bluuebunny/crossref_metadata_2025_split huggingface dataset:
Absence of pharmacokinetic interaction between ofloxacin and fenbufen in rats
Authors: Katagiri Yoshihiro , Naora Kohji , Ichikawa Nobuhiro , Hayashibara Masakazu , Iwamoto Kikuo 
Published: April 2011

Abstract
The possible pharmacokinetic interaction between a new quinolone and fenbufen was investigated by comparing the plasma concentration-time profiles and serum protein binding of ofloxacin, fenbufen and its active metabolite, felbinac, in rats. The rats were administered intravenous doses of ofloxacin (5 mg kg−1), fenbufen (10 mg kg−1) alone or concomitantly. The plasma elimination half-lives were about 55 min in both groups. A slight elevation of plasma concentration of ofloxacin and a small decrease of its total body clearance were observed after its coadministration with fenbufen. The extent of ofloxacin binding to rat serum tended to be slightly reduced by fenbufen which coexisted at relatively high concentrations. Plasma concentration-time curves, pharmacokinetic parameters and serum protein binding of fenbufen and felbinac were not affected by the coadministration with ofloxacin. These results suggest that any substantive pharmacokinetic interaction may be unlikely after the concomitant administration of ofloxacin and fenbufen.
Visceral Leishmaniasis: Drug Carrier System Characteristics and the Ability to Clear Parasites from the Liver, Spleen and Bone Marrow in Leishmania donovani Infected BALB/c Mice
Authors: Carter K C , Dolan T F , Alexander J , Baillie A J , Mccolgan C 
Published: April 2011

Abstract
The efficacy of various sodium stibogluconate formulations against Leishmania donovani has been investigated using a BALB/c mouse model of visceral leishmaniasis. Only one therapy, multiple dosing with drug loaded sonicated vesicles, liposomes or niosomes, was found to be effective against parasites in the liver, spleen and bone marrow. Other treatments significantly reduced parasite liver burdens but either failed to effect spleen and bone marrow parasites, or were effective but toxic. Prophylactic treatment with sodium stibogluconate preparations, six days before infection, reduced parasite multiplication in the liver (free, niosomal and liposomal drug) and the spleen (sonicated, drug loaded niosomes only), but had no suppressive effect on bone marrow parasite burdens compared with controls. These results indicate that in-vivo sodium stibogluconate persists in some compartments at parasiticidal concentrations and that failure to reach this concentration at some sites of infection such as bone marrow, is the cause of treatment failure and relapse.
The Enhanced Daily Excretion of Urinary Methylamine in Rats Treated with Semicarbazide or Hydralazine May Be Related to the Inhibition of Semicarbazide-sensitive Amine Oxidase Activities
Authors: Lyles G A , Mcdougall S A 
Published: April 2011

Abstract
The effects of amine oxidase inhibitors upon the daily urinary excretion of monomethylamine (MMA), dimethylamine (DMA), trimethylamine (TMA) and ammonia in the rat have been examined. Administration of hydralazine (5 mg kg−1) or semicarbazide (100 mg kg−1); drugs which irreversibly inhibit semicarbazide-sensitive amine oxidases (SSAO) but not monoamine oxidase (MAO), enhanced MMA excretion by around three- to six-fold above pretreatment levels, whereas no effect of pargyline (25 mg kg−1), a selective irreversible inhibitor of MAO was found. No apparent changes in DMA or TMA excretion in response to drug-treatment were observed. Ammonia excretion also was generally unchanged except for an apparent marked increase (approximately four-fold) over the 24 h following semicarbazide, a result which might be explained if ammonia is a degradation product of semicarbazide metabolism in the rat. With recent evidence that MMA is a substrate in-vitro for SSAO activities, results here may indicate that SSAO or related enzymes are involved in endogenous MMA turnover.
Definition of the In-vivo Binding of [3H]Spiperone in Rat Brain Using Substituted Benzamide Drugs
Authors: Chivers J K , Reavill C , Jenner P , Marsden C D 
Published: April 2011

