate between these two α1-adrenoceptor subtypes which are differently affected by phenylephrine and noradrenaline.
Analysis of the effects of adenosine in skinned bovine coronary artery
Authors: Ramagopal Mudumbi V , Mustafa S Jamal 
Published: April 2011

Abstract
We have investigated the mechanism of adenosine-induced relaxation in relation to its effects on intracellular organelles in Triton X-100- and saponin-skinned bovine coronary arteries. In intact coronary arteries, high K+ and prostaglandin F2α caused sustained contractions, whereas caffeine produced transient contractions. Triton X-100 treatment abolished these contractions. However, Triton X-100-skinned coronary arteries were responsive to added free calcium. There was no significant difference between calcium concentration-response curves obtained in the absence and presence of adenosine (50 μm). Unlike Triton X-100, in saponin-skinned arteries, caffeine produced transient contractions but high K+ and prostaglandin F2α did not. Adenosine had no effect on caffeine-induced contractions in saponin-skinned coronary arteries. These data suggest that adenosine had no direct inhibitory effect on either the contractile apparatus or calcium release from sarcoplasmic reticulum in coronary arteries.
An in-vitro study of chloroquine transport in the rat submaxillary gland
Authors: Onyeji C O , Dixon P A F , Ogunbona F A 
Published: April 2011

Abstract
The uptake and efflux of chloroquine by the rat submaxillary gland in-vitro were studied under various incubation conditions. Variations in the extracellular pH significantly affected both the uptake and efflux of the drug. Increasing chloroquine concentration significantly decreased the uptake. Uptake was also decreased significantly (P &lt; 0·05) when compared with control conditions (pH 7·40, 37·5°C, O2 aeration, 6 × 10−6 m chloroquine) by the following experimental variations: aeration of the incubation medium with N2 instead of O2; decrease of bath temperature from 37·5 to 4°C; addition of metabolic inhibitors, cyanide (10−3 m), iodoacetic acid (10−3 m) and o-nitrophenol (10−3 m). Cimetidine (10−3 m), a known organic cationic inhibitor, had no significant effect on chloroquine uptake when compared with control values. These results show that the uptake of chloroquine by the rat submaxillary gland in-vitro is concentration-dependent and this is indicative of possible saturable binding sites for the drug in the gland. These results suggest that the transfer of chloroquine across the submaxillary gland may be mediated by an active transport process. On the other hand, it is possible that the apparent active transport process implicated in this study could be a consequence of chloroquine ion trapping in the acidic interior of lysosomes.
Influence of inhibition of extraneuronal uptake and of O-methylation on the hyperglycaemia caused by sympathomimetic amines in depancreatized rats
Authors: Proença Jorge , Guimarães Serafim 
Published: April 2011

Abstract
This study aimed at testing whether the O-methylating system (extraneuronal uptake + O-methylation) modulates, in-vivo, β-adrenoceptor-mediated responses. The influences of U-0521 (3,4-dihydroxymethylpropiophenone, an inhibitor of catechol-O-methyl transferase (COMT)) and hydrocortisone (an inhibitor of extraneuronal uptake) on the hyperglycaemia evoked by isoprenaline and adrenaline were compared. Both inhibitors enhanced the increase of the plasma glucose level induced by either isoprenaline (0·36 nmol kg−1 min−1) or adrenaline (0·55 nmol kg−1 min−1). The enhancement caused by U-0521 developed faster than that caused by hydrocortisone, but was of the same magnitude. This is the first report of supersensitivity to sympathomimetic amines caused by inhibition of either COMT or extraneuronal uptake in-vivo and for a response not involving smooth muscle cells.
Evaluation of Ion-exchange Microspheres as Carriers for the Anticancer Drug Doxorubicin: In-vitro Studies
Authors: Chen Yan , Burton Mark A , Codde James P , Napoli Sylvia , Martins Ian J , Gray Bruce N 
Published: April 2011

