bluuebunny/crossref_metadata_2025 huggingface dataset:
Synthesis of Novel Derivatives of Aroylaminoalcohols and 3-Amino-substituted 1-Phenylpropanols with Potential Anti-inflammatory and Immunomodulating Activities
Authors: Gavalas Antonis M , Hadjipetrou Lygeri , Kourounakis Panos N
Published: April 2011

The synthesis of aroylaminoalcohols and 3-amino-substituted 1-phenylpropanols is described. These novel basic compounds have potent anti-inflammatory activity, significantly inhibiting rat paw oedema induced by a variety of phlogistic agents as a result of the release of inflammatory mediators such as histamine, 5-hydroxytryptamine, kinins, prostaglandins or leukotrienes.

The biological activity of a selected, representative number of these compounds was examined on adjuvant-induced arthritis, a good animal model for rheumatoid arthritis in man. The results show that 3-(1-hydroxymethylpropylamino)-1-phenylpropan-1-one hydrochloride (2) and 3-(3-hydroxypiperidin-1-yl)-1-phenylpropan-1-one hydrochloride (4) effectively suppress the secondary lesions of adjuvant arthritis. 2-(3-Hydroxy-3-phenylpropylamino)-butan-1-ol hydrochloride (6) had no preventive activity in this animal model. In addition, several of the compounds suppressed the mitogenic responses of T-lymphocytes to concanavalin A, suggesting direct or indirect action on lymphocytes and therefore possible immunosuppressive properties. Finally, we investigated the in-vitro effects of compounds 2 and 4 on production of interleukins 1 and 2 (IL-1 and IL-2). We found that compound 4 suppressed the in-vitro production or action of IL-2 and IL-1. In contrast, compound 2 significantly increased the IL-1 activity of arthritic macrophages while reducing the ability of normal and arthritic splenocytes to produce or release IL-2.

Our data suggest that compounds 2 and 4 have immunomodulatory properties that influence T lymphocyte functions.
Mathematical Modelling of Drug Transport in Emulsion Systems
Authors: Yoon Kyung Ae , Burgess Diane J
Published: April 2011

Two mathematical models for the prediction of drug transport in triphasic (oil, water and micellar) emulsion systems as a function of micellar concentration have been developed and these models were evaluated by comparing experimental and simulated data. Fick’s first law was used to derive a transport model for hydrophilic drugs, assuming that the oil/water (o/w) partitioning process was fast compared with membrane transport and therefore drug transport was limited by the membrane. Consequetive rate equations were used to model transport of hydrophobic drugs in emulsion systems assuming that the o/w interface acts as a barrier to drug transport.

Benzoic acid and phenol were selected as hydrophilic model drugs. Phenylazoaniline and benzocaine were selected as hydrophobic model drugs. Transport studies at pH 3.0 and 7.0 were conducted using side-by-side diffusion cells. According to the hydrophilic model, an increase in micellar concentration is expected to decrease drug transport rates. The effective permeability coefficients (Peff) of drugs were calculated using an equation relating Peff and the total apparent volume of drug distribution (determined experimentally using drug/membrane permeability and partition coefficient values). The hydrophobic model was fitted to the experimental data for the cumulative amount of model drug in the receiver cells using a weighted least-squares estimation program (PCNONLIN). The oil/continuous phase partitioning rates (k1) and the membrane transport rates (k2) were estimated.

The goodness of fit was assessed from the correlation coefficients of plots of predicted versus experimental data. The predicted data were consistent with the experimental data for both the hydrophilic and hydrophobic models.
In-vivo Calibration of Microdialysis Probe by Use of Endogenous Glucose as an Internal Recovery Marker: Measurement of Skin Distribution of Tranilast in Rats
Authors: Hashimoto Yoshitaka , Murakami Teruo , Kumasa Chinami , Higashi Yutaka , Yata Noboru , Takano Mikihisa
Published: April 2011

To estimate the absolute concentration of substrates surrounding a microdialysis probe in-vivo, we developed a simple calibration method using endogenous glucose as an internal recovery marker and determined the skin distribution of tranilast (N-(3,4-dimethoxycinnamoyl)anthranic acid), an anti-allergic agent, in rats.

This calibration method was based on the assumption that the concentration of glucose in the extracellular fluid of skin tissues is the same as that in plasma and that the in-vivo recovery ratio of glucose to tranilast by microdialysis is the same as that estimated in-vitro. Based on these assumptions, the dialysate concentrations of tranilast and glucose recovered from cutaneous microdialysis, glucose concentration in plasma, and in-vitro recovery ratio of tranilast to glucose by microdialysis were determined for the estimation of absolute unbound concentration of tranilast in the extracellular fluid of skin tissues. In an in-vitro study employing plasma containing tranilast, the unbound concentration of tranilast in plasma estimated from the dialysate concentration was just comparable with that determined by ultrafiltration methods. Also in an in-vivo study under steady-state plasma concentration of tranilast in rats, the estimated concentration of tranilast in the skin extracellular fluid was the same level as the unbound concentration of tranilast in plasma. Using the present calibration method, the skin distribution of tranilast administered into the intestinal loop or transdermally was continuously monitored in a quantitative manner.
Influence of Nimodipine on Vasoconstrictor Responses Hindquarters Vascular Bed of the Cat
Authors: Champion Hunter C , Kadowitz Philip J
Published: April 2011

The beneficial effects of the calcium-entry blocking agent, nimodipine, on the cerebral circulation have been extensively studied but less is known about its peripheral vascular effects. In the present study, the effects of nimodipine on vasoconstrictor responses were investigated in the hindquarters vascular bed of the cat under constant-flow conditions.

