bluuebunny/crossref_metadata_2025_split huggingface dataset:
Manganese Ions Induce Tonic Contraction after Relaxation in a High-K+ Medium in Ileal Longitudinal Smooth Muscle of Guinea-pig
Authors: Nasu T , Murase H , Shibata H 
Published: April 2011

Abstract
In ileal longitudinal muscle 5Mm Mn2+ inhibited completely the K+ (60 Mm)-induced tonic tension to the base line; however, the tension progressively increased to above the level of original tonic response evoked by K+ after 3 h in the presence of Mn2+. Tetrodotoxin (5 × 10−5 m) had no influence on the tension development in the presence of Mn2+ in the high-K+ medium. Mn2+ also increased the tension in a high-K+, Ca2+-free medium. The Ca2+ antagonist, gallopamil (10−6 m) inhibited the development of tension in the presence of Mn2+ in the high-K+ medium. The 45Ca uptake determined by the lanthanum method remained unchanged from control levels after 3 h of the 5 Mm Mn2+ application in the high-K+ medium in spite of the development of the tension. The manganese uptake in the high-K+ medium, increased in accordance with the increase of duration of 5 Mm Mn2+ application. Gallopamil inhibited manganese uptake in the high-K+ medium. These results suggest that Mn2+ firstly reduces K+-induced tension by inhibition of Ca2+ influx; subsequently, Mn2+ ions accumulate in the intracellular compartments through voltage-operated Ca2+ channels and may activate contractile proteins in the ileal muscle.
Effect of Aminoethylpyrroles on Carrageenan-induced Inflammation and on Lipid Peroxidation in Rats: Some Structural Aspects
Authors: Demopoulos Vassilis J , Rekka Eleni 
Published: April 2011

Abstract
Nine 3-(2-aminoethyl)pyrrole derivatives were investigated as anti-inflammatory agents in the carrageenan-induced rat paw oedema model and as antioxidants in the non-enzymatic lipid peroxidation assay. It was found that the derivatives which were substituted with a p-toluenesulphonyl group exhibited considerable anti-inflammatory activity and some also showed antioxidant properties. However, the presence of a p-toluenesulphonyl group did not invariably lead to activity. A structural feature which was essential for both activities was the aminoethyl side chain. Although a relationship between the antiinflammatory and the antioxidant activities was not apparent, the combination of these properties could be useful.
Effects of In-vivo Administration of Taurine and HEPES on the Inflammatory Response in Rats
Authors: Stapleton Philip P , Mahon Tara M , Nowlan Peter , Bloomfield Frederick J 
Published: April 2011

Abstract
The effect of in-vivo administration of N-2-hydroxyethylpiperazine-N’-2-ethane sulphonic acid (HEPES) and taurine on rat paw oedema and reactive oxidant production was examined. Carrageenan-induced paw oedema was attenuated following intraperitoneal injection of HEPES. Chemiluminescence production by isolated peripheral blood mononuclear cells (PBMC) was reduced in HEPES-treated rats. Taurine-treated rats did not exhibit attenuation of paw oedema using subcutaneous or intraperitoneal administration but intracerebroventricular administration produced a significant reduction at a dosage of 4·0 μmol. No reduction in chemiluminescence production was observed by PBMC using subcutaneous or intraperitoneal administration of taurine, but intracerebroventricular administration produced a significant reduction at a dosage of both 0·4 and 4·0 μmol. Intravenous injection of [14C]HEPES or [3H]taurine demonstrated rapid clearance with a significantly longer half-life of HEPES compared with taurine. These results support previous reports of anti-inflammatory activity of taurine when administered centrally. The lack of anti-inflammatory effect when taurine was administered subcutaneously or intraperitoneally may be a consequence of rapid distribution or clearance. The greater anti-inflammatory effects of HEPES compared with taurine may be due to its slower distribution or clearance in-vivo.
Binding Potency of 6-Nitroquipazine Analogues for the 5-Hydroxytryptamine Reuptake Complex
Authors: Mathis Chester A , Taylor Scott E , Enas Joel D , Akgün Eyup 
Published: April 2011

