bluuebunny/crossref_metadata_2025 huggingface dataset:
Solution-structure of a Peptide Designed to Mimic the C-terminal Hexapeptide of Endothelin
Authors: van der Walle C F , Bansal S , Barlow D J
Published: April 2011

The peptide: Ac-cyclo(Cys-His-Leu-Asp-Cys)-Ile-Trp-OH, has been designed by computer-aided molecular-modelling techniques to mimic the proposed α-helical conformation of the C-terminal hexapeptide of endothelin.

Two-dimensional proton nuclear magnetic resonance spectra were acquired for the peptide dissolved in d6-DMSO or D2O-H2O and the distance and angle constraints incorporated into simulated annealing experiments. Conformers generated from the D2O-H2O data superposed on the corresponding main-chain atoms in the crystal structure of endothelin 1 and the solution structure of BQ-123 with root mean square co-ordinate differences of 0·9 Å and 0·77 Å, respectively. The peptide did not elicit antagonism of endothelin-induced in-vitro contractions of rabbit aorta (endothelin A receptor) or rabbit bronchus (endothelin B receptor) preparations.

Because the peptide can adopt a conformer which closely matches the equivalent residues in the endothelin 1 crystal structure and in BQ-123, we suggest BQ-123 does not necessarily mimic the endothelin C-terminal region to achieve its antagonism, and that a helical conformation of the endothelin C-terminal hexapeptide does not favour its interaction at the endothelin B receptor.
Effect of Different β-Adrenergic Agonists on the Intestinal Absorption of Galactose and Phenylalanine
Authors: Díez-Sampedro Ana , Pérez Mercedes , Cobo M Teresa , Martínez J Alfredo , Barber Ana
Published: April 2011

Nutrient transport across the mammalian small intestine is regulated by several factors, including intrinsic and extrinsic neural pathways, paracrine modulators, circulating hormones and luminal agents. Because β-adrenoceptors seem to regulate gastrointestinal functions such as bicarbonate and acid secretion, intestinal motility and gastrointestinal mucosal blood flow, we have investigated the effects of different β-adrenergic agonists on nutrient absorption by the rat jejunum in-vitro.

When intestinal everted sacs were used the β2-agonist salbutamol had no effect either on galactose uptake by the tissue or mucosal-to-serosal flux whereas mixed β1- and β2-agonists (isoproterenol and orciprenaline) and β3-agonists (BRL 35135, Trecadrine, ICI 198157 and ZD 7114) inhibited galactose uptake and transfer of D-galactose from the mucosal-to-serosal media across the intestinal wall (although the inhibiting effects of isoproterenol and Trecadrine were not statistically significant). In intestinal everted rings both Trecadrine and BRL 35135 clearly reduced galactose uptake, the effect being a result of inhibition of the phlorizin-sensitive component. Total uptake of phenylalanine by the intestinal rings was also reduced by those β3-adrenergic agonists.

These results suggest that β1 and β3-adrenergic receptors could be involved in the regulation of intestinal active transport of sugars and amino acids.
Nicotine-induced Perturbations on Heart Rate, Body Temperature and Locomotor Activity Daily Rhythms in Rats
Authors: Pelissier Anne Laure , Gantenbein Manon , Bruguerolle Bernard
Published: April 2011

The aim of this study was to evaluate the influence of nicotine on the daily rhythms of heart rate, body temperature and locomotor activity in unrestrained rats by use of implanted radiotelemetry transmitters.

The study was divided into three seven-day periods: a control period, a treatment period and a recovery period. The control period was used for baseline measurement of heart rate, body temperature and locomotor activity. During the treatment period three rats received nicotine (1 mgkg−1, s.c.) at 0900 h. Three rats received saline under the same experimental conditions. Heart rate, body temperature and locomotor activity were continuously monitored and plotted every 10min. During the three periods a power spectrum analysis was used to determine the dominant period of rhythmicity. If daily rhythms of heart rate, body temperature and locomotor activity were detected, the characteristics of these rhythms, i.e. the mesors, amplitudes and acrophases, were determined by cosinor analysis, expressed as means ± s.e.m. and compared by analysis of variance.

Nicotine did not suppress daily rhythmicity but induced decreases of amplitudes and phase-advances of acrophases for heart rate, body temperature and locomotor activity. These perturbations might result from the effects of nicotine on the suprachiasmatic nucleus, the hypothalamic clock that co-ordinates biological rhythms.
Effect of Particle Size and Coating Level on the Diffuse Reflectance of Wax Matrices
Authors: Dredán J , Zelkó R , Antal I , Bihari E , Rácz I
Published: April 2011

The aim of this study was to examine the influence of particle size and extent of coating on the diffuse-reflectance spectra of wax matrices containing embedded potassium chloride.

Near-infrared spectroscopy was used to analyse the diffuse-reflectance characteristics of the prepared multi-particulate matrices without destructive sample preparation. A 2-factor, 3-level face-centred central composite design was selected to construct a second-order polynomial model which described the effect of particle size and amount of coating on the intensity of the diffusely reflected light. A non-linear model was used to demonstrate the effect of the selected parameters on the intensity of the reflected light; good correlation was obtained between experimental and predicted results. The results indicated that the extent of coating and the particle size of the examined systems in the selected particle size-range modified the intensity of the reflected light.