Nimodipine decreased hindquarters vascular resistance and inhibited vasoconstrictor responses to BAY K8644 (methyl-1,4-dihydro-2,6-dimethyl-3-nitro-4-(2-trifluoromethyl-phenyl)-pyridine-phenyl)-pyridine-5-carboxylate) and noradrenaline, to the α1-adrenoceptor agonists phenylephrine and methoxamine, and the α2-adrenoceptor agonists BHT 933 (2-amino-6-ethyl-4,5,7,8-tetrahydro-6H-oxazolo[5,4-d]azepine dihydrochloride) and UK 14304 (5-bromo-6-(2-imidazoline-2-yl-amino)quinoxaline). In addition to inhibiting α-adreno-ceptor-mediated responses, nimodipine decreased responses to the vasoactive peptides angiotensin II and endothelin-1. Both the vasodilatory actions and inhibitory effects of nimodipine on vasoconstrictor responses were dose-dependent when the calcium antagonist was infused at rates of 0.1 and 1 μg min−1. The results of the present study suggest that vasoconstrictor responses to α-adrenoceptor agonists and to the vasoactive peptides are dependent, in part, on an extracellular source of calcium.

It is concluded that nimodipine and related dihydropyridine calcium-entry blocking agents may be effective in the treatment of peripheral vascular disorders in which adrenergic tone is increased or plasma levels of angiotensin II or endothelin-1 are elevated.
Tocolytic Effect of the Cyclooxygenase-2 Inhibitor, Meloxicam: Studies on Uterine Contractions in the Rat
Authors: Yousif Mariam H , Thulesius Olav
Published: April 2011

The objective of this study was to assess the tocolytic activity of meloxicam, a novel cyclooxygenase-2 inhibitor, in a comparative study with the non-steroidal anti-inflammatory drug, indomethacin.

The in-vitro tocolytic effect of meloxicam and indomethacin (10−9-10−5M) was evaluated on spontaneously-contracting uterine strips from non-pregnant rats and from rats at various stages of pregnancy. The rhythmic motility of the strips was reproducibly maintained over several hours. The effect of drugs was evaluated from the extent of inhibition of the frequency and amplitude of contractions. Both indomethacin and meloxicam induced dose-dependent inhibitory effects, with meloxicam being slightly more potent in all groups studied, particularly in early pregnancy.

These results suggest that meloxicam, which has fewer side-effects than cyclooxygenase-1 inhibitors, could be a potentially useful tocolytic agent in the treatment of premature labour.
Determination of Trace Lithium in Human Erythrocytes by Electrothermal Atomic-absorption Spectrometry with Pyrocoated Graphite Tubes and Integrated Platform
Authors: Decosterd L A , Buclin T , Dafflon M , Leeman C , Bélaz N , Magnin J-L , Biollaz J
Published: April 2011

Electrothermal graphite-furnace atomic-absorption spectroscopy with pyrocoated graphite tubes, integrated platform and matrix modification was used to determine submicromolar concentrations of trace lithium in human red blood cells.

Matrix-matched samples were used to establish calibration curves for concentrations up to 0.58 μM. (addition-calibration method) with satisfactory linearity (r2 > 0.99) and intra-and inter-day variability (CV < 11.4%). The median concentration of trace lithium in the cells of 40 healthy Caucasian volunteers devoid of medical or psychiatric history was 0.23 μM (inter-quartile range 0.20–0.30). The levels of trace lithium in the red blood cells correlated (r2 = 0.83) with plasma concentrations (median 0.13 μM, inter-quartile range 0.11–0.19) measured in the same blood sample. Dietary factors (e.g. consumption of lithium-containing mineral water) affected both levels. The red blood cell/plasma lithium ratio had a median value of 1.57 (inter-quartile range 1.16–2.07), implying that trace lithium is accumulated in erythrocytes. This contrasts with most reports of red blood cell/plasma ratio, measured during therapeutic treatment with lithium, for which the average value is 0.5–0.8, albeit for much higher concentrations of lithium (approx. 500–800 μM).

The proposed analytical method has the required sensitivity and accuracy for determination of trace lithium in red blood cells and makes it possible to perform epidemiological studies to assess human exposure to environmental lithium in diet and beverages, and inter-individual variations in trans-membrane and renal lithium kinetics at the submicromolar level.
Multiple Human Cytochromes Contribute to Biotransformation of Dextromethorphan In-vitro: Role of CYP2C9, CYP2C19, CYP2D6, and CYP3A
Authors: von Moltke Lisa L , Greenblatt David J , Grassi Jeffrey M , Granda Brian W , Venkatakrishnan Karthik , Schmider Jürgen , Harmatz Jerold S , Shader Richard I
Published: April 2011

Cytochromes mediating the biotransformation of dextromethorphan to dextrorphan and 3-methoxymorphinan, its principal metabolites in man, have been studied by use of liver microsomes and microsomes containing individual cytochromes expressed by cDNA-transfected human lymphoblastoid cells.