Abstract
The ability of some substituted benzamide drugs to define in-vivo the binding of [3H]spiperone to brain dopamine receptors in rats was assessed using behaviourally effective doses in comparison with haloperidol. As judged using haloperidol, [3H]spiperone identified dopamine receptors in the substantia nigra, striatum, tuberculum olfactorium and. hypothalamus, but not in frontal cortex or nucleus accumbens. The substituted benzamide compounds alizapride, metoclopramide, clebopride and YM 09151-2 prevented the accumulation of [3H]spiperone in the substantia nigra, striatum, tuberculum olfactorium and hypothalamus. However, YM 09151-2 also caused displacement of [3H]spiperone accumulation in the nucleus accumbens and frontal cortex. (±)-Sulpiride, (±)-sultopride, amisulpiride and prosulpride all prevented the accumulation of [3H]spiperone in the hypothalamus but were ineffective in one or more of the other regions containing dopamine receptors defined by [3H]spiperone. The isomers of sulpiride and sultopride stereoselectively defined the accumulation of [3H]spiperone in dopamine containing brain regions. The (-)-isomers of both drugs prevented the accumulation of [3H]spiperone in the substantia nigra, striatum, tuberculum olfactorium and hypothalamus. In contrast, (+)-sulpiride and (+)-sultopride were ineffective. Selected substituted benzamide drugs can be used to define the interaction of ligands with dopamine receptors in-vivo. These substances may be useful in PET studies in man. The isomers of some substituted benzamine drugs may be used to define dopamine receptors in-vivo by enantiomeric selectivity.
Effects of Anti-inflammatory Drugs on Interleukin 1-induced Cartilage Proteoglycan Resorption In-vitro: Inhibition by Aurothiophosphines but no Influence from Perturbed Eicosanoid Metabolism
Authors: Rainsford K D 
Published: April 2011

Abstract
A range of anti-inflammatory drugs having varying effects on eicosanoid metabolism and other actions was studied for their potential to inhibit α-interleukin 1 (IL-1)-induced cartilage proteoglycan resorption in-vitro. No significant effects on resorption were observed with inhibitors of cyclo-oxygenase, lipoxygenase or mixed inhibitors of both these enzymes, and no influence on IL-1 effects was observed with added eicosanoids. Among the clinically used disease modifying anti-arthritic agents, only auranofin and the immunoregulatory agent, tilomisole, were found effective in inhibiting resorption. Some auranofin analogues having chloride or nitrate leaving groups that inhibit DNA polymerase-α were found to be potent inhibitors of IL-1 induced resorption.
The influence of structure on the accumulation of caffeine induced by methyl xanthine derivatives
Authors: Segura Jordi , Roberts David J , Tarrus Emili 
Published: April 2011

Abstract
In rats given caffeine (25 mg kg−1 p.o.) and 1,3,8-trisubstituted xanthine (1,3,8-TSX) derivatives (10 mg kg−1 p.o.) the accumulation of the former in plasma was 300% higher than that in control animals given caffeine alone. The effect on caffeine accumulation appears to be independant of the nature of the N3 substituent and its absence in rats given 1,3-disubstituted xanthines (1,3-DSX) instead of 1,3,8-TSX suggests that the presence of the C8-methyl group in the latter compounds is responsible for the accumulation phenomenon. The results of our previous work imply that these observations in this rat model can be extrapolated to man.
Interaction between the cardiovascular effects of Clonidine and the κ-opioid agonist U-50,488H in the anterior hypothalamic area of the rat brain
Authors: Verberne Anthony J M , Louis William J 
Published: April 2011

Abstract
In thiobutabarbitone-anaesthetized rats, microinjection of Clonidine (1–40 nmol) into the anterior hypothalamic area (AHy) produced dose-dependent reductions in mean arterial blood pressure and heart rate. Microinjection of the κ-opioid agonist U-50,488H (3 and 10 nmol) did not modify these parameters. Simultaneous co-administration of Clonidine (4 nmol) and U-50,488H (10 nmol) into the AHy resulted in significant potentiation of the clonidine-induced hypotension and marked attenuation of the bradycardia. A lower dose of U-50,488H (3 nmol) coadministered with Clonidine (4 nmol) did not influence the cardiovascular responses to Clonidine. These findings suggest that AHy neurons involved in the cardiovascular responses to Clonidine may be modulated by κ-opioid receptor stimulation.
Solid State Adsorption of Antibiotics onto Sorbitol
Authors: Nikolakakis I , Newton J M 
Published: April 2011

