bluuebunny/crossref_metadata_2025_split huggingface dataset:
Estimation of Elastic Recovery, Work of Decompression and Young's Modulus Using a Rotary Tablet Press
Authors: Dwivedi S K , Oates R J , Mitchell A G 
Published: April 2011

Abstract
Capping and lamination occur when the bonds within a tablet cannot withstand the elastic recovery during decompression. To estimate tablet recovery, it is necessary to subtract the machine recovery from the total recovery during decompression. A direct relationship between the force and machine deformation is applied in a novel fashion to calculate in-die tablet recovery on a Manesty Betapress and to estimate the Young's modulus, E, of various solids from the recovery data. The E values of about twenty-five pharmaceutical solids were found to be in reasonable agreement with literature values. This procedure allows in-process analysis of tablet recovery and gives E without the use of specialized equipment.
A Comparison of Glycine, Sarcosine, N,N-Dimethylglycine, Glycinebetaine and N-Modified Betaines as Liposome Cryoprotectants
Authors: Lloyd Andrew W , Baker James A , Smith Geoffrey , Olliff Cedric J , Rutt Ken J 
Published: April 2011

Abstract
Glycinebetaine has previously been shown to be effective at reducing leakage from liposomes which are frozen then thawed. This study involved the preparation of a series of N-modified betaines and the comparison of their cryoprotective activities with those of glycine, sarcosine, N,N-dimethylglycine and glycinebetaine. All the compounds investigated, with the exception of (dimethyloctylammonio)acetate, reduced the degree of leakage, after freezing and thawing, with additive concentrations up to 0·6 m. Reducing the degree of N-terminal methylation of glycinebetaine appeared to increase the leakage from liposomes at additive concentrations between 0·2 and 0·6 m. (Dimethylethylammonio)acetate, (dimethyl-isopropylammonio)acetate and (N,N,N',N'-tetramethylethylenediammonio)-N,N'-diacetate appeared to be no more effective than glycinebetaine, whereas improved protection was afforded by (triethylammonio)acetate and (diethylmethylammonio)acetate at most concentrations. This study demonstrates that the cryoprotective activity of glycinebetaine may be improved with modifications to the N-terminal.
Effects of lithium and haloperidol on human sperm motility in-vitro
Authors: Shen Meng-Ru , Yang Rei-Cheng , Chen Shun-Sheng 
Published: April 2011

Abstract
Two psychotropic drugs, lithium and haloperidol, were evaluated for their in-vitro effects on sperm motility using a transmembrane migration method. Sperm motility was measured either immediately after semen had been mixed with the drug or after a 2 h incubation period at 37°C. Lithium inhibited human sperm motility in a dose-dependent manner with an EC50 of 10 Mm when the semen-lithium mixture had been incubated. Sperm motility was increased to 127% of control when semen had been incubated with 0027 μm haloperidol; this concentration was within the therapeutic range.
Tetrandrine and Isotetrandrine, Two Bisbenzyltetrahydroisoquinoline Alkaloids from Menispermaceae, with Rat Uterine Smooth Muscle Relaxant Activity
Authors: D'Ocón Pilar , BláZquez M Amparo , Bermejo Almudena , Anselmi Elsa 
Published: April 2011

Abstract
The effects of two bisbenzyltetrahydroisoquinoline alkaloids, 1S, 1′S tetrandrine and its isomer 1R, 1′S isotetrandrine, were investigated in rat isolated uterus in order to identify the mechanism of relaxant action and to study the influence of the absolute configuration on the activity of these alkaloids. Both inhibited the uterine contraction induced by high K+, acetylcholine and oxytocin. In Ca2+-free medium, isotetrandrine relaxed the sustained contraction induced by oxytocin but tetrandrine did not. The relaxant effects of the alkaloids may be due to blockade of calcium influx through specific channels. Tetrandrine and isotetrandrine modify the calcium channel in a nonreversible manner whilst only isotetrandrine acts intracellularly. Tetrandrine shows a more specific relaxant activity as a calcium entry blocker.
Design, Synthesis and Biological Activity of a Series of Torasemide Derivatives, Potent Blockers of the Na+ 2Cl− K+ Co-transporter: In-vitro Study
Authors: Masereel B , Lohrmann E , Schynts M , Pirotte B , Greger R , Delarg J 
Published: April 2011

