bluuebunny/crossref_metadata_2025_split huggingface dataset:
Immunological control of drug absorption from the gastrointestinal tract: the mechanism whereby intestinal anaphylaxis interferes with the intestinal absorption of bromthymol blue in the rat
Authors: Yamamoto Akira , Utsumi Eriko , Sakane Toshiyasu , Hamaura Takeshi , Nakamura Junzo , Hashida Mitsuru , Sezaki Hitoshi 
Published: April 2011

Abstract
Rats were immunized intraperitoneally with ovalbumin and the disappearance of bromthymol blue (BTB) from the intestinal lumen, its accumulation in the tissue, and its net absorption were examined by means of an in-situ recirculation technique during local anaphylaxis. The disappearance of BTB from the intestinal lumen and its net absorption were significantly reduced, but there was no significant effect on its accumulation in the tissue. The pH value of the luminal solution and the perfusate volume were not influenced by intraluminal challenge with the antigen in ovalbumin-immunized rats. In addition, no significant effect was observed on intestinal permeability to BTB in the in-vitro everted sac technique. The intestinal blood flow, measured by a hydrogen clearance method, was not reduced significantly by the intraluminal exposure to antigen. There was enhanced Evans Blue leakage and mucus release in the perfusate after intraluminal challenge with ovalbumin in ovalbumin-immunized rats, but not in non-immunized rats. A significant increase of BTB binding with macromolecular substances in the perfusate was observed during the local anaphylaxis. These findings suggest that the decreased absorption of BTB is due to the interaction with the macromolecular substances in the perfusate during local anaphylaxis.
Activities of novel polyhydroxylated cardiotonic steroids purified from nuchal glands of the snake, Rhabdophis tigrinus
Authors: Azuma Hiroshi , Sekizaki Satomi , Akizawa Toshifumi , Yasuhara Tadashi , Nakajima Terumi 
Published: April 2011

Abstract
Seven novel polyhydroxylated steroids were isolated from the nucho-dorsal glands of the snake, Rhabdophis tigrinus. Biological activities of these steroids in inhibiting (Na+ + K+)ATPase and in producing positive inotropic action were examined in comparison with those of ouabain and gamabufotalin. Gamabufotalin was approximately 10 times more potent than ouabain in inhibiting (Na+ + K+)ATPase. Two compounds, compounds III and XIII, of the seven, produced nearly equipotent enzyme inhibitory activity to ouabain. The activity of the remaining five was relatively low among the compounds tested. All compounds exhibited more or less positive inotropic action in the papillary muscle preparations. The ranking order of the potency was: gamabufotalin &gt; ouabain and compound IV &gt; compound III and XIII &gt; compound I, II, XII and XIV.
Transport of phenobarbitone into the intestinal lumen and the biliary tract following i.v. administration to rats
Authors: Arimori Kazuhiko , Nakano Masahiro 
Published: April 2011

Abstract
The exsorption of intravenously administered phenobarbitone into the lumen of the small intestine of rats has been examined by an in-situ single-pass perfusion technique. The levels of the drug in the bile were about twice that in serum. Moreover, it was shown that the drug was appreciably exsorbed into the intestinal lumen. The exsorption rates of the drug into the perfusates were not very different between isotonic phosphate buffers at pH 6.0 and 8.0. The amounts of phenobarbitone exsorbed into the perfusate and excreted into the bile were 6.47 and 0.45% of the dose for isotonic phosphate buffer at pH 6.0, and were 6.09 and 0.54% of the dose for isotonic phosphate buffer at pH 8.0.
The effect of antidepressants on ethylmorphine and imipramine N-demethylation in rat liver microsomes
Authors: Daniel Wladyslawa , Melzacka Miroslawa 
Published: April 2011

Abstract
The effects of single and multiple doses of desipramine, amitriptyline or citalopram on the rat liver microsomal cytochrome P-450 level and on the rate of ethylmorphine and imipramine demethylation in-vitro have been investigated. Desipramine, amitriptyline or citalopram when given to rats as a single dose, did not affect the level of cytochrome P-450 in the liver microsomes, however, there was a tendency towards acceleration of imipramine, and particularly ethylmorphine, demethylation. Prolonged administration of desipramine and citalopram, but not amitriptyline, elevated the microsomal level of cytochrome P-450 and accelerated the rate of ethylmorphine demethylation. All the drugs investigated, when given chronically, inhibited the rate of imipramine demethylation. Since demethylation of ethylmorphine and imipramine in a CO atmosphere was inhibited by ca 90% for the former and only by 58% for the latter, it can be assumed that prolonged administration of the drugs investigated has two different effects on the oxygenase systems in rat liver microsomes: on the one hand they stimulate the cytochrome P450 oxygenase system involved in ethylmorphine demethylation and, on the other, they inhibit the other microsomal oxygenase system involved in demethylation of imipramine.
Cooling-induced augmentation of the contractile response of the golden hamster tracheal muscle to substance P in-vitro
Authors: Ishii Takeo , Shimo Yasuo 
Published: April 2011