In-vitro formation of dextrorphan from dextromethorphan by liver microsomes was mediated principally by a high-affinity enzyme (Km (substrate concentration producing maximum reaction velocity) 3–13 μM). Formation of dextrorphan from 25 μM dextromethorphan was strongly inhibited by quinidine (IC50 (concentration resulting in 50% inhibition) = 0.37 μm); inhibition by sulphaphenazole was approximately 18% and omeprazole and ketoconazole had minimal effect. Dextrorphan was formed from dextromethorphan by microsomes from cDNA-transfected lymphoblastoid cells expressing CYP2C9, −2C19, and −2D6 but not by those expressing CYP1A2, −2E1 or −3A4. Despite the low in-vivo abundance of CYP2D6, this cytochrome was identified as the dominant enzyme mediating dextrorphan formation at substrate concentrations below 10 μM. Formation of 3-methoxy-morphinan from dextromethorphan in liver microsomes proceeded with a mean Km of 259 μM. For formation of 3-methoxymorphinan from 25 μM dextromethorphan the IC50 for ketoconazole was 1.15 μM; sulphaphenazole, omeprazole and quinidine had little effect. 3-Methoxymorphinan was formed by microsomes from cDNA-transfected lymphoblastoid cells expressing CYP2C9, −2C19, −2D6, and −3A4, but not by those expressing CYP1A2 or −2E1. CYP2C19 had the highest affinity (Km = 49 μM) whereas CYP3A4 had the lowest (Km = 1155 μM). Relative abundances of the four cytochromes were determined in liver microsomes by use of the relative activity factor approach. After adjustment for relative abundance, CYP3A4 was identified as the dominant enzyme mediating 3-methoxymorphinan formation from dextromethorphan, although CYP2C9 and −2C19 were estimated to contribute to 3-methoxymorphinan formation, particularly at low substrate concentrations.

Although formation of dextrorphan from dextromethorphan appears to be sufficiently specific to be used as an in-vitro or in-vivo index reaction for profiling of CYP2D6 activity, the findings raise questions about the specificity of 3-methoxymorphinan formation as an index of CYP3A activity.
Differential Efficacy of Vasodilators in Hypercholesterolaemic Rabbits
Authors: Rozsa Zsuzsanna , Pataricza Janos , Nemeth Jozsef , Papp Julius Gy
Published: April 2011

The effects of hypercholesterolaemia on the endothelium-dependent and -independent vascular reactivity of the superior mesenteric artery has been examined in anaesthetized rabbits in-vivo. Rabbits were fed with either standard or cholesterol-enriched diet for 24 weeks. Plasma lipids and changes in the endothelin content of plasma and vascular tissue were measured in the superior mesenteric artery and in the thoracic aorta. The functional severity of atherosclerosis was determined by examining vascular responses in the isolated thoracic aorta. The blood flow in the superior mesenteric artery was measured by transit-time flowmetry and drugs were injected through an intra-abdominal aortic catheter.

Acetylcholine (5, 10, 20 μg kg−1) elicited dose-dependent, mesenteric vasodilation in normocholesterolaemic rabbits. In hypercholesterolaemic animals the response to acetylcholine was completely abolished and even became a vasoconstriction. Endothelin levels in plasma and in the vascular tissue were significantly elevated in hypercholesterolaemic animals compared with controls. Cromakalim at a dose of 3 μg kg−1, elicited similar mesenteric vasodilation in hypercholesterolaemic and normocholesterolaemic animals.

These experiments show that the endothelium-dependent responses of the superior mesenteric artery to acetylcholine are functionally impaired by prolonged hypercholesterolaemia, that this altered vascular reactivity is associated with the elevation of endothelin levels in the circulation and in vascular tissues, and that in hypercholesterolaemia the mesenteric vasodilator effect of the K+-channel opener cromakalim is entirely preserved, suggesting that severe hypercholesterolaemia does not depress the function of ATP-sensitive potassium channels in mesenteric vascular smooth muscle.
Anti-inflammatory Effects of South American Tanacetum vulgare
Authors: Schinella Guillermo R , Giner Rosa-María , Recio MaríA Del Carmen , de Buschiazzo Perla Mordujovich , Ríos José-luis , Máñez Salvador
Published: April 2011

In recent years the role of phenolic compounds and sesquiterpene lactones, particularly parthenolide, in the anti-migraine and anti-inflammatory effects of Tanacetum parthenium (Asteraceae) has attracted much attention. However, the closely-related cosmopolitan species T. vulgare has remained outside the mainstream of research in this field.

After treating the aerial parts of T. vulgare with dichloromethane and methanol, and applying conventional column and thin-layer chromatographic techniques, it was possible to isolate from the moderately lipophilic fractions the principles responsible for the anti-inflammatory activity of this plant against the mouse-ear oedema induced by 12-O-tetradecanoylphorbol 13-acetate. These were identified by ultraviolet and nuclear magnetic resonance spectroscopy as parthenolide (93% oedema inhibition at 0.5 mg/ear, ID50 (dose of drug inhibiting the oedema by 50%) = 0.18 μmol/ear) and the methoxyflavones jaceosidin (80% oedema inhibition at 0.5 mg/ear, ID50 = 0.50 μmol/ear), eupatorin, chrysoeriol and diosmetin.

Because in molar terms the potency of parthenolide was nearly three times greater than that of the most active of the flavones and because it is obtained from the plant in considerably larger amounts, the flavonoids must only be partially responsible, and to a minor extent, for the observed in-vivo anti-inflammatory local effect.
Poly(acrylamide-co-monoethyl Itaconate) Hydrog Devices for Cytarabine Release in Rats
Authors: Gomez C , Blanco M D , Bernardo M V , Sastre R L , Teijón J M
Published: April 2011

This study has tested the application of three different copolymeric poly(acrylamide-comonoethyl itaconate; A/MEI) hydrogels, 90A/10MEI, 75A/25MEI and 60A/40MEI, on the release of cytarabine (ara-C).

