bluuebunny/crossref_metadata_2025_split huggingface dataset:
Stable Anticonvulsant Action of Benzodiazepines During Development in Rats
Authors: Kubová H , Mareš P , Vorlíček J 
Published: April 2011

Abstract
The anticonvulsant action of midazolam and clonazepam was studied in 168 immature rats in three age groups (12, 18 and 25 days old). Epileptic after-discharges of the spike-and-wave type accompanied by clonic seizures of facial and forelimb muscles induced by stimulation of sensorimotor cortex were used as a model. The solvent used for clonazepam exhibited a tendency to anticonvulsant action in 12-day-old rats. On the contrary, a proconvulsant action was seen in 25-day-old animals. The action of both benzodiazepines was identical and did not change substantially during development. The highest dose used (1 mg kg−1, i.p.) shortened the duration of epileptic after-discharges, the two lower doses (0·1 and 0·02 mg kg−1, i.p.) suppressed the progressive prolongation with repeated stimulations seen under control conditions. Motor correlates of stimulation remained practically uninfluenced by the two benzodiazepines, myoclonic seizures accompanying epileptic after-discharges were attenuated by the highest dose of both drugs.
Treatment of Antigen-Induced Arthritis in Rabbits by the Intra-articular Injection of Methylprednisolone, 90Y or Chlorambucil
Authors: Green K L , Foong W C 
Published: April 2011

Abstract
Rabbits with a bilateral antigen-induced arthritis were injected intra-articularly (i.a.) in one joint with methylprednisolone (1 mg), 90Y (18·5 MBq) or chlorambucil (1 mg) as a single dose. The severity of arthritis was determined by measuring joint swelling and skin surface temperature, macroscopic and histological changes in the joint being assessed 8 weeks after induction of arthritis when the rabbits were killed. Methylprednisolone injected at the time of antigen challenge or 3 weeks later caused a reduction in joint swelling and temperature (P &lt; 0·05) for 1 to 6 weeks after injection. 90Y had an initial proinflammatory effect lasting several days, but later caused a modest reduction in joint swelling for up to 4 weeks (P &lt; 0·05). Eight weeks after induction of arthritis, neither methylprednisolone nor 90Y-treated joints showed any significant reduction in erosion or histopathology compared with control arthritic joints. Chlorambucil injected 1 week after antigen challenge caused a rapid reduction in joint swelling which was maintained for the duration of the study. Joint surface temperature was reduced to a lesser extent. Eight weeks after induction of arthritis, chlorambucil-treated joints showed a decrease (P &lt; 0·05) in all of the parameters of disease pathology assessed. Treatment with chlorambucil intra-articularly was clearly more effective than with methylprednisolone or 90Y at the doses employed and deserves further study as a potential treatment for chronic synovitis.
Effects of turpentine oil pretreatment on β-blocker pharmacokinetic parameters in rats
Authors: Murai-Kushiya Mami , Okada Satoshi , Kimura Toshio , Hasegawa Ryuichi 
Published: April 2011

Abstract
Turpentine oil treatment (0·2 mL kg−1, s.c.) was used to increase the plasma concentration of α1-acid glycoprotein (0·13 mg mL−1 in control rats) to 1·72 mg mL−1 after 2 days, and allow assessment of its effects on the pharmacokinetics and stereoselective binding of three β-blockers. Racemates (5 mg kg−1) were administered intravenously to control and turpentine oil-pretreated rats and the plasma concentrations were determined up to 90 min. Stereoselective analysis showed the apparent distribution volume and the area under plasma concentration-time curves (AUC) of R-(+)-propranolol to be, respectively, one-quarter and twice those of the S-(–)-enantiomer and differences in pharmacokinetic parameters between the two were magnified by turpentine oil pretreatment. Pharmacokinetic parameters of oxprenolol enantiomers were essentially similar for the controls but after turpentine oil pretreatment, a higher affinity of the R-(+)-enantiomer for plasma was observed. Acebutolol enantiomers behaved non-stereospecifically throughout. These results were consistent with predictions from the in-vitro stereospecific binding properties of these agents to purified rat α1-acid glycoprotein.
Liquid chromatographic determination of magnolol in urine collected from volunteers after a single dose of Saiboku-To, an oriental herbal medicine for bronchial asthma
Authors: Homma Masato , Oka Kitaro , Kobayashi Hitoshi , Nhtsuma Tomoyuki , Yamamoto Shinobu , Itoh Hisao , Takahashi Noriyuki 
Published: April 2011

