bluuebunny/crossref_metadata_2025_split huggingface dataset:
Physicochemical interactions of praziquantel, oxamniquine and tablet excipients
Authors: Prankerd Richard J , Ahmed Sayed M 
Published: April 2011

Abstract
A differential scanning calorimetry and infrared spectrophotometry study of potential interactions between oxamniquine and praziquantel, two synergistic anti-parasitic drugs, indicated that they did not interact on fusion. Mixtures of the two drugs with each of nine common pharmaceutical excipients (Ac-Di-Sol, Avicel, Crospovidone, calcium phosphate, magnesium stearate, starch, lactose, PEG 6000, stearic acid) appeared to interact only with stearic acid. These results suggested that a combination solid dosage form was feasible.
Physicochemical properties of oxamniquine indicate a new polymorphic form
Authors: Prankerd Richard J , Ahmed Sayed M 
Published: April 2011

Abstract
New dissolution rate, chemical stability and thermal analysis data are reported for an anti-schistosomal drug, oxamniquine. A slow dissolution rate (40–70% in 1 h) was found, which may contribute to its erratic clinical response. The drug was found to be chemically stable in water for at least 21 days at 37°C. Dissolution rate and thermal analysis evidence is presented for a previously unreported polymorph (Form III). This form appears to be intermediate in physical stability between the known Forms I and II.
The use of albumin microspheres in the treatment of carrageenan-induced inflammation in the rat
Authors: Lewis D A , Field W N , Hayes K , Alpar H O 
Published: April 2011

Abstract
Free hydrocortisone, hydrocortisone incorporated into microspheres and empty microspheres have been administered orally to rats with carrageenan-induced hindpaw inflammation. Hydrocortisone administered in particles was effective at a lower dose than free steroid in reducing inflammation. Inflammatory exudates were able to release steroid from the microspheres by proteolytic degradation.
Amorphism and Physicochemical Stability of Spray-dried Frusemide
Authors: Matsuda Yoshihisa , Otsuka Makoto , Onoe Mika , Tatsumi Etsuko 
Published: April 2011

Abstract
The physicochemical properties of amorphous forms of frusemide, prepared by spray-drying at 50 or 150°C, and their hygroscopic stability at temperatures of 25 and 40°C, and at 0 and 75% relative humidity were investigated. The glass transition temperature of the amorphous form A was 44·2°C as measured by differential scanning calorimetry, while that of the amorphous form B was 54·4°C. The activation energies for glass transition and crystallization processes were calculated from the differential scanning calorimetry thermograms of amorphous forms A and B, respectively. Stability determined by X-ray diffraction at 0% relative humidity, 25 and 40°C suggested that form B was more stable than form A. However, the stability of form A at 75% relative humidity and 25 and 40°C was similar to that of form B.
Pig Ear Skin as an In-vitro Model for Human Skin Permeability
Authors: Dick Ian P , Scott Robert C 
Published: April 2011

Abstract
Pig skin has been shown to have similar histological and physiological properties to human skin and has been suggested as a good model for human skin permeability. In this series of experiments, the in-vitro permeability of pig ear skin was compared with human (abdominal) skin and rat (dorsal) skin using both hydrophilic (water, mannitol, paraquat) and lipophilic (aldrin, carbaryl, fluazifop-butyl) penetrants. Pig skin was found to have a closer permeability character than rat skin to human skin, particularly for lipophilic penetrants. Electrical conductivity measurements across pig skin membranes showed that skin conductivity could be a useful method for assessing the integrity of membranes, particularly when used in conjunction with water permeability assessments.
The Mitigating Effects of Phosphatidylcholines on Bile Salt- and Lysophosphatidylcholine-induced Membrane Damage
Authors: El-Hariri Linda M , Marriott Christopher , Martin Gary P 
Published: April 2011