The drug was incorporated in gels by placing it in the polymerization feed mixture and discs loaded with 5–50 mg ara-C were obtained. The amount of swelling at equilibrium in saline solution (NaCl, 0.9% w/w) was between 78 and 82% w/w, depending on the composition of the copolymer. The diffusion studies followed Fick’s second law. The diffusion coefficients for swelling of the gels were between 9.30 times 10−11 m2 s−1 and 37.42 times 10−11 m2 s−1; those for release of ara-C were between 3.42 times 10−11 m2 s−1 and 10.25 times 10−11 m2 s−1. The activation energies for swelling were in the range 16.60± 2.59-21.85± 1.78 kJ mol−1; those for ara-C release were 28.13±3.1–29.7±4.6 kJ mol−1. To determine the applicability of these copolymers, 75A/25MEI gel was subcutaneously implanted in rats and the plasma concentration of the drug was determined by high-performance liquid chromatography. The concentration of ara-C in plasma (range 17.67±5.68-10.76±2.15 μg mL−1) was maintained during the first stages (2–8 h) and no drug was detected after 32 h. This route of administration was compared with intraperitoneal injection of the drug.

In conclusion, ara-C can be incorporated in hydrogels and released in a pharmacologically active form. The concentration of ara-C in plasma is maintained for long enough to improve therapeutic results.
Resistance to Densification, Tensile Strength and Capsule-filling Performance of some Pharmaceutical Diluents
Authors: Nikolakakis I , Aragon O Ballesteros , Malamataris S
Published: April 2011

The purpose of this study was to compare some indicators of capsule-filling performance, as measured by tapped density under different conditions, and elucidate possible quantitative relationships between variation of capsule fill-weight (%CV) and gravitational and inter-particle forces (attractive or frictional) derived from measurements of particle size, true density, low compression and tensile strength. Five common pharmaceutical diluents (lactose, maize starch, talc, Emcocel and Avicel) were investigated and two capsule-filling methods (pouring powder and dosator nozzle) were employed.

It was found that for the pouring-type method the appropriateness of Hausner’s ratio (HR), Carr’s compressibility index (CC%) and Kawakita’s constant (α) as indicators of capsule fill-weight variation decreases in the order α > CC% > HR; the appropriateness of these indicators also decreases with increasing cylinder size and with impact velocity during tapping. For the dosator-type method the appropriateness of the indicators decreases in the order HR > CC% > α, the opposite of that for the pouring-type method; the appropriateness of the indicators increases with decreasing cylinder size and impact velocity. The relationship between %CV and the ratio of inter-particle attractive to gravitational forces calculated from measurements of particle size and true density (Fvdw/Wp) was more significant for the pouring-type capsule-filling method. For the dosator-type method a significant relationship (1% level) was found between %CV and the product of Fvdw/Wp and a function expressing the increase, with packing density (pf), in the ratio of frictional to attractive inter-particle forces derived from compression (P) and tensile-strength (T) testing, d(log(P/T))/d(pf).

The value of tapped density in predictions of capsule-filling performance is affected by the testing conditions in a manner depending on the filling method applied. For the pouring-type method predictions can be based on the ratio of attractive (inter-particle) to gravitational forces, whereas for the dosator-type method the contribution of frictional and attractive forces should, because of packing density change, also be taken into account.
Acid-catalysed Hydrolysis and Benzodiazepine-like Properties of 5-(Dialkylamino)- and 5-(Alkylthio)-substituted 8-Chloro-6-phenyl-6H-[1,2,4]triazolo[4,3-a][l,5]benzodiazepines in Mice
Authors: Caccia Silvio , Grossi Giancarlo , Fracasso Claudia , Nacca Angelo , Cagnotto Alfredo , Mennini Tiziana , Ghia Marco , Roma Giorgio
Published: April 2011

The in-vitro and in-vivo hydrolysis of two benzodiazepine compounds has been studied to evaluate their in-vivo activity in mice.

Compounds RL 218 and RL 236, selected as representative examples of N,N-dialkyl-8-chloro-6-phenyl-6H-[1,2,4]triazolo[4,3-a][1,5]benzodiazepin-5-amines (1) and of their 5-(alkylthio) substituted analogues (2), were rapidly hydrolysed to the corresponding 8-chloro-6-phenyl-4H-[1,2,4]triazolo[4,3-a][1,5]benzodiazepin-5(6H)-one 3 (RL 214) in aqueous acidic solution at pH 1.5. This reaction also occurred extensively in mice when compounds RL 218 and RL 236 were given orally but not intraperitoneally. Both compounds were active against pentylenetetrazole-induced lethal convulsions in mice only when administered orally. After administration of pharmacologically effective oral doses (ED50, the dose protecting 50% of mice), at the time of assessment of the antipentylenetetrazole activity, mean brain concentrations of RL 218 and RL 236 were below the limits of sensitivity of the analytical procedure whereas brain concentrations of their metabolite RL 214 were comparable with that present after an oral equiactive dose of this compound itself. RL 214 but not RL 218 or RL 236 had in-vitro affinity for brain benzodiazepine receptors.

These results indicate that the anticonvulsant activity of RL 218 and RL 236 in mice depends essentially on their in-vivo transformation into the common active metabolite RL 214 which most probably arises as a result of acid catalysed hydrolysis in the gastric juice.
Transepithelial Transport of Large Particles in Rat: a New Model for the Quantitative Study of Particle Uptake
Authors: Limpanussorn J , Simon L , Dayan A D
Published: April 2011

The transport of large particles across the intestinal mucosa and the mechanisms of transfer of the particles into the body are still little understood.