Abstract
The in-vitro inhibition constants (Ki) of nine structural analogues of the potent 5-hydroxytryptamine (5-HT)-uptake inhibitor, 6-nitroquipazine, were determined to assess the structure-affinity relationship of these derivatives. The goal of these studies was to determine those positions on 6-nitroquipazine that could be derivatized without significantly decreasing the affinity of the drug for the binding site, so that radiolabels such as 123I, 76Br or 18F might be appended for in-vivo imaging studies of the 5-HT reuptake system. Using bromine as a steric probe, the rank order of potency of bromine-substituted 6-nitroquipazine analogues for inhibiting the binding of [3H]paroxetine to the 5-HT reuptake binding site was: 8-&lt;3-&lt;7-&lt;4-&lt;5-bromo. The in-vitro equipotent molar ratio (EPMR, Ki (analogue)/Ki(6-nitroquipazine)) of the 5-bromo analogue was 0·57, indicating that this analogue had greater affinity for the 5-HT reuptake complex than 6-nitroquipazine. Derivatization at the 5-position with fluorine and iodine also resulted in potent compounds with EPMR values of 1·1 and 0·83, respectively. Substitution of quipazine with bromo, cyano, and formyl groups at the 6-position produced less potent compounds than the 6-nitro group. Based upon the high affinities of the 5-bromo-, 5-fluoro- and 5-iodo-6-nitroquipazines for the 5-HT reuptake complex, these compounds are candidates for radiolabelling for in-vivo studies of the 5-HT reuptake site.
Analgesic Effects of Callus Culture Extracts from Selected Species of Phyllanthus in Mice
Authors: Santos Adair R S , Filho Valdir C , Niero Rivaldo , Viana Ana M , Moreno Fabio N , Campos Maria M , Yunes Rosendo A , Calixto Joóo B 
Published: April 2011

Abstract
The aim of this study was to evaluate the analgesic effect of the methanolic extract from callus culture of Phyllanthus tenellus, P. corcovadensis and P. niruri in several models of pain in mice. The extracts (medium containing 2,4-dichlorophenoxyacetic acid) of P. corcovadensis, P. niruri and P. tenellus (3–90 mg kg−1, i.p.) caused graded inhibition of abdominal constrictions induced by acetic acid (0·6%), with ID50 (i.e. dose that reduced response of control by 50%) values of about 30, 19 and &gt;30 mg kg−1, respectively. The extract of callus of Phyllanthus obtained in indole-3-butyric acid and indole-3-acetic acid media (3–90 mg kg−1, i.p.) caused a similar analgesic effect. In the formalin test, the extract of P. tenellus obtained in indole butyric acid medium (3–100 mg kg−1, i.p.) inhibited only the second phase of formalin-induced pain with an ID50 value of about 100 mg kg−1. Both the indole acetic acid and indole butyric acid methanolic extracts of P. tenellus and P. corcovadensis (10–100 mg kg−1, i.p.) dose-dependently inhibited both phases of formalin-induced pain (ID50 values for the second phase were approx. 100 and 52 mg kg−1, respectively). However, the extract of callus from Phyllanthus failed to affect formalin-induced paw oedema, as well as the response to radiant heat in the tail-flick test. In addition, the analgesic effect of morphine, but not the analgesic effects caused by Phyllanthus callus extract, was fully antagonized by naloxone. Preliminary phytochemical analysis revealed the presence of several compounds having no apparent relationship with alkaloids or flavonoids but showing the presence of phenols. These results indicate that, similar to previous reported data from the extract of P. corcovadensis, the methanolic extracts of callus culture of P. niruri, P. corcovadensis and P. tenellus exhibit potent analgesic properties against neurogenic and inflammatory pain that seem to be unrelated to the activation of opioid mechanisms.
Properties of the binding sites of [3H]9-methyl-7-bromoeudistomin D in bovine aortic smooth muscle microsomes
Authors: Adachi Masatoshi , Fang Yano-Il , Yamakuni Toru , Kobayashi Junichi , Ohizumi Yasushi 
Published: April 2011

