bluuebunny/crossref_metadata_2025_split huggingface dataset:
Visual recovery using small dilating eye drops
Authors: Gray R H , Franklin S J , Reeves B C 
Published: April 2011

Abstract
It is well established that reduced size dilating eye drops of 1% tropicamide and 10% phenylephrine (micro drops) are effective for clinical purposes. Excellent pupil dilatation (mydriasis) is achieved and pupil constriction does not occur in response to light. In this study, the effect of micro drops of 1% tropicamide on distance and near visual recovery was compared with standard drops in a group of 20 healthy volunteers. For each person studied, one eye was selected at random to be tested first with the standard drop size, and then after a minimum of one week, the same eye was again tested using a drop of the same drug one fifth standard size. An iris photograph, Snellen visual acuity at 6 m, and reading visual acuity was obtained for each test procedure: before drop instillation and at 30 min, 1, 2 and 4 h after drug instillation. Use of the micro drops caused a small but statistically significant improvement in the rate of recovery of distance and near visual acuity. These findings, allied to the known beneficial effects of reduced systemic absorption using micro drops, lend further weight to the argument that mydriasis may be achieved more safely, with fewer side effects, and with earlier return of normal vision when reduced size drops are used. It is hoped that practical micro drop dispensers will be developed.
Dispositional study of opioids in mice pretreated with sympathomimetic agents
Authors: Dambisya Yoswa M , Chan Kelvin , Wong Chak-Lam 
Published: April 2011

Abstract
Brain and plasma levels of morphine and codeine were determined by an assay method involving solid-phase extraction and ion-pair reversed phase HPLC. Detection was by a variable wavelength UV-detector (for codeine) and an amperometric electrochemical detector (for morphine) coupled in series. Ephedrine or phenylpropanolamine pretreatment did not interfere with the plasma disposition of morphine, evidenced by overlapping plasma concentration-time profiles. Brain opioid levels were equally unaffected by sympathomimetic pretreatment. The relative ratios of brain to plasma concentrations at the time corresponding to the respective peak anti-nociceptive activity for morphine and codeine revealed no significant differences. It is concluded that single doses of ephedrine and phenylpropanolamine do not affect the disposition of morphine and codeine in mice.
Anorectic activity of fluoxetine and norfluoxetine in mice, rats and guinea-pigs
Authors: Anelli M , Bizzi A , Caccia S , Codegoni A M , Fracasso C , Garattini S 
Published: April 2011

Abstract
The present study aimed to establish the role of the metabolite norfluoxetine in the anorectic activity of fluoxetine, and to relate the anorectic doses (ED50) to the brain concentrations of the parent drug and its metabolite. Fluoxetine showed anorectic activity at increasing intraperitoneal doses (ED50 = 391, 34·7 and 21·7 μmol kg−1 in mouse, rat and guinea-pig, respectively) and norfluoxetine was slightly more active (24·3, 22·9 and 19·1 μmol kg−1, respectively) in all three species. In terms of maximum concentration (Cmax) and area under the curve (AUC) within the experimental period (0–90 min), brain concentrations varied widely and were poorly related to the dose; guinea-pig appeared to be much more sensitive to fluoxetine than was mouse or rat. Administered norfluoxetine was present in the brain of the three species in approximately the same order as fluoxetine, i.e. lower in guinea-pig than in mouse or rat. The Cmax and AUC of norfluoxetine after fluoxetine administration was 50–60% of the values after an equiactive dose of norfluoxetine in mouse and guinea-pig, and more than 80% in rat.
The effect of thymidine on the antibacterial and antiviral activity of zidovudine
Authors: Shepherd A J , Barr P , Lewin C S 
Published: April 2011

Abstract
The effect of thymidine and deoxyadenosine on the antiviral and antibacterial effect of zidovudine was studied in human immunodeficiency virus type 1 (HIV-1) Escherichia coli and Salmonella typhimurium. In quantitative assays, 10 μg mL−1 thymidine was shown to increase the 50% inhibitory concentration (IC50) of zidovudine for HIV-1 by approximately 100-fold and to reduce zidovudine (1 μm)-induced protection of C8166 cells from 204 to 0·18 log syncytial-forming units. Thymidine also antagonized the antibacterial effect of zidovudine for two E. coli and three S. typhimurium species in a dose-dependent manner; 10 μg mL of thymidine increased the minimum inhibitory concentration of zidovudine for E. coli strains by 10–40-fold and for S. typhimurium strains by three-fold. Deoxyadenosine reduced the minimum inhibitory concentration of zidovudine against all five bacterial strains but had no effect on the IC50 of zidovudine for HIV-1, nor did it significantly reverse the antagonism of the antibacterial and antiviral activity of thymidine. The induction of the SOS response in E. coli was reversed in a dose-dependent manner by thymidine while the presence of deoxyadenosine increased induction of the SOS response by zidovudine at suboptimal concentrations.
Effects of long-term laxative treatment on neuropeptides in rat mesenteric vessels and caecum
Authors: Milner Pamela , Belai Abebech , Tomlinson Annette , Hoyle Charles H V , Sarner Shula , Burnstock Geoffrey 
Published: April 2011