Abstract
Saiboku-To is an anti-asthmatic herbal remedy which consists of ten herbal extracts. To investigate the clinical relationship between the effects and chemical components of Saiboku-To, a simple and sensitive high-performance liquid chromatographic method (HPLC) for determination of magnolol, one of the major urinary products, was developed. Organic solvent extraction of urinary magnolol was conducted by diatomaceous earth column rapid-flow fractionation using ethanol/dichloromethane (8/92, v/v). Recovery rates of magnolol were more than 99% with coefficient of variations less than 6% in the concentration range 9·7–970 ng mL−1. Subsequent HPLC determination of magnolol was achieved using a conventional silica-gel column, a mobile phase mixture of acetic acid/diethyl ether/n-hexane (0·2/17·0/82·8, v/v), and a UV-absorption detector set at 290 nm. Calibration was on the basis of peak height ratio between magnolol and flavone as an internal standard. The method was used to demonstrate excretion profiles of magnolol in healthy and asthmatic subjects following single administration of Saiboku-To.
A Sulphonylthiourea (BM 20) Related to Torasemide: a new Loop Diuretic with Relative Potassium-sparing Properties
Authors: Masereel B , Schynts M , Krzesinski J M , Pirotte B , Rorive G , Delarge J 
Published: April 2011

Abstract
A series of sulphonylthioureas related to torasemide, a high ceiling loop diuretic, were synthesized and found to inhibit the Na+ 2Cl− K+ co-transporter of the thick ascending limb of the loop of Henlé. Their diuretic properties were studied (30 mg kg−1) after oral administration to rats. Lipophilic derivatives, very active in-vitro, were found inactive orally and intraperitoneally in rats. The four most active compounds were examined for their dose-dependent diuresis. Three of them showed a potency, water and electrolyte excretion similar to torasemide. The fourth molecule, a sulphonylthiourea (BM 20), exhibited relative potassium-sparing properties and a minimal diuretic dose of 0·001 mg kg−1, 200 times lower than torasemide.
Biological Evaluation of Compounds with -NCS- Group or Derived from Thiazole and Imidazole. Activity on Prostaglandin Synthetase Complex
Authors: Moulard ThéRése , Lagorce Jean F , Thomes Jean C , Raby Claude 
Published: April 2011

Abstract
The effects of compounds with activity against thyroid peroxidase were tested on the activity of hydroperoxidase and cyclo-oxygenase of the prostaglandin synthetase complex in-vitro. Active compounds were found to inhibit the peroxidase, and the cyclo-oxygenase function. These compounds were also found to have anti-inflammatory activity as demonstrated by the reduction of carrageenan-induced oedema of the hind paw of the rat. Indomethacin and non-steroidal anti-inflammatory drugs tested under the same conditions were shown to have activity towards the cyclo-oxygenase rather than the peroxidase function of the prostaglandin synthetase complex. A common feature of the active compounds was the presence of an -NCS- linkage or free -SH group.
Effect of okadaic acid on histamine release from rat peritoneal mast cells activated by anti-IgE
Authors: Takei Masao , Mitsui Hideki , Endo Koichi 
Published: April 2011

