bluuebunny/crossref_metadata_2025_split huggingface dataset:
Generation of prostaglandin E-like material by the guinea-pig trachea contracted by histamine
Authors: Grodzinska L , Panczenko B , Gryglewski R J 
Published: April 2011

Abstract
Challenges of the superfused (1 ml min−1) trachea with histamine (100–200 μg) result in the release of prostaglandin E-like material (3–25 ng in terms of prostaglandin E2) but no prostaglandin F-like activity has been detected in the superfusate. This release is blocked by indomethacin (1 μg ml−1) and then the contractile action of histamine is enhanced. It is concluded that the release of a prostaglandin E-like material by histamine from tracheal smooth muscles is a self-defensive mechanism protecting against the strong constriction of airways. The maximal relaxation of trachea by isoprenaline (50–500 μg) is not accompanied by the release of a prostaglandin-like material.
Non-ionic surfactants and membrane transport of thioridazine in goldfish
Authors: Florence A T , Gillan J M N 
Published: April 2011

Abstract
Polysorbate 80, which has been widely used in studies of the effects of surfactants on drug absorption, increases the rate of absorption of some drugs at concentrations near its critical micelle concentration (cmc). To determine whether all non-ionic surfactants were capable of inducing this effect, the effects of six commercial non-ionic surfactants on thioridazine absorption in goldfish have been compared with the effect of polysorbate 80. The reciprocal death time (T−1) determined when the fish were immersed in the solution under study was the index of absorption rate used. Not all surfactants tested increased T−1. Cremophor EL (polyoxyethylated castor oil), Atlas G1295 (a polyoxyethylene fatty glyceride), Atlas G1300 (a polyoxyethylene glyceride ester) had no effect below their cmc’s. Those surfactants that did increase T−1 [polysorbate 80 (a polyoxyethylene sorbitan monooleate), Atlas G1790 (a polyoxyethylene lanolin derivative), G2162 (a polyoxyethylene oxypropylene monostearate) and Renex 650 (a polyoxyethylene alkyl aryl ether)] display the concentration-dependent behaviour reported previously–a decrease in absorption rate when the surfactant concentration is increased above its cmc. The factor determining whether or not the surfactant will increase absorption rate appears to be the configuration of the surfactant molecule rather than its hydrophile-lipophile balance or its surface activity.
Quantitative determination of morphine in biological samples by gas-liquid chromatography and electron-capture detection
Authors: Dahlström Bengt , Paalzow Lennart 
Published: April 2011

Abstract
A highly sensitive method for the determination of morphine in plasma and brain samples down to 500 pg ml−1 in plasma and 100 pg in 30 mg of brain tissue is described. This sensitivity is in the range of that described for radioactive and radioimmunological techniques. The samples (50–500 μl) are extracted with toluene–butanol (9:1) at pH 8.9 and then re-extracted into 0.1N sulphuric acid and back extracted to a toluene–butanol phase at pH 8.9. The pentafluoro-propionic anhydride derivatives of morphine and the internal standard nalorphine were quantitatively determined by gas–liquid chromatography with a 3H electron capture detector.
Dextromethorphan inhibits 5-hydroxytryptamine uptake by human blood platelets and decreases 5-hydroxyindoleacetic acid content in rat brain
Authors: Ahtee Liisa 
Published: April 2011

Abstract
The effect of dextromethorphan on the uptake and metabolism of 5-hydroxytryptamine (5-HT) was studied in human blood platelets and in rat brain. In the concentration of 120 nM dextromethorphan inhibited the uptake of 5-HT (1 μM) into platelets by 50%. The corresponding concentrations of imipramine and methadone under similar conditions were 22 and 590 nM, respectively. Dextromethorphan (20 to 40 mg kg−1) decreased the concentration of brain 5-hydroxyindoleacetic acid (5-HIAA) and the probenecid-induced accumulation of 5-HIAA time- and dose-dependently. However, dextromethorphan did not alter the pargyline-induced changes in brain 5-HT metabolism. Dextromethorphan-induced changes in brain 5-HT metabolism could arise from the inhibition of the reuptake of 5-HT into neurons.
Evidence for a central α-sympathomimetic action of Clonidine in the rat
Authors: Finch L , Buckingham R E , Moore R A , Bucher T J 
Published: April 2011