Abstract
In order to investigate the toxic effects of long-term treatment with anthraquinone laxatives, rats were fed either chocolate alone, or chocolate adulterated with senna or danthron (1,8-dihydroxyanthraquinone) for 5 months. Mesenteric blood vessels and the outer muscle layers of the caecum, together with the myenteric plexus, were examined using ultrastructural, histochemical, immunohistochemical and immunoassay techniques. There was no ultrastructural evidence of degeneration in either the mesenteric vessels or the caecum. In the mesenteric vessels, levels of neuropeptide Y were significantly reduced in the danthron-fed rats, but levels of substance P (SP), calcitonin gene-related peptide (CGRP) and vasoactive intestinal polypeptide (VIP) were unaffected by all treatments. In the caecum, VIP-, SP- and CGRP-immunoreactivity and catecholamine-fluorescence were unchanged by the laxative treatments.
Illicitly Imported Heroin Products (1984 to 1989): Some Physical and Chemical Features Indicative of Their Origin
Authors: O'Neil Philip J , Pitts Jane E 
Published: April 2011

Abstract
Samples taken from seizures of imported illicit heroin preparations of known geographical origin have been examined. The typology developed in two previous surveys of illicit heroin products is applicable to many of the samples studied in this work, although significant changes have occurred in the chemical profile of illicit heroin products from certain geographical regions. It remains possible, however, to give an opinion as to the origin of many samples of illicit heroin of unknown provenance. The observation in the previous surveys that unrelated samples of illicit heroin possess unique chemical profiles has been confirmed by the present results.
Opioid Properties of Some Isomeric Derivatives of Phencyclidine
Authors: Casy A F , Dewar G H , Al-Deeb O A A 
Published: April 2011

Abstract
The phencyclidine analogues (±)-α-, (±)-β-, and (+)-α- and (–)-α-4-hydroxy-3-methyl-4-phenyl-l-(1-phenylcyclohexyl)piperidine, all with known relative and absolute stereochemistry, have been prepared, and their analgesic potencies related to corresponding prodines. In contrast to the prodines, the (±)-α-phencyclidine analogue was a more potent analgesic than its diastereoisomer, while in agreement with observations in the prodine series, the 3R, 4S-α-enantiomer displayed substantially greater potency than its mirror image form.
Investigation of the Interaction Mode of Phenothiazine Neuroleptics with α1-Acid Glycoprotein
Authors: Miyoshi Toshimi , Sukimoto Katsuaki , Otagiri Masaki 
Published: April 2011

Abstract
The interaction of phenothiazine neuroleptics with α1-acid glycoprotein (AGP) and desialylated AGP (asialoAGP) has been investigated by fluorescence, circular dichroism spectroscopy and by equilibrium dialysis. The binding parameters of phenothiazines obtained from fluorescence agreed closely with those obtained from circular dichroism and equilibrium dialysis. The binding affinities (nK) to AGP were slightly higher than binding affinities to asialoAGP. Attempts to correlate binding affinities with partition coefficients suggested that hydrophobic forces were mainly involved in the binding of phenothiazine neuroleptics to AGP and asialoAGP. However, electrostatic interaction was also found to be involved as suggested by experimental data obtained from the influence of oleic acid and caesium chloride on the drug binding to the two proteins.
Effects of Anaesthetic Agents on Pressor Response to β-Blockers in the Rat
Authors: Abdelrahman Aly , Wang Yong-Xiang , Pang Catherine C Y 
Published: April 2011

