bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pharmacokinetic Study of Zonisamide in Patients Undergoing Brain Surgery
Authors: Ieiri Ichiro , Morioka Takato , Kim Sonyori , Nishio Shunji , Fukui Masashi , Higuchi Shun 
Published: April 2011

Abstract
To test whether the concentration of the anticonvulsant zonisamide in erythrocytes reflects the brain concentration and the clinical response of the drug, its pharmacokinetics were studied in nine patients undergoing surgery for brain tumour. Erythrocyte, total, and free serum concentrations in samples drawn on the day of brain surgery were compared with levels on a day after the operation. In three patients zonisamide and its major metabolite, 2-sulphamoylacetylphenol, were also analysed in urine. The area under the curve of the free and the erythrocyte concentration did not differ between the two study phases whereas the area under the curve of the total serum concentration was significantly lower on the day of the operation, and this was associated with significant increases in total clearance (15.4 compared with 12.7 mL kg−1 h−1, P &lt; 0.05, n = 9) and renal clearance (5.4 compared with 3.3 mL kg−1 h−1, P &lt; 0.05,n=3), and non-significant change in non-renal clearance (7.7 on the day of operation compared with 8.4 mL kg−1 h−1 on the post-operation day, n = 3). Zonisamide distribution was also altered by the operative procedure, as evidenced by a higher volume of distribution (1.48 compared with 0.87 L kg−1, P &lt; 0.05, n = 9). The binding of zonisamide was characterized on both days. Zonisamide binding to erythrocytes seemed to occur by two processes: a saturable process and a non-saturable linear process. The maximum binding capacity to erythrocytes (31.6 vs 29.7 μg mL−1) did not differ on the two days; however, increases in the dissociation binding constant (+28%) and the proportionality constant (+24%) were observed on the day of the operation, suggesting that the zonisamide concentration in erythrocytes was greater on the day of the operation.
Brain surgery appears to be one of the possible factors altering the rate of elimination of zonisamide and the uptake of the drug by erythrocytes.
Effects of 5-Hydroxytryptamine Agonists on Myoelectric Activity of the Forestomach and Antroduodenal Area in Sheep
Authors: Plaza M A , Arruebo M P , Murillo M D 
Published: April 2011

Abstract
To increase knowledge of the role of 5-hydroxytryptamine (5-HT) receptors in the regulation of reticuloruminal, omasal and antroduodenal myoelectric activity in sheep, the effects of 5-HT agonists on forestomach and antroduodenal myoelectric activity have been investigated in conscious sheep. 5-Carboxamidotryptamine, methysergide, α-methyl-5-HT, 2-methyl-5-HT, cisapride, zacopride or metoclopramide were infused intravenously for 5 min and myoelectric recordings were obtained from electrodes chronically implanted in the reticulum, rumen (dorsal sac), omasal body, abomasal antrum and duodenal bulb.
The integrated activity of the reticular and ruminal spike bursts was modified only by the highest doses of α-methyl-5-HT, 2-methyl-5-HT, metoclopramide and cisapride. A phase III-like activity pattern was recorded in the antroduodenal area with all 5-HT-ergic agents and a dose-dependent inhibition of myoelectric activity was recorded in both reticulorumen and omasum at the same time as the antroduodenal effects. In the forestomach, methysergide alone induced inhibition of ruminal secondary contractions; 5-HT, α-methyl-5-HT, cisapride and metoclopramide, moreover, evoked an initial dose-dependent increase in antral activity.
These results suggest that 5-HT1; 5-HT2, 5-HT3 and 5-HT4 receptors are involved in the regulation of the migrating myoelectric complex in sheep and in the genesis of forestomach hypomotility that is occasionally recorded concomitantly with the spontaneous duodenal phase III in sheep. 5-HT4 receptors also have a prokinetic action in the antral area.
Effects of Polyacrylic Polymers on the Degradation of Insulin and Peptide Drugs by Chymotrypsin and Trypsin
Authors: Bai Jane P F , Chang L L , Guo J H 
Published: April 2011

