bluuebunny/crossref_metadata_2025_split huggingface dataset:
Assessment of gelling in insulin solutions for infusion pumps
Authors: Hutchison K G 
Published: April 2011

Abstract
Prolonged, gentle agitation of U100 insulin solutions containing various ingredients has shown that gelling can take place. The extent of gelling was evaluated by low shear rheometry and quantified in terms of the effective molecular weight increase using the method of reduced variables. Maximal viscosities of gelled systems in excess of 100 Pas were achieved. From a knowledge of the hydrodynamics of infusion pump systems, the reduction in insulin delivery rate caused by an increase in viscosity can be calculated. In commercial, syringe-driven pumps, pressure differentials as high as 104 Nm−2 and shear rates in excess of 104 s−1 can occur, although the flow is invariably laminar.
The effects of K+-depolarization medium, chelating agents and thiol groups on cadmium uptake and efflux in the guinea-pig taenia coli
Authors: Nasu T , Koshiba H 
Published: April 2011

Abstract
Cadmium uptake by taenia coli was dose-dependent, achieving equilibrium after approximately 60 min of incubation. The SH-blocker, N-ethylmaleimide inhibited cadmium uptake. When muscles were washed with normal medium or that containing 0.5 mM EDTA following 0.5 mM Cd2+ treatment for 60 min, the tissue cadmium concentration reached equilibrium levels after 60 min and approximately 43 or 27% of the initial tissue cadmium concentration was retained, respectively. Both glutathione and dithiothreitol also increased cadmium efflux. However the contractions of glycerinated taenia coli caused by Ca2+ and Mg-ATP, completely returned to control values after washing with 0.5 mM EDTA medium following 0.5 mM Cd2+ treatment for 60 min, suggesting that EDTA seems to exert intracellular effects in glycerinated taenia coli. These results suggest that SH-dependent mechanisms in cadmium uptake play a role in intact taenia coli. In addition, in intact taenia coli, Cd2+ are accumulated in intracellular compartments which EDTA cannot reach and may exert an inhibitory action on internal sites in the cells.
Route- and dose-dependent pharmacokinetics of hexobarbitone in the rat: a re-evaluation of the use of sleeping times in metabolic studies
Authors: Van Der Graaff M , Vermeulen N P E , Breimer D D 
Published: April 2011

Abstract
The metabolic clearance (CL) and half-life of racemic hexobarbitone and sleeping time were studied in rats following intra-arterial (i.a.), intraperitoneal (i.p.) and oral (p.o.) administration, at dose levels of 25 and 100 mg kg−1 of its sodium salt. CLp.o. was higher than CLi.a. at both 25 and 100 mg kg−1. CLi.a. and CLi.p. values were much lower, but CLi.p. was higher than CLi.a. at 25 mg kg−1 and lower than CLi.a. at 100 mg kg−1. There was no distinct dependency of the half-lives on route of administration, but a slight increase upon increasing the dose was observed. Hexobarbitone blood concentrations at which the rats awoke were significantly higher after 100 mg kg−1 i.p. than after 100 mg kg−1 i.a., although there was only a small difference in sleeping time. It is postulated that the rate of uptake of the barbiturates into the portal system after i.p. administration is so high that transient saturation of hepatic first-pass metabolism occurs. Therefore neither CLi.p. nor sleeping times can be used as an accurate reflection of drug-metabolizing enzyme activity in the rat; instead CLp.o. should be used.
Ionization constants and partition coefficients of 1-arylpiperazine derivatives
Authors: Caccia S , Fong M H , Urso R 
Published: April 2011

Abstract
The ionization constant (pKa and liposolubilities (log P) of fourteen 1-arylpiperazines were determined by n-octanol/buffer partition. pKa varied little across the entire series. Log P values ranged from less than 1 to about 2 for the highly lipophilic derivatives of the preset series. The results are discussed in relation to the extent to which these derivatives, known to be centrally active, may enter the brain.
Gastrointestinal transit of an osmotic tablet drug delivery system
Authors: Wilson C G , Hardy J G 
Published: April 2011

Abstract
The gastrointestinal transit of a radiolabelled osmotic tablet drug delivery system has been monitored in groups of young and elderly healthy subjects, using gamma scintigraphy. The gastric emptying and small intestinal transit times were similar for both groups of subjects. The units were observed to move through the gastrointestinal tract at about the same rate as the released contents, arriving at the caecum on average 7 h after dosing. The data suggest that tablet adhesion to the mucosal surface is unlikely to be the mechanism responsible for the side effects reported for the indomethacin formulation Osmosin.
Effect of the absorption enhancer, Azone, on the transport of 5-fluorouracil across hairless rat skin
Authors: Sugibayashi Kenji , Hosoya Ken-ichi , Morimoto Yasunori , Higuchi William I 
Published: April 2011