Abstract
It has been shown that paradoxical pressor response to a β-adrenoceptor antagonist occurs in conscious rats pretreated with an α-adrenoceptor antagonist. This study examines the influence of anaesthetic agents on mean arterial pressure (MAP) response to a η-blocker. Cumulative dose-response curves of propranolol (non-selective), ICI 118,551 (β2-selective) and atenolol (β1-selective) were constructed in phentolamine-treated rats anaesthetized with urethane, pentobarbitone or halothane. I.v. injections of all three β-blockers caused dose-dependent increases in MAP in urethane-anaesthetized rats. In halothane-anaesthetized rats, propranolol and atenolol did not alter MAP while ICI 118,551 caused a small dose-dependent increase in MAP. In the presence of pentobarbitone, none of the β-blockers raised MAP. In the second series of experiments, a single i.v. bolus dose of propranolol was given in phentolamine-treated rats anaesthetized with pentobarbitone, amobarbitone, ketamine or chloralose. Propranolol did not affect MAP in rats anaesthetized with pentobarbitone, amobarbitone and chloralose but it partially reversed the hypotensive effect of phentolamine in ketamine-anaesthetized rats. In the third series, propranolol or atenolol was i.v. injected in pentobarbitone-anaesthetized rats treated with both phentolamine and adrenaline. Both propranolol and atenolol raised MAP. Our results show that anaesthetic agents differentially affect the MAP response to a β-blocker.
The Optical Resolution of Racemic Chlorpheniramine and Its Stereoselective Pharmacokinetics in Rat Plasma
Authors: Sakurai Eiichi , Yamasaki Seiji , Iizuka Yukisumi , Hikichi Noboru , Niwa Hiroshi 
Published: April 2011

Abstract
An ovomucoid-conjugated column has been developed for the chiral stationary-phase liquid chromatographic resolution of racemic chlorpheniramine with a quantitation limit of 0·05 μg mL−1. The assay was used to study the stereoselective kinetics of chlorpheniramine enantiomers in rats. After bolus intravenous administration of racemic chlorpheniramine maleate (20 mg kg−1), plasma concentration of the (–)-form was higher than that of the (+)-form. In the elimination phase, the concentrations of (+)- and (–)-chlorpheniramine in the plasma declined biexponentially with half-lives of 18·2 and 50·0 min, respectively. Although there was no significant difference in blood-to-plasma concentration ratio of both enantiomers, the apparent total blood clearance of (+)-chlorpheniramine was twice as large as that of the (–)-isomer. Binding of (–)-chlorpheniramine to rat plasma protein was stronger than that of (+)-chlorpheniramine suggesting stereoselective pharmacokinetics may be due to a difference in the plasma protein binding.
An Improved Model for Studies on Transdermal Drug Absorption In-vivo in Rats
Authors: Vollmer U , Müller B W , Wilffert B , Peters T 
Published: April 2011

Abstract
In rats, transdermal drug absorption can be studied under physiological conditions by cannulating the peripheral skin vein, draining the area of the skin which is used for drug application, and collecting the blood. This method leads to decreased blood volume, which causes a reduction in skin blood flow and limits the maximal duration of the experiment. We improved the model by replacing the collected blood with blood from donor animals, so enabling the measurement of transdermal absorption over a period of 5 h under near constant conditions of blood pressure, haematocrit and skin blood flow. The model was applied to the transdermal absorption of [3H]prazosin and [3H]scopolamine and their permeability coefficients, fluxes and lag-times were determined. The model is suitable for measurements of transdermal drug absorption under in-vivo conditions, both for comparison of absorption profiles of different drugs and of the same drug in different formulations.
Phorbol Dibutyrate Induces Contractions in Bovine Cerebral Arteries by an Extracellular Calcium-independent Mechanism
Authors: Encabo Araceli , Ferrer Mercedes , Marín Jesús , Peiró Concepción , Redondo Juliana , De Sagarrat Ma Rosa , Balfagón Gloria 
Published: April 2011

Abstract
The aim of the present study was to analyse the ability of phorbol 12,13-dibutyrate (PDB) to activate protein kinase C (PKC), measured by its capacity to translocate the enzyme from the cytosol to the membrane fraction, as well as to induce vasconstrictive responses in segments from branches of bovine cerebral arteries. PDB (0·1 μm) produced a marked translocation of PKC activity from the cytosolic to the membranous fraction. This drug induced concentration-dependent contractions which were slow in onset. The contraction elicited by PDB was reduced by the PKC inhibitor, staurosporine (1 and 10 Nm), but unaltered by both Ca2+-free medium containing 3 Mm EGTA and the Ca2+-channel antagonist, nifedipine (1 μm). Preincubation of segments with PDB (10 and 30 Nm) reduced the vasoconstriction elicited by 5-hydroxytryptamine (5-HT) in a concentration- and preincubation time-dependent manner. These data indicate that bovine cerebral arteries possess cytosolic and membranous PKC activities, that the vasoconstrictive responses induced by PDB were independent of extracellular Ca2+, that cytosolic C-kinase is translocated to the membrane and probably down-regulated by PDB, and that this enzyme is not involved in 5-HT responses, but is down-regulated by PDB.
Effects of NZ-107 on Airway Inflammation and Cell Activation in Guinea-pigs
Authors: Iwama Takehisa , Nagai Hiroichi , Koda Akihide 
Published: April 2011