Abstract
The purpose of this study was to determine whether carbopol polymers, polyacrylic acid polymers, can inhibit lumenal degradation of insulin, calcitonin and insulin-like growth factor I (IGF-I) by trypsin and chymotrypsin and to understand whether reducing the pH of the incubation medium by these polymers results in inhibition. Further, the effects of carbopol polymers on the in-situ absorption of insulin were studied in rats.
In saline, carbopol polymers at 1% and 4% (w/v%) inhibited close to 100% of trypsin and chymotrypsin activities against insulin. In 50 mM Tris buffer, carbopol polymers, including 934P, 974P and 971P, at 0&#x006d;̇1% only weakly inhibited degradation of calcitonin and insulin by both enzymes; however, as the polymer concentration increased to 0&#x006d;̇4%, degradation of insulin, calcitonin, and IGF-I by both enzymes was complete or almost complete. When the Tris buffer was increased to 100 mM, no inhibition was observed at 0&#x006d;̇1%. Determination of the final pH of the incubation medium in the presence of polymers revealed that the inhibitory effects of carbopol polymers correlated with the final pH. When the incubation medium has no or low buffer capacity to buffer the protons released by carbopol polymers, these polymers are able to reduce the pH much lower than the optimum pH for the enzyme activities, and thus inhibit proteolytic degradation. When the buffer capacity of the incubation medium increases, the inhibitory effects of carbopol polymers weaken. In-situ absorption of insulin revealed that carbopol polymers improved insulin absorption and induced a significantly greater decline in blood glucose levels.
It is concluded that carbopol polymers with strong bioadhesive properties also can inhibit lumenal degradation of peptide hormones, offering multiple advantages for their uses in oral drug delivery.
Prolonged Immune Response Evoked by a Single Subcutaneous Injection of Microcapsules Having a Monophasic Antigen Release
Authors: Sah Hongkee , Chien Yie W 
Published: April 2011

Abstract
A model antigen, bovine serum albumin (BSA), was successfully incorporated into microcapsules fabricated from blends of poly(d,l-lactide-co-glycolide) and poly(d,l-lactide). The microcapsules possessed diameters ranging from 10 to 100 μm and exhibited a continuous monophasic release of the protein in-vitro for 3 weeks.
They were found to enhance its immunogenicity, thereby potentiating the anti-BSA antibody response following a single subcutaneous injection in mice and rabbits. Enzyme-linked immunosorbent assays demonstrated that the microcapsules provoked high-titre and long-lived immunoglobulin G immune responses over a period of 192 days in mice. When rabbits were immunized by a single subcutaneous injection of BSA-loaded microcapsules, a high level of anti-BSA antibody was still present in the sera obtained at 17 weeks post-injection. The immunization protocol using the BSA-loaded microcapsules was superior to that using BSA dissolved in saline or adsorbed to alum.
These microcapsules providing the controlled release of antigens may be valuable in designing better vaccine formulations.
The role of Gastric Mucosal Sulphydryls in the Ulcer-protecting Effects of Cisapride
Authors: López A , Motilva V , De La Lastra C Alarcón , Martín M J , La Casa C 
Published: April 2011

