bluuebunny/crossref_metadata_2025_split huggingface dataset:
In-vivo Microdialysis Measurement of 5-Hydroxytryptamine and its Metabolites, 5-Hydroxyindoleacetic Acid and N-Acetyl 5-Hydroxytryptamine, in Rat Blood: Effects of Histamine-receptor Antagonists
Authors: Sakurai Eiichi , Monura Akio , Yamakami Jun , Hikichi Noboru 
Published: April 2011

Abstract
The blood concentrations of 5-hydroxytryptamine (5-HT) and its metabolites, 5-hydroxyindoleacetic acid (5-HIAA) and N-acetyl 5-HT were assayed by in-vivo microdialysis and a highly sensitive HPLC procedure that was originally developed to analyse CNS mediators. We investigated the effects of histamine-receptor antagonists on 5-HT metabolism and its release into the blood of rats.
The mean basal levels of 5-HT, 5-HIAA and N-acetyl 5-HT in the blood measured by in-vivo microdialysis were 77.2 ± 9.4, 20.3 ± 1.5 and 1.89 ± 0.15 pmol mL−1, respectively. These levels were not significantly affected by an intraperitoneal injection of saline, and remained at constant levels for at least 8 h after administration of saline. After an intraperitoneal injection of 5-HT hydrochloride (0.5 mg kg−1), 5-HT was soon detected in the blood of the jugular vein. 5-HIAA also quickly appeared in the blood and declined monoexponentially from 60 min after injection. In contrast, N-acetyl 5-HT slowly appeared in the blood and it reached a maximal level at 270 min. The 5-HT and N-aceryl 5-HT levels in dialysates from rat jugular vein were significantly increased by intraperitoneal pyrilamine (2.0 mg kg−1), (+)-chlorpheniramine (2.0 mg kg−1) and cimetidine (20.0 mg kg−1). However, there was no increase in the 5-HIAA concentration after an intraperitoneal injection of these histamine-receptor antagonists, demonstrating that the 5-HT released from various cells containing 5-HT was predominantly metabolized to N-acetyl 5-HT by N-acetyltransferase. Moreover, thioperamide did not affect the basal levels of 5-HT, 5-HIAA or N-acetyl 5-HT.
Because the recovered 5-HT, 5-HIAA and N-acetyl 5-HT in the dialysate is directly proportional to the free fraction in the blood, in-vivo microdialysis is a reliable method of examining 5-HT metabolism and its release into the blood.
Determination of Captopril in Human Blood by an Enzyme-linked Immunosorbent Assay
Authors: Jehanli Ahmed M T , Arafat Towfiq , Al-Shami Munzir 
Published: April 2011

Abstract
An immunoassay for the quantitation of the angiotensin-converting enzyme inhibitor, captopril in human plasma is described.
Antisera very specific for captopril were produced by immunization with captopril conjugated to bovine serum albumin or porcine thyroglobulin via the drug's thiol group. The antibodies were used to develop an enzyme-linked immunosorbent assay (ELISA) with a detection limit of 0.3 ng mL−1 and intra- and inter-assay coefficients of variation of 7 and 12%, respectively. Apart from stabilizing captopril by the addition of N-ethyl maleimide, the assay was used to detect the drug in human plasma without further extraction or purification.
Our immunoassay provides a very sensitive and rapid (four hours) alternative for the study of captopril pharmacokinetics.
Protective Effect of Butylated Hydroxyanisole on Adriamycin-induced Cardiotoxicity
Authors: Vora Jayesh , Khaw Ban-An , Narula Jagat , Boroujerdi Mehdi 
Published: April 2011