Abstract
The effects, at pH 7·0, of a series of 0·2 Mm phosphatidylcholines (PC), namely dicaproyl-PC (DCPC), didecanoyl-PC (DDPC), dilauroyl-PC (DLaPC), dimyristoyl-PC (DMPC), dipalmitoyl-PC (DPPC), dioleoyl-PC (DOPC) and dilinoleoyl-PC (DLPC) and a series of 0·2 Mm fatty acid salts (namely sodium myristate, palmitate, stearate, oleate and linoleate) upon the erythrocyte haemolysis induced by 2 Mm sodium taurodeoxycholate (STDC) were determined. The influence of egg PC and dihexadecyl phosphate (DHDP) concentration upon the haemolysis induced by 1·4 Mm sodium deoxycholate (SDC), 2 Mm STDC and 0·1 Mm lysophosphatidylcholine (LPC) were also established. A bile salt: egg PC mole ratio of 0·5 virtually abolished the haemolysis induced by SDC and STDC, whereas the same ratio of LPC: egg PC only reduced haemolysis from 65 to 40% (maximum haemolysis). DHDP had no effect on the haemolytic action of SDC or STDC. The salts of the fatty acids were non-haemolytic, and when mixed with STDC did not affect the level of haemolysis induced by the bile salt. In contrast, DDPC and DLaPC enhanced the haemolysis of STDC and DCPC had no effect, whereas DMPC, DPPC, DSPC, DOPC, DLPC and egg PC all reduced haemolysis. Maximum reduction was determined for DMPC and egg PC. The mixed micelle preparation temperature (either room or 60°C) and temperature of incubation (either 20°C for 30 min or 37°C for 5 min) had only minor effects on the net haemolysis induced by STDC. These findings may be of significance in understanding the aetiology of certain gastrointestinal diseases and in determining whether mixed bile salt micelles have a role as drug penetration enhancers.
Effects of Isosorbide-5-mononitrate and Isosorbide-2-mononitrate on the Contractile and Electrical Activity and on the Content of Cyclic Nucleotides in Isolated Heart Muscles of the Guinea-pig and Dog
Authors: Atanassova R , Spassov G , Balansky R , Boev K 
Published: April 2011

Abstract
Isosorbide-5-mononitrate and isosorbide-2-mononitrate, the metabolites of isosorbide dinitrate, were studied for their effects on the contractile and electrical activity and on the content of cyclic nucleotides in isolated heart muscles of guinea-pig and dog. Isosorbide-5-mononitrate at all concentrations tested and isosorbide-2-mononitrate at low concentrations did not produce significant changes in the mechanical activity of guinea-pig heart preparations. Isosorbide-2-mononitrate in concentrations above 10−4 m inhibited the contractility and shortened the action potential of guinea-pig and dog heart muscle. Neither mononitrate had an effect on cAMP concentration but both induced a significant elevation of cGMP content in guinea-pig heart tissue, the effect of isosorbide-2-mononitrate being greater.
Correlation of extrusion forces, raw materials and sphere characteristics
Authors: Baert L , Fanara D , Remon J P , Massart D 
Published: April 2011

Abstract
This communication reports on the correlation between extrusion forces and sphere characteristics. Dicalcium phosphate dihydrate, α-lactose monohydrate and anhydrous β-lactose were models for respectively an insoluble, a medium soluble and a highly soluble drug and were used to produce spheres. Phase diagrams for ternary mixtures consisting of microcrystalline cellulose, water and a third excipient were constructed. The region where good spheres were obtained correlated well with the area of extrusion forces between 630 and 1260 N. This correlation was seen for the insoluble, the medium and the highly soluble products.
Effects of senna and its active compounds rhein and rhein-anthrone on PAF formation by rat colon
Authors: Mascolo N , Autore G , Izzo A A , Biondi A , Capasso F 
Published: April 2011

