bluuebunny/crossref_metadata_2025_split huggingface dataset:
Relaxation by Calcium Antagonists of Potassium-contracted Trachea from Normal and Sensitized Guinea-pigs: Influence of Epithelium and the Surface of Drug Entry
Authors: Roman M , Pascual R , Iriarte C F , Villanueva M M , Ortiz J L , Cortijo J , Morcillo E 
Published: April 2011

Abstract
A technique by which drug access was restricted to either the mucosal or the adventitial surface of tracheal rings, isolated from normal (unsensitized) or sensitized guinea-pigs, was used to study the role of the epithelium in the relaxation produced by calcium antagonists (verapamil, nifedipine, cinnarizine and flunarizine) of K+-induced contraction. In trachea from normal guinea-pigs, the relaxation to verapamil for unrestricted or mucosal drug entry was reduced in the absence of epithelium, whereas the relaxation produced by nifedipine, cinnarizine or flunarizine was unchanged. In sensitized trachea, the relaxation elicited by the calcium antagonists tested was similar in intact and epithelium-denuded tracheal rings irrespective of the surface of drug entry. These results confirm that the epithelium influences the relaxation to verapamil. This modulatory effect is absent in sensitized trachea and is not shared by other calcium antagonists.
Use of 1-Anilino-8-napthalenesulphonate as an Ion Probe for the Potentiometric Study of the Binding of Sulphonamides to Bovine Serum Albumin and Plasma
Authors: Angelakou A , Valsami G , Koupparis M , Macheras P 
Published: April 2011

Abstract
The binding of sulphafurazole, sulphamethizole and sulphamethoxazole to bovine serum albumin (BSA) and human plasma has been studied in-vitro by potentiometry using an electrode selective for the ion probe 1-anilino-8-napthalenesulphonate (ANS). The method requires two separate potentiometric titrations of the binder solution with ANS in the absence and in the presence of sulphonamides. ANS displaced sulphonamides from the first-class of binding sites of both binders. The binding constants for sulphonamide-BSA interactions were higher than those for sulphonamide-human plasma. The expansion of the least linear limit of the response curve of the electrode down to 10−7 m in the presence of BSA was also demonstrated. The reverse reaction, i.e. the displacement of the probe from the binding sites induced by the sulphonamides, was also explored. The proposed method is suitable for studying competitive binding interactions in biological specimens.
Different Mechanism of Relaxation Induced by Aporphine Alkaloids in Rat Uterus
Authors: Ivorra M Dolores , Martinez Francisco , Serrano Angel , D’Ocon Pilar 
Published: April 2011

Abstract
We have examined the uterine relaxant action of three aporphine molecules (S-glaucine, S-boldine and R-apomorphine) in two experimental conditions, with and without calcium in the bathing solution, and compared these effects with those obtained with the calcium antagonists verapamil and diltiazem. The present study shows that the alkaloids relax the uterine muscle but with different mechanisms of action. In Ca2+-containing solution all three alkaloids relaxed the uterus previously contracted by KCl or acetylcholine, but in Ca2+-free medium only R-apomorphine was able to relax oxytocin-induced contraction. The calcium antagonists, verapamil and diltiazem, relaxed KCl- or acetylcholine-induced contraction in Ca2+-containing solution, whereas they only relaxed oxytocin-induced contraction in Ca2+-free medium at much higher doses. These results suggest that glaucine and boldine behave as specific calcium entry blockers without affecting the contractile machinery or intracellular Ca2+ levels as apomorphine does. The absolute configuration (S-glaucine and S-boldine vs R-apomorphine) may account for this different action.
Inhibitory Activity of Camptothecin Derivatives Against Acetylcholinesterase in Dogs and Their Binding Activity to Acetylcholine Receptors in Rats
Authors: Kawato Yasuyoshi , Sekiguchi Masayasu , Akahane Kouichi , Tsutomi Yumi , Hirota Yasuhide , Kuga Hiroshi , Suzuki Wataru , Hakusui Hideo , Sato Reiki 
Published: April 2011