Abstract
Pharmacomodulation of the torasemide molecule, a loop diuretic inhibiting Na+ 2Cl− K+ co-transport in the thick ascending limb of the loop of Henlé has been performed in order to obtain new long-acting diuretics. The aim of this study was to decrease the metabolism of the drug and to slow down its rate of excretion by increasing its hydrophobicity. The present study describes the synthesis and the inhibitory potency of new torasemide derivatives in the bioassay system of the cortical thick ascending limb of rabbit. A correlation between the lipophilicity (log P') of these substances and their activity as inhibitors of the Na+ Cl− K+ co-transporter was observed. The present design led to compounds more active than torasemide. Structure-activity relationships permit us to propose an interaction model between torasemide derivatives and the Na+ 2Cl− K+ co-transport system of the cortical thick ascending limb.
Induction of propranolol metabolism in the Hep G2 human hepatoma cell line
Authors: Steiner Alain , Walle U Kristina , Walle Thomas 
Published: April 2011

Abstract
Metabolism of propranolol by the human hepatoma cell line Hep G2 was studied. Although metabolism qualitatively was similar to that in-vivo, the P450-mediated N-desisopropylation clearly predominated. Pretreatment of cells with 3-methylcholanth-rene increased the activity of this pathway 14-fold, whereas phenobarbitone had no effect. This is similar to the pathway-selective inductive response observed for cigarette smoking in-vivo. As in-vivo, secondary metabolism of N-desisopropylpropranolol was extensive. This could, however, be completely blocked by 0·1 μm clorgyline, a potent MAO type A inhibitor. As in human liver microsomes, the stereochemistry of propranolol metabolism demonstrated a preference for the R(+)-enantiomer. These observations emphasize the usefulness of the Hep G2 cell line as a model of man.
Metabolic Activation of Sennoside C in Mice: Synergistic Action of Anthrones
Authors: Yamauchi Kazuko , Shinano Kayoko , Nakajima Kazuko , Yagi Teruyo , Kuwano Shigeaki 
Published: April 2011

Abstract
Sennosides A and C directly injected into the caecum of mice showed equal purgative activity. Intracaecal administration reduced time to onset of diarrhoea induced by sennoside C from about 3 h after oral administration to about 24 min. At 2·3 h after oral administration of sennoside C., nearly equimolar amounts of aloe-emodin anthrone and rhein anthrone were detected in the large intestine of mice. The purgative effect of oral sennoside C could be reduced by pretreating mice with chloramphenicol. This was observed as a decreased formation of total anthrones in the large intestine. Both anthrones and an equimolar mixture of both anthrones directly injected into the caecum exerted a purgative effect, although the activity was lower for aloe-emodin anthrone. The intracaecal ED50 values were 54·5 (24·1–89·6), 11·4 (5·0–15·7) and 11·2 (6·1–14·6) μmol kg−1 for aloe-emodin anthrone, rhein anthrone and an equimolar mixture of both anthrones, respectively. We concluded that aloe-emodin anthrone and rhein anthrone, formed mainly by intraluminal bacterial action, are the true active metabolites of sennoside C in mice and that both anthrones synergistically exert their purgative effects on mice.
The Effects of Labetalol and Dilevalol on Isolated Cardiovascular Preparations of the Guinea-pig and Rat
Authors: Doggrell Sheila A 
Published: April 2011

Abstract
Differing effects of labetalol and dilevalol on cardiovascular preparations have been reported. I have studied the effects of labetalol and dilevalol on the contractile responses of the rat and guinea-pig left atria and rat portal vein. On the guinea-pig left atria low concentrations of labetalol (≥ 10−8 m) and of dilevalol (≥ 10−7 m) inhibited to a small extent the responses to electrical cardiac stimulation, which is indicative of membrane stabilizing activity. Labetalol (≥ 3× 10−8 m) and dilevalol (≥ 10−8 m) caused surmountable antagonism of the isoprenaline responses of the atria and the pA2 values were 8·60 and 8·98 at the β1-adrenoceptors of the rat left atria and 7·90 and 8·31, respectively, on the guinea-pig left atria which has functional β1 and β2-adrenoceptors. Labetalol and dilevalol (both at ≥ 10−7 m) attenuated the spontaneous contractile activity of the rat portal vein and the attenuation to labetalol at 10−6 m was abolished by ICI 118,551 which illustrates that the labetalol-induced attenuation is β2-adrenoceptor mediated. The isoprenaline attenuation responses of the portal vein were inhibited by labetalol and dilevalol (both at ≥ 10−7 m) and the pA2 value for the labetalol at β2-adrenoceptors was 7·59. It is concluded that labetalol and dilevalol are β1-adrenoceptor selective antagonists.
Simultaneous Determination of Bufadienolides in the Traditional Chinese Medicine Preparation, Liu-Shen-Wan, by Liquid Chromatography
Authors: Hong Z , Chan K , Yeung H W 
Published: April 2011

