bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Disposition of Quinine in the Rat Isolated Perfused Liver: Effect of Dose Size
Authors: Coleman M D , Timony G , Fleckenstein L 
Published: April 2011

Abstract
We have investigated the pharmacokinetics of both free and total quinine in the rat isolated perfused liver at three doses, 6.25, 12.5 and 25 mg. The plasma concentrations of free and total quinine decayed biexponentially over 4 h. However, on increasing dose, the terminal half-life of free and total quinine showed marked increases ranging from 12.4 ± 3.7 min at 6.25 mg to 176.0 ± 153 min at 25 mg (total quinine). Quinine clearance was reduced approximately by half as the dose was doubled. At 10 min post dosage, quinine extraction at the 6.25 mg dose (56 ± 16.3%) was more than twice that of the highest dose (25 mg, 25.0 ± 6.5%). Free quinine at the 6.25 mg dose was cleared at ∼ 100% of perfusate flow, whereas at 25 mg, clearance was less than one fifth of that value. Unchanged quinine elimination in bile was low, with less than 1 % of the parent drug being detected at the 12.5 and 25 mg doses. Relatively little parent drug was recovered from the liver at 4 h. At the 25 mg dose, ≤ 6% was recovered as parent drug. HPLC analysis revealed some polar metabolites of quinine in the bile and in the liver homogenates. Dose dependent kinetics of quinine were demonstrated in this study, as hepatic extraction of quinine decreased with increasing dose and input concentration.
Stimulatory Effects of 5-Hydroxytryptamine on Fluid Secretion and Transmural Potential Difference in Rat Small Intestine are Mediated by Different Receptor Subtypes
Authors: Beubler E , Coupar I M , Hardcastle J , Hardcastle P T 
Published: April 2011

Abstract
The rise in transmural potential difference (PD) and the fluid secretion induced by 5-hydroxytryptamine (5-HT) were measured in rat small intestine in-vivo. Both cisapride and ketanserin abolished the 5-HT-induced rise in systolic blood pressure mediated by 5-HT2 receptors. Cisapride inhibited the 5-HT-induced increases in the transintestinal PD, but over the same dose range it had no effect on the fluid secretion induced by 5-HT. In contrast, ketanserin caused a dose-dependent reduction in 5-HT-induced fluid secretion at doses that failed to influence the rise in PD. It is concluded that different receptors are responsible for the effects of 5-HT on fluid secretion and electrical activity in the rat small intestine.
Improved synthetic routes to the novel thromboxane receptor antagonist ICI 192605: activity of synthetic 1,3-dioxane intermediates
Authors: Brown George R , Foubister Alan J , Hudson Julian A 
Published: April 2011

Abstract
A study of the synthetic routes to the thromboxane receptor antagonist ICI 192605 4(Z)-6-(2-o-chlorophenyl-4-o-hydroxyphenyl-1,3-dioxan-cis-5-yl) hexenoic acid is described which led to an improvement in overall synthetic yield from 20 to 55%. In-vitro thromboxane receptor antagonist data are reported for the novel 1,3-dioxane synthetic intermediates. These data indicated that shortening of the side chain in an appropriately substituted 2,2-dimethyl-1,3-dioxane (e.g. ICI 180080) from a heptenoic acid, to a hexenoic acid, had little effect on thromboxane receptor antagonist potency (pA2 = 7.5 rabbit thoracic aorta for the heptenoic acid ICI 180080 and pA2 = 6.9 for the corresponding hexenoic acid. Human platelet aggregation pA2 values were 6.7 and 7.0, respectively).
The significance of removing oxygen-derived free radicals in the treatment of acute and chronic duodenal ulceration in the rat
Authors: Salim Aws S 
Published: April 2011