Abstract
The effect of the percutaneous absorption enhancer, Azone, on the transport of 5-fluorouracil across hairless rat skin has been investigated by an in-vitro permeation technique using 2-chamber diffusion cells. Azone (3% w/v) emulsions were used. Azone enhanced the permeability of drug 10–100 times across the full-thickness skin although there was a lag time about 10 h. The long lag time, however, disappeared with Azone pretreatment. Azone also affected the transport across stripped skin. These results suggest that Azone mainly affects the stratum corneum. It seems to change the diffusivity of drug in that layer and is not so effective against diffusivities in the epidermis and dermis.
Three different ways in which 5-hydroxytryptamine can affect cholinergic activity in guinea-pig isolated ileum
Authors: Sanger G J 
Published: April 2011

Abstract
The effects of 5-hydroxytryptamine (5-HT) have been studied on electrically-evoked contractions mediated by cholinergic nerves in guinea-pig isolated ileum. Low concentrations of 5-HT (0.0001-0.01 μg ml−1) caused a sustained increase in submaximal, electrically-evoked contractions. Higher concentrations of 5-HT (0.1–10 μg ml−1) initially evoked a fast, rapidly-fading contraction of the muscle. Subsequently, 5-HT 0.1–10 μg ml−1 caused a sustained reduction in the height of the electrically-evoked contractions. The effects of 5-HT 0.01 and 0.1 μg ml−1 on the electrically-evoked contractions were not blocked by methysergide 0.1 μg ml−1 or by hexamethonium 10 μg ml−1, and may be due to changes in neuronal acetylcholine (ACh) release, since contractions evoked by exogenous ACh were unaffected by 5-HT. The results therefore imply that 5-HT can affect gut cholinergic activity in at least three different ways, two of which may modulate evoked ACh release by mechanisms which may be insensitive to tachyphylaxis.
The effect of sodium lauryl sulphate, cetrimide and polysorbate 20 surfactants on complex coacervate volume and droplet size
Authors: Duquemin Sarah Jane , Nixon J R 
Published: April 2011

Abstract
The effects of sodium lauryl sulphate (SLS), cetrimide and polysorbate 20 surfactants at concentrations below, at and above their critical micelle concentration (CMC) on the complex coacervation of varying concentrations of gelatin and acacia have been described. The overall effect of increasing concentration of SLS was to reduce the weight of coacervate formed. The addition of increasing concentrations of cetrimide produced an increase in the weight of coacervate. The two lowest concentrations of polysorbate 20 produced an increase in coacervate weight while the highest concentration, above the CMC, reduced the coacervate weight. These effects have been explained in terms of shielding of electrostatic attractions between gelatin and acacia polyions by adsorption of ionic and non-ionic surfactant molecules onto the polyions. The addition of surfactants influenced the size distribution of the coacervate droplets that were produced. It is believed that the reduction in interfacial tension by the aggregation of surfactant molecules at the coacervateequilibrium liquid interface permitted the formation of smaller coacervate droplets.
The use of strain gauges for radial stress measurement during tableting
Authors: Huckle P D , Summers M P 
Published: April 2011

Abstract
The influence of size, configuration and positioning of die wall strain gauges on the measurement of radially transmitted stress developed during tableting was investigated. Calibration of strain gauges attached to a cutaway die wall was achieved by compression of rubber-like materials in the die, Breon Polyblend 504 being more effective than red rubber for this purpose. Hysteresis of response observed when calibrating a thin-walled die was possibly due to excessive distortion of the weakened die wall although the extent of this hysteresis varied with calibration material. The use of full bridge arrangements produced an increase in response when the compression site was moved away from the gauges. The opposite effect was seen when half bridge arrangements, using two active gauges, were used. The paradoxical effect observed when full bridge arrangements were used was shown to be due to straining of the compensating gauges. The dependence of die wall response on compact position was substantially reduced by the use of multiple gauges mounted along the die length and connected together to form a single gauge on each side of the die.
Effect of phenobarbitone on the pharmacokinetics and tissue levels of amiodarone in the rat
Authors: Fruncillo Richard J , Bernhard Ronald , Swanson Brian N , Vlasses Peter H , Ferguson Roger K 
Published: April 2011