Abstract
The effect of okadaic acid, a potent inhibitor of protein phosphatase 1 and 2A, on histamine release from mast cells has been investigated. Okadaic acid strongly and dose-dependently inhibited histamine release from mast cells induced by anti-IgE. The IC50 value of okadaic acid on histamine release induced by anti-IgE was 3·2 Nm. However, okadaic acid failed to inhibit histamine release induced by A23187 and compound 48/80. Moreover, okadaic acid showed no effect on the initial rise in intracellular Ca2+, Ca2+-mobilization from intracellular Ca2+-stores and the generation of inositol trisphosphate. These results suggest a possible involvement of protein phosphatase 2A in the histamine release from mast cells induced by anti-IgE.
Selective inhibition of NS-398 on prostanoid production in inflamed tissue in rat carrageenan-air-pouch inflammation
Authors: Futaki N , Arai I , Hamasaka Y , Takahashi S , Higuchi S , Otomo S 
Published: April 2011

Abstract
NS-398 (N-(2-cyclohexyloxy-4-nitrophenyl) methane sulphonamide), a newly synthesized potent non-steroidal antiinflammatory drug (NSAID) has a much lesser degree of toxicity, as compared with presently available NSAIDs. We have investigated the inhibition of prostanoid production in inflammatory exudate, gastric mucosa and renal papillary tissue, following oral administration to carrageenan-air-pouch rats. The ID50 values of NS-398 in the inflammatory exudate, gastric mucosa and renal papillary tissue were 0·18, 62·2 and 261·7 mg kg−1, respectively. In contrast, indomethacin decreased the PGE2 concentration in the inflammatory exudate, gastric mucosa and renal papillary tissue, with the same dose range, the ID50 values being 0·23, 0·14 and 0·15 mg kg−1, respectively. The same tendency was seen for 6-keto-prostaglandin F1 and thromboxane B2. Moreover, NS-398 inhibited excess PGE2 production in inflamed tissue but did not affect physiological production of PGE2 in non-inflamed tissue. Indomethacin, in both inflamed and non-inflamed tissues, inhibited PGE2 production to the same degree. These results indicated that NS-398 has some specificity for inflamed tissue, by inhibiting prostanoid synthesis, and this effect may explain the decreased side-effects of this drug.
SR 48968, A Novel Non-peptide Tachykinin NK-2-Receptor Antagonist, Selectively Inhibits the Non-Cholinergically Mediated Neurogenic Contraction of Guinea-pig Isolated Bronchial Muscle
Authors: Kamikawa Yuichiro , Shimo Yasuo 
Published: April 2011

Abstract
We have examined the actions of SR 48968 ((S)-N-methyl-N-[4-(4-acetylamino-4-phenyl piperidino)-2-(3,4-dichlorophenyl)butyl]benzamide), a novel non-peptide tachykinin NK-2-receptor antagonist, on the response evoked by electrical field stimulation or by acetylcholine and neurokinin A on guinea-pig isolated airway smooth muscle. Electrical field stimulation (1–32 Hz, 0·3 ms, 30 V for 20 s) evoked a biphasic response in a frequency-dependent manner, consisting of a cholinergically-mediated fast contraction followed by a non-adrenergically-mediated relaxation in tracheal muscle and by a noncholinergically-mediated slow contraction in bronchial muscle. SR 48968 (0·01–1 μm) caused a concentration-dependent inhibition of non-cholinergically mediated contraction of bronchial muscle, without significant influence on cholinergically and non-adrenergically-mediated responses. Submaximal contractions of tracheal and bronchial muscles evoked by exogenous neurokinin A (10–300 Nm) were markedly inhibited by SR 48968 (0·1–1 μm), but those by exogenous acetylcholine (1–3 μm) were slightly inhibited by the antagonist. The results indicate that in guinea-pig isolated bronchial muscle, SR 48968 selectively inhibited non-cholinergically mediated neurogenic contraction via antagonism of NK-2 receptors.
Dopamine Antagonists Can Inhibit Methamphetamine Sensitization, But Not Cocaine Sensitization, When Assessed by Ambulatory Activity in Mice
Authors: Kuribara Hisashi , Uchihashi Yoshitaka 
Published: April 2011

