bluuebunny/crossref_metadata_2025_split huggingface dataset:
The in-vitro metabolism of [14C]pentobarbitone and [14C]phenobarbitone by hamster liver microsomes
Authors: SEAGO A , GORROD J W 
Published: April 2011

Abstract
The metabolism of [14C]pentobarbitone and [14C]phenobarbitone has been reinvestigated using an in-vitro hepatic microsomal system (Syrian hamsters, Aroclor 1254 induction). The incubation system was routinely supplemented with EDTA (1 mM) and a substrate concentration study revealed the metabolism of [14C]pentobarbitone to be concentration-dependent, with the greatest overall metabolism (&gt;50%) occurring at 0.054 μmol per 3.5 mL. With [14C]phenobarbitone as substrate, overall metabolism was extremely low (3%) and independent of substrate concentration. Addition of further cofactors to the incubation mixture at 20 min intervals over an extended period resulted in almost complete metabolism of [14C]pentobarbitone (100 min), 3′-hydroxypentobarbitone and 3′-oxopentobarbitone being identified as metabolites together with many minor, unidentified products. With [14C]phenobarbitone as the substrate, cofactor addition up to 120 min resulted in 8% overall metabolism; p-hydroxyphenobarbitone was identified as a product of metabolism; other minor products were unidentified. The metabolism studies failed to produce a metabolite having the properties of the N-hydroxylated product of either [14C]pentobarbitone or [14C]phenobarbitone within the detection limits available (0.02% of 0.5 μmol per incubate).
Erythrocyte binding of cephalosporins
Authors: Derendorf Hartmut 
Published: April 2011

Abstract
A rapid sample preparation and HPLC technique was used to study the erythrocyte binding properties of six cephalosporins at therapeutic concentrations. The negligible red blood cell partition coefficients indicated that only small amounts of the cephalosporins were taken up by the blood cells at all drug concentrations. Thus, plasma concentrations were about twice as high as the respective blood concentrations. Blood/plasma ratios solely depended on the haematocrit and were independent of the extent of protein binding.
Inhibitory effect of phenothiazines on the binding of [3H]perazine to α1-acid glycoprotein
Authors: Schley J 
Published: April 2011

Abstract
A system is described which allows the determination of the afffinity constant of unlabelled drugs to α1-acid glycoprotein (α1-AGP) by displacing [3H]perazine from the binding protein with equilibrium dialysis. All drugs investigated appear to bind to only one site at the α1-AGP molecule. From experiments, in which the chemical structure of the displacers was varied, the fragment 21–31 of the amino acid sequence appears to be a candidate for hydrophobic interactions. The glutamic acids 177 and 178 of the α1-AGP molecule could be involved in ionic interactions with the side chain of phenothiazine derivatives. The relevance of α1-AGP for drug binding, distribution, and the possible reasons for insufficient correlation between psychotropic plasma concentration and therapeutic response is discussed.
Macrophage activation through phagocytosis of muramyl dipeptide encapsulated in gelatin microspheres
Authors: Tabata Yasuhiko , Ikada Yoshito 
Published: April 2011

Abstract
Gelatin microspheres containing muramyl dipeptide (MDP) were prepared by crosslinking with glutaraldehyde. They were added to mouse peritoneal macrophages (PMs) to potentiate the tumour growth inhibitory activity. The PMs which had internalized the microspheres exhibited growth inhibitory activity to syngeneic, allogeneic, and xenogeneic tumour cells. A similar effect was observed for PMs incubated with free MDP, but the MDP encapsulated in the microspheres was more efficient in enhancing the PM activity than the free MDP. In addition*** PMs were activated in much shorter periods upon incubation with the microsphere-encapsulated MDP. The duration of activity could be controlled for up to 7 days by changing the extent of crosslinking of microspheres. Dose-response experiments established that microsphere-encapsulated MDP is able to activate PMs to inhibit growth of tumour cells at concentrations approximately 2000 times lower than the free MDP present in media. The activity of PMs was also acquired on intraperitoneal injection of the microspheres, in contrast to PMs with the free MDP.
Probenecid-induced accumulation of 5-hydroxyindoleacetic acid and homovanillic acid in rat brain
Authors: Emanuelsson Britt-Marie , Paalzow Lennart , Sunzel Maria 
Published: April 2011

