bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effects of the pyrones, maltol and ethyl maltol, on iron absorption from the rat small intestine
Authors: Barrand Margery A , Callingham Brian A , Hider Robert C 
Published: April 2011

Abstract
The pyrones, 3-hydroxy-2-methyl-4-pyrone (maltol) and 3-hydroxy-2-ethyl-4-pyrone (ethyl maltol) chelate iron with a high affinity and selectivity. The resulting 1:3 (metal-igand) complexes, being neutral, are able to partition readily across cell membranes and thus may facilitate iron transport across the intestinal wall. Absorption of radioactive iron (59Fe) in the presence of these pyrones was investigated in male rats 1, 2, 4 and 6 h after intraduodenal administration of a 7 μg dose and compared with that of 59Fe given as the sulphate, gluconate, fumarate or complexed to EDTA. Total body absorption and distribution were calculated from the 59Fe content of various tissue samples. With all the iron preparations used, blood levels of 59Fe were highest 1 h after injection whilst the 59Fe content at the major site of deposition, i.e. the bone marrow, increased up to 6 h. No 59Fe was found in the urine. Total body absorption of 59Fe was significantly higher from the pyrones than from the other four preparations. Over the dose range 0.7–700 μg, the proportion of 59Fe absorbed from both iron maltol and iron sulphate decreased with increasing dose. Enhanced 59Fe uptake from maltol was evident at 0.7–70 μg but not at 700 μg suggesting that use of these pyrones will not result in iron overload. Absorption of 59Fe given into the stomach was slower in onset but was sustained longer presumably via a steady delivery of iron to the duodenum from the gastric reservoir. The presence of excess maltol to maintain the integrity of the neutral 1:3 iron-maltol complex under a variety of physiological conditions did not appear critical in-vivo for effective iron absorption. There was no difference in 59Fe uptake between maltol, ethyl maltol or a mixture of ethyl maltol and maltol. 59Fe uptake was significantly enhanced in iron-deficient animals. Within 1 min of i.v. injection of iron complexed to maltol or ethyl maltol, 59Fe became associated with a plasma protein of molecular ratio similar to that of transferrin. With EDTA this process was much slower, i.e. up to 60 min. The half-life of 59Fe in the blood was similar whether administered as the maltol, ethyl maltol, sulphate or EDTA; at the 110 μg iron dose it was 133 ± 8 min and at 1 μg it was 74 ± 10 min in iron-replete animals and 44 ± 5 min in iron-deficient animals. The rate of absorption from the duodenum of 59Fe given as maltol, ethyl maltol or as iron sulphate increased with increasing dose but the shape of the absorption curve depended on the rate of movement of iron along the intestine. It is concluded that the pyrones, maltol and ethyl maltol, are able to enhance the initial stages of iron uptake from the intestinal lumen, possibly by holding the iron in a readily absorbable form, but do not influence subsequent iron distribution and so may provide safe and palatable alternatives to those iron preparations presently available for the treatment of iron deficiency.
The binding of the benzimidazole dye H8208 to DNA and to polyinosinic-polycytidylic acid
Authors: Bardsley Hazel J , Sharples Derek , Grèzes Jean-René 
Published: April 2011

Abstract
The benzimidazole dye H8208 (2-(4-aminophenyl)-5-(4-methylpiperazin-1-yl)benzimidazole) has been shown to intercalate into calf thymus DNA and into polyinosinic-polycytidylic acid (a model for A conformation DNA) by a variety of spectroscopic techniques. The binding affinity of the dye was found to be similar to both nucleic acids.
Kinetics of hydrolysis of meclofenoxate hydrochloride in human plasma
Authors: Yoshioka Sumie , Aso Yukio , Uchiyama Mitsuru 
Published: April 2011

Abstract
The kinetics of hydrolysis of meclofenoxate hydrochloride in human plasma have been compared with those of clofibrate. The hydrolysis rate in fractionated plasma was determined in the presence and absence of a plasma esterase inhibitor, tetraethyl pyrophosphate. The kinetic data indicated that clofibrate decomposed only by esterase-induced hydrolysis, which was inhibited by binding of clofibrate to plasma proteins. In contrast to clofibrate, meclofenoxate decomposed rapidly in human plasma via spontaneous hydrolysis as well as esterase-induced hydrolysis. The spontaneous hydrolysis appeared to be inhibited by some components present in the esterase fraction isolated from plasma, while no significant inhibition of the hydrolysis by protein binding was observed.
Solubilities and intrinsic dissolution rates of sulphamethoxazole and trimethoprim
Authors: Dahlan Rajudin , Mcdonald Charles , Sunderland V Bruce 
Published: April 2011