Abstract
The repeated subcutaneous administration of methamphetamine (2 mg kg−1) and cocaine (10 mg kg−1) at 3–4 day intervals induced sensitization to their ambulation-increasing effects in mice. Subcutaneous administration of SCH 23390 (R-(+)-7-chloro-8-hydroxy-1-phenyl-2,3,4,5-tetrahydro-1H-3-benzazepine; 0·003–0·03 mg kg−1) and YM-09151–2 (cis-N-(1-benzyl-2-methylpyrrolidin-3-yl)-5-chloro-2-methoxy-4-methylaminobenzamide; 0·003–0·03 mg kg−1), the selective dopamine D1 and D2 antagonists, respectively, reduced dose-dependently the acute ambulation-increasing effect of methamphetamine. The development of methamphetamine sensitization was inhibited when it was administered in combination with either SCH 23390 or YM-09151–2 in the repeated administration schedule. Although SCH 23390 (0·01–0·1 mg kg−1) and YM-09151–2 (0·01–0·1 mg kg−1) also reduced the ambulation-increasing effect of cocaine (10 mg kg−1), neither drug inhibited the cocaine sensitization. Mice given cocaine with SCH 23390 (0·03 mg kg−1) or YM-09151–2 (0·03 and 0·1 mg kg−1) showed higher sensitivity than those given cocaine alone. The present results suggest that, although both the dopamine D1 and D2 antagonists reduce the acute stimulant effects of both methamphetamine and cocaine, they are only effective for inhibition of the methamphetamine sensitization. Mechanisms other than the dopaminergic system appear to be involved in the cocaine sensitization.
Human Serum Albumin Conformational Changes as Induced by Tenoxicam and Modified by Simultaneous Diazepam Binding
Authors: Brée F , Urien S , Nguyen P , Tillement J P , Steiner A , Vallat-Molliet C , Testa B , Visy J , Simonyi M 
Published: April 2011

Abstract
The binding of tenoxicam to human serum albumin has been shown by affinity chromatography proton titration and equilibrium dialysis to be dependent on the neutral to basic conformational change of the protein. The influence of diazepam on the interaction was also investigated using the same techniques, suggesting that diazepam increases the association of tenoxicam to albumin. Affinity chromatography revealed that the reciprocal effect also occurs. Displacement studies indicated that diazepam causes a significant increase in the affinity of tenoxicam to its main binding site, albumin site I, which is different from the diazepam site (site II). Tenoxicam seemed to cause an allosteric change in the conformation of the protein during its own binding, as did warfarin. The mechanism of this effect was a pH-dependent conformational change of albumin induced by electrostatic forces within the protein. Diazepam induced a distant accommodation of the protein, an effect accompanied by an enhanced inhibition of the release of protons from albumin.
Inhibition of Intestinal Motility and Secretion by Flavonoids in Mice and Rats: Structure-activity Relationships
Authors: Di Carlo G , Autore G , Izzo A A , Maiolino P , Mascolo N , Viola P , Diurno M V , Capasso F 
Published: April 2011

Abstract
Intraperitoneal administration of some flavonoids (apigenin, flavone, kaempferol, morin, myricetin, naringin and rutin; 12·5–50 mg kg−1) significantly (P &lt; 0·05–0·01) reduced small (28–69%) and large (83–134%) intestinal transit in mice. Other flavonoids (naringenin, silibinin, silymarin and taxifolin, 100–200 mg kg−1) reduced (23–41%; P &lt; 0·5–0·01) intestinal transit at doses of 100–200 mg kg−1 while hesperitin, catechin and phloridzin (up to 200 mg kg−1) had no effect. This effect was antagonized by yohimbine (87–96%) and phentolamine (87–91%) but not by prazosin, propranolol, atropine, hexamethonium, mepyramine, cyproheptadine and naloxone. Yohimbine (92–96%) also antagonized the inhibitory effect of flavonols (12·5–50 mg kg−1) (P &lt; 0·05–0·01) on intraluminal accumulation of fluid and diarrhoea induced by castor oil. By contrast, verapamil potentiated the flavonol effect. It is suggested that these effects, influenced by the structure of the molecules, are mediated by α2-adrenergic receptors and calcium.
Effects of Alkylxanthines on Contractility of Diaphragm Fibres Isolated from Normal and Sensitized Guinea-pigs
Authors: Orón J D , Cortijo J , Perpiñá M , Morcillo E J 
Published: April 2011