Abstract
A single or a prolonged oral administration of senna (60 mg kg−1) to rats did not increase either colonic PAF (platelet activating factor) content or intraluminal release of acid phosphatase. A similar result was observed in the colonic tissue of rats perfused in-vitro with rhein (1–300 μg mL−1) or rhein-anthrone (1–300 μg mL−1). A single or prolonged administration of castor oil (2 mL) to rats increased both colonic PAF content and intraluminal release of acid phosphatase. Colonic tissue of rats perfused in-vitro with calcium ionophore A23187 (1 and 10 μg mL−1) formed large amounts of PAF and acid phosphatase. Since PAF can mediate intestinal damage and acid phosphatase is a marker of cellular injury, we conclude that senna and its derivatives, rhein and rheinanthrone, are well tolerated in rats.
Further studies on the anti-nociceptive effect of vasopressin
Authors: Ramaswamy S , Shewade D G , Tyagi M G , Bapna J S 
Published: April 2011

Abstract
The possible interactions of pathways which mediate anti-nociception when stimulated by (α2-adrenoceptor agonists and arginine vasopressin (AVP) were investigated. Yohimbine, an α2-antagonist, failed to modify the anti-nociceptive response of AVP. However, clonidine pretreatment, in sub-effective and effective doses, potentiated the anti-nociceptive response of a sub-effective dose of AVP. This potentiation was attenuated by yohimbine and completely anatagonized by naloxone. These studies suggest that pathways related to the opioidergic system and those stimulated by α2-agonists may be utilized by AVP in eliciting the anti-nociceptive response.
Effects of benzodiazepine administration on A1 adenosine receptor binding in-vivo and ex-vivo
Authors: Kaplan Gary B , Cotreau Monette M , Greenblatt David J 
Published: April 2011

Abstract
The adenosine receptor has been implicated in the central mechanism of action of benzodiazepines. The specific binding of an A1-selective adenosine antagonist radioligand, [3H]8-cyclopentyl-1,3-dipropylxanthine, was measured in-vivo in mice treated with alprazolam (2 mg kg−1, i.p.), lorazepam (2 mg kg−1, i.p.) and vehicle. Binding studies were performed in-vivo and ex-vivo in mice receiving continuous infusion of alprazolam (2 mg kg−1 day−1), lorazepam (2 mg kg−1 day−1) and vehicle by mini-osmotic pumps for 6 days. Continuous infusion of alprazolam and lorazepam significantly decreased specific binding by 34 and 53%, respectively, compared with vehicle treatment (P &lt; 0·01). Single doses of alprazolam and lorazepam induced a similar trend in specific binding in-vivo (P = 0·07). There were no alterations in A1 -receptor density (Bmax) or affinity (Kd) in cortex, hippocampus or brainstem in ex-vivo studies. Benzodiazepine treatment may diminish A1- receptor binding in-vivo by inhibiting adenosine uptake or by direct occupancy of the A1 adenosine receptor recognition site.
Non-Michaelis–Menten Type Hepatic Uptake of Liposomes in the Rat
Authors: Harashima Hideyoshi , Kume Yoshihiro , Yamane Chizu , Kiwada Hiroshi 
Published: April 2011

Abstract
The objective of this study was to verify the methodology for measuring uptake clearance of liposomes and to characterize kinetically the saturable hepatic uptake of liposomes through phagocytosis. The correction of vascular space was important in the evaluationof hepatic uptake. The efflux of liposomes from liver was shown to be negligible, by a repeated dose study, and thus, hepatic clearance can be obtained by the hepatic uptake divided by the area under the blood concentration-time curve (AUC). The determinant parameter which describes the saturability of uptake clearance of liposomes, independent of infusion rate, was investigated, using the data of an in-vivo constant infusion study, where infusion rate-dependent saturable hepatic clearance was observed. The mean blood concentration failed to obtain an infusion rate-independent function. On the other hand, the AUC could explain the saturability of hepatic clearance for every infusion rate by a unique relationship. The hepatic uptake amount could also explain this saturability, independent of infusion rate. These kinetic characteristics are inconsistent with Michaelis–Menten type kinetics, therefore a new model is required to describe the saturable hepatic clearance in the disposition of liposomes.
A Novel Prodrug of Salicylic Acid, Salicylic Acid-glycylglycine Conjugate, Utilizing the Hydrolysis in Rabbit Intestinal Microorganisms
Authors: Nakamura Junzo , Asai Kumiko , Nishida Koyo , Sasaki Hitoshi 
Published: April 2011