Abstract
The influence of pH on the dissolution rates and solubilities of sulphamethoxazole and trimethoprim have been examined. Sulphamethoxazole was evaluated in buffers of ionic strength 0.5 mol dm−3 over the pH range 0.45–7.8 and at 25, 32 and 37 °C. The minimum solubility of sulphamethoxazole was 28.1 mg/100 mL at pH 3.22 and 25 °C. Solubilities increased significantly with both increased and decreased pH. Intrinsic dissolution rates demonstrated a linear relationship with the solubility data. Trimethoprim solubility was both buffer- and pH-dependent. In both water and hydrochloric acid solution at 32 °C the solubility of trimethoprim increased from 50 mg/100 mL in water at pH 8.54 to a maximum of 1550 mg/100 mL at pH 5.5. This maximum solubility was in excess of that predicted theoretically and may be due to supersaturation. Below pH 2 the solubility of protonated trimethoprim diminished from 1125 mg/100 mL with decreasing pH. This was due to the common ion effect. Intrinsic dissolution rates increased as pH was decreased with hydrochloric acid from 6.00 to 1.78, but decreased at pH 1.48 due to the common ion effect. Dissolution profiles of trimethoprim showed complex patterns dependent upon pH. The profile was zero-order at pH 6.00 and became distinctly stepwise at pH 5.5, this effect becoming less pronounced at lower pH values. This was reconciled in terms of the rate of formation of trimethoprim hydrochloride on the surface of the disc and the differing dissolution rates of this species and trimethoprim. A simple relationship between solubility and dissolution rate was not observed.
A preliminary pharmacokinetic study of the antimalarial drugs, proguanil and chlorproguanil
Authors: Watkins W M , Chulay J D , Sixsmith D G , Spencer H C , Howells R E 
Published: April 2011

Abstract
Pharmacokinetic parameters for cycloguanil and chlorcycloguanil, the active metabolites of proguanil (Paludrine] and chlorproguanil (Lapudrine) have been measured in a bioassay which assesses the in-vitro growth inhibition of a cycloguanil- and chlorcycloguanil-sensitive strain of Plasmodium falciparum produced by dilutions of plasma collected after oral administration of the pro-drugs. A single compartment model is applicable for cycloguanil with mean rate constants of elimination of 0.0624 h−1 and availability of 0.2398 h−1. The elimination profile for chlorcycloguanil indicates partition of drug into more than one compartment. In 2 of 10 subjects dosed with proguanil and 1 of 11 subjects dosed with chlorproguanil, the active metabolite levels were significantly lower than the mean for the other subjects. Abnormally low cycloguanil or chlorcycloguanil plasma levels may be of importance in relation to effective prophylaxis against malaria.
Saturable uptake of cefixime, a new oral cephalosporin without an α-amino group, by the rat intestine
Authors: Tsuji Akira , Hirooka Hideki , Terasaki Tetsuya , Tamai Ikumi , Nakashima Emi 
Published: April 2011

Abstract
The mechanism of intestinal uptake of cefixime, a new oral cephalosporin antibiotic, has been examined using the everted jejunum of rats. The initial uptake rates were apparently pH-dependent with the maximum rate at pH 5.0 and a 3-fold reduction at pH 7.0. The uptake at pH 5.0 followed mixed-type kinetics involving saturable and non-saturable processes in a manner similar to that for several amino-β-lactam antibiotics. Cefixime uptake was inhibited significantly by 20 mM permeants such as cyclacillin, cephradine, benzylpenicillin, propicillin, glycyl-L-proline and glycyl-glycine. Replacement of Na+ in the medium with choline produced a slight but significant inhibition of cefixime uptake. In spite of the absence of significant inhibition by the amino acids glycine and proline, the dipeptide, glycyl-L-proline in Na+-free medium showed a marked inhibitory effect. The inhibition kinetics of cefixime uptake by glycyl-L-proline and cyclacillin were consistent with competitive-type inhibition. This study provides the first evidence of saturable intestinal uptake of a cephem antibiotic without an α-amino group in the side chain, suggesting transport through the dipeptide carrier system(s).
Influence of β-adrenoceptor-mediated relaxation on α-adrenoceptor-mediated contraction of rat pulmonary artery to adrenaline or noradrenaline
Authors: O'donnell Stella R , Wanstall Janet C , Mustafa Marianna B H 
Published: April 2011

