bluuebunny/crossref_metadata_2025_split huggingface dataset:
First-pass Metabolism of Peptide Drugs in Rat Perfused Liver
Authors: Taki Yoko , Sakane Toshiyasu , Nadai Tanekazu , Sezaki Hitoshi , Amidon Gordon L , Langguth Peter , Yamashita Shinji 
Published: April 2011

Abstract
To elucidate the extent and mechanisms of the first-pass metabolism of peptide drugs in the liver after oral administration, a liver perfusion study was performed in rats using metkephamid, a stable analogue of methionine enkephalin, and thyrotropin-releasing hormone (TRH), as model peptides.
The fraction of intact metkephamid recovered after single-pass constant perfusion through rat liver reached steady-state very quickly, and it was concluded that metkephamid was hydrolysed enzymatically at the surface of hepatocytes or endothelial cells of microvessels, or both, rather than being taken up by hepatocytes. The fraction of metkephamid recovered intact was approximately 40% under protein-free conditions but increased to 70–75% on addition of bovine serum albumin (BSA) to the perfusate. The fraction of metkephamid bound to BSA was approximately 50% under these conditions, implying that only the free fraction of metkephamid in the plasma was metabolized in the liver. Calculations based on the tube model showed that approximately 30–35% of metkephamid absorbed from the intestine undergoes first-pass metabolism before entering the systemic circulation in-vivo. In contrast, the fraction of TRH metabolized in the liver was less than 10%, indicating a remarkably low contribution of first-pass metabolism to the bioavailability of TRH.
These results show that hepatic first-pass metabolism of metkephamid contributes to its low systemic bioavailability. After intestinal absorption free metkephamid is rapidly hydrolysed on the surface of hepatocytes or endothelial cells, rather than being taken up by hepatocytes. This information has important implications in the oral delivery of many kinds of peptide.
Changes in Thyroid Hormone Concentrations after Administration of Ashwagandha Root Extract to Adult Male Mice
Authors: Panda Sunanda , Kar Anand 
Published: April 2011

Abstract
The importance of ashwagandha root extract in the regulation of thyroid function with special reference to type-I iodothyronine 5′-monodeiodinase activity in mice liver has been investigated.
Although the root extract (1.4 g kg−1) administered daily for 20 days by gastric intubation increased serum 3,3′,5-triiodothyronine (T3) and tetraiodothyronine (T4) concentrations and hepatic glucose-6-phosphatase activity, hepatic iodothyronine 5′-monodeiodinase activity did not change significantly. Furthermore, ashwagandha root extract significantly reduced hepatic lipid peroxidation, whereas the activity of antioxidant enzymes such as superoxide dismutase and catalase were increased.
These findings reveal that the ashwagandha root extract stimulates thyroidal activity and also enhances the antiperoxidation of hepatic tissue.
The Absence of Stereoselective P-Glycoprotein-mediated Transport of R/S-Verapamil Across the Rat Jejunum
Authors: Sandström Rikard , Karlsson Anders , Lennernäs Hans 
Published: April 2011