Abstract
Rats infused for 24 h with pentagastrin (4 μg kg−1 min−1) and carbachol (0.8 μg kg−1 min−1) developed acute duodenal ulceration (100%) and hyperchlorhydria (69 ± 5.3 μmol h−1 vs 14 ± 0.9 μmol h−1, P &lt; 0.001, n = 10). The animals were then given daily by gavage, saline, allopurinol with dimethyl sulphoxide (DMSO) or cysteine with methyl methionine sulphonium bromide (MMSB). Two days after the infusion, 10 rats (100%) given saline and 7 rats (70%) given allopurinol and DMSO, or cysteine and MMSB, showed duodenal ulceration. Five days after the infusion, 8 rats (80%) given saline, 3 rats (30%) given allopurinol and DMSO, and 2 rats (20%) given cysteine and MMSB had duodenal ulceration. Seven days after the infusion, only 5 rats (50%) given saline still had duodenal ulceration. Daily intramuscular injection of reserpine (0.1 mg kg−1) for 6 weeks produced chronic duodenal ulceration (90%) and hyperchlorhydria (47 ± 31 μmol h−1 vs 12 ± 0.9 μmol h−1, P &lt; 0.001, n = 10). Animals were then given daily by gavage, saline, allopurinol and DMSO, or cysteine and MMSB. Five days after reserpine, 10 rats (100%) given saline, 8 rats (80%) given allopurinol and DMSO, and 7 rats (70%) given cysteine and MMSB showed duodenal ulceration. Ten days after reserpine, 9 rats (90%) given saline, 3 rats (30%) given allopurinol and DMSO, and 4 rats (40%) given cysteine and MMSB had duodenal ulceration. Fifteen days after reserpine, 8 rats (80%) receiving saline and only one rat (10%) receiving allopurinol and DMSO or cysteine and MMSB had duodenal ulceration. Twenty days after the reserpine treatment only 6 rats (60%) given saline still had duodenal ulceration. The results show that removing oxygen-derived free radicals stimulates the healing of acute and chronic duodenal ulceration in the rat.
The Effect of Oral Activated Charcoal on the Systemic Clearance of Gentamicin in Rabbits with Acute Renal Failure
Authors: Hasan M M , El-Sayed Y M , Abdelaziz A A 
Published: April 2011

Abstract
The effect of oral administration of activated charcoal on total body clearance of gentamicin administered intravenously (2 mg kg−1) has been studied in normal rabbits and rabbits with induced renal failure. Gastric intubation of a single dose (10 g) of activated charcoal to normal rabbits produced a significant reduction in gentamicin serum concentrations compared to control. Significant differences between treated and control groups, compatible with enhancement of gentamicin elimination, were observed in the calculated pharmacokinetic parameters (Kel, t 1/2, CL and AUC). To examine whether renal failure could augment the effect of activated charcoal in enhancing the systemic clearance of gentamicin, uranyl nitrate was used (0.75 mg kg−1, i.v.) to induce acute renal failure in rabbits. The derived pharmacokinetic parameters of gentamicin during the control phase in these animals were consistent with severe renal failure. The administration of activated charcoal, 2.5 h following gentamicin injection, produced a steeper decline in gentamicin concentration-time profiles and significant changes in Kel, t 1/2 and CL. The Kel and CL values increased to about 200%, while the t 1/2 value decreased to about 50%. The apparent changes in the pharmacokinetic parameters induced by charcoal administration were more marked in rabbits with renal failure than in normal rabbits; however, induction of renal failure did not augment the charcoal-induced clearance of gentamicin quantitatively.
Liver Damage Induced by Intrabiliary Turpentine in Rats
Authors: Martinková J , Rýdlová I , Šubrtová D , Palička V 
Published: April 2011

Abstract
Inflammation of the rat bile duct induced by administration of turpentine into it has been used to study the influence of the impaired duct on liver function. Turpentine was dissolved in olive oil 1:1000 and 1:500. A 2 h ligation of the bile duct was used to promote a local effect. Contemporary groups of intact, sham-operated, control rats (given 0.9% NaCl by intrabiliary injection) and animals with total chronic obstruction were compared to assess the significance of changes. Serum concentrations of total and conjugated bilirubin, cholesterol and creatinine, activities of S-alanine-aminotransferase, S-aspartate aminotransferase and alkaline phosphatase, mortality of rats, and also total body weight compared with the weight of the liver, were investigated on days 1, 4, 8, 12, 16, 32 and 64 after surgery and turpentine, or following ligation of the bile duct. An increase in bilirubin and cholesterol, an augmentation of enzymatic activity and the histological changes were indicative of hepatotoxicity or cholestasis. The turpentine concentration - effect, manifested in body-weight change, suggests some specificity of the effect. There were no changes in serum creatinine arterial blood pressure, heart rate or portal blood pressure, when turpentine was administered by the intrabiliary route. These results suggest primary liver damage.
The Coating and the Encapsulation of an Interactive Powder Mixture and its Application to Sustained Release Preparations
Authors: Yoshizawa H , Koishi M 
Published: April 2011