Abstract
The antihypertensive effects of Clonidine (0.15 mg kg−1, i.p.) were studied in conscious DOCA/saline hypertensive rats having chronically implanted arterial cannulae. The response to Clonidine was markedly reduced by simultaneously administered desipramine (3 mg kg−1, i.p.), antagonized dose-dependently by piperoxan (2–10 mg kg−1, i.v.) and prevented by pretreatment with phentolamine (0.2 mg, i.c.v.). Pretreatment with 6-hydroxydopamine (3 × 250 μg, i.c.v.), halo-peridol (1 mg kg−1, i.p.), p-chloro-N-methylamphetamine (3.5 mg kg−1, i.p.) or 5, 6-dihydroxytryptamine (50 μg and 25 μg, i.c.v.) did not significantly modify the antihypertensive response. It is concluded that the antihypertensive response to Clonidine is mediated via stimulation of central α-adrenoceptors and is independent of central dopaminergic receptors and intact central serotoninergic neurons. The necessity for intact central noradrenergic neurons remains uncertain.
Tyrosine hydroxylase activity in rat brain regions after chronic treatment with ±-propranolol
Authors: Peters D A V , Mazurkiewicz-Kwilecki I M 
Published: April 2011

Abstract
Rats were injected twice daily with ±-propranolol (6 mg kg−1 day−1) for 14 days and killed 16 h after the final injection. Tyrosine hydroxylase activity was measured in both soluble and particle-bound forms in various brain regions. The activity of the soluble enzyme was not significantly altered by propranolol treatment in any of the brain regions studied. The tyrosine hydroxylase activity in the particulate fraction was significantly increased in corpus striatum and unchanged in other brain regions. The propranolol concentrations in the various brain regions in this chronic study were far lower than necessary to produce a significant change in tyrosine hydroxylase activity in acute experiments. It was concluded that chronic propranolol treatment produces a persistent increase in bound tyrosine hydroxylase activity in rat corpus striatum.
Oxotremorine- and atropine-induced changes of dopamine metabolism in the rat striatum
Authors: Javoy France , Agid Yves , Glowinski Jacques 
Published: April 2011

Abstract
The effects of various doses of oxotremorine and of atropine (30 min, i.p.) on the metabolism of dopamine were examined in the striatum of the rat. Changes in striatal dopamine metabolism were estimated by following either the accumulation of [3H] dopamine 15 min after intravenous injection of [3H] tyrosine or the accumulation of dopa (taken as an index of dopamine synthesis) in animals pretreated with a dopa decarboxylase inhibitor Ro4–4602. Oxotremorine, 0·1 mg kg−1, and atropine, 1 mg kg−1, did not affect dopamine metabolism. Oxotremorine, 0·5 and 1·5 mg kg−1, did not modify dopamine concentrations but increased the accumulation of [3H]dopamine. The drug enhanced dopa formation in animals pretreated with Ro4–4602. Atropine, 5 and 20 mg kg−1, increased the accumulation of [3H]dopamine but did not affect dopamine concentrations. The accumulation of dopa was not modified there being no difference from the saline value in animals pretreated with the dopa decarboxylase inhibitor. Thus at high doses oxotremorine stimulated dopamine metabolism and atropine reduced dopamine utilization.
Evidence for a clorgyline-resistant monoamine metabolizing activity in the rat heart
Authors: Lyles G A , Callingham B A 
Published: April 2011

