bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Possible Mechanism of Interaction between Xanthines and Quinolone
Authors: Hasegawa Takaaki , Nadai Masayuki , Kuzuya Takafumi , Muraoka Isao , Apichartpichean Ruttikorn , Takagi Kenzo , Miyamoto Kenichi 
Published: April 2011

Abstract
To clarify the mechanism of interaction between theophylline and enoxacin, the effects of enoxacin and its metabolite, 4-oxo-enoxacin, on the disposition of new xanthine derivatives, 1-methyl-3-propylxanthine (MPX) and 3-propylxanthine (enprofylline), as models of theophylline have been investigated in rats. Pretreatment with enoxacin significantly delayed the elimination of MPX from plasma. No significant change in the volume of distribution of MPX was observed in the presence of enoxacin, but the total body clearance of MPX was significantly decreased by approximately 60 and 80% after pretreatment with 25 and 100 mg kg−1 of enoxacin, respectively. The amount of the decrease in total body clearance depended on the dose of enoxacin. 4-Oxo-enoxacin had little or no effect on MPX disposition. A newly developed quinolone, NY-198, which does not affect the disposition of theophylline, also did not affect the disposition of MPX. Enoxacin also had no effect on the disposition of enprofylline. These results indicate that the mechanism for decrease in theophylline clearance induced by enoxacin may not be due to its metabolite, 4-oxo-enoxacin, but to enoxacin itself, and that enoxacin does not inhibit solely the elimination process depending on cytochrome P450 isoenzyme for N-demethylation. It is likely that enoxacin has no influence on the renal excretion of xanthines.
Prevention by a Ginkgo biloba Extract (GBE 761) of the Dopaminergic Neurotoxicity of MPTP
Authors: Ramassamy Charles , Clostre François , Christen Yves , Costentin J 
Published: April 2011

Abstract
In mice implanted subcutaneously with osmotic minipumps releasing the neurotoxic agent N-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) for 7 days (105 μg h−1/mouse) (∼ 100 mg kg−1 day−1) a significant reduction (∼ 25%) in the striatal dopaminergic nerve endings was observed. This neurotoxic effect was prevented by the semi-chronic ingestion of a Ginkgo biloba extract for 17 days (GBE 761, ∼ 100 mg kg−1 day−1). The high concentrations (∼ 1 g L−1) at which GBE 761 in-vitro either prevented the uptake of [3H]dopamine by synaptosomes prepared from striatum, or prevented the specific binding of the pure dopamine uptake inhibitor [3H]GBR 12783 to membranes prepared from striatum suggests that the prevention of the MPTP neurotoxicity does not depend on an inhibition of the MPTP uptake by dopamine neurons. This is also suggested by the lack of prevention of the in-vitro striatal binding of [3H]GBR 12783 administered i.v. at a tracer dose, in mice pretreated for 8 days with GBE 761 (100 mg kg−1 p.o.) and receiving a supplementary gastric administration of GBE 761 (100 mg kg−1) 1 h before testing. Similar treatment with GBE 761 did not modify the toxicity for dopamine neurons of 6-hydroxydopamine (20 μg) directly injected into the striatum of rats.
The pharmacokinetics of artemisinin after oral, intramuscular and rectal administration to volunteers
Authors: Titulaer H A C , Zuidema J , Kager P A , Wetsteyn J C F M , Lugt Ch B , Merkus F W H M 
Published: April 2011

Abstract
The pharmacokinetics after oral, intramuscular and rectal administration of artemisinin, a new potent antimalarial drug, to healthy volunteers has been examined. The study was set-up as a four-way cross-over design with a wash-out period of one week between the test days. In ten volunteers artemisinin concentrations in serum were monitored using a reversed phase HPLC assay with UV detection after derivatization. After oral administration, artemisinin was rapidly but incompletely absorbed, the mean absorption time was 0.78 h and the bioavailability relative to the intramuscularly injected suspension in oil 32%. The mean residence time of the latter (10.6 h) was 3 times that of the oral formulation (3.4 h). This seems to enable a twice daily dosage regimen for the intramuscular oil injection, while the oral formulation necessitates a more frequent dosing interval. After intramuscular injection and rectal administration of an aqueous suspension, very low and variable artemisinin concentrations in serum were observed, probably indicating a poor and erratic absorption.
Rat Paw Oedema and Mast Cell Degranulation Caused by Two Phospholipase A2 Enzymes Isolated From Trimeresurus mucrosquamatus Venom
Authors: Wang Jih-Pyang , Teng Che-Ming 
Published: April 2011