Abstract
Phenobarbitone pretreatment has been shown to increase amiodarone total clearance and decrease amiodarone elimination half-life after a single intravenous amiodarone dose in the rat. Coadministration of phenobarbitone with amiodarone for 7 days resulted in decreased tissue amiodarone levels compared to controls. These results may have Implications for patients undergoing therapy with amiodarone and concomitant potent enzyme inducing drugs.
Effect of phenobarbitone on the distribution and elimination of imipramine in rats
Authors: Lin Tsu-Han , Sawada Yasufumi , Sugiyama Yuichi , Iga Tatsuji , Hanano Manabu 
Published: April 2011

Abstract
The effect of phenobarbitone on the steady state volume of distribution (Vdss) and the total body blood clearance (CLtot, b) of imipramine and the serum concentration of its metabolite, desipramine was examined. The serum disappearance of imipramine after an 8 mg kg−1 i.v. dose followed a biexponential decline in both control and phenobarbitone-treated rats while the concentration of its metabolite increased in the phenobarbitone-treated rats then rapidly declined compared with that in control rats. Since CLtot, b was nearly equal to the hepatic blood flow (QH), QH may be the rate-determining step of imipramine elimination. In the control rats the Vdss of imipramine was large at 19.9 litre kg-1. In the phenobarbitone-treated rats the pharmacokinetic parameters, biological half-life (t 1/2) and Vdss significantly decreased to approximately 23-40% while CLtot, b increased to 126% of those in the control rats, although the latter difference was not statistically significant. The blood-to-plasma concentration ratios (RB) of imipramine and desipramine decreased in the phenobarbitone-treated rats. The urinary excretion ratios of imipramine and desipramine, to the dose of imipramine over 8 h, were &lt;1.5% in both groups. These ratios were not significantly changed in the phenobarbitone-treated rats. It was concluded that the significant decrease in t 1/2 of the phenobarbitone-treated rats may not be attributed to the changes in CLtot,b and/or in the urinary excretion, but mainly to the decrease in Vdss.
Induction of drug metabolizing enzymes in the liver of rats infested with Fasciola hepatica
Authors: Galtier P , Larrieu G , Lesca P 
Published: April 2011

Abstract
Adult, male rats were infected with 20 metacercariae of Fasciola hepatica given orally, other rats were left untreated. Five weeks after infestation, some animals received phenobarbitone, 3-methylcholanthrene, β-naphthoflavone or Arochlor 1254, to induce liver drug metabolizing enzymes. Fascioliasis provoked decreases in aminopyrine N-demethylase, aniline hydroxylase, the mutagenic activity of cyclophosphamide and cytochrome P-450 concentration in untreated or phenobarbitone or Arochlor pretreated rats. In contrast, cytochrome b5, NADPH cytochrome c reductase, ethyoxycoumarin O-deethylase and the enzymatic activation of ethidium bromide were not affected by fascioliasis whatever pretreatment was given. Fascioliasis decreased liver drug metabolizing enzymes which were specifically induced by both phenobarbitone and Arochlor, this could be due to either the specific action of toxic excretions of flukes or to the particular localization of tissue damage within the liver lobule.
Flumezapine and zotepine: 5-hydroxytryptamine antagonism not involved in the lack of synergism of these antipsychotic drugs with amfonelic acid in rats
Authors: Fuller Ray W , Snoddy Harold D 
Published: April 2011

Abstract
Two antipsychotic drugs, flumezapine and zotepine, resembled clozapine, not spiperone, in not acting synergistically with amfonelic acid to elevate striatal concentrations of 3,4-dihydroxyphenylacetic acid (DOPAC) in rats. Since flumezapine, zotepine and clozapine antagonize 5-hydroxytryptamine (5-HT) receptors with potency similar to their potency in antagonizing dopamine receptors, the possibility that 5-HT receptor blockade prevented their synergism with amfonelic acid was considered. Methiothepin, a potent 5-HT antagonist and dopamine antagonist, mimicked spiperone in causing a marked increase in striatal DOPAC in amfonelic acid-treated rats, indicating that 5-HT antagonism is not involved in the lack of synergism of flumezapine and zotepine with amfonelic acid.
Absorption of delayed-release prednisolone in ulcerative colitis and Crohn's disease
Authors: Thomas P , Richards D , Richards A , Rogers L , Evans B K , Dew M J , Rhodes J 
Published: April 2011