Abstract
The accumulation of 5-hydroxyindoleacetic acid (5-HIAA) and homovanillic acid (HVA) in rat brain has been examined after probenecid infusion over 8 h. At plasma probenecid concentrations of 200-400 μg mL−1 a steady state level in the accumulation of 5-HIAA and HVA was achieved, the increase above the endogenous levels being 135% and 65%, respectively. When the plasma concentration of probenecid rose above 400 μg mL−1 there was further accumulation of both 5-HIAA and HVA probably induced by increased neuronal activity or toxicity due to probenecid. The explanation for the plateau of 5-HIAA and HVA obtained over the plasma probenecid concentration interval of 200-400 μg mL−1 could be that the levels were reached when there was complete inhibition of active transport, and when the rate of formation of the metabolites equalled the rate of elimination by alternative routes i.e. bulk flow and diffusion. Therefore when probenecid is used to inhibit the active transport of acid monoamine metabolites across the blood-brain barrier, its plasma concentration should be within the range of 200-400 μg mL−1.
Desensitization of β-adrenoceptors following repeated injections of 2-substituted 4-phenylquinolines
Authors: Alhaider A A 
Published: April 2011

Abstract
The chronic effects of five 2-substituted 4-phenylquinoline derivatives on the sensitivity of the noradrenergic cyclic AMP-generating system in the rat brain cortex have been determined, and compared with those of the typical and atypical antidepressants imipramine and trazodone, respectively. Acute treatment (single i.p. dose of 20 mg kg−1) and sub-chronic treatment (20 mg kg−1 daily for 10 days) induced no significant desensitization of the β-adrenoceptors. However, chronic treatment (20 mg kg−1 daily for 3 weeks) significantly decreased the isoprenaline-induced increase in cyclic AMP, suggesting desensitization. This effect, coupled with previous findings, points to a potential role of these compounds as antidepressants.
Postsynaptic α1-adrenoceptor mechanisms in rat vas deferens and ageing
Authors: Takayanagi I , Maeda O , Koike K 
Published: April 2011

Abstract
Postsynaptic α1-adrenoceptor mechanisms in vasa deferentia isolated from 3, 6, 18 and 40 week-old rats were studied by analysis of the concentration-response curve of noradrenaline and the Scatchard plot of specific binding of [3H]prazosin to microsomal fractions. The maximum tension developed by noradrenaline also increased with age from 3 to 18 weeks. The efficacy of noradrenaline and capacity of the maximum binding sites of [3H)prazosin increased with increasing age, while the dissociation constants of noradrenaline (KA) and prazosin (Kd) were not changed with age. The increase of the maximum tension was proportional to the increase in efficacy. The increase of efficacy for noradrenaline in the vasa deferentia from rats of different ages is due to the increase in the total concentration of postsynaptic α1-adrenoceptors.
Comparative biodistribution of methotrexate and monoclonal antibody-methotrexate complexes in mice
Authors: Pimm M V , Caten Jane E , Clegg Jane A , Jacobs Elisabeth , Baldwin R W 
Published: April 2011

Abstract
The biodistribution of radiolabelled methotrexate and immune complexes of methotrexate and a murine monoclonal anti-methotrexate antibody has been compared in mice. Complexes formed in-vitro with the antibody, but not with control immunoglobulin. The complexes were, characteristically, acid labile. In-vivo, blood levels, organ distribution and whole body catabolism of methotrexate in immune complexes were similar to those of free antibody, and markedly different from those of free drug. These findings suggest the feasibility of prolonging the survival of drugs and altering in-vivo distribution using complexes with monoclonal antibodies.
The Effect of Drug-specific Active Immunization on Digoxin and Benzylpenicillin Disposition in the Bile Duct-cannulated Rat
Authors: Johnston P C , Stevenson I H , Hewick D S 
Published: April 2011

Abstract
Rats were immunized with a digoxin-human serum albumin conjugate i.m. This resulted in a several hundred-fold increase in plasma radioactivity and a 90% reduction in biliary drug elimination when [3H]digoxin (10 μg kg−1, i.v.) was subsequently injected into anaesthetized bile duct-cannulated rats. It was calculated that about 90% of the drug dose remained antibody-bound within the plasma compartment, with essentially no drug distributing into organs such as the heart and liver. Digoxin-specific antibody levels, determined by equilibrium dialysis, were high in the plasma but at least an order of magnitude lower in the bile. Immunization via Peyer’s patches did not increase antibody levels in the bile. Immunization (i.m.) with a benzylpenicillin-human serum albumin conjugate gave specific antibody plasma titres with values less than 10% of those obtained after immunization with a digoxin-protein conjugate. However, although subsequent injection of the hapten (40 μg kg−1, [14C]benzylpenicillin, i.v.) was associated with much lower increases and decreases in plasma and biliary radioactivity, respectively, they were still statistically significant. It appears that endogenously-formed drug-specific antibodies, when present in the blood, will inhibit drug distribution and elimination. It is unlikely that their secretion in the bile plays a significant role in mediating biliary drug hapten elimination.
Some Pharmacological Properties of the Circular Smooth Muscle Layer of the Rat Vas Deferens
Authors: Brito Alba R M Souza , Jurkiewicz Aron 
Published: April 2011

