bluuebunny/crossref_metadata_2025_split huggingface dataset:
Protective effect of GABA and sodium valproate on stress-induced gastric lesions in guinea-pigs
Authors: Miñano F J , Serrano J S , Durán J A , Sancibrián M 
Published: April 2011

Abstract
γ-Aminobutyric acid (GABA) and sodium valproate (VPA) inhibit the formation of stress-induced gastric ulcers in guinea-pigs. The present study was conducted to evaluate the effect of these drugs on the development of cold- and restraint-induced gastric ulcers in guinea-pigs. In control saline-pretreated animals, a 3 h exposure to cold and restriction resulted in the production of gastric ulcers in 9 out of 10 animals. GABA (200 mg kg−1 oral, i.p.) completely prevented the development of gastric ulcers. VPA (100 and 200 mg kg−1 i.p.) exerted no significant effects on the development of gastric ulcers. GABA (100 mg kg−1 oral and i.p.) and VPA (oral) also exhibited partially protective activity. It is suggested that GABA may participate in a physiological modulation of the gastric mucosal barrier, by increasing its resistance to stress-induced lesions.
The plasto-elasticity and compressibility of coated powders and the tensile strengths of their tablets
Authors: Ejiofor Obi , Esezobo S , Pilpel N 
Published: April 2011

Abstract
A study has been made of the effects produced on the tensile strength, brittle fracture index (BFI), ‘plasto-elasticity’ ratio, ER/PC, and yield pressure (1/KH derived from Heckel plots) of sodium salicylate and calcium carbonate as a result of coating their particles with increasing amounts of silicones and polysorbates before subjecting them to compression to form tablets. The coatings act as lubricants reducing bond formation due to plastic deformation of particles. They caused a reduction in the tensile strengths and yield pressures of the tablets but increased their BFI values and their ER/PC ratios. Tablets of calcium carbonate tended to cap or laminate when their BFI value was &gt;0.7 and their ER/PC ratio was &gt;7. Sodium salicylate whose BFI values were all &lt;0.7 produced satisfactory tablets when their ER/PC ratio was &lt;10 but tended to cap or laminate when it was &gt;10.
The prophylactic efficacy of various simulators against intoxication with the organophosphate soman: structure-activity studies
Authors: Van Helden H P M , Benschop H P , Wolthuis O L 
Published: April 2011

Abstract
The effects were investigated of structural variations of the soman simulator pinacolyl dimethylphosphinate on its efficacy to prevent secondary failure of oxime-induced recovery of neuromuscular transmission and death after soman intoxication. The simulators were administered prophylactically to atropinized, HI-6 treated rats, dosed with 6 or 8 × LD50 soman. In these new simulators the pinacolyl moiety was varied, the phosphonyl oxygen atom was replaced by sulphur, or the phosphorous-bound methyl groups were replaced by ethyl or methoxy groups. All these variations appeared to be less active than pinacolyl dimethylphosphinate. Intravenously, the latter compound was very effective at a dose of 12 μmol kg−1; its i.v. LD50 appeared to be higher than 1 mmol kg−1.
In-vitro study of the enkephalinergic hypothesis for non-adrenergic, non-cholinergic innervation in the cat stomach
Authors: Lefebvre R A , Bogaert M G , De Schaepdryver A F 
Published: April 2011

Abstract
It has been suggested that enkephalins are involved in the gastric relaxation induced by stimulation of the non-adrenergic, non-cholinergic vagal fibres in the cat stomach. Experiments were therefore performed on strips of cat stomach. With longitudinal and circular gastric fundus and corpus strips from reserpinized cats, non-adrenergic, non-cholinergic relaxatory responses could be elicited by transmural electrical stimulation in Tyrode solution containing atropine and 5-hydroxytryptamine. Morphine, leu-enkephalin and met-enkephalin did not influence the tone of the strips or the relaxation evoked by stimulation at 8 Hz, and neither did the opioid antagonist, naloxone. These results do not support the enkephalinergic hypothesis for the non-adrenergic, non-cholinergic vagal fibres in the cat stomach.
The effect of glycerol-induced acute renal failure upon cardiac reactivity in the rat: influence of indomethacin treatment and renal pedicle ligation
Authors: Yates M S , Askey Elizabeth A , Wilmot Susan E , Bowmer C J 
Published: April 2011

