bluuebunny/crossref_metadata_2025_split huggingface dataset:
Different Influence of Endothelium in the Mechanical Responses of Human and Cat Isolated Cerebral Arteries to Several Agents
Authors: Conde M Victoria , Marco Emilio J , Fraile M Luz , Benito J Miguel , Moreno M Jesús , Sanz M Luz , De Pablo Angel L López 
Published: April 2011

Abstract
The present work was undertaken to elucidate the role of the vascular endothelium in the changes of isometric tension elicited by different compounds in isolated cylinders of human and cat cerebral arteries and cat pulmonary arteries. Endothelium removal by rubbing significantly reduced the relaxing response to acetylcholine (ACh) of isolated segments of all the arteries. The same treatment did not modify the contraction elicited by 5-hydroxytryptamine (5-HT) in the human and cat cerebral segments but increased the contractile effect of the amine in cat pulmonary arteries. The mechanical responses to vasopressin, ATP and adenosine in isolated segments of cat cerebral arteries were unaffected after removing the endothelial layer. L-Arginine, but not D-arginine (10−5 M), enhanced significantly the relaxation induced by increasing doses of ACh in unrubbed cat cerebral arteries whereas it did not modify the response to ACh in rubbed ones. However, L-arginine had no effect on the dose-response curve to 5-HT in both kinds of preparation and did not change the tone in precontracted unrubbed cat cerebral segments. These results suggest that the endothelium of the cerebrovascular bed plays a minor role in regulating the mechanical response induced by several vasoactive agents, although it retains its ability to produce an endothelium-derived relaxing factor.
Structure-pharmacokinetic Relationships among the N1, N3-Alkylxanthines in Rats
Authors: Apichartpichean Ruttikorn , Hasegawa Takaaki , Nadai Masayuki , Kuzuya Takafumi , Nabeshima Toshitaka 
Published: April 2011

Abstract
The pharmacokinetics of four N3-alkylxanthine and four N1-methyl-N3-alkylxanthine derivatives has been investigated in rats after intravenous administration of the individual alkylxanthines. The concentration of N1, N3-alkylxanthine in plasma and urine was determined by HPLC. A one-compartment model adequately described the plasma concentration time data. The steady-state volume of distribution (Vss) was calculated using model-independent methods. The relation between Vss and unbound drug fraction in plasma (fu) was significantly correlated (Vss = 0.844fu + 0.119; r = 0.999, P &lt; 0.01), indicating that the differences in fu among these xanthine derivatives is mainly responsible for differences in Vss. The decrease in Vss and increase in plasma protein binding with lipophilicity reflected a relatively constant tissue affinity. The total body clearance increased with lipophilicity with the exception of the first three lower congeners which were almost completely excreted unchanged in urine, mainly via active tubular secretion. Renal elimination was markedly reduced by the presence of a methyl group at the N1-position. Renal clearance decreased with increasing lipophilicity, due to increased tubular reabsorption whereas non-renal (hepatic) clearance increased with increasing lipophilicity.
Transdermal delivery of insulin by ultrasonic vibration
Authors: Tachibana Katsuro , Tachibana Shunro 
Published: April 2011

Abstract
Ultrasonic vibration has been used to deliver insulin through the skin of hairless mice fasted overnight and partially immersed in an aqueous solution of insulin (20 units mL−1). The skin surface was exposed to ultrasonic vibration in two ultrasonic energy ranges (3000–5000 Pa and 5000–8000 Pa) at 48 kHz for 5 min. Blood glucose concentration was measured before and after exposure to insulin and ultrasonic vibration. In the group subjected to the lower energy vibrations, blood glucose fell rapidly to reach 34 ± 11.9% of control values in 120 min, while when the animals were exposed to higher energy vibrations, the fall in blood glucose was 22.4 ± 3.9% of control values at 120 min. The values remained low for the length of the experiment (240 min). Those exposed to insulin alone or ultrasonic vibration alone revealed no significant change in blood glucose concentration. It is postulated that ultrasonic vibration may alter skin permeability resulting in the absorption of insulin. That the blood glucose decrease was greater at the higher of the two energy ranges, suggests this factor could control insulin delivery.
Akinesia due to catecholamine depletion in mice is prevented by caffeine. Further evidence for an involvement of adenosinergic system in the control of motility
Authors: Popoli Patrizia , Caporali Maria Grazia , De Carolis Arsenia Scotti 
Published: April 2011