Abstract
We have studied the potential stereoselective transport and metabolism of R/S-verapamil in rat jejunum, in-situ.
A regional single-pass perfusion of the rat jejunum was performed on 24 rats in six separate groups. The effective permeability (Peff) was assessed for three different concentrations of verapamil, 4, 40 and 400 mg L−1. The Peff of each enantiomer was also determined at 400 mg L−1 when chlorpromazine (10 mM) was added to the perfusion solution. Two other groups of rats received R/S-verapamil as an intravenous infusion and the intestinal secretion and metabolism were studied by simultaneously perfusing the jejunum with a control or with chlorpromazine (10 mM) added. The concentrations in the outlet perfusate of each enantiomer of verapamil and norverapamil were assayed with HPLC. R/S-Verapamil is a high permeability drug in the proximal rat small intestine throughout the luminal concentration range studied and complete intestinal absorption was expected. There was an increase of Peff from 0.42 times 10−4 cm s−1 to 0.80 times 10−4 cm s−1 (P &lt; 0.05) at concentrations from 4 to 400 mg L−1, respectively. The observed concentration-dependent jejunal Peff and fraction absorbed (P &lt; 0.05) of R/S-verapamil is consistent with the saturation of an efflux mechanism. When chlorpromazine (a P-glycoprotein inhibitor/substrate) was added the jejunal Peff increased to 1.47 times 10−4 cm s−1. There was no difference between the Peff of the two enantiomers in any of these experiments. The efflux of R/S-norverapamil into the rat jejunum was high after intravenous administration of R/S-verapamil, suggesting extensive metabolism in the enterocyte.
In conclusion, both R/S-verapamil enantiomers are P-glycoprotein substrates, but there is no stereoselective transport of R/S-verapamil in the rat jejunum. The results also suggests that R/S-norverapamil is formed inside the enterocytes.
Circadian Changes in the Pharmacokinetics and Pharmacodynamics of Azosemide in Rats
Authors: Han Kye S , Lee Myung G 
Published: April 2011

Abstract
The circadian changes in the pharmacokinetics and pharmacodynamics of azosemide were investigated after intravenous and oral administration of the drug (10 mg kg−1) to rats at 1000 or 2200 h.
After intravenous administration of azosemide the percentage of the dose excreted in 8-h urine as unchanged azosemide was significantly higher in the 1000 h group than in the 2200 h group (41.7 compared with 28.9%) and this resulted in a significant increase in 8-h urine output (84.7 compared with 36.6 mL/100 g). After intravenous administration the time-averaged renal clearance (CLR) of azosemide was significantly faster (2.86 compared with 1.76 mL min−1 kg−1) and urinary excretion of sodium (46.4 compared with 25.9 mmol/100 g) and chloride (35.6 compared with 18.8 mmol/100 g) increased significantly in the 1000 h group. However, after oral administration, the percentages of oral dose of azosemide excreted in 8-h urine as unchanged azosemide were significantly higher (1.88 compared with 0.67%) and the CLR of azosemide was significantly faster (3.64 compared with 0.79 mL min−1 kg−1) in the 2200 h group. This could be at least partly because of increased absorption of azosemide from the gastrointestinal tract in the 2200 h group; the percentages of oral dose of azosemide recovered from the gastrointestinal tract in 8 h as unchanged azosemide was significantly smaller (5.7 compared with 13.2%) in the 2200 h group. The pharmacodynamic parameters of azosemide were not significantly different after oral administration of the drug to both groups of rats.
If these data could be extrapolated to man, the intravenous dose of azosemide could be modified on the basis of circadian time.
A THEORY OF PERCEPTUAL CONSTANCY
Authors: TAYLOR J. G. , PAPERT S. 
Published: April 2011

A terminology is developed for perceptual constancy which permits useful mathematical treatment. This is illustrated by discussing a particular form of constancy for which mathematics is particularly simple. Other cases which need more elaborate mathematics can be discussed in same way.This formulation of constancy problem enables empiricist approach to perception to be formulated more concretely. Instead of saying simply that learning is involved we are able to go some way towards saying what has to be learnt.It is suggested that constancy can be established by conditioning each element of an ‘ equivalence class’ of states of stimulation to same group of responses. This idea needs much more elaboration and investigation (Taylor, 1956), and we do not maintain that it is only possible mechanism.Experimental results on protracted wearing of distorting spectacles are reported and discussed in light of above principles.
EFFECTS OF PROPAGANDA ON RECALL, RECOGNITION AND BEHAVIOUR
Authors: BELBIN EUNICE 
Published: April 2011

