bluuebunny/crossref_metadata_2025_split huggingface dataset:
Laxatives and the production of autacoids by rat colon
Authors: Capasso F , Mascolo N , Autore G , Romano V 
Published: April 2011

Abstract
The effects of some laxatives were examined on the formation of histamine, 5-hydroxytryptamine (5-HT) and prostaglandin-like material (PG-LM) by rat intestine in-vitro. Castor oil, senna, sulphosuccinate and bisacodyl, but not mannitol or lactulose, in doses that cause laxation, increased the formation of histamine, 5-HT and PG-LM. Indomethacin or hydrocortisone reduced the increase of PG-LM formation. The data support the idea that the laxative effects of these intestinal secretagogues are due to increased intestinal production of PG-LM, histamine and 5-HT.
Spectrofluorimetric analysis and buccal absorption of mediroxamine
Authors: Randhawa M A , Blackett A N , Turner P 
Published: April 2011

Abstract
Medifoxamine is a new investigational antidepressant drug. Its buccal absorption at pH 5–9, which can be considered as an in-vivo model of passive drug transfer through a lipid membrane, was studied in six normal, healthy volunteers to predict its pharmacokinetic profile in man. Maximum absorption of medifoxamine occurred at pH 8, which is close to its pKa (8.5).
Mechanism of dissolution of cholesterol-calcium bilirubinate compressed discs in monooctanoin
Authors: Mulligan S C , Corrigan O I 
Published: April 2011

Abstract
The dissolution of cholesterol monohydrate and calcium bilirubinate (neutral salt) mixtures in monooctanoin was investigated using the static disc method. The intrinsic dissolution rate of calcium bilirubinate was orders of magnitude (∼ 1000 fold) lower than that of cholesterol. Cholesterol release decreased as its weight fraction in the solid decreased. In model systems containing below 50% cholesterol dissolution became negligible. The release profiles deviated from the classical model for dissolution from two component mixtures. The observed dissolution profiles of both components were greater than predicted by theory. Anomalous positive curvatures in dissolution profiles suggested that calcium bilirubinate initially reduced the surface area available for cholesterol dissolution. A model, taking into account the change in surface area, was used to fit the cholsterol dissolution data. The results were consistent with the reported relationship between human gallbladder stone cholesterol content and average stone weight loss.
Factors influencing the tissue distribution of coenzyme Q10 intravenously administered in an emulsion to rats: emulsifying agents and lipoprotein lipase activity
Authors: Kimura Akio , Yamaguchi Hiroyuki , Watanabe Keiichi , Hayashi Masahiro , Awazu Shoji 
Published: April 2011

Abstract
The tissue distribution of coenzyme Q10 (CoQ10) administered intravenously in an emulsion prepared with egg yolk phosphatidylcholine (PC), egg yolk sphingomyelin (SPM) or a combination of PC and a polyoxyethylene derivative of hydrogenated castor oil (HCO-60) (PC + HCO-60) was investigated. The disappearance from the plasma of CoQ10 administered in three different emulsions of lipid particle size less than 0.5 μm varied with the particular emulsifer. Its disappearance occurred most rapidly from the PC emulsion; with the addition of HCO-60, its disappearance was much slower. In the reticuloendothelial system, the concentration of CoQ10 was higher in the spleen, for both the SPM and PC + HCO-60 emulsions than for the PC emulsion. HCO-60 reduced the CoQ10 distribution in the liver from the PC emulsion. Differences in disappearance rates from the plasma are thus considered to be due to the extent of CoQ10 distribution in the liver. CoQ10 concentration in the heart, a target organ, was greatest with the PC emulsion. Its distribution was related to lipoprotein lipase (LPL) activity in this organ. The effects caused by HCO-60, however, could not be explained by LPL activity alone. CoQ10 distribution in the adrenal gland and kidney can be explained partly by LPL activity but in the presence of HCO-60, the distribution mechanism apparently involves other factors.
Enhanced myocardial necrosis induced in rats by the combined administration of hydralazine and prenalterol
Authors: Joseph Xavier , Balazs Tibor 
Published: April 2011

Abstract
The cardiotoxic effects of hydralazine and prenalterol, given alone and in combination, were assessed in rats and rabbits. Acute myocardial necrosis was induced by a single administration of each drug alone in rats. However, the incidence and severity of lesions were markedly enhanced when both drugs were given in combination. Rats that received the same treatment for 10 consecutive days showed minimal or no acute necrosis, demonstrating the development of a resistance to further cardiotoxic effects of the drugs. Rabbits showed only minimal lesions when either drug was used alone and no enhancement of lesions when they were given in combination. From these data, it is concluded that the possibility of a cardiotoxic interaction exists when these drugs are used in combination and that the heavy rat (500–600 g) is a more sensitive model than the rabbit for studies of this nature.
Optimizing the pentetrazol infusion test for seizure threshold measurement
Authors: Nutt D J , Taylor S C , Little H J 
Published: April 2011