Abstract
A camptothecin derivative, 7-ethyl-10-[4-(1-piperidino)-1-piperidino]carbonyloxycamptothecin (CPT-11), shows a potent antitumour activity in experimental tumour models and in clinical trials. However, CPT-11 induced early diarrhoea and vomiting at high dose levels in clinical studies and showed an acetylcholine-like action on the guinea-pig ileum and trachea. In the present study, we investigated the activities of camptothecin derivatives in inhibiting acetylcholinesterase (AChE) and in binding to muscarinic acetylcholine receptors (AChR). CPT-11 inhibited AChE and binding of the specific ligand to AChR with respective 50% inhibition concentrations of 0·2 and 5 μm. These inhibitions were induced by camptothecin derivatives having an amino group at the C-10 position (or the C-4 position of hexacyclic derivatives), but were not or were only slightly induced by the others. Early defecation and vomiting in dogs were observed after intravenous injection of DU-6596 and DU-6888, two hexacyclic derivatives having the aminomethyl group at the C-4 position, and of CPT-11. DU-6174, however, which has a hydroxy group at this position, induced no early defecation and little vomiting. Plasma concentrations of CPT-11, DU-6596 and DU-6888 after intravenous treatment at doses causing such early adverse effects were maintained for 1 h or longer at levels sufficient to inhibit AChE. These results suggest that the inhibition of AChE by camptothecin derivatives with an amino group at the C-10 position (or the C-4 position) relates to the early defecation or diarrhoea and vomiting.
Inhibition of Endogenous Acetylcholine Release by Blockade of Voltage-dependent Calcium Channels in Enteric Neurons of the Guinea-pig Colon
Authors: Marino Franca , Marcoli Manuela , De Ponti Fabrizio , Lecchini Sergio , Castelletti Carlo Maria , Frigo Gian Mario 
Published: April 2011

Abstract
The effects on acetylcholine release from the guinea-pig colon of the N-type calcium channel blocker ω-conotoxin GVIA (ω-conotoxin), the L-type calcium channel blocker nifedipine and the putative blocker of T-type channels, flunarizine, have been investigated. Endogenous basal acetylcholine release and electrically (1 Hz, 1 ms, 450 mA)-evoked overflow in the presence of cholinesterase inhibitor were studied. ω-Conotoxin (1–10 nM) and nifedipine (0·03–3 μm) dose-dependently inhibited basal and electrically-evoked acetylcholine release. Maximal inhibition of basal or electrically-evoked acetylcholine release was about 40% for nifedipine and about 75% for ω-conotoxin. The potency of nifedipine was inversely related to the external calcium concentration: its EC50 value in low-calcium medium (0·5 Mm) was as low as 12 Nm. Flunarizine inhibited acetylcholine release only at concentrations higher than 0·2 μm. Our results are consistent with an involvement of N- and L-type calcium channels in the control of the endogenous acetylcholine release from the guinea-pig colon.
Effect of Hepatotoxic Doses of Paracetamol and Carbon Tetrachloride on the Serum and Hepatic Carboxylesterase Activity in Mice
Authors: Huang Tien L , Villalobos Sergio A , Hammock Bruce D 
Published: April 2011