It can be concluded that near-infrared spectroscopy is a sensitive means of measuring not only the particle size of powders (substrates and their mixtures), but also that of coated multi-particulate systems.
An Investigation of the Mechanism of Flux Across Polydimethylsiloxane Membranes by use of Quantitative Structure-Permeability Relationships
Authors: Cronin M T D , Dearden J C , Gupta R , Moss G P
Published: April 2011

Quantitative structure-permeability relationships (QSPRs) based on readily calculated parameters have been developed to study penetration across a polydimethylsiloxane membrane.

Maximum steady-state flux values for 256 compounds through a polydimethylsiloxane membrane were taken from previous studies. Forty-three physicochemical parameters were calculated for each compound and their significance to flux determined. Removal of fourteen outliers enabled derivation of a significant three-parameter QSPR based on the number of hydrogen-bond acceptor and donor groups and sixth-order path molecular connectivity. Models based on parameters important for penetration across human skin (log P and molecular weight) were comparatively poor.

This model suggests that the mechanism of flux across a polydimethylsiloxane membrane is based mainly on hydrogen-bonding effects; as such it occurs via a mechanism of action different from that of penetration of the skin in man.
Chitosan-EDTA Conjugate: A Novel Polymer for Topical Gels
Authors: Valenta Claudia , Christen Barbara , Bernkop-Schnürch Andreas
Published: April 2011

A recently developed chitosan-EDTA conjugate, neutralized with sodium hydroxide (NaChito-EDTA), has been tested for possible topical use. The technical properties and microbial stability of NaChito-EDTA have been compared with those of carmellose sodium (NaCMC), hydroxypropylmethylcellulose (HPMC), sodium polycarbophil (NaPCP) and sodium carbopol 980 (NaC980), well established gelatinizing agents.

NaChito-EDTA forms stable, colourless, completely transparent hydrogels at a polymer concentration of 0.5%. Of the polymers tested the novel polymer had the lowest incompatibility with multivalent cations and with ethanol, and much the best swelling properties. After 28 days of incubation at room temperature the rates of growth of the complete bacterial spectrum occurring in demineralized water and of Escherichia coli, serving as model strain representative of Gram-negative bacteria, were at least 2 log and 5–7 log, respectively, lower in NaChito-EDTA gels than in the other hydrogels. This antimicrobial activity of NaChito-EDTA can be explained by its highest binding affinity towards magnesium, which stabilizes the outer membrane of Gram-negative bacteria. However, this antimicrobial effect is insufficient to guarantee microbial stability. Further results showed that the antimicrobially acting polypeptide nisin can be recommended as an alternative novel preservative for NaChito-EDTA gels, because its antimicrobial spectrum could also be increased towards Gram-negative bacteria in combination with chelating excipients.

NaChito-EDTA seems, therefore, to be a promising novel polymer for topically-used gels, with advantages over well established gelatinizing agents.
Effect of Cyclosporin on Liver Antioxidants and the Protective Role of Vitamin E in Hyperoxaluria in Rats
Authors: Adhirai Marimuthu , Selvam Ramasamy
Published: April 2011

This study aimed to evaluate whether administration of cyclosporin to hyperoxaluric rats affects liver antioxidant status, and whether pretreatment with vitamin E reverses the effect.

Male Wistar rats were divided into two major groups of 40. One group was given vitamin E. Both major groups were then divided into four subgroups which received vehicle (olive oil), cyclosporin in olive oil (50 mg kg−1), 3% ammonium oxalate or cyclosporin + 3% ammonium oxalate for three days. The activities of liver lactate dehydrogenase, glycolic acid oxidase and xanthine oxidase, and the level of malondialdehyde, an indicator of lipid peroxidation, increased when cyclosporin was administered to hyperoxaluric rats. The levels of antioxidants ascorbic acid, vitamin E and reduced glutathione and the activities of glutathione-metabolizing enzymes were altered significantly when hyperoxaluric rats were treated with cyclosporin. All these enzymes and antioxidants showed highly significant correlation values, r. These changes were restored to near normal by pretreatment with vitamin E.

These findings suggest that cyclosporin-induced hepatotoxicity is aggravated in hyperoxaluria. This was almost totally prevented by pretreatment with vitamin E.
Biochemical and Pharmacological Characteristics of 3-Butyryl-8-methoxy-4-[(2-thiophenyl)amino]quinoline, a New Proton-pump Inhibitor, in Rabbit Gastric Microsomes and in Rats
Authors: Kim Kyu Bong , Chang Man Sik , Chung Young Kuk , Sohn Sang Kwon , Kim Sung Gyu , Choi Wahn Soo
Published: April 2011

We have investigated the properties of the newly synthesized proton-pump inhibitor, 3-butyryl-8-methoxy-4-[(2-thiophenyl)amino]quinoline (YJA20379–6), on gastric mucosal proton-pump (H+/K+-ATPase) activity, gastric acid secretion and gastroduodenal lesions in experimental rats.

YJA20379–6 markedly inhibited H+/K+-ATPase activity in rabbit isolated gastric mucosal microsomes, confirming its classification as a proton-pump inhibitor. The inhibitory efficacy of YJA20379-6 on the proton pump was approximately 14-times higher than that of omeprazole at pH 7.4. YJA20379–6 given intraduodenally had a potent inhibitory effect on gastric secretion in pylorus-ligated rats (ED50 22.9 mg kg−1) but was less active than omeprazole. Pretreatment of rats with YJA20379-6 dose-dependently protected the gastric mucosa from damage induced by water-immersion stress, indomethacin and absolute ethanol, and the duodenal mucosa from damage induced by mepirizole. Repeated administration of YJA20379-6 also dose-dependently accelerated the spontaneous healing of acetic acid-induced gastric ulcers.

