bluuebunny/crossref_metadata_2025_split huggingface dataset:
Antiarrhythmic, Electrophysiological and Haemodynamic Effects of Prolonged Oral Dosing with Org 7797 in the Anaesthetized Rat
Authors: Delbressine L , Harris N , Kane K A , Muir A W , Winslow E 
Published: April 2011

Abstract
The antiarrhythmic, electrophysiological and haemodynamic effects of chronic oral administration of Org 7797 ((16α,17β)-17-methylamino-oestra-1,3,5(10)-triene-3,16-diol-(Z)-2-butonedioate) were studied in rats. During dosing (10 mg kg−1 twice a day for 10 days) no effects on the electrocardiogram, monitored in conscious animals, were observed despite modest reductions (15–18%) in the maximum rate of depolarization of papillary muscle excised 1 or 6 h after completion of the dosing regime. Following anaesthesia, Org 7797 reduced the severity of arrhythmias induced by coronary artery occlusion and prevented the accompanying decrease in the ventricular fibrillation threshold (VFT) at 1 h after completion of dosing. By 6 h the effect on VFT had waned but protection against ischaemia-induced arrhythmias was retained despite a substantial decrease in Org 7797 plasma levels. Drug treatment did not modify arterial blood pressure, heart rate or stroke volume. We conclude that Org 7797 given chronically via the oral route exerts antiarrhythmic actions which may, at least in part, be due to sodium-channel block. In addition, our results suggest the presence of an active metabolite. The protective effects of Org 7797 were seen in the absence of electrocardiographic or haemodynamic changes suggesting that multiple oral doses of Org 7797 do not compromise normal cardiac function.
The Long Term Stability of Mechlorethamine Hydrochloride (Nitrogen Mustard) Ointment Measured by HPLC
Authors: Cummings J , MacLellan A , Langdon S J , Smyth J F 
Published: April 2011

Abstract
HPLC has been applied to determine the stability of mechlorethamine hydrochloride (nitrogen mustard) formulated as an ointment in white soft paraffin (10 mg drug, 50 g paraffin and 1 mL acetone). A new solubilization technique is described for extraction of the drug from the ointment for HPLC analysis which has an extraction efficiency of 76·1% with a coefficient of variation of 10·4%. Stored at 4°C the drug content of the ointment remained stable for at least 84 days and stored at 37°C the drug content remained stable for at least 40 days. In comparison aqueous solutions of mechlorethamine at the same concentration, fully degraded after 4 days. These data will aid hospital pharmacists decide on a standardized protocol for the controlled usage of the ointment which is both safe and cost-effective.
Stability of GR63178A, a Novel Pentacyclic Pyrroloquinone Anticancer Compound, in Aqueous Solutions and Biological Fluids
Authors: French Raymond C , Cummings Jeffrey , Nicolson Margaret , Smyth John F 
Published: April 2011

Abstract
The effect of temperature, pH, light, drug concentration and aeration on the stability of aqueous solutions of GR63178A, a novel anticancer compound, has been investigated. The effect of light upon the stability of GR63178A in a clinical infusion system and in biological fluids, has also been investigated. A high performance liquid chromatographic assay was used to separate the parent compound from a number of degradation products. Data presented here demonstrate that GR63178A is stable in aqueous solutions at normal ambient temperatures in neutral or alkaline pH ranges. The compound is unstable when exposed to light (t½ 3·2–233 min) and shows an inverse relationship between concentration and rate of degradation. The drug is also unstable under acidic conditions, but shows a more limited spectrum of degradation products than those arising from photolysis.
Controlled Release of Oral Drugs from Cross-linked Polyvinyl Alcohol Microspheres
Authors: Thanoo B C , Sunny M C , Jayakrishnan A 
Published: April 2011

Abstract
A new technique for the preparation of cross-linked polyvinyl alcohol (PVA) microspheres containing various drugs is described. An aqueous solution of PVA containing various concentrations of glutaraldehyde was dispersed as droplets in liquid paraffin using a suitable stabilizing agent. Cross-linking of PVA droplets with glutaraldehyde was induced by an acid catalyst (HCl) which was produced by the addition of small quantities of benzoyl chloride into the dispersion medium. Microspheres containing drugs such as aspirin, griseofulvin and nicotinic acid were prepared by carrying out the cross-linking reaction in the presence of such drugs. The drug release studies were carried out in simulated gastric and intestinal fluids without enzymes at 37°C. It was observed that increase in the cross-linking density of the microspheres reduced the drug release rate considerably, suggesting that the release profiles could be controlled by changing the cross-linking density. It was also observed that a higher rate of release was obtained from smaller beads.
Oral Sustained-release Drug Delivery Systems using Polycarbonate Microspheres Capable of Floating on the Gastric Fluid
Authors: Thanoo B C , Sunny M C , Jayakrishnan A 
Published: April 2011