Abstract
Seizure thresholds in mice were determined using the pentetrazol infusion method. Concentration of infusate and rate of infusion were varied to assess the optimal parameters for seizure threshold detection. Seizure threshold elevations were produced by flurazepam and threshold decreases by FG 7142. An infusion rate of 1.1 ml min−1 was best for detecting both increases and decreases in threshold. However a concentration of 2.5 mg ml−1 gave optimal measurement of elevations in threshold whereas decreased thresholds were best detected with a concentration of 10 mg ml−1.
Ultrasonically mediated solute permeation through polymer barriers
Authors: Julian Thomas N , Zentner Gaylen M 
Published: April 2011

Abstract
The effects of ultrasound on the permeation of benzoic acid through polydimethylsiloxane, and hydrocortisone through cellulose was investigated. Ultrasonic irradiation resulted in a 23% increase in the permeability coefficient of hydrocortisone in a cellulose film. A 14% increase in permeability coefficient was observed for benzoic acid in a polydimethylsiloxane film. The effects of ultrasound on stagnant aqueous diffusion layers, membrane-solution interfacial temperature, membrane integrity, and diffusant stability were investigated. These factors were not responsible for the observed increases in permeability.
Determination of cotinine in biological fluids of non-smokers by packed column gas-liquid chromatography
Authors: Feyerabend C , Bryant A E , Jarvist M J , Russell M A H 
Published: April 2011

Abstract
A method is described for the analysis of cotinine in plasma, saliva and urine using packed-column gas-liquid chromatography, which is sufficiently sensitive and reproducible for quantitative study of the low levels resulting from exposure of non-smokers to other people's smoke. The lower limit of detection of cotinine in these fluids was 100 pg ml−1. The coefficient of variation over the range 0.25 to 2.0 ng ml−1 averaged 7.7%. In a sample of 85 non-smokers the concentrations of cotinine in plasma correlated 0.82 with those in urine and saliva, while the correlation between the saliva and urine concentrations was 0.91. Saliva cotinine concentrations were quantitatively related to passive exposure to parental smoking in a population study of 569 non-smoking schoolchildren.
Acute effect of nicotine on the striatal dopaminergic system in the rat
Authors: Fung Yiu K , Lau Yuen S 
Published: April 2011

Abstract
The acute effects of nicotine (1.5 mg kg−1 day−1) on the striatal dopaminergic system have been examined in the rat. Twenty-four hours after nicotine treatment, spontaneous locomotor activity in response to apomorphine or (+)-amphetamine and the binding of [3H]spiperone to striatal particulates were determined. Pretreatment of nicotine did not alter the characteristics of [3H]spiperone binding to striatal dopamine receptors. The nicotine treatment did not affect the apomorphine-induced locomotor activity, however, the (+)-ampnetamine-stimulated locomotor activity was attenuated. These results suggest that nicotine acutely alters the presynaptic dopaminergic activity without significantly affecting the postsynaptic dopaminergic function.
Studies on metronidazole tablet formulations
Authors: Itiola O A , Pilpel N 
Published: April 2011

Abstract
Incorporating polyvinylpyrrolidone, gelatin and methylcellulose binding agents in a metronidazole formulation alters the tensile strength, disintegration and dissolution times of the tablets by reducing their wettability as measured by the adhesion tension of water. Correlations have been established between the disintegration times, D and the dissolution times t50, t90 and t1 (derived from the equation of Noyes & Whitney). A correlation has also been established between the adhesion tension of water on the tablets and the disintegration and dissolution times. These correlations depend on the nature and concentration of binder used.
Investigation of the binding of various tricyclic neuroleptics and antidepressants to α1-acid glycoprotein
Authors: Schley J , MÜLler-Oerlinghausen B 
Published: April 2011

Abstract
Recent studies have shown that the interaction of various tricyclic neuroleptics and antidepressants with isolated α1-acid glycoprotein occurs at one common binding site and with relatively high association constants. The aim of the present study was to find differences in the binding of some phenothiazines, thioxanthenes, and several other drugs reported to bind α1-AGP. The findings suggest that the affinity of the phenothiazines and thioxanthenes depends primarily on the existence of the tricyclic skeleton and is generally increased by the basic side chain. Substituents at position 3 of the phenothiazine nucleus influence the affinity in a variable way. The losses of radioactivity by non-specific absorptions to the dialysing chambers were considered for the calculation of the association constants. No correlation between association constants and the antipsychotic potency of neuroleptic drugs could be detected.
Effects of several ergosines on adenylate cyclase activity in synaptosomal membranes of the bovine caudate nucleus
Authors: Šoškić V , Petrović Jelena 
Published: April 2011