Abstract
Fine cohesive isoprenaline HCl particles adhered to the surface of coarser potato starch particles to form interactive mixtures. These were coated with magnesium stearate by dry mixing. To check if there was a lowering of homogeneity in the latter stage, the degree of mixing was investigated before and after adding magnesium stearate. The surface appearance of magnesium stearate-coated interactive mixtures became smoother as mixing time increased or the temperature of the powder bed during mixing was raised. Ultimately, the magnesium stearate encapsulated the particles of interactive mixture. The coated interactive mixtures improved sustained release of isoprenaline HCl over the starch mixtures alone, the effect depending on the density of the magnesium stearate. Only in encapsulated mixtures was the release rate of drug decreased as the amount of magnesium stearate increased. The release of isoprenaline HCl from the interactive mixtures followed first-order kinetics. A linear relationship existed between the first-order rate constant and the reciprocal thickness of the magnesium stearate film, indicating a diffusion-controlled system with the film having some pores.
Comparison of the Antisecretory Effects of Loperamide and Loperamide Oxide in the Jejunum and the Colon of Rats In-vivo
Authors: Beubler Eckhard , Badhri Pramila 
Published: April 2011

Abstract
The antidiarrhoeal effect of loperamide is caused by its antimotility and antisecretory properties. In-vivo experiments in the rat jejunum and colon have been performed to compare the antisecretory effect of loperamide with the effect of its prodrug, loperamide oxide. Both loperamide and loperamide oxide administered intraluminally, equally and dose dependently (2 to 250 μg mL−1) reduced PGE2-induced net fluid secretion (32 ng min−1 i.a.) in the jejunum and colon. The antisecretory effect of both drugs is blocked by naloxone (1 mg kg−1 s.c). It is concluded that loperamide oxide administered intraluminally is reduced to loperamide and has the same antisecretory potency as loperamide in jejunum and colon. The effect appears to be mediated via opiate receptors. The observation that loperamide cannot be detected in the colonic lumen two h after oral administration suggests that the drug is delivered from the blood stream to the site of action after absorption in the small intestine.
Comparison of intestinal and peritoneal dialysis of theophylline and phenobarbitone in rats
Authors: Arimori Kazuhiko , Hashimoto Yoshiko , Nakano Masahiro 
Published: April 2011

Abstract
Intestinal dialysis of drugs by oral administration of activated charcoal has been compared with peritoneal dialysis in rats. The average amounts of theophylline transported over 120 min into the intestinal lumen and the peritoneal cavity were 15.7 and 16.5% of the intravenous dose (10 mg kg−1), respectively, showing no significant difference, whereas the amount of the same intravenous dose of phenobarbitone transported from the blood into the intestinal lumen (7.8%) was significantly smaller than that entering the peritoneal cavity (12.5%). The net water flux showed that secretion predominated in the peritoneal transport whilst absorption predominated in the intestinal transport for both drugs. However, the net water flux in the intestinal lumen after intravenous theophylline (as aminophylline) was significantly smaller than that following phenobarbitone. The differences in transport across the two membranes could be due to differences in the intrinsic properties of the membranes, such as the surface area, the thickness of the membrane and the distribution of blood vessels. Differences could also be due to differences in the pharmacological effects of the drugs.
Effects of clenbuterol treatment on the responses to vasodilators in urethane-anaesthetized rats
Authors: Kazanietz Marcelo G , Gutkind Jorge S , Enero María Amelia 
Published: April 2011

Abstract
Seven or 14 days of treatment with the β2-adrenoceptor agonist clenbuterol, 0.3 mg kg−1, s.c., twice daily, increased the basal mean blood pressure in normotensive urethane-anaesthetized rats. The elevated pressure values were maintained until 48 h after the end of the 14 day treatment. Clenbuterol treatment decreased the vasodilatory responses to the β-adrenoceptor agonist isoprenaline and adenosine, agents which act through an increase in intracellular cyclic AMP. Decreased responses were maintained until 48 h after a 14 day treatment with clenbuterol. On the other hand, its administration to rats for 14 days did not modify the vasodilator responses to acetylcholine or sodium nitroprusside, two agents that exert their effects by enhancing cyclic GMP. The increase in mean blood pressure in urethane-anaesthetized rats after clenbuterol treatment may be a consequence of a reduced vasodilator β2-adrenoceptor-mediated response to circulating catecholamines.
Mast Cell Degranulating Peptide: A Multi-functional Neurotoxin
Authors: Ziai M Reza , Russek Shelley , Wang Hsuei-Chin , Beer Bernard , Blume Arthur J 
Published: April 2011