These results suggest that YJA20379-6 has potent anti-secretory and anti-ulcer effects which are exerted by suppression of H+/K+-ATPase activity in gastric parietal cells. YJA20379–6 might be useful for the clinical treatment of peptic ulcer diseases.
The 5-HT and α-Adrenoceptor Antagonist Effect of Four Benzylisoquinoline Alkaloids on Rat Aorta
Authors: Catret M , Ivorra M D , D’ocón M P , Anselmi E
Published: April 2011

The action of four benzylisoquinoline alkaloids (two aporphines—glaucine and apomorphine, a benzylisoquinoline—papaverine and a bisbenzyltetrahydroisoquinoline—antioquine) on 5-HT-induced contraction in rat thoracic aorta has been examined and compared with that of the control drugs: ketanserin, nifedipine, prazosin and phentolamine. The relaxant action on 5-HT-induced contraction was contrasted with that on the contraction induced by noradrenaline and KCl.

The results obtained with control drugs show that ketanserin has clear selectivity for 5-HT receptors, whereas prazosin and phentolamine have high selectivity for the α1-adrenoceptor and nifedipine seems to have a more potent effect on KCl-induced contraction than on that induced by 5-HT or noradrenaline. The contraction evoked by 5-HT (10 μm) was inhibited in a concentration-dependent manner by all the alkaloids. The order of potency was: papaverine = glaucine > apomorphine > antioquine. Papaverine had a non-specific relaxant action on 5-HT-, noradrenaline- and KCl-induced contraction, antioquine had a weak relaxant action on the agonist assays, and glaucine and apomorphine inhibited noradrenaline- and 5-HT-induced contraction more potently than they inhibited the K+-depolarized response.

These results indicate that the aporphines assayed, S-glaucine and R-aporphine, had selective action against agonist (noradrenaline or 5-HT)-induced contraction rather than against KCl-depolarization of rat aorta. In contrast papaverine, a benzylisoquinoline alkaloid, relaxes all agents used non-selectively as could be expected from the lack of specificity that characterizes this alkaloid.
Interaction Between Substance P and β-Adrenergic Agonists in the Modulation of the Secretion of Fluid and Protein by the Rat Submandibular Gland
Authors: Iwabuchi Yoshiki , Kimura Tomohiko
Published: April 2011

The interactions between substance P and β-adrenergic agonists such as isoprenaline, dobutamine and terbutaline in the control of the secretion of fluid and protein from the rat submandibular gland have been examined.

Substance P elicited large volumes of saliva whereas isoprenaline, dobutamine and terbutaline elicited small volumes only. The secretion of fluid in response to substance P was markedly enhanced when substance P was administered in combination with isoprenaline or dobutamine but not when it was administered in combination with terbutaline. Isoprenaline elicited large amounts of protein, whereas substance P elicited small amounts. The secretion of protein in response to isoprenaline did not change when isoprenaline was administered in combination with substance P. The secretion of fluid and protein induced by substance P in combination with isoprenaline was antagonized by metoprolol and by spantide, but it was unaffected by pretreatment with ICI118551.

These results suggest that in the rat submandibular gland stimulation of β1-adrenoceptors but not of β2-adrenoceptors potentiates the secretion of fluid that is induced by stimulation of tachykinin receptors, whereas stimulation of tachykinin receptors does not enhance the secretion of protein that is induced by stimulation of β1-adrenoceptors.
Compatibility of Tropisetron with Glass and Plastics. Stability under Different Storage Conditions
Authors: Brigas F , Sautou-Miranda V , Normand B , Geneve S , Chopineau J
Published: April 2011

The compatibility of tropisetron (pure undiluted 1 mg mL−1 and diluted with 5% glucose or 0–9% NaCl (saline)) with glass, poly(vinyl chloride), polypropylene or polyethylene containers has been studied over a period of two weeks. The drug solutions were exposed to different light and temperature conditions. Tropisetron was assayed by high-performance liquid chromatography.

The results show that undiluted tropisetron is stable in polypropylene syringes for two weeks under all the storage conditions tested (daylight at room temperature, dark at room temperature, refrigerator at 4°C). Some variations in concentration were observed after dilution of tropisetron but these remained within 10% of the initial concentration. Tropisetron can be stored undiluted at 1 mg mL−1 in polypropylene syringes, although it is preferable to perform dilutions extemporaneously. Tropisetron diluted with 5% glucose or saline can be kept equally well in glass, poly(vinyl chloride) (Travenol bags) or polyethylene (ecoflac) containers.
Water-soluble β-Cyclodextnns in Paediatnc Oral Solutions of Spironolactone: Preclinical Evaluation of Spironolactone Bioavailability from Solutions of β-Cyclodextrin Derivatives in Rats
Authors: Kaukonen Ann M , Lennernäs Hans , Mannermaa Jukka-Pekka
Published: April 2011

Water-soluble derivatives of β-cyclodextrin have been considered for solubilization of spironolactone in the formulation of a safe liquid preparation for premature infants. The oral absorption of spironolactone was studied in rats to evaluate the need to adjust spironolactone dosage in prospective clinical studies. Spironolactone was administered in solutions of sulphobutyl ether β-cyclodextrin (SBE7) or dimethyl-β-cyclodextrin (DM-β-CyD) and also as spironolactone-containing powder papers (reference preparation). Spironolactone in SBE7 solution was administered intravenously to assess the extent of intestinal absorption from the different formulations.