Abstract
The carboxylesterase activity in the serum and liver of untreated Swiss-Webster mice, and in mice administered hepatotoxic doses of either CCl4 or paracetamol was studied. In addition to p-nitrophenyl acetate (p-NpAc) and diethylsuccinate, a sensitive, spectrophotometric substrate, methyl β-(1-pentylthio) propiothioate was used to determine the esterase activity. At 24 h after treatment with CCl4 (1 mL kg−1), the liver esterase activity in the soluble fraction acting on p-NpAc was increased 1·7-fold whereas the microsomal esterase activity decreased by one-half. The serum esterase activity increased 2·4- to 3·4-fold depending upon the substrate used. Esterase activity assays of sliced gels from isoelectric focusing (IEF) of serum from mice treated with CCl4 indicated the presence of at least three additional esterase peaks when compared with serum of control mice. These peaks correlated with esterase bands visualized after staining the IEF gel with 1-naphthyl acetate. Furthermore, these esterase bands matched closely the esterase bands from microsomes of normal mice. The serum esterase activity was analysed at 4, 8, 12 and 24 h after paracetamol (400 mg kg−1) treatment. Serum esterase activity remained unchanged or decreased marginally depending on the treatment time and substrate used. Serum glutamic oxalacetic transaminase levels in CCl4- and paracetamol-treated mice, however, were significantly elevated compared with control mice. These results suggest that acute liver damage might cause the release of carboxylesterase activity to the soluble intracellular and extracellular compartments, including blood serum, with some but not all toxicants. The results also indicate that the different modes of action of the two chemicals may account for the difference in the serum carboxylesterase activity of the experimental animals.
Evaluation of the Inhibitory Activity on Serine and Aspartic Proteases of 4-Amino-4H-1,2,4-triazole and 5-Aminothiazole Derivatives Structurally Related to β-Lactam Antibiotics
Authors: Vilain Anne-Cécile , Pirotte Bernard , Vergely Isabelle , Boggetto Nicole , Masereel Bernard , Schynts Marc , Delarge Jacques , Reboud-Ravaux Michèle 
Published: April 2011

Abstract
Twenty new derivatives of 4-amino-4H-1,2,4-triazole and 5-aminothiazole have been examined for their inhibitory potential towards serine and aspartic proteases. Upon prolonged incubation with enzyme, the phenylacetylaminothiazolium salts exhibit progressive, time-dependent inhibition of chymotrypsin according to a first-order process. The formation of a tetrahedral transition state-like complex by attack of the active-site serine at the C2-position of the pseudobase form of the thiazolium may be responsible for the observed effect. Triazolium salts appeared to be simple competitive inhibitors of this enzyme, effective in the Mm range concentration. Poor inhibitions of trypsin and pepsin were also obtained in the triazolium series. In spite of their structural analogy with β-lactams, the selected derivatives failed to inhibit human leucocyte elastase.
Mesulergine antagonism towards the fluoxetine anti-immobility effect in the forced swimming test in mice
Authors: Cesana R , Ceci A , Ciprandi C , Borsini F 
Published: April 2011

Abstract
The anti-immobility effect of fluoxetine (40 mg kg−1) in the forced swimming test in mice was antagonized by the 5-HT1c/2 antagonist mesulergine (7·5 mg kg−1) and the dopamine D2 antagonist (±)-sulpiride (12.5 mg kg−1) but not by the 5-HT2/1C antagonist ritanserine (2 mg kg−1), the 5-HT1A/1B antagonist (–)-propranolol (20 mg kg−1) or the 5-HT3 antagonist DAU 6215 (0·1 mg kg−1). All compounds were administered intraperitoneally (i.p.) 6 min before fluoxetine, given i.p. 30 min before testing. The anti-immobility effect of fluoxetine was also prevented by pretreat-ment with p-chlorophenylalanine (300 mg kg−1 twice daily for 3 days) which produced an 80% reduction of 5-HT in brain. The results suggest that fluoxetine reduces immobility time in mice forced to swim, by acting indirectly through a mesulergine-sensitive site, probably the 5-HT1C receptor.
Modulation of (–)-sulpiride-induced increase in electrically-evoked release of dopamine from rat striatal slices
Authors: Yamada Shigeto , Yokoo Hideyasu , Nishi Syogoro 
Published: April 2011

