bluuebunny/crossref_metadata_2025_split huggingface dataset:
Protective effect of salicylate against 2,4-dinitrophenol-induced protein thiol loss in the small intestine of rats
Authors: Nishihata Toshiaki , Suzuka Takumi , Yata Noboru , Sakai Kiyoshi 
Published: April 2011

Abstract
The effect of the content of protein thiols and non-protein thiols in the tissue of the rat small intestinal loop on the absorption of cefmetazole has been investigated. 2,4-Dinitrophenol (DNP), at a concentration of 500 μM, caused rapid protein thiol loss, followed by non-protein thiol loss, along with a decrease of cefmetazole absorption by the intestine. The coadministration of 75 mM salicylate with DNP inhibited the effect of DNP on protein thiols and cefmetazole absorption but not on non-protein thiol loss by DNP.
The Oral Disposition of Zinc Following the Use of an Anticalculus Toothpaste Containing 0.5% Zinc Citrate
Authors: Gilbert R J , Ingram G S 
Published: April 2011

Abstract
Zinc is retained in the mouth after use of a toothpaste containing 0.5% zinc citrate. More than one third of the dose was found to be retained after normal brushing. Elevated zinc levels were also found in plaque. Saliva zinc levels were significantly above background for at least 2 h after brushing. In-vitro experiments demonstrated that zinc can bind to the pellicle-coated tooth surface and can subsequently desorb into saliva. Plaque can calcify to form calculus containing appreciable levels of hydroxyapatite. Zinc adsorbs to hydroxyapatite inhibiting crystal growth. Levels of zinc in plaque were found to be considerably higher than those taken up by hydroxyapatite in an in-vitro test of crystal growth inhibition indicating the potential of zinc to inhibit calculus formation.
Sex-related Differences in Disposition and Response to Phenprocoumon in Rats
Authors: Trenk D , Jähnchen E , Øie S 
Published: April 2011

Abstract
The pharmacokinetics and the pharmacological response to phenprocoumon have been studied in female and male inbred Lewis-Wistar rats. A significantly lower clearance was found in female than in male rats (7.9 ± 1.4 vs 24.5 ± 2.5 mL h−1 kg−1, respectively; t = 15.09, P &lt; 0.001) as well as a lower apparent volume of distribution (288 ± 46 vs 617 ± 105 mL kg−1; t = 7.58, P &lt; 0.001) and a longer half-life (25.5 ± 3.4 vs 17.5 ± 1.8 h; t = 5.16, P &lt; 0.001). The binding of phenprocoumon was higher in female than in male rats (fu: 0.0096 ± 0.0008 vs 0.0124 ± 0.0007, respectively; t = 6.66, P &lt; 0.001). The total (C) as well as the unbound concentration (Cu) needed to elicit a 50% decrease in the prothrombin complex synthesis rate was substantially higher in female rats: C50 was 377 ± 98 ng mL−1 in female and 155 ± 29 ng mL−1 in male rats (t = 5.32, P &lt; 0.001), whereas Cu50 was 3.6 ± 0.7 ng mL−1 in female and 1.9 ± 0.3 ng mL−1 in male rats (t = 5.50, P &lt; 0.001). However, because of the lower clearance and volume of distribution and the longer half-life in female rats, the female rats experienced a higher cumulative effect than male rats to 0.34 mg kg−1 i.v. doses.
Time-dependent distribution and excretion of radiolabelled, semipermeable, stable magnetic microcapsules
Authors: Povey A C , Godeneche D , O'Neill I K 
Published: April 2011

Abstract
The time-dependent excretion and potential body retention of magnetic polyethyleneimine (PEI) microcapsules, methylated with [14C]methyl iodide have been investigated after intragastric administration to mice. Gastric emptying was rapid but about 10% of the administered dose was still present in the stomach after 6 h; the number of microcapsules within the small intestine remained approximately constant over 1–6 h. Excretion of microcapsules in the faeces was virtually complete (98.7% excretion within 72 h), with small amounts of radioactivity excreted via the urine or as [14C]CO2. There was no detectable adsorption or retention of microcapsules within the body as measured by either a whole-body autographic study or by direct quantitation of tissue radioactivity.
Prodrug behaviour of nicotinoylmorphine esters
Authors: Broekkamp C L , Oosterloo S K , Rijk H W 
Published: April 2011