Abstract
Cardiac chronotropic responses to isoprenaline, carbachol and electrical stimulation of the cervical sympathetic and vagal nerves were recorded in rats with glycerol-induced acute renal failure (ARF) and control rats. The experiments involving electrical stimulation of cardiac nerves were performed in rats which either had been pretreated with indomethacin (1 mg kg−1 twice daily for 2 days) or had undergone acute bilateral renal pedicle ligation. The findings from this investigation indicate that the reduced chronotropic responses to vagal stimulation in rats with glycerol-induced ARF are due to a reduction in acetylcholine release mediated by prostaglandins possibly originating from the damaged kidneys. The diminished response to cervical sympathetic stimulation results from a decreased postsynaptic response to β-adrenoceptor stimulation.
Pharmacokinetics of intravenously administered glutathione in the rat
Authors: Ammon H P T , Melien M C M , Verspohl E J 
Published: April 2011

Abstract
By means of an open two compartment model with a distribution and elimination phase, the pharmacokinetic properties of intravenously administered GSH (reduced glutathione) have been investigated in the rat. After a bolus injection of four various GSH doses (50 to 300 μmol kg−1), arterial plasma concentrations of GSH, GSSG (= oxidized glutathione), total thiols and soluble thiols minus GSH were elevated and then rapidly decreased non-exponentially. With increasing dose, the rate constant for drug elimination and plasma clearance increased from 0.84 to 2.44 ml min−1 and the half-life of the elimination phase decreased from 52.4 to 11.4 min. Both the apparent volume of distribution and the degree of penetration of GSH into the tissues were diminished with increasing dose (from 3.78 to 1.33 litres kg−1 and from 6.00 to 0.51 as k12/k21, respectively). The data indicate that GSH is rapidly eliminated. This is mainly due to rapid oxidation in plasma rather than by increased tissue extraction or volume distribution. Thus plasma GSH levels appear to be quickly regulated by which the body may maintain concentrations within narrow physiological limits.
Ketanserin potentiates the prejunctional inhibitory effect of 5-hydroxytryptamine on rat vas deferens
Authors: Moritoki Hideki , Fukuda Hiroshi , Kanaya Jun , Ishida Yukio 
Published: April 2011

Abstract
5-Hydroxytryptamine (5-HT) slightly inhibited the twitch contractions of rat vas deferens caused by single pulse field stimulation at 0.1 Hz. The inhibitory effect of 5-HT was much less in the epididymal portion than in the prostatic portion of the vas deferens. Ketanserin potentiated the prejunctional inhibitory effect of 5-HT and attenuated its stimulatory effect. This potentiation was observable only in the epididymal portion, of the vas deferens. Cyproheptadine and mianserin, but not methysergide, had essentially similar potentiating effects to those of ketanserin. These results suggest that the 5-HT receptor that mediates prejunctional inhibition is not of the 5-HT2 type, and that ketanserin acts by suppressing the 5-HT-induced stimulatory effect, which is possibly mediated by a postjunctional 5-HT2 receptor, thus unmasking the inhibitory effect of 5-HT.
Inhibitory effects of sympathomimetic drugs on cholinergically mediated contractions of guinea-pig isolated tracheal muscle
Authors: Kamikawa Yuichiro , Shimo Yasuo 
Published: April 2011

Abstract
The experiments examine the actions of sympathomimetic drugs on the responses evoked by electrical field stimulation or by acetylcholine in guinea-pig tracheal strip chains. Electrical field stimulation evoked contractions which were cholinergically mediated, in the presence of guanethidine (10 μm) and indomethacin (2 μm). All the sympathomimetic drugs tested caused a concentration-dependent reduction in the height of these contractions. Inhibitory effects of isoprenaline and terbutaline were largely prevented by propranolol (2 μm) alone, whereas those of clonidine, oxymetazoline, lidamidine and WHR1370 were prevented by yohimbine alone (2 μm). Treatments with both propranolol and yohimbine were required to prevent the inhibitory effects of noradrenaline, adrenaline and dopamine. Contractions evoked by exogenous acetylcholine (0.1–3 μm) were also inhibited by all catecholamines and terbutaline, but not by clonidine, oxymetazoline, lidamidine and WHR1370. The inhibitory effects were antagonized by propranolol (2 μm) alone. The results suggest that in guinea-pig isolated tracheal muscle, sympathomimetic drugs can inhibit cholinergic neurotransmission not only by postjunctional β2-adrenoceptors but also by prejunctional α2-adrenoceptors.
Analgesic and anti-inflammatory activities in rats of α-(3,5-di-t-butyl-4-hydroxybenzylidene)-γ-butyrolactone (KME-4), and its intestinal damage
Authors: Hidaka Takayoshi , Hosoe Kazunori , Yamashita Toshiaki , Watanabe Kiyoshi , Hiramatsu Yasuzo , Fujimura Hajime 
Published: April 2011