Abstract
Adriamycin has a wide spectrum of antitumour activity with dose-related cardiotoxicity as a major side effect. This cardiotoxicity has been suggested to result from the generation of oxygen free radicals. The objective of the present study was to investigate the influence of the antioxidant, butylated hydroxyanisole co-therapy on the cardiotoxicity of adriamycin, in-vivo.
The aqueous solubility of butylated hydroxyanisole was enhanced by inclusion complex formation with hydroxypropyl-β-cyclodextrin. The extent of drug-induced myocardial damage in rats was assessed using intravenous “in-labelled antimyosin Fab and chronological changes in serum creatine kinase levels. There was a dose-related increase in myocardial antimyosin uptake in rats, which reached a plateau at an adriamycin dose of 10 mg kg−1. The antimyosin uptake at this dose (% dose g−1 = 0.1942 ± 0.0150, n = 8) was significantly reduced by co-administration of butylated hydroxyanisole with adriamycin (10 mg kg−1 of each) to 0.1462 ± 0.0116 (n = 5, P &lt; 0.05).
Assessment of cardiotoxicity in the rats was also performed by measuring serial changes in serum creatine kinase levels. Increasing doses of adriamycin caused an increase in serum creatine kinase levels with peak values obtained between 2 and 8 h after dosing. These values decreased upon co-administration of butylated hydroxyanisole with adriamycin at 10 mg kg−1, each and 30 mg kg−1, each by 29 and 41%, respectively. On the other hand, butylated hydroxyanisole did not inhibit the tumouricidal activity of adriamycin as investigated in-vitro using the NMU rat mammary adenocarcinoma cell-line.
The significant reduction in anthracycline cardiotoxicity by butylated hydroxyanisole coadministration may result from its scavenging action on adriamycin-mediated free-radical formation or its enhancement of activity of enzymes involved in the metabolism of adriamycin.
Involvement of Prostaglandins and 5-Hydroxytryptamine in the Contractile Effect of Platelet-activating Factor in Rat Isolated Gastric Corpus
Authors: Martínez-Cuesta M A , Barrachina M D , Moreno L , Calatayud S , Esplugues J 
Published: April 2011

Abstract
The present study characterizes the nature of the response to the platelet-activating factor (PAF) in isolated gastric corpus with and without mucosa.
PAF (10-8 M) induced contraction of rat isolated gastric corpus strips followed by desensitization of this tissue. Incubation of strips with the specific PAF-receptor antagonist WEB 2086 (5 × 10-8 − 5 × 10-5 M), the prostaglandin blocker indomethacin (10-6 M) and the 5-hydroxytryptamine antagonist methysergide (10-5 M) reduced significantly the contraction induced by PAF. Neither of the histamine H1/H2 antagonists diphenhydramine (10-6 M) or cimetidine (10-5 M) affected the contraction induced by PAF. In contrast with the whole gastric corpus, in mucosa-free strips, the contractile effect of PAF was not modified by methysergide.
The present study supports the view that the effect of PAF is mediated by activation of specific PAF receptors and the release of prostaglandins and 5-hydroxytryptamine in isolated gastric corpus. Furthermore, our results suggest a role of the gastric mucosa via the release of 5-hydroxytryptamine which contributes to the contractile effect of PAF in the gastric smooth muscle.
Membrane-bound Phosphodiesterases in Rat Myocardium
Authors: Kaasik Allen , Ohisalo Jorma J 
Published: April 2011

Abstract
Isoenzyme-specific phosphodiesterase (PDE) inhibitors are potential positive inotropic drugs. For evaluating such drugs in experimental models and to understand the physiological roles of the different isoenzymes, it is necessary to know what isoenzymes are present in the tissues studied. Rat myocardium has been reported to be devoid of the particulate cGMP-inhibited cAMP-PDE (type III isoenzyme). Here we re-evaluate the isoenzyme profile of rat myocardium.
The cAMP-PDE isoenzyme patterns were studied by ion-exchange chromatography using siguazodan and rolipram, specific inhibitors of type III and IV isoenzymes, respectively. In contrast to earlier reports, type III isoenzyme was abundant in the particulate fraction. PDE III-specific antibodies depressed PDE activity and stained bands in Western blot with molecular masses 64 and 71 kDa. Type III isoenzyme of myocardial membranes was found to be unstable at 37°C which may explain why earlier investigators have failed to demonstrate its presence.
The data presented in this paper show that rat heart particulate fraction contains two low Km PDE isoenzymes, type III and type IV, in equal activities. Thus, in contrast to previous reports, this paper clearly shows the presence of considerable amounts of membrane-bound type III PDE isoenzyme in rat myocardium.
Trifluoperazine is More Effective than Chlorpromazine in Releasing Oxygen from Haemoglobin and Myoglobin
Authors: Bhattacharyya Jaya , Bhattacharyya Maitree , Chakraborti Abhay Sankar , Chaudhuri Utpal , Poddar Ramendra Kumar 
Published: April 2011