Abstract
This review discusses our present knowledge of the structure and activities of the mast cell degranulating peptide (MCDP). This peptide is a basic, 22 amino acid residue component of honey bee venom with striking immunological and pharmacological activities. MCDP is a potent anti-inflammatory agent, but at low concentrations it is a strong mediator of mast cell degranulation and histamine release. MCDP is also an epileptogenic neurotoxin, an avid blocker of the potassium channels and can cause a significant lowering of the blood pressure in rats. Some of the biological activities of MCDP appear to have distinct mechanisms and may represent a good illustration of the structure-function relationship.
The influence of density on the gastrointestinal transit of pellets
Authors: Devereux J E , Newton J M , Short M B 
Published: April 2011

Abstract
The gastric emptying, intestinal transit and caecum arrival times of 1 mm pellets of density 1.5 and 2.8 g cm−3 have been assessed in fed and fasted volunteers by means of gamma-scintigraphy. The pellets were prepared by extrusion/spheronisation, coated with ethylcellulose and labelled with technetium-99m. The position of the pellets in the gastro-intestinal tract was followed by a double-headed gamma camera to allow detailed information over a period of up to 10 h. Analysis of variance established that there was a highly significant difference in the time for 50% of the pellets to empty from the stomach both in fed and fasted states. The 2.8 g cm−3 pellets had an extended resident time in both the fed and fasted states. The gastric emptying time was prolonged in the fed state. There was no significant difference in intestinal transit time between the two formulations nor whether the volunteers were fed or fasted. The caecum arrival time was therefore modified only by the gastric emptying time.
The in-situ absorption of antipyrine as a measure of intestinal blood flow in Fluosol-DA haemodiluted rats
Authors: Shrewsbury Robert P , White Lisa G 
Published: April 2011

Abstract
The effect of moderate Fluosol-DA haemodilution on intestinal blood flow has been investigated in the rat. Antipyrine in-situ intestinal absorption is blood flow limited, and did not alter 0.5, 24, 48, or 72 h after haemodilution with 40 mL kg−1 Fluosol. Thus the intestinal blood flow rate is maintained as part of the physiological response to ensure adequate perfusion of the vital organ.
Effect of Surface Characteristics of Theophylline Anhydrate Powder on Hygroscopic Stability
Authors: Otsuka Makoto , Kaneniwa Nobuyoshi , Kawakami Katsumi , Umezawa Osamu 
Published: April 2011

Abstract
The hygroscopicity of theophylline anhydrate has been investigated by gas adsorption and hydration kinetic methods. Type I theophylline anhydrate was obtained by recrystallization from distilled water at 95°C, and type II was obtained by dehydration of theophylline monohydrate. The X-ray diffraction pattern of types I and II agreed with the data of theophylline anhydrate. However, the diffraction peaks of the (200) and (400) planes of type I were much stronger than those of type II. The particles of type I were clear crystalline-like single crystals. However, the particles of type II had many cracks. The gas affinity balance (H/N) of type II, measured by gas adsorption, was about 7 times that of type I. After the hygroscopicity of types I and II had been tested at various levels of relative humidity (RH) at 35°C, type I was stable at less than 82% RH, but transformed into the monohydrate at more than 88% RH. Type II was stable at less than 66% RH and transformed into the monohydrate at less than 75% RH. The hydration data of type I at 88% RH and type II at 75% RH were calculated for hydration kinetics using various solid-state kinetic models, but no particular model could be preferred from these data.
Changes in Intracellular Ca2+ Produced in the Mouse Diaphragm by Neuromuscular Blocking Drugs
Authors: Kimura I , Kondoh T , Kimura M 
Published: April 2011