Abstract
When benzylamine was used as substrate, a component of the total monoamine oxidase (MAO) activity in the rat heart was found to be resistant to inhibition by clorgyline. The proportion of the total activity represented by this component, decreased as the rat grew. It was also inhibited by both semicarbazide and isoniazid but not by potassium cyanide. Inhibitor studies with MAO in subcellular fractions showed that this component was more concentrated in the microsomal and soluble fractions. However, it could not be concluded that the activity was entirely a soluble enzyme. Determination of quasi-Michaelis constants (“Km”) for total benzylamine oxidizing activity revealed a high (“Km” of approximately 10−5M) and low (“Km” of approximately 5 times 10−4M) affinity component. The high affinity component was inhibited by semicarbazide and the low affinity component by clorgyline. In the presence of 10−3M clorgyline, the high affinity component showed substrate inhibition at higher substrate concentrations. The possibility is discussed that the clorgyline-resistant activity is due to an amine-oxidizing activity distinct from mitochondrial MAO.
Effect of surfactant monomers on chloramphenicol association to an albuminlecithin complex: a model for modified drug absorption
Authors: Alhaique F , Giacchetti D , Marchetti M , Riccieri F M 
Published: April 2011

Abstract
The binding of chloramphenicol to an albumin-lecithin complex in the presence or absence of premicellar concentrations of both ionic and non-ionic surfactants has been examined. Long chain, strong ionic detergents, such as sodium dodecyl sulphate or cetyltrimethylammonium bromide, severely perturb protein structure and eventually allow full separation of the complex into lecithin and albumin-detergent complexes. The dissociation process is reversible upon the removal of the detergent by exhaustive dialysis. After the splitting of the complex, the amount of antibiotic associated with the lipid-protein mixture increases. Structural alteration of the albumin-lecithin complex and the increase in the binding of chloramphenicol have an effect on the transfer rate of this antibiotic across an artificial barrier consisting of an aqueous dispersion of the same complex, as observed in a model system. It is suggested that a reversible alteration in membrane structure, and consequently in membrane permeability, might be easily effected, at the molecular level, through a reversible dissociation of structural lipoproteins into their components, operated by premicellar concentrations of ionic surfactants. This represents a tentative picture of the possible events taking place within the membrane and modifying the absorption rate of a drug, when it is associated with surfactants in a pharmaceutical preparation.
The effect of blending on the rheological properties of gelatin solutions and gels
Authors: Robinson John A J , Kellaway Ian W , Marriott Christopher 
Published: April 2011

Abstract
The effect of blending on rheological properties for an acid and alkaline processed gelatin has been investigated. Blending of weak gels (1·0–3·5% w/v at 25°), resulted in a decrease in gel rigidity whereas in the stronger gels (5–50% w/v at 25°) and solutions (18% and 30% w/v at 35°), an increase occurred. The decrease in structure in the weak gels is considered to be due to coulombic effects, minimum strength occurring for a mixture which possessed zero charge in solution. A tentative explanation for effects in rigid gels and concentrated solutions is offered.
Metabolism of Δ1-tetrahydrocannabinol by the isolated perfused dog lung. Comparison with in vitro liver metabolism
Authors: Widman Marianne , Nordqvist Marianne , Dollery Colin T , Briant Robin H 
Published: April 2011

Abstract
The metabolism of (—)-Δ1-tetrahydrocannabinol (Δ1-THC) has been studied in the isolated perfused dog lung. After intravascular administration of [3H]-Δ1-THC there was an overall biotransformation of 12%. Two major metabolites were isolated and identified as 3“-hydroxy-Δ1-THC and 4”-hydroxy-Δ1-THC. 7-Hydroxy-Δ1-THC was also present together with small amounts of 6α-hydroxy-Δ1-THC and 6β-hydroxy-Δ1-THC. An in vitro experiment using a dog liver microsomal preparation was also carried out and showed that the major metabolites were 6β-hydroxy-Δ1-THC and 6α-hydroxy-Δ1-THC. 7-Hydroxy-Δ1-THC and 1,2-epoxy-hexahydrocannabinol were also isolated together with small amounts of 3“-hydroxy-Δ1-THC and 4”-hydroxy-Δ1-THC. The side-chain hydroxylated compounds are hitherto undescribed metabolites of Δ1-THC.
Determination of low concentrations of the quaternary ammonium compound thiazinamium methylsulphate in plasma and urine
Authors: Jonkman Jan H G , Wijsbeek Jaap , Boer Suse Hollenbeek Brouwer-de , de Zeeuw Rokus A , van Bork L E , Orie N G M 
Published: April 2011