Abstract
Two phospholipase A2 (PLA2) enzymes, TMVPLA2 I and TMVPLA2 II, isolated from Trimeresurus mucrosquamatus venom (TMV) induce rat hind-paw oedema in a dose-dependent manner. This response is suppressed by pretreatment with diphenhydramine, methysergide or compound 48/80, which reduces tissue histamine content. In isolated mast cells, TMVPLA2 I and TMVPLA2 II cause concentration-, time-and calcium-dependent release of histamine and β-glucuronidase. This effect is inhibited by disodium cromoglycate, mepacrine, nordihydroguaiaretic acid, piriprost and BW 755C, but not by aspirin or indomethacin. These observations indicate that the mast cell plays a predominant role in TMVPLA2 I-and TMVPLA2 II-induced paw oedema, and that venom PLA2 enzyme needs an intact lipoxygenase pathway to induce mast cell degranulation.
A Survey of the Antibacterial Activity of Some New Zealand Honeys
Authors: Allen K L , Molan P C , Reid G M 
Published: April 2011

Abstract
To assess the variation in antibacterial activity of honey a survey was carried out on 345 samples of unpasteurized honey obtained from commercial apiarists throughout New Zealand. Most of the honeys were considered to be monofloral, from 26 different floral sources. The honeys were tested against Staphylococcus aureus in an agar well diffusion assay, with reference to phenol as a standard. Antibacterial activity was found to range from the equivalent of &lt; 2% (w/v) phenol to 58% (w/v) phenol, with a median of 13·6 and a standard deviation of 12·5. Neither the age of the honey samples nor whether they had been processed by the apiarist was associated with lower activity. However, the difference between floral sources in the antibacterial activity was very highly significant. Kanuka (Kunzea ericoides (A. Rich.) J. Thompson. Family: Myrtaceae), manuka (Leptospermum scoparium J. R. et G. Forst. Family: Myrtaceae), ling heather (Calluna vulgaris (L.) Hull. Family: Ericaceae) and kamahi (Weinmannia racemosa Linn. f. Family: Cunoniaceae) were shown to be sources likely to give honey with high antibacterial activity. When antibacterial activity was assayed with catalase added to remove hydrogen peroxide, most of the honeys showed no detectable antibacterial activity. Only manuka and vipers bugloss (Echium vulgare L. Family: Boraginaceae) honeys showed this type of activity in a significant proportion of the samples. The high antibacterial activity of manuka honey was in many cases due entirely to this non-peroxide component.
Pharmacokinetics of Anti-HIV Nucleosides in Microswine
Authors: Swagler Anne R , Qian Mingxin , Gallo James M 
Published: April 2011

Abstract
The objective of the study was to determine if the micropig (Sus scrofa) would serve as an animal model for the anti-HIV nucleosides 3′-azido-3′-deoxythymidine (AZT), 2′,3′-dideoxyinosine (ddI), and 2′,3′-dideoxycytidine (ddC). Four adult male micropigs were administered i.v. 20 mg kg−1 AZT, 20 mg kg−1 ddI, both as 10 min infusions, and 5 mg kg−1 ddC, as an i.v. bolus. At least 12 days separated each drug administration. Following each drug administration, blood samples were collected by venipuncture and urine was collected by placement of the animals in metabolism cages. Concentrations of parent drug and AZT's glucuronide metabolite were quantitated in plasma and urine by HPLC. Data were analysed by non-compartmental methods to obtain pharmacokinetic parameters for each drug. Total and renal clearances for AZT, 0·482 ± 0 058 and 0·326±0·075 L h−1 kg−1, respectively, and for ddI, 0·500±0057 and 0·337 ± 0·100 L h−1 kg−1, showed that these drugs were eliminated primarily by renal excretion rather than by liver metabolism as in man. ddC's clearances were similar to rates in man. Volume of distribution at steady state values were 0·784 ± 0·071, 1·192±0·288 and 0·886±0·199 L kg−1 for AZT, ddI and ddC, respectively. Half-life values for AZT, ddI and ddC were 1·39±0·127, 2·585 ± 0·243 and 1·832 ± 0·380 h, respectively. Based on these findings, the micropig could be an appropriate model for the study of ddC in man, but not for AZT of ddI.
β-Adrenoceptor Profile of Ractopamine HCl in Isolated Smooth and Cardiac Muscle Tissues of Rat and Guinea-pig
Authors: Colbert Walter E , Williams Patricia D , Williams Gail D 
Published: April 2011