Abstract
The absorption and urinary excretion of [3 H]prednisolone after oral ingestion was examined using hard gelatin capsules with and without a coating of Eudragit-S which delayed release of the contents. In 6 patients with ulcerative colitis absorption was delayed until the preparation reached the colon but the total absorption was unchanged. In 6 patients with Crohn's disease and ileal strictures the preparation broke proximal to the stricture and absorption was delayed until this occurred (within 4-12 h). In 5 patients with Crohn's disease and intestinal resections the capsules broke unreliably.
Gloss measurement on film coated tablets
Authors: Rowe R C 
Published: April 2011

Abstract
The gloss of film coated tablets has been assessed using a commercially available specular glossmeter modified to measure the specular reflectance of individual flat-faced, film-coated tablets. For all the pigmented film formulations studied, there was a decrease in gloss with increasing pigment concentration, the magnitude of the decrease being dependent on the pigment used. Film coatings prepared using an aqueous coating system had a much lower gloss reading than those prepared using an organic solvent coating system. Increasing the mean particle size of an inert filler particle resulted in a minimum gloss reading at intermediate particle sizes, while increasing the polymer concentration resulted in a significant decrease in gloss. In the latter case a power law equation was found to fit the data relating the percentage decrease in gloss with the percentage increase in roughness. The results are consistent with the known theories of specular reflectance and illustrate the potential of this rapid and simple technique in the optimization of film formulation and process variables during product development.
Models for evaluating the anti-inflammatory effects of inhibitors of arachidonic acid metabolism
Authors: Blackham A , Norris A A , Woods F A M 
Published: April 2011

Abstract
Inhibitors of arachidonic acid metabolism were characterized by their ability to modulate slow reacting substance (SRS) and prostaglandin E2 (PGE2) release from stimulated mouse peritoneal macrophages in-vitro. Differential effects of cyclo-oxygenase (CO) and lipoxygenase (LO) enzyme inhibitors and compounds which inhibit both enzymes were demonstrated using several animal models of inflammation. Carrageenan-impregnated sponges implanted subcutaneously in rats and immune-complexes injected intraperitoneally in mice produced inflammatory responses characterized respectively by polymorphonuclear (PMN) cell infiltration and by increased vascular permeability. Dual CO/LO inhibitors (eg. BW 755c and timegadine) were capable of suppressing both parameters and reduced SRS and PGE2 formation in-vivo. In contrast, selective CO inhibitors (e.g. indomethacin, naproxen and R-830) were less active against permeability, and potentiated SRS release. Although selective CO inhibitors reduced PMN migration, this occurred at doses which exceeded those required for inhibition of PGE2. Compounds possessing LO inhibitory activity suppressed the cellular component of an Arthus type reaction in the rat pleural cavity, but were less active than selective CO inhibitors against carrageenan-induced paw oedema in rats.
The effect of phenothiazine and dibenzazepine pretreatment on the metabolism of methamphetamine in rats
Authors: Mori M , Fujita M , Kozuka H 
Published: April 2011

Abstract
There was marked variation between p-hydroxylation and N-demethylation of methamphetamine in rats. Within 24 h, 10.4,24.7 and 41% of the administered methamphetamine was excreted in urine unchanged, p-hydroxymethamphetamine (p-OH-MP, free plus conjugated) and also as amphetamine, respectively. Treatment by imipramine, desipramine, chlorpromazine, perphenazine and propericiazine 8 h before the administration with methamphetamine completely inhibited the urinary excretion of p-OH-MP whereas the excretion of amphetamine was enhanced by about 700 to 800%. This effect was also observed in rats treated with imipramine 16 and 24 h before methamphetamine. Phenothiazine and dibenzazepine derivatives reverse the degree of p-hydroxylation and N-demethylation of methamphetamine in-vivo in rats.
Postreceptor effect of metformin on insulin action in mice
Authors: Lord J M , Puah J A , Atkins T W , Bailey C J 
Published: April 2011

Abstract
To investigate the possibility that metformin (dimethylbiguanide) modifies insulin-mediated glucose metabolism by an effect that is independent of insulin receptor binding, glycogenesis and insulin binding were measured in soleus muscles isolated from streptozocin diabetic mice after treatment with 60 mg kg−1 metformin daily for 10 weeks. This dose of metformin increased insulin-stimulated glycogenesis but did not affect insulin binding in the soleus muscles of streptozocin diabetic mice. The results suggest that metformin can influence postreceptor sites of insulin action independently of insulin receptor binding.
Dose-dependent presystemic elimination of propranolol due to hepatic first-pass metabolism in rats
Authors: Iwamoto Kikuo , Watanabe Jun 
Published: April 2011