Abstract
Polycarbonate microspheres loaded with aspirin, griseofulvin and p-nitroaniline were prepared by a solvent evaporation technique. High drug loading (&gt; 50%) was achieved by this process. Drug-loaded microspheres were found to float on simulated gastric fluid and intestinal fluid. Drug-release studies were carried out in these fluids at 37°C. Increasing the drug to polymer ratio in the microspheres increased both their mean particle size and the release rate of the drugs. It was concluded that sustained delivery of drugs could be effected using this matrix.
Red Blood Cell Partitioning, Protein Binding and Lipophilicity of Six Phenothiazines
Authors: Marroum P J , Curry S H 
Published: April 2011

Abstract
Hexane-water partition coefficients, pKa values, protein binding and red blood cell partitioning were studied with six phenothiazine drugs. Red cell partitioning was independent of drug concentration, and there was no correlation between partitioning and physicochemical characteristics. Red cell partitioning could be used indirectly to estimate protein binding, but two potential pitfalls of general importance were found. Failure to consider drug binding of glassware and haematocrit changes were shown to induce incorrect estimates of both red cell partitioning and protein binding, as well as hexane-water partition coefficients.
Fc-Receptor-mediated Targeting of Antibody-bearing Liposomes Containing Dideoxycytidine Triphosphate to Human Monocyte/Macrophages
Authors: Betageri G V , Black C D V , Szebeni J , Wahl L M , Weinstein J N 
Published: April 2011

Abstract
Liposomes bearing surface-attached antibody (L-Ab) molecules can be used for various purposes including the immunospecific delivery of drugs or other materials to antigenic target cells. In this study, L-Ab were prepared to deliver an anti-human immunodeficiency virus (HIV) drug, dideoxycytidine triphosphate (ddCTP) to human monocyte/macrophages. Cells of the monocyte/macrophage lineage are an important reservoir of HIV-1. A mouse monoclonal antibody IgG2a was labelled with 125I and modified using N succinimidyl-3-(2-pyridyldithio)propionate (SPDP) as a heterobifunctional reagent in order to conjugate with liposomes to produce a covalent bond (thioether). SPDP-modified antibody was incubated with liposomes containing 5 mol% of maleimido phenyl butyrate phosphatidylethanolamine (MPB-PE) at room temperature (21°C) for 24 h. L-Ab were separated from free and aggregated antibodies by centrifugation. L-Ab were characterized by measuring particle size and binding to anti-mouse IgG-sepharose. Ninety five per cent of the liposomal (L-Ab) lipid label was bound to anti-mouse IgG-sepharose, whereas only 7% of plain liposomes were bound, indicating non-specific binding. Uptake of L-Ab was measured in human monocyte/macrophages as a function of time and compared with that of plain liposomes. The uptake increased with time and it was 4–6 times greater than that of plain liposomes although part of that effect may have been due to unreacted MPB groups.
Effects of Vanadate on Responses of Guinea-pig Isolated Trachea to Spasmogens
Authors: Cortijo J , Santamaría P , Antón M , Villagrasa V , Morcillo E 
Published: April 2011

Abstract
The effects of vanadate on the contractility of the guinea-pig isolated trachea was examined. Vanadate (0·1 Mm) produced a sustained contraction that was abolished in Ca2+-free EGTA (0·1 Mm)-containing physiological salt solution but was resistant to verapamil (1 μm). Vanadate (0·1 Mm) depressed tracheal responses to CaCl2 (in Ca2+-free depolarizing solution), KCl, acetylcholine, histamine and 5-hydroxytryptamine. For vanadate (10 μm), the inhibition of spasmogenic responses only reached statistical significance for histamine and 5-hydroxytryptamine. Caffeine (1 Mm)-induced spasm (trachea at 20°C in the presence of indomethacin (2·8 μm)) was not affected by vanadate (10 μm-0·1 Mm). Vanadate (0·1 Mm) slightly depressed the responses to KCl (50 Mm), acetylcholine (1 Mm), histamine (1 Mm) or 5-hydroxytryptamine (0·1 Mm) observed in Ca2+-free EGTA (0·1 Mm)-containing physiological salt solution. Vanadate (0·5 Mm) depressed Ca2+ (20 μm)-induced contraction of trachea which had been chemically skinned of its plasmalemmal membranes. The mechanism of the inhibitory effect of vanadate on tracheal responses to a variety of spasmogens remains obscure, but, under in-vitro conditions, vanadate clearly does not induce hyper-reactivity of airway smooth muscle to spasmogens.
Calcium Antagonism and Structure-affinity Relationships of Terfenadine, a Histamine H1 Antagonist, and Some Related Compounds
Authors: Zhang M Q , Caldirola P , Timmerman H 
Published: April 2011