Abstract
The hydrolysis of salicylic acid-glycylglycine conjugate (salicyl-glycylglycine) following oral, intravenous, intracaecal and rectal administration (434, 72, 36 and 36 μmol kg−1, respectively: equivalent to salicylic acid) was examined in rabbits to develop a novel prodrug of salicylic acid. Salicylic acid was detected in the blood 2 h after oral administration of salicyl-glycylglycine and it reached a maximum level (55·6 μg mL−1) at 15 h, whereas a small amount of salicyl-glycylglycine was found in the blood. In contrast, unchanged salicyl-glycylglycine was found mainly in the blood following its intravenous administration, suggesting the involvement of presystemic deconjugation in the hydrolysis of salicyl-glycylglycine. Immediate and very extensive salicyclic acid formation in the caecum was observed following intracaecal administration of salicyl-glycylglycine, suggesting that the intestinal microorganisms were responsible for the biotransformation of this compound. In-vitro incubation of salicyl-glycylglycine with caecal content showed that salicyl-glycylglycine was hydrolysed efficiently in the caecum. Consequently, the blood concentration of salicylic acid was prolonged extensively following rectal administration of salicylglycylglycine, indicating the usefulness of salicyl-glycylglycine as a prodrug of salicylic acid.
α1-Adrenoceptor Subtypes in Bovine Prostate
Authors: Maruyama Keiko , Tsuchihashi Hiroshi , Baba Shoko , Mano Fumie , Nagatomo Takafumi 
Published: April 2011

Abstract
The object of this study was to examine the existence and characteristics of α1-adrenoceptor subtypes in the bovine prostate using the radioligand binding assay method. [3H]Prazosin was used as the radioligand and its binding sites in bovine prostate were classified into two subtypes. One subtype showed a high affinity (α1High, Kd: 101·1 Pm and Bmax: 11·8 fmol (mg protein)−1) and the other had a low affinity (α1Low, Kd: 3371·4 Pm and Bmax: 50·5 fmol (mg protein)−1). Although the same pKi values of clorethylclonidine, p-aminoclonidine, benoxathian and dibenamine to both α1High and α1 Low binding sites in bovine prostate tissue were observed, other α1 antagonists used in this study had different pKi values for the two α1-adrenoceptor subtypes. The existence and binding characteristics of α1-adrenoceptor subtypes in bovine prostate were clarified. It is possible that agents selective for one site may contribute to the development of better drugs for the treatment of bladder outlet obstructions of men with benign prostatic hyperplasia.
Inhibitory Effects of Tiamulin on Contractile and Electrical Responses in Isolated Thoracic Aorta and Cardiac Muscle of Guinea-pigs
Authors: Nakajyo Shinjiro , Hara Yutaka , Hirano Shin-Ichi , Agata Naoki , Shimizu Kazumasa , Urakawa Norimoto 
Published: April 2011

Abstract
The inhibitory effect of tiamulin, an antibiotic produced by Pleurotus mutilis, on contractile and electrical responses in isolated thoracic aorta and cardiac muscle of guinea-pigs was studied. In the thoracic aorta, tiamulin with an IC50 of 9·7 × 10−6 m inhibited sustained contractions induced by isosmotically added 60 Mm KCl. The inhibitory effect of tiamulin on a Ca2+-induced contraction in a depolarized muscle was competitively antagonized by raising external Ca2+ concentration. Bay K 8644 (10−7 m) antagonized tiamulin's inhibition of the Ca2+ -induced contraction. Tiamulin (2×10−5 m) decreased the elevated cytoplasmic Ca2+ level measured by the fura 2 AM method in the depolarized muscle. In high K+-isoprenaline-treated left atria, tiamulin (2 × 10−5–2 × 10−4 m) produced negative inotropic effects. On the other hand in the membrane action potential of papillary muscles, tiamulin (2 × 10−6–2 × 10−4 m) produced decreases in action potential and durations and 2 × 10−4 m tiamulin depressed the slow response action potential in depolarized muscles. Tiamulin produced prolongations of the PR interval in ECG, negative chrono- and inotropic effects, and an increase in perfusion flow in guinea-pig isolated and perfused hearts. These effects of tiamulin on the aorta or cardiac muscle were similar to those of verapamil and nifedipine. These results suggest that both the inhibitory action of tiamulin on the high K+-induced contraction in the aorta and the negative inotropic effect of tiamulin on the cardiac muscle are due to an inhibition of Ca2+ entry through the voltage-dependent Ca2+ channels of cells of both these muscles.
Feverfew Extracts and Parthenolide Irreversibly Inhibit Vascular Responses of the Rabbit Aorta
Authors: Barsby R W J , Salan U , Knight D W , Hoult J R S 
Published: April 2011