Abstract
Vas deferens preparations were perfused in-vitro through the lumen and externally with a modified Tyrode solution alone or containing drugs. Contractions of the circular (internal) smooth muscle layer were recorded as changes in the pressure of internal perfusion. Contractions of the longitudinal (external) layer were simultaneously recorded through a tension transducer. When the organ was perfused through the lumen, the circular layer contracted after addition of methacholine (pD2 = 413), and noradrenaline (pD2 = 5.00), and relaxed after addition of isoprenaline (pD2 = 5.22). These effects were also observed when the drugs were perfused externally, although with lower values of pD2 for noradrenaline and methacholine. The circular fibres were less sensitive when compared with the longitudinal fibres perfused externally with the above agonists. Methacholine-induced contractions of the circular layer were competitively antagonized by atropine (pA2 = 8.53), indicating the presence of muscarinic receptors. The effects induced by noradrenaline and isoprenaline were antagonized by indoramin (pA2 = 7.78), and timolol (pA2 = 8.68), respectively, indicating the presence of α- and β-adrenoceptors. The effect of noradrenaline was potentiated by cocaine and denervation, indicating the presence of neuronal uptake, and by corticosterone, indicating the presence of extraneuronal uptake in the circular layer.
Selectivity of Neutrophil 5-Lipoxygenase and Cyclo-oxygenase Inhibition by an Anti-inflammatory Flavonoid Glycoside and Related Aglycone Flavonoids
Authors: Moroney M-A , Alcaraz M J , Forder R A , Carey F , Hoult J R S 
Published: April 2011

Abstract
A newly described plant-derived flavonoid, hypolaetin-8-glucoside, which has anti-inflammatory and gastroprotective actions in-vivo, and its corresponding aglycone, hypolaetin, have been compared with 14 other flavonoids for inhibition of eicosanoid generation via the 5-lipoxygenase and cyclo-oxygenase pathways in elicited rat peritoneal leukocytes stimulated with calcium ionophore. Comparable results for the inhibitory profiles of the compounds were obtained using either radioimmunoassay of released eicosanoids or radio-TLC of metabolites formed from labelled arachidonate, but there were differences in absolute potency of the inhibitors. Hypolaetin-8-glucoside was a weak but selective inhibitor of 5-lipoxygenase (IC50 56 μM vs 5-lipoxygenase; &gt; 1000 μM vs cyclo-oxygenase), whereas the aglycone hypolaetin was a more potent and selective 5-lipoxygenase inhibitor (IC50 4.5 μM vs 70 μM). Results with three other glycoside/aglycone pairs confirmed that addition of sugar residues greatly reduces inhibitory potency whilst retaining selectivity against 5-lipoxygenase. Analysis of 12 aglycone flavonoids showed that inhibitory potency and selectivity against 5-lipoxygenase is conferred by the presence of 3′4′-vicinal diol (catechol) in ring B as part of a 3,4-dihydroxycinnamoyl structure as proposed by others and by incorporation of additional hydroxyl substituents. In contrast, “cross-over” of inhibitory selectivity is observed in compounds containing few hydroxyl substituents (with none in ring B) which are selective against cyclo-oxygenase. These results are discussed in relation to possible mechanisms of hypolaetin-8-glucoside’s protective actions and the concept that these inhibitory effects of flavonoids cannot be ascribed to a unitary free radical scavenging action.
Effects of indomethacin and diclofenac on some functions of polymorphonuclear neutrophils
Authors: Berradia N , Marchand-Arvier M , Humbert J C , Vigneron C 
Published: April 2011

Abstract
The effects in-vitro of two non-steroidal anti-inflammatory drugs, diclofenac and indomethacin, have been studied on human polymorphonuclear functions. Adhesivity and chemotaxis were decreased by the two drugs, but in a manner that varied with the attractant used. As shown by the nitro blue tetrazolium slide test, all cells remained active but the production of oxygen metabolites by opsonized zymosan was decreased in the presence of diclofenac.
4-Methylpyrazole alters phenobarbitone hypnotic concentrations in rats
Authors: Ramzan Iqbal 
Published: April 2011

