bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Effect of Some Preservatives Used in Nasal Preparations on the Mucus and Ciliary Components of Mucociliary Clearance
Authors: Batts A H , Marriott C , Martin G P , Wood C F , Bond S W 
Published: April 2011

Abstract
Efficient mucociliary clearance is a function of the physical properties of the mucus coupled to appropriately functioning cilia and may be altered by substances affecting ciliary beat frequency (CBF). Therefore the effect of preservatives on CBF was investigated using a photoelectronic technique. Methyl-p-hydroxybenzoate, propyl-p-hydroxybenzoate, chlorbutol and chlorocresol inhibited beat frequency, an effect which was reversible upon rinsing out the first three compounds but not chlorocresol. The effect of chlorhexidine and phenylmercuric borate on CBF was complicated by an interaction with chloride ions in the media used. EDTA did not appear to be ciliotoxic, while the effect of benzalkonium chloride was variable. Thiomersal halted ciliary beating after 40–100 min. Mucociliary clearance may also be affected by an alteration of the physical properties of the mucus layer, therefore the effect of each compound on the rheological properties of purified pig gastric mucus glycoprotein was investigated. None of the preservatives significantly altered the viscoelastic properties of the gel, measured using dynamic techniques.
Cyclosporin Treatment Alters Prostanoid and Thromboxane Production by Rat Isolated Kidney Mitochondria
Authors: Erman Arie , Chen-Gal Batia , Rosenfeld Joseph 
Published: April 2011

Abstract
This study was designed to investigate the effects of chronic treatment with cyclosporin A (CSA) on the endogenous synthesis of prostanoids (PGs) and thromboxane (Tx) by renal isolated medullary and cortical mitochondria. The administration of CSA, dissolved in 10% ethanol in olive oil, to male Wistar rats (20 mg kg−1 day−1 i.p.) for 14 days resulted in alterations in mitochondrial biosynthesis of immunoreactive PGs. The endogenous synthesis of thromboxane by medullary and cortical mitochondria isolated from CSA-treated rats was significantly enhanced by 120 and 55%, respectively, whereas the synthesis of prostaglandin E2 by medullary mitochondria was reduced by 35%. The synthesis of prostaglandin F2, and prostacyclin was not affected by CSA treatment. The conversion of exogenous arachidonic acid to PGs and Tx by cortical mitochondria isolated from CSA-treated rats was significantly increased. In addition, CSA treatment resulted in i) a reduced acylation of arachidonic acid into medullary phospholipids by 25% and into medullary and cortical triglycerides by 33 and 27%, respectively, and ii) an increase in cortical and medullary triglycerides. We suggest that the alterations in the endogenous mitochondrial production of PGs and Tx caused by CSA, may play a role in the impairment of membrane mediated functions.
Pharmacological modulation of 2-methyl-carbamate-PAF induced rat paw oedema
Authors: Castro-Faria-Neto H C , Silva P M R , Martins M A , Silva P S , Henriques M G O M , Cordeiro R S B , Vargaftig B B 
Published: April 2011

Abstract
Intraplantar injections of 2-methyl-carbamate-PAF (2-MC) (0.125-16.0 μg/paw) into the rat paw were followed by a bell-shaped dose response curve for inflammatory oedema, with an ascending phase at 0.125-2.0 μg/paw, and a descending phase at 4.0–16.0 μg/paw. The inflammatory response to 2-MC was partially inhibited by pre-treatment with aspirin (200 mg kg−1), NDGA (100 mg kg−1), dexamethasone (0.1 mg kg−1), verapamil (50 mg kg−1) and by a specific PAF antagonist BN 52021 (5–10 mg kg−1). The cyclo-oxygenase inhibitors indomethacin (2 mg kg−1) and piroxicam (1.8 mg kg−1) as well as antihistamine meclizine (40 mg kg−1) and ranitidine (50 mg kg−1) failed to block the oedematogenic response to 2-MC. Our data suggest that 2-MC induced rat paw oedema is mediated by PAF-acether receptors and is partially dependent on arachidonate lipoxygenase pathway and extracellular Ca2+.
Presence of non-cholinergic motor transmission in human isolated bladder
Authors: Luheshi G N , Zar M A 
Published: April 2011