Abstract
(–)-Sulpiride (10 Nm-10 μm) in the superfusate, dose-dependently increased the electrically-evoked release of dopamine from rat striatal slices. (+)-Sulpiride had little effect on evoked release of dopamine up to 10 μm. Apomorphine inhibited electrically evoked release of dopamine, and this effect of apomorphine was antagonized by (–)-sulpiride. SCH23390 and forskolin had no effect on the (–)-sulpiride-induced increase in evoked release of dopamine. Treatment with the irreversible dopamine-receptor antagonist N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline caused a significant increase in evoked release of dopamine and prevented the (–)-sulpiride-induced increase in the evoked release of dopamine. These results indicate that the (–)-sulpiride-induced increase in evoked release of dopamine is due to antagonism of the activation of dopamine autoreceptors by endogenously released dopamine.
Effect of chlorpromazine on mouse ambulatory activity sensitization caused by (+)-amphetamine
Authors: Hirabayashi Makizo , Tadokoro Sakutaro 
Published: April 2011

Abstract
The development of sensitization to the ambulation-increasing effect of (+)-amphetamine (2·5 mg kg−1) was found to be dose-dependently inhibited when 1 or 2 mg kg−1 chlorpromazine was administered concomitantly, and the sensitization to (+)-amphetamine was almost completely suppressed when co-administered with 4 mg kg−1 chlorpromazine. Following a challenge dose of 2·5 mg kg−1 (+)-amphetamine, mice pretreated with (+)-amphetamine alone or with (+)-amphetamine plus 1 or 2 mg kg−1 chlorpromazine showed similar marked enhancement of the sensitization. However, mice that had been given (+)-amphetamine plus 4 mg kg−1 chlorpromazine displayed only slight enhancement of the effect compared with the activity level in saline-pretreated mice.
Chemical and Physicochemical Characterization of Petrolatums Used in Eye Ointment Formulations
Authors: De Muynck C , Lalljie S P D , Sandra P , De Rudder D , Van Aerde P , Remon J P 
Published: April 2011

Abstract
Petrolatums from different manufacturers were characterized by viscosity measurements, oil number and ratio of low to high mol. wt components (capillary gas chromatography). Viscosity measurements and oil numbers of original materials did not correlate with the viscosity of the processed material in eye ointments. The ratio of high carbon number components to the low carbon number components was a reliable predictor for the viscosity of the formulation.
Pulmonary Uptake of Liposome-associated α-Tocopherol Following Intratracheal Instillation in Rats
Authors: Suntres Z E , Hepworth S R , Shek P N 
Published: April 2011

Abstract
This study examined the uptake and subcellular distribution of α-tocopherol in the lung following intratracheal instillation of liposome-associated α-tocopherol in rats. The liposomal suspension was composed of dipalmitoylphosphatidylcholine (DPPC) and α-tocopherol (molar ratio 7:3), labelled with [3H]α-tocopherol and [14C]cholesterol. Following intratracheal administration of the liposomal preparation (2 mg α-tocopherol/animal), the recovery of [3H]α-tocopherol in the lung was maximal (87% of initial dose) 1 h after treatment; thereafter, α-tocopherol levels remained relatively high (no less than 73% of initial dose) for the rest of the 72-h experimental period. This treatment effect resulted in a 16-fold increase in pulmonary total α-tocopherol concentration 72 h post-instillation. No radioactivity was detected in the blood, liver, kidney, pancreas, spleen and heart of animals during the 72-h experimental period. [3H]α-Tocopherol was recovered largely from cytosolic (45%) and nuclear (36%) fractions of lung and to a lesser extent, from microsomal (11%) and mitochondrial (9%) fractions. Chromatographic analysis of the subcellular fractions revealed that [3H]α-tocopherol was co-eluted with 14C-labelled liposomal lipids. Our in-vitro study, involving the incubation of Fe3+-ADP (a pro-oxidant) with mitochondrial or microsomal fractions isolated from lung tissues of animals treated with liposome-associated α-tocopherol, provided evidence that α-tocopherol levels present in the membranes of these subcellular fractions were sufficient to protect against oxidant-induced lipid peroxidation. α-Tocopherol in the rat lung can be greatly increased by the intratracheal instillation of α-tocopherol entrapped in DPPC-liposomes, suggesting that this liposomal preparation may be used as an effective prophylactic agent against oxidant-induced lung injury.
Effects of Long-term Oral Administration of NZ-105, a Novel Calcium Antagonist, With or Without Propranolol in Spontaneously Hypertensive Rats
Authors: Shudo Chizuru , Masuda Yukinori , Sakai Toshinori , Tanaka Sakuya , Shigenobu Koki , Kasuya Yutaka 
Published: April 2011