Abstract
The present study was designed to examine the role of endogenous sulphydryls (SHs) in the gastro-protection induced by cisapride (CIS) (10, 25 and 50 mg kg−1 i.p.), a potent benzamide stimulating gastrointestinal motility in mucosal injury induced by 50% v/v ethanol. Results were compared with those of 5−hydroxytryptamine (5−HT) (10 mg kg−1).
Ethanol mucosal damage was significantly reduced by treatment with CIS and 5−HT. On the contrary, administration of n-ethylmaleimide (NEM) (10 mg kg−1) an SH alkylator, markedly worsened lesion formation and counteracted the protective effect of CIS. Rats pretreated with CIS significantly increased the total sulphydryls as reflected in the non-protein and protein fractions however, 5−HT treatment showed a fall in the non-protein level.
The present results suggest that 5−HT-ergic dependent mechanisms have no relation to the gastro-protection afforded by CIS in this experimental model. It is possible that mucosal SHs could be involved.
Oral Cavity Absorption of (R)−8−Hydroxy−2−(di-n-propylamino)tetralin and (S)−8−Acetyl−2−(di-n-propylamino)tetralin in the Rat
Authors: Yu Hong , Liu Ye , Hacksell Uli , Lewander Tommy 
Published: April 2011

Abstract
The present communication reports on the efficacy of (R)−8−OH-DPAT ((R)−8−hydroxy−2−(di-n-propylamino)tetralin) and (S)-LY−41 ((S)−8−acetyl−2−(di-n-propylamino)tetralin) in displaying the 5−HT1A syndrome and decreasing body temperature after administration of the compound subcutaneously into the gastric ventricle or into the oral cavity in the rat.
The dose range eliciting a clear-cut 5−HT1A syndrome and hypothermia after oral cavity administration was 1/10-1/30 that of the gastric ventricle dose range, but 10−30 times higher than the dose range used for subcutaneous administration of both (R)−8−OH-DPAT and (S)-LY−41. Determination of the concentrations of (R)−8−OH-DPAT in plasma and brain tissue confirmed a higher bioavailability after oral cavity than after gastric ventricle administration; plasma and brain tissue concentrations of the drug were found to be approximately 3 times those after 10 μmol kg−1 orally than after 100 μmol kg−1 gastroventrically at 15−60 min after administration of (R)−8−OH-DPAT.
These findings suggest that the oral cavity may be an important site for drug delivery of 8−OH-DPAT, LY−41 and other compounds with a low gastrointestinal bioavailability.
Pharmacokinetics and Brain Distribution of Magnolol in the Rat after Intravenous Bolus Injection
Authors: Tsai T H , Chou C J , Chen C F 
Published: April 2011

Abstract
The pharmacokinetics of magnolol in rats was studied after 2, 5, or 10 mg kg−1 intravenous bolus injection. Plasma concentration-time profiles of magnolol were fitted by a two-compartment open model. There were no significant differences in the elimination half-life, the total body clearance, steady-state volume of distribution, or mean residence time. The area under the plasma-time curve and area under the moment-time curve of magnolol appears to increase proportionally from a dose of 2 to 10 mg kg−1. These results suggest that magnolol possesses linear pharmacokinetics. Notwithstanding, brain concentration of magnolol showed no significant difference among various regions (cerebral cortex, olfactory bulb, hippocampus, striatum, cerebellum, brain stem and rest of brain) after 10 min of magnolol (5 mg kg−1 i.v.) administration, the mean brain drug concentration was approximately fourfold that of magnolol in plasma.
Involvement of σ-Receptors in the Increase in Contraction of Mouse Vas Deferens Induced by Exogenous ATP
Authors: Matsuno Kiyoshi , Kobayashi Tetsuya , Mita Shiro 
Published: April 2011