Abstract
Atropine-sensitivity of the motor transmission in the isolated detrusor preparation from human bladder has been examined. The preparations were contracted by electrical field stimulation consisting either of short trains of pulses or of long trains of pulses. Part of the stable response to short-train stimuli (28%) was resistant to atropine, was not potentiated by physostigmine and was blocked by tetrodotoxin. The stable responses to long-train stimuli were fully blocked by atropine. It is concluded that the detrusor of the bladder in man, in common with other mammalian species, contains a non-cholinergic component in its motor transmission, and that prolonged stimulation with long-train stimuli causes an extinction of the non-cholinergic motor transmission, probably through depletion of transmitter stores in the nerve-terminals.
Electrophoretic Study of Nitrofurantoin in Aqueous Suspensions. Effect of the Addition of a Polymeric Thickener
Authors: Gallardo V , Delgado A , Parera A , Salcedo J 
Published: April 2011

Abstract
The electrophoretic mobility of nitrofurantoin (based on the microelectrophoresis method) has been studied in dilute dispersions of the drug. Specifically, the effect of NaCl, CaCl2 and AlCl3, pH, and a thickener, Carbopol 934, was determined. The electrophoretic mobility (μ) increases in absolute terms when the pH is raised between 3 and 9, although μ remains negative in this pH range. The variation of absolute mobility (|μ|) with NaCl concentration shows a pronounced maximum for a concentration of about 10−4 M. However, when the concentration of CaCl2 in the medium is increased, |μ| decreases steadily. The effect of AlCl3 concentration on the mobility is markedly influenced by the pH of the dispersing medium although a general trend is observed for μ to become more positive with increasing concentration of the salt. Finally, Carbopol 934 appears to impart an extra negative charge to the nitrofurantoin surface, since higher negative mobilities were measured in the presence of the polymer.
Pharmacokinetics, Bioavailability, Metabolism, Tissue Distribution and Urinary Excretion of γ-L-Glutamyl-L-dopa in the Rat
Authors: Cummings J , Matheson L M , Maurice L , Smyth J F 
Published: April 2011

Abstract
γ-L-Glutamyl-L-dopa (gludopa) is believed to be a dopamine prodrug specific for the kidney. Its pharmacokinetics have been studied in the rat given 50 mg kg−1 intravenously (i.v.) and 60 mg kg−1 intraperitoneally (i.p.). By the i.v. route, elimination followed apparent first order kinetics and was biphasic with a t 1/2α of 7 min and terminal half-life of 67 min. After i.p. administration absorption was rapid (t 1/2ab 6 min), elimination was monophasic with a terminal half-life almost identical following i.v. dosing (65 min), and bioavailability was 40%. In tissues (liver and kidney) gludopa was biotransformed to four intact catecholic products (L-dopa, dopamine, DOPAC and γ-L-glutamyl-dopamine) which appeared quickly (peaks at 15 min) and which were almost completely cleared by 4 h. Dopamine was the major kidney metabolite accounting for 69% of total catechol content with an AUC 31 times greater than in liver where it accounted for only 34% of total catechols. In rat urine eight major metabolites (5.7% of the dose) and at least 12 minor metabolites were detected of all of which 85% was dopamine. A higher percentage of the dose was excreted as intact catechols in man (15.7%) but fewer metabolites were detected (L-dopa, dopamine, DOPAC). It is confirmed that gludopa is kidney specific in rat but that the pharmacological effects of dopamine are likely to be short lived due to rapid clearance. Gludopa appears to be less dopamine specific in man.
Zinc Acexamate Inhibits Gastric Acid and Pepsinogen Secretion in the Rat
Authors: Bulbena Oriol , Esplugues Juan V , Escolar Ginés , Gil Luz , Navarro Carmen , Esplugues Juan 
Published: April 2011

Abstract
Pretreatment with zinc acexamate (25–100 mg kg−1 i.p.) inhibited acid and pepsinogen secretion in the pylorus-ligated rat. Zinc acexamate (5–50 mg kg−1 p.o.) also inhibited the increases in acid secretion induced by carbachol (10 μg kg−1) and 2-deoxy-D-glucose (200 mg kg−1) in the perfused stomach of the anaesthetized rat. A delayed antisecretory effect was observed with this drug on histamine induced responses. High concentrations of zinc acexamate (10−5-10−2 M) did not modify the in-vitro activity of pepsin. Administration of zinc acexamate resulted in an increase in the presence of pepsinogen at the mucosal level. A morphological examination of the gastric mucosa confirmed an accumulation of zymogencontaining granules in the gastric chief cells of zinc acexamate-treated rats (50 mg kg−1 p.o.). These results indicate that zinc acexamate decreases acid and pepsinogen secretion in-vivo, and this may explain its antiulcer activity.
A Comparison of the Effects of Nicotine and (+)-Amphetamine on Rat Behaviour in an Unsignalled Sidman Avoidance Schedule
Authors: Balfour D J K 
Published: April 2011