Spironolactone and the metabolites 7α-thiospirolactone, 7α-thiomethylspirolactone and canrenone were determined in rat serum after intravenous administration of spironolactone. Half-lives for spironolactone, 7α-thiomethylspirolactone and canrenone were 0.72 ± 0.17, 1.5 ± 0.3 and 2.2 ± 0.3 h, respectively. Although, according to Cmax values, 7α-thiomethyl-spirolactone was the major serum metabolite in rats, higher AUC (area under the serum concentration-time curve) values were obtained for canrenone. After oral administration of spironolactone the bioavailabilities evaluated from the AUC values of 7α-thiomethylspirolactone were 27.5 ± 9.3%, 81.3 ± 28.8% and 82.8 ± 28.6% for powder papers, DM-β-CyD and SBE7 solutions, respectively.

The oral absorption of spironolactone by rats was better after administration of spironolactone in SBE7 and DM-β-CyD solutions than after administration as powder papers. Both cyclodextrin formulations enhanced spironolactone bioavailability to a similar extent despite some deacetylation of spironolactone in the presence of SBE7. A reduction of spironolactone dosage would be recommended during clinical studies with premature infants. These results indicate that SBE7 could be a safe and suitable excipient for the solubilization of spironolactone in paediatric formulations.
Ionic-diffusion Potential-dependent Transport of a New Quinolone, Sparfloxacin, Across Rat Intestinal Brush-border Membrane
Authors: Iseki Ken , Hirano Takeshi , Tsuji Kaori , Miyazaki Shozo , Takada Masahiro , Kobayashi Michiya , Sugawara Mitsuru , Miyazaki Katsumi
Published: April 2011

The mechanism of uptake of sparfloxacin, a new quinolone, by intestinal brush-border membrane vesicles was investigated to clarify whether there is a common transport process for new quinolones mediated by the diffusion potential across the intestinal membrane bilayer.

Sparfloxacin was taken up pH-dependently by rat intestinal brush-border membrane vesicles, behaviour analogous to that of organic cations including enoxacin and ciprofloxacin. Transient overshooting uptake of this quinolone was observed in the presence of an outward H+ gradient. Momentary dissipation of the H+ gradient by addition of carbonyl cyanide p-(trifluoromethoxy)phenylhydrazone did not affect the uptake of sparfloxacin, and a marked but incomplete reduction in the H+-sensitive overshooting uptake of sparfloxacin was apparent in the voltage-clamped brush-border membrane vesicles. Furthermore, a valinomycin-induced K+-diffusion potential (interior negative) and an inward Cl—-diffusion potential stimulated the initial uptake of Sparfloxacin at pH 5.5. Sparfloxacin uptake was inhibited by tetracaine and imipramine. The inhibitory effect of these cations correlated well with changes in membrane surface charges induced by the presence of tetracaine or imipramine.

These results indicate that sparfloxacin transport across the brush-border membrane depends upon the inside-negative ionic diffusion potential, that the H+- or K+-diffusion-potential-dependent uptake of sparfloxacin by intestinal brush-border membrane vesicles is affected by the membrane surface potential and that inhibition of sparfloxacin uptake originates from changes in the membrane surface potential caused by the organic cations.
Adenosine Receptor mRNA Levels During Postnatal Renal Maturation in the Rat
Authors: Morton M J , Sivaprasadarao A , Bowmer C J , Yates M S
Published: April 2011

Adenosine may affect the pattern of intrarenal blood flow during renal development. It provides an angiogenic stimulus for the growth of new blood vessels and may be involved in compensatory renal growth. It is therefore of interest to investigate the expression of adenosine receptor genes during postnatal renal development. In the present study this was carried out by measuring adenosine receptor mRNA levels in rats aged between 2 and 60 days.

The order of abundance of adenosine receptor mRNA levels in 60-day-old rats was A2A > A2B ≥ A1 > A3. A1 receptor mRNA levels showed only small changes with increasing age although, by contrast, A3 receptor mRNA increased markedly with age with levels at 60 days twenty-fold greater than at 2 days. A2A receptor mRNA levels declined during renal maturation with transcript numbers four- to fivefold that at 12–18 days compared with numbers at 60 days. By contrast to the A2A receptor, there were no significant changes in the renal levels of A2B receptor mRNA during kidney maturation.

During postnatal renal maturation, the levels of mRNA for A2A and A3 adenosine receptor subtypes undergo marked changes which may be related to functional maturation, morphological development, or both.
Alteration of Activities of Hepatic Antioxidant Defence Enzymes in Developing Chick Embryos After Glucocorticoid Administration - A Factor to Produce Some Adverse Effects?
Authors: Lee Jung Wha , Iwatsuru Motoharu , Nishigori Hideo
Published: April 2011

Liver tissue is one of the principal targets of glucocorticoids, therefore changes in the balance between hepatic oxidative and reductive capacity may greatly influence adverse effects of glucocorticoid therapy. In this study, effects of glucocorticoid on the activities of hepatic antioxidant defence enzymes were examined by using developing chick embryos.

After the administration of 0.25 μmol hydrocortisone sodium succinate, a typical glucocorticoid, to 15-day-old chick embryos, glutathione peroxidase, glutathione reductase, catalase and superoxide dismutase in the liver generally began to decrease at around 4 h, reaching 60–70% of control levels between 24 and 48 h. These changes were observed much earlier than the elevation of the hepatic thiobarbituric acid reacting substance (TBARS) level which began to increase from 20 h, reaching about six times the control level at 48 h after hydrocortisone administration. Conversely, the elevated TBARS level decreased back to the normal level with the recoveries of these enzyme activities. Furthermore, it was found that the aniline hydroxylase activity, measured as a marker of oxidative activity, began to increase after around 12 h.

