bluuebunny/crossref_metadata_2025_split huggingface dataset:
Endothelium-dependent Vasorelaxant and Anti-aggregatory Effect and Mechanism of Action of Some Antifibrinogen RGD (Arg-Gly-Asp-containing) Peptides
Authors: Torday Ladislaus L , Pataricza János , Balogh Gábor E , Zarándi Márta , Penke Botond , Papp Julius Gy 
Published: April 2011

Abstract
Vasorelaxation caused by some antifibrinogen RGD (Arg-Gly-Asp-containing) peptides and their basic mechanism of action was studied on rabbit isolated thoracic aortic rings preconstricted with 0.25 μM phenylephrine.
GRGDS (Gly-Arg-Gly-Asp-Ser-OH) and RGDV (Arg-Gly-Asp-Val-OH) caused dose-dependent relaxation. RGDS (Arg-Gly-Asp-Ser-OH) had a biphasic effect (a transient relaxation followed by a contraction) while GRGDS-[SE] (Gly-Arg-Gly-Asp-Ser(SO3)-OH) did not change the isometric tone of precontracted aortic preparations. GRGDS and RGDV exerted no relaxing effect on endothelium-denuded blood vessels suggesting that the vascular action of these peptides was entirely dependent on the presence of functionally intact endothelium. L-NG-Nitro-arginine (30 μM) attenuated the relaxation induced by GRGDS and abolished that induced by RGDV. All of the four RGD congeners inhibited ADP-induced aggregation of human platelets.
These findings indicate that the relaxant effect of RGDV is mediated exclusively by the nitric oxide pathway, but GRGDS could cause, besides nitric oxide release, the release of another substance which is different from nitric oxide. Because the rank order of the vasorelaxant potencies of RGD peptides differed from that found for their anti-aggregatory activities, a vascular effector mechanism mediated by an RGD-recognizing structure other than the known glycoprotein IIb/IIIa-like RGD-binding site is suggested.
Protective Effects of Selenomethionine against Cisplatin-induced Renal Toxicity in Mice and Rats
Authors: Rao Mahadev , Rao M N A 
Published: April 2011

Abstract
The effect of selenomethionine on the toxicity of cisplatin has been studied in mice and rats.
When selenomethionine (0.5–4 mg kg−1) was administered intraperitoneally to mice 1 h before intraperitoneal cisplatin (6 mg kg−1), the toxicity of cisplatin, as measured by loss of body weight and blood urea nitrogen and serum creatinine levels, was reduced significantly. The protection was dose-dependent but less when given orally. Similar results were obtained with rats. Deterioration of renal function was characterized by reduced creatinine clearance, and increased excretion of urinary protein was significantly reversed. Partial but significant protection was also observed against capsulation-induced reduction of white blood-cell count. Protective properties were further demonstrated by increased survival of mice pretreated with selenomethionine compared with the lethality observed for animals given cisplatin only.
These results suggested that selenomethionine protects against cisplatin-induced renal and other toxicity. The study has many clinical implications in cancer chemotherapy and needs further investigation.
Enhancement by Terpenes of 5-Fluorouracil Permeation through the Stratum Comeum: Model Solvent Approach
Authors: Moghimi H R , Williams A C , Barry B W 
Published: April 2011

Abstract
5-Fluorouracil permeates the stratum corneum through the intercellular pathway. 5-Fluorouracil is hydrophilic and, therefore, its partitioning from the aqueous region into the hydrocarbon interior of stratum corneum lipids is expected to be an important stage of its permeation and a target for some permeation enhancers. It has also been reported that complexation plays a role in the enhancement effect of some accelerants. These mechanisms have been investigated.
For partitioning-permeation studies, isooctane was chosen as a model of the hydrocarbon interior of stratum corneum lipid bilayers and the effects of 26 different terpene enhancers on the solubility of 5-fluorouracil in isooctane were measured. Results were then compared with the effects of the same enhancers on the permeation of 5-fluorouracil through the epidermis in man. The stoichiometry of interaction of cineole and limonene with 5-fluorouracil were also studied to reveal possible complex formation. Solubility studies revealed good correlation between solubility and enhancement ratios for the majority of terpenes, indicating that one mechanism by which terpenes increase permeation of the stratum corneum by 5-fluorouracil is by improvement of partitioning. Stoichiometry studies showed that cineole can form 1:1 or higher complexes with 5-fluorouracil. With limonene, only a weak 1:1 complex was indicated. Data obtained using epidermis from man show that the enhancement effect of cineole toward 5-fluorouracil is much higher than that of limonene.
These data reveal that terpenes might increase the permeation of 5-fluorouracil through the stratum corneum as a result of complex formation and a form of facilitated transport.
N-Dealkylation of Chlorimipramine and Chlorpromazine by Rat Liver Microsomal Cytochrome P450 Isoenzymes
Authors: Valoti Massimo , Frosini Maria , Palmi Mitri , de Matteis Francesco , Sgaragli Gianpietro 
Published: April 2011