Abstract
A new calcium antagonist, NZ-105 ((±)-2-[benzyl(phenyl)amino]ethyl 1,4-dihydro-2,6-dimethyl-5- (5,5-dimethyl-2-oxo-1,3,2-dioxaphosphorinan-2-yl)-4-(3-nitrophenyl)-3-pyridinecarboxylate hydrochloride ethanol) (10 mg kg−1, p.o.), showed slow-onset hypotensive effect in spontaneously hypertensive rats (SHRs). The tachycardia evoked by NZ-105 was completely prevented when combined with a β-adrenoceptor blocker, propranolol (20 mg kg−1), which did not affect the hypotensive response to NZ-105. In long-term administration experiments for 12 weeks with SHRs, the systolic blood pressure in the control group increased with age and the heart rate was stable throughout the period. NZ-105 (10 mg kg−1 day−1) alone and its combined treatment with propranolol (20 mg kg−1 day−1) maintained the systolic blood pressure and heart rate at a low level compared with the control group. The hypotensive action of NZ-105 was reproducible after repeated dosing for 12 weeks. Long-term administration of propranolol affected neither the elevation of the systolic blood pressure nor the heart rate substantially. The heart weight per body weight was significantly reduced after the chronic combination of both drugs, suggesting that the cardiac hypertrophy accompanying hypertension was prevented.
The Existence of Conformationally Labile (Preformed) Drug Binding Sites in Human Serum Albumin as Evidenced by Optical Rotation Measurements
Authors: Walji F , Rosen A , Hider R C 
Published: April 2011

Abstract
The ability of certain drugs to induce conformational changes in human serum albumin has been examined by differential optical rotation measurements at 233 nm. At drug: protein molar ratios ([D]/[P]) of unity, the optical rotation increased, decreased or remained the same depending on the drug used. The change in the optical rotatory dispersion (ORD) signal was investigated as a function of the drug concentration. Drug-protein interactions were relatively specific. There exists at least one, and possibly more, stable preformed high affinity sites for the binding of drugs to albumin. At low [D]/[P] ratios, the ORD titration curves suggest that the high affinity sites are conformationally labile and that the albumin molecule is flexible.
Application of the WATR Technique for Water Suppression in 1H NMR Spectroscopy in Determination of The Kinetics of Hydrolysis of Neostigmine Bromide in Aqueous Solution
Authors: Ferdous Abu J , Waigh Roger D 
Published: April 2011

Abstract
Both ammonium chloride and guanidinium chloride were used to secure water suppression in 1H NMR spectra using the ‘Water Attenuation by T2 Relaxation’ (WATR) technique. The effect of phosphate buffer in the suppression was investigated over a range of pH values at 80 MHz. The spin-spin relaxation time of water protons at 80 MHz was found to reach a minimum at pH 7·3 in the presence of 0·1 m phosphate buffer and 1 m guanidinium chloride; these conditions were therefore chosen for subsequent use of the WATR technique in a study of the kinetics of hydrolysis of neostigmine bromide. The method was found to be very convenient for studies of the hydrolysis of this representative amide.
Comparative study of the rat uterine smooth muscle relaxant activity of three bisbenzyltetrahydroisoquinolines with tetrandrine
Authors: Zafra-Polo M Carmen , Tormos M José , Cortes Diego , Anselmi Elsa 
Published: April 2011