These results suggested that TBARS levels were possibly produced by the suppression of antioxidant defence abilities and the significant induction of oxidative activity in the liver by glucocorticoid. As the elevated TBARS in the liver can be distributed to tissues, TBARS will be involved in the occurrence of some of the glucocorticoid-induced adverse effects such as cataract formation.
Partial-solubility Parameters of Naproxen and Sodium Diclofenac
Authors: Bustamante Pilar , Peña Ma Angeles , Barra Jerome
Published: April 2011

The expanded Hansen method was tested for determination of the solubility parameters of two non-steroidal anti-inflammatory drugs, naproxen and sodium diclofenac. This work describes for the first time the application of the method to the sodium salt of a drug. The original dependent variable of the expanded Hansen method, involving the activity coefficient of the drug, was compared with the direct use of the logarithm of the mole fraction solubility lnX2 in the solubility models.

The solubility of both drugs was measured in pure solvents of several chemical classes and the activity coefficient was obtained from the molar heat and the temperature of fusion. Differential scanning calorimetry was performed on the original powder and on the solid phase after equilibration with the pure solvents, enabling detection of possible changes of the thermal properties of the solid phase that might change the value of the activity coefficient. The molar heat and temperature of fusion of sodium diclofenac could not be determined because this drug decomposed near the fusion temperature. The best results for both drugs were obtained with the dependent variable lnX2 in association with the four-parameter model which includes the acidic and basic partial-solubility parameters δa and δb instead of the Hansen hydrogen bonding parameter δh. Because the dispersion parameter does not vary greatly from one drug to another, the variation of solubility among solvents is largely a result of the dipolar and hydrogen-bonding parameters, a fact that is being consistently found for other drugs of small molecular weight.

These results support earlier findings with citric acid and paracetamol that the expanded Hansen approach is suitable for determining partial-solubility parameters. The modification introduced in the expanded Hansen method, i.e. the use of lnX2 as the dependent variable, provides better results than the activity coefficient used in the original method. This is advantageous for drugs such as sodium diclofenac for which the ideal solubility cannot be estimated. This paper shows for the first time that the method is suitable for determination of the partial-solubility parameters of a sodium salt of a drug, sodium diclofenac.
First-pass Metabolism of 5-Fluorouracil in Rats
Authors: Yuasa Hiroaki , Gu Jian , Hayashi Yayoi , Watanabe Jun
Published: April 2011

The first-pass metabolism of 5-fluorouracil has been investigated in rats to compare systemic bioavailability after administration by different routes, the bioavailability after intravenous bolus administration being defined as unity.

Bioavailability after oral administration (Fpo) was compared with that after intraintestinal administration into the closed loop (Floop) in conscious rats. Fpo was very low and variable (0.28 ± 0.30, mean ± s.d.), in agreement with earlier studies in man, but comparable with Floop (0.33 ± 0.05), suggesting insignificant loss of 5-fluorouracil by degradation in the gastrointestinal lumen or by faecal excretion. The bioavailability after intraportal vein administration (Fipv) was compared with Floop in rats anaesthetized with pentobarbital, anaesthesia being used to maintain a stable portal drug infusion that mimics the sustained input of drug into the portal blood flow after intra-intestinal administration. Fipv was smaller than unity (0.68 ± 0.03), suggesting significant hepatic first-pass metabolism, but higher than Floop (0.31 ± 0.10), suggesting significant first-pass metabolism in the intestinal mucosa. The intestinal bioavailability for passage through the epithelial mucosa (Fi) was estimated, from the ratio of Floop to Fipv, to be 046.

The study revealed that both the liver and intestinal mucosa are responsible for the extensive first-pass metabolism of 5-fluorouracil after oral administration. This first-pass metabolism might be similar to that in man, in which the oral bioavailability is reportedly similar to that in the rats used in this study. The findings in this study should be of help in monitoring ways of improving oral 5-fluorouracil therapy.
Different Contributions of the Endothelin ETA Receptor to Hypertension Induced by Acute or Chronic Inhibition of Nitric Oxide Synthesis
Authors: Hashimoto Norio , Kuro Toshihiko , Taira Shima , Matsumura Yasuo
Published: April 2011

The effects of FR139317(R)2-[(R)-2-[S)-2-[[1-(hexahydro-1H-azepinyl)]carbonyl] amino-4-methyl-pentanoyl] amino-3-[3-(1-methyl-1H-indoyl)]propionyl]-amino-3-(2-pyridyl)propionic acid), an endothelin ETA receptor antagonist, on systemic and renal haemodynamic responses and excretory responses to chronic or acute nitric oxide (NO) synthase inhibition with NG-nitro-L-arginine (NOARG) have been examined.

An intravenous bolus injection of FR139317 (10 mg kg−1) to chronic NO-deficient hypertensive rats (2.74 mM NOARG in drinking water for 4 weeks) elicited only a slight decrease in mean arterial pressure (MAP), to the same extent as seen in normotensive control rats. Injection of this drug induced no alteration of the renal haemodynamics of this chronic hypertensive model. Urine formation in control rats was significantly reduced by administration of FR139317. No significant decrease in urine formation was observed in the chronic NO-deficient rats. Acute intravenous injection of NOARG (5 mg kg−1) induced a gradual and significant increase in MAP, with a significant decrease in renal blood flow. A slight but insignificant diuretic effect was observed. In animals pretreated with FR139317 (10 mg kg−1 i.v.) NOARG induced a significantly less potent increase in MAP, whereas similar renal haemodynamic responses to NOARG were observed. In contrast to the FR139317-untreated group, urine formation tended to decrease after administration of NOARG. These results suggest that endothelin, via the ETA receptor, contributes to the systemic pressor response to acute NO synthase inhibition, although renal vasoconstriction and functional changes induced by acute NO synthase inhibition are independent of ETA receptor-related effects.