Abstract
In agreement with the results of previous studies, the withdrawal of nicotine from rats trained on an unsignalled Sidman avoidance schedule under the influence of the drug (0.4 mg kg−1 given subcutaneously 3 min before each training session) was associated with a reduction in lever-pressing responses (P &lt; 0.05) and an increase in the number of shocks received (P &lt; 0.01). The number of shocks received by the withdrawn rats was also greater (P &lt; 0.05) than the number of shocks received by rats trained and tested with saline, whereas the number of lever-pressing responses recorded for saline-treated rats was not influenced significantly by the drug used during training. The subcutaneous administration of (+)-amphetamine (0.5 mg kg−1 30 min before the test session) stimulated lever-pressing in rats trained with saline or nicotine and abolished the increase in the number of shocks received by the nicotine-withdrawn rats, but had no significant effect on the number of shocks received by rats trained with saline. The number of shocks received by the rats trained on the schedule with (+)-amphetamine but tested after an injection of saline was also greater (P &lt; 0.05) than the number of shocks received by rats trained and tested with saline. It is concluded that the disruption in shock avoidance performance observed for the nicotine- and (+)-amphetamine-withdrawn rats may reflect the development of dependence upon the stimulant properties of these drugs.
Inhibition of Metoprolol Metabolism by Chloroquine and other Antimalarial Drugs
Authors: Lancaster D L , Adio R A , Tai K K , Simooya O O , Broadhead G D , Tucker G T , Lennard M S 
Published: April 2011

Abstract
The ability of a series of antimalarial drugs to impair the metabolism of metoprolol in rat and man has been examined. Chloroquine was a potent inhibitor in rat liver microsomes (Kj value for metoprolol α-hydroxylation = 0.18 μM and for O-demethylation = 0.36 μM). The other antimalarial drugs also inhibited metoprolol oxidation. Quinine was similar to chloroquine in potency, while quinidine, primaquine and mefloquine were slightly less potent. Chloroquine also inhibited metoprolol oxidation in human liver microsomes, although it was about two orders of magnitude less potent than in the rat and the extent of impairment varied greatly between individual livers. Intraperitoneal administration of chloroquine to anaesthetized rats decreased the clearance of metoprolol (40 mg tartrate salt kg−1 i.p.) to 54, 34, 20 and 26% of the control value at doses of 2.5, 4.0, 25 and 40 mg kg−1, respectively. We conclude that antimalarial treatment might have contributed to a previously reported difference in the metabolic pattern of metoprolol between Caucasians and Nigerians.
Smoking, eicosanoids and ulcerative colitis
Authors: Motley R J , Rhodes J , Williams G , Tavares I A , Bennett A 
Published: April 2011

Abstract
In this study, which is the first of its kind using normal tissue samples that are very difficult to obtain, we have investigated the hypothesis that smoking protects against ulcerative colitis by altering the colonic mucosal formation of prostaglandins and related substances. Colonic mucosa biopsied from healthy young men produced prostaglandin E, 6-keto-PGF1α (formed from PGI2), leukotriene B4 and leukotriene C4/D4/E4 as determined by radioimmunoassay. With each substance, the median yield was lower in the group of smokers who smoked 3 cigarettes in the 2 h before biopsy, than in the non-smokers. However, with each eicosanoid the statistical probability approached only the 10% level, but the fact that the trend was the same for all eicosanoids somewhat strengthens the possibility of a real difference between the groups.
The Retention of Entrapped Molecules within Erythrocyte Ghosts During Cryopreservation
Authors: Brearley C A , Hodges N A , Olliff C J 
Published: April 2011

Abstract
In view of the interest in erythrocyte ghosts and carrier erythrocytes as potential drug delivery systems, this work was undertaken to determine conditions facilitating the retention of entrapped molecules during cryopreservation. Upon freeze-thaw treatment intact erythrocytes and erythrocyte ghosts displayed different damage profiles with respect to cryoprotectant concentration. Non-penetrating cryoprotectants showed optimum protection of intact cells at 0.4-0.5 M; this optimum was not observed with ghosts, in which damage decreased with concentration up to 1 0 M. The concentration optimum for intact cells was not abolished by oxidative or reductive treatments suggesting that its absence in ghosts is not due to altered protein-protein or protein-lipid interactions. The extent of freeze-thaw damage to ghosts was influenced by the qualitative ionic composition of a cryoprotectant-free suspending medium, with 10–12% haemolysis observed in the presence of Li+ and Mg2+ but &gt; 60% for Na+, Cs+, K+ and NH4+ with increasing loss following that order. The release on freezing of entrapped haemoglobin, inulin and sucrose was found to be inversely proportional to their molecular weights.
Inhibition of Dapsone-induced Methaemoglobinaemia in the Rat Isolated Perfused Liver
Authors: Coleman M D , Hoaksey P E , Breckenridge A M , Park B K 
Published: April 2011