Abstract
The ability of two types of sorbitol, instant and crystalline, to hold antibiotics permanently after mixing has been assessed by an air sieving technique. Sorbitol instant was found to have a greater adsorption capacity and binding strength than crystalline sorbitol. The six antibiotics studied were found to fall roughly into two groups of different adsorption capacities: (1) pivampicillin, cephalexin monohydrate and erythromycin ethylsuccinate, and (2) ampicillin trihydrate, amoxycillin trihydrate and cloxacillin sodium. The former have slightly higher levels of adsorption than the latter. A negative linear relationship was found between the amount of antibiotic adsorbed onto dry sorbitol and that originally added to sorbitol. When adsorption is expressed as the weight of drug adsorbed per unit weight of sorbitol, an ‘apparent’ Langmuir isotherm results. This suggests that there are a number of adsorption sites available for holding drug particles, these sites being different for the different antibiotics.
The Effect of Machine Speed on the Consolidation of Four Directly Compressible Tablet Diluents
Authors: Armstrong N Anthony , Palfrey Lynn P 
Published: April 2011

Abstract
The reduction in porosity of a powder bed on compression was found to be a function of the velocity of the punch of the press. Substances which consolidated principally by fragmentation showed relatively little velocity dependence. However, the more important deformation was in a powder’s consolidation mechanism, the greater the dependence on punch velocity and hence tablet press speed.
Transport characteristics of [3H]-chlorpromazine across rat small intestinal brush border membrane
Authors: Saitoh Hiroshi , Kawai Shinji , Iseki Ken , Miyazaki Katsumi , Arita Takaichi 
Published: April 2011

Abstract
The transport mechanism of chlorpromazine, a tertiary amine, has been investigated using brush border membrane vesicles isolated from rat small intestine. Chlorpromazine was taken up rapidly by the vesicles the uptake being mainly due to binding to the membrane. The transport of chlorpromazine into the intravesicular space was facilitated by the transmembrane electrical potential difference (inside negative) induced by valinomycin or sodium thiocyanate. This facilitating effect was observed only when the transmembrane electrical potential difference was induced after chlorpromazine uptake had reached a steady state. In the initial phase of chlorpromazine uptake, there was no effect. Therefore, it is suggested that both rapid binding to brush border membrane and transmembrane electrical potential difference (inside negative) across the membrane plays a significant role in the transport processes of chlorpromazine through the intestinal epithelium.
Phenolic analogues of diastereoisomeric 2-methyl reversed esters of pethidine
Authors: Casy A F , Dewar G H , Pascoe R A 
Published: April 2011

Abstract
The preparation and stereochemical characterization of α- and β-isomers of 1,2-dimethyl-4–m-hydroxyphenyl-4-propiony-loxypiperidine are described. Both the α (axial 4-aryl/chair) and β (equatorial 4-aryl/chair) isomers were of low potency or inactive in mice antinociceptive tests. Shortcomings of the α-isomer as a model for the 4-arylpiperidine moiety of morphine are discussed.
Biodegradation Rate of Embolized Protein Microspheres in Lung, Liver and Kidney of Rats
Authors: Willmott N , Chen Yan , Goldberg J , Mcardle C , Florence A T 
Published: April 2011

Abstract
The targeting and sustained release characteristics of cytotoxic drug-loaded protein microspheres may prove useful in the therapeutic chemoembolization of solid tumours. Because biodegradation rate of embolized particles will influence rate of incorporated drug release and duration of exposure, this parameter was studied for microspheres (10–30 μm mean diam.) prepared from the proteins albumin and casein, that we have previously used as carriers for doxorubicin. As a measure of microsphere loss in-vivo the radionuclide 125I was chosen because it can be covalently bound to proteins and also homogeneously distributed throughout the matrix. Radiolabelled microspheres were administered to rats both intravenously (lung as target organ, 1·4-2·2 mg/100 g) and via the hepatic artery (liver as target organ, 0·4-0·8 mg/100 g). In both cases it was observed that the casein system biodegraded more slowly than the albumin in-vivo. Thus, time taken for loss of 50% of embolized microspheres from lung was: albumin 2·0 days; casein 3·5 days and from liver: albumin 3·6 days; casein 6·8 days. Microsphere “debris” did not markedly accumulate in other organs. In-vitro experiments showed that microspheres were stable in serum and that albumin microspheres were not innately more sensitive to enzymic digestion than casein. The results may be useful in estimating duration of exposure of target organs to drug-loaded microsphere systems prepared from these proteins.
Study on Transport of Disopyramide into the Intestinal Lumen Aimed at Gastrointestinal Dialysis by Activated Charcoal in Rats
Authors: Arimori Kazuhiko , Nakano Masahiro 
Published: April 2011