Abstract
Morphine and its nicotinoyl esters, dinicotinoylmorphine (nicomorphine), 6-mononicotinoylmorphine (6-MNM) and 3-mononicotinoylmorphine (3-MNM) were tested in mice for central activity to obtain time-effect profiles of these compounds in rats. Two effects, analgesia with the hot plate test and locomotor stimulation in activity cages were measured and nicomorphine, 6-MNM and 3-MNM were found to have a faster onset of action compared with morphine. The effects of 3-MNM and morphine lasted longer than the effect of nicomorphine and 6-MNM. The prodrug behaviour of 3-MNM and nicomorphine for morphine and 6-MNM, respectively, is discussed.
Propranolol uptake with high capacity by rat perfused lung
Authors: Iwamoto Kikuo , Watanabe Jun , Yonekawa Hina 
Published: April 2011

Abstract
Lung isolated from 7-week-old rats was perfused with pH 7.4 Krebs-Ringer bicarbonate buffer solution (35 mL) containing 1 to 100 μg mL−1 of propranolol and 3% BSA at the recirculation rate of 8 mL min−1. Almost parallel bi-exponential drug concentration-time curves were obtained at the initial load lower than 10 μg mL−1, whereas relatively slow, mono-exponential decline was found after perfusion at 100 μg mL−1. Pharmacokinetic analysis for the perfusate propranolol concentration-time curves when loaded at 1 to 10 μg mL−1 yielded almost comparable values for the pulmonary perfusion clearance (0.387 ± 0.092 to 0.486 ± 0.095 mL min−1 g−1). In contrast, this parameter was significantly reduced at 100 μg mL−1 (0.113 ± 0.042 mL min−1 g−1). The present findings suggest a trend towards saturation kinetics in the in-vitro pulmonary clearance of propranolol.
Multiple Compression and Plasto-elastic Behaviour of Paracetamol and Microcrystalline Cellulose Mixtures
Authors: Yu H C M , Rubinstein M H , Jackson I M , Elsabbagh H M 
Published: April 2011

Abstract
Radial tensile strength, friability, ER/PC (elastic recovery/plastic compression) ratio and energy ratio analyses were evaluated for various mixtures of paracetamol and microcrystalline cellulose (Avicel). A good correlation occurred between the energy ratio and the other variables. Linear relationships were found between log tensile strength and percentage energy ratio and also between radial tensile strength and stress relaxation energy. Capping occurred when the percentage energy ratio was greater than 15% and the ER/PC ratio greater than 1.5. To produce tablets with acceptable tensile strength and friability, the percentage energy ratio for Avicel/paracetamol should be greater than 10%. The optimal mixture of the two powders, as far as the tensile strength, friability and absence of capping were concerned, was found to be 50% w/w Avicel, 50% w/w paracetamol.
Effects of a Perfluorochemical Blood Substitute on Diazepam Binding by Human Albumin
Authors: Graben R D , Parsons D L 
Published: April 2011

Abstract
The binding of 0.4 μg mL−1 diazepam and 0.75 mol diazepam mol−1 of albumin by a perfluorochemical (PFC) emulsion, Fluosol-DA, 20%, by human serum albumin (HSA), and by their mixtures, has been examined at ambient temperature. The concentration of free diazepam was determined by standard centrifugation followed by supernatant ultrafiltration. Non-specific loss of diazepam occurred to the ultrafiltration device. This loss was independent of drug concentration and a correction factor was employed to calculate the true free diazepam concentration. Diazepam was extensively bound by the PFC emulsion. The percent free diazepam increased as the emulsion concentration decreased, while the binding of diazepam appeared to be independent of drug concentration. Diazepam did not partition into the pure PFC liquids, indicating that emulsion-bound diazepam is only associated with the emulsifiers of the droplets. Diazepam was extensively bound by HSA and the percent free diazepam increased as drug concentration increased or as HSA concentration decreased. The PFC emulsion significantly displaced HSA bound diazepam in all mixtures examined. Studies with the individual and combined components of the emulsion indicated that this displacement is largely attributed to the oleic acid component and, to a much smaller degree, the Pluronic F-68 component of the emulsion.
Binding of Drugs to Human Skin: Influencing Factors and the Role of Tissue Lipids
Authors: Walter K , Kurz H 
Published: April 2011