These results imply that action of endothelin via the ETA receptor is not involved in the maintenance of sustained hypertension induced by chronic NO synthase inhibition.
Inhibition of 15-Hydroxyprostaglandin Dehydrogenase Activity in Rabbit Gastric Antral Mucosa by Panaxynol Isolated from Oriental Medicines
Authors: Fujimoto Yohko , Sakuma Satoru , Komatsu Sawako , Sato Daisuke , Nishida Hiroko , Xiao Yong-Qing , Baba Kimiye , Fujita Tadashi
Published: April 2011

Panaxynol is a polyacetylene compound with anti-inflammatory and anti-platelet-aggregatory effects isolated from commonly used oriental medicines. The effects of panaxynol on the activity of prostaglandin-synthesizing and catabolizing enzymes in the rabbit gastric antral mucosa have been examined.

At concentrations ranging from 25 to 200 μM panaxynol had no effect on the synthesis of prostaglandins E2, F2α and D2 from exogenous arachidonic acid in the microsomal fraction of the gastric mucosa whereas at 25–200 μM it dose-dependently inhibited the activity of 15-hydroxyprostaglandin dehydrogenase (PGDH), which catalyses the initial step of prostaglandin catabolism, in the cytosolic fraction. The concentration required for 50% inhibition (IC50) was approximately 25 μM. Inhibition of PGDH by panaxynol was non-competitive with regard to NAD+ and prostaglandin E2.

These results suggest that panaxynol has the potential to inhibit PGDH activity in gastric mucosa, possibly as a result of pharmacological activity.
Pharmacological Properies of Pteleprenine, a Quinoline Alkaloid Extracted from Orixa japonica, on Guinea-pig Ileum and Canine Left Atrium
Authors: Seya Kazuhiko , Miki Izumi , Murata Kiyoshi , Junke Hisae , Motomura Shigeru , Araki Tsutomu , Itoyama Yasuto , Oshima Yoshiteru
Published: April 2011

We have investigated the pharmacological properties of pteleprenine, a quinoline alkaloid, on contractile responses of the guinea-pig ileum and on inotropic responses of the canine left atrium.

Although pteleprenine (0·1–1 μM) had no effect on the contraction of the ileum induced by acetylcholine at 10 μM it significantly inhibited acetylcholine-induced contraction of the ileum. Pteleprenine (0·1–10 μM) reduced nicotine induced-contraction of the ileum in a concentration-dependent manner yet had no maximum relaxant effect even at a concentration of 10 μM From Schild analysis the pA2 of pteleprenine on the guinea-pig ileum was found to be 6-6. The contraction of the ileum induced by 10 μM 1,1-dimethyl-4-phenylpiperazinium, a specific agonist of nicotinic acetylcholine. receptors, was concentration-dependently suppressed by 10 nM-10 μM pteleprenine. In contrast, 0.1–10 μM pteleprenine did not antagonize the acetylcholine- and nicotine-induced negative inotropic contractile responses of the canine left atrium. These results show that pteleprenine has inhibitory action against nicotinic acetylcholine receptors in the guinea-pig ileum but not in the canine left atrium. Our findings also suggest that pteleprenine might be a novel lead compound as a nicotinic receptor antagonist.
Behavioural Pharmacological Characteristics of Honokiol, an Anxiolytic Agent Present in Extracts of Magnolia Bark, Evaluated by an Elevated Plus-maze Test in Mice
Authors: Kuribara Hisashi , Stavinoha William B , Maruyama Yuji
Published: April 2011

Honokiol, a neolignane derivative of Magnolia bark, has central depressant action and, at much lower doses, anxiolytic activity. We have investigated the characteristics of the behavioural effects of honokiol by means of an elevated plus-maze test.

In the plus-maze test a single oral dose of 20 mg kg−1 honokiol significantly prolonged the time spent in the open arms of the maze, suggesting anxiolytic effect. Moreover, when honokiol was administered daily for seven days and the plus-maze test was conducted 3 or 24 h after the last administration, significant prolongation of the time in the open arms was manifested even for doses of 0.2 mg kg−1. The maximum effect was observed for doses of 0.5 mg kg−1. Honokiol at any dose in both single and repeated administration schedules caused neither change in motor activity nor disruption of traction performance. Orally administered diazepam, 0.5–2 mg kg−1, caused dose-dependent prolongation of the time spent in the open arms of the maze with a significant increase in motor activity at 1 mg kg−1, and dose-dependent disruption of traction performance. The changes in the plus-maze performance after treatment for seven days with 0.2 mg kg−1 honokiol and after a single treatment with 1 mg kg−1 diazepam were almost equivalent. The effect of honokiol (0.2 mg kg−1, treatment for seven days) was inhibited by subcutaneous flumazenil (0.3 mg kg−1) and (+)-bicuculline (0.1 mg kg−1) and by intraperitoneal CCK-4 (50 μg kg−1) and caffeine (30 mg kg−1). The anxiolytic effect of diazepam (1 mg kg−1) was also inhibited by flumazenil and bicuculline. However, the combined administration of diazepam with caffeine enhanced the effect, and diazepam completely reversed the effect of CCK-4.