Abstract
The administration of reserpine with α-methyl-p-tyrosine (2.5 and 200 mg kg−1 i.p., 24 and 3 h before the test, respectively) induced a marked akinesia in mice. This effect was significantly and dose-dependently reversed by the methylxanthine, caffeine. The anti-akinetic effect of caffeine within a pattern of catecholamine depletion has been interpreted as a dopamine mimetic activity of this drug. The possible involvement of the adenosine system in this effect of caffeine is discussed.
Effects of ginsenoside-Rb2 on adenine nucleotide content of rat hepatic tissue
Authors: Yokozawa Takako , Fujitsuka Naoki , Yasui Teruhito , Oura Hikokichi 
Published: April 2011

Abstract
In comparison with non-diabetic rats, the tissue ATP content of diabetic rats is lower and the AMP content higher. However, daily intraperitoneal administration of ginsenoside-Rb2 for several days resulted in an increase of tissue ATP content and a decrease of AMP content, characterized by an increase in the adenine nucleotide content, as well as improvement of energy charge. Thus, ginsenoside-Rb2 administration caused a change in the pattern of metabolism, activating the ATP supply system.
Effects of dextran sulphate on renal dysfunctions induced by gentamicin as determined by the kidney perfusion technique in rats
Authors: Kikuchi Shinji , Aramaki Yukihiko , Nonaka Homare , Tsuchiya Seishi 
Published: April 2011

Abstract
The effect of dextran sulphate on accumulation of gentamicin within the renal cortex and on renal functional changes induced by gentamicin has been investigated using the rat renal perfusion technique. Gentamicin accumulation decreased by the co-administration of dextran sulphate, the degree being proportional to dextran sulphate concentration. The filtered load of gentamicin was unaffected by dextran sulphate. The perfusion of kidney with gentamicin brought about a decrease in the reabsorption of Na+ and an increase in the rate of urine flow with no effect on that of glomerular filtration. The addition of dextran sulphate in the perfusate resulted in the resumption of these levels to those of the control. Dextran sulphate thus apparently interacts with gentamicin in the lumen of proximal tubules to inhibit the reabsorption of gentamicin by proximal tubular cells, and prevents the renal dysfunctions induced by gentamicin.
The Influence of Myrj 59 on the Solubility, Toxicity and Activity of Amphotericin B
Authors: Tasset C , Préat V , Roland M 
Published: April 2011

Abstract
The effect of Myrj 59 (a polyoxyethyleneglycol derivative of stearic acid) on amphotericin B (Am B) solubility, toxicity and activity has been investigated. We showed that Myrj 59 could solubilize the antibiotic. Moreover, it also decreased and abolished the haemolytic activity of the drug by increasing the resistance of the red blood cells and impairing the interaction of Am B with the cellular membrane cholesterol, but it did not modify the in-vitro antifungal activity of the drug. On the other hand, Myrj 59 did not decrease the acute in-vivo toxicity of the drug (LD50 and nephrotoxicity). In a previous study we have shown that a polyoxyethyleneglycol derivative of cholesterol could solubilize Am B and was able to decrease the in-vitro and in-vivo toxicity of the antibiotic without altering its in-vitro antifungal activity. The results of the present study suggest that the cholesterol moiety of the surfactant is not necessary to decrease the in-vitro lytic activity of the drug but could play a role in the reduction of the in-vivo toxicity.
Competitive Protein-binding Radioassay of Thiamine in Simple Solutions and in Multivitamin Pharmaceuticals
Authors: Kozik Andrzej , Wróabel Radoslawa , Turyna Izabela 
Published: April 2011

Abstract
A competitive inhibition radioassay of thiamine is described using a gel obtained by coupling a buckwheat-seed thiamine-binding protein to CNBr-activated Sepharose. The sample to be analysed is incubated with gel suspension and [14C]thiamine and after centrifugation the radioactivity of the supernatant is measured. The method is simple and specific, and applicable over a thiamine concentration range 0.5-5 μM with a coefficient of variation typically below 5%. The gel is reusable and stable for several months. Applicability of the method for direct determination of thiamine in multivitamin pharmaceuticals is demonstrated.
Suppression of the Purgative Action of Rhein Anthrone, the Active Metabolite of Sennosides A and B, by Indomethacin in Rats
Authors: Yagi Teruyo , Miyawaki Yoshie , Nishikawa Atsuko , Yamauchi Kazuko , Kuwano Shigeaki 
Published: April 2011