Abstract
The investigational sympathomimetic amine, ractopamine hydrochloride, has been profiled for adrenergic activity in selected smooth and cardiac muscle preparations. There was no significant interaction of ractopamine with α-adrenergic receptors in the rat vas deferens at concentrations up to 10−5 m. However, ractopamine produced a concentration-dependent increase in the force and rate of contractions of atria isolated from normal and reserpinized guinea-pigs (EC50= 1 × 10−7 m). These increases were submaximal compared with isoprenaline (70–85%), suggesting partial agonist activity at the β1-receptor site. Ractopamine completely relaxed the KCl-contracted guinea-pig trachea and rat costo-uterine smooth muscle to their resting tensions (EC50 = 3 × 10−7 and 5·5 × 10−8m, respectively), indicative of full β2-agonist properties. Propranolol blocked the response of ractopamine in isolated tracheal and atrial tissues (pA2 = 7·70), demonstrating a β-adrenergic mechanism of activity. Ractopamine also exhibited antagonism of the response of the guinea-pig trachea to the β-agonist, isoprenaline. Relative to other β-agonists, ractopamine was 100-fold more potent than the phenethanolamines, salbutamol and ritodrine, at the β1-adrenoceptor, and approximately 7- to 11-fold more potent than ritodrine, but only one-sixth to one-tenth as potent as salbutamol at the β-adrenoceptor. Thus, ractopamine possesses significant β1- and β2-agonist properties. The submaximal stimulation of the force and rate of atrial contractions is indicative of a partial β1-agonist, while the maximal relaxation of tracheal and costo-uterine smooth muscle is characteristic of a full β2-agonist.
Pirarubicin-induced Endothelium-dependent Relaxation in Rat Isolated Aorta
Authors: Hirano Shin-Ichi , Agata Naoki , Hara Yutaka , Iguchi Hiroshi , Shirai Masataka , Tone Hiroshi , Urakawa Norimoto 
Published: April 2011

Abstract
The mechanism of relaxation produced by pirarubicin [(2″R)-4′-O-tetrahydropyranyladriamycin, THP] has been studied in rat isolated aorta. THP (1·5 × 10−6–4·5 × 10−5 m) markedly relaxed contractions induced by noradrenaline (10−7 m) in the aorta with endothelium, but not in that without endothelium. The relaxation induced by 1·5 × 10−5 m THP was inhibited by methylene blue (5 × 10−6 m), hydroquinone (10−4 m), phenidone (5 × 10−5 m), haemoglobin (10−6 m) and p-bromophenacyl bromide (5×10−5 m), but not by indomethacin (2·5 ×10−5 m). The relaxation induced by THP (1·5 × 10−7 − 4·5 × 10−5 m) was inhibited by NG-nitro-l-arginine (10−5 m), but enhanced by superoxide dismutase (10 units mL−1) or by L-arginine (10−2 m). However, the THP-induced relaxation was not inhibited by various receptor antagonists such as atropine (10−6 m), cimetidine (10−5 m), diphenhydramine (3 × 10−6 m) and [D-Pro4, D-Trp7,9,10]-substance P(4–11) (1·5 × 10−6 m). In fifteen anthracycline analogues, THP and 13-dihydropirarubicin (both with a tetrahydropyranyl group) produced endothelium-dependent relaxations. These results suggest that the THP-induced relaxation which is probably mediated by endothelium-derived relaxing factor (EDRF) was not produced by an activation of muscarine, histamine H1 or H2, or substance P receptor, and further that the tetrahydropyranyl group must play an important role in the THP-induced relaxation.
Receptor binding at two different temperatures to discriminate agonist and antagonist behaviour of adenosine A1 receptor ligands in rat brain
Authors: Borea Pier Andrea , Varani Katia , Malaguti Valeria , Gilli Gastone 
Published: April 2011

Abstract
The inhibitory binding constants, Ki, at the adenosine A1 receptor in rat brain have been measured at 0 and 25°C for 25 typical ligands. The Ki ratios at the two temperatures are greater and smaller than unity for adenosine agonists and xanthine antagonists, respectively. These results suggest that two-temperature measurements of in-vitro Ki constants represent a simple method of discriminating between in-vivo agonistic and antagonistic behaviour of A1 adenosine receptor ligands.
Inhibition of lipid peroxidation by methylated analogues of uric acid
Authors: Nishida Y 
Published: April 2011

Abstract
The effects of purines and methylated purine analogues on hydrogen peroxide- and ozone-induced lipid peroxidation in human erythrocyte membranes were studied in-vitro. Many purines and purine analogues showed a suppressive effect on the formation of thiobarbituric acid reactive materials. 1,3-Dimethyluric acid and 1,3,7-trimethyluric acid showed high potency in prevention of lipid peroxidation. These effects were shown to be concentration dependent and were more potent at low concentrations of hydrogen peroxide and ozone. 1,3-Dimethyluric acid and 1,3,7-trimethyluric acid may be useful as antioxidants.
Peak Offset Times as an Indication of Stress Relaxation During Tableting on a Rotary Tablet Press
Authors: Dwivedi S K , Oates R J , Mitchell A G 
Published: April 2011