Abstract
Concentration-response (contraction) curves to either adrenaline or noradrenaline were obtained on isolated ring preparations of pulmonary artery from rats. In preparations from young rats the curve for adrenaline was bell-shaped, unless β-adrenoceptors were blocked with propranolol (1 × 10−6 M). The maximum contraction to adrenaline was less in the absence than in the presence of propranolol. In preparations from aged rats the adrenaline curve was no longer bell-shaped, even in the absence of propranolol. This reflected a decrease in the β-adrenoceptor-mediated relaxant responses of preparations from aged rats, seen as a separation between the concentration-response (relaxation) curves to adrenaline on preparations (phenoxybenzamine-treated, KCl-contracted) from young and aged rats. In preparations from young rats the noradrenaline curve was not bell-shaped, but if the preparations were from young rats treated with thyroxine (T4), then a bell-shaped curve for noradrenaline was obtained, unless β-adrenoceptors were blocked by propranolol. These data could be explained by an increase in β-adrenoceptor-mediated relaxant responses of preparations from T4-treated rats, seen as a separation in the concentration-response (relaxation) curves to noradrenaline on preparations from control and T4-treated rats, respectively. Thus (i) α-adrenoceptor-mediated contractile responses of rat pulmonary artery preparations, to adrenaline or noradrenaline, can be attenuated by activation of β-adrenoceptors, mediating relaxation, and (ii) the extent of this attentuation changes under the influence of factors, such as ageing or T4-treatment, which modify β-adrenoceptor-mediated relaxation in this blood vessel type.
Differentiation of calcium antagonists with respect to their effects in normal and skinned taenia caeci preparations
Authors: Cortijo J , Foster R W , Small R C 
Published: April 2011

Abstract
In taenia preparations, depolarized by a K+-rich medium, Ca2+ caused contraction and cinnarizine (0.4–100 μM), trifluoperazine (2–100 μM) and verapamil (0.02–10 μM) caused concentration-dependent antagonism of Ca2+, displacing the Ca2+ log concentration-effect curve to the right and depressing the maximal response. Equieffective (IC75) antispasmogenic concentrations were selected. The antispasmogenic effects of verapamil were readily offset by removing the drug from the bathing fluid but those of the other drugs were not. The calcium antagonists (antispasmogenic IC75) were then tested for spasmolytic activity in tissues generating tension in response to the EC80 of Ca2+. Verapamil was more effective in producing spasmolysis than cinnarazine or trifluoperazine. In skinned taenia preparations, verapamil (100 μM) did not inhibit Ca2+-induced contractions. High concentrations of cinnarizine (100 μM) and trifluoperazine (100 μM) inhibited Ca2+-induced activation of the contractile proteins. However, antispasmogenic IC75s from intact taenia were not able to produce this effect on skinned preparations. It is concluded that there are differences between calcium antagonists. The action of verapamil on intact taenia is mainly exerted on the plasma membrane. Cinnarizine and trifluoperazine act both on the plasma membrane and upon the intracellular contractile machinery.
Dissolution mechanism of tablets produced from coated lactose powder
Authors: Igwilo C , Pilpel N 
Published: April 2011

Abstract
The use of the equation of Kitazawa et al in the analysis of the dissolution process of tablets produced from lactose powder coated with paraffin has suggested either an initial breaking of the tablets into particles that subsequently break down into smaller particles or a progressive breaking of the tablet into smaller particles. The former produces a change in rate constant from k1 to k2.
Effects of applied load and particle size on the plastoelasticity and tablet strength of some directly compressible powders
Authors: Esezobo S , Pilpel N 
Published: April 2011

Abstract
Correlations have been established between the particle size and packing fraction of microcrystalline cellulose, calcium phosphate dihydrate, corn starch and lactose, and the elastic recovery, stress relaxation, and tensile strengths of their tablets.
Enhanced gastrointestinal absorption of drugs in rats pretreated with the synthetic immunomodulator, levamisole
Authors: Utsumi Eriko , Yamamoto Akira , Kawaratani Toshitaka , Sakane Toshiyasu , Hashida Mitsuru , Sezaki Hitoshi 
Published: April 2011