Abstract
The effects of NZ-107 on some airway inflammation models and the generation of superoxide anion (O2−) were studied in guinea-pigs. Airway inflammation was caused by intra-tracheal injection of murine recombinant interleukin-5 (mrIL-5, 15 μg/animal), inhalation of platelet-activating factor (PAF, 0·003%) and intra-tracheal injection of leukotriene B4 (LTB4, 10 μg/animal). NZ-107 (4-bromo-5-(3-ethoxy-4-methoxybenzylamino)-3(2H)-pyridazinone) at a dose of 50 mg kg−1, intraperitoneally reduced mrIL-5- and PAF-induced eosinophilia. This compound at a dose of 25 and 50 mg kg−1 also suppressed LTB4-induced eosinophilia and neutrophilia in bronchoalveolar lavage fluid (BALF). On the other hand, prednisolone at a dose of 20 mg kg−1, i.p., prevented the increased number of macrophages, eosinophils and neutrophils induced by mrIL-5, the increased number of eosinophils induced by PAF and the increased number of eosinophils and neutrophils induced by LTB4 in BALF. Furthermore, both drugs reduced mrIL-5- or PAF-induced increase in the number of airway epithelial cells in BALF. The generation of O2− was measured by the method of cytochrome C reduction. NZ-107 (10–100 μg mL−1) attenuated PAF- and FMLP-induced O2− production from macrophages and reduced PAF-induced O2− generation by eosinophils but had no effect on that from neutrophils. These results indicate that NZ-107 prevents the increased number of pulmonary eosinophils and airway epithelial cells and the activation of macrophages and eosinophils, suggesting that NZ-107 may be useful as a remedy for airway inflammatory diseases such as bronchial asthma.
Different Modes of Blockade by p-Phenylene-polymethylene Bis-ammonium Compounds of the Nicotinic Acetylcholine Receptor Channel in Skeletal Muscle Cells of Mice
Authors: Nojima Hiroshi , Kimura Ikuko , Muroi Masashi , Kimura Masayasu 
Published: April 2011

Abstract
The structure-activity relationships of five newly synthesized p-phenylene-polymethylene bis-ammonium (PMBA: C6H4[(CH2)nN+R3]2) compounds were investigated on the blockade of the nicotinic acetylcholine receptor (nAChR) channel. The cell-attached patch clamp configuration was used to measure single-channel currents in the endplate region of single flexor digitorum brevis muscle cells of adult mice. The bis-trimethylammonium compounds PMBA-1 (n = 4, R = CH3) and PMBA-23 (n = 6, R = CH3) produced channel opening above 0·3 μm and open channel blockade above 10 and 3 μm, respectively. The bis-triethylammonium compounds PMBA-43 (n = 1, R = CH2CH3) and PMBA-24 (n = 6, R = CH2CH3) showed no channel opening action, but PMBA-21 (n = 4, R = CH2CH3) opened channels weakly at 3 and 10 μm. These bis-triethylammonium compounds exerted different blocking actions on acetylcholine-activated channel currents. Above 10 μm PMBA-43, like tetraefhylammonium, blocked open channels by decreasing the mean open time by rapid partial closing of the channel during the open-phase. At 10 μm, PMBA-21 blocked open and closed channels by decreasing the opening frequency by means of an irregular sequence of short pulses. At 0·3 μm, PMBA-24 blocked closed or nonconducting channels by decreasing the opening frequency without producing changes in mean open time. These results indicate that by lengthening the distance between two nitrogen atoms in the bis-triethylammonium group of PMBA, open channel blockade changes to closed channel blockade. PMBA compounds were classified into three types of nAChR channel blockers: PMBA-43 as an open, PMBA-21 as an open and closed, and PMBA-24 as a closed or nonconducting channel blocker.
In-vitro Permeability to Salicylic Acid of Human, Rodent, and Shed Snake Skin
Authors: Harada Kayo , Murakami Teruo , Kawasaki Eiko , Higashi Yutaka , Yamamoto Shoso , Yata Noboru 
Published: April 2011

Abstract
In-vitro permeability to salicylic acid of human, rodent, and shed snake skin has been examined for the purpose of selecting model membranes for human skin corresponding to different anatomic sites, since a marked regional variation is suggested among the different sites. The greatest permeability to salicylic acid was observed in the scrotum, that of the sole was negligible. The cheek, neck, and inguinal skin seemed more permeable than the breast, back, thigh, lower leg, or foot skin. Shed snake and skin of hairless rat were found to show similar permeability to human breast and thigh skin. Wistar rat and nude mouse skin showed similar permeability to human cheek, neck, and inguinal skin.
Light stability of molsidomine in infusion fluids
Authors: Vandenbossche G M R , De Muynck C , Colardyn F , Remon J P 
Published: April 2011