Abstract
The effect of temperature on the substance P-induced contraction of the isolated tracheal strip-chain preparation from the golden hamster has been examined. A decrease of bath temperature from 37 to 20°C augmented the contractile response of the trachea caused by substance P. Similar cooling-induced augmentation was observed in the contractile responses to caffeine and carbachol, but not to fratassium chloride. The increased responsiveness with lowered temperature of the trachea to substance P may be due to the acceleration of Ca2+ release from an intracellular storage site.
[125I] Spiperone is not a useful ligand for studying the CHAPS solubilized dopamine D-2 receptor from rat striatum
Authors: Kilpatrick G J , Jenner P , Marsden C D 
Published: April 2011

Abstract
The interaction of [125I]spiperone and [3H]spiperone with CHAPS solubilized preparations of rat striatal tissue has been compared. Only about 15% of [125I]spiperone binding was displaced by sulpiride compared with about 67% of [3H]spiperone binding. In the presence of (+)-butaclamol the displacement of [125I]spiperone was twice that found with sulpiride suggesting an interaction with sites other than D-2 receptors. The specific binding of [125I]spiperone was not saturable within the maximum concentration range that could be employed and its affinity for soluble preparations was far lower than that of [3H]spiperone. Despite its very high specific activity [125I]spiperone offers no advantage over [3H]spiperone in the identification of dopamine receptors in soluble tissue preparations.
Mechanical properties of some pigmented and unpigmented aqueous-based film coating formulations applied to aspirin tablets
Authors: Okhamafe Augustine O , York P 
Published: April 2011

Abstract
The Brinell hardness and Young's modulus of pigmented and unpigmented films of hydroxypropyl methylcellulose alone, and in combination with either polyethylene glycol 400 (plasticizer) or polyvinyl alcohol, which were applied to aspirin tablets, have been measured. Generally hardness and modulus data showed similar trends. The hardness and modulus of hydroxypropyl methylcellulose fell in the presence of polyethylene glycol 400 as a result of its plasticizing action. On the other hand, the hardness and modulus of the film former rose slightly when polyvinyl alcohol was initially incorporated, probably due to the crystalline phase of the additive, and then decreased when the level of the additive was further raised. Hardness and modulus were higher in films pigmented with talc than in those containing titanium dioxide because of the plate-like shape of talc and its greater interaction with the polymer systems. Some correlation was found between the Young's moduli of the applied films and those of the corresponding free films, with the moduli of the latter two 2–5 times greater. Ageing at 37°C and 75% r.h. was found to cause a decrease in the mechanical properties of the unplasticized film coating systems probably as a result of decreased molecular order and enhanced polymer chain mobility.
Functional evidence for the existence of a capsaicin-sensitive innervation in the rat urinary bladder
Authors: Santicioli Paolo , Maggi Carlo Alberto , Meli Alberto 
Published: April 2011

Abstract
Capsaicin (0.03–3 μm) induces contractions of the rat isolated bladder which are unaffected by either atropine (3 μm) or tetrodotoxin (0.5 μm). In the presence of capsaicin (0.1 μm) an enhancement of field stimulation-induced contractions was observed. Capsaicindesensitization did not modify the height of these. The neurogenic nature of the capsaicin-induced contractions was proved by the observation that ‘chronic’ (48 h) denervation prevented, while ‘acute’ (2 h) denervation did not modify the effect of capsaicin. Denervated bladders maintained their responsiveness to acetylcholine but not to field stimulation. Isolated bladders from rat pups (1–2 days old) did not respond to capsaicin while strong contractile responses to acetylcholine or field stimulation were obtained in these preparations. In bladders from two week old animals, capsaicin produced similar contractions to those observed in preparations from adult animals. The bladders from rats receiving a high dose of capsaicin (50 mg kg−1 s.c.) at birth were heavier than those of their age-matched, vehicle-treated controls. Isolated bladders from 2 month old animals pretreated with capsaicin at birth were unresponsive to capsaicin while responsiveness to acetylcholine, substance P or field stimulation was unaffected compared with that of vehicle-treated controls. These experiments provide evidence that a capsaicin-sensitive innervation exists in the rat urinary bladder which undergoes a postnatal development at end organ level.
Effect of the anticonvulsant denzimol on the disposition of diazepam in the rat
Authors: Caccia S , Conforti L , Conti I 
Published: April 2011