Abstract
The role of different cytochrome P450 isozymes (CYP) in the N-demethylation of chlorimipramine and chlorpromazine has been investigated in liver microsomes from rats by studying the effects of multiple subchronic doses of chlorimipramine, chlorpromazine, phenobarbital and β-naphthoflavone on the N-demethylation of ethylmorphine, mono-N-demethyl-chlorimipramine and chlorpromazine and on the hydroxylation of aniline.
With control microsomes, CYP-dependent metabolism of chlorimipramine and chlorpromazine (100 nmol; 30 min incubation) resulted in the formation of predominantly chlorimipramine (46.5 ± 4.9 nmol) whereas chlorpromazine (14.1 ± 0.9 nmol) accounted for only part of the overall metabolism of chlorpromazine. Multiple doses of chlorimipramine increased the capacity of microsomes to N-demethylate ethylmorphine (9.8 ± 0.73 and 6.08 ± 0.06 nmol min−1 (mg protein)−1 for chlorimipramine-treated and control rats, respectively) as well as itself (4.65±0.25 and 3.10±0.33 nmol min−1 (mg protein)−1, respectively). Multiple doses of chlorpromazine induced aniline-hydroxylase activity (1.11 ± 0.16 and 0.94 ± 0.06 nmol min−1 (mg protein)−1 for chlorimipramine and control microsomes, respectively) but the capacity to N-demethylate itself was unchanged. Phenobarbital treatment induced ethylmorphine N-demethylation activity, but did not affect N-demethylation activity, towards chlorimipramine and chlorpromazine. In control microsomes the N-demethylation capacity of chlorimipramine or chlorpromazine (0.160±0.025 and 0.015±0.003 nmol min−1 (mg protein)−1, respectively) was one order of magnitude lower than that of chlorimipramine or chlorpromazine. The capacity to N-demethylate either chlorimipramine or chlorpromazine was increased by treatment with either phenobarbital or β-naphthoflavone. In control microsomes, sulphaphenazole markedly inhibited both chlorimipramine-N-mono- and di-N-demethylation, whereas quinidine markedly inhibited the rate of formation of chlorpromazine.
The CYP2C and CYP2D subfamilies seem to be involved in the mono N-demethylation of chlorimipramine and chlorpromazine, respectively. Moreover the CYP1A and CYP2B subfamilies might participate in the N-demethylation of either chlorimipramine or chlorpromazine. This could have important implications in the clinical use of chlorimipramine and chlorpromazine in view of the genetic polymorphism of CYP2C and CYP2D isozymes in man.
Efflux Transport of Tolbutamide Across the Blood-brain Barrier
Authors: Takanaga Hitomi , Murakami Hideyasu , Koyabu Noriko , Matsuo Hirotami , Naito Mikihiko , Tsuruo Takashi , Sawada Yasufumi 
Published: April 2011