Abstract
The influence of artificial light, daylight or stimulated sunlight on the stability of molsidomine was investigated. In static experiments an 80 μg mL−1 solution of molsidomine in saline was stored in an unprotected infusion bag. During dynamic experiments the molsidomine solution (80 μg mL−1) was dropped at 12·5 mL h−1 from an unprotected infusion bag, from an infusion bag covered with aluminium-foil, or from an infusion bag protected with a UV-cover. Either unprotected infusion tubing or infusion tubing with a UV-filter were connected to the infusion bags. Static as well as dynamic experiments showed a half-life of about 20 min for the unprotected molsidomine solutions, when placed behind a window during a sunny day. Protection from light of the infusion bag but not of the infusion tubing had only a minor influence on the drug half-life. Protection of the infusion bag and the infusion tubing with a UV-filter increased the half-life to several days. These results confirm that both the infusion bag and the infusion tubing need adequate light protection during molsidomine administration.
Hydrolysis of Partially Saturated Egg Phosphatidylcholine in Aqueous Liposome Dispersions and the Effect of Cholesterol Incorporation on Hydrolysis Kinetics
Authors: Grit Mustafa , Zuidam Nicolaas J , Underberg Willy J M , Crommelin Daan J A 
Published: April 2011

Abstract
Hydrolysis kinetics of partially hydrogenated egg phosphatidylcholine (PHEPC) were studied as a function of pH, temperature, buffer concentration, ionic strength, and the effect of cholesterol incorporation. Results showed that PHEPC has a maximum stability at around pH 6·5. General acid base catalysis was observed for acetate, HEPES and Tris buffers. Increasing the ionic strength of the buffer solutions did not influence the hydrolysis kinetics. The relationship between the observed hydrolysis rate constants and the temperature could adequately be described by the Arrhenius equation. Incorporation of cholesterol did not affect the hydrolysis kinetics. This result indicates that the hydrolysis kinetics of PHEPC do not depend on the changes in bilayer rigidity induced by cholesterol incorporation. Cholesterol is stable under the experimental conditions used in this study; no changes were observed in cholesterol concentration over the experimental time interval.
Hydrolysis and Stability of Acetylsalicylic Acid in Stearylamine-containing Liposomes
Authors: Habib Muhammad J , Rogers James A 
Published: April 2011

Abstract
The hydrolysis and the stabilization of acetylsalicylic acid (ASA) in liposomes at 30°C were studied. The liposomes consisted of dimyristoylphosphatidylcholine (DMPC) and stearylamine. At pH 4·0 and 8·0, the pseudo-first-order rate constants (kobs) in DMPC: stearylamine (2:1 mole ratio) liposomes were approximately 60% of the values in control solutions (kB) if ASA was incorporated via the organic phase. In contrast, when ASA was added via the aqueous phase, kobs = kB at pH 4·0 but kobs &lt; kB at pH 8·0 and kobs increased with the fraction of stearylamine in the liposomes. However, when ASA was added via the organic phase, reactions occurred which resulted in the loss of ASA as a function of the time period between phase admixture and the point of film hydration. A product of the reactions was determined by IR and TLC to be N-stearylacetamide. Both the initial loss of ASA and the increase in stability decreased as the DMPC: stearylamine mole ratio increased. A mechanism of aminolysis occurring in the organic solvent and at liposome surfaces between ASA and stearylamine or DMPC at pH 8·0 has been suggested. It is concluded that the orientation of ASA and the ordered structural environment of the bilayers minimizes the aminolytic and hydrolytic reactions.
In-vitro Bioadhesion of a Buccal, Miconazole Slow-release Tablet
Authors: Bouckaert Stefan , Remon Jean-Paul 
Published: April 2011

Abstract
The bioadhesive characteristics of thermally modified starch/polyacrylic acid (PAA) tablets, containing miconazole nitrate, were determined. The detachment force and work of adhesion were significantly affected by the ratio of drum-dried waxy maize starch and PAA. Pure PAA showed the highest detachment force and work of adhesion while the lowest force and work of adhesion were observed for pure starch. There was a pronounced effect of molecular weight of PAA on the bioadhesive characteristics. Miconazole nitrate did not influence bioadhesion up to a concentration of 30%. The influence of additives was negligible and fluctuations of pH did not influence the bioadhesive strength of the tablet.