A series of experiments were conducted in which Road Safety Posters were displayed in a waiting room. Their effect was measured by: (a) amount of information from posters which was applied to interpretation of photographs showing faulty traffic situations (Use scores); and (b) amount of information contained on posters which could be recalled (Recall scores). An attempt was made to investigate reasons why on some occasions or with some subjects information was recalled more than it was used, and why on other occasions or by other subjects it was used more than it was recalled.Four types of propaganda were displayed. Each had a significant effect on use scores, but there was no significant difference between effects of these four types on either use or recall. However, previous experience of subjects was shown to have a considerable effect on results. over‐sixties, although comparatively bad at recalling propaganda, had use scores which compared favourably with those of younger subjects. subjects who had car‐driving experience used information from posters to a significantly greater extent than non‐drivers. On other hand, drivers did not recall propaganda any better than non‐drivers. There was also a tendency for naval rating subjects to use more of information than they recalled and for students to recall as much or more than they used. When tests were applied up to a period of 14 days after display of propaganda there was a widening disparity between use and recall scores. At 14 days subjects still showed a slight tendency to use information although they were not able to remember it.An attempt is made to explain these results by suggesting that when a subject is presented with an incidental learning situation, meaningfulness he extracts from material and his method of organizing it depends on his previous learned responses to similar material. Where his previous experience has entailed incorporation of information into his activity, then new material to be learned is likely to have meaning in relation to its practical application, a response which favours retention of information for use in other tasks, but not necessarily for recall. If his previous experience has been learning by memorizing, his response to new material will be organized accordingly; he is likely to learn in order to recall.
SOME STUDIES OF PERCEPTION IN RELATION TO AGE
Authors: WALLACE JEAN G. 
Published: April 2011

A series of experiments to discover extent of age differences in visual perception when temporal integration was required suggested that:

Whore displays were simple, performance of different age groups was nearly equal, but with increasing complexity of displays older subjects were relatively increasingly slow in making correct identifications.
With complex displays there was a relationship between degree of correct identification and (a) cumulative viewing time; (b) amount of display seen at one moment, such that an increase in both led to a greater improvement in performance of older subjects than an increase in either time or amount alone. Given a sufficient increase, performance of older subjects equalled that of younger.
greater difficulty of older subjects with complex material appeared to be due mainly to greater amount of temporal integration required with such material.
AN EXPERIMENTAL INQUIRY INTO CONCEPT OF PERCEPTUAL DEFENCE
Authors: SINGER BERNARD R. 
Published: April 2011

Experiments on concept of perceptual defence can be considered as result of two research interests: (1) attempts to relate experimental work to clinical findings and (2) attempts to determine precise variables involved in association between personality and perception. concept of perceptual defence is based on fact that subjects appear to show higher thresholds to taboo words and that autonomic responses to such words may be made before they are correctly recognized. This concept has been criticized on grounds that results may be more simply interpreted in terms of factors of word frequency and of suppression of responses by subject. Other work has attempted to show that individual performance requires prime consideration.This study has attempted to take account of these factors. A word‐association test consisting of most frequent words in Thorndike and Lorge count was given to all subjects. On basis of each subject's results, two lists were prepared for each subject, each list consisting of emotional and neutral words. A tachistoscopic presentation to subject of one list was followed two weeks later by a presentation of second list. It was found that six of twelve subjects showed higher and two subjects lower thresholds to emotional words on both occasions. correlation between two tests in terms of individual performance was highly significant.Analysis of this and other experiments shows that importance of factors of word frequency when familiar material is used remains to be determined. Further, some means of studying such factors other than by use of word counts is necessary. It is suggested that a quantifiable ‘hypothesis’ or ‘set’ theory possesses greatest advantages for an understanding of this area of research.
DETERMINANTS OF EMOTIONALITY IN RAT
Authors: BROADHURST P. L. 
Published: April 2011