Abstract
For a series of ten drugs with different physicochemical properties, binding to human skin (epidermis and corium) was determined. Epidermis was obtained by suction blistering, and corium was sliced with a microtome (0.2 mm). Binding experiments were performed in dialysis chambers, containing labelled drug solutions. All drugs investigated were bound to epidermis and corium. With one exception, epidermal drug binding was significantly higher than corial binding. Nevertheless, a good correlation between binding of drugs to both skin fractions could be found. In a range from 10−7 to 10−3 mol L−1 binding of drugs to both skin fractions is linear and not saturable. A good correlation was found between binding and lipophilicity of drugs, determined as the partition coefficients between an organic phase (octanol or heptane) and phosphate buffer of pH 7.0. The results show that binding to epidermis and corium is not saturable and depends on lipophilicity of drugs, indicating unspecific binding. Further binding experiments were performed with lipid-depleted tissue. Since drug binding to lipid-depleted samples and control samples differ only to a moderate extent, it is suggested, that tissue lipids play a marginal role on drug binding. Hence, drugs are bound to human skin by other components like proteins.
Vasoactive Intestinal Polypeptide as Possible Mediator of Relaxation in the Rat Gastric Fundus
Authors: de Beurme F A , Lefebvre R A 
Published: April 2011

Abstract
Relaxations were induced in longitudinal muscle strips of the rat gastric fundus by stimulation of non-adrenergic non-cholinergic (NANC) neurons and by administration of vasoactive intestinal polypeptide (VIP) or isoprenaline. The effect of antiserum against vasoactive intestinal polypeptide (VIP antiserum) and of control serum on these relaxations was investigated. Incubation with VIP antiserum (dilution 1/50) for 1 h almost completely prevented the relaxation by VIP. It partially prevented the relaxation evoked by electrical stimulation while the relaxation induced by isoprenaline was not influenced. Control serum decreased the VIP- and stimulation-induced relaxations much less than did VIP antiserum. In addition, the effect of the putative VIP antagonist (4Cl-D-Phe6, Leu17) VIP was studied on the relaxations induced by NANC neuron stimulation and by VIP. The VIP antagonist (3.10−5 M, incubation time 10 min) had a relaxatory effect itself but had no influence on either VIP- or stimulation-induced relaxations. The results with VIP antiserum confirm the involvement of VIP in the inhibitory NANC neurotransmission of the rat gastric fundus.
External control of drug release: controlled release of insulin from a hydrophilic polymer implant by ultrasound irradiation in diabetic rats
Authors: Miyazaki Shozo , Yokouchi Chizuko , Takada Masahiko 
Published: April 2011

Abstract
The development of a polymeric system capable of delivering insulin in-vivo at increased rates on demand by an external ultrasound irradiation is reported. Implants composed of EVA1 copolymer and insulin were placed subcutaneously in diabetic rats. When the diabetic rats receiving implants containing insulin were exposed to an ultrasound irradiation, a sharp drop in the blood glucose levels was observed after the irradiation, indicating a rapid rate of release of insulin in the implanted site.
Inhibition of histamine N-methyltransferase activity in guinea-pig pulmonary alveolar macrophages by nicotine
Authors: Gairola C , Godin C S , Houdi A A , Crooks P A 
Published: April 2011

Abstract
Both S-(−)- and R-(+)-nicotine enantiomers are inhibitors of histamine Nτ-methylation activity in guinea-pig pulmonary alveolar macrophage cultures, exhibiting IC50 values of 7 and 8 μM, respectively. S-(−)-Nicotine is not biotransformed under the conditions of the experiment, however, R-(+)-nicotine undergoes significant N-methylation to produce N-methylnicotinium ion. S-(−)-Nicotine appears to inhibit the N-methylation of its optical antipode by the alveolar nicotine N-methyltransferase. The results indicate that a contributing factor in the toxicology of cigarette smoke inhalation may be due to the inhibition of pulmonary metabolism of histamine by nicotine.
A rapid and sensitive high-performance liquid chromatographic method for the determination of diclofenac sodium in serum and its use in pharmacokinetic studies
Authors: El-Sayed Yousry M , Abdel-Hameed Mohamed E , Suleiman Mohammad S , Najib Naji M 
Published: April 2011

Abstract
A rapid, and sensitive high-performance liquid chromatographic method has been developed for the determination of diclofenac sodium in serum using flufenamic acid as the internal standard. Serum protein was precipitated with acetonitrile. The drugs were eluted from a 5 μm C-8 reversed-phase column at ambient temperature with a mobile phase consisting of acetonitrile-water (50:50% v/v) adjusted to pH 3.3 with glacial acetic acid, at a flow rate of 2 mL min−1 with UV detection at 280 nm. Each analysis required no longer than 10 min. Quantitation was achieved by the measurement of the peak-height ratio and the relative and absolute recoveries varied from 90 to 98%. Detection limits for diclofenac sodium in serum is 25 ng mL−1. Intraday coefficients of variation (CV) ranged from 2.47 to 4.61 % and interday CVs from 3.52 to 7% at three different concentrations. Preliminary stability tests showed that diclofenac sodium is stable for at least 2 weeks in serum after freezing. The method is applied for the determination of the pharmacokinetic parameters of diclofenac after administration of two formulations (enteric-coated tablet and slow-release tablet), to a healthy male volunteer.
Digitonin-solubilized histamine H1-receptors bind to polyethylenimine-treated glass-fibre filters
Authors: Treherne J M , Young J M 
Published: April 2011