Abstract
The influence of denzimol. a new imidazole derivative with anticonvulsant properties, on the disposition of diazepam (1 mg kg−1) was investigated in the rat. Denzimol pretreatment significantly increased plasma and brain concentrations of the benzodiazepine, consistent with reduced total clearance. The results suggest that the increase of diazepam brain concentrations by denzimol may produce enhancement of diazepam activity in the rat.
Enhancement of the dissolution rate of a poorly water-soluble drug (tolbutamide) by a spray-drying solvent deposition method and disintegrants
Authors: Takeuchi Hirofumi , Handa Tetsurou , Kawashima Yoshiaki 
Published: April 2011

Abstract
The dissolution rate of a poorly water-soluble drug, tolbutamide, was improved by spray-drying a diluted ammonia solution of the drug containing either a low-substituted hydroxypropylcellulose (L-HPC) or partly pregelatinized corn starch (PCS) as disintegrants. With L-HPC the resultant particles were agglomerates of disintegrant with drug on the surface and within the particles, while particles formed with PCS were composed of a single core of PCS on which the drug was deposited. The deposited drug crystals were very fine because the rapid solvent evaporation restricted crystal growth. The spray-dried particles prepared with PCS had a structure similar to that of an ordered mix. The drug dissolution rate from the spray-dried particles was more rapid than that of the powdered drug alone or with disintegrant and could be attributed to separation of the layer of fine drug crystals from the surface of the particles by swelling of disintegrant. PCS enhanced the drug dissolution rate compared with systems using corn starch. The dissolution rate also depended on the drug content of the particles which was higher than that in ordered mixtures or conventional solvent deposition systems. This system described also had the advantage of avoiding the use of organic solvents.
l-Dopa esters as potential prodrugs: effect on brain concentration of dopamine metabolites in reserpinized mice
Authors: Cooper D R , Marrel C , Van De Waterbeemd H , Testa B , Jenner P , Marsden C D 
Published: April 2011

Abstract
The intraperitoneal administration of l-Dopa and a series of ester prodrugs of l-Dopa to reserpinized mice produced elevations of striatal and tuberculum olfactorium homovanillic acid (HVA) and 3,4-dihydroxyphenylacetic acid (DOPAC) levels. Differences in the pattern of change produced by individual drugs, compared with l-Dopa, were observed. Only the phenoxyethyl ester caused elevations of both striatal and tuberculum olfactorium HVA and DOPAC, greater than those measured following l-Dopa administration. Overall the m-trifluoromethylbenzyl, phenylethyl, p-chlorophenylethyl and p-methoxyphenylethyl ester prodrugs produced greater elevations of striatal and tuberculum olfactorium HVA, but not DOPAC, compared with l-Dopa. The administration of the 2-tetrahydropyranylmethyl derivative only enhanced striatal HVA and striatal and tuberculum olfactorium DOPAC concentrations. Changes of HVA and DOPAC tissue concentrations following administration of the 2-hydroxypropyl, n-propyl, methyl, ethyl and 2-(1-methoxy)propyl ester prodrugs were comparable with those produced by the administration of l-Dopa itself. The alterations in striatal and tuberculum olfactorium HVA and DOPAC levels observed did not correlate with the ability of these compounds to elicit locomotor activity in reserpinized mice.
Isolated tissue and binding studies of YM-17690, a novel and non-analogous leukotriene agonist
Authors: Tomioka Kenichi , Yamada Toshimitsu , Teramura Kyoko , Terai Michio , Hidaka Kazuyuki , Mase Toshiyasu , Hara Hiromu , Murase Kiyoshi 
Published: April 2011