Abstract
[3H]9-Methyl-7-bromoeudistomin D ([3H]MBED), a powerful caffeine-like Ca2+ releaser, binds to the caffeine binding site of terminal cisternae of skeletal muscle sarcoplasmic reticulum and activates Ca2+-induced Ca2+ release. Properties of the binding site of [3H]MBED were investigated in aortic smooth muscle. The specific activity was higher in microsomes than in other fractions. [3H]MBED binding sites in smooth muscle microsomes were of a single class with a high affinity (KD 50 Nm), comparable with that in skeletal muscle sarcoplasmic reticulum. Caffeine competitively inhibited [3H]MBED binding, indicating MBED shares the same binding site with caffeine. Solubilization and fractionation of the microsomes gave two fractions of [3H]MBED binding activities. These results suggest that, in smooth muscle, there are multiple binding sites of [3H]MBED and caffeine, which might correspond to different pharmacological actions of caffeine on smooth muscle. Therefore, [3H]MBED, which binds to the different binding sites of caffeine, is useful as a probe for investigation of the actions of caffeine at the molecular level.
Casein as a Carrier Matrix for 5-Fluorouracil: Drug Release from Microspheres, Drug-protein Conjugates and In-vivo Degradation of Microspheres in Rat Muscle
Authors: Latha M S , Jayakrishnan A , Rathinam K , Mohanty M 
Published: April 2011

Abstract
Glutaraldehyde cross-linked casein microspheres were loaded with 5-fluorouracil (5-FU) from concentrated aqueous solutions of the drug after the microspheres were synthesized and cleaned. In-vitro release of the drug was examined in phosphate buffer in the absence and in the presence of protease at 37°C. Drug release data showed that only about 20% of the drug is released in the absence of protease even after 5 days, while digestion of the matrix with protease released the entrapped drug completely in about 24 h. A protein-drug conjugate was synthesized via carbamoyl linkage using 6-(5-FU-1-yl)hexyl isocyanate and the drug release was examined in phosphate buffer at 37°C. Release from the protein-5-FU conjugate was slower compared with the release from microspheres in the presence of protease. Implantation of placebo microspheres of different cross-linking densities in the gluteal muscle of rats showed no adverse tissue reactions over a one-year period. Histopathological examination of the tissues containing injected microspheres suggested that the biological life of casein microspheres in muscle is about 6 months, which is three times that of cross-linked albumin microspheres.
In-vivo and In-vitro Targeting of a Murine Sarcoma by Gelatin Microparticles Loaded with a Glycan (PS1)
Authors: Lou Yan , Groves Michael J , Klegerman Melvin E 
Published: April 2011

Abstract
PS1, a complex polysaccharide derived from Mycobacterium bovis (Bacillus Calmette-Guérin, BCG) with considerable antitumour activity in-vivo, was loaded onto gelatin microparticles (mean diam. 1·45 μm) at a level shown to not produce the burst effect often seen with drug-loaded micro-particulate systems. In-vitro dissolution experiments had demonstrated a sustained-release behaviour, with a half-life of approximately 8 h for what is an extremely water-soluble material. These PS1/gelatin systems had no measurable cytotoxicity against an S180 murine sarcoma cell in-vitro although fibronectin-mediated targeting of the microparticles for the tumour cells could be demonstrated. Injection into mice, with the S180 cells, of PS1 solutions or suspensions of PS1-loaded gelatin microparticles resulted in almost identical dose-related suppression for the tumour cell growth. When injected at intervals following injection of the tumour cells, however, for a period of 24–48 h there was a relatively enhanced activity of the formulated PS1, compared with the aqueous solution, after which both formulated and unformulated material became progressively less effective.
Absorption of Organic Anions as Model Drugs Following Application to Rat Liver Surface In-vivo
Authors: Nishida Koyo , Sato Norihito , Sasaki Hitoshi , Nakamura Junzo 
Published: April 2011