Abstract
A sensitive and selective method for the quantitative determination of the quaternary ammonium antiacetylcholine-compound thiazinamium methylsulphate (Multergan) in plasma and urine is described. The procedure is based on ion pair extraction of the compound with iodide as the counter ion. This is followed by gas chromatography using an alkali flame ionization detector. The detection limit is 2 ng ml−1 with a recovery of 88·0 ± 6·2% from plasma, 91·4 ± 4·6% from urine. The described method can also be applied to other quaternary ammonium compounds.
Cerebral monoamine metabolism in guinea-pigs with ascorbic acid deficiency
Authors: Saner A , Weiser H , Hornig D , da Prada M , Pletscher A 
Published: April 2011

Abstract
Guinea-pigs kept on a diet deficient in vitamin C showed, after 3 weeks, a marked decrease of ascorbic acid in brain and blood leucocytes as well as of the activity of alkaline phosphatase in blood plasma. Pair-fed animals did not exhibit these changes. The α-methyl-p-tyrosine (αMpT)-induced diminution of noradrenaline in the hypothalamus and the rest of the brain was attenuated in pair-fed animals, but restored in guinea-pigs deficient in ascorbic acid. The cerebral noradrenaline content (without administration of αMpT) showed a decrease in both pair-fed and ascorbic acid deficient animals. The noradrenaline of the heart exhibited a similar tendency. The αMpT-induced dopamine decrease in the striatum of ascorbic acid deficient animals was attenuated and the dopamine content (without αMpT administration) decreased. Pair-fed animals showed a similar tendency. The striatal concentration of homo-vanillic acid (HVA) was diminished in both pair-fed and ascorbic acid deficient guinea-pigs. The cerebral content of 5-hydroxy-indoleacetic acid showed a decrease in pair-fed as well as in ascorbic acid deficient animals. It is concluded that ascorbic acid deficiency enhances the turnover of brain noradrenaline, whereas under-nutrition without ascorbic acid deficiency (pair-feeding) diminishes the turnover of cerebral noradrenaline, 5-hydroxytryptamine and striatal dopamine.
A study of the human metabolism of secbutobarbitone
Authors: Gilbert J N T , Powell J W , Templeton J 
Published: April 2011

Abstract
The urinary excretion of secbutobarbitone (I) and its metabolites has been studied quantitatively using combined gas chromatographymass spectrometry. After a single oral dose was given to healthy male volunteers, unchanged drug (5–9%), 2′-hydroxysecbutobarbitone (II, 1·7–3·2%), 2′-oxosecbutobarbitone (III, less than 1%), and the carboxylic acid (IV, 24–34%) were found. The kinetics of the excretion process were studied.
The identification and analysis of the metabolic products of mephentermine
Authors: Beckett A H , Bélanger P M 
Published: April 2011