Abstract
The bufadienolide compounds (bufalin, cinobufagin and resibufogenin), major constituents of Chansu in Liu-Shen-Wan (LSW), were determined by reverse phase high performance liquid chromotography. The procedure involves a preliminary extraction of the bufadienolides from LSW with chloroform using ultrasonication and subsequent evaporation to dryness of the chloroform extract. The residue of the chloroform extract was dissolved in methanol and separated on a Merck LiChrosorb RP-18 column. Methanol: water (74:26) was used as mobile phase. The compounds were satisfactorily separated with good chromatographic peaks. Good coefficients of correlation (r &gt; 0·999) were obtained from the calibration of peak areas with concentrations for the 3 bufadienolides. Results of analysis showed that there were differences between the contents of bufadienolides in 11 LSW samples of different origin available to the public in Hong Kong where at present there is no legal control over the sale of traditional Chinese medicines. The variability of quantities of bufadienolides in Chansu may be a hazard to the public.
A Semi-empirical Study of some Clavulanic Acid Derivatives in Relation to their Activity as β-Lactamase Inhibitors
Authors: Fernández Berta , Ríos Miguel A 
Published: April 2011

Abstract
Clavulanic acid and some of its derivatives are inhibitors of β-lactamases and hence enhance the activity of antibiotics such as cephaloridine, amoxycillin and ampicillin against β-lactamase-producing bacteria. Several empirical structure-activity relationships have been proposed for these compounds; bearing these findings in mind, we have carried out a semi-empirical structural study on clavulanic acid and twelve of its derivatives lacking the carboxyl group. We relate our results to the available activity data, focusing on features such as planarity at the N atom, charge distribution and the orientation of the substituents, all of which are related to the activity of these systems.
The disposition of nifurtimox in the rat isolated perfused liver: effect of dose size
Authors: González-Martin Guillermo , Ponce Graciela , Inostroza Verónica , González Mario , Paulos Claudio , Guevara Alfredo 
Published: April 2011

Abstract
The disposition of nifurtimox was studied in the rat isolated perfused liver using a recirculating system. The drug was administered as a bolus (5·0, 15·0 or 30·0 μg mL−1), and its disappearance was monitored by analysing perfusate samples. In all experiments perfusate disappearance was monoexponential, and no significant difference was found between the three doses for the elimination constant (0·016, 0·011 and 0·012 min−1, respectively), half-life (46·6, 65·8 and 66·8 min, respectively), extraction rate (0·128, 0·091 and 0·099, respectively) and distribution volume (41·1, 47·3 and 30·7 mL g−1, respectively). At 30 μg mL−1 the hepatic clearance was lower than the other concentrations of nifurtimox (0·66, 0·51 and 0·34 mL min−1 g−1, respectively). Relatively little parent drug was recovered from the liver at the end of the perfusions. In summary, nifurtimox is cleared slowly from the rat isolated perfused liver, is poorly extracted by hepatocyte cells and is completely metabolized from 2 to 4 h after perfusion.
The Urinary Excretion of Tryptophan and Tryptophan Metabolites in the Chronic Ethanol-fed Rat
Authors: Bonner Adrian B , Brien Sarah , Preedy Victor R 
Published: April 2011

Abstract
An investigation was made into the hypothesis that chronic ethanol ingestion disturbs the metabolism of tryptophan which is reflected by alterations in the urinary excretion of the metabolites 5-hydroxyindoleacetic acid (5-HIAA), anthranillic acid (AA) and indoleacetic acid (IAA). In particular, we investigated whether experimental chronic alcoholism is associated with a decrease in the tryptophan metabolite ratios as suggested in the literature. Male Wistar rats were chronically fed a nutritionally-complete liquid diet in which ethanol comprised 35% of total calories: controls were pair-fed identical amounts of the same diet in which ethanol was replaced by isocaloric glucose. At 6 weeks, 24 h urine samples were collected for the analysis of tryptophan, 5-HIAA, AA and IAA by HPLC. During ethanol-feeding there were reductions in the daily urinary excretion (i.e. μmol/24 h) of tryptophan (–57%, P = 0·026) and concomitant increases in 5-HIAA excretion (62%, P = 0·057). Expression of data in terms of lean tissue mass (i.e. urinary creatinine) revealed identical conclusions. An analysis was performed on the molar ratios of these urinary analytes. The tryptophan: total metabolite ratio was significantly decreased (by −53%), but the AA: total metabolite ratio was not significantly altered (P = 0·102). The ratios 5-HIAA/AA and 5-HIAA/IAA were slightly increased, but they did not attain statistical significance (P &gt; 0·351). It was concluded that chronic ethanol feeding is associated with significant changes in the urinary excretion of tryptophan and its related metabolites. Many of the above changes were contrary to previous clinical data and this may be due to dietary and nutritional deficiencies or to alterations in the diurnal pattern of 5-hydroxytryptamine and tryptophan metabolism.
The effect of reserpine and stress on feeding behaviour in the light and dark phases of the diurnal cycle in rats
Authors: Gorka Z , Adamik P 
Published: April 2011