Abstract
The effect of levamisole on drug absorption from the rat small intestine has been investigated by means of an in-situ recirculation technique. The absorption of salicylic acid, sulphanilamide and aminopyrine was significantly increased by the intraperitoneal administration of levamisole (2 mg) 1 day before the absorption studies, but there was no significant effect on absorption from the small intestine of indomethacin, bromthymol blue, sulphafurazole (sulfisoxazole), quinine, sulphanilic acid, phenol red (phenolsulfonphthalein), l-tryptophan and fluorescein isothiocyanate-dextrans. The effect of levamisole on the absorption from the small intestine of salicylic acid was marginally dose- and time-dependent, the maximal effect being observed after pretreatment with 2 mg of levamisole 1 day before the absorption studies. Sulphanilamide, similarly, was better sorbed from the small intestine and also from the stomach in the presence of levamisole. The intraperitoneal administration of levamisole may influence the absorption of some low molecular weight drugs from the gastrointestinal tract.
Binding parameters and microbiological activity of macrolides, lincosamides and streptogramins against Staphylococcus aureus
Authors: Fournet M P , Barre J , Zini R , Deforges L , Duval J , Tillement J P 
Published: April 2011

Abstract
Parameters of erythromycin binding to Staphylococcus aureus were measured in-vitro using an equilibrium method with [3H]erythromycin. The dissociation constant of the complex, erythromycin-S. aureus sensitive strain, was KD = 0.11 μM. The maximal binding, representing the density of binding sites was 14 847 molecules/cell. No binding was detectable on the constitutive resistant strain. Macrolides, streptogramins and lincosamides displaced bound [3H]erythromycin by a competitive process indicating that these compounds share common binding sites on the bacteria, i.e. 50 S ribosomal subunits. A good correlation (r = 0.99) was demonstrated between the corresponding inhibition constants (Ki) and the minimal inhibitory concentration. It is proposed that knowledge of the binding parameters provides a good indication of bacterial susceptibility and may serve as a useful adjunct in developing new compounds.
Tamoxifen inhibits 5-lipoxygenase in human polymorphonuclear leucocytes
Authors: Tavares I A , Stamford I F , Bennett A 
Published: April 2011

Abstract
Breast cancer patient survival is increased by tamoxifen, and we therefore need to understand how this drug exerts its effect. We describe a novel action of tamoxifen, the inhibition of LTB4 and 5-HETE production from [14C]-arachidonic acid by human polymorphonuclear leucocytes.
Potentiation of contractile response and increase in tissue sodium content induced by aconitine in the guinea-pig vas deferens
Authors: Ohizumi Yasushi , Kajiwara Akiko 
Published: April 2011

Abstract
Aconitine potentiated the contractile response of the guinea-pig vas deferens and increased the tissue Na and Ca content. These effects were abolished in the presence of tetrodotoxin. These results suggest that aconitine causes an increasing Na+ permeability of the smooth muscle membrane to increase Ca2+ availability and thus induces potentiation.
Evaluation of electrical conductivity-temperature curves using a mathematical model: temperature-dependent changes during thawing of frozen aqueous pharmaceuticals
Authors: VAN GORP J A , SALEMINK P , VERMEULEN M , BANKEN P 
Published: April 2011

Abstract
The information contained in the electrical conductivity curves of pharmaceuticals measured as a function of temperature can be represented by a small set of parameters. This is achieved by approximating the electrical conductivity curve as a number of consecutive steps, using a suitable empirical model. The three parameters describing each step are: transition temperature, slope factor and step height. The validity of the calculated transition temperatures was established by applying the model to electrical conductivity curves measured on aqueous solutions of KCl, NaCl and on a KCl-NaCl mixture. It appears that the transition temperatures calculated for these inorganic salts are in good agreement with the respective eutectic temperatures reported in the literature. Subsequently, the method was applied to the corticosteroids prednisolone sodium succinate and prednisolone disodium phosphate. The mathematical model yields a satisfactory fit for both experimental conductivity curves. The actual consequences of freeze-drying an aqueous solution of prednisolone sodium succinate below and above the respective transition temperatures calculated are discussed in relation to the experimental conductivity data.
Influence of solvent on the availability of testosterone propionate from oily, intramuscular injections in the rat
Authors: AL-HINDAWI M K , JAMES K C , NICHOLLS P J 
Published: April 2011

Abstract
The suggestion that the biological response to an oily intramuscular injection of testosterone ester is regulated by rapid accumulation of the steroid in body fat, followed by a slow release, has been tested by comparing the release rates of 14C-labelled testosterone propionate from different solvents following intramuscular injection into rats. Disappearance from the injection site was rectilinearly related to in-vitro partition coefficients, but elimination of radioactivity in urine and faeces was significantly longer, and the same for all four solvents. Testosterone and testosterone propionate were found in equal concentration in body fat, 2 and 3 days after injection, but their concentrations were too low to form an effective depot. It is suggested that the delay in release, and the independence of the delay on the nature of the solvent is a consequence of biliary recycling of testosterone.
Depressant action of oxybutynin on the contractility of intestinal and urinary tract smooth muscle
Authors: TONINI M , RIZZI C A , PERUCCA E , DE PONTI F , D'ANGELO L , DEL VECCHIO A , CREMA A 
Published: April 2011