Abstract
YM-17690, 3-[4-carboxymethoxy-3-[p-(4-phenylbutoxy)benzamido]phenyl]prpionic acid, produced a dose-dependent contraction of guinea-pig ileum and its EC50 value was 1·6 times 10−8M. The response was not affected by pretreatment with atropine, mepyramine, indomethacin, dazoxiben and AA-861 (a 5-lipoxygenase inhibitor), but was inhibited by FPL-55712 (an LTD4 and LTE4 antagonist). YM-17690 induced dose-dependent contractions of guinea-pig lung parenchyma and trachea with EC50 values of 3·9 times 10−9 and 2·2 times 10−8M, respectively. Pretreatment of these tissues with FPL-55712 resulted in a parallel shift of the YM-17690 dose-response curves to the right. The pA2 values for FPL-55712 in lung parenchyma and trachea were 7·41 and 8·21, respectively, and the slopes of the regression lines of Schild plots were 1·00 and 1·02, respectively. YM-17690 produced a dose-dependent inhibition of [3H]LTD4 binding to guinea-pig lung membranes and its pKi value was 9·28. However, the compound showed only 25% inhibition of [3H]TLC4 binding to guinea-pig hippocampus membranes, even at 10−5M. These results suggest that YM-17690 is a selective leukotriene (LTD4 and LTE4) agonist and that it will therefore be a valuable tool in the study of actions of leukotrienes and for the characterization of their receptors.
Interactions of aminoglutethimide with analgesics using antinociceptive tests in mice
Authors: Rao Sheila , Nicholls Paul J 
Published: April 2011

Abstract
The action of aminoglutethimide in alleviating bone pain in women with metastatic breast cancer may be due to either an inherent analgesic effect or an interaction with other analgesic drugs. These possibilities have been investigated in mice by conventional antinociceptive tests. In the abdominal constriction test, aminoglutethimide alone had a dose-related antinociceptive activity. A low dose (which had no pharmacological activity) when co-administered with an effective sub-maximal dose of the analgesic, potentiated the effects of the non-steroidal anti-inflammatory drugs (NSAIDs) tested. In the tail immersion test, aminoglutethimide was inactive and did not enhance the antinociceptive activity of the centrally acting analgesics. As cytochrome P450-dependent routes which are inhibited by aminoglutethimide are not involved in the metabolism of the NSAIDs studied, an interaction at the drug metabolism level cannot explain these results. The NSAID-like activity of aminoglutethimide provides some evidence that the drug's mode of action may involve more than the suppression of oestrogen biosynthesis.
An investigation of sex-linked differences to the toxic and to the pharmacological actions of difenacoum: studies in mice and rats
Authors: Winn M J , Clegg J A D , Park B K 
Published: April 2011

Abstract
We have investigated the actions of the coumarin anticoagulant, difenacoum, in male and female rats and mice. In our first experimnt difenacoum (0.5 mg kg−1) killed 50% of male mice within 9 days of its administration, whereas no female mice died during this study. In a second group of experiments, the anticoagulant effect of difenacoum in male and female rats was determined. Under resting conditions, the prothrombin complex activities (PCA) of male and female rats were not significantly different. Over the first 24 h after administration of difenacoum (0.4 mg kg−1 i.p.), there was a monoexponential fall in PCA in both sexes. However, 6, 12 and 24 h after difenacoum, the PCA in male rats was significantly (P &lt;0.05) lower than in female rats. PCA began to recover over the subsequent 48 h in both sexes, during which time there was marked variability in recovery in female rats. The difference between the onset of action of difenacoum in male and female rats did not appear to be due to a greater rate of elimination of the drug in female rats, since the plasma concentrations of difenacoum 24 h after its administration were the same in both sexes. The concentration of vitamin K1 in rat liver was also investigated. Vitamin K1 levels were 35.1 ± 18.6 ng (g liver)−1 (male), and 29.4 ± 5.4 ng (g liver)−1 (females) in control rats, but 24 h after difenacoum, vitamin K1 levels were either very low, or undetectable in all rats. It is, therefore, possible that the difference between the responses to difenacoum in males and females was due to a greater rate of breakdown of vitamin K-dependent clotting factor precursors in male rats and mice, compared with female rats and mice.
Depression of oxidative metabolism of aspirin in mice via an interferon-associated mechanism in relation to Reye's syndrome
Authors: Dolphin C T , Caldwell J , Smith R L 
Published: April 2011

Abstract
Interferon synthesis was induced in inbred strains of mice with either polyriboinosinic-polyribocytidylic acid or Newcastle disease virus. The strains, BALB/cBy and C57BL/6By, respond to Newcastle disease virus by producing ‘low’ and ‘high’ levels of serum interferon, respectively. 24 h after interferon induction mice received [carboxyl-14C]-aspirin orally. The metabolic conjugation of aspirin was little changed after either treatment while the urinary excretion of gentisic acid, a minor product of metabolic oxidation, was significantly depressed after polyriboinosinic-polyribocytidylic acid in both strains and in C57BL/6By mice after Newcastle disease virus. The results suggest that such a metabolic impairment in aspirin metabolism would not significantly affect salicylate clearance and hence are unlikely to be directly related to the aetiology of Reye's syndrome which has been associated with both a prodromal viral infection and aspirin therapy.
Comparison of the effects of Fe2+ and Cu2+ on prostaglandin synthesis in rabbit kidney medulla slices
Authors: Fujita Tadashi , Ohtani Noboru , Aihara Midori , Nishioka Kazuyuki , Fujimoto Yohko 
Published: April 2011