Abstract
The effects of σ-receptor ligands on the twitch contraction elicited by the exogenous application of adenosine 5′-triphosphate (ATP) in the unstimulated mouse vas deferens were studied.
(-)-Pentazocine, 1,3−di(2−tolyl)guanidine (DTG) and two pairs of optical isomers of 3−(3−hydroxyphenyl)-N-(1−propyl)piperidine (3−PPP) and N-allylnormetazocine (SKF−10,047) potentiated the exogenous application of ATP-induced twitch-type contraction in a concentration-dependent manner, while (+)-pentazocine did not affect it. The order of potentiating ability was: (+)−3−PPP&gt;(-)-pentazocine&gt;(-)-SKF−10,047&gt; DTG&gt;(-)−3−PPP&gt;(+)-SKF−10,047. On the other hand, haloperidol and rimcazole, putative σ-receptor antagonists, suppressed this twitch contraction. In addition, these antagonists significantly blocked the (+)-3−PPP- and (-)-pentazocine-induced potentiation at concentrations which did not affect contractions per se.
These findings indicate that the exogenous application of ATP-induced twitch contraction in the mouse vas deferens is regulated by σ-receptors. In addition, the present ranking order suggests that the σ-receptor potentiating the ATP-induced twitch contraction at post-junctional sites may differ from the σ1- and/or σ2-receptor subtypes.
Correlation of Pharmacological Properties of a Group of Hypolipaemic Drugs by Molecular Topology
Authors: Cercós-Del-Pozo R A , Pérez-Giménez F , Gálvez-Alvarez J , Salabert-Salvador M T , Garcia-March F J , Antón-Fos G M 
Published: April 2011

Abstract
This investigation was undertaken to test the ability of the molecular connectivity model to predict the percentage of plasma protein binding, the percentage of total cholesterol reduction and oral LD50 in rats of a group of hypolipaemic drugs using multi-variable regression equations with multiple correlation coefficients, standard error of estimate, degrees of freedom, F-Snedecor function values, Mallow's CP and Student's t-test as criteria of fit.
Regression analyses showed that the molecular connectivity model predicts these properties. Corresponding stability (cross validation) studies were made on the selected prediction models which confirmed their goodness of fit.
The results also demonstrated that the presence of substituents and molecular volume, determine the value of these properties in hypolipaemic drugs.
Intestinal Absorption Studies on Peptide Mimetic α-Methyldopa Prodrugs
Authors: Wang Hui-Po , Lu Hsiao-Hwa , Lee Jia-Shuai , Cheng Chih-Yuan , Mah Jin-Ran , Ku Ching-Yi , Hsu Wenlie , Yen Chen-Fang , Lin Chun-Jung , Kuo Harng S 
Published: April 2011

Abstract
Two dipeptide mimetic prodrugs, 1 and 2, and two tripeptide mimetic prodrugs, 3 and 4, of l-α-methyldopa were evaluated for intestinal absorption by in-situ single-pass rat jejunal perfusion studies and by in-vitro uptake experiments in brush-border membrane vesicles (BBMVs) prepared from rat intestine. In the perfusion studies, compound 1 demonstrated a 3.5-fold increase in permeability (Pm* = 2.27) as compared with that of α-methyldopa (Pm* = 0.65), indicating that this prodrug was better absorbed in the intestine than its parent drug. Other prodrugs showed no significant improvement in intestinal permeability. The results correlated with the results of BBMV uptake studies. In the presence of an inward proton gradient, compound 1 showed Michaelis-Menton saturable kinetics of BBMV uptake with a low value of Km (0.06 ± 0.13 mm) and a high value of Vmax/Km (36.38 nmol (mg protein)−1/30 s mm−1) at a low concentration range and a linear uptake at high concentrations with Kd = 0.14 ± 0.02 mm. Compounds 2 and 3 were mainly taken up in BBMVs via passive diffusion. Compound 4 was taken up in BBMVs basically via the carrier-mediated transport system, while the rate of uptake was much lower than that of compound 1. The uptake of compounds 1 and 4 was significantly inhibited by dipeptides l-Gly-l-Pro and l-Gly-l-Phe, and cephradine, a β-lactam known to be transported via the dipeptide carrier system, indicating that both compounds were taken up in BBMVs via the H+-coupled dipeptide-mediated transport system. In contrast to the complicated uptake profile of α-methyldopa, the higher rate of BBMV uptake with less variation demonstrated on compound 1 suggested that the attached nonessential amino acid moiety, d-phenylglycine, is a feasible delivery tool in carrying the parent drug through the intestine.
Effect of Policosanol on Foam-cell Formation in Carrageenan-induced Granulomas in Rats
Authors: Noa M , De La Rosa M C , Más R 
Published: April 2011