Abstract
The extent of oxygen release from two heme proteins, haemoglobin and myoglobin have been studied in the presence of trifluoperazine and chlorpromazine (5–1000 μM).
At a molar ratio (drug: protein) of 1.5, the release of oxygen from haemoglobin was 4 and 15% in the presence of chlorpromazine and trifluoperazine respectively, while from myoglobin the corresponding values were 20 and 40%.
The findings were attributed to the greater extent of local conformational change around tryptophan moieties of each of the proteins induced by trifluoperazine.
Effect of Bakuchiol on Leukocyte Functions and Some Inflammatory Responses in Mice
Authors: Ferrándiz María Luisa , Gil Blanca , Sanz María Jesús , Ubeda Amalia , Erazo Silvia , González Ernesto , Negrete Rosa , Pacheco Sergio , Payáa Miguel , Alcaraz Maráa José 
Published: April 2011

Abstract
The effects of bakuchiol, a meroterpenoid isolated from the leaves of Psoralea glandulosa L., on phospholipase A2 (PLA2) activity from different sources, human neutrophil responses, zymosan air pouch and topical inflammation in mice, were investigated.
This natural product was a weak inhibitor of secretory and intracellular PLA2 but dose-dependently reduced the formation of LTB4 and TXB2 by human neutrophils and platelet microsomes, respectively. In addition, bakuchiol inhibited degranulation in human neutrophils, whereas superoxide generation was not affected. In mice, bakuchiol decreased cell migration, myeloperoxidase activity and eicosanoid levels in the air pouch inflammation induced by zymosan. After topical administration, this compound was effective as an inhibitor of oedema and myeloperoxidase activity in the 12-O-tetradecanoylphorbol 13-acetate (TPA)-induced ear oedema and significantly reduced the PGE2 content and ear oedema in the arachidonic acid-induced response.
Bakuchiol is a natural anti-inflammatory agent able to control leukocytic functions such as eicosanoid production, migration and degranulation in the inflammatory site.
Transient Relaxation of Plasmid DNA in Escherichia coli by Fluoroquinolones
Authors: Matsuo Miki , Ohtsuka Yoshihisa , Kataoka Kazuhiro , Mizushima Tohru , Sekimizu Kazuhisa 
Published: April 2011

Abstract
We examined the influence of fluoroquinolones (norfloxacin, enoxacin, ofloxacin, levofloxacin, and sparfloxacin) on DNA supercoiling of plasmids in Escherichia coli cells by analysis with agarose gel electrophoresis in the presence of chloroquine.
All the fluoroquinolones tested immediately induced DNA relaxation. The relaxed DNA was re-supercoiled, and the process was sensitive to chloramphenicol, suggesting that newly synthesized proteins participate in the reaction. The concentrations of fluoroquinolones required for DNA relaxation were much higher than those required for cell killing.
The bactericidal effect of fluoroquinolones is apparently related to mechanisms other than DNA relaxation.
The Blood-brain Barrier: Principles for Targeting Peptides and Drugs to the Central Nervous System
Authors: Begley David J 
Published: April 2011