Abstract
The liver alcohol dehydrogenase inhibitor, 4-methylpyrazole, has been tested for its ability to change the hypnotic concentrations of phenobarbitone (phenobarbital) in rats. Following a single dose of 1 mmol kg−1 i.v., administered 60 min before phenobarbitone, 4-methylpyrazole shortened the onset time and reduced the dose of phenobarbitone required to produce loss of righting reflex. Consistent with this, phenobarbitone concentrations in serum (both total and free), brain and in cerebrospinal fluid at onset of hypnosis were about half in 4-methylpyrazole compared with saline-treated rats. These results suggest that acute 4-methylpyrazole pretreatment increases the central nervous system sensitivity to phenobarbitone and presumably other barbiturates; an effect apparently distinct from its inhibition of liver alcohol dehydrogenase.
Characterization of Sodium Carboxymethylcellulose-Gelatin Complex Coacervation by Viscosity, Turbidity and Coacervate Wet Weight and Volume Measurements
Authors: Koh Geok-Lay , Tucker Ian G 
Published: April 2011

Abstract
A sodium carboxymethylcellulose (SCMC) and gelatin coacervation system has been evaluated and characterized and the effects of pH and colloid mixing ratio on the coacervation process investigated. The colloid mixing ratio at which optimum coacervation occurred varied with the coacervation pH. A viscometric investigation of various isohydric SCMC-gelatin mixtures was used to predict optimum conditions for complex coacervation. Optimum coacervation occurred at pH 3.5 at a SCMC-gelatin weight ratio of 3:7 for the SCMC complex coacervation system. Turbidity data confirmed these viscometric results. Coacervate wet weight and volume measurements could not be used to predict optimal coacervation conditions due to changes in the coacervate morphology with mixing ratio. At pH values where coacervation did not occur, the viscosity showed unexpected positive deviations from additive behaviour.
Mechanisms of the Antiallergic Action of N-Methylmequitazine (LG 30435)
Authors: Subissi Alessandro , Del Monte Marco 
Published: April 2011

Abstract
LG 30435 (N-methylmequitazine) was assayed in passive lung (PLA) and cutaneous (PCA) anaphylaxis in guinea-pigs and rats. At doses from 0.3 to 3 μmol kg−1 i.v., it produced a dose-dependent inhibition of guinea-pig PLA and of rat PCA and PLA, while the parent compound was ineffective or poorly effective up to 3 μmol kg−1. An attempt was made to elucidate the mechanism of LG 30435′s action in these anaphylactic models, by means of various antagonists. It was tentatively concluded that different mechanisms are involved in the protective action of LG 30435 in each of the three models: histamine antagonism, possibly accompanied by an inhibition of the effects of peptido-leukotrienes in guinea-pig PLA; histamine antagonism in rat PCA and 5-hydroxytryptamine antagonism in rat PLA, possibly accompanied by a mast-cell stabilizing action in both cases. LG 30435 is devoid of smooth muscle relaxant effects on the airways and its demonstrated anticholinergic and anti-PAF effects do not appear to be involved in its antiallergic action.
The effects of interacting variables on the tensile strength, disintegration and dissolution of paracetamol tablets
Authors: Zubair S , Esezobo S , Pilpel N 
Published: April 2011

Abstract
A factorially designed scheme has been used to analyse the separate and combined effects of packing fraction (P), nature of binder (N) and concentration of binder (C) on the tensile strength, disintegration and dissolution (t50%) times of paracetamol tablets. In general, P has the greatest effect on tensile strength, disintegration and dissolution times followed by C then N. For the variables in combination, the ranking of the effects on tensile strength, for the PVP/gelatin formulations, are P × N &gt; N × C &gt; P × C and for the PVP/tapioca formulations are P × C = N × C &gt; P × N. For disintegration and for dissolution, the ranking for the PVP/gelatin formulations are P × C &gt; P × N = N × C and P × N &gt; P × C &gt; N × C, respectively, and for the PVP/tapioca formulations are P × N &gt; N × C = P × C. The results also show that tapioca acts as a binding agent when included in paracetamol tablet formulations, but it is a weaker binder than either PVP or gelatin. It is thus required in a higher concentration to produce tablets of comparable physical properties with those formulated with PVP or gelatin.
Oral absorption of metronidazole in rabbits irradiated with cobalt-60 gamma radiation
Authors: Bhatt Padmanabh P , Nimbkar Anil Y 
Published: April 2011

Abstract
The absorption of oral metronidazole in control rabbits and in rabbits irradiated with cobalt-60 gamma radiation was studied. It was observed that the bioavailability of metronidazole was significantly reduced in irradiated animals the reduction being dependent on the dose of radiation. The maximum decrease in absorption was seen 48 h post-irradiation.
Zacopride, a potent 5-HT3 antagonist
Authors: Smith W W , Sancilio L F , Owera-Atepo J B , Naylor R J , Lambert L 
Published: April 2011