Fluorescent polystyrene latex particles (2 μm diam.) were administered orally to young male Sprague-Dawley rats in doses of 2.33 times 103, 2.33 times 106 and 2.33 times 109 particles. After 60 min, Peyer’s patches and Peyer’s patch-free tissues were collected from the small intestine and colon. A novel technique was used to exclude non-translocated particles adherent to the mucosal surface; the intestinal epithelium was stripped from the intestine by immersion in Hanks’ balanced salt solution containing 1.5 mM EDTA. Particles in solubilized samples of intact and epithelium-stripped Peyer’s patches and Peyer’s patch-free intestinal tissue and colon were quantified by fluorescence microscopy. The location of particles within the intact and epithelium-stripped gut samples was revealed by confocal microscopy. Particles were shown to have been taken up along the entire length of the small and large intestines via both Peyer’s patches and the normal intestinal epithelium. The number of particles detected in the distal region was greater than in the proximal part of the small intestine, although the difference was not statistically significant.

This study has revealed that large numbers of non-translocated particles adhered to the mucosal surface resulting in a high background count. The assay system was considerably improved by the epithelium-stripping technique. The process of transepithelial uptake is a potentially important route of uptake of toxic, immunologically active and radioactive substances. These particles are much larger than the conventionally accepted upper limit for absorbed materials.
Influence of Ammonium Chloride on the Tissue Distribution of Anticholinergic Drugs in Rats
Authors: Ishizaki Junko , Yokogawa Koichi , Nakashima Emi , Ohkuma Shoji , Ichimura Fujio
Published: April 2011

Ammonium chloride (NH4***C1) increases lysosomal pH and thereby abolishes intralysosomal accumulation of drugs. Its effect on the tissue distribution of biperiden and trihexyphenidyl in rats has been investigated.

The tissue-plasma concentration ratios (Kp) of these drugs in various tissues were determined by infusion studies at steady-state in the presence or absence of NH4***C1. Treatment with NH4***C1 reduced the Kp values for both drugs, causing the largest reduction in Kp in the lung (52.1 to 11.8 for biperiden and 59.5 to 18.9 for trihexyphenidyl; ratios of decrease 0.77 and 0.68, respectively), followed by the heart and kidneys, with relatively small reductions in the brain, gut, muscle and fat. Subcellular fractionation studies in the lung indicated that the subcellular fraction-plasma concentration ratio of each drug at the steady state (Kp,sf) was reduced by treatment with NH4***C1, with the largest decrease in the post-nuclear fraction (ratio of decrease 0.82 for biperiden and 0.74 for trihexyphenidyl), followed by the nucleus, microsomes and supernatant, in that order. A strong correlation was found between the ratio of decrease in Kp,sf after NH4***Cl treatment and the specific activity of acid phosphatases, a marker of lysosomes, in each fraction (biperiden, r = 0.948; trihexyphenidyl, r = 0.945).

These results suggest that acidic organelles contribute significantly to the distribution kinetics of anticholinergic drugs.
Possibility of Partial Absorption of Nicardipine by Routes Other Than the Hepato-portal System After Oral Administration in Rats
Authors: Mizumura Junko , Watari Nobutoshi , Higuchi Shigesada
Published: April 2011

The systemic availability of nicardipine after different routes of administration has been examined in rats, with particular attention to differentiating oral absorption from intestinal and hepatic metabolism. The quantities of nicardipine and its metabolite were determined by capillary column gas chromatography.

A linear relationship was shown between the hepatic first-pass effect and dose after hepato-portal administration of nicardipine; the hepatic first-pass effect was calculated to be approximately 80%. However, the availability after oral and rectal administration was found to be more than twice that observed after hepato-portal administration. Partial avoidance of the hepatic first-pass effect after oral and rectal administration are estimated to be 37.3% and 35.2%, respectively, assuming that all absorbed molecules pass through the liver.

These findings suggest that the absorption of nicardipine after oral administration also occurs by routes other than the hepato-portal system.
In-vitro Characterization of YM872, a Selective, Potent and Highly Water-soluble α-Amino-3-hydroxy-5-methylisoxazole-4- propionate Receptor Antagonist
Authors: Kohara Atsuyuki , Okada Masamichi , Tsutsumi Rie , Ohno Kazushige , Takahashi Masayasu , Shimizu-Sasamata Masao , Shishikura Jun-Ichi , Inami Hiroshi , Sakamoto Shuichi , Yamaguchi Tokio
Published: April 2011

The in-vitro pharmacological properties of (2,3-dioxo-7-(1H-imidazol-***1-yl)-6-nitro-1,2,3,4-tetrahydro-1-quinoxalinyl)-acetic acid monohydrate, YM872, a novel and highly water-soluble α-amino-3-hydroxy-5-methylisoxazole-4-propionate (AMPA)-receptor antagonist were investigated.

YM872 is highly water soluble (83 mg mL−1 in Britton-Robinson buffer) compared with 2,3-dihydroxy-6-nitro-7-sulphamoyl-benzo(F)quinoxaline (NBQX), 6-(1H-imidazol-1-yl)-7-nitro-2,3(1H,4H)-quinoxalinedione hydrochloride (YM90K) or 6-cyano-7-nitroquinoxa-line-2,3-dione (CNQX). YM872 potently inhibits [3H]AMPA binding with a Ki (apparent equilibrium dissociation constant) value of 0.096 ± 0.0024 μM. However, YM872 had very low affinity for other ionotropic glutamate receptors, as measured by competition with [3H]kainate (high-affinity kainate binding site, concentration resulting in half the maximum inhibition (IC50) = 4.6 ± 0.14 μm), [3H]glutamate (N-methyl-D-aspartate (NMDA) receptor glutamate binding site, IC50 > 100 μM) and [3H]glycine (NMDA receptor glycine-binding site, IC50 > 100 μM). YM872 competitively antagonized kainate-induced currents in Xenopus laevis oocytes which express rat AMPA receptors, with a pA2 value of 6.97 ± 0.01. In rat hippocampal primary cultures, YM872 blocked a 20-μM AMPA-induced increase of intracellular Ca2+ concentration with an IC50 value of 0.82 ± 0.031 μM, and blocked 300-μM kainate-induced neurotoxicity with an IC50 value of 1.02 μM.