Abstract
Calcium channel affinity of terfenadine and its optical isomers was determined by the displacement of [3H]nitrendipine on rat cerebral cortex membranes. Terfenadine showed a pKd of 6·36±0·03 whereas its R(+)-isomer (VUF4567) had a pKd value of 6·39±0·03 and the S(–)-isomer (VUF4568) had a pKd of 6·40 ± 0·04. The same affinity between the enantiomers suggests that the binding domain on the membrane is not sterically restricted towards the part of the molecule in which the chiral centre is present. The characteristics of terfenadine in regulating [3H]nitrendipine binding were similar to those of some other diphenyl-alkylamine type calcium antagonists. It allosterically altered the binding affinity for nitrendipine and acted at the same site linked to the calcium channel as gallopamil. A structure-affinity relationship among a group of terfenadine analogues is discussed.
Urinary excretion of hexafluoroisopropanol glucuronide and fluoride in patients after sevoflurane anaesthesia
Authors: Jiaxiang Ni , Sato Nobuyoshi , Fujii Kohyu , Yuge Osafumi 
Published: April 2011

Abstract
The excretion of sevoflurane metabolites in the urine collected every 12 h after sevoflurane anaesthesia was measured by ion exchange chromatography. A metabolite, which was converted on incubation with glucuronidase to hexafluoroisopropanol was detected in the urine. The maximum excretion was found in the first 12 h after anaesthesia, none was found in the last collection 3 days after anaesthesia. The excretion half-life for the metabolite was calculated to be 55 h. A significant increase in the urinary excretion of organic and inorganic fluoride was also observed during the first 12 h after anaesthesia. The cumulative organic and inorganic fluoride excretion in the 3 days after sevoflurane anaesthesia was 1588 and 856 μmol, respectively (ratio = 1·85). The excreted half-lives for organic and inorganic fluoride were calculated to be 4028 and 2069 min, respectively. Our study showed that a hexafluoroisopropanol glucuronide is excreted in the urine, and the major part of urinary metabolites of sevoflurane, organic and inorganic fluoride, are excreted within 2 days of sevoflurane inhalation in man.
Intraduodenal delivery of intrinsically and extrinsically labelled CaCO3 in the rat: effect of solubilization on calcium bioavailability
Authors: Kanerva R L , Webb D R , Andon M B , Smith K T 
Published: April 2011

Abstract
The dissolution of CaCO3 before intraduodenal administration was found to be an important factor determining calcium (Ca) bioavailability. Extrinsically and intrinsically labelled 47CaCO3 preparations were sequentially dissolved by serial additions of HCl. Aliquots of these preparations were collected before (no HCl added) and during the solubilization process and administered intraduodenally to rats. Whole body 47Ca retention 72 h post-dose was used as a measure of Ca bioavailability. Although dissolution of CaCO3 significantly increased Ca bioavailability (p &lt; 0·001), Ca from both intrinsically and extrinsically labelled CaCO3 was absorbed and retained to some extent without prior acid dissolution. Due to a disproportionately high concentration of 47Ca on the particle surface, extrinsically labelled 47CaCO3 overestimated bioavailability when unsolubilized or partially solubilized CaCO3 preparations were used (P &lt; 0·05). These data indicate that dissolution is a determining factor for Ca bioavailability from CaCO3. Incomplete dissolution will significantly limit but not completely prevent Ca bioavailability. The disintegration and dissolution characteristics of commercial CaCO3 preparations, which vary widely, may produce important differences in Ca absorption.
Effect of Thyrotropin-releasing Hormone on Pentobarbitone-induced Sleep in Rats: Continuous Treatment with a Sustained Release Injectable Formulation
Authors: Hashimoto Tadatoshi , Wada Takeo , Fukuda Naohisa , Nagaoka Akinobu 
Published: April 2011