Abstract
α-(3,5-Di-t-butyl-4-hydroxybenzylidene)-γ-butyrolactone (KME-4), an anti-inflammatory drug, possesses analgesic activity in rat models. In the acetic acid-induced writhing test, the oral ED50 values for KME-4, indomethacin, naproxen and ibuprofen were 5.2, 3.8,7.0 and 18.6 mg kg−1, respectively, and the relative order of potency of these drugs correlated with their inhibitory effect on acetic acid-induced vascular permeability in rats. KME-4 also had analgesic activity in the tests of Randall-Selitto and adjuvant arthritic flexion, but the dose required was greater than that needed in the writhing test. KME-4 (10 mg kg−1 day−1 orally) has a preventive effect against adjuvant-induced arthritis in rats, and its efficacy was more potent than indomethacin (2 mg kg−1 day−1) as judged from various parameters determined. When administered orally to rats once daily for 12 days, KME-4 caused perforating ulceration of the small intestine but this action was less potent than the effect of indomethacin, naproxen and ibuprofen.
The effect of digoxin-specific active immunization on digoxin toxicity and distribution in the guinea-pig
Authors: Andrews M , Hewick D S , Stevenson I H 
Published: April 2011

Abstract
In guinea-pigs intravenously infused with digoxin, prior immunization using a digoxin-human serum albumin conjugate increased by 3- and 2.4-fold, respectively, the digoxin doses causing the first signs of cardiotoxicity and death. At death, serum digoxin concentration was four times higher in immunized than in control animals. In the immunized guinea-pigs 50% of the serum digoxin was protein bound, presumably mainly to digoxin-specific antibodies, since in the controls the bound fraction was only 1–2%. Generally, tissue digoxin concentrations were not increased to the same extent as the lethal dose, and in the heart and lungs the increase was not significant. With cardiac (ventricle) subcellular fractions, there was no difference between control and immunized animals in the digoxin concentration of the ‘microsomal’ pellet. This subfraction contains the plasma membrane and the associated sodium pumps which are considered to be the sites at which the pharmacologically active digoxin binds. It seems likely, therefore, that the greater digoxin resistance in the immunized animals can be explained on the basis of reduced drug access to the site of action within the heart.
The components of Melissa officinalis L. that influence protein biosynthesis in-vitro
Authors: Chlabicz J , Gałsiński W 
Published: April 2011

Abstract
An investigation of an inhibiting activity of a substance(s) in a tanninless extract from Melissa officinalis leaves on protein biosynthesis in-vitro has been made. At least two components which inhibited protein biosynthesis were present in the extract; these were caffeic acid and an unidentified glycoside. Freshly prepared buffered solutions of caffeic acid inhibited protein biosynthesis less than solutions stored for several days at room temperature (20 °C). In this case derivatives of caffeic acid were formed, which may be responsible for the increase in the inhibitory effect of stored caffeic acid solution. An inhibitor, in the homogeneous state, was also isolated from the glycoside fraction of M. officinalis. Studies on the mechanism of the action of this inhibitor revealed its effect is to use the result of a direct interaction with elongation factor EF-2, and the blocking of the binding reaction of EF-2 with ribosomes.
The effect of pH and concentration on α-methyldopa absorption in man
Authors: Merfeld A E , Mlodozeniec A R , Cortese M A , Rhodes J B , Dressman J B , Admidon G L 
Published: April 2011