Abstract
This study investigates the effects of alkylxanthines on twitch tension generated by electrical stimulation (supramaximal pulses, 0·2 ms duration, 1 Hz) of diaphragm muscle fibres isolated from normal and actively-sensitized guinea-pigs. Caffeine, theophylline and theobromine increased, in a concentration-dependent manner (50–500 μm), twitch tension in normal and sensitized diaphragm. Caffeine (500 μm) enhanced contractility to a greater extent than theophylline or theobromine. Twitch potentiation by caffeine (500 μm) was significantly greater in sensitized diaphragm. Verapamil (0·1–100 μm) did not alter twitch contractions in the absence or presence of alkylxanthines in normal or sensitized strips. Dantrolene (0·01–100 μm) depressed, in a concentration-dependent fashion, twitch contractions of normal and sensitized diaphragm. The inhibitory concentration 50% (expressed as —log IC50) was 6·78 ± 0·13 in normal tissues and 6·15 ± 0·11 in sensitized tissues (n = 6 in each group; P &lt; 0·05). Exposure to Ca2+-free, EGTA (0·1 Mm)-containing medium, depressed twitch contraction of normal diaphragm to a lesser extent than that of sensitized diaphragm. Methylxanthines reversed depression of twitch contractions produced by exposure to dantrolene (5 μm) or a Ca2+ -free medium. Adenosine (1–1000 μm) was without effect whereas enprofylline (50–500 μm) enhanced diaphragm contractility in normal tissues. This indicates that blockade of adenosine receptors is not involved in the inotropic effect of alkylxanthines in guinea-pig diaphragm. Results from this study suggest that alkylxanthines enhance diaphragm contractility in the guinea-pig by releasing intracellular Ca2+ and promoting extracellular Ca2+ entry through verapamil-insensitive pathways. An alteration of Ca2+ movements and stores may be present in the sensitized diaphragm.
Inhibition of Rat Acute Inflammatory Paw Oedema by Dihemiphthalate of Glycyrrhetinic Acid Derivatives: Comparison with Glycyrrhetinic Acid
Authors: Inoue Hideo , Inoue Kazuko , Takeuchi Tadao , Nagata Nobuyuki , Shibata Shoji 
Published: April 2011

Abstract
The anti-inflammatory profile of dihemiphthalate compounds of glycyrrhetinic acid derivatives in acute rat paw oedema induced by various vasoactive agents was compared with the parent compound. Three dihemiphthalate compounds (the di-sodium salt of 18 β-olean-12-ene-3β,30-diol di-O-hemiphthalate, 18β-olean-9(11),12-dione-3β,30-diol di-O-hemiphthalate and olean-11,13(18)-diene-3β,30-diol di-O-hemiphthalate), significantly inhibited development of carrageenan-induced rat paw oedema during the first 3 h (ED50 70, 90, and 108 mg kg−1 respectively, p.o.), while glycyrrhetinic acid (ED50, 200 mg kg−1) showed a significant inhibition of paw oedema 3 h after carrageenan treatment. The dihemiphthalate compounds also suppressed mouse paw oedema induced by histamine, bradykinin, and PAF acether at doses of less than 100 mg kg−1. However, these compounds failed to inhibit 5-HT-induced mouse paw oedema. Glycyrrhetinic acid had little effect on mouse paw inflammation induced by the above irritants. The three compounds at 10−7-10−4 m, inhibited histamine-induced contraction of guinea-pig isolated ileum. However, concentration-response curves to 5-HT and bradykinin were not affected by the same compounds. These results suggest that the dihemiphthalate compounds modulate vascular permeability caused by endogenous vasoactive agents as one of the anti-inflammatory mechanisms. This action is quite different from that of glycyrrhetinic acid.
Regulation of Adrenergic Receptors in the Rat Kidney
Authors: Lübbecke F , Schneider D , Schütterle G 
Published: April 2011