These results suggest that, in contrast with diazepam, honokiol selectively induces an anxiolytic effect with less liability of eliciting motor dysfunction and sedation or dis-inhibition. The combined effects of the drug also revealed that the mechanism of anxiolytic effect of honokiol is partially different from that of diazepam.
THE “PSYCHOLOGICAL INTERPRETATION OF LANGUAGE.”
Authors: HOCART A. M.
Published: April 2011

Current psychological interpretation of the language of savages—Its neglect of the social context—The social factors underlying the presence or absence of linguistic distinctions—The importance of historical factors.
PRINCIPLE OF INDIVIDUATION AND CO‐ORDINATES OF CONDUCT*
Authors: RAVEN J. C.
Published: April 2011

Theories can be of two kinds, ‘disciplines of thought’ or ‘speculative hypotheses’. ‘principle of individuation’ provides a discipline of thought capable of embracing mathematical equation, dimensions of physics, biological interaction between individual and environment, and psychosomatic problems encountered in medicine and in so‐called para‐psychology. It indicates not only lines along which divergent schools of psychological thought and inquiry have developed; it gives order and clarity to various interpretations of conduct suggested, and hypotheses put forward for experimental investigation without which collection of data becomes confused and unproductive. It also gives statistical treatment of quantitative studies their appropriate place and function as a means of determining degree to which any qualities assessed are in fact genuine co‐ordinates of conduct and dimensions of personality.
DISPLAY‐CONTROL RELATIONSHIPS ON CIRCULAR AND LINEAR SCALES
Authors: LOVELESS N. E.
Published: April 2011

variation in tracking performance between different quadrants of a circular scale has been shown to be attributable mainly to ambiguity of display‐control relationships on this scale, in that motion of pointer may be viewed as either rotary or translatory. dominant tendency is to view it as rotary, a clockwise control movement being associated with a clockwise pointer movement; but there is a significant secondary tendency to view it as translatory, a clockwise control movement being associated with a displacement of pointer upwards or to right, according to quadrant in which target lies. two tendencies conflict when target is in lower and right‐hand quadrants, where performance is consequently poorer. Performance is also affected by position in visual field as such.

It has been verified that a clockwise control movement is expected to send pointer to right on a horizontal linear scale and upward on a vertical linear scale. Performance on horizontal scale is no better than that obtained on circular scale under optimal conditions, but unambiguity of linear scale renders it preferable where erroneous reactions are to be avoided.
COGNITIVE INFERENCE IN PERCEPTUAL ACTIVITY
Authors: VERNON M. D.
Published: April 2011

Whenever sensory data are scanty or ambiguous, or incongruities occur in perceptual situation, observers tend to employ processes of inferential thinking to arrive at satisfactory identifications., Such inferential thinking also appears when observer is called upon to make accurate judgements about events which ordinarily might not be closely observed. In making inferences, observers utilize schematically organized knowledge and tendencies to react which they have acquired, either through experiences which are common to everyone as they grow up, or as result of particular individual experiences and training. Thus some inferences and judgements are closely similar in different individuals, while others show marked individual differences. Evidence supporting this thesis is given in examples drawn from everyday life and from experimental investigations.
AN EXPERIMENTAL INVESTIGATION OF SEWING‐MACHINE SKILL
Authors: SINGLETON W. T.
Published: April 2011

An attempt was made to measure transfer effects which occur when receptor or effector modes of an element of sewing skill are changed. pre‐transfer task required operation of an industrial sewing machine for about twenty years. Under these conditions no transfer was detected. It is concluded that this particular skill is dependent on utilization of particular receptor and effector modes with which it was originally acquired. It is suggested that transfer experiments are not likely to be fruitful unless learning is controlled and, in case of motor skills, adequate attention is paid to way in which peripheral system is being utilized.
ON SOME PSYCHOPHYSICAL TECHNIQUES EMPLOYING A SINGLE MANIPULANDUM
Authors: WEISKRANTZ LAWRENCE
Published: April 2011

Four techniques are described which permit single bar‐press apparatus to be used for generation of psychophysical functions. Bate of response is a useful dependent variable for measuring strength of behaviour associated with negative stimulus in two of methods. When a warning signal is introduced with discrete negative and positive stimuli, situation becomes logically akin to traditional infra‐human psychophysical procedures. Bate of response is then no longer useful as a variable, but because any given response does not alter animal's geographical position, bar‐pressing situation offers certain advantages over traditional procedures. These advantages are incorporated in two remaining techniques described.
PREDICTION OF EXAMINATION MARKS OF MECHANICAL ENGINEERING STUDENTS AT KING'S COLLEGE, NEWCASTLE
Authors: GARSIDE R. F.
Published: April 2011

correlation coefficients between examination marks of 108 University engineering students and various predictors are given. It is concluded that School Certificate, G.C.E. (Advanced Level) or Higher National Certificate (A1) results provide best prediction of engineering marks.
SHAPE RECOGNITION IN RATS
Authors: DODWELL P. C.
Published: April 2011