Abstract
We have investigated the disposition of dapsone (DDS, 1 mg) in the rat isolated perfused liver in the absence and the presence of cimetidine (3 mg). After the addition of DDS alone to the liver there was a monoexponential decline of parent drug concentrations and rapid formation of DDS-NOH (within 10 min) which coincided with methaemoglobin formation (11.7 ± 3.0%, mean ± s.d.) which reached a maximum (22.6 ± 9.2%) at 1 h. The appearance of monoacetyl DDS (MADDS) was not apparent until 30–45 min. Addition of cimetidine resulted in major changes in the pharmacokinetics of DDS and its metabolites. The AUC of DDS in the presence of cimetidine (1018.8 ± 267.8 μg min mL−1) was almost three-fold higher than control (345.0 ± 68.1 μg min mL−1, P &lt; 0.01). The half-life of DDS was also prolonged by cimetidine compared with control (117.0 ± 48.2 min vs 51.2 ± 22.9, P &lt; 0.05). The clearance of DDS (3.0 ± 0.55 mL min−1) was greatly reduced in the presence of cimetidine (1.03 ± 0.26 mL min−1 P &lt; 0.01). The AUC0.3 h for DDS-NOH (28.3 ± 21.2 μg min mL−1) was significantly reduced by cimetidine (8.1 ± 3.40 μg min mL−1, P &lt; 0.01). In contrast, there was a marked increase in the AUC0.3 h for MADDS (32.7 ± 25.8 μg min mL−1) in the presence of cimetidine (166.0 ± 26.5 μg min mL−1 P &lt; 0.01). The methaemoglobinaemia associated with DDS was reduced to below 5% by cimetidine. Hence, a shift in hepatic metabolism from bioactivation (N-hydroxylation) to detoxication (N-acetylation) caused by cimetidine, was associated with a fall in methaemoglobinaemia. These data suggest that the combination of DDS with a cytochrome P450 inhibitor might reduce the risk to benefit ratio of DDS.
Comparison of Propranolol and Sotalol Pharmacokinetics in Obese Subjects
Authors: Poirier J M , le Jeunne C , Cheymol G , Cohen A , Barré J , Hugues F C 
Published: April 2011

Abstract
Six obese subjects (mean ± s.d.: 145.1 ± 16.7% of ideal body weight) were randomly assigned to a single i.v. dose either of (±)-propranolol base (0.108 mg kg−1 of ideal body weight) or of (±)-sotalol base (1.06 mg kg−1 of ideal body weight). Each subject received the other drug 7 days later. Pharmacokinetic parameters were compared with those obtained previously in non-obese control subjects. In obese subjects, the pharmacokinetic data calculated for sotalol were comparable with those measured in controls (total body clearance = 9.4 ± 2.9 L h−1; volume of distribution during the terminal phase = 79.8 ± 19.8 L or 0.9 ± 0.2 L kg−1; terminal half-life = 6.2 ± 1.6 h). For propranolol, total clearance (44.3 ± 15.9 L h−1) and volume of distribution (230.5 ± 48.2 L or 2.7 ± 0.7 L kg−1) were significantly less than control values. The terminal half-life (3.9 ± 1.1 h), was not significantly increased. These results could be explained by altered tissue blood flow and a decreased metabolic capacity of the liver in obese subjects.
Stereoselective hydrolysis of O-acetyl propranolol as prodrug in human serum
Authors: Takahashi Koichi , Haginaka Jun , Tamagawa Satoko , Nishihata Toshiaki , Yasuda Hiroyuki , Katagi Toyoshi 
Published: April 2011