Abstract
An open crossover study of the absorption of α-methyldopa has been conducted in normal healthy adult male volunteers in whom a triple lumen perfusion tube had been placed. Three volunteers were perfused on separate occasions with 0.1 mM α-methyldopa at pH 4.5, 6.0 and 7.4. Three other volunteers were perfused on separate occasions with 0.1, 1.0 and 10 mM α-methyldopa at pH 6.0. Two additional subjects were perfused with 0.1 mM α-methyldopa at pH 6.0. Absorption was not a linear function of concentration above 1 mM α-methyldopa. There was also a weak trend toward greater absorption near pH 6.0. At higher concentrations of drug in the perfusion solution (10 vs 1 mM), the free fraction of α-methyldopa in plasma samples was increased significantly. Thus, although absorption of α-methyldopa is more efficient at lower concentrations, bioavailability may not be substantially enhanced due to increased sulphation in the gut wall. Comparison of permeabilities with previous results from our laboratories suggests the rat is a good model for predicting the behaviour of α-methyldopa after its oral administration to man.
Effects of antimalarial drugs on interleukin 1-induced cartilage proteoglycan degradation in-vitro
Authors: Rainsford K D 
Published: April 2011

Abstract
Previous studies having shown that chloroquine and hydroxychloroquine could reduce interleukin 1 (IL-1)-induced cartilage degradation in-vitro, the effects of a range of antimalarial drugs on the cartilage proteoglycan degrading actions of porcine leucocyte (pI 4.8) α-interleukin 1 (syn. catabolin) have been examined using the standard bovine nasal cartilage culture system. The anti-IL-1 effects in this system were specific to several aminoquinoline and aminoacridine analogues having a side chain with a tertiary amino group similar to that of chloroquine. Aminoquinoline compounds devoid of this side chain and the tertiary amino, as well as pyrimidines or biguanides with antimalarial activity were without effect. Mefloquine, the most potent of the compounds active against porcine α-IL-1, was only equipotent with chloroquine and its hydroxyanalogue against human recombinant α-IL-1. This suggests that there may be subtle differences in the receptors for these drugs and interleukins in bovine cartilage. The results provide further evidence for the specificity and utility of antimalarial drugs in the treatment of chronic inflammatory conditions, especially in relation to actions on IL-1.
The effect of food on the bioavailability and kinetics of the anticancer drug amsacrine and a new analogue, N-5-dimethyl-9-[(2-methoxy-4-methylsulphonylamino)phenylamino]-4 acridinecarboxamide in rabbits
Authors: Paxton James W 
Published: April 2011

Abstract
Both amsacrine and its analogue, N-5-dimethyl-9-[(2-methoxy-4-methylsulphonylamino)phenylamino]-4-acridinecarboxamide (CI-921) are absorbed from the gastrointestinal tract in rabbits. The mean bioavailability for amsacrine was 50% ± 17 (s.d.) in non-fasting animals, and was significantly increased in fasting animals (mean, 90% ± 10). The bioavailability for CI-921 (mean, 26% ± 11) in the non-fasting animal was significantly less than that found for amsacrine, but this difference disappeared in the fasting animal when the bioavailability of CI-921 was significantly increased to 69% ± 23. Oral administration of both agents resulted in significantly prolonged elimination half-lives and mean residence times compared to the i.v. infusion, but no significant difference was observed in these parameters between the fasting and non-fasting state. This study suggests that oral dosing may be a possible alternative route for the administration of these anticancer agents.
Luminal acid in stress ulceration and the antiulcer action of verapamil in rat stomachs
Authors: Koo M W L , Cho C H , Ogle C W 
Published: April 2011

Abstract
The role of luminal acid and the influence of the antisecretory action of verapamil in stress ulcer prevention in rat stomachs have been studied. Intraperitoneally injected verapamil. 4 mg kg−1, inhibited gastric acid secretion and ulcer formation, however, a 2 mg kg−1 dose, which did not significantly influence acid output, also had an antiulcer effect. Intraperitoneal injection of bethanechol, 1.2 or 3.6 mg kg−1, increased gastric acid output, but did not influence stress-induced ulcer formation. Oral administration of HCl, 25 or 50 μequiv, aggravated stress ulceration in a dose-dependent manner; this lesion-worsening effect was prevented by pretreatment with verapamil or bethanechol. The gastric luminal acid content in 2 h pylorus-ligated rats was similar in the groups given either bethanechol or HCl. These findings indicate that the antisecretory action of verapamil may not account for its antiulcer effect. It is suggested that endogenous and exogenous luminal acid may have different influences on stress ulcer formation.
Liquid penetration as a method of assessing the wettability and surface energy of pharmaceutical powders
Authors: Buckton G , Newton J M 
Published: April 2011