Abstract
Samples prepared from chloroform extracts of fresh leaves of feverfew (Tanacetum parthenium) strongly inhibited responses of rabbit aortic rings to phenylephrine, 5-hydroxytryptamine, thromboxane mimetic U46619 (9,11-dideoxy-11α,9α-epoxy-methano-PGF2α), and angiotensin II, but the inhibition to contractions induced by potassium depolarization was much less. The inhibition was concentration- and time-dependent, non-competitive, and irreversible, and also occurred in endothelium-denuded preparations. The feverfew extracts also caused a progressive loss of tone of pre-contracted aortic rings and appeared to impair the ability of acetylcholine to induce endothelium-dependent relaxations of the tissue. These effects were mimicked by a purified preparation of an α-methylenebutyrolactone, parthenolide, obtained from the extract. Our results demonstrate a nonspecific and potentially toxic response to feverfew on the vasculature.
Nicotinate Esters: Their Binding to and Hydrolysis by Human Serum Albumin
Authors: Steiner Alain , Mayer Joachim M , Testa Bernard 
Published: April 2011

Abstract
Nicotinate esters were studied for their binding to, and hydrolysis by, human serum albumin. Some esters (ethyl, isopropyl, t-butyl, cyclohexyl, benzyl) were bound but not hydrolysed, while others (2-chloroethyl, 2-butoxyethyl) displayed the opposite behaviour; 1-carbamoylethyl ester was neither bound nor readily hydrolysed. Only p-methoxyphenyl nicotinate was both a ligand and a substrate, and its rate constants of binding and hydrolysis were calculated in a stepwise procedure using a kinetic model.
Phenobarbitone Population Pharmacokinetics from Routine Clinical Data: Role of Patient Characteristics for Estimating Dosing Regimens
Authors: Yukawa Eiji , Higuchi Shun , Aoyama Toshinobu 
Published: April 2011

Abstract
Routine clinical pharmacokinetic data collected from patients receiving phenobarbitone have been analysed to evaluate the role of patient characteristics for estimating dosing regimens. The data were analysed using NONMEM, a computer program designed for population pharmacokinetic analysis that allows pooling of data. The pharmacokinetic model of phenobarbitone was described using a one-compartment steady-state model. The effect of a variety of developmental and demographic factors on clearance was investigated. NONMEM estimates indicated a nonlinear function of total body weight as the optimum adjustment of phenobarbitone clearance. Concomitant administration of phenobarbitone and other antiepileptic drugs showed a decrease of phenobarbitone clearance in young children. The dosing method based on clearance values obtained by NONMEM analysis allowed the prediction of the steady-state concentration as a function of maintenance dose with acceptable error for therapeutic drug monitoring.
Digoxin Population Pharmacokinetics from Routine Clinical Data: Role of Patient Characteristics for Estimating Dosing Regimens
Authors: Yukawa Eiji , Mine Hisanori , Higuchi Shun , Aoyama Toshinobu 
Published: April 2011