Abstract
Absorption of organic anions (phenol red, bromphenol blue and bromosulphonphthalein) has been studied after their application to rat liver surface in-vivo, employing a cylindrical glass cell (i.d. 9 mm, area 0·64 cm2). Each drug appeared gradually in the blood with the peak level at about 1 h, after which its concentration declined slowly. Absorbed model drug was efficiently excreted into the bile. These observations appear to indicate the possibility of drug absorption from liver surface membrane. Absorption of model drugs was estimated to be more than 59% in 6 h. The biliary recovery and metabolism of phenol red did not change as compared with that after intravenous administration.
Liposome and Multiple Emulsion Formulations Augment the Anticalcifying Efficacy of Phosphocitrate in a Cutaneous Calcergy Model
Authors: Kamperman Harold , Sallis John D 
Published: April 2011

Abstract
The anticalcifying agent phosphocitrate was incorporated into phosphatidylcholine/cholesterol liposomes by reverse-phase evaporation. The compound was entrapped to the extent of 11.6% (mol mol−1 of lipid) and the liposomes exhibited prolonged retention of the compound when incubated with rat plasma.
Phosphocitrate's ionic contribution in solution adversely influenced the encapsulation efficiency but improvements were made through ion-pairing with the quaternary ammonium detergent cetrimide, or with the inclusion of stearylamine in the lipid phase. The liposomal dose that could be practically administered in-vivo was restricted to 2.5 mg phosphocitrate kg−1 day−1. The formulation of a multiple emulsion preparation of phosphocitrate, however, offered an alternative delivery mode permitting infrequent dosing to be successfully investigated. In a rat calcergy model, both vehicles effectively reduced the formation of induced subcutaneous calcified plaques at doses for which the phosphocitrate salt alone was inactive.
The current formulations demonstrate that the therapeutic efficacy of phosphocitrate can be markedly improved through an appropriately designed drug delivery system, signalling a new approach for the future therapeutic application of this compound.
Liposome-incorporated Dexamethasone Palmitate Inhibits In-vitro Lymphocyte Response to Mitogen
Authors: Benameur H , Latour N , Schandene L , Van Vooren J P , Flamion B , Legros F J 
Published: April 2011

Abstract
The use of liposomes for the pulmonary delivery of corticosteroid is an area that is under active investigation. We have recently developed a novel liposomal corticosteroid preparation based on the incorporation of dexamethasone palmitate (DMP) within the bilayer of small unilamellar vesicles (SUVs) made of egg yolk phosphatidylcholine (EPC) and cholesterol; molar ratio EPCC: cholesterol: DMP, 4:3:0.3.
In the present study, the biological activity of DMP-SUVs was evaluated using the lymphocyte transformation test with peripheral blood mononuclear cells (PBMCs) and a δ-interferon production assay. Results showed that DMP-SUVs (but not empty SUVs) inhibited [3H]thymidine uptake and δ-interferon production by concanavalin A-stimulated PBMCs by 94 and 96%, respectively, at a concentration corresponding to 10−6 M dexamethasone. The inhibition by DMP-SUVs was found to require a 24-h pre-incubation with unstimulated PBMCs, suggesting that interaction of SUVs with lymphocytes may be altered by mitogen stimulation.
We conclude that our DMP liposomal preparation is biologically active and may be considered a promising alternative to conventional local glucocorticoid therapy.
Effects of Chronic Nitric Oxide Synthase Inhibition on TNB-induced Colitis in Rats
Authors: Pfeiffer C J , Qiu B S 
Published: April 2011