Abstract
The effects of several ergosines and different dopamine agonists and antagonists on the activity of dopamine-sensitive adenylate cyclase in synaptosomal membranes of the bovine caudate nucleus were comparatively studied. Among ergot alkaloid derivatives used, ergosinine was the most active in stimulating adenylate cyclase activity. Ergosine, bromoergosine, dihydroergosine, dihydroergocryptine and lisuride also stimulated this enzyme. Dihydroergosinine, bromodihydroergosine and bromoergocryptine did not affect adenylate cyclase activity. Saccharino derivatives of both ergosine and ergosinine were inactive. When used in higher concentrations, ergosine, ergosinine, dihydroergocryptine and lisuride inhibited dopamine-stimulated adenylate cyclase whereas other ergot alkaloid derivatives examined did not. If the extent of dopamine-sensitive adenylate cyclase stimulation is considered as a measure of dopaminergic activity, examination of the structure/dopaminergic activity relationship showed that modifications of ergot alkaloid molecules such as isomerization in position 8, hydrogenation of Δ9(10)-double bond, or introduction of bromine into position 2 of the molecule, lead to a significant decrease of stimulatory effects of adenylate cyclase. Introduction of a saccharino group into position 2 of the molecule caused a total loss of stimulatory activity of both ergosine and ergosinine, probably because of the size of the saccharino residue.
Use of lipid microspheres as a drug carrier for antitumour drugs
Authors: Mizushima Y , Shoji Y , Kato T , Fukushima M , Kurozumi S 
Published: April 2011

Abstract
9-Oxo-15-hydroxy-Δ7,10,13-prostatrienoic acid methyl ester (Δ7PGA1), an antitumour drug was incorporated into lipid microspheres of 0.2 μm diameter (lipo-Δ7-PGA1). In in-vivo experiments, lipo-Δ7-PGA1 had a significantly greater antitumour activity than free Δ7-PGA1 against P388 leukaemia. Lipo-Δ7-PGA1, slightly, but significantly, prolonged the survival time of mice inoculated with L1210 leukaemia, whereas free Δ7-PGA1 did not. Against MM46 ascites tumour, the survival time after treatment with 10 mg kg−1 of lipo-Δ7-PGA1 was significantly greater than that after the same dose of free Δ7PGA1. The results suggest that lipid microspheres can be used as drug delivery carriers for lipid soluble antitumour agents.
Re-evaluation of the L-dopa loading effect on dopamine metabolism in rat striatum
Authors: El Gemayel G , Trouvin J H , Prioux-Guyonneau M , Jacquot C , Cohen Y 
Published: April 2011

Abstract
Investigation by HPLC with electrochemical detection of dopamine (DA) metabolism in rat striatum after L-dopa + benserazide treatment allowed quantification of the time course evolution of DA, 3,4-dihydroxyphenylacetic acid and homovanillic acid levels. Furthermore, four peaks which did not appear in controls, were detected in treated striatum. One was identified as 3-methoxytyrosine, the level of which was still high 9 h after treatment. 3-Methoxytyrosine, has been detected previously in plasma of parkinsonian patients treated with L-dopa, and the disturbance in DA metabolism could explain some of the side-effects induced by that treatment.
Effect of some vasodilators on cat femoral arteries
Authors: Marin J , Salaices M , De Gregorio A 
Published: April 2011

Abstract
Adenosine, cyclic-AMP (cAMP), papaverine and 1-methyl-3-isobutylxanthine (MIX) evoked dose-dependent vasodilatation in cat femoral arteries precontracted with 75 mM K+. The vasodilator response induced at maximal concentration used was: papaverine &gt; MIX &gt; adenosine = cAMP. With regard to the potency of relaxant effects (IC10) the order was MIX = cAMP = papaverine &gt; adenosine. The dilatation elicited by papaverine, adenosine and cAMP was increased by MIX. Preincubation with adenosine enhanced the relaxation induced by MIX and reduced that produced by cAMP. These results indicate that the effects of adenosine and cAMP seem not to be mediated by specific surface receptors but by a cAMP-dependent mechanism. The interference between adenosine and cAMP could be due to competition for a similar site and/or mechanism.
Muscarinic receptors on rat ileal villus and crypt cells
Authors: Wahawisan Ruchaneekorn , Wallace Lane J , Gaginella Timothy S 
Published: April 2011