Abstract
Phentermine (Ib), N-hydroxymephentermine (Ic) and N-hydroxyphentermine (Id) were identified as metabolic products after in vitro incubation of mephentermine (Ia) with rabbit liver microsomal fractions. Compounds Ia, Ib and Ic were also identified as excretion products in the urine of a human subject given a single dose of mephentermine (Ia) sulphate. Derivatization with acetic anhydride, trifluoroacetic anhydride and the trimethylsilyl donor reagent N,O-bis-(trimethylsilyl)-trifluoroacetamide (BSTFA) or hexamethyldisilazane (HMDS) were used for qualitative identification of the metabolic products Ib–Id by g.l.c.-mass spectrometry and for quantitative determination of Ia–Id after extraction from rabbit hepatic homogenates. The synthesis of N-hydroxymephentermine (Ic) and the properties of the metabolic products are reported.
Factors influencing the excretion and relative physiological availability of pethidine in man
Authors: Chan K , Kendall M J , Wells W D E , Mitchard M 
Published: April 2011

Abstract
Factors influencing the urinary excretion of pethidine, norpethidine and pethidine N-oxide have been examined. The proportion of a dose of pethidine excreted unchanged or as norpethidine depends on the urinary pH and the route of administration. Older people appear to metabolize more of the drug and therefore excrete less unchanged pethidine. The rate of excretion of pethidine in acid urine is directly proportional to the plasma pethidine concentration and under these conditions the relative physiological availability of pethidine has been determined. It has not been possible to explain variations in the amounts of pethidine excreted as the N-oxide.
α-Methyl derivatives of biogenic amines as inhibitors of monoamine oxidase
Authors: Inoue F , Robinson J B , Stansfield Susan A 
Published: April 2011

Abstract
The values of Km app and Vmax for three natural substrates of monoamine oxidase have been determined at various stages in the isolation of the enzyme from rat liver tissue. The results are consistent with the presence in the enzyme preparation of at least two distinct molecular forms of the enzyme.
Using the α-methyl derivatives of the natural substrates as inhibitors of the enzyme, the substrate dependence of Ki further substantiates this view. In addition, the kinetics of the inhibition suggest that the value of Km app may not for all substrates, necessarily be a measure of the affinity of the substrate for the enzyme.
Comparative study of the effects of mianserin, a tetracyclic antidepressant, and of imipramine on uptake and release of neurotransmitters in synaptosomes
Authors: Raiteri Maurizio , Angelini Francesco , Bertollini Alberto 
Published: April 2011

Abstract
The effects of mianserin, a tetracyclic antidepressant, on uptake and release of [3H]noradrena-line (3H-NA), [3H]dopamine (3H-DA), [3H]-5-hydroxytryptamine(3H-5-HT) and [3H]γ-aminobutyric acid (3H-GABA) in synaptosomes from different areas of the rat brain were investigated in a comparative study with the tricyclic antidepressant imipramine. Mianserin and imipramine were inhibitors of 3H-NA uptake in the hypothalamus, but could not increase 3H-NA release from noradrenergic nerve endings. This behaviour was similar to that of (+)-amphetamine. Both mianserin and imipramine had essentially no effect on 3H-DA transport mechanisms in striatal synaptosomes. (+)-Amphetamine, in contrast, strongly affected both 3H-DA uptake and release. Imipramine was stronger than mianserin in inhibiting 3H-5-HT accumulation by striatal synaptosomes. In contrast, mianserin stimulated 3H-5-HT release whereas imipramine was ineffective. Mianserin had virtually no inhibitory activity on 3H-5-HT uptake by rat blood platelets. Imipramine was a modest inhibitor of 3H-GABA accumulation by whole brain synaptosomes; mianserin had no effect. Both drugs did not alter 3H-GABA release. These results indicate that mianserin interferes in a way different from that of tricyclic antidepressants with the neurotransmitter transport mechanisms at the presynaptic level.
The absorption of warfarin from the rat small intestine in situ
Authors: Iulkunen R J K 
Published: April 2011