Abstract
Gastrointestinal first-pass elimination of propranolol and the effect of dose (1.0, 2.5, 5.0 and 10.0 mg kg−1) on its systemic availability were studied in male Wistar rats which received the drug intravenously, orally or intraportally. The plasma elimination half-life was not altered either by the route of administration or the dose. There was no gastrointestinal first-pass metabolism of propranolol, since the same systemic availability was obtained after oral and intraportal administration. Hepatic clearance was estimated to be constant at any dose. In contrast, the hepatic intrinsic clearance was found to be largely dependent on the portal dose.
Pharmacological actions of ifenprodil in the rat isolated anococcygeus muscle
Authors: Adeagbo A S O , Magbagbeola A O 
Published: April 2011

Abstract
The effect of ifenprodil on the contractile responses of the rat anococcygeus muscle to noradrenaline, methoxamine, carbachol, potassium chloride and calcium chloride has been examined. Ifenprodil (10−8-10−7M) non-competitively antagonized noradrenaline and methoxamine-induced contractions while carbachol-induced responses were unaffected. Similarly, contractile responses to KCl (in tissues from reserpinized animals, or tissues bathed in Tyrode containing 10−6M phentolamine) and CaCl2 in tissues bathed with Ca2+-free depolarizing solution were blocked non-competitively by ifenprodil (10−7-10−6M). These findings suggest that ifenprodil possesses α-adrenoceptor antagonist activity, with intrinsic Ca2+ blocking properties.
Flow defects in wet powder mass extrusion
Authors: Harrison P J , Newton J M , Rowe R C 
Published: April 2011

Abstract
Surface impairment, in the form of the flow defects roughness and sharkskinning, has been shown to occur with microcrystalline cellulose/lactose/water mixes on extrusion under varying process conditions. These defects result from the imbalance of stresses at the outer wall of the extrudate on leaving the die and can be avoided by changing the process conditions that are known to affect these stresses, e.g. the length of the die, the velocity of throughput and the moisture content of the formulation.
The use of gamma scintigraphy to follow the gastrointestinal transit of pharmaceutical formulations
Authors: Christensen F N , Davis S S , Hardy J G , Taylor M J , Whalley D R , Wilson C G 
Published: April 2011

Abstract
The technique of gamma scintigraphy has been used to follow the transit of a solution and a pellet formulation in the gastrointestinal tract of healthy volunteers. The emptying of the formulations from the stomach and their arrival at the caecum could be quantified, thereby allowing calculation of transit times for the small intestine. Gastric emptying was affected by the nature of the formulation, i.e. liquid or solid. However, transit through the small intestine was independent of the nature of the administered material.
The effect of formulation on oesophageal transit
Authors: Channer K S , Virjee J P 
Published: April 2011

Abstract
The oesophageal transit of barium sulphate in small or large, heavy or light capsules or film coated and plain oval tablets was measured during fluoroscopy in five separate studies involving 175 subjects. Transit of large, but not small capsules was significantly faster than plain oval tablets in both erect and supine subjects (P &lt; 0 05). Heavy large capsules entered the stomach in all subjects within 20 s, whereas in all other studies some subjects retained dosage forms in the oesophagus for over 5 min. The transit of heavy capsules was significantly faster than light capsules in erect subjects (P &lt; 0.0005). Light capsules tended to have faster transit times than heavy capsules in the supine position. Film coating significantly enhanced oval tablet transit in erect (P &lt; 0.00003) and supine subjects (P &lt; 0.05). When large capsules of equal weight but less dense than film coated oval tablets were directly compared, the tablet transit was significantly superior in the erect subjects (P &lt; 0.0001). In supine subjects the transit of the light capsule was significantly faster (P &lt; 0.005). It is concluded that different drug formulations can have significant effects on oesophageal transit, and hence on the development of drug induced oesophageal ulceration.
Effect of sodium azide and sodium selenite on prostaglandin synthesis in rabbit kidney medulla slices
Authors: Fujimoto Yohko , Yamamoto Taku , Niwase Nobuyuki , Fujita Tadashi 
Published: April 2011

Abstract
Sodium azide, a catalase inhibitor, stimulated the generation of medullary prostaglandin E2, while the glutathione peroxidase activator sodium selenite inhibited it. These results suggest that hydroperoxides play an important role in the control of prostaglandin synthesis.