Abstract
Experiments were carried out in-vitro using segments of guinea-pig ileum, taenia caeci, ureter and detrusor. In the ileum, oxybutynin (30, 100 nM) competitively antagonized acetylcholine-induced contractions but did not alter those induced by histamine. Higher concentrations of oxybutynin (up to 10 μM) induced a non-competitive depression of responses to both agonists and caused a parallel shift to the right of the Ca2+-induced contractions in taenia caeci strips bathed in a Ca2+-free, high-K+ medium. In the ureter, oxybutynin (1–10 μM) impaired rhythmic muscular contractions in normal medium and after CaCl2 addition in Ca2+-free medium. Similarly to verapamil (10, 30 μM), oxybutynin (10, 30 μM) depressed both the cholinergic and non-adrenergic, non-cholinergic components of the electrically-induced contractions of detrusor strips. It is concluded that oxybutynin has anticholinergic properties and, at higher concentrations, exerts a direct spasmolytic activity possibly mediated by blockade of the transmembrane Ca2+ fluxes responsible for smooth muscle contraction.
Sodium nitroprusside: pharmacological aspects of its interaction with hydroxocobalamin and thiosulphate
Authors: HEWICK D S , BUTLER A R , GLIDEWELL C , McINTOSH A S 
Published: April 2011

Abstract
Hydroxocobalamin (HOCb), when mixed with sodium nitroprusside (SNP) in a 10:1 or 1:1 molar ratio and injected (i.v.) into the anaesthetized rat, prolonged the depressor response to SNP by 25–50%, but did not affect the degree of blood pressure lowering. Both the ‘onset’ and ‘offset’ components of the response were prolonged. Injecting [14C]SNP along with a 10-fold molar excess of HOCb resulted in a 2- to 3-fold elevation of plasma radioactivity which was maintained during the first 10 min of a 40 min experimental period. These effects of HOCb on the pharmacodynamics and pharmacokinetics of SNP are probably due to complex formation between the two compounds. Sodium thiosulphate (ST) added to SNP (12:1 molar ratio) had no effect on the depressor response to SNP. This mixing of ST and SNP had a less-marked influence on the plasma [14C]SNP-derived radioactivity than occurred with HOCb. There was no initial elevation of radioactivity, but the levels were raised by 50–60% at 4, 6 and 10 min. Since the depressor response to SNP was unaffected by ST, it is presumed that the higher concentrations of radioactivity were due to inactive degradation products rather than the active species itself.
Does brain 3,4-dihydroxyphenylacetic acid reflect dopamine release?
Authors: Soares-da-Silva P 
Published: April 2011

Abstract
After sulpiride (75 mg kg−1) administration, a significant increase in dopamine, 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) occurred in the rat striatum. No attenuation in the sulpiride-induced dopamine and DOPAC increase was seen in the striatum from rats previously treated with benztropine (25 mg kg−1). On the other hand, in the benztropine + sulpiride-treated group, HVA levels were significantly lower compared with those of rats to which only sulpiride had been given. The results presented suggest that under appropriate conditions, as when sulpiride is used, dopamine can be deaminated before its release has occurred.
Temporal changes in bupivacaine kinetics
Authors: Bruguerolle Bernard , Prat Marin 
Published: April 2011

Abstract
The chronokinetics of bupivacaine have been examined in the mouse. Different groups of adult male NMRI mice maintained under controlled environmental conditions received a single intraperitoneal injection of bupivacaine (20 mg kg−1) at one of four different fixed time points in a 24 h period i.e. 1000, 1600, 2200 and 0400h. Blood samples were taken 0.25, 0.5, 0.75, 1, 1.5, 3, 4 and 6 h after drug administration and total serum levels of bupivacaine were determined by a gas-liquid chromatography with a flame ionization detector. Statistically significant temporal changes were found in the following pharmacokinetic parameters: highest Cmax value = 0.900 ± 0.080 μg mL−1 at 2200h (amplitude, maximum-minimum/mean × 100, is 64%); highest Cmax/Tmax ratio = 3.596 ± 0.339 at 2200h (amplitude = 85%); highest β elimination half-life, T½β;, = 3.950 ± 0.246 h at 2200h (amplitude = 35%); area under concentration curve (AUC0∞) was not found to be significantly different among the hours of administration. The temporal kinetic changes demonstrated suggest a possible circadian difference in bupivacaine efficacy and/or toxicity.