Abstract
Differences between the effects of depolarizing and competitive neuromuscular blocking drugs on Ca2+-aequorin luminescences (Ca2+ transients) emitted during twitches were compared in indirectly-stimulated diaphragm muscles of mice. Succinylcholine enhanced intracellular Ca2+ transients at concentrations of 1.3-2.5 μM and inhibited them at concentrations of 5.0–50 μM, demonstrating a biphasic response as in the case of twitch tensions. However, the response to Ca2+ transients was two to three times more sensitive than the response to twitch tension. Decamethonium 2.4–96 μM and carbachol 5.5–109 μM produced similar results. In contrast, pancuronium and (+)-tubocurarine inhibited them in the same concentration ranges. The relation between Ca2+ transients and twitch tensions was hyperbolic and was computer-simulated by the Hill equation in the case of succinylcholine, decamethonium and carbachol, whereas it was represented by a single exponential equation in the case of pancuronium, (+)-tubocurarine, and submaximal nerve-stimulation voltage. Spontaneous Ca2+ transients, on the other hand, were generated only in response to depolarizing drugs at concentrations having a neuromuscular blocking effect. These results suggest that depolarizing and competitive neuromuscular blocking drugs affect intracellular Ca2+ mobilization by different routes mediated by acetylcholine receptors.
The Preservation of Functional Activity of Smooth Muscle and Endothelium in Pig Coronary Arteries after Storage at −190°C
Authors: Schoeffter Philippe , Müller-Schweinitzer Else 
Published: April 2011

Abstract
Pig coronary arteries have been investigated in-vitro using fresh tissue or after storage at −190°C in foetal calf serum containing 1.8 M dimethyl sulphoxide. Attention was paid to modulation of contractile activity and endothelium-dependent relaxation. After cryopreservation of the arteries maximal contractile responses to both 5-hydroxytryptamine (5-HT) and prostaglandin F2α (PGF2α) were markedly reduced and the pD2 values for both agonists were slightly, but significantly, diminished. Nevertheless, 5-HT antagonism by ketanserin and pizotifen was unchanged. Endothelium-independent relaxant responses of precontracted arteries to isoprenaline, forskolin, 3-isobutyl-1-methylxanthine, nitroprusside, atriopeptin III and cromakalim were generally unchanged after storage. Mechanical removal of the endothelium by rubbing enhanced the contractile response to PGF2α in both fresh and stored arteries to a similar extent. In addition, endothelium-dependent relaxant responses to both 5-HT and substance P were well maintained, suggesting release of endothelium-derived relaxing factor by the stored arteries. The evidence suggests that after cryopreservation of pig coronary arteries at −190° C mechanisms of relaxation, in particular those which are endothelium-dependent, are well maintained.
Negative inotropic effect induced by diethylamiloride (DEA) in rabbit myocardium
Authors: PEREZ M D , FUEYO J , BARRIGON S 
Published: April 2011

Abstract
The effects of the Na+/H+ exchange blocking drug diethylamiloride (DEA) on mechanical function have been studied in the rabbit isolated, arterially perfused interventricular septum. At concentrations of 10−6-10−5 M, DEA induced a significant, dose-dependent, negative inotropic effect (a 54% decrease from control values at the highest concentration), which was slow to develop. After a 45 min washout, recovery was almost complete (95 ± 3.4%). At concentrations &gt; 5 × 10−5 M, DEA induced a rapid and marked decrease in developed tension, associated with a progressive decrease in excitability and incomplete recovery. Resting tension was not significantly modified at any of the concentrations tested. At &gt; 10−6 M DEA enhanced significantly the transient negative inotropic effect of the brief intracellular acidosis induced by removal of NH4Cl perfusion, both by decreasing the minimal value of developed tension and by increasing the time required to produce this effect. These effects suggest that the dose-dependent DEA negative inotropic effect could be mediated by a progressive intracellular acidosis produced by inhibition of the Na+/H+ exchange system.
The Parenteral Controlled Release of Liposome Encapsulated Chloroquine in Mice
Authors: Titulaer H A C , Eling W M C , Crommelin D J A , Peeters P A M , Zuidema J 
Published: April 2011

Abstract
Free (0.6 mg), and liposome encapsulated chloroquine (0.6, 3 mg), were injected intraperitoneally, intramuscularly and subcutaneously in mice. Intraperitoneal administration of liposome-encapsulated chloroquine resulted in high and long lasting concentrations of chloroquine in the blood compared with intraperitoneal administration of free chloroquine. After administration of the liposome-encapsulated chloroquine the concentrations in the spleen were also higher, indicating that chloroquine liposomes reached the blood compartment intact after intraperitoneal administration. After intramuscular and subcutaneous administration the chloroquine liposomes acted as a local depot, giving a slower release from the subcutaneous fat layer than from the muscle depot. After the 0.6 mg dose a burst effect was found at about 7 h in most of the animals; this was not found after the 3 mg dose. This finding and the slower release after the 3 mg dose than after the 0.6 mg dose could be explained by the formation of aggregates after the injection.