Abstract
The substituted benzamide derivative zacopride was found to antagonize competitively the effects of 5-hydroxytryptamine (5-HT) on the guinea-pig ileum, the rabbit vagus nerve and the von Bezold Jarisch reflex in the rat. The potency of zacopride was comparable with that of ICS 205–930 and it is concluded that zacopride possesses 5-HT3 receptor antagonizing properties.
Prolonged apparent half-life of Δ1-tetrahydrocannabinol in plasma of chronic marijuana users
Authors: Johansson Eva , Agurell Stig , Hollister Leo E , Halldin Magnus M 
Published: April 2011

Abstract
The aim of this study was to characterize the elimination half-life of Δ1-tetrahydrocannabinol in blood plasma in chronic marijuana users. The subjects smoked four cigarettes during a two day period, each cigarette containing 15 mg deuterium-labelled Δ1-tetrahydrocannabinol. The plasma concentrations of deuterium-labelled tetrahydrocannabinol were measured for 13 days using gas chromatography-mass spectrometry equipped with selected ion monitoring. The elimination half-life for Δ1-tetrahydrocannabinol in blood plasma was calculated to be 4.1 ± 1.1 days (range 2.9–5.0 days) from the two week plasma level curves. Albeit the present results are based upon a small sample, an elimination half-life of Δ1-tetrahydrocannabinol in blood plasma of about 4 days is more in line with apparent half-life excretion of Δ1-tetrahydrocannabinol metabolites in the urine of chronic marijuana smokers.
Buffer and pH Effects on Propranolol Binding by Human Albumin and α1-Acid Glycoprotein
Authors: Ravis W R , Parsons D L , Wang S J 
Published: April 2011

Abstract
Propranolol binding to isolated human α-1-acid glycoprotein (AGP) and human albumin (HSA) was studied by equilibrium dialysis at 37°C. With AGP (0.067%) and HSA (4%), total propranolol concentration was varied from 0.7 to 93 000 ng mL−1. Over this concentration range the percentage drug bound to HSA declined from 49 to 39% while that to AGP declined from 68 to 4%. Two classes of sites were identified on AGP with n1k1 = 8.50 × 104 M−1 and n2k2 = 3.12 × 104 M−1. With a pH 7.4 phosphate buffer, propranolol binding to AGP was greatest when the protein was initially dissolved in pH 7.4 water compared with pH 7.2 water or the phosphate buffer. Thus, the method of AGP solution preparation affected propranolol binding by this protein. For both AGP and HSA, greater drug binding was noted with phosphate buffers in comparison with a physiological buffer. With phosphate buffers, decreasing pH from 7.4 to 7.0 decreased propranolol binding by AGP, while decreasing pH from 7.7 to 7.4 had little effect. With HSA, the percent propranolol bound consistently decreased on lowering pH from 7.7 to 7.0.
The Effects of Salicylate Concentration on the Uptake of Salicylate and Cefmetazole into Rat Isolated Small Intestinal Epithelial Cells
Authors: Suzuka Takumi , Yata Noboru , Sakai Kiyoshi , Nishihata Toshiaki 
Published: April 2011

Abstract
The uptake of salicylate into rat isolated small intestinal epithelial cells reached an equilibrium within 15 min, but that of cefmetazole alone did not. The presence of salicylate at concentrations greater than 50 mM accelerated the uptake of cefmetazole, which reached equilibrium within 5 min. At equilibrium, the uptake clearance of salicylate (μmol (g protein)−1 M−1 initial salicylate concn) was greater than that of cefmetazole. The uptake clearance of salicylate during the first several minutes was concentration-dependent, and a ‘super-uptake’ clearance of salicylate, greater than equilibrium values, was observed when 100 mM salicylate was present. This indicates that some mechanism, other than a simple diffusion process, may be involved in salicylate uptake into these cells.
Sustained anti-adherence activity of taurolidine (Taurolin) and noxythiolin (Noxyflex S) solutions
Authors: Blenkharn J Ian 
Published: April 2011

Abstract
Taurolidine (2% w/v) and noxythiolin (1% w/v and 2.5% w/v) solutions inhibit the adherence in-vitro of Escherichia coli and Staphylococcus aureus to human epithelial and fibroblast cells. This effect, demonstrable after 30 min exposure of cells to test drugs, persists after removal of the active compound. Significantly reduced adherence of bacteria is apparent for 5 h after taurolidine treatment and for 6 h after treatment with 2.5% noxythiolin. Anti-adherence activity of taurolidine and noxythiolin may contribute to the observed clinical efficacy of these agents.