Abstract
The in situ absorption from the rat small intestine of the weakly acidic drug, warfarin (pKa 5·05), at 200 μg ml−1 in the instilled fluid with initial pH levels of 3, 5, 7 or 8 has been examined. These initial pH's in the buffer changed rapidly towards neutrality. The buffers at pH's 3 and 5 probably caused different amounts of warfarin precipitation, which resulted in different rates of warfarin disappearance from the instilled fluid which paralleled the initial rates of accumulation of warfarin in (or on) the intestinal wall. Where greater drug precipitation had probably occurred the initial rates of absorption into the plasma were slower. At the initial pH of 3 and by solubilization of warfarin with propylene glycol, the rate of absorption was similar to that from a fluid of pH 7. Propylene glycol in 15% solution did not affect the system significantly. The relatively high transfer of warfarin into octanol from buffer solution at pH 7 might indicate that the small fraction of unionized drug (1:100) at pH 7 is enough for remarkable transfer of this highly lipid-soluble drug.
A dual action of 5-hydroxytryptamine on the ovarian suspensory ligament of the rat
Authors: Davis W G 
Published: April 2011

Abstract
5-Hydroxytryptamine has a dual effect on the spontaneously contracting rat ovarian ligament, in vitro, a contraction which is antagonized by the prior administration of methysergide and a relaxation of the ligament observed in the methysergide-treated preparation. The relaxatory effect was not antagonized by propranolol or tetrodotoxin but treatment of the ligament with indomethacin abolished this response. Prostaglandins of the E series produced an inhibition, and PGF2α; a contraction of the ligament. Thin layer chromatographic separation indicates that 5-HT causes the release of a PGE2-like substance which relaxes the ovarian suspensory ligament.
Colorimetric analysis of immunogenic impurities in acetylsalicylic acid
Authors: Bundgaard Hans 
Published: April 2011

Abstract
A rapid and convenient colorimetric method is described for the quantitative determination of the immunogenic impurities in acetylsalicylic acid, acetylsalicylsalicylic acid and acetylsalicylic anhydride. The method involves initial aminolysis of the compounds by ammonia to give salicylamide and subsequent coupling of this with 4-amino-phenazone in the presence of an oxidizing agent. In conjunction with a previously described method for analysis of the anhydride the method allows a specific determination of acetylsalicylsalicylic acid in concentrations down to 0–005%. Applying the methods to 15 different commercial acetylsalicylic acid samples and formulations, acetylsalicylic anhydride and acetylsalicylsalicylic acid were found to be present in amounts ranging from 0001 to 0·024% and from 0·006 to 0·58 % (w/w), respectively.
A method for screening diuretic agents in the mouse: an investigation of sexual differences
Authors: Hill T W K , Randall P J 
Published: April 2011

Abstract
Acetazolamide, aminophylline, frusemide, ethacrynic acid and triamterene were tested for diuretic action at dosages of 3, 10 and 30 mg kg−1 (s.c.) in male and female mice. Each drug significantly raised sodium excretion and all but acetazolamide elevated urine volume and chloride excretion. Potassium excretion was significantly raised by acetazolamide and frusemide. Acetazolamide and triamterene evoked urinary alkalinization whereas frusemide and ethacrynic acid reduced urinary pH. Female mice were markedly more sensitive than males to the diuretic, natriuretic, chloruretic and urinary acidifying actions of ethacrynic acid.
Brain tyrosine hydroxylase activity and systolic blood pressure in rats treated with either deoxycorticosterone and salt or angiotensin
Authors: Rylett P , Dean H G , Lee M R 
Published: April 2011

Abstract
The hypertension induced in adult male rats by doca/salt was found to be accompanied by a significant rise in whole brain tyrosine hydroxylase (TH) activity. A smaller hypertensive effect, produced by angiotensin (750 ng kg−1 daily) was also accompanied by a proportional rise in whole brain TH activity. The specific antagonists spironolactone and saralasin completely blocked both responses in the doca/salt- and angiotensin-treated animals respectively and spironolactone showed a partial inhibition of the effects of angiotensin. In all the animals treated there was a clear correlation between systolic blood pressure and whole brain TH activity. The significance of these changes is discussed in the light of the central mechanism of hypertension.