Abstract
During powder compaction on a Manesty Betapress, peak pressures, Pmax, are reached before the punches are vertically aligned with the centres of the upper and lower compression roll support pins. The interval between the time taken to reach this alignment and the time to reach Pmax is defined as the peak offset time, toff. The duration of toff depends on the ability of the compacted powder to relieve stress and is an indication of the predominant mechanisms of particle deformation during consolidation. Thus, at a given Pmax, short toff values are characteristic of materials that consolidate mainly by brittle fracture while longer values indicate an increase in plastic flow. On the Betapress, the decrease in stress during toff occurs under conditions approaching constant strain and toff therefore, is an indirect measure of stress relaxation. Stress relaxation, and hence toff, decreases with increase in Pmax due to the reduction in the porosity of the compact and consequent restriction of plastic flow into the void spaces. In addition to Pmax, the effects of variables such as punch head geometry, press speed and formulation on toff are reported.
Predisposition to Uterine Microbial Contamination in the Guinea-pig Following Administration of Mucolytic Drugs and Steroid Hormones
Authors: Malhi Jaspal S , Gard Paul R , Hanlon Geoffrey W 
Published: April 2011

Abstract
Using guinea-pigs as a mammalian model, the effects of bromhexine hydrochloride, ethinyloestradiol, norethisterone acetate and prednisolone acetate on uterine microbial status were determined. Those drugs known to decrease mucus viscoelasticity predisposed to the entry of vaginal bacteria into the uterus, probably due to reduction of the cervical mucus barrier. Norethisterone acetate, which increases cervical mucus viscoelasticity, reduced these effects. The effects produced by the steroid hormones were independent of their immunosuppressive effects. The results also suggest that prednisolone acetate may exert oestrogenlike actions on cervical mucus.
IgG- and IgE-mediated Histamine Release from Superfused Guinea-pig Airway Tissues
Authors: Van Amsterdam Ronald G M , Santing Ruud E , De Boer Jacob , Brouwer Frans , Zaagsma Johan 
Published: April 2011

Abstract
Anaphylactic histamine release and the inhibition by the β-adrenoceptor agonist fenoterol has been investigated using lung and tracheal tissues from two groups of guinea-pigs, differently sensitized to respond with IgG or IgE antibodies, respectively. A superfusion method was introduced and compared with classical batch incubation. The difference between IgG- and IgE-mediated histamine release during superfusion of both tissues was much greater than the difference obtained during batch-incubations. Fenoterol inhibited IgG-mediated histamine release during superfusion at lower concentrations and to a larger extent than the release from IgE-sensitized tissues. The inhibition by fenoterol was less pronounced after batch-wise incubations, preincubation at 0°C abolished the quantitative difference of IgG- and IgE-mediated histamine release from lung slices as well as the difference in β-adrenergic inhibition. It is concluded that the new superfusion procedure for airway tissues enhances the sensitivity of antigen-induced histamine release for pharmacological modulation, compared with batch-wise incubation. In addition, the effects of 0°C pretreatment show that cooled transport and storage of airway tissue should be considered with care.
The Effect of Fever on Quinine and Quinidine Disposition in the Rat
Authors: Mansor S M , Ward S A , Edwards G 
Published: April 2011

Abstract
The pharmacokinetics of quinine and its diastereoisomer quinidine has been investigated in normal and febrile rats. Endotoxin-induced fever in rats resulted in an increased quinine clearance (CL) (4·49 ± 1·45 vs 1·38 ±0·65 L h−1 kg−1, P &lt; 0001) and volume of distribution (Vd) (42·6 ± 8·8 vs 28·9 ± 10·3 L kg−1, P &lt; 0·05) with a concomitant shortening of the elimination half-life (t½) (7·1 ±2·5 vs 15·9 ± 5·9 h, P &lt; 0·01). With quinidine, however, fever resulted in an increased CL (3·95 ± 1·05 vs 1·89 ± 0·60 L h−1 kg−1, P &lt; 0·002) with no change in Vd and a significant decrease in t½ (5·1 ±0·7 vs 10·1 ±2·8 h, P &lt; 0·001). In both studies there was no significant difference in hepatic microsomal protein or cytochrome P450 content. Neither drug accumulated in the liver but low concentrations of quinidine were present in the heart 24 h after administration. In-vitro studies suggest that temperature does not alter the binding of either drug. These data suggest that fever enhances the clearance of quinine and quinidine. These findings may offer some additional explanation of the lack of serious quinine and quinidine toxicity during the treatment of malaria infection, even after large dosages of the drug administered during the initial period of treatment when fever is most intense.
Protein binding of cefpiramide in the plasma of various species
Authors: Ohshima Taeyuki , Hasegawa Takaaki , Johno Ikuo , Kitazawa Shikifumi 
Published: April 2011