Abstract
A direct high-performance liquid chromatographic method was developed for the assays of the enantiomers of O-acetyl propranolol. Using this procedure, the stereochemical characteristics on hydrolysis of racemic O-acetyl propranolol as a prodrug have been studied in phosphate buffer (pH 7.4) and in 90% human serum. In the phosphate buffer, no difference in the hydrolysis rate between the esters of (R)- and (S)-propranolol was observed. In 90% human serum, the hydrolysis of the esters was accelerated, and the hydrolysis rate of the ester of (R)-isomer was about three times faster than that of the ester of (S)-isomer. The interconversion between (R)- and (S)-isomer was not observed during the hydrolysis of prodrug in buffer and in human serum. These results indicated that hydrolysis of O-acetyl propranolol occurs stereoselectively in human serum.
In-vivo and in-vitro hepatoprotective effect of 4-thia-prostaglandin E1 and 7-fluoroprostacyclin in rats
Authors: Koyama Tamotsu , Uno Hiroshi , Ishii Shigeyuki , Bannai Kiyoshi , Hasato Atsuo , Makita Tokutaro 
Published: April 2011

Abstract
4-Thia-prostaglandin E1 and to a lesser extent 7-fluoroprostacyclin showed a potent protective effect against carbon tetrachloride-induced liver injury in-vivo and in-vitro in rat.
Comparison of Calculated and Experimentally Determined Punch Displacement on a Rotary Tablet Press Using both Manesty and IPT Punches
Authors: Oates R J , Mitchell A G 
Published: April 2011

Abstract
An indirect method of calculating punch displacement on a rotary tablet press from measurements of the change in punch force with the turret position was in good agreement with direct measurements of punch displacement made using a linear variable displacement transducer (LVDT)-slip ring system. The direct measurements were made during the compaction of three direct compression agents using Manesty punches. However, the agreement between calculated and experimentally determined punch displacements was unsatisfactory when IPT punches were used. The IPT punches have a much flatter punch head profile than the Manesty punches. Due to this difference, the analytic equation does not accurately describe the dynamics of the press under normal operating conditions. Terms in the analytic equation, determined originally under static conditions, were re-evaluated under dynamic conditions for both sets of tooling using the LVDT-slip ring system. Excellent agreement for both IPT and Manesty punches was found between punch displacement calculated using the revised analytic equation and direct experimental measurements. Punch displacements determined from punch head profile and machine geometry only, without taking machine deformations into account, were shown to differ widely from the calculated and experimental values.
The effect of nefopam and its enantiomers on the uptake of 5-hydroxytryptamine, noradrenaline and dopamine in crude rat brain synaptosomal preparations
Authors: Rosland Jan Henrik , Hole Kjell 
Published: April 2011

Abstract
The effect of (±),(+) and (—)-nefopam on the uptake of 5-hydroxytryptamine (5-HT), noradrenaline and dopamine in synaptosomal preparations from rat forebrain, hippocampus and striatum has been investigated. All three forms of nefopam inhibited the amine uptake in the investigated structures, the order of potency being(+) &gt; (±) &gt; (—). (+)-Nefopam was 7–30 times more potent than (—)-nefopam. The same order of potency has also been found for the antinociceptive effect of these three forms, however, the differences were smaller. Inhibition of 5-HT and noradrenaline uptake may not be the sole mechanism underlying the analgesic effect of nefopam.
Relaxant and β2-adrenoceptor blocking activities of (±)-, (+)-and (—)-pindolol on the rat isolated aorta
Authors: Doggrell Sheila A 
Published: April 2011

Abstract
The KCl contracted rat aorta is relaxed by procaterol, (±)-,(+)-and (—)-pindolol. The relaxations to procaterol, but not to (±)-pindolol, were prevented by ICI 118,551 at 10−6 M. The relaxations to (±)-pindolol are, therefore, not due to β-adrenoceptor agonism. At 10−7 M ICI 118,551, (±)-, (+)-and (-)-pindolol were β2-adrenoceptor antagonists as they inhibited the relaxant responses of the aorta to procaterol.
Evaluation of Methodology for Assessing Release Characteristics of Thermosoftening Vehicles
Authors: Kopcha Michael , Tojo Kakuji J , Lordi Nicholas G 
Published: April 2011

Abstract
Methodology has been devised for the testing and evaluation of the mechanistic release of drug or markers from thermosoftening materials, as represented by the Gelucire class of excipients, which could be predictive. Release of a drug (anhydrous theophylline) and a marker (D&C yellow No. 10) was determined using a calibrated stationary disc/rotating fluid system. Of the fourteen commercially available Gelucire excipients, six were investigated in detail (G46/07, G48/09, G50/02, G50/13, G53/10, G62/05) and found to have biphasic release profiles. Lipid soluble materials demonstrated predominantly diffusion-controlled release, while water-dispersible materials absorbed water and showed signs of swelling which led to erosion as an additional component of the release characteristics.