Abstract
Ileal villus and crypt cells exhibit morphological and biochemical differences which may be responsible for functional differences in relation to ion transport. Cholinergic agonists act directly on epithelial cell muscarinic receptors, but it is not known if these receptors exist on both villus and crypt cells. Using the potent muscarinic antagonist [3H](−)-quinuclidinyl benzilate (QNB) we have determined the distribution of muscarinic receptors in rat ileal villus and crypt cells. Plasma membrane preparations from ileal villus and crypt cells possessed a specific, saturable, and high affinity QNB binding site with apparent dissociation constants of 0.23 ± 0.05 and 0.21 ± 0.04 nM (mean ± s.e., n = 6) and densities of 92.2 ± 2.8 and 90.1 ± 16.2 fmol (mg protein)−1, respectively. Both types of cells showed similar potencies for agonist and antagonist competition of QNB binding. The muscarinic receptors in membrane fractions from villus cells were found primarily on the basolateral membrane rather than on the brush border membrane. Secretion induced by cholinergic stimulation of the small intestine might, therefore, be due to an effect on both villus and crypt cells as both types contain muscarinic receptors. Furthermore, such stimulation also may result in mucin secretion, as goblet cells were present in the preparation we studied, and receptors on these cells may have contributed to the amount of binding of [3H]QNB.
A comparison of the antagonisms by neostigmine and diaminopyridine against the neuromuscular block caused by cobrotoxin and (+)-tubocurarine
Authors: Chang C C , Su M J , Hong S J , Shieh B H , Chiou L C 
Published: April 2011

Abstract
Cobrotoxin was about 11-fold more potent than (+)-tubocurarine on a weight basis in blocking neuromuscular transmission in mouse isolated phrenic nerve-diaphragm preparations. Neostigmine and diaminopyridine increased the concentrations of cobrotoxin for 70% inhibition of indirect contraction by 290 and 320%, and increased those of (+)-tubocurarine by 180 and 230%, respectively. More than additive increases were obtained when neostigmine and diaminopyridine were used simultaneously. Cobrotoxin, however, was only 6-fold more toxic than (+)-tubocurarine after intraperitoneal injection in mice. The lethal dose of (+)-tubocurarine was increased by 80% when both antidotes were used together, but only by 15–20% when used alone. In contrast, the lethality of cobrotoxin was not decreased by these drugs. Unexpectedly, the time to death after treatment with cobrotoxin was shortened when mice were pretreated with these antidotes.
Fluidized bed film coating of an interactive powder mixture to produce microencapsulated 2–5 μm particles
Authors: Thiel W J , Sberna F J 
Published: April 2011

Abstract
Previous work has shown an interactive (ordered) powder mixture, formed from 2–5 μm salicylic acid and a coarse spray-dried sugar, is stable when fluidized. The micronized material adheres to the carrier during fluid bed air suspension and may be film coated with a polymer. This process offers a novel method of microencapsulating very fine particulates, providing a way of manufacturing enteric-coated and sustained release microdose drug delivery systems. Different processing conditions were used in an attempt to optimize the retention of micronized model drug beneath the film. The effect of altering the following variables was investigated; polymer spray rate, addition of a third component which adhered to the binary adhesion units, and different materials of construction for the mixer used to form the interactive mixture. The microencapsulated adhesion units retained 90–95% of the micronized model drug. A statistical evaluation of the content uniformity showed that a very uniform dispersion was formed (CV &lt;5%, 99% confidence). Multilayer film-coated adhesion units were also produced using a sequence of mixing and coating operations. This process offers a method of film coating microdose quantities of a drug, to produce a free flowing product, possessing excellent content uniformity.
The kinetics of 4-nitrophenol conjugation by perfused livers and hepatic microsomes from streptozocin-induced diabetic rats
Authors: Morrison M H , Barber H E , Foschi P G , Hawksworth G M 
Published: April 2011

Abstract
The formation of both glucuronide and sulphate conjugates of 4-nitrophenol is deficient in perfused livers from male diabetic rats. Experiments with ‘native’ hepatic microsomes demonstrated that the defect in glucuronidation is due to a decrease in the maximal velocity of the reaction. There is no alteration in the affinity of the glucuronyltransferase for 4-nitrophenol. Non-linear regression analysis of the 4-nitrophenol liver perfusate concentrations snowed that the elimination follows saturable Michaelis-Menten kinetics. Clearance values in ‘native’ microsomal preparations and in perfused livers were calculated and found to be similar in both systems. This provides evidence that glucuronyltransferase is ‘native’ in the intact liver.
Yohimbine affects the evoked overflow of neurotransmitters from rat brain slices by more than one mechanism
Authors: Hagan R M , Hughes I E 
Published: April 2011