Abstract
Rhein anthrone (12.48 mg kg−1) produces watery and mucoid diarrhoea approximately 20 min after intracaecal administration to rats. Pretreatment with the prostaglandin (PG) biosynthesis inhibitor indomethacin (10 mg kg−1, i.p.) only delayed and did not completely block the onset of the induced diarrhoea. Rhein anthrone stimulated PGE2 release into the rat colonic lumen and the increased release was depressed by indomethacin. Rhein anthrone also accelerated large intestinal transit and this acceleration could be partly inhibited by indomethacin, which was probably responsible for the delay in the onset of diarrhoea. Indomethacin prevented the enhanced water, K+ and mucus secretion and the reduced Na+ absorption in the colon which were induced by rhein anthrone. The net water secretion could not be reversed to net absorption and the mucus secretion was only slightly depressed by indomethacin. Thus, our findings suggest that other mechanisms, together with the PG-dependent mechanism, are involved in the purgative action of rhein anthrone in rats.
Moment Analysis of Drug Disposition in Rat Kidney: Role of Basolateral Membrane Transport in Renal Transepithelial Transport of p-Aminohippurate
Authors: Saito Yoshihiro , Tanigawara Yusuke , Okamura Noboru , Shimizu Hiromasa , Kamiya Akira , Hori Ryohei 
Published: April 2011

Abstract
The determining step in transepithelial transport of p-aminohippurate (PAH) in renal tubular secretion has been elucidated in the rat isolated perfused kidney. The method was based upon a multiple indicator dilution experiment and non-compartmental moment analysis. Single-pass dilution curves were obtained from venous and urinary effluents after simultaneous intra-arterial injections of Evans blue with albumin, [3H]inulin and [14C]PAH. Probenecid was used as a transport inhibitor and dissolved in both perfusate and injection solution. The urinary excretion of PAH decreased depending on the probenecid concentration, while that of inulin was not affected. No correlation was observed between the amount of secretion and the mean residence time of secreted PAH in renal epithelial cells (T̈cell). Since T̈cell ought to be affected by the rate of secretion from cells to lumen, it was suggested that the secretion rate was independent of the amount secreted. In contrast, the amount of PAH excreted via tubular secretion showed a linear correlation with the volume of distribution in the kidney and the apparent rate constant for tubular uptake of PAH. Since these kinetic parameters reflect the transport from blood into cells across the basolateral membranes of renal epithelial cells, the present results demonstrated that basolateral membrane transport is a determining step in the transcellular transport of PAH and that the major effect of probenecid is the inhibition of transport from blood into cells.
Peripheral Pharmacokinetic Handling and Metabolism of L-Dopa in the Rat: The Effect of Route of Administration and Carbidopa Pretreatment
Authors: Rose S , Jenner P , Marsden C D 
Published: April 2011

Abstract
The effect of carbidopa (L-α-methyldopa hydrazine; 25 mg kg−1 i.p.) pretreatment on the pharmacokinetics and peripheral metabolism of orally and intra-aortically administered L-3,4-dihydroxy-phenylalanine (L-dopa; 50 mg kg−1) has been examined in rats. Following intra-aortic (i.a.) administration, plasma levels of the drug declined biexponentially. Pretreatment with carbidopa resulted in higher plasma concentrations after i.a. administration of L-dopa, but had no effect on the half-life (t1/2) for its distribution or elimination. Oral L-dopa gave peak plasma concentrations at 1.5 h and then a log-linear decline between 1.5 and 6 h. Pretreatment with carbidopa also produced higher plasma concentrations of L-dopa given orally, and the t1/2 for its elimination tended to be increased compared with values achieved after the drug alone. Pretreatment with carbidopa decreased volume of distribution and total plasma clearance and increased area under the curve (0-∞) after L-dopa i.a. and increased AUC0-∞ after L-dopa p.o. The fraction of the oral dose absorbed through the gut was not affected. Carbidopa pretreatment enhanced the accumulation of 3-O-methyldopa and decreased dopamine levels in plasma after both i.a. and oral administration of L-dopa. Higher plasma concentrations of 3,4-dihydroxyphenylacetic acid and homovanillic acid (HVA) were detected in the plasma after i.a. rather than oral administration of L-dopa and pretreatment with carbidopa greatly reduced these plasma concentrations. However, following oral L-dopa, only HVA levels were reduced by carbidopa pretreatment. The rat model displays similar peripheral pharmacokinetics and metabolism of L-dopa to those reported in human studies, and may be used for further investigations into the pharmacokinetic handling of the drug.
Pentazocine-induced Catecholamine Efflux from the Dog Perfused Adrenals
Authors: Fukumitsu Kazuo , Sumikawa Koji , Hayashi Yukio , Kinouchi Keiko , Yoshiya Ikuto 
Published: April 2011