Abstract
The use of a liquid penetration technique to assess the wettability and surface energy of a series of barbiturates, including the use of bicomponent systems, has been critically evaluated. Values of apparent contact angles (θ) obtained using the Washburn relationship (1921) and the Carli & Simioni correction (1979) were found to reflect the practically derived wettability of the powders. Values of γc obtained from modified Zisman plots and from Neumann's equation of state did not realistically describe the surface energies of the powders. The nature of alcohol-water mixtures has been examined to assist elucidation of the theoretical problems associated with the technique and to offer a possible explanation for the inadequacies of the surface energy results.
Content uniformity of microdose tablets (dosage 1 μg-10 mg) produced by fluid bed granulation of interactive mixtures
Authors: Thiel W J , Nguyen L T , Sberna F J 
Published: April 2011

Abstract
Tablets (100 mg), containing microdose quantities of micronized model drug (1 μg-10 mg), were produced from interactive powder mixtures which had been fluid bed granulated. Granulation prevents adhesion unit and constituent segregation occurring during compression. Single tablet assays were performed on 100 tablets from each batch. The content of tablets fell within ±15% of the mean, and the coefficient of variation was &lt;5% (99% confidence) for all batches. Skewness in the content distribution showed little evidence of superpotent tablets and indicated the absence of significant agglomerates of particles of the micronized component. However, there was some indication that the mixtures produced were not totally agglomerate free. These results demonstrate that the true potential of interactive mixing may be realized, provided segregation in the mixture can be eliminated. The distribution of micronized model drug, as a function of carrier particle size, was determined for the different concentration mixtures before and after granulation. When 0.1–2% interactive mixtures were sieved gently, the proportions of micronized material adhering to the different size fractions of carrier were similar. However, the very low concentration mixtures (0.01–0.03%) proved to be relatively unstable, a significant proportion of the micronized component being transferred from the mixtures to the metal surfaces of the sieves. Granulation of the mixtures in a fluidized bed produced a uniform distribution of micronized material throughout the different sized granules. These granules were stable during vibration on the sieves and when compressed. All samples of tablets met the United States Pharmacopeia XXI content uniformity requirements.
Evidence that sensory neurons participate in the non-cholinergic, non-adrenergic contractile response of the guinea-pig ileum
Authors: Matušák Ondrej , Bauer Viktor 
Published: April 2011

Abstract
The possible role of non-cholinergic, non-adrenergic (NCNA) nerves in responses of the guinea-pig terminal ileum to transmural nerve stimulation (TNS) and that of sensory nerves in NCNA responses were investigated. The action of acetylcholine was almost abolished in the presence of histamine, whereas the contractions elicited by TNS were changed to frequency-dependent contraction followed by a secondary relaxation. Guanethidine did not alter the contractions or secondary relaxations. Atropine abolished the action of acetylcholine and transiently suppressed the responses to low (up to 2 Hz) and attenuated (by about 50%) those to high (4 to 20 Hz) frequency stimulation. The remaining complex NCNA response was the sum of the excitatory and inhibitory responses. During desensitization to capsaicin, and in its presence, the NCNA contractions were reduced, whereas the relaxations were not significantly enlarged. The present results suggest that besides the cholinergic innervation, the excitatory and inhibitory NCNA innervation also participates in the responses of the guinea-pig ileum to TNS even without suppression of cholinergic and adrenergic transmission, and that the sensory nerves are, at least to some extent, involved in the NCNA excitatory response.
Pharmacological activity of amantadine: effect of N-alkyl substitution
Authors: Dunn John P , Henkel James G , Gianutsos Gerald 
Published: April 2011

Abstract
Alkyl substitution on the nitrogen atom of the anti-parkinsonian drug amantadine resulted in changes in its pharmacological potency. Greater behavioural stimulation (i.e. increased motor activity) was observed following s.c. injection of several of the analogues, with optimal activity produced by N-n-propyl substitution. These molecular changes did not alter the activity of amantadine on inhibition of dopamine uptake or its weak affinity for dopamine receptors in-vitro. Several of the analogues were more effective than the parent compound in increasing the concentration of dopamine metabolites (suggesting an increase in dopamine utilization) following systemic injection, and these effects generally followed the same pattern as observed in the test of behavioural activity. These results provide further support for the concept that the activity of amantadine may be improved by molecular alterations, although the pharmacological basis for this activity remains obscure.