bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effect of Sodium Naproxen on Inflammatory Response Induced by Anterior Chamber Paracentesis in the Rabbit
Authors: Bucolo Claudio , Spadaro Angelo 
Published: April 2011

Abstract
This study evaluated the effect of sodium naproxen (a reversible competitive inhibitor of cyclo-oxygenase) and phenylephrine (a mydriatic α-adrenergic agent) eye drops in maintaining atropine mydriasis in the rabbit after paracentesis. Moreover, to assess the influence of these treatments on vascular and cellular inflammatory responses in the rabbit eye, several biochemical parameters were considered.
Anterior chamber paracentesis significantly reduced atropine-induced mydriasis and a parallel elevation of proteins, polymorphonuclear leucocytes (PMNs), prostaglandin E2 (PGE2) and leukotriene B4 (LTB4) levels in the secondary aqueous humour (obtained 120 min later) was observed. A significant increase in PMNs in the aqueous humour and a parallel increase in myeloperoxidase activity, a measure of PMN infiltration, in the iris-ciliary body were detected. Atropine-induced mydriasis was maintained in rabbits treated with either sodium naproxen or phenylephrine eye drops. However, only in the former group were the inflammatory parameters significantly reduced, with the exception of aqueous LTB4 levels.
The inhibition of the protein influx in the aqueous humour and of the miosis produced by sodium naproxen can be related to the high drug levels in the aqueous humour that were effective in inhibiting the cyclo-oxygenase pathway of arachidonic acid metabolism, whereas the effects on PMN infiltration appear to be independent of significant release of the potent chemotactic agent LTB4, synthesized via the 5-lipoxygenase pathway.
The Transmucosal Absorption of Recombinant Human Interferon-α B/D Hybrid in the Rat and Rabbit
Authors: Bayley Deborah , Temple Cathy , Clay Val , Steward Alan , Lowther Nicholas 
Published: April 2011

Abstract
For therapeutic proteins such as interferon-α B/D, a non-parenteral route of delivery is desirable. Possible sites of administration include the various regions of the gastrointestinal tract and airways, and this paper reports the bioavailability of interferon-α B/D via these routes in the rat and rabbit.
Apart from the stomach, detectable levels of interferon-α B/D in the serum were achieved via all routes. Bioavailabilities were less than 1%, except from the lung (6·8% in the rat) and nasal cavity (2·9% in the rabbit). Absorption from the gastrointestinal tract was similar for both species, but in the nasal cavity of the rabbit was sixfold that of the rat, and in the lung of the rat was tenfold that in the rabbit. Absorption from all routes, except the buccal cavity, resulted in detectable biochemical changes in the liver of the rabbit.
Comparison with reports from other groups show differences in the extent of absorption of interferon-α B/D and of natural or homologous recombinant interferon-α. The non-parenteral delivery of biochemically active amounts of interferon-α B/D is thus demonstrated.
The Influence of Uptake from the Gastrointestinal Tract and First-pass Effect on Oral Bioavailability of (Z)-alkyloxyimino Penicillins
Authors: Mizen Linda , Berry Valerie , Woodnutt Gary 
Published: April 2011

Abstract
We have investigated the contribution of uptake from the gastrointestinal tract and first-pass effect to the poor oral bioavailability of a series of (Z) -alkyloxyimino penicillins in mice.
Investigative studies in gut sacs and perfused small intestine demonstrated that these penicillins were able to pass across the mucosal epithelium although to a lesser extent than amoxycillin and cyclacillin, both of which exhibit excellent oral bioavailability in man and animals. In the jejunal gut sacs the mucosal to serosal flux for BRL 44154 was approximately half that of amoxycillin and four times less than that of cyclacillin, and for all, uptake was pH dependent. The serosal to mucosal fluxes were however similar for these compounds and significantly lower than mucosal to serosal fluxes, suggesting involvement of carrier mechanisms in uptake from the mucosal surface. The order of results for the alkyloxyimino penicillins paralleled that observed for oral bioavailability in the mouse.
For the alkyloxyimino penicillins, between 5·5 and 9·9% was taken up from the perfused intestine, values which were significantly less than those for amoxycillin (13·2%) and cyclacillin (33·3%). However, uptake was concentration-dependent for BRL 44154 as it was for amoxycillin, thus confirming the possible use of carrier mechanisms in absorption.
These observations suggest that the poor peripheral blood concentrations of the alkyloxyimino penicillins achieved after oral dosing were not a consequence of the inability of the compounds to cross the mucosal epithelium. The biliary clearance of the alkyloxyimino penicillins was, however, considerably greater than for amoxycillin and cyclacillin, a finding which may well have been a contributory factor to the comparatively low peripheral concentrations of BRL 44154 and its analogues achieved after oral administration.
Differential Relaxant Responses of Guinea-pig Lung Strips and Bronchial Rings to Sodium Nitroprusside: A Mechanism Independent of cGMP Formation
Authors: Fred Wong W S , Roman Carlos R , Fleisch Jerome H 
Published: April 2011