An experiment was designed to establish optimum conditions for using Hall's open‐field test of emotionality in white rat. A large (N = 192) factorial design permitted simultaneous evaluation of following components of test which were thought to be productive of emotional responses: size of test arena, intensity of illumination and intensity of sound. effects of pre‐trial shock, food deprivation and sex difference were also investigated. Other variables were strictly controlled.results, principally analysed in terms of defecation and ambulation scores, show that females defecate significantly less than males and ambulate more, that noise is a potent factor in evoking emotional elimination and light less so. Arena size does not affect defecation, but rats run farther in a larger arena. Pre‐trial shock reduces defecation, whereas food deprivation has no significant effect. Interactions are few, and mostly concern sex differences in response.It is concluded that test can yield sensitive indicators of an emotional response, and that this response is susceptible, within limits, to experimental control. implications for use of test are discussed.
PERCEPTUAL AND PERSONALITY DYNAMICS IN REACTIONS TO AMBIGUITY
Authors: HAMILTON VERNON 
Published: April 2011

A battery of tests designed to elicit differential responses to a variety of ambiguous situations was administered to groups of Control and Neurotic subjects. data show marked individual differences and considerable evidence for intra‐individual consistency in avoidance/non‐avoidance of ambiguous situations. A high percentage of significant correlations suggests that tests measure few, closely related variables. Age and intelligence are only minimally involved. evidence is taken to be consistent with a theory of cognitive control of environment mediated via perceptual attitudes operative at varying levels of individual.To test influence of controlling and restrictive personality factors on reactions towards ambiguous situations, groups of anxious, hysterical and obsessional psychiatric patients were compared for tendencies to avoid ambiguity. Neurotic subjects were generally shown to avoid ambiguity more than Controls, and Conversion Hysterics and Obsessionals avoided ambiguous situations more than Anxiety States. It is suggested that avoidance of ambiguity serves to avoid anxiety and conflict. similarity in behaviour between Obsessionals and Conversion Hysterics is interpreted as being due to functional similarity and aims of neurotic symptoms of these two clinical groups.
SURPRISE, ISOLATION, AND STRUCTURAL CHANGE AS FACTORS AFFECTING RECALL OF A TEMPORAL SERIES
Authors: GREEN ROBERT T. 
Published: April 2011

SummaryTwo experiments are considered which throw light on certain aspects of what has become known as the von Restorff effect. The first is designed to find out whether items in a serial learning task are favoured in recall because unexpected change attracts attention. The results show that change as such, expected or unexpected, has an effect, though unexpected change does have a somewhat greater effect on recall scores. Subjective reports suggest that this is due, at least in part, to the fact that when the instructions are understood they serve to direct attention. The second experiment directly attacks the question of whether ‘isolation’ has any distinct effect on probability of recall, and demonstrates that structural change in a temporal series is the crucial variable.
A ‘CRESPI EFFECT’ IN MALE IMBECILES
Authors: O'CONNOR N. , CLARIDGE G. S. 
Published: April 2011

In order to test the effects on performance of an interchange in incentive level forty male imbeciles were divided into four equal matched groups on the basis of two initial trials on a simple dexterity task. For a further ten trials two groups worked under non‐incentive conditions and two under incentive conditions, in which they were encouraged to reach a goal based on their previous performance. On the last trial one incentive group was changed to control conditions and one control group to incentive conditions, the other two groups continuing as before. The experiment was continued for a further seven trials.Results indicated that groups given the incentive from the beginning of learning separated significantly from those receiving no incentive. When one of the latter groups was given an incentive, however, its performance increase showed a typical Crespi type ‘elation’ effect, performance reaching, and maintaining, a level greater than that of subjects who had received the incentive from the beginning of learning. The effect was found to be a group trend rather than a response typical of all subjects.A comparable decrease in incentive level was found to have little marked effect on performance level, which established itself at a point intermediate between the performance levels of subjects who continued to receive an incentive and of subjects who had received no incentive at all. This finding confirmed earlier work with defectives, showing that incentives would have relatively permanent effects on the attitude or set, and hence on the performance level of imbeciles.
EXPLANATORY POWERS OF THE FRACTIONAL ANTEDATING RESPONSE MECHANISM
Authors: RITCHIE BENBOW F. 
Published: April 2011