Abstract
The presence of the blood-brain barrier (BBB), reduces the brain uptake of many drugs, peptides and other solutes from blood. Strategies for increasing the uptake of drugs and peptide-based drugs include; structural modifications to increase plasma half-life; improving passive penetration of the BBB by increasing the lipophilicity of the molecule; designing drugs which react with transporters present in the BBB; and reducing turnover and efflux from the central nervous system (CNS).
Potential Protein Kinase C Inhibitors. 8,9,10,11α:-Tetrahydro-7αH-7,11-methano-12,12-dimethylcycloocta[de]naphthyl-9-amines
Authors: Wilson Martin P , Bowman Ralph E , Smith H John , Nicholls Paul J , Hewlins Michael J E 
Published: April 2011

Abstract
The synthesis of the 9α- and 9β-epimers of 8, 9, 10, 1 1α-tetrahydro-7αH-7, 11-methano-12, 12-dimethylcycloocta [de] naphthyl-9-amine is described.
Reaction between Ferriprotoporphyrin IX and the Antimalarial Endoperoxide Artesunate Gives an Intermediate Species with Enhanced Redox Catalytic Activity
Authors: Adams Paul A , Berman Peter A 
Published: April 2011

Abstract
The kinetics of the reaction between ferri(Fe(III) protoporphyrin IX (haemin) and the potent sesquiterpene endoperoxide antimalarial artesunate are shown to be consistent with a three-step, two-intermediate mechanism, with the final product possessing a degraded tetrapyrrole ring system. Microscopic rate constants for the mechanism have been evaluated. The redox catalytic capability of the haem artesunate complex is shown to be approximately fourfold that of haemin alone, suggesting a possible mechanism of action of the drug.
Receptor Binding Affinities and Biological Activities of Linear and Cyclic Melanocortins in B16 Murine Melanoma Cells Expressing the Native MC1 Receptor
Authors: Sahm Ulrike G , Olivier George W J , Branch Sarah K , Moss Stephen H , Pouton Colin W 
Published: April 2011

Abstract
Cyclic α-melanocyte-stimulating hormone (α-MSH) analogues produced by disulphide bridging (e.g. [Cys4,Cys10]α-MSH) are known to be almost equipotent to the native hormone in amphibian skin bioassays and as a consequence have been proposed as a paradigm for the active conformation of native MSH at the pigment cell MC1 receptor. However this proposal has been somewhat speculative as there is no published data comparing biological activity of cyclic MSH analogues with data on receptor binding. This study addresses this problem by comparing tyrosinase stimulatory activity with their receptor binding affinity in B16 murine melanoma cells expressing the native MC1 melanocortin receptor.
Cyclic [Cys4,Cys10] α-MSH showed almost the same affinity for the MC1 receptor as α-MSH, but the linear analogue [Cys4,Cys10]α-MSH bound less strongly. Both had biological activities similar to that of the natural ligand. Introduction of D-Phe into the ring in position 7 increased both affinity and activity of the cyclic compound.
The study suggests that the intrinsic efficacy of cyclic [Cys4,Cys10]α-MSH analogues is similar to native α-MSH. Our studies support the proposal that the cyclic structure serves as a good model for the active conformation of linear α-MSH.
P2T Purinoceptor Antagonists. A QSAR Study of Some 2-Substituted ATP Analogues
Authors: Tomkinson N P , Marriott D P , Cage P A , Cox D , Davis A M , Flower D R , Gensmantel N P , Humphries R G , Ingall A H , Kindon N D 
Published: April 2011

Abstract
FPL67085MX represents the first in a class of novel, highly potent and selective P2T purinoceptor antagonists which are inhibitors of adenosine diphosphate (ADP)-induced platelet aggregation in-vitro.
In an early series of compounds we studied the effect of variation of the adenine 2-substituent on potency and derived quantitative structure-activity relationships (QSARs) between the properties of the molecules and their biological activity. This work has recently been revisited using comparative molecular-field analysis (CoMFA) and the comparison of the predictions from the two methods is discussed along with their relative merits in terms of compound design.
The model suggests that the receptor for these molecules has a narrow lipophilic cleft, which is occupied by the adenine 2-substituent.
Airway Reactivity to Inhaled Spasmogens 18–24 h after Antigen-challenge in Sensitized Anaesthetized Guinea-pigs
Authors: Johnson Alexia , Broadley Kenneth J 
Published: April 2011