Abstract
The plasma protein binding of cefpiramide in man, dog, rabbit and rat was examined. Cefpiramide was more strongly bound to human plasma than to animal plasma and was exclusively bound to albumin. The characteristics of the protein binding of cefpiramide is one of the factors influencing the extrapolation of drug disposition from animals to man.
Chronic electroconvulsive shock alters hypothermic response of B-HT 920 and SKF 38393 in rats
Authors: Verma Anita , Kulkarni S K 
Published: April 2011

Abstract
The hypothermic response of B-HT 920, a D2-dopamine agonist remained unaltered while that of apomorphine, a mixed D1-/D2-agonist was significantly reduced following chronic electroconvulsive shock (ECS) treatment. SKF 38393 (5 mg kg−1), a selective D1-agonist potentiated the hypothermic response of B-HT 920 in non-ECS-treated rats. The response of the combination was, however, attenuated following chronic ECS treatment. These observations suggested a reduction in Di-receptor density following chronic ECS treatment in rats.
Pharmacokinetics of Valproic Acid in Guinea-pigs with Biliary Abnormality
Authors: Yu Hsiu-Ying , Shen Yu-Zen 
Published: April 2011

Abstract
To explore whether biliary cannulation, biliary obstruction or gall bladder obstruction could alter the disposition of valproic acid, guinea-pigs were subjected to common bile duct cannulation or ligation, gall bladder-neck ligation or sham surgery as a control. They were then given an intravenous (i.v.) dose of sodium valproate (50 mg kg−1) and the pharmacokinetics of valproic acid in each group were compared. In the cannulated group, significant decreases (P &lt; 0·05) in the area under the elimination curve (AUC), the volume of distribution at steady-state (Vdss) and the mean residence time (MRT) were observed. Significant increases (P &lt; 0·05) in the elimination rate constant (kz) and total clearance (CLtot) of valproic acid were noted. In the biliary obstructed guinea-pigs, the Vdss was significantly decreased (P &lt; 0·05). In the gall bladder obstructed guinea-pigs, there was a secondary peak of valproate plasma concentration, and the kz was significantly decreased. The biliary excretion of unchanged and conjugated valproic acid was 2·0 ± 0·7 (s.e.m.) and 19·7 ±3·6 (s.e.m.) % of dose, respectively, and was almost completely reabsorbed in the enterohepatic recycling. Urinary excretion of unchanged and conjugated valproic acid, as well as non-conjugate metabolic clearance of valproic acid, were not significantly different among the four groups. The results suggest that the pharmacokinetics of valproic acid in guinea-pigs are particularly sensitive to interruption of the enterohepatic cycle. Biliary obstruction may elevate plasma concentrations owing to the decreased Vdss of valproic acid. Gall bladder obstruction may cause fluctuation of valproate plasma concentrations. The data indicate that the apparent total clearance of valproic acid is significantly less than the intrinsic clearance owing to enterohepatic recycling.
Potentiation of gastric toxicity of ibuprofen by paracetamol in the rat
Authors: Bhattacharya Salil K , Goel R K , Bhattacharya Sujit K , Tandon R 
Published: April 2011

Abstract
A fixed dose combination of ibuprofen (400 mg) and paracetamol (325 mg) is by far the most extensively prescribed medicament for a variety of musculoskeletal disorders in India. Following clinical observations that this drug combination induces significant adverse effects, its gastric toxicity was investigated in rats. Ibuprofen (25 mg kg−1 p.o., twice daily × 5 days), paracetamol (20 mg kg−1 p.o, twice daily × 5 days), and a combination of the two, had no significant effect on free and total gastric acidity in pylorusligated rats. Ibuprofen induced visible gastric ulceration whereas paracetamol did not. However, the combination of these two drugs had an additive effect inducing severe gastric erosions, ulcerations and bleeding. The augmented toxicity of this drug combination appeared to be a consequence of attenuated gastric mucin activity and reduction in the gastric muco-protective barrier. This investigation indicates the likely hazard of an irrational fixed dose drug combination.