The fractional antedating response mechanism is used by Spence to explain the fact that rats can anticipate the consequences of their responses and can make choices based on these anticipations. The present paper examines the logic of this explanation, shows the kinds of assumptions required by it, and derives an experimental test of this explanation.This derivation assumes that fractional eating reactions in black and in white boxes are different reactions. While this assumption is not required to explain Kendler's experiment or Spence's paradigm, it is required to explain the latent learning and reasoning phenomena in many other experiments.As a consequence, the negative results of the experiment reported in this paper suggest either that the fractional reaction explanation is false, or that it is trivial in the sense that it is appropriate only to those latent learning phenomena where the alternative consequences are distinguished by different consummatory responses.
REMEMBERING ADVANCE CUES DURING SEARCHING
Authors: MACKWORTH N. H. , MACKWORTH J. F. 
Published: April 2011

A classification is given of the various ways in which advance information may be displayed to help performance, and a distinction is drawn between two kinds of work. These are tasks in which advance information (1) always remains on view until after action has been taken, and (2) is displayed but must be memorized, because it disappears before action is required.A particular laboratory task of order search has been studied; this has the advantage that the facts needed for a series of decisions are displayed all the time, and therefore do not need to be remembered. But such a display also has the disadvantage that information needed for use at the moment cannot easily be selected from many other details. Visual searching can be greatly simplified by providing additional advance cues which emphasize in turn each objective as it requires attention. However, if these advance cues point to objectives which are too far ahead, once again difficulties arise in the memorizing of these extra cues.The experiments described below investigated the size of the advance store, which was the number of advance cues which could be memorized at any given instant for successful work; this advance store did not include any advance cues currently on the display.Studies of the advance store demonstrated that serial work greatly reduced the normal immediate memory span. Only two advance cues could be memorized to help subsequent performance at slow working speeds, and at fast speeds only one such cue could be remembered. The advance time was also much less with the faster work.The limiting factor for anticipation span at the fast speeds was apparently the time available for perception and memorizing. In keeping with this was the further result that grouping the advance cues together in time gave better performance, and some of the possible reasons for this have been discussed.
THE OPTIMAL PERCEPTUAL LOAD IN A PACED AUDITORY INSPECTION TASK
Authors: POULTON E. C. 
Published: April 2011

A paced auditory inspection task was presented at four levels of perceptual load and three rates of critical signals. The aim was to determine whether there was an optimal range of perceptual load, over which deterioration in performance with time would be minimal. Beyond this optimal range, where the load was either too great (soon producing ‘mental fatigue’), or too small (soon producing ‘boredom’), greater deterioration was to be expected. The experimental results supported the hypothesis.The task with the smallest perceptual load presented critical signals only once about every 4 mins. on average. This vigilance task gave significantly more errors than a task with a greater perceptual load and a higher rate of critical signals. Conditions were designed to maintain motivation in both cases. Thus the poorer performance is unlikely to have been due simply to inadequate motivation.
A RESULT IN VISUAL AESTHETICS
Authors: ALEXANDER CHRISTOPHER 
Published: April 2011

Subjects were given eight forms and asked to sort them in a number of ways on the basis of overall similarity; they were also asked to state the order of their preferences among the forms. From the data generated, four tentative results emerged:

By giving ourselves an appropriate verbal set, we can make ourselves see (and categorize) a group of forms in many different ways. It appears, however, that there is a natural way of categorizing them which is independent of any verbal set, and which depends on the formation of visual non‐verbal concepts.
Preference for the forms is dependent on the way the forms are seen—on the visual similarity dimensions. But the dependence is incomplete. It might perhaps be better called a linkage—comparable to the linkage between hue and brightness.
The peculiarly weak nature of this linkage suggests the hypothesis that the beauty of a form cannot be explained in terms of any visible qualities or attributes that it has, but only in terms of the operations performed in the brain of the observer.
Aesthetic discrimination is independent of all other kinds of perceptual discrimination.