Abstract
The binding of [3H]mepyramine to histamine H1-receptors solublized from guinea-pig cerebellum by 1% digitonin could be assayed by adsorption of the receptor-bound [3H]ligand to glass-fibre filters pretreated with 0.3% polyethylenimine (PEI). Nonspecific binding was higher than in parallel experiments in which the bound and free [3H]ligand was separated by gel-filtration on Sephadex G-25 columns, but the parameters characterizing the inhibition curves were otherwise similar. The PEI-treated filter method could also be used to assay [3H]-(+)-N-methyl-4-methyl-diphenhydramine ([3H]QMDP) binding to solubilized H1-receptors, but the level of non-specific binding was higher and was only satisfactorily defined by icotidine or temelastine. A particular utility of the PEI-treated filter assay will be in measurements of the kinetics of H1-receptor-ligand interactions.
Effects of Tapioca Obtained From Cassava (Manihot utilissima) on the Disintegration and Dissolution Rates of Paracetamol Tablets
Authors: Esezobo S , Zubair S , Pilpel N 
Published: April 2011

Abstract
The properties of tapioca obtained from cassava (Manihot utilissima) have been evaluated. Its binding effect in tablets of paracetamol on the disintegration and dissolution rates was compared with tablets prepared with polyvinylpyrrolidone and gelatin. The nature and amount of the binders were found to alter the disintegration and dissolution rates of the tablets by reducing their wettability as measured by the adhesion tension of water. A linear relationship has been found to exist between the adhesion of water on the tablets and their disintegration and dissolution rates.
Mediators of the Plasma Extravasation Response to Silver Nitrate in the Rat Skin, Subplantar Region and Ankle Joint
Authors: Fyfe Margaret C , Chahl Loris A 
Published: April 2011

Abstract
Plasma extravasation responses to silver nitrate (AgNO3), histamine, 5-hydroxytryptamine (5-HT), bradykinin and prostaglandin E1 (PGE1) in the abdominal skin, hindpaw ankle joint and subplantar region of rats have been investigated using the Evans blue dye leakage technique. All substances tested produced plasma extravasation and combination of low doses (5 × 10−10mol) of either histamine or bradykinin with PGE, (5 × 10−10mol) exhibited potentiation of responses of all regions. Responses to AgNO3 (1 × 10−6mol) were significantly reduced by the H1 receptor antagonist, mepyramine, only in the abdominal skin, but the H2 receptor antagonist metiamide reduced the responses at subplantar and ankle joint regions. Indomethacin significantly reduced the AgNO3 responses at the ankle joint only, but aprotinin reduced it at the other two regions. In rats pretreated with a combination of all antagonists the residual plasma extravasation response to AgNO3 was very small, indicating that the response could be almost totally accounted for by the combined actions of mast cell amines, kinins and prostanoids. The finding that prostanoids played a major role in the plasma extravasation response of the rat ankle joint to AgNO3 indicated that this model would be useful for the screening of non-steroidal anti-inflammatory drugs.
The effect of some tricyclic antidepressants on the inhibition of mouse brain monoamine oxidase in-vivo by phenelzine
Authors: Green A L , O'Grady J E , Vass M 
Published: April 2011

Abstract
Four tricyclic antidepressants, amitriptyline, imipramine, desipramine and iprindole have been shown to partially protect mouse brain monoamine oxidase in-vivo from the irreversible enzyme inhibition produced by subsequent injection of phenelzine. Levels of protection were similar when the enzyme was assayed with selective substrates (5-hydroxytryptamine and phenethylamine) for both the A and B forms of the enzyme. Although other explanations cannot at this stage be ruled out, these observations are consistent with the tricyclic antidepressants acting as reversible inhibitors of brain monoamine oxidase in-vivo.
Hypothermia induces supersensitivity of mouse vas deferens to adrenergic agonists: evidence for postjunctional α2-adrenoceptors
Authors: Goncalves J , Proenca J , Albuquerque A A , Paiva M Q 
Published: April 2011