These results show that YM872 is a potent and highly water-soluble AMPA antagonist with great potential for treatment of neurodegenerative disorders such as stroke.
An Investigation of the Actions of the Essential oils of Manuka (Leptospermum scoparium) and Kanuka (Kunzea ericoides), Myrtaceae on Guinea-pig Smooth Muscle
Authors: Lis-Balchin Maria , Hart S L
Published: April 2011

The two New Zealand tea-tree oils, Manuka (Leptospermum scoparium J.R. et G. Forst) and Kanuka (Kunzea ericoides (A. Rich) J. Thompson), Myrtaceae have been used as folk medicines for treating diarrhoea, colds and inflammation but their pharmacological action has not been investigated. Their mode of action was therefore studied on the field-stimulated guinea-pig ileum.

Both Manuka and Kanuka oils induced a spasmolytic effect but Kanuka produced an initial contraction. The spasmolytic action of both oils was the result of a post-synaptic mechanism. Action involving adrenoceptors or cGMP was not considered likely, neither did the oils behave like calcium- or potassium-channel openers. There is some evidence that Manuka acts through cAMP whereas the mode of action of Kanuka is as yet undetermined.

The results indicate that the use of these oils as relaxants in aromatherapy might be valid, although their mode of action is not identical.
Nepetalactone: A New Opioid Analgesic from Nepeta caesarea Boiss.
Authors: Aydin Süleyman , Beis Rana , Öztürk Yusuf , Hüsnü K , Baser C
Published: April 2011

The essential oils of Nepeta species including Nepeta phyllochlamys P. H. Davis, N. nuda L. ssp. nuda, and N. caesarea Boiss. have been screened by use of the tail-flick and tail immersion (52.5°C) methods.

Of the species studied, only N. caesarea showed significant analgesic activity, besides marked sedation, which was also blocked by naloxone, indicating involvement of opioid receptors. Moreover, it was only active on mechanical, not thermal, algesic response which suggests specificity for specific opioid receptor subtypes, excluding μ-opioid receptors.

Because 4aα,7α,7aα-nepetalactone is the main component of the essential oil of N. caesarea, and is present at very high levels (92–95%), it is concluded that 4aα,7α,7aα-nepetalactone is the active principle and has a specific opioid receptor subtype agonistic activity.
THE LIMITS OF GENETIC AND OF COMPARATIVE PSYCHOLOGY1
Authors: CALKINS MARY WHITON
Published: April 2011

Synopsis.

The distinction between these two branches of Psychology.

Genetic Psychology, incompatible with the Humian position, presupposes as its ‘unit’ the conscious self. This involves distinguishing psychical development from biological. Individual and social factors of developing consciousness.

The initial problem of Comparative Psychology is to determine the criterion of consciousness. The ‘continuity theory’ maintains that life implies consciousness; the ‘mechanistic theory’ denies consciousness in organisms whose actions are unvaried reflexes. So far as they differ neither theory proves its own thesis or refutes that of its opponent: both agree in recognising consciousness where there are adapted reactions.

A survey of the relevant facts known shows that the scope of comparative psychology is after all as wide as animal life.

The problem of the nature of animal consciousness at different stages: in the minimal form of consciousness clearly ascertained, where truth and error generate the habit of purposeful reaction, imagination is implied. But even the higher animals seem only to react to concrete situations which they very imperfectly analyse. The question how far there is a social factor in animal development can only be settled when we have an objective test of true imitation.

Child psychology: the comparative method alone applicable to infancy: later the child's own introspection may supplement the study of its thoughts, imitations, and self‐assertiveness.
AFFECT IN THE DREAM
Authors: RIVERS W. H. R.
Published: April 2011

Affect in the dream and the concept of censorship. The nightmare as a failure of wish‐fulfilment; character of affect due to this failure; partial failure and degrees of unpleasant affect. Infantile character of nightmare. Influence on affect of mental level action in the dream.
SOME CHARACTERISTICS OF GOOD JUDGES OF OTHERS*
Authors: TAFT RONALD
Published: April 2011

A group of forty subjects, undergoing a ‘living‐in’ assessment programme, were tested on their ability to make accurate analytic judgements about their peers. This ability was found to correlate positively with certain background variables such as urban origin, previous working experience, none or few siblings, being a student in natural sciences (versus social science), and certain cognitive abilities. good judges, as opposed to poor ones, tended to be stable, serious and socially passive persons, task oriented and socially detached. No relationship was found between ability to judge others and artistic ability, ability to play roles, sociability, femininity or ability to judge self. findings are explained in terms of a special ability, availability of appropriate judgemental frames of reference, and presence of motivation towards making objective social judgements. good judges are typically extraceptive and poor judges intraceptive.
LISTENING BETWEEN AND DURING PRACTISED AUDITORY DISTRACTIONS
Authors: BROADBENT D. E.
Published: April 2011

Subjects were instructed to answer a rapid series of questions, and during series a buzzer was sometimes sounded. Some subjects were instructed to make a reaction to this buzzer; this produced an interference with speech task, both at instant of buzz and also between buzzes. latter interference was reduced by previous practice at buzzer reaction, but former was not.