Abstract
Both yohimbine (0.1–10 μm) and phentolamine (10 μm) increased the tritium overflow evoked by electrical stimulation (3Hz, 2 ms, 18 mA for 120s every 20 min) of rat brain cortex slices previously incubated with [3H](−)-noradrenaline. At their maximally effective concentrations, neither of these compounds produced an effect which was fully maintained over the 1 h of the experiment, but the decline in effect of yohimbine (1.25 μM) was more marked, falling sharply to reach, after 1 h, 25% of the effect observed after 20 min, whereas phentolamine only declined to 60% of the effect after 20 min. In rat brain cortex slices previously incubated with [3H]5-hydroxytryptamine ([3H]5-HT), the tritium overflow evoked by electrical stimulation (3 Hz, 2 ms, 40 mA for 120 s) was increased by yohimbine (0.1–1 μM) and phentolamine (0.1–10 μM), but a higher concentration of yohimbine (10 μM) decreased evoked overflow below the levels seen in the absence of either drug. It is concluded that, at concentrations effective in inhibiting the presynaptic α-adrenoceptor-mediated mechanisms controlling transmitter release in rat brain slices, a non-a-adrenoceptor-mediated, possible local anaesthetic, action of yohimbine contributes to the overall effect of this drug on transmitter overflow.
Stimulation by noradrenaline of inositol phospholipid breakdown in the rat hippocampus: effect of the ambient potassium concentration
Authors: Fowler Christopher J , O'Carroll Anne-Marie , Court Jennifer A , Candy John M 
Published: April 2011

Abstract
The stimulation by noradrenaline (NA) of inositol phospholipid (PI) breakdown has been studied using rat hippocampal miniprisms. Pretreatment with the monoamine oxidase inhibitor, pargyline, potentiated the stimulation produced by NA. On the other hand, pargyline pretreatment did not affect the stimulation of PI breakdown by the α1-adrenoceptor agonist phenylephrine. NA- and phenylephrine-stimulated PI breakdown were enhanced by increasing the ambient potassium concentration in the assay from 5,88 to 18.2 mM. This enhancement did not, in the case of NA, change either the EC50 value for this agonist (2–3 μM) or the pA2 value for the competitive antagonism of the stimulation by the α1-antagonist prazosin (pA2 value 9.2). Time-courses of the NA-stimulated PI turnover in different brain regions indicated that the rate of stimulation was in the order frontal cortex &gt; hypothalamus ≥ hippocampus ≫ cerebellum.
A sensitive high performance liquid chromatographic assay of a new metabolite of ampicillin in man
Authors: Haginaka Jun , Wakai Junko 
Published: April 2011

Abstract
A sensitive, high-performance liquid chromatographic method has been developed for the determination of piperazine-2,5-dione, a new metabolite of ampicillin, in human urine. Piperazine-2,5-dione was separated from human urine on a C18-column using phosphate buffer-methanol (pH 3.5) as eluent. Subsequently, the effluent underwent a postcolumn reaction with mercurous chloride and was then detected at 305 nm. It was found that piperazine-2,5-dione was also excreted in the urine of a volunteer dosed with ampicillin.
Uridine-induced hyperthermia in the rabbit
Authors: Cradock J C , Vishnuvajjala B R , Chin T F , Hochstein H D , Ackerman S K 
Published: April 2011

Abstract
Uridine injection in 0.6% saline elevated rabbit temperatures (mean = 0.9 °C) in the USP XX pyrogen test. Hyperthermia was delayed in onset and peaking 3–4 h post injection, but the injection was negative in the limulus amoebocyte lysate (LAL) assay. Uridine from five lots of different sources exceeded USP XX limits in the rabbit pyrogen test and proved negative in the LAL assay. Because the dose of uridine was high, several procedures were used to determine if an impurity was the cause of temperature elevation. Uridine remained pyrogenic in spite of ultrafiltration (10 000 nominal mol. wt), recrystallization and preparative scale HPLC. Sterile filtration and autoclaving also did not affect the response. Hyperthermia, therefore, appears to be an inherent property of uridine. Uridine was also found to release endogenous pyrogen in-vitro from human mononuclear cells. Uridine has been reported to induce fever in man, thus the USP rabbit pyrogen test predicted for the clinical response.