Abstract
Hypothermia-induced potentiation of α-adrenoceptormediated responses of the mouse vas deferens to noradrenaline is mainly caused by inhibition of the sites of loss. However, even after blockade of the sites of loss for noradrenaline or when using methoxamine (which is not a substrate for uptake or metabolism) hypothermia still causes a significant increase in responsiveness. This remaining supersensitivity was shown to be an increased receptor affinity. Furthermore, hypothermia revealed contractile responses to low concentrations of UK 14304 (an α2-agonist).
Characterization of Albumin-Alginic Acid Complex Coacervation
Authors: Singh O N , Burgess D J 
Published: April 2011

Abstract
Complex coacervation of albumin and alginic acid has been investigated to characterize this process, and to prepare a microencapsulation system suitable for the encapsulation of live cells, protein and polypeptide drugs. The optimum conditions of pH, ionic strength and total polyion concentration were in accordance with predictions based on the method of Burgess & Carless (1984). Albumin/alginic acid complex coacervation appears to fit the Vies-Aranyi model for complex coacervation. Coacervation was limited compared with other polypeptide/polysaccharide systems such as gelatin and acacia, with albumin/ alginic acid complex precipitates rather than complex coacervates forming under certain conditions. In particular coacervation was limited to concentrations below 0·5% w/v. At concentrations between 0·35 and 0·5% w/v both complex coacervation and precipitation occurred, and at concentrations above 0·5% w/v only precipitation was detected. The albumin/alginic acid complex coacervate is very viscous and this together with the limited conditions governing the occurrence of coacervation makes this system unsuitable for the preparation of microcapsules.
Locomotor Behaviour of Selective Dopamine Agonists in Mice: Is Endogenous Dopamine the Only Catecholamine Involved?
Authors: Pichler Ludwig , Pifl Christian 
Published: April 2011

Abstract
The purpose of the study was to determine the effect alone and in combination of the selective dopamine (DA) agonists SKF 38393 (D1-) and B-HT 920 (D2-) on the locomotor activity of reserpine pretreated mice (5 mg kg−1 i.p.). After 4 h, reserpine-B-HT 920 (up to 20 mg kg−1 s.c.) did not induce locomotor activity whereas SKF 38393 was markedly effective at high doses (≥ 30 mg kg−1 s.c). In contrast, at 24 h, reserpine-B-HT 920 (0·2–6 mg kg−1 s.c.) elicited considerable locomotor activity and SKF 38393 (1–100 mg kg−1 s.c.) was effective at lower doses when compared with the corresponding 4 h reserpine experiments. When, however, these animals additionally received α-methyl-p-tyrosine (αMPT; 300 mg kg−1 i.p., at 4 h before the DA agonists) neither B-HT 920 (0·2–20 mg kg−1 s.c.) nor SKF 38393 (1–100 mg kg−1 s.c.) had an effect of their own. When B-HT 920 was tested in the presence of a fixed-dose of SKF 38393 (10 or 3 mg kg−1 s.c., combination experiments) B-HT 920 (0·6–20 mg kg−1 s.c.) induced considerable locomotor activity at 4 h post reserpine. At 24 h post reserpine the dose-response curve of B-HT 920 (0·06–20 mg kg−1 s.c.) was shifted to the left and the maximum effect was greatly increased. When additional αMPT was given, the dose response curve was the same but the maximum effect was markedly reduced. When SKF 38393 was tested in the presence of a fixed-dose of B-HT 920 (2 mg kg−1 s.c.; combination experiments) this resulted in a dose response curve in the range of 0·3–10 mg kg−1 s.c. at 4 h post reserpine. At 24 h post reserpine the curve shifted to the left by approximately a factor of 30 (0·1–3 mg kg−1 s.c.) and the maximum effect was markedly increased. Additional αMPT shifted the curve to the right by a factor of approximately 30 without a substantial change in the maximum effect. It is concluded that simultaneous stimulation of D1- and D2- receptors is necessary to elicit locomotor activity in mice. From dose response analysis of experiments with additional αMPT it is furthermore concluded that endogenous noradrenaline may play an additional modulatory role.
A note on the use of salicylate saliva concentration in clinical pharmacokinetic studies
Authors: Khan Azhar Z , Aarons Leon 
Published: April 2011

Abstract
A sequential approach is presented to the problem of determining the minimum number of blood samples needed to calculate the plasma to saliva concentration ratio to a required precision. The method was applied to salicylate concentrations obtained from six rheumatoid arthritis patients. In order to achieve a 10 per cent coefficient of variation in the plasma to saliva salicylic acid concentration ratio, on average 9 samples were required for total plasma concentration and 8 samples for unbound concentration. In some cases it was not possible to achieve the required precision with the given number of samples. Correlation of salicylic acid concentrations in saliva with total and unbound plasma concentration were equally as good. The limitations of saliva data in clinical pharmacokinetic studies are discussed.