Abstract
In an attempt to determine the reason for the low brain distribution of tolbutamide, we have demonstrated the transport of tolbutamide from the brain to the blood via a non-P-glycoprotein efflux transport system which is inhibited by sulphonamides. We evaluated the directional transport of tolbutamide across the blood-brain barrier by means of an in-vivo brain-tissue distribution study and experiments on in-vitro transcellular transport and uptake in cultured mouse-brain capillary endothelial cells (MBEC4).
The brain-to-unbound-plasma concentration ratio of [14C]tolbutamide increased in the presence of high concentrations of unlabelled tolbutamide or sulphonamide at steady-state in-vivo. The brain-to-blood concentration ratios of [14C]tolbutamide were very low compared with that of [3H]propranolol obtained by in-vivo integration plot analysis. From the in-vitro transcellular transport study using a monolayer of MBEC4 cells, we found that the abluminal-to-luminal flux of [14C] tolbutamide was higher than the reverse flux. Both luminal-to-abluminal and abluminal-to-luminal transport of tolbutamide were saturable. The maximum transport rate (Jmax), the half-saturation concentration (Kt), and the first-order rate constant (kd) were 65.9 ± 29 pmol min−1 (mg protein)−1, 7.54 ± 4.4 μM, and 4.89 ± 0.34 μL min−1 (mg protein)−1, respectively, for luminal-to-abluminal transport, and 128 ± 66 pmol min−1 (mg protein)−1, 5.59 ± 4.2 μM, and 4.43 ± 0.86 μL min−1 (mg protein)−1, respectively, for abluminal-to-luminal transport. At therapeutic plasma concentrations of tolbutamide (1–16.9 μM), the efflux rate would be faster than the influx rate. The estimated net efflux was consistent with the very low in-vivo brain distribution of tolbutamide. The efflux process observed in MBEC4 cells was inhibited by sulphonamides such as sulphaphenazole, sulphamethoxazole and sulpha-dimethoxine whereas the steady-state uptake of [14C]tolbutamide was not affected by either cyclosporin or verapamil, specific inhibitors of P-glycoprotein.
These findings suggest that tolbutamide is partly transported from the brain via the non-P-glycoprotein-efflux transport system, which is inhibited by sulphonamides.
Effects of KW-5092 on Antroduodenal Coordination and Gastric Emptying in Guinea-pigs
Authors: Kishibayashi N , Karasawa A 
Published: April 2011

Abstract
KW-5092 (2-[1-[2-[[5-(piperidinomethyl)-2-furanyl]methylamino]ethyl]imidazonylidin-2-ylidenene]malononitrile fumarate) is a novel gastroprokinetic agent with both acetylcholine release facilitatory and acetylcholinesterase inhibitory activity. We have investigated the effects of KW-5092 on antroduodenal coordination and gastric emptying in guinea-pigs.
In the guinea-pig isolated gastroduodenal preparation, KW-5092 at 3 times 10−7 to 3 times 10−6 M significantly increased antroduodenal coordination. The effect of KW-5092 was almost completely inhibited by atropine or tetrodotoxin. Cisapride, a gastroprokinetic agent with acetylcholine release facilitatory activity, also increased coordination whereas neither acetylcholine nor the acetylcholinesterase inhibitor neostigmine affected it. In-vivo, KW-5092 and cisapride enhanced gastric emptying whereas neostigmine delayed it.
These results suggest that acetylcholine release facilitation, but not acetylcholinesterase inhibition, is involved in the enhancement by KW-5092 of antroduodenal coordination and gastric emptying.
Plasma and Muscle Polyamine Levels in Aerobically Exercised Rats Treated with Salbutamol
Authors: Cepero M , Cubría J C , Reguera R , Balaña-Fouce R , Ordónez C , Ordóñez D 
Published: April 2011

Abstract
The induction of hypertrophy of cardiac and skeletal muscles has been studied after treatment with two different salbutamol dosages, therapeutic and doping.
Treatment of rats subjected to a physical training schedule with repeated doses (16 μg kg−1 per day or 3 mg kg−1 per day) of salbutamol, a specific β-adrenergic agonist, induced a marked increase in both skeletal and heart-muscle weight, whereas total body weight did not change significantly. Adrenergic involvement of salbutamol-linked muscle hypertrophy was demonstrated by co-administration of the non-specific β-adrenergic antagonist, propranolol (20 mg kg−1 per day). Salbutamol-induced muscle hypertrophy was associated with an increase in serum, skeletal-muscle and heart levels of the naturally occurring polyamines putrescine, spermidine and spermine.
These observations suggest the involvement of polyamines in muscle hypertrophy and the possible role of blood polyamines as exposure biomarkers in β-adrenergic-muscle hypertrophy.
Concentration- and Region-dependent Intestinal Permeability of Fluvastatin in the Rat
Authors: Lindahl Anders , Sandström Rikard , Ungell Anna-Lena , Lennernäs Hans 
Published: April 2011