Abstract
A comparison study of doxorubicin loading, release characteristics and stability within sodium and hydrogen forms of ion-exchange resin microspheres has been performed. It was demonstrated that resins in the Na+ form, although having lower drug loading capacity, showed similar release profiles to resins in the H+ form but still maintain all the drug activity. Resins in the H+ form, despite having high drug loading capacity, caused drug degradation within microspheres due to their strong acidic nature. Therefore, in comparison with the H+ form, resins in the Na+ form can be considered as better carriers for doxorubicin in terms of sustaining the release of drug and maintaining drug activity. Other factors such as the degree of resin cross-linkage and drug/resin mixing time have also been examined in relation to drug loading and release characteristics. Overall, this study demonstrated the significance of the characteristics of matrix materials and their influence on the drug activity and microsphere performance in-vitro.
Effects of Proteolytic Enzyme Inhibitors as Absorption Enhancers on the Transdermal Iontophoretic Delivery of Calcitonin in Rats
Authors: Morimoto Kazuhiro , Iwakura Yasushi , Nakatani Emi , Miyazaki Makoto , Tojima Hideki 
Published: April 2011

Abstract
The effects of proteolytic enzyme inhibitors, aprotinin, soybean trypsin inhibitor and camostat mesilate as absorption enhancers on the transdermal iontophoretic delivery of salmon calcitonin (SCT) have been examined in rats. The dermal absorption of SCT was evaluated with hypocalcaemic effect. Application of SCT (12·5 int. units/rat) onto abdominal skin did not produce any hypocalcaemic effect. This produced a small hypocalcaemic effect with cationic iontophoresis (drug phase, anode; reference phase, cathode; high frequency pulses of 1 V at 10 kHz, 2h). Furthermore, camostat mesilate (1 Mm) and aprotinin (106 int. units mL−1) enhanced the hypocalcaemic effects on the application of SCT with iontophoresis. These hypocalcaemic effects were highest with the pH 4·0 preparation compared with those of the pH 5·5, pH 7·0 and pH 8·0 preparations. However, soybean trypsin inhibitor did not change the hypocalcaemic effects. This was because the soybean trypsin inhibitor is a relatively high molecular weight peptide (mol. wt 8000) and an anion at used pH, and therefore was not absorbed through rat skins with cation iontophoresis.
Effect of Cocaine on Tritium Overflow Evoked from Vasa Deferentia Previously Loaded with [3H]Noradrenaline by Stimulation Using Different Types of Electrode
Authors: Bedwell A M , El-Mas M , Hughes I E 
Published: April 2011

Abstract
In mouse and guinea-pig vasa deferentia previously incubated with [3H]noradrenaline, electrical stimulation applied through parallel electrodes (transmurally) increased overflow of tritium 2- to 5-fold above the resting value. Electrical stimulation applied using methods involving more substantial conduction of nerve impulses in neuronal elements in the tissues evoked a tritium overflow which was smaller (70%) than that evoked by transmural stimulation. Cinchocaine (25 μm), tetrodotoxin (0·5 μm) or the absence of calcium effectively abolished evoked overflow in both tissues whichever method of stimulation was used. In mouse vas deferens, cocaine (10 μm) did not alter overflow evoked by either transmural or axonal stimulation while 100 μm produced a reduction. In guinea-pig vas deferens, cocaine (10 μm) produced a statistically significant increase in evoked overflow of about 50% or more with both transmural and axonal stimulation. As in mouse vas deferens, 100 μm cocaine produced a reduction. It is concluded that the action of cocaine is independent of these methods of stimulation and that some difference in the arrangement of the noradrenergic nerves in the two species may account for the differential effect of cocaine observed.
Effects of (±)-, (+)- and (—)-Celiprolol on the Rat Left Atria and Portal Vein
Authors: Doggrell Sheila A 
Published: April 2011