Abstract
The relaxant activity of three bisbenzyltetrahydroisoquinolines—obaberine, popisonine and lindoldhamine—was examined in rat isolated uterus and their inhibitory potencies were compared with that of tetrandrine. All alkaloids tested relaxed KCl-depolarized rat uterus and totally or partially inhibited oxytocin-induced rhythmic contractions. The degree of methylation of the free phenolic hydroxy groups and the loss of one diarylether bridge influence the potency of relaxant action of these alkaloids. Only alkaloids with absolute configuration 1R,1′S or 1R1′R acted intracellularly, promoting relaxation of contractile responses induced by oxytocin or vanadate in a Ca2+-free medium.
The effect of therapeutic doses of paracetamol on liver function in the rat perfused liver
Authors: Khedun S M , Maharaj B , Leary W P , Naicker T 
Published: April 2011

Abstract
The isolated liver perfusion technique was used to study the effect of therapeutic doses of paracetamol on hepatic gluconeogenesis and bromosulphthalein clearance from the perfusate and biliary excretion of the dye in the rat. Six groups of rats were studied; those in the three experimental groups were given 0·02 g kg−1 paracetamol daily for ninety days. The livers of animals in the control group and in one of the experimental groups were perfused with a medium containing pyruvate. The animals in the second experimental and control group were perfused with a medium containing bromosulphthalein (10 mg/100 mL). The livers of the third experimental and control group were subjected to histological examination. The rate of glucose formation and glucose concentrations were decreased, while, lactate levels and lactate: pyruvate ratios were increased in paracetamol-treated rats. The mean concentration of bromosulphthalein in the perfusate and biliary excretion of the dye were decreased. Macro and micro vesicular fatty change was present in the livers of paracetamol-treated rats. This study demonstrates that chronic administration of therapeutic doses of paracetamol to rats adversely affects liver function, as evidenced by impaired gluconeogenesis and bromosulphthalein clearance from the perfusate, and excretion of the dye into the bile, and provides histological evidence of hepatic damage in rats.
Dopamine depresses non-adrenergic, non-cholinergic neurotransmission in the rat bladder
Authors: Lot Theodore Y 
Published: April 2011

Abstract
The effects of dopamine on non-adrenergic, non-cholinergic (NANC) neurotransmission have been investigated using rat bladder strips in-vitro. Dopamine administered alone did not produce any effect on the bladder but it depressed responses to NANC nerve stimulation in a dose-related fashion. All doses of dopamine employed depressed KCl-evoked contractions of the bladder to similar extents. The depressant action of dopamine on NANC transmission was not mediated by blockade of purinergic receptors, but was partially reversed by haloperidol. It is suggested that depression of NANC neurotransmission induced by dopamine in the rat bladder is partly mediated by dopaminergic receptors.
Comparison of the effects of KRN2391 and other coronary dilators on porcine isolated coronary arteries of different sizes
Authors: Kasai Hideo , Jinno Yasuhiro , Kaneta Soichiro , Fukata Yuzo , Fukushima Hideaki , Ogawa Nobuyuki 
Published: April 2011

Abstract
The present study was performed to determine whether KRN2391 (N-cyano-N′-(2-nitroxyethyl)-3-pyridinecarboximidamide monomethanesulphonate), a novel vasodilator, shows different effects on porcine isolated coronary arteries of different sizes. The vasodilating effects of KRN2391 on porcine large (2·5–3·0 mm outer diam.) and small (0·8–1·0 mm) coronary arteries were also compared with those of cromakalim, nicorandil, nifedipine, nitroglycerin and adenosine. The relaxant effects of these drugs were examined in coronary arteries contracted by 25 Mm KCl. Nitroglycerin caused greater relaxation in large vessels than in small vessels. In contrast, adenosine, nifedipine and cromakalim caused greater relaxation in small vessels. However, there was no difference between large and small vessels in the relaxing effects of KRN2391 and nicorandil. These unique features of KRN2391 and nicorandil appear to be beneficial in ischaemic heart disease.