Abstract
Nitric oxide (NO) synthesis is increased in ulcerative colitis, but the role of NO in colitis is poorly understood. The present study employed NW-nitro-L-arginine methyl ester (L-NAME), a nitric oxide synthase inhibitor, in rats to evaluate the effect of NO on 2,4,6-trinitrobenzenesulphonic acid (TNB)-induced colitis.
L-NAME solutions were placed in subcutaneous, osmotic mini-pumps which continuously released L-NAME at 0.042, 0.208, 0.417, or 1.667mgkg−1 h−1. L-NAME dose-dependently enhanced lesions in TNB-induced colitis. The two higher doses of L-NAME significantly increased colonic mucosal damage, although there was slight, nonsignificant reduced lesion formation with the lowest dose of L-NAME, 0.042 mgkg−1 h−1. A single dose of L-NAME at 100 mgkg−1 subcutaneously injected daily in TNB-treated rats also increased lesions, and these ulcerogenic actions of L-NAME were reversed by L-arginine but not by D-arginine (both at 500mgkg−1, s.c). Only the highest dose of L-NAME (mini-pump) significantly depressed myeloperoxidase (MPO) activity. Faecal occult bleeding showed a close relationship with severity of colitis.
These findings suggest that there may exist a balance between NO protective and aggressive effects. In TNB-induced colitis, antagonism of endogenous NO generation was intensified, whereas slight inhibition of NO synthesis reduced lesions. Variations in responses, related to timing or dose changes in L-NAME, may reflect the differences in inducible vs constitutive NO synthase isoforms.
Comparison of Behavioural Effects of Repeated Treatment with Methamphetamine plus Scopolamine and Methamphetamine Alone on Behavioural Sensitization and Conditioned Response
Authors: Yui Kunio , Miura Takao , Sugiyama Kimihito , Ono Mamoru , Nagase Moriharu 
Published: April 2011

Abstract
We investigated how repeated treatments with methamphetamine (4.0mgkg−1, i.p.) plus scopolamine (0.5mgkg−1, i.p.) and methamphetamine alone effected behavioural sensitization and conditioned response in rats.
Repeated methamphetamine plus scopolamine treatment induced a more progressive and enduring enhancement of focused stereotyped behaviour than repeated methamphetamine treatment. Stereotyped behaviour induced by methamphetamine plus scopolamine was reproduced by challenge injections of methamphetamine plus scopolamine, methamphetamine, and to a lesser extent by scopolamine challenges.
The methamphetamine plus scopolamine-sensitized rats were conditioned to a low frequency tone (300 Hz, 100 dB) associated with the drug state. They exhibited a conditioned response to pairings of the tone (conditioned stimulus) and placebo injections. However, they did not respond to the tone alone or the placebo injections alone.
The methamphetamine-sensitized rats failed to demonstrate any conditioning; only the repeated methamphetamine plus scopolamine treatment induced sensitization to the drug-associated tone. Pairings of exteroceptive conditioned stimulus-interoceptive unconditioned stimulus associations may provide an important source for conditioning to the tone associated with the drug state.
We conclude that behavioural sensitization may operate via a reciprocal balance between the dopaminergic and cholinergic inhibitory systems, in favour of a dopaminergic dominance. Conditioning to the drug-associated tone may be mediated via a reciprocal balance between the two transmitter systems.
857-860Anti-inflammatory Effect of Magnolol, Isolated from Magnolia officinalis, on A23187-induced Pleurisy in Mice
Authors: Wang Jih-Pyang , Ho Tsing-Fen , Chang Ling-Chu , Chen Chien-Chih 
Published: April 2011