Abstract
Differing effects of (±)-celiprolol at β-adrenoceptors have been reported. The effects of (±)-, (+)- and (—)-celiprolol on the contractile responses of the rat left atria and portal vein have therefore been studied. (±)-Celiprolol did not augment the responses of the atria to electrical stimulation and is therefore not an agonist at β1-adrenoceptors. Prolonged treatment with (±)-celiprolol attenuated the contractile activity of the vein and this effect was blocked by ICI 118,551 and is therefore mediated by agonism at β2-adrenoceptors. The pA2 values for (±)-, (+)- and (–)-celiprolol at the β1-adrenoceptors of the atria were 8·0, 6·0 and 8·6, respectively. On the portal vein, (±)- and (–)-celiprolol produced non-parallel rightward shifts of log isoprenaline attenuation curves with a reduction in isoprenaline maximum responses. This effect of (±)-celiprolol on the vein was not due to slowly reversible antagonism, as the inhibitory effect of (±)-celiprolol was readily reversible.
Anorectic Activity of Fluoxetine and Norfluoxetine in Rats: Relationship Between Brain Concentrations and In-vitro Potencies on Monoaminergic Mechanisms
Authors: Caccia S , Bizzi A , Coltro G , Fracasso C , Frittoli E , Mennini T , Garattini S 
Published: April 2011

Abstract
The present study was aimed at establishing the importance of brain monoamine uptake and release mechanisms in the anorectic activity of fluoxetine, relating them to the actual brain concentrations of the parent drug and its metabolite norfluoxetine after anorectic doses in rats. Both compounds showed anorectic activity when administered intraperitoneally, norfluoxetine being slightly more active (ED50 = 22·9 μmol kg−1) than fluoxetine (ED50 = 35·0 μmol kg−1) despite the fact that the metabolite is about ten times less potent than the parent drug in inhibiting 5-hydroxytryptamine (5-HT) uptake. Comparing the brain concentrations of norfluoxetine, in terms of maximum concentrations (Cmax) and area under the curve (AUC), after the ED50 of fluoxetine or synthetic norfluoxetine, it also appeared that the metabolite plays a major role in the anorectic effect of the parent drug in rats. Brain Cmax of fluoxetine (48·7 μm) and norfluoxetine (21·7 and 27·3 μm after metabolite and drug, respectively) were several times those blocking 5-HT uptake in-vitro (0·5 μm), making it unlikely that fluoxetine (directly or through its metabolite) reduces food intake by specifically blocking 5-HT neuronal uptake. Brain Cmax of fluoxetine but particularly norfluoxetine were more compatible with those capable in-vitro of affecting catecholaminergic mechanisms, such as inhibition of dopamine and noradrenaline uptake and enhancement of dopamine release. These results together with recent in-vitro findings that the parent compound and its active metabolite induce tritium release from hippocampal synaptosomes previously loaded with [3H]5-HT suggest that mechanisms other than inhibition of 5-HT uptake are involved in the anorectic action of these compounds in rats.
Evidence against Substance P as a neurotransmitter at the neuroepithelial junction in rat colonic mucosa
Authors: Burleigh David E , Yull Derek N 
Published: April 2011

Abstract
Substance P (SP) caused a concentration-dependent increase in short-circuit current of rat isolated colonic mucosal preparations (ED50 10 Nm). The SP antagonist [d-Arg1, d-Pro2, d-Trp7,9, Leu11]SP (50 μm) did not increase short-circuit current. Tetrodotoxin (3·1 μm) reduced the effect of a maximum concentration of SP (300 Nm). This reduction was increased when tetrodotoxin was given with [d-Arg1, d-Pro2, d-Trp7,9, Leu11]SP. Increases in short-circuit current produced by electrical field stimulation were not reduced by [d-Arg1, d-Pro2, d-Trp7,9, Leu11]SP. It is concluded that SP is not a transmitter at the neuroepithelial junction in rat colonic mucosa.