Abstract
Policosanol is a new cholesterol-lowering drug isolated and purified from sugar-cane wax. which prevents the development of lipofundin-induced lesions and foam-cell formation in New Zealand rabbits and Wistar rats. This study was conducted to examine the effects of policosanol on foam-cell formation in carrageenan-induced granulomas in rats.
Eighteen Wistar rats were randomly distributed in three experimental groups which received orally for 20 days Tween 20 H2O as vehicle (control group) or policosanol at 2.5 or 25 mg kg−1. At the 11th day. lipofundin was injected intrapcritoneally for 8 days to induce formation of foam cells in the granuloma. At day 13, carrageenan was injected subcutaneously for granuloma induction and seven days later animals were killed. A significant reduction of the foam-cell formation in granulomas of policosanol-treated rats was observed.
It is concluded that policosanol prevents the development of foam cells in carrageenan-induced granulomas (extravascular medium) in rats.
The Effect of Acetylation and Deacetylation on the Disposition of Dapsone and Monoacetyl Dapsone Hydroxylamines in Human Erythrocytes In-vitro
Authors: Coleman Michael D , Pahal Kuldip Kaur , Gardiner John M 
Published: April 2011

Abstract
The fates of both dapsone and monoacetyl hydroxylamine have been studied in terms of acetylation and deacetylation within the human erythrocyte in-vitro.
A comparison between the two metabolites showed equipotency in methaemoglobin generation at 15 min, although the monoacetyl derivative was the more rapid haemoglobin oxidizer. Within the erythrocytes, both dapsone and monoacetyl hydroxylamines were found to undergo acetylation, deacetylation and diacetylation. Of the inhibitors of acetylation studied, folate caused an increase in methaemoglobin formation associated with both metabolites, which led to a rise in both acetylated and non-acetylated amine formation. Amethopterin was associated with a rise in hydroxylamine mediated methaemoglobin formation which coincided with a fall in acetylated products.
It is possible that the hydroxylamines undergo erythrocytic processes of acetylation and deacetylation before methaemoglobin-mediated reduction to their respective amines.
Preparation of Poly(D,L-lactide) and Copoly(lactide-glycolide) Microspheres of Uniform Size
Authors: Shiga K , Muramatsu N , Kondo T 
Published: April 2011

Abstract
In an attempt to prepare monodisperse poly(D,L-lactide) and copoly(lactide-glycolide) microspheres, a novel emulsification technique (membrane emulsification) was employed and the preparation conditions which might affect the monodispersity were evaluated.
With this technique nearly monodisperse poly(D,L-lactide) and copoly(lactide-glycolide) microspheres were successfully prepared and their sizes were controllable only by making use of microporous glass membranes of different pore sizes. However, in the present system of emulsion (methylene chloride/water) the surfactant used was limited to ionic ones and the amount of polymers available for the formation of microspheres was inevitably too small in concentration to entrap sufficient amounts of drug. As for the drug release, the effect of particle size was not appreciable but the method of solvent removal gave a great influence; the solvent extraction method showed a more drug-sustaining effect than did the solvent evaporation method.
The present results suggest the possibility of making drug-loaded and biodegradable monodisperse micro-spheres.
Effect of Nifedipine on the Elimination of Theophylline in the Rabbit Subjected to Hypoxia or to an Inflammatory Reaction
Authors: Barakat M , du Souich P 
Published: April 2011