Abstract
The anaesthetized allergic guinea-pig was used to assess changes in airway reactivity to four different inhaled spasmogens: methacholine, 5-hydroxytryptamine (5-HT), histamine and the thromboxane A2 mimetic, 9,11-dideoxy-9α,11α-methano-epoxy-PGF2α (U-46619). Reactivity was determined 18 to 24 h after challenge of ovalbumin-sensitized guinea-pigs with inhaled ovalbumin. This time coincides with the appearance of a late-phase bronchoconstriction in these animals. Sensitivity to the spasmogen was assessed from the concentration-response curve for the increase in pulmonary inflation pressure (PIP) in ovalbumin- and saline-challenged sensitized animals.
When methacholine, 5-HT or histamine were the spasmogens there was no hyper-reactivity. The geometric mean EC50 values (i.e. the concentrations inducing half the maximum effect) obtained from the dose-response curves for methacholine (73 (42–129) and 94 (66–134) μg mL−1), 5-HT (1.5 (0.81–3.03) and 1.1 (0.51–2.24 μg mL−1) and histamine (39 (21–75) and 72 (32–162) μg mL−1) did not differ significantly (P &gt; 0.05) between saline- and ovalbumin-challenged animals, respectively. However, when U-46619 was the spasmogen, ovalbumin-induced airway hyper-reactivity was observed as a leftwards shift of the concentration-response curve and the EC50 value for ovalbumin-challenged animals (8.1 (5.1–13) ng mL−1) was significantly (P &lt; 0.05) less than the value for control animals (39 (21–75) ng mL−1).
Our findings suggest that airway hyper-reactivity is not ‘non-specific’, but instead depends on the chosen spasmogen. The absence of hyper-reactivity with certain spasmogens was not a result of poor delivery, because all spamogens caused a bronchoconstriction by the inhaled route. It was also not associated with the model because ozone has been shown to induce hyper-reactivity to inhaled methacholine and 5-HT. Because airway hyper-reactivity to both inhaled histamine and agonists at muscarinic receptors is regularly seen in man, the anaesthetized guinea-pig might not be the ideal model for assessing airway hyper-reactivity after antigen challenge and its modification by anti-asthma drugs.
Intestinal Absorption of Stable Cyclic Glycylphenylalanine: Comparison with the Linear Form
Authors: Mizuma Takashi , Masubuchi Satoshi , Awazu Shoji 
Published: April 2011

Abstract
The absorption, especially the stability and transportability, of the cyclic peptide cyclic glycylphenylalanine (cyclo(Gly-Phe)) and the linear peptides glycylphenylalanine, glycyl-d-phenylalanine and phenylalanylglycine have been studied in rat small intestine.
Linear peptides were degraded on the mucosal side and only glycyl-d-phenylalanine appeared on the serosal side. However, cyclo(Gly-Phe) was stable on the mucosal side and appeared on the serosal side. Furthermore, the absorption clearance of cyclo(Gly-Phe) was higher than that of glycyl-d-phenylalanine. In the presence of the peptidase inhibitor bestatin, the degradation of linear peptides was reduced and linear peptides appeared on the serosal side, but only phenylalanylglycine, which is transported by the oligopeptide transporter, was absorbed faster than cyclo(Gly-Phe). The absorption clearance of cyclo(Gly-Phe) was reduced as its concentration was increased from 125 μm to 500 μm. Furthermore, the absorption clearance of cyclo(Gly-Phe) at 125 μm was reduced at 4°C or in the presence of glycylsarcosine and cephalexin, which are transported by the oligopeptide transporter.
These results indicated that cyclo(Gly-Phe) was stable enough to be absorbed and was transported in part by the oligopeptide transporter rather than completely by passive diffusion.
Comparison of the Effects of Cimetidine and Ranitidine on the Pharmacokinetics of Disopyramide in Man
Authors: Jou Ming-Jeng , Huang Shung-Chieh , Kiang Fu-Mei , Lai Miao-Ying , Chao Pei-Dawn Lee 
Published: April 2011