Abstract
The biochemical mechanism subserving smooth muscle relaxant effects of sodium nitroprusside was examined on U46619, 9, 11-dideoxy-9α, 11α-methanoepoxy PGF2α, precontracted guinea-pig lung strips and hilar bronchial rings.
Lung strips were resistant to the relaxant action of sodium nitroprusside or sodium nitrite (NaNO2), whereas they markedly relaxed to 8-bromo-cyclic GMP (8-Br-cGMP), a membrane permeable analogue of cGMP. Precontracted bronchial rings completely relaxed to sodium nitroprusside, NaNO2, or 8-Br-cGMP in a concentration-dependent manner. Sodium nitroprusside (10 μm) substantially raised tissue cGMP level in lung strips. Conversely, sodium nitroprusside had no detectable effect on cGMP levels in bronchial rings. In the presence of 10 μm dipyridamole, an agent which preferentially inhibits cGMP-specific phosphodiesterase, cGMP levels in lung strips treated with sodium nitroprusside was significantly enhanced, but sodium nitroprusside demonstrated no relaxant effect on the preparations. However, dipyridamole potentiated sodium nitroprusside-induced precontracted bronchial ring relaxation without affecting the bronchial tissue cGMP level. In the presence of 10 μm LY83583 (6-anilino-5,8-quinoline-dione), a specific cGMP concentration-lowering agent, sodium nitroprusside-mediated elevation of cGMP level in lung strips was significantly reduced with no effect on the functional response. LY83583 demonstrated no inhibitory effect on either relaxation or cGMP level in bronchial rings treated with sodium nitroprusside.
Our results suggest that precontracted smooth muscle in lung strips and in hilar bronchi respond distinctly to sodium nitroprusside. Furthermore, sodium nitroprusside mediates bronchial smooth muscle relaxation by mechanisms unrelated to cGMP.
Pharmacological Properties of 403U76, a New Chemical Class of 5-Hydroxytryptamine- and Noradrenaline-reuptake Inhibitor
Authors: Ferris R M , Brieaddy L , Mehta N , Hollingsworth E , Rigdon G , Wang C , Soroko F , Wastila W , Cooper B 
Published: April 2011

Abstract
403U76 (5-chloro-[[2-[(dimethylamino)methyl]phenyl]thio]benzene-methanol hydrochloride) is a potent, competitive, inhibitor of 5-hydroxytryptamine (5-HT) and noradenaline reuptake into rat brain synaptosomes. Inhibition of 5-HT uptake in-vivo by 403U76 was demonstrated by potentiation of the behavioural effects of 5-hydroxytryptophan in rats and mice and blockade of p-induced depletion of 5-HT in rats.
The firing of 5-HT-ergic dorsal raphe neurons in rats was decreased after intravenous administration of low doses of 403U76 as would be predicted for a 5-HT uptake inhibitor. 403U76 antagonized tetrabenazine-induced sedation, an effect associated with inhibitors of noradrenaline uptake, but not with inhibitors of 5-HT uptake. Thus 403U76 affects noradrenergic as well as 5-HT-ergic neurotransmission in-vivo. Potential anxiolytic activity was indicated by reductions in isolation-induced vocalizations in neonates after 403U76 treatment.
Low intravenous doses of 403U76 were well tolerated and had no sustained cardiovascular effects. There were no deleterious behavioural side-effects at active doses. Effects observed on isolated tissues or transmitter receptors occurred only at very high concentrations and were pharmacologically unimportant. Thus 403U76 can be considered a potential antidepressant/anxiolytic agent that is a potent, selective inhibitor of 5-HT and noradrenaline reuptake.
Evaluation of In-vivo Transdermal Absorption of Cyclosporin with Absorption Enhancer Using Intradermal Microdialysis in Rats
Authors: Nakashima Mikiro , Zhao Mei Feng , Ohya Hisami , Sakurai Masaharu , Sasaki Hitoshi , Matsuyama Kenji , Ichikawa Masataka 
Published: April 2011

Abstract
The purpose of this study was to evaluate the effect of absorption enhancer on in-vivo transdermal absorption of cyclosporin using intradermal microdialysis in rats. Cyclosporin oily solutions (0.5, 2, 8% w/v) were prepared from Sandimmun (10% w/v oily oral preparation of cyclosporin) by diluting with olive oil. 1-[2-(Decylthio)ethyl]azacyclopentan-2-one (HPE-101) and glycerin were added to the cyclosporin formulation as an absorption enhancer at various concentrations between 1 and 20%. These formulations were applied to the shaved abdomen of rats treated with intradermal microdialysis at a flow rate of 2.5 μL min−1 for 6 h.
Cyclosporin was immediately detected and attained a plateau in the dermal dialysate after topical application of cyclosporin oily solution alone. Cyclosporin levels in the dialysate increased with increasing cyclosporin concentrations in the formulation from 0.5 to 8% (w/v). HPE-101 did not influence cyclosporin absorption at concentrations less than 6% (w/v). Addition of 10% (w/v) HPE-101 significantly enhanced an apparent absorption rate of cyclosporin by 4.9 times. However, 20% (w/v) HPE-101 did not show the enhancing activity. On the other hand, addition of glycerin at concentrations of 6, 10, and 20% (v/v) significantly enhanced an apparent absorption rate of cyclosporin by 3.0, 64, and 6.9 times, respectively. The time lag for cyclosporin absorption was less than 0.21 h in all tested cases.
This microdialysis study shows that glycerin is a suitable enhancer for improving the in-vivo cyclosporin absorption from the skin.
Effect of the Hydroalcoholic Extract of Rauwolfia ligustrina on Smooth and Cardiac Muscles In-vitro
Authors: De Medeiros Cleane L Costa , Calixto João B 
Published: April 2011

Abstract
The actions of the hydroalcoholic extract (HE) of Rauwolfia ligustrina (the whole plant) on agonist-induced contractions were analysed in the rat uterus and guinea-pig ileum and trachea, and also in rat atrium contracting spontaneously in-vitro.
The HE (100–400 μg mL−1) caused concentration-dependent rightward shifts of the concentration-response curves and reduced the maximal contraction induced by oxytocin, bradykinin, angiotensin II, prostaglandin F2α and acetylcholine