If buzzer was one of two possible signals for a two‐choice reaction, interference at moment of buzz was greater, suggesting that situation is most easily described in terms of information theory. But previous practice in this case causes subject to perform secondary task in a way which requires less information and so interferes less. effect of practice in’ automatizing’ a task is thus real, but has important limitations.
USE OF EEG IN STUDY OF IMAGERY
Authors: BARRATT P. E.
Published: April 2011

An experiment was designed to test hypothesis that suppression of amplitude of alpha rhythm provides a reliable objective index of visual imagery under two conditions of problem solution, namely, solving a ‘verbal’ problem and solving a ‘visual’ problem. Sixty‐nine subjects were examined in following way: first, preliminary ‘runs’ were made with each subject for EEG recording under conditions (a) eyes‐shut, relaxed and (b) eyes‐open, relaxed, yielding base lines for comparison; secondly, EEG recordings were made under conditions (a) concurrently with solution of ‘verbal‐reasoning’ problem and (b) concurrently with solution of ‘visual‐reasoning’ problem.

It was found that, although visual content of awareness during two problem‐solution periods as reported by subjects differed markedly, suppression of alpha rhythms occurred under both conditions, amplitudes in both cases falling about half‐way between two values recorded in preliminary ‘runs’. There was, however, a greater suppression effect in case of the’ visual’ problem. results, as a whole, therefore, suggest that hypothesis is not tenable, since ‘imagery’ appears to be only one of many factors that may produce suppression effects. This conclusion is supported by a breakdown of subject sample, according to reports of imagery on verbal problem, which showed that there was no difference in basic patterns as between those who visualized verbal problem and those who did not.

Repeated solution in a check period, immediately following solution period, made no significant difference to suppression of alpha in verbal problem, but did so in visual problem. suggested interpretation follows Fisher (1916) in regarding this as a possible decrease in image content.
A NOTE ON SCALE PRODUCT AND RELATED METHODS OF SCORING ATTITUDE SCALES
Authors: BUTCHER H. J.
Published: April 2011

Attitude scales constructed by Thurstone's method of equal‐appearing intervals may also be scored by Thurstone's method or by Likert's or by a combination of two. Some possible advantages of a combined method are described.

Three variants of such a combined method are distinguished, and their characteristics discussed. In case of two of these, no evidence is found to show that they possess any advantage over Likert's method of scoring, and some evidence seems to indicate that they do not. For third (Scale Product method of Eysenck & Crown, 1949), higher reliability is claimed by its authors, but insufficient information is available about details of method for this claim to be tested.
THE ROLE OF PAST EXPERIENCE IN APPARENT MOVEMENT: A REVALUATION
Authors: TOCH HANS H. , ITTELSON WILLIAM H.
Published: April 2011

An attempt is made to provide a theoretical framework within which data concerning effect of stimulus connotations on perceived movement might be evaluated. Jones's & Bruner's (1954) results, and those of our own study, have been examined in this context.

In both cases, it was possible to demonstrate that loading through meaning, to be effective, had to be compatible with generalized past experiences with movement, or (from a structuralist viewpoint) with physiological mechanisms underlying movement perception.

Jones's & Bruner's failure to obtain satisfactory positive results could thus be regarded as due to their underestimation of determinants underlying stroboscopie movement as such. Similarly, successful loading with an adaptation of von Schiller's paradigm could be anticipated, given fact that equipotential movement alternatives were provided. extent of phenomenal results of loading through connotation was assumed to provide a measure of influence of relevant past experiences.
ASSESSMENT OF ANXIETY AS AN INTERVENING VARIABLE IN DELINQUENT BEHAVIOUR OF M.D. SUBJECTS. GALVANIC SKIN RESPONSE AND LEG‐PERSISTENCE INDICES
Authors: TONG JOHN E.
Published: April 2011

Anxiety is accepted as a stimulus‐produoing response or learnable drive to which certain delinquent behaviour is conditioned by drive reduction, and relationship between fear, anxiety and pain resistance is discussed. leg‐persistence test is regarded as a pain‐resistance test and is shown to be correlated with galvanic skin response fear reactivity. Persistence scores are shown to vary amongst delinquents according to hypothetical degree of stress engendered by their previous misbehaviour and current hospital confinement. High anxiety (low persistence) subjects are found to be more unstable than others; age and intelligence to have no bearing upon scores, but psychotic involvement to alter distributions markedly. data are discussed in terms of behaviour theory and Eysenck typology.
PERSONALITY AND PERCEPTION: CONSTANCY EFFECT AND INTROVERSION
Authors: ARDIS J. AMOE , FRASER ELIZABETH
Published: April 2011

An investigation of relationship between shape constancy and introversion‐extroversion was carried out, using as subjects twenty‐four first‐year Psychology students of Aberdeen University; twelve introverts and twelve extroverts, selected on basis of Minnesota TSE scale. Results showed (a) that introverts showed lower constancy effect than extroverts and (b) that there was a tendency for men to show greater constancy effect than women.

There was also some suggestion of presence of a learning factor in perceptual process which also distinguished introverts from extroverts. These results are discussed in light of previous investigations. Hypotheses, which are shortly to be tested, and which might account for findings, are advanced.
THE QUALITATIVE INVESTIGATION OF INTELLIGENCE
Authors: McCOLSKEY ANN SHEDDEN
Published: April 2011

A battery of seven intellectual tasks, designed for the qualitative examination of intelligence, was administered to thirty‐five (experimental) children of superior ability and thirty‐five (control) children of average ability, matched for age and other variables, and selected by a set of multiple criteria, including teachers' opinions, grades, and intelligence and achievement tests.