Abstract
The mode of action and the time course of the effects of continuous thyrotropin-releasing hormone (TRH) treatment using a two-week sustained release injectable formulation of TRH-containing copoly(±)-lactic/glycolic acid) microspheres (TRH-SR) on pentobarbitone-induced sleeping time were studied in rats. Subcutaneous treatment with TRH-SR at doses corresponding to 0·05 and 0·2 mg of TRH kg−1 day−1 caused a dose-related shortening of pentobarbitone-induced sleeping time with a minimum effective dose (MED) of 0·05 mg kg−1 day−1, without affecting the body weight gain. On the other hand, the MED of TRH when given as a bolus subcutaneous injection was 40 mg kg−1. The effect of TRH-SR treatment was blocked by intraperitoneal scopolamine (0·1 mg kg−1) and mecamylamine (2 mg kg−1) but not by scopolamine methyl bromide (0·1 mg kg−1). The results indicate that continuous TRH treatment using TRH-SR causes shortening of pentobarbitone-induced sleeping time at doses lower than those required using bolus injection and probably by a mechanism involving the central cholinergic system.
Kinetic Evaluation of the Ciliotoxicity of Methyl- and Propyl-p-hydroxybenzoates Using Factorial Experiments
Authors: Jian L , Po A Li Wan 
Published: April 2011

Abstract
The ciliotoxicity of methyl-p-hydroxybenzoate (methyl paraben, MHB) and propyl hydroxybenzoate (propyl paraben, PHB) was investigated. It is shown that at the concentrations used (0·28 and 0·38 Mm) PHB exerted only mild toxicity. The MHB solutions used (1·18 and 2·36 Mm) were much more ciliotoxic. There was, however, an order of magnitude difference in the concentrations used as a result of constraints imposed by their differing aqueous solubilities. There was no evidence of synergism in the ciliotoxicity of the two compounds when the MHB concentration was raised from 1·18 to 2·36 Mm and the PHB concentration was raised from 0·28 to 0·38 Mm in a 22 factorial experiment. At those levels the two compounds showed additive effects. On the other hand, clear synergism was evidenced by the fact that the ciliotoxicity of both MHB and PHB was dependent on whether the cilia were exposed to each hydroxybenzoate singly or in combination. The results combined with those of an earlier study, indicate that it is not possible to improve the selectivity of antimicrobial activity without also increasing ciliotoxicity.
Suppressive Effects of Hyaluronic Acid on Elastase Release from Rat Peritoneal Leucocytes
Authors: Akatsuka Masahiro , Yamamoto Yumiko , Tobetto Kenji , Yasui Tadashi , Ando Takao 
Published: April 2011

Abstract
Effects of hyaluronic acid on the release of elastase from rat peritoneal leucocytes were studied by measuring the leucocyte elastase activity using a synthetic peptide substrate. Leucocyte elastase release was induced by opsonized zymosan, 12-O-tetradecanoyl phorbol-13-acetate (TPA) and N-formyl-l-methionyl-l-leucyl-l-phenylalanine combined with cytochalasin B. Calcium ionophore A23187 potentiated the action of TPA on leucocyte elastase release, whereas hyaluronic acid inhibited leucocyte elastase release regardless of the method of stimulation. Inhibitory effects of hyaluronic acid were dependent on its concentration and molecular weight. Hyaluronic acid of the highest molecular weight (2·0 × 106) indicated a potent inhibitory effect on elastase release. Our present findings suggest that hyaluronic acid may elicit an anti-inflammatory effect by inhibiting leucocyte elastase-dependent pathological processes.
Differential effects of the (+)- and (–)-gossypol enantiomers upon Entamoeba histolytica axenic cultures
Authors: González-Garza María Teresa , Matlin Stephen A , Mata-Cárdenas Benito D , Said-Fernández Salvador 
Published: April 2011

Abstract
The in-vitro anti-amoebic effects of (±)-, (+)-, (–)-gossypol and emetine were tested against axenic trophozoites from five Entamoeba histolytica strains. The (–)-isomer was more active than the racemate and the (+)-isomer. These results indicate that the gossypol anti-amoebic activity is mainly due to its content of (–)-gossypol in all strains tested.
Absence of desensitization to the relaxant activity of streptozotocin in isosorbide dinitrate-tolerant rat aorta
Authors: Uma Serdar , BalcioḡLu Aygül 
Published: April 2011