Reasons are given for doubting whether certain of Lashley's experiments, purporting to be investigations of shape discriminations, really are such. In particular his finding concerning square‐circle discrimination cannot be held to lend support to Deutsch's theory of shape recognition. An experiment is reported which shows that rats can discriminate square from circle under certain conditions of pre‐training, and do so under these conditions by responding to horizontal base of square; response is transferred to other shapes having a horizontal base, but not to shapes lacking it. There is some evidence to show that this happens for small shapes‐where Deutsch's system could be operative‐and this is therefore evidence against his theory. A theory of shape recognition is proposed of same logical type as Deutsch's, which accounts for results here reported, accords well with other known characteristics of shape recognition in primitive visual systems, and presents less difficulties than Deutsch's system as a possible neurological model.
INDIVIDUAL DIFFERENCES IN INTENTIONAL AND INCIDENTAL LEARNING
Authors: PLENDBRLEITH MAVIS , POSTMAN LEO
Published: April 2011

This study investigates the role of linguistic habits in the intentional and incidental learning of verbal materials. Linguistic habits determine the differential responses made to the stimulus materials during practice. The stronger the differential responses evoked by the stimulus items the better they are recalled. Similarly, individual differences in amount of recall reflect variations in the strength (conventionality) of differential responses. These relationships are more pronounced when learning is incidental than when it is intentional, and also are stronger with nonsense than with meaningful learning materials.
RUBELLA DEAF CHILDREN: A RORSCHACH STUDY EMPLOYING MUNROE INSPECTION TECHNIQUE*
Authors: BINDON D. MAKJORIR
Published: April 2011

With procedure altered to eliminate the deaf subjects' language handicap, the Rorschach test treated by the Munroe Inspection Technique was given to three matched groups of 16‐year‐old children: (a) thirty‐six rubella deaf, (b) fifteen born deaf through causes other than maternal rubella, or who had gone deaf before the age of two, and (c) thirty non‐deaf. All quantitative and qualitative results for both deaf groups were strikingly similar: neither cause of deafness, degree of deafness nor the residential factor was found to have had any collateral influence on their performances (P > 0.1 in all cases). A criterion score of >2 statistically selected Munroe checklist entries differentiated both deaf groups from the hearing group (P < 0.001 in both cases). It is contended that the rigid personality pattern found to be common to the deaf is not abnormal, but subnormal (immature or undeveloped). It is contended also that their arrested personality maturation is relatively permanent and is not so much due to deafness itself, as to its consequences—a retardation in normal language development which has hindered the process of socialization, and hence full personality development.
PREVIOUS KNOWLEDGE AND MEMORY
Authors: POULTON E. C.
Published: April 2011

This paper is concerned: (a) with the relationship between previous knowledge and memory, (b), with differences between recall and recognition, and (c) with set for time of memory test while learning. Subjects listened to 144 short statements, half of which were true and half false. They had to rate each statement on a five‐point scale for certainty of their truth or falsehood. A test of memory was then carried out for half of the statements, and another test was given a week later for the other half. In each test, half the statements had to be completed (recall), and each of the remaining statements had to be discriminated from a paired statement which resembled it in a standard way (recognition). While rating the statements, half the subjects did not expect a test of memory at all, a quarter were led to expect an immediate test, and the remaining quarter were led to expect a test in a week. After the first test of memory, no subjects were led to expect a second test. A control group of subjects took a test of ‘memory’ without hearing the statements.

It was found that a subject was more likely to be certain that a false statement was false, than that a true statement was true. For both true and false statements, memory was best for statements about whose truth the subject was certain, and worst for statements about whose truth he had no idea. The control subject was much less successful than the experimental subject, but tended to score on the same statements. Previous knowledge can thus assist both genuine memory and also guess‐work.

With memory for a particular word as a criterion, there was no difference between recall and two‐choice recognition when the word was in a statement about whose truth the subject was certain and correct, and memory was tested almost immediately. But recognition was more successful than recall when the word was in a statement about whose truth the subject had no idea, or when memory was tested after a week, although differences were only significant in the latter case.

Recognition was found to be a less sensitive measure of previous knowledge than recall. Success in recognition was determined to a considerable extent by factors intrinsic to the test of recognition. Part of the reduced sensitivity of recognition was attributed to this cause.

Immediate memory was best when a test of memory was expected immediately, and worst when no test was expected, but the differences were not significant. If anything, the trend for memory after a week was in the reverse direction.
MEASURES OF SUBJECTIVE PROBABILITY
Authors: COHEN JOHN , DEARNALEY E. J. , HANSEL C. E. M.
Published: April 2011

The question, which arose in an earlier investigation, of the transposability of estimates made on different ranges (‘out of five’, ‘out of ten’, etc.) is subjected to experiment. The degree of transposability is found to be a function of age.
FACTORS AFFECTING INDUCTIVE PREDICTIONS
Authors: GREEN R. T.
Published: April 2011

Two guessing tasks which appear highly similar in nature nevertheless evoke opposite trends in predictive behaviour. Attempts to generate both sets of results from the same simple principles fail because of the different implicit assumptions the subject makes about the nature of the task. It would seem that one of the assumptions that the subject tends to make when required to employ inductive reasoning, at least in the laboratory situation, is that a certain amount of stimulus variability is to be expected.

The theoretical implications are that, far from being contradictory or mutually exclusive, the gestalt and behaviourist accounts of the learning process are complementary. Only by recognizing that some aspects of the learning process are continuous while other aspects are discrete and that both S–R learning at an unverbalized level and conscious hypothesis testing go on side by side, is it possible to make sense of the more complex type of learning situation where a temporal pattern is involved.

An attempt to analyse pre‐solution guessing behaviour tends to favour a non‐continuous hypothesis, but in certain respects the question is still open to a more sophisticated interpretation.