Abstract
The characteristics of exsorption and/or excretion of disopyramide into the gastrointestinal lumen have been investigated after intravenous administration of the drug at doses of 10 and 30 mg kg−1 to rats by the in-situ single pass perfusion technique. Disopyramide was appreciably excreted into the bile where its levels were approximately ten-fold higher than those in the serum. The exsorption rate of disopyramide and mono-N-dealkyldisopyramide (MND) into the perfusate was increased with an increase in the serum level following an increase from 10 to 30 mg kg−1 in the dose of disopyramide. The average amounts of disopyramide exsorbed into the perfusate were 17·0 and 18·4% at the dose of 10 and 30 mg kg−1, respectively, whereas those of MND were less than 1 % at both doses of disopyramide. Oral administration of activated charcoal reduced the serum disopyramide levels after intravenous administration of the drug (20 mg kg−1) compared with the control treatment. By oral administration of activated charcoal, t 1/2 and AUC were decreased to 89 and 82%, respectively, and Cltot was increased to 122% compared with the corresponding control treatment. Vd was not different between the treated rats and control rats. These results suggest that the oral administration of activated charcoal can enhance the clearance of disopyramide and MND from the blood.
Effect of Pyridoxamine on Semicarbazide-sensitive Amine Oxidase Activity of Rabbit Lung and Heart
Authors: Buffoni F , Banchelli G , Bertocci B , Raimondi L 
Published: April 2011

Abstract
Rabbit lung and heart show clorgyline-resistant benzylamine oxidase activity which is sensitive to semicarbazide (SSAO) and α-amino-guanidine. This SSAO activity is inhibited by pyridoxamine with an IC50 of 6·3 × −6 M for lung and of 1·1 × 10−5 M for heart, the inhibition being non-competitive and only partially reversed by dialysis at 4°C. Semicarbazide, α-aminoguanidine and pyridoxamine show a similar time-dependent type of inhibition of rabbit lung and heart SSAO.
Protein Binding of Salicylic and Salicyluric Acid in Serum from Malnourished Children: The Influence of Albumin, Competitive Binding and Non-esterified Fatty Acids
Authors: Ashton J Michael , Bolme Per , Zerihun Getnet 
Published: April 2011

Abstract
The serum protein binding of salicylic and salicyluric acid has been determined by ultrafiltration in 60 children after administration of oral salicylate. The children were classified according to nutritional status: well-nourished (n = 12), underweight (n = 12), marasmic (n = 17) marasmic-kwashiorkor (n = 7) and kwashiorkor (n = 12). Salicylic acid free fractions were 0·106 ± 0·026, 0·114 ±0069, 0·141 ± 0·037, 0·285 ± 0·279 and 0·438 ± 0·190 in the five groups, respectively. Salicyluric acid free fractions were 0·184 + 0·057, 0·280 ± 0·282, 0·236 ± 0·114, 0·484 ± 0·497 and 0·646 ± 0·261, respectively. The degree of binding was dependent on serum albumin levels, ligand concentrations and non-esterified fatty acids (NEFA). The NEFA/albumin ratio ranged from 0·05 to 6·6. The fitting of a one-site Scatchard binding model to the collective data was improved when a decrease was allowed for in the number of binding sites in proportion to NEFA concentrations. Salicyluric acid binding could be fitted only when inhibition of the parent compound was included. Binding was not affected by age or sex. The major determinants of salicylate binding in sera from malnourished children have thus been identified.
Determination of microscopic dissociation constants of 3-hydroxy-α-(methylamino)methyl-benzenemethanol by a spectral deconvolution method
Authors: Quintero B , Baena E , Cabeza M C , Thomas J , Alvarez J M 
Published: April 2011

Abstract
Microscopic dissociation constants of 3-hydroxy-α-(methylamino)methyl-benzenemethanol have been calculated from the titration spectrophotomeric data (c = 3·8 × 10−4 M. Ionic strength = 0·16; buffer system: H3BO3/KOH) by application of a spectral deconvolution method. The results found (pKa = 9·48; pKb = 9·71; pKc = 10·12 and pKd = 9·88) are in good concordance with those obtained from the conventional regression linear method (pKa = 9·45; pKb = 9·77; pKc = 10·14 and pKd = 9·81).
Stimulation of postsynaptic D2− dopamine receptors by B-HT 958 is revealed by co-treatment with the D1− receptor agonist SKF 38393
Authors: Andén Nils-Erik , Grabowska-Andén Maria 
Published: April 2011