Abstract
Chronic daily application of (±)-isoprenaline induced a selective-down regulation of β-adrenoceptors in the kidney: the concentration of [3H]dihydroalprenolol binding sites was significantly lowered by isoprenaline treatment while [3H]prazosin and [3H]rauwolscine binding, representing α1-and α2-adrenoceptors, respectively, was not markedly altered. Since the proportion of high- and low-affinity sites for the non-selective α- but relatively β1-selective agonist (–)-noradrenaline remained constant and since in [3H]dihydroalprenolol competition experiments the high- and low-affinity site ratio fitted well to the β1/β2 relation, determined independently by employing ICI 118551 as a β2-selective ligand, a parallel decrease of both β1- and β2-adrenoceptor density can be concluded.
Comparison of site-dependent degradation of peptide drugs within the gut of rats and rabbits
Authors: Bai Jane P F , Chang Li-Ling 
Published: April 2011

Abstract
Intestinal luminal degradation of neurotensin and acetyl-neurotensin-(8–13) within the gut of rats and rabbits was compared using brush-border membranes. Patterns of differential proteolysis of these two peptides within the intestine were similar within the same species and between the species. In both rats and rabbits, jejunal brush-border membranes had the highest proteolytic activities degrading neurotensin and acetylneurotensin-(8–13), and caecal or ileocaecal brush-border membranes had the lowest activities. In both species, patterns of site-dependent degradation of neurotensin and acetylneurotensin-(8–13) agreed with the distribution profiles of endopeptidase-24.11 and angiotensin-converting enzyme within the gut. The distal intestine of rats and rabbits has the lowest activities degrading these two compounds. The results demonstrate that distribution of peptidases within the gut will affect site-dependent degradation and absorption of peptide drugs.
Dark effect of 8-methoxypsoralen on human erythrocytes
Authors: Gawron Antoni , Pawlikowska BoŻena 
Published: April 2011

Abstract
Furanocoumarin 8-methoxypsoralen (8-MOP) (1–100 μg mL−1) in the dark showed a protective affect against hypotonic haemolysis of the erythrocyte membrane. However, the effect against heat-induced haemolysis was dependent on the concentration of 8-MOP; lower concentrations of 8-MOP showed an inhibiting effect, whereas higher concentrations caused acceleration of haemolysis. 8-MOP was not able to induce haemolysis in isotonic solution at 20 or 37 C. Reaction of erythrocytes with 8-MOP in the dark resulted in a shrinkage of the cells and alterations of their shapes. We conclude that modification of erythrocyte membrane by 8-MOP proceeds via reaction with membrane lipids and proteins. This indicates that the effect on the cell membrane plays an important role in the mechanism of the action of 8-MOP on the cells.
Deep Tissue Penetration of Bases and Steroids after Dermal Application in Rat
Authors: Singh Parminder , Roberts Michael S 
Published: April 2011

Abstract
The local deep tissue penetration of bases such as diazepam, antipyrine, iodoantipyrine, haloperidol and steroids such as hydrocortisone, fluocinolone acetonide, testosterone and progesterone after dermal application as aqueous solutions was studied in a rat model. The extent of local, as distinct from systemic delivery, for each solute was assessed by comparing the tissue concentrations obtained below a treated site with those in contralateral tissues. Local direct penetration was evident for all solutes below the applied site, although depth of penetration varied between individual solutes. A physiological pharmacokinetic model was employed to estimate local tissue concentrations of various compounds after dermal application.