Abstract
The purpose of this study was to investigate the mechanisms of transport of fluvastatin across the intestinal mucosa in various regions of the intestine in the rat. In-situ single-pass perfusions of the jejunum, ileum and colon were performed and the effective permeability (Peff) of fluvastatin, antipyrine and D-glucose were assessed in each region, at three different perfusate fluvastatin concentrations (1.6, 16 and 160 μM). The effect of lovastatin acid on the bi-directional transport of fluvastatin across the ileal mucosa was also studied.
The Peff of fluvastatin was found to be dependent both on the intestinal region and on the concentration in the intestinal lumen (P &lt; 0.001). Fluvastatin had the lowest Peff (0.55±0.10 times 10−4 cm s−1) in the jejunum at 1.6 μM, and the highest Peff (1.0±0.16 times 10−4 cm s−1) in the colon at 160 μM. The highest concentration of fluvastatin increased the average absorption of water from the intestine by 209% (P &lt; 0.05), and the average Peff of D-glucose by 29% (P &lt; 0.05). The presence of excess lovastatin acid (100 μM, compared with fluvastatin 1.6 μM) at the luminal side increased the average absorption of water by 218% (P &lt; 0.001), and the Peff of fluvastatin in the ileum and the colon by 44 and 50%, respectively (P &lt; 0.05). The presence of lovastatin acid on the luminal side in the ileum also increased the blood-to-lumen transport (exsorption) of fluvastatin by 43% (P &lt; 0.001).
The increased intestinal absorption of fluvastatin at higher concentrations does not suggest that substantial absorption occurs by any carrier-mediated process in the absorptive direction. The increased bi-directional transport when lovastatin acid was added to the lumen suggests that fluvastatin is not a P-glycoprotein substrate. Instead, the concentration-dependent increase in the absorption of fluvastatin, water and D-glucose suggests a direct effect of fluvastatin on the transcellular passive transport.
Intestinal Uptake of Particulate Material by Dexamethasone-treated Rats: Use of a Novel Technique to Avoid Intestinal Mucosal Contamination
Authors: Limpanussorn J , Simon L , Dayan A D 
Published: April 2011

Abstract
The aim of this study was to investigate the effect of immune suppression on the uptake of particles across the wall of the intestine and the dissemination of the particles to systemic organs.
Normal and dexamethasone-immunosuppressed rats were dosed orally with 0.5 mL distilled water or fluorescent polystyrene latex particle suspension containing 2.33 times 109 2-μm diameter particles. One hour after particle dosing, the animals were killed by CO2 asphyxiation. The intestinal tissues and systemic organs were sampled for particle quantitation. To avoid contamination by particles adherent to intestinal mucosa the epithelium of intestinal tissue samples was removed before quantification. The number of fluorescent particles in tissues was determined by fluorescence microscopy of digests of selected samples. The uptake of particulate material across the intestinal wall was significantly (P &lt; 0.05) increased in rats treated with dexamethasone but the number of particles transferred to systemic organs did not differ from values found for control animals.
The results suggest that although dexamethasone increased intestinal permeability the apparatus or mechanisms involved in particle transport to distal sites were not affected during immune suppression.
TOWARDS AN INFORMATION‐FLOW MODEL OF HUMAN BEHAVIOUR*
Authors: MACKAY DONALD M. 
Published: April 2011

This paper is concerned with behaviour possible in an information‐flow system intended explicitly as a hypothetical model for comparison with human information‐handling system. A statistically self‐organizing system is described in which not only normal homeostatic behaviour but also such activities as invention of fruitful hypotheses, imagination of fictitious situations, and like would find a natural place. Discussion is confined mainly to manner of concept‐formation and concept‐handling in such a system. It has been suggested that correlate of perception (as distinct from reception) is activity which organizes an outwardly directed internal matching response to signals from receptors. This organizing activity amounts logically to an internal representation of feature in incoming signals to which it is adaptive, i.e. feature which is thus ‘perceived’.A hierarchic structure is postulated wherein much of organizing activity is concerned with modifying probabilities of other activity. Abstract concepts and hypotheses are represented by ‘sub‐routines’ of such organizing activity. These can in principle be evolved as a result of experience in a manner analogous to‐or at least fruitfully comparable with‐process of learning and discovery; and it is not necessary for designer to predetermine, nor possible for him to foresee, all conceptual categories in terms of which information received by system may be structured. Particular attention is directed to conditions under which such a process of concept‐formation could take place with sufficient rapidity.Some of symptoms of psychopathology find apparent correlates in possible modes of malfunction of such a system. But in this, as in other respects, it is not intended to press resemblances; intention is rather to stimulate critical comparisons, in order that differences between information‐flow model and real thing may continually lead to progressive refinement and enlarged understanding.
SEX DIFFERENCES IN PREFERENCES FOR SHAPES: A CROSS‐CULTURAL REPLICATION
Authors: JAHODA G. 
Published: April 2011