Abstract
This study was performed to assess whether nifedipine could prevent the decrease in hepatic cytochrome P450 induced by acute moderate hypoxia or an inflammatory reaction. Rabbits were subjected Jo acute moderate hypoxia (PaO2 »37 mmHg), with or without pretreatment with nifedipine (0.5 mg kg−1 subcutaneously every 8 h, for 48 h). Another group received 5 mL of turpentine subcutaneously with or without pretreatment with nifedipine (0.5 mg kg s.c. every 8 h, for 72 h). The kinetics of 2.5 mg kg−1 of theophylline were studied in all rabbits up to 8 h, at which time total cytochrome P450 and malondialdehyde were assessed in the liver.
Compared with control rabbits, hypoxia and an inflammatory reaction increased theophylline plasma concentrations, as a result of a decrease in theophylline systemic clearance. Both experimental conditions reduced hepatic cytochrome P450 by 40 to 50% and increased hepatic malondialdehyde by approximately 50% (P &lt; 0.05). In control animals, pretreatment with nifedipine did not influence theophylline kinetics, the liver content in cytochrome P450 or malondialdehyde. Pretreatment with nifedipine partially prevented the hypoxia- and the inflammation-induced decrease in liver cytochrome P450; however, nifedipine did not prevent the decrease in theophylline clearance or the increase in liver malondialdehyde.
It is concluded that nifedipine affords a partial protection against hypoxia- or inflammation-induced hepatic cellular injury.
Toxicodynamic Analysis of Cardiac Effects Induced by Four Cholinesterase Inhibitors in Rats
Authors: Yamamoto Koujirou , Shimizu Miho , Ohtani Hisakazu , Hayashi Masahiro , Sawada Yasufumi , Iga Tatsuji 
Published: April 2011

Abstract
The cardiac effect of edrophonium (2–20 μmol kg−1), pyridostigmine (0.5-5 μmol kg−1), neostigmine (0.05-0.5 μmol kg−1) and ambenonium (0.02-0.3 μmol kg−1) was investigated after intravenous administration to rats.
For pyridostigmine and neostigmine, the heart rate decreased in a dose-dependent manner, and then gradually recovered to the basal level at about 10 min. Rapid decrease of heart rate was observed after edrophonium and ambenonium administration, and rapid recovery to the basal level within 1 min. For ambenonium, a dose-dependent tachycardiac response was observed. The time-course of heart rate change was analysed by the effect-compartment model. Significant correlation was observed between bradycardiac EC50 values obtained by effect-compartment model analysis and inhibitory constant (Ki) to acetylcholinesterase in-vitro, suggesting that the bradycardiac response was induced by inhibition of this enzyme and following elevation of acetylcholine concentration in the synaptic cleft. On the other hand, the tachycardiac EC50 values of edrophonium and ambenonium based on the effect-compartment model analysis were similar to dissociation constants (Kd) of these drugs to muscarinic receptors in-vitro, suggesting that the tachycardiac activity of these drugs may be associated with antagonistic activity to postsynaptic muscarinic receptors.
We conclude that, clinically, edrophonium and ambenonium are safer drugs than pyridostigmine and neostigmine, at least as regards muscarinic side-effects, including bradycardia.
Effect of Silymarin on Different Acute Inflammation Models and on Leukocyte Migration
Authors: De La Puerta R , Martinez E , Bravo L , Ahumada M C 
Published: April 2011

Abstract
In-vivo anti-inflammatory activity of silymarin was tested in different acute inflammation experimental models.
In carrageenan-induced paw oedema in rats, silymarin given orally reduced in a dose-dependent manner the food-pad abscesses (ED50 = 62.42 mg kg−1). In xylene-induced ear mouse inflammation, silymarin applied topically was more effective than administered intraperitoneally, with effects comparable with those of indomethacin. Silymarin also produced a dose-dependent inhibition of leukocyte accumulation in inflammatory exudates following intraperitoneal injection of carrageenan in mice; silymarin significantly reduced the number of neutrophils. Silymarin was unable to inhibit phospholipase A2 in an in-vitro assay.
Besides its known anti-oxidative properties and its ability to act as a radical scavenger, these results suggest that silymarin exerts an important anti-inflammatory action in-vivo by reducing oedema with the effect markedly influenced by the inhibition of neutrophil migration into the inflamed site.