Abstract
The effect of reserpine (2·5 mg kg−1 subcutaneously) and stress (3 h restraint) on food and water consumption and body weight change in the light and dark phases of the diurnal cycle in rats was investigated. Reserpine increased water intake and body weight loss in the light phase (250 and 180% of the control, respectively). In the dark phase the reserpinized rats consumed less food and water (20 and 30% of the control, respectively) and body weight gain was reversed (–250% of the control). After stress, rats consumed more food and water (200 and 500% of the control, respectively) and their body weight loss was diminished (60% of the control) in the light phase. In the dark phase the consumption of food and water in the stressed rats was diminished (80 and 85% of the control, respectively) without any change in body weight gain. The dark/light phase ratio for food consumption, water intake and body weight change (gain/loss) was highly statistically significant in the stressed and reserpine-treated rats. The results indicate that evaluation of behaviour in animal models should be carried out during both phases of the diurnal cycle.
Dependency of salivary excretion of mexiletine on the plasma concentration in rats
Authors: Nagasako Sadao , Iwamoto Kikuo , Hayashibara Masakazu , Katagiri Yoshihiro 
Published: April 2011

Abstract
The effect of steady-state plasma concentrations on the salivary excretion of mexiletine was investigated following simultaneous bolus intravenous injection of the loading dose (2·7 or 16·1 mg kg−1) and constant-rate intravenous infusion of the maintenance dose (15 or 102 μg min−1 kg−1) in male Wistar rats. Parotid and mandibular saliva was collected separately by stimulating salivation with a constant-rate infusion of pilocarpine (50 μg kg−1 min−1) in each rat. The low and high steady-state levels of mexiletine in blood plasma were attained at 0·259 + 0·123 and 1·616 ± 0·475 μg mL−1, respectively, within the first 1–2 h after drug administration. Similarly, the two different steady-states in both parotid and mandibular saliva were attained. Although the mexiletine levels in both types of saliva were lower than that in plasma, the drug level in parotid saliva was always higher than that in mandibular saliva at any steady-state (P &lt; 0·001 or 0·01). In parotid saliva, the high steady-state produced greater saliva to plasma drug concentration ratios (S/P ratio, 0·475 + 0·160) than that (0·386±0·131) at the low steady-state (P &lt; 0·05). The S/P ratio for mandibular saliva at the high (0·204 ± 0·060) steady-state was also greater than that at the low (0·158 ± 0·050) steady-state (P &lt; 0·01). These changes in the S/P ratio could not be explained by the pH for either parotid or mandibular saliva, but partially by the change in the unbound fraction of the drug which tended to be consistent with that in the ratio for both salivary glands. These findings suggest that the salivary excretion of mexiletine may be dependent on the plasma unbound concentration in rats.
Long-term Effects of the Anticholinesterases Sarin and Soman on Latencies of Muscle Action Potentials in Mouse Diaphragm Muscle
Authors: Smith A P 
Published: April 2011

Abstract
In-vivo administration of the irreversible anticholinesterases sarin and soman has been shown to produce long-term effects on latency and variability of latency of muscle action potentials in in-vitro mouse diaphragm muscle preparations. The maximum observed effects occurred three days post-soman administration and seven days post-sarin administration, and were no longer detectable 28 days later. With both anticholinesterases the increase in latency, and variability of latency, was reduced by pyridostigmine pretreatment. Therapeutic administration of pralidoxime mesylate effectively prevented the sarin-induced effects when given after a delay of 24 h. In contrast, the effectiveness of pralidoxime mesylate declined rapidly when its administration was delayed following soman. These findings are consistent with this action of soman and sarin being a product of acetylcholinesterase inhibition. The results obtained with sarin suggest that a period of acetylcholinesterase inhibition in excess of 24 h is required to trigger the events leading to the production of this long-term effect.
Uptake of Concentrated Perfluorocarbon Emulsions into Rat Lymphoid Tissues
Authors: Bentley P K , Johnson O L , Washington C , Lowe K C 
Published: April 2011