Abstract
The effect of in-vitro isosorbide dinitrate (ISDN)-induced tolerance on the vasodilatory actions of streptozotocin, a nitric oxide containing compound, and papaverine was studied in rat aortic strips precontracted by phenylephrine. Aortas made tolerant to ISDN remained fully responsive to streptozotocin but exhibited a greater response to low concentrations of papaverine compared with control strips. Methylene blue produced parallel displacement to the right of the relaxant concentration-effect curves of both ISDN and streptozotocin, whereas responses to only low concentrations of papaverine were significantly antagonized. These results indicate that the relaxant activity of streptozotocin is due to the stimulation of guanylate cyclase and impaired activity of this enzyme is not likely to be the operating mechanism for nitrate tolerance. It is also suggested that the vasodilating action of papaverine is partly dependent on the tissue cGMP level.
Antidiarrhoeic activity of quercitrin in mice and rats
Authors: Gálvez J , Crespo M E , Jiménez J , Suárez A , Zarzuelo A 
Published: April 2011

Abstract
Quercitrin, a flavonoid isolated from Euphorbia hirta, shows antidiarrhoeic activity at doses of 50 mg kg−1, against castor oil- and PGE2-induced diarrhoea in mice, but not when magnesium sulphate is used as a cathartic agent. It also delays rat small intestinal transit if this is accelerated with castor oil. However, the flavonoid does not modify the fluid transport across the colonic mucosa when it is administered intraluminally, either in normal conditions or when this transport is altered by PGE2 or sodium picosulphate. However, quercetin, the aglycone of quercitrin, increases the colonic fluid absorption only in the presence of secretagogue compounds, such as PGE2 and sodium picosulphate. It is concluded that the antidiarrhoeic activity of quercitrin is due to its aglycone, quercetin, which is released by the glycoside in the intestine.
Investigation of Synergism between Combinations of Ciprofloxacin, Polymyxin, Sulphadiazine and p-Aminobenzoic acid
Authors: Richards R Michael E , Xing Dorothy K L 
Published: April 2011

Abstract
Subinhibitory concentrations of combinations of any two of ciprofloxacin, colistin (or polymyxin B), sodium sulphadiazine and p-aminobenzoic acid were shown by checkerboard minimum inhibitory concentration determinations to have synergistic inhibitory activity against Pseudomonas aeruginosa and to have either synergistic or additive activity against Staphylococcus aureus. In addition, sulphadiazine plus either ciprofloxacin or polymyxin showed markedly enhanced killing activity against both P. aeruginosa and S. aureus. p-Aminobenzoic acid plus either ciprofloxacin or polymyxin also demonstrated enhanced killing activity against P. aeruginosa but these combinations were less effective in enhancing activity against S. aureus. Ciprofloxacin in combination with polymyxin had a marked synergistic effect against P. aeruginosa but only a slight synergistic effect against S. aureus. These findings indicate a potential usefulness for the synergistic combinations against P. aeruginosa and S. aureus in the clinical situation; that is, they indicate an extended role for sulphonamides and support a potential role for p-aminobenzoic acid as enhancers of the activity of primary antibacterial agents such as ciprofloxacin and polymyxin. We suggest that for a second antibacterial to enhance the activity of ciprofloxacin, it may be necessary for the second antibacterial to increase cell permeability so increasing bacterial uptake of ciprofloxacin.
Post-UV Survival and Mutagenesis in DNA Repair-proficient and -deficient Strains of Escherichia coli K-12 Grown in 5-Azacytidine to Inhibit DNA Cytosine Methylation: Evidence for Mutagenic Excision Repair
Authors: Radnedge L , Pinney R J 
Published: April 2011

Abstract
Inhibition of cytosine methylation by growth in 5-azacytidine (5-azaC), did not affect the sensitivities to DNA damage induced by exposure to ultraviolet light (UV) of Escherichia coli K-12 strains AB1157 dcm+, which is fully DNA repair-proficient, LR68 (a dcm derivative of ABU57), JC3890 dcm+ uvrB, deficient in error-free excision repair, TK702 dcm+ umuC, deficient in error-prone repair, or TK501 dcm+ uvrB umuC, which lacks both excision repair and error-prone repair. However, growth in 5-azaC increased the post-UV survival of strains AB2463 recA(Def), AB2470 recB and AB2494 lexA(Ind−), which are deficient in the induction or expression of recombination repair or error-prone repair of DNA. Spontaneous mutation frequencies were increased in strains LR68, AB2463, AB2470 and AB2494 by growth in 5-azaC, but remained unaltered in strains AB1157, JC3890, TK702 or TK501. Growth in 5-azaC significantly increased UV-induced mutation frequencies in strains AB2463 and AB2470, significantly reduced UV-induced mutation in strain JC3890, but had little effect on UV-induced mutation in the other strains. The results suggest that 5-azaC may induce a normally error-free DNA repair pathway to become error-prone and therefore genotoxic.