Abstract
The motor activity of reserpine-treated mice was used to study effects of B-HT958 (2-amino-6-(p-chlorobenzyl)-4H-5,6, 7, 8-tetrahydrothiazolo-[5, 4-d]-azepine) on postsynaptic dopamine and noradrenaline receptors. The motor activity was only slightly stimulated by B-HT 958 or by the D1− receptor agonist SKF 38393 but it was markedly increased by the two drugs given in combination. The effect of B-HT 958 peaked earlier following low rather than high doses. The enhanced motor activity was inhibited by the D2− receptor antagonist sulpiride or the D1− receptor antagonist SCH 23390, indicating that it was caused by stimulation of both receptor types. The results suggest that B-HT 958 stimulates postsynaptic D2− receptors in addition to D2− autoreceptors and that its blockade of postsynaptic α2-adrenoceptors is of no importance for the motor activity.
Hyperglycaemia as a factor affecting κ-opiate agonist-induced inhibition of the gastrointestinal transit in mice
Authors: Ramabadran K , Bansinath M , Turndorf H , Plug M M 
Published: April 2011

Abstract
The effects of highly selective κ-opiate agonists were assessed on the gastrointestinal motility in normoglycaemic and hyperglycaemic conditions in mice. Chronic hyperglycaemia was induced by streptozocin injection (200 mg kg−1 i.p.), 7–8 days before the experiment. Acute hyperglycaemia was induced by glucose injection (5 g kg−1 i.p.) at the time of opiate administration. The κ-opiate agonists, U-50488H and U-69593 (1, 3 and 10 mg kg−1) were injected (i.p.) just before the charcoal meal. The animals were killed 45 min later and the distance travelled by the test meal was measured. In the normoglycaemic mice, both κ-agonists significantly (P&lt;0.05) inhibited the meal transit and this effect was significantly (P&lt;0.05) augmented in acute hyperglycaemic animals. However, in chronic hyperglycaemic animals U-50488H failed to inhibit the charcoal meal transit, while U-69593 produced anti-transit effect comparable to that observed in normoglycaemic mice. These results demonstrate that κ-opiate agonists produce anti-transit effects in mice and that these effects are enhanced during acute hyperglycaemia. The disparity of anti-transit effects of κ-opiate agonists in acute vs chronic hyperglycaemia supports the hypothesis that elevated glucose levels are not the primary mechanism for the altered response to opiates observed in the experimental models of diabetes.
The Effects of Autoclaving on the Physical Properties and Biological Activity of Parenteral Heparin Preparations
Authors: Menzies A R , Benoliel D M , Edwards H E 
Published: April 2011

Abstract
Heparin ampoules have been autoclaved at 115°C, 121°C, 126°C and 130°C for time intervals up to 50 min and the biological potency and physicochemical integrity of the preparations assessed. The anticoagulant activity, determined with the APTT assay, did not change significantly for the autoclaved samples but a decrease was observed using the BP assay. Autoclaving was also associated with a depolymerization process, as confirmed by high performance liquid chromatography, and the formation of ‘species’ with an absorption in the UV spectrum. However, autoclaving had no detrimental effect on the integrity of the anionic sites on heparin. It is proposed that Maillard-type reactions are responsible for these observations and the results indicate that autoclaving could be used to sterilize parenteral heparin solutions.
Pharmacokinetic Modelling of the Effect of Activated Charcoal on the Intestinal Secretion of Theophylline, using the Isolated Vascularly Perfused Rat Small Intestine
Authors: de Vries Michiel H , Rademaker Carin M A , Geerlings Charles , van Duk Aalt , Noordhoek Jan 
Published: April 2011

Abstract
The effect of activated charcoal administration on the secretion of theophylline from the blood into the intestinal lumen has been examined by use of the rat isolated vascularly perfused small intestine. A closed two compartment model was used to analyse the vascular and luminal concentration-time curves obtained. An equation was derived to calculate the time-dependent intestinal clearance. From control experiments it was concluded that theophylline is secreted by a diffusional transport system through the intestinal wall. The intestinal clearance declined rapidly with time as a result of the concomitant increase in luminal theophylline concentration. After 120 min a steady state between the vascular and luminal perfusate was established. Administration of activated charcoal in the lumen had a profound effect on the kinetics of the drug. The vascular steady state concentration was depressed dramatically. The theophylline clearance remained nearly constant with time, because the blood to lumen concentration gradient was maximized. The maximal value for the intestinal theophylline clearance was estimated to be 0·88 mL min−1 and it equalled the value for the intestinal blood flow at the absorptive site. By use of the concept of absorptive site blood flow, the maximal effect of charcoal on systemic theophylline clearance could be adequately predicted for rats, dogs and man. Activated charcoal administration is only useful to enhance the systemic clearance of drugs or toxicants if that clearance is of the same order of magnitude as the absorptive site blood flow or lower.