Abstract
The effects of injecting (10–30 mL kg−1) either perfluorodecalin (FDC) emulsions of increasing phase fraction (20–60% w/v) or the commercial formulation, Fluosol, on lymphoid tissues have been studied for up to 7 days in male rats. Tissue weights increased by up to 123% (P &lt; 0·05) in proportion with quantity of perfluorochemical (PFC) injected, with spleen responses consistently greater than those of the liver. PFC droplets recovered from these tissues at 72 h after injection of 30% (w/v) FDC emulsion (10 mL kg−1) had mean diameters in the 1–10 μm range, with those from the spleen being larger than those from the liver. Recovered droplet diameters were considerably greater than freshly-prepared emulsion mean particle sizes (0·21–0·25 μm). These results suggest that coalescence of emulsion droplets following accumulation in lymphoid tissues is a pre-requisite for the eventual excretion of PFC vapour through the lungs.
1,3-Diacylaminopropan-2-ols and Corresponding 2-Acyl Derivatives as Drug Carriers: Unexpected Pharmacological Properties
Authors: Lambert D M , Neuvens L , Mergen F , Gallez B , Poupaert J H , Ghysel-Burton J , Maloteaux J-M , Dumont P 
Published: April 2011

Abstract
The design of lipid vectors (pseudotriglycerides, PTGs), achieved by the amide isosteric substitution of the ester moieties of 1,3-diacylglycerols, is based on the structural similarity with natural triglycerides facilitating the passage of pharmacological agents across biological membranes. 2-S-Acetylthiorphan (hemiacetorphan) pseudotriglycerides, Z-glycine pseudotriglycerides and 1,3-diacylaminopropan-2-ols vector molecules differing by the nature of the acid side-chain are examined in acute toxicity, radioligand binding and guinea-pig ileum experiments. These evaluations have led us to distinguish two types of compounds. Linear derivatives, palmitoyl and decanoyl, are devoid of toxicity and intrinsic activity. Cyclic derivatives, which contain in the acyl chain a phenyl, cyclohexyl, cyclopentyl or adamantoyl ring, present additional properties. Cyclic derivatives of hemiacetorphan are lethal after intravenous administration. The mortality is governed by the 2-hemiacetorphan moiety in the cyclic vector molecules. Hemiacetorphan alone is also lethal. Cyclic vector molecules and related compounds inhibit the contractile response of the guinea-pig ileum induced by electrical stimulation, histamine or acetylcholine (noncompetitive antagonism) whereas linear entities and parent compounds are not active. In particular, the 2-hemiacetorphan 1,3-diadamantoylamide PTG presents pD'2 values 7·87 ± 0·29 (vs histamine) and 7·97 ± 0·12 (vs acetylcholine).
Immune Response to Nasal Delivery of Antigenically Intact Tetanus Toxoid Associated with Poly(l-lactic acid) Microspheres in Rats, Rabbits and Guinea-pigs
Authors: Almeida A J , Alpar H O , Brown M R W 
Published: April 2011

Abstract
Tetanus toxoid was adsorbed onto poly(l-lactic acid) microspheres. Analyses by sodium dodecyl sulphate-polyacrylamide gel electrophoresis and Western blotting suggest that the formulation procedure does not affect the stability or the antigenic properties of the protein. After nasal administration to guinea-pigs, the resulting preparation enhanced the immune response to the tetanus toxoid when compared with the free antigen. The increase in systemic immunoglobulin G titre was almost immediate in the group treated with the adsorbed tetanus toxoid (time zero, 140; week 2, 1550; week 4, 2760), reaching 36000 two weeks after the booster (week 7), whereas the free antigen produced an immune response similar to that found in non-treated animals. In a parallel experiment, latex particles of a similar size to poly(l-lactic acid) microspheres, administered to both rats and rabbits, were detected in the blood stream. These findings with tetanus toxoid demonstrate the use of microsphere delivery systems for nasal application of antigens. These had a profound effect on the immune response, and indicate possibilities for overcoming some of the barriers to drug absorption in general.
Local and Systemic Actions of Loperamide on Fluid Transport and Transmural Potential Difference Across Rat Small Intestine
Authors: Goldhill J , Hardcastle J , Hardcastle P T 
Published: April 2011

Abstract
The ability of loperamide to influence intestinal fluid transport was assessed using a dual loop preparation. Loperamide was applied to the lumen of the oral, but not the aboral loop, yet basal and prostaglandin-stimulated fluid transport was affected in both, indicating that the drug can act systemically in addition to any local actions. Loperamide had both pro-absorptive and anti-absorptive effects, the latter only occurring when basal fluid absorption was high. The effects of loperamide were greater in the aboral loop to which it was available only via the systemic route. This difference may reflect the absence of counteracting local influences in the aboral loop or a variation in the sensitivity of different regions of the gut to loperamide.