Under the conditions of this study, superior intelligence was characterized, with significant frequency, by a variety of qualities, including: coherence and productivity of informal thought processes; a facility for abstracting conceptual principles as against ‘situation‐bound’ responses; conceptual flexibility; perseverance and independence of structure (or aid) in complex problems; attentiveness and spontaneous perception of incongruities. It is felt that this approach to intelligence can ultimately produce a more fertile, inductive quantification, in dimensional terms.
THE EFFECTS OF INCENTIVES ON THE PERFORMANCE OF DEFECTIVE IMBECILES
Authors: WALTON D. , BEGG T. L.
Published: April 2011

The present experiment was designed to inquire into the effects of different incentive conditions on the performance of male imbeciles. In particular the aim was to clarify further the effect of goal‐striving and encouragement on performance in uncontaminated experimental groups. The experiment was suggested, first, because the previous results in the field had been equivocal, and secondly, since inquiry into the trainability of imbeciles had been encouraging. The latter results suggested how imperative it was to determine the best incentive conditions to be employed in any experimental workshop in which such work was being undertaken.

Forty‐eight imbeciles were used. On the basis of their first performance on the Leg Persistence Test they were divided into four matched groups of 12 subjects each and asked to perform under different motivating conditions. There were four incentive conditions used—‘Control’, ‘Goal’, ‘Competition’ and ‘Encouragement’. The experiment continued at the rate of one trial per day over twenty trials. As far as possible each of the four groups was tested on the same day for the equivalent trial number. The four groups were also found to be closely matched on the basis of intelligence.

There can be little doubt that incentives improve the performance of imbeciles on a dull routine task. In contrast, under conditions of indifference their performance deteriorates. No support was gained for Gordon's contention that imbeciles respond to goal conditions of motivation better than when encouraged. In the present study competition and encouragement appear to be the best conditions of motivation.
A PATTERN RECOGNITION METHOD OF LEARNING MORSE CODE
Authors: ALLAN M. D.
Published: April 2011

This study is concerned with a comparison between the traditional ‘analytic’ method of learning the morse code, and a ‘Gestalt’ approach called the Pattern Recognition method. The Pattern Recognition technique consists of transmitting characters right from the start at a speed corresponding to 20 words per minute. There is no preliminary memorizing of the alphabet. All the pupils have to do is to listen to the whole character (i.e. a letter or a number) transmitted at 20 words per minute and, when the instructor has written its meaning on the blackboard, to copy it down. This sort of drill is continued until all the 36 characters (26 letters and 10. numerals) are instantly recognized by their distinctive sound patterns. The pilot experiment showed that pupils trained by the Pattern Recognition method had a significantly better knowledge of the alphabet, after the same amount of training, than pupils trained analytically. As an applied technique in a short intensive course, the Pattern Recognition method produced significantly fewer unsatisfactory pupils during the training period. In a long course, where pupils practised at whatever speed they were capable, pupils trained by the Pattern Recognition method arrived at high speeds earlier than those trained analytically.
THE DEVELOPMENT OF INDEPENDENT MUSCULAR CONTROL OF SEPARATE EYELIDS IN TWO RACIAL GROUPS, EUROPEAN AND POLYNESIAN
Authors: SUTTON P. R. N.
Published: April 2011

The ability to control separate eyelids independently (‘the voluntary winking ability’) is studied in 527 subjects of European stock and in 262 Polynesians, with the following results: (1) In both groups, there is a significant correlation between voluntary winking ability and age. (2) Winking ability of the males is not significantly greater than that of the females. (3) In children under 10 years of age, the incidence of non‐winking is significantly higher than in the remaining subjects. (4) In the European group, but not in the Polynesian, the incidence of those who could wink both eyes readily and with approximately equal facility is significantly lower in those who are 10 years and under, than in subjects over 10. (5) In those subjects of European stock who could wink one eye only or could wink one eye more easily than the other, a preponderance of the use of the left eye for winking is found. This is mainly due to the preference for winking the left eye which is seen in those who are under 10 years. However, in the Polynesians there is no significant difference between the frequency of winking each eye.
THE EFFECT OF SET ON ACCURACY OF AUDITORY PERCEPTION
Authors: TALLAND GEORGE A.
Published: April 2011

Two complementary experiments are reported which compare the facilitatory effects of (a) sets established in various ways, and (b) different conditions of confirmation, on accurate recognition of words presented aurally, and on systematic distortion of words incongruent with the set.

Sets, whether explicitly established by instruction, or implicitly arrived at from cues embedded in the test material, significantly increase the incidence of accurate perception. The presence of incongruent stimuli does not noticeably reduce the facilitatory effect of a set, not even when confirmation is considerably delayed. Wide spacing of confirmatory stimuli is least conducive to the maintenance of a set.

While one set is in operation, and facilitates veridical perception, another set is unlikely to develop, even though conditions for its emergence are furnished by the stimulus material. However, if an initially established and subsequently confirmed set ceases to facilitate correct perception, it will be replaced by another appropriate set; more rapidly if only some of the words presented were congruent with it, more gradually if all were confirmatory.

Explicit sets elicit the highest incidence of distortion in accordance with expectancy, more particularly if confirmation is delayed or intermittent.

In facilitating accurate perception, double sets are less effective than single sets, whether all stimuli are confirmatory or some are incongruent. The differential effect cannot be attributed to the heterogeneous composition of the stimulus material, nor is it manifested in a manner consistent with a model of reciprocal inhibition exerted by the two sets on one another. The results agree with an inhibitory theory of set according to which sets operate by raising the thresholds of perception for all that is incongruent. The relative lowering of thresholds for the congruent would thus be a secondary effect, as distinct from the hypothetical neural model which accounts for this psychological law in terms of short‐circuiting of pathways.