Abstract
The effects of Fe2+ and Cu2+ on the generation of medullary prostaglandins E2 and F2α have been compared. Fe2+ markedly promoted the lipid peroxidation of rabbit kidney medulla slices. The lipid peroxidation induced by Fe2+ inhibited both prostaglandin E2 and prostaglandin F2α formation to a similar extent. While Cu2+ produced only a small increase in lipid peroxidation, it had a powerful inhibitory effect on prostaglandin E2 formation. Simultaneously, prostaglandin F2α production was increased. In the presence of Cu2+ the net increased amount of prostaglandin F2α was much smaller than the net decreased amount of prostaglandin E2 (15–20%). These results suggest that Cu2+ has the potential to modulate prostaglandins E2 and F2α synthesis by affecting endoperoxide E2 isomerase or endoperoxide reductase independent of its peroxidative action.
The relationship of the pharmacokinetics of chloroquine to dose in the rabbit
Authors: Aderounmu A Fadeke , Lindstrom Bjorn , Ekman Lena 
Published: April 2011

Abstract
Four albino rabbits were treated with 4 different doses of chloroquine phosphate (30–50 mg kg−1) given intragastrically and 10 others were given the hydrochloride (2.5–12.5 mg kg−1 i.v.). The i.v. doses were given as bolus into the median ear vein over 5–8 min. Samples (3–5 mL) of whole blood were subsequently collected at intervals for up to 6 weeks and analysed by HPLC. From the results, log concentration-time curves were drawn and the i.v. data fitted by computer to 3-compartment (8 rabbits) or 2-compartment curves (2 rabbits). The area under the curve (AUC) and half-lives were calculated for the different doses. A plot of AUC versus dose yielded a straight line but the half-lives showed wide inter-individual variation from the same doses.
On the mechanism of transport of salicylate and p-hydroxybenzoic acid across human red cell membranes
Authors: Joy M M , Cutler D J 
Published: April 2011

Abstract
The pH-dependence of efflux of salicylate and p-hydroxybenzoic acid (PHB) from human red cells indicates that the un-ionized species penetrates the membrane. No effect of the anion channel blocker 4,4′-diisothiocyano-2,2′-disulphonic stilbene was observed. The temperature-dependence of efflux suggests that the energy barrier to transport of salicylate and PHB is the transfer of the acids from water into the membrane, rather than transport through the membrane interior. Intracellular binding of both acids was found to be pH-dependent.
Anthelmintic properties of Polygonum glabrum
Authors: Muddathir A K , Balansard G , Timon-David P , Babadjamian A , Yagoub A K , Julien M J 
Published: April 2011

Abstract
A pure anthelmintic substance (PGA) has been isolated from the methanol-aqueous extract of the leaf of Polygonum glabrum Willd., a semi-aquatic Sudanese species of the family Polygonaceae. The antiparasitic in-vitro activity of several fractions isolated from the plant, has been examined comparatively with that of PGA. PGA also showed molluscicidal activity against Biomphalaria glabrata and Limnea truncatula Müll. Structural determination of PGA was attempted following data analysis of UV, IR, 13C NMR, 1H NMR and MS spectra and suggests that PGA is a terpenoid.
Selectivity and specificity for α1-adrenoceptor blocking activity of R(-)- and S(+)-YM-12617 orally administered to pithed, spontaneously hypertensive rats
Authors: Honda Kazuo , Momose Noriko , Nakagawa Chieko 
Published: April 2011

Abstract
The selectivity and specificity for α1-adrenoceptor blocking activity of the optical isomers of YM-12617 have been examined in pithed, spontaneously hypertensive rats. R(-)-YM-12617 and prazosin (1 mg kg−1 p.o.) produced 360- and 88-fold rightward shifts, respectively, of the dose-response curve of control to phenylephrine, whereas S(+)-YM-12617 (1 mg kg−1 p.o.) failed to cause a shift. Based on dose ratio, R(-)-YM-12617 was 320 times more potent as an α1-adrenoceptor antagonist than S(+)-YM-12617. This potency ratio corresponded to that formed in an in-vitro study. Both R(-)- and S(+)-YM-12617 hardly affected the UK-14304, angiotensin II, vasopressin and isoprenaline dose-response curves. These results suggest that R(-)-YM-12617 exerted selective α1-adrenoceptor blocking activity and its activity was specific for α1-adrenoceptors.