Abstract
This study has been undertaken to determine whether pentazocine induces catecholamine efflux from the adrenal medulla as a mechanism for its sympathomimetic effect. Dog isolated adrenals were perfused retrogradely with modified Locke's solution. The efflux of catecholamines from dog perfused adrenals was increased from the resting output of 0.18 ± 0.04 μg min−1 (mean ± s.e.), to 0.47 ± 0.13 μg min−1 by the administration of pentazocine (50 μM). The pentazocine-induced catecholamine efflux was dose-dependent in the 50–400 μM dose range. This effect of pentazocine was not inhibited by either a combination of atropine and (+)-tubocurarine, or verapamil, in contrast to acetylcholine-induced catecholamine release. There was no significant difference in potency among stereoisomers, i.e. (+)-, (—) and (+)-pentazocine, in inducing catecholamine efflux. Naloxone did not influence the effects of either (+)-or (—)-pentazocine. The interaction of pentazocine with acetylcholine-induced catecholamine release was also examined. Both (+)-and (—)-pentazocine inhibited acetylcholine-induced catecholamine release dose-dependently, and these inhibitory effects were not reversed by naloxone. Acetylcholine-induced catecholamine release was accompanied by increased dopamine-β-hydroxylase release, whereas pentazocine-induced catecholamine efflux was not. These results suggest that pentazocine directly acts on the adrenal medulla to induce catecholamine efflux via a non-exocytotic mechanism, and that opioid receptors do not play a role in this action.
An Investigation into the Effects of Aminoguanidine Treatment on the Plasma and Blood of Free-fed and Dietary-restricted Rats
Authors: Preedy Victor R , Hammond Barry 
Published: April 2011

Abstract
An investigation has been made into the effect of oral aminoguanidine (50–60 mg kg−1 day−1) on the blood biochemistry of male Wistar rats which either had free access to food or were dietary-restricted (50% of the food consumed by the free access group). In control rats (i.e. without aminoguanidine treatment) three weeks of food restriction caused significant increases in plasma sodium and albumin and the erythrocyte count, haematocrit and haemoglobin. There were reductions in plasma calcium, phosphate, alkaline phosphatase activity, urea, triglycerides, creatinine, glucose and the red cell volume. Similar effects of food restriction were observed in aminoguanidine-treated rats. Aminoguanidine ingestion in free-fed animals caused a reduction in plasma creatinine concentration. In dietary-restricted rats, aminoguanidine ingestion reduced plasma sodium and total plasma proteins (largely as a result of a decline in albumin), and increased plasma urea concentrations. Aminoguanidine was added to plasma of control rats in-vitro to determine whether it interfered with the assay of urea and creatinine. At concentrations of 0.1 to 10 mg mL−1, aminoguanidine had no effect on urea determinations. However, aminoguanidine significantly reduced the apparent concentration of plasma creatinine by between 7 to 81%. The changes in plasma analytes in aminoguanidine-treated rats may be indicative of minor hepatic perturbations or kidney function, but the data also imply that prior nutritional state is a determinant of aminoguanidine effects.
Disposition of Hexobarbitone and Antipyrine in DOCA-hypertensive Rats
Authors: Ben-Zvi Z , Hreash F , Kaplanski J 
Published: April 2011

Abstract
The disposition of antipyrine and hexobarbitone, and their effects on drug metabolizing hepatic enzymes have been investigated in DOCA-hypertensive rats. Antipyrine pharmacokinetic parameters were the same in hypertensive and control animals. Hexobarbitone sleeping time was longer in hypertensive rats compared with controls, while the activity of hepatic hexobarbitone hydroxylase was the same in both groups. Hepatic aminopyrine-N-demethylase activity was elevated in hypertensive rats while aniline hydroxylase and aryl hydrocarbon hydroxylase were lower. Glucuronyl transferase was the same in both groups. The sensitivity of the central nervous system of hypertensive rats to hexobarbitone was not altered, as determined by hexobarbitone concentration in blood and in brain. The total hepatic blood flow (arterial and portal) was significantly increased. Thus it is suggested that the difference in the disposition of the two drugs is probably not due to drug metabolizing enzyme activity. It is likely that the increase in total hepatic blood flow and rapid saturation of hepatic hexobarbitone metabolizing enzymes have significant roles in the slower metabolism and increased activity of hexobarbitone in hypertensive rats as compared with control rats.
Relative anti-inflammatory effect of oral dexamethasone-β-D-glucoside and dexamethasone in experimental inflammatory bowel disease in guinea-pigs
Authors: Friend D R , Phillips S , Mcleod A , Tozer T N 
Published: April 2011