Abstract
Routine clinical pharmacokinetic data collected from patients receiving digoxin have been analysed to evaluate the role of patient characteristics for estimating dosing regimens. The data were analysed using NONMEM, a computer program designed for population pharmacokinetic analysis that allows pooling of data. The pharmacokinetic model of digoxin was described using a one-compartment steady-state model. The effect of a variety of developmental and demographic factors on clearance was investigated. NONMEM estimates indicate that digoxin clearance was influenced by the demographic variables of age, total body weight, serum creatinine and sex. The interindividual variability in digoxin clearance was modelled with additive error with an estimated standard deviation of 46·15 L day−1 and the intraindividual variability, or residual error was 0·209 ng mL−1. The dosing method based on clearance values obtained by NONMEM analysis allowed the prediction of the steady-state concentration as a function of maintenance dose with acceptable error for therapeutic drug monitoring.
PAF formation by human gastrointestinal mucosa/submucosa in-vitro: release by ricinoleic acid, and inhibition by 5-aminosalicylic acid
Authors: Capasso F , Tavares I A , Bennett A 
Published: April 2011

Abstract
Human isolated gastrointestinal mucosa/submucosa incubated with ricinoleic acid (12·5–100 μg mL−1) or the calcium ionophore A23187 (10 μg mL−1) released platelet-activating factor (PAF) as determined by a scintillation proximity assay after extraction and purification. 5-Aminosalicylic acid (25–100 μg mL−1) inhibited PAF release by ricinoleic acid in a concentration-dependent manner, and 50 μg mL−1 reduced the effect of A23187. We suggest that PAF may play a role in the taxation and mucosal damage by ricinoleic acid released from castor oil.
Nifedipine-morphine interaction: a further investigation on nociception and locomotor activity in mice
Authors: Pavone Flaminia , Battaglia Mario , Sansone Mario 
Published: April 2011

Abstract
Nociception and locomotor activity were tested in mice (C57BL/6 and DBA/2 strains), receiving the dihydropyridine calcium-channel blocker nifedipine, alone or combined with morphine. The calcium antagonist did not change the reaction time to thermal stimulation (tail-flick test), when administered alone, but combinations of nifedipine and morphine prolonged tail-flick latencies less than did the opiate alone. Nifedipine decreased locomotion in both strains, reduced the hypermotility induced by morphine in C57 mice, and enhanced the locomotor depression induced by the opiate in DBA mice. A comparison of the effects of nifedipine with those of the non-calcium antagonist vasodilator, hydralazine, suggests that the interactions with morphine were not exclusively related to neuronal changes produced by calcium channel blockade, but also to haemodynamic factors. In fact, except for the lack of interference with morphine-induced hypermotility in C57 mice, hydralazine, given alone or in combination with morphine, produced effects similar to those of nifedipine.
Stimulation of postsynaptic 5-HT1A receptors is responsible for the anticonflict effect of ipsapirone in rats
Authors: Przegaliṅski E , Chojnacka-Wojcik E , Filip M 
Published: April 2011

Abstract
Ipsapirone (1·25–10 mg kg−1), a non-benzodiazepine anxiolytic drug with high affinity for 5-hydroxytryptamine1A (5-HT1A) receptors, increased dose-dependently the number of punished licks in the drinking conflict test (Vogel test) in rats. The anticonflict effect of the drug administered at a dose of 5 mg kg−1 was not modified in animals with lesions of 5-HT neurones, produced by p-chloroamphetamine (PCA, 2× 10 mg kg−1). The anticonflict effect of ipsapirone in PCA-pretreated rats was antagonized by the 5-HT1A receptor and α1-adrenoceptor antagonist NAN-190 (1-(2-methoxyphenyl)-4-[4-(2-phthalimmido)]butylpiperazine hydrobromide; 0·5–1 mg kg−1), but not by the selective α1-adrenoceptor blocker prazosin (0·5 mg kg−1). Neither NAN-190 nor prazosin affected the punished response in PCA-pretreated rats. The present results indicate that the anticonflict effect of ipsapirone depends on stimulation of postsynaptic 5-HT1A receptors.