A shape‐preference test was designed by McElroy on basis of ‘a possible corollary of psychoanalytic theory’ and administered to Scottish schoolchildren. In accordance with predictions there was a significant tendency, increasing with age, for boys to prefer round shapes (disguised female symbols) and for girls to prefer rectilinear ones (disguised male symbols). McElroy suggested alternative hypotheses that might, in his view, account equally well for effects obtained.In present study McElroy's main alternative hypotheses were examined and it appeared that, as formulated by him, they could not be used to predict results in Accra. It was shown, however, that psychoanalytic hypothesis did permit a definite prediction: in a cultural situation where there is less repression, one would expect sex differences to be smaller. test was given in a modified form, which made more detailed analysis possible. A greatly reduced, but still significant, sex difference was in fact obtained. Age changes, contrasting with those found in Scotland, were also shown to be consistent with psychoanalytic hypothesis. It was further suggested that some of specific Freudian interpretations of symbols may have to be reconsidered.
‘ABNORMAL BEHAVIOUR’ INDUCED BY NITROUS OXIDE
Authors: STEINBERG HANNAH 
Published: April 2011

Psychological changes induced in normal volunteers by inhalations of nitrous oxide are described. Some of these changes resembled psychiatric symptoms, for example illusions and hallucinations, perseverations, and ‘dissociated’ states.There was no relation between individual differences in number of changes reported, ratings for emotional stability, and cognitive impairment attributable to drug.Possible relations between normal, drug‐induced, and other forms of abnormal behaviour are discussed.
PSYCHOLOGICAL REFRACTORY PHASE*†
Authors: MARILL THOMAS 
Published: April 2011

A reaction‐time experiment was performed in which S was presented with two lights and two hand‐keys. A flash of left light served as a stimulus to press left key with left hand; right light to press right key with right hand. Trials were given in which both lights flashed; interval between flashes being randomly selected from nine possible values ranging from 0 to 600 msec, various intervals occurring with equal probability.If s1 and s2 are prior and subsequent of a pair of stimuli calling forth responses r1 and r2, respectively, it was found: (a) that presenting s2 during s1‐s2 interval has no systematic effect on this interval; (6) that s2‐r2 interval varies markedly as a function of s1‐s2 interval, with s2‐r2, longest for short s1‐s2.
CONFLICT AND CHOICE TIME
Authors: BERLYNE D. E. 
Published: April 2011

Four variables have been suggested as determinants of degree of conflict: (1) number, (2) nearness to equality in strength, (3) absolute strength, and (4) degree of incompatibility, of competing response tendencies. first two, but not others, have figured in investigations relating reaction time to information theory. Three experiments were carried out to test effects of all these variables on choice time. Two types of choice RT were recorded: first, forced‐choice RT (i.e. traditional choice RT), for which one stimulus was presented at a time, each stimulus having its appropriate response; and second, free‐choice RT, for which two or more stimuli were presented together, S having to respond to any one of them.principal findings were as follows. (1) Both types of choice RT were longer when number of alternative responses was increased. (2) Free‐choice RT's were invariably longer than forced‐choice RT's, confirming influence of equality of strength. (3) Forced‐choice RT's were inversely related to stimulus intensity, which was regarded as a factor influencing absolute strength of response tendencies. Free‐choice RT's were shortest at intermediate of three intensity levels studied and significantly longer at highest and lowest levels. proportion by which free‐choice RT's exceeded forced‐choice RT's increased with stimulus intensity. (4) Degree of physiological incompatibility did not affect free‐choice RT's, although physiologically incompatible responses produced longer forced‐choice RT's. (5) There were no significant differences between RT's of S's with high and low neuroticism scores.expediency of continuing to include degree of physiological incompatibility among determinants of degree of conflict is called in question by results. Otherwise, choice time, apart from time taken up by eye movements, etc., which may be shorter with more intense stimuli, appears to increase with degree of conflict. results are discussed in light of various theoretical models, derived from Hull's principle of behavioural oscillation, Miller's theory of conflict, information theory, and Hebb's theory of cortical disruption.
A FACTORIAL STUDY OF INTROVERSION‐EXTRAVERSION
Authors: HILDEBRAND H. P. 
Published: April 2011

AbstractPrevious research suggested that Jung's Theory of Psychological Types could best be examined by factorial methods. Two orthogonal factors of neuroticism and introversion‐extra version were hypothesized in order to explain Jung's theory. A varied neurotic population was examined on a large battery of tests, and factors identified as ‘neuroticism’, ‘g’ and ‘introversion‐extra version’ extracted. Further evidence confirming Jung's theories was given by using regression equations and factor scores which enabled criterion groups not included in the original matrix to be correctly identified.