Abstract
In the present study, A23187-induced pleurisy in mice was used to investigate the anti-inflammatory effect of magnolol, a phenolic compound isolated from Chinese medicine Hou p'u (cortex of Magnolia officinalis).
A23187-induced protein leakage was reduced by magnolol (10mgkg−1, i.p.), indomethacin (10mgkg−1, i.p.) and BW755C (30mgkg−1, i.p.). A23187-induced polymorphonuclear (PMN) leucocyte infiltration in the pleural cavity was suppressed by magnolol and BW755C, while enhanced by indomethacin. Like BW755C, magnolol reduced both prostaglandin E2 (PGE2) and leukotriene B4 (LTB4) levels in the pleural fluid of A23187-induced pleurisy, while indomethacin reduced PGE2 but increased LTB4 formation. In the rat isolated peripheral neutrophil suspension, magnolol (3.7 μM) and BW755C (10 μM) also suppressed the A23187-induced thromboxane B2 (TXB2) and LTB4 formation.
These results suggest that magnolol, like BW755C, might be a dual cyclo-oxygenase and lipoxygenase inhibitor. The inhibitory effect of magnolol on the A23187-induced pleurisy is proposed to be, at least partly, dependent on the reduction of the formation of eicosanoids mediators in the inflammatory site.
Esters of L-Dopa: Structure-hydrolysis Relationships and Ability to Induce Circling Behaviour in an Experimental Model of Hemiparkinsonism
Authors: Brunner-Guenat Michele , Carrupt Pierre-Alain , Lisa Giuseppe , Testa Bernard , Rose Sarah , Thomas Kerrie , Jenner Peter , Ventura Paolo 
Published: April 2011

Abstract
A number of carboxylate esters of L-dopa, some of which are novel, were examined for their physicochemical and biological properties. A few esters of tyrosine and phenylalanine were included for comparison.
The compounds displayed great differences in their lipophilicity and stability towards chemical and enzymatic (human plasma) hydrolysis. Within subseries, relationships exist between structural properties and rate constants of chemical or enzymatic hydrolysis. In an experimental model of hemiparkinsonism (circling behaviour in rats), some of the L-dopa esters (the isopropyl, sec-butyl and 2-(tetrahydropyr-anyl)methyl esters) showed an activity distinctly greater than that of L-dopa, although the difference was not statistically significant.
Cytotoxicity, Cell Cycle Kinetics and Morphonuclear-induced Effects of Vinca Alkaloid Anticancer Agents
Authors: Pauwels Olivier , Kiss Robert , Pasteels Jean-Lambert , Atassi Ghanem 
Published: April 2011

Abstract
The effects of four Vinca alkaloids (vinblastine, vincristine, vindesine and vinorelbine) on three neoplastic cell lines (the MXT mouse mammary cell line and the T24 and J82 bladder cell lines) were studied at three biological levels, i.e. cell proliferation, cell cycle kinetics and morphonuclear characteristics. These effects were studied by means of digital cell image analysis on Feulgen-stained nuclei. The aim of the present work was to characterize the effects specifically induced by Vinca alkaloids as compared with those obtained previously with other pharmacological classes of anticancer drugs.
The results show that Vinca alkaloids inhibit the cell proliferation of neoplastic cell lines at a concentration of 10***-8 M except in the case of the J82 cell line, for which only a slowing down of cell proliferation was observed. Concerning the cell cycle kinetics, the results show that the Vinca alkaloids induce an accumulation of cells in the mitosis phase. This accumulation of mitotic cells was maximal after 15 h incubation in the presence of the drugs. A study of the morphonuclear-induced effects of Vinca alkaloids showed that the variance of the optical density (VOD) is strongly influenced by these Vinca alkaloids. The development of the VOD was parallel with the development of the percentage of mitosis; thus, the VOD enabled the Vinca alkaloid-induced effects to be specifically characterized from a morphonuclear point of view. On the other hand, the results show that the mean value of the variance of the optical density was very highly correlated (P &lt; 0***.001) with the efficiency of the Vinca alkaloids in terms of cytotoxicity.
In clinical studies, the analysis of the development of this parameter would make it possible to assess the response to chemotherapy in the case of patients treated with Vinca alkaloids.