Abstract
The widely prescribed antiulcer agents cimetidine and ranitidine have the potential to affect the absorption, metabolism or renal excretion of disopyramide. This study investigated the effect of a single oral dose of cimetidine or ranitidine on the pharmacokinetics of disopyramide and mono-N-dealkyldisopyramide in six healthy volunteers. The treatment was conducted in a randomized cross-over design. Serum levels and urinary recoveries of disopyramide and mono-N-dealkyldisopyramide were assayed by HPLC.
Cimetidine significantly elevated the maximum plasma concentration of disopyramide, the area under the plasma concentration-time curve and the total amount of disopyramide excreted unchanged in the urine, but the serum profile of mono-N-dealkyldisopyramide was not significantly affected. The effects of ranitidine on the pharmacokinetics of disopyramide and mono-N-dealkyldisopyramide were not significant. The interaction between cimetidine and disopyramide occurred mainly at the site of absorption.
The results indicate that cimetidine, but not ranitidine, significantly increased the absorption of orally administered disopyramide.
Pharmacokinetics of N4-Octadecyl-1-β-d-Arabinofuranosylcytosine in Plasma and Whole Blood after Intravenous and Oral Administration to Mice
Authors: Rentsch Katharina M , Schwendener Reto A , Schott Herbert , Hänseler Edgar 
Published: April 2011

Abstract
N 4-octadecyl-1-β-d-arabinofuranosylcytosine (NOAC) is a new cytotoxic derivative of cytosine arabinoside with improved cytotoxic activity and stability against deamination. Its pharmacokinetics were studied in mice.
The drug was administered intravenously and orally to ICR mice to assess its pharmacokinetic parameters in plasma and whole blood. The lipophilic drug was administered in small unilamellar liposomes 100–400 nm in diameter. The concentrations of NOAC in plasma and erythrocytes were determined by high-performance liquid chromatography (HPLC). When given orally a rather low amount of the delivered NOAC was absorbed as the unchanged drug, resulting in a bioavailability of 11% from the plasma and 12.9% from whole blood. As shown elsewhere, the amount of drug absorbed is sufficient to provide excellent cytotoxic activity in the L1210 leukemia and in human xenograft models after oral administration. The mean residence time of NOAC after intravenous administration was 3.5 h in plasma and 6 h in whole blood giving NOAC a terminal half-life in blood substantially longer than that of cytosine arabinoside. After oral administration the mean residence time was 18 h in plasma and whole blood.
In summary, NOAC has a prolonged half-life after intravenous administration compared with cytosine arabinoside. The distribution of NOAC in blood is highly dependent on its mode of administration.
Pharmacokinetics of Intragastrically Administered Digoxin in Rabbits with Experimental Bile Duct Obstruction
Authors: Wójcicki M , Drozdzik M , Sulikowski T , Gawronska-Szklarz B , Wójcicki J , Rózewicka L , Skowron J , Zielinski S , Musial H D , Zakrzewski J 
Published: April 2011

Abstract
A change in the functioning of the liver as a result of experimental cholestasis could result in a change in the biotransformation of drugs. The aim of this study was to evaluate the effect of extrahepatic cholestasis on the pharmacokinetics of digoxin.
The investigation was performed on male rabbits randomly divided into two groups: sham-operated and animals with bile-duct ligation. Digoxin (0.02 mg kg−1) was administered intragastrically as a single dose. Biomedical and anatomo-pathological tests and pharmacokinetic assays were performed before the operation and on the 6th day after surgery. A significant increase in area under the serum concentration-time curve and in mean residence time, a decrease in total body clearance, a reduction in the volume of distribution and increases in maximum concentration and the time to reach maximum concentration were observed in animals with the bile-duct ligation.
These results suggest reduced elimination of digoxin in animals with obstructive cholestasis.