Abstract
The relative anti-inflammatory effect of dexamethasone and a prodrug, dexamethasone-β-D-glucoside, has been assessed in guinea-pigs with experimentally-induced inflammatory bowel disease (IBD). The glucoside prodrug is designed to reach the large intestine following oral administration. The active agent is liberated when the prodrug is hydrolysed by glycosidases of colonic bacteria. Guinea-pigs were administered degraded carrageenan in their drinking water to produce experimental IBD. Starting on day 15, dexamethasone (1.3 μmol kg−1) or dexamethasone-β-D-glucoside (1.3 or 0.65 μmol kg−1) was administered by gastric intubation once daily for 5 days. Relative to control animals, the drug and prodrug treatments significantly (P &lt; 0.05) reduced the total number of caecal ulcers. While there was no difference statistically between the drug and prodrug treatments, the data suggest that a lower dose of dexamethasone, administered as its glucoside prodrug, could reduce side-effects without reduced efficacy. These results support the hypothesis that localized delivery of dexamethasone to the large bowel can improve pharmacotherapy of IBD by reducing the side-effects associated with corticosteroids.
Disposition of the hypolipidaemic agent, 6-amino-2-mercapto-5-methylpyrimidine-4-carboxylic acid, in Sprague-Dawley rats
Authors: Hall Iris H , Wong Oi T , Wyrick Steven D , Simlot Rupendra , Shrewsbury Robert P 
Published: April 2011

Abstract
The disposition of [2-14C] 6-amino-2-mercapto-5-methyl-pyrimidine-4-carboxylic acid has been determined in rats following intravenous and oral administration. A two-compartment pharmacokinetic model fitted to the blood and urinary data predicted its maximum terminal (β) half-life to be 38 h. Urinary and faecal excretion accounted for approximately 30 and 8% of the administered radioactivity, respectively. The parent compound accounted for 88% of the urine radioactivity after oral administration. In a tissue distribution study, the largest percentages of radioactivity were found in the skin and carcass; by 24 h, all other organs contained less than 1% of the administered radioactivity. The drug was highly water soluble, not extensively bound to plasma proteins, nor taken up by red blood cells. The drug uptake by human fibroblasts or rat aorta cells appeared to be by passive diffusion.
Protection of acetylcholinesterase by meptazinol in mice exposed to di-isopropyl fluorophosphate. Comparison with physostigmine
Authors: Galli Alessandro , Mori Francesca 
Published: April 2011

Abstract
The protective action of meptazinol against acute diisopropyl fluorophosphate (DFP) intoxication has been evaluated in mice by measuring the effects on the DFP LD50 of the pretreatment of the animals with increasing doses of the drug. Meptazinol at the doses 15, 30 and 45 mg kg−1 injected 15 min before DFP caused a dose-dependent increase in the DFP LD50, resulting in protection ratios equal to 2.1, 4.8 and 9.7, respectively, in the absence of atropine and 2.5, 4.7 and 8, respectively, in the presence of atropine sulphate (17.4 mg kg−1) therapy. Under the same experimental conditions, the protective ratio of 0.1 mg kg−1 physostigmine sulphate was 2.2 and 7.3 in the absence and presence of atropine therapy, respectively. In separate experiments, the time course of acetylcholinesterase (AChE) activity recovery was evaluated in the brain and diaphragm of mice pretreated with meptazinol (30 mg kg−1) or physostigmine (0.1 mg kg−1) 15 min before poisoning with DFP (8 mg kg−1). Ten minutes after poisoning, residual AChE activity in the brain averaged 4, 47 and 15% of that in controls in animals pretreated with atropine alone, atropine plus meptazinol or atropine plus physostigmine, respectively. Twenty four hours after poisoning, brain AChE activity averaged 31 and 47% of that in controls in mice protected by meptazinol and physostigmine, respectively. The data from the diaphragm closely paralleled those from the brain. It is concluded that high doses of meptazinol exert antidotal action against acute DFP poisoning in the mouse comparable in efficacy with that of physostigmine combined with atropine. This action is most probably due to the ability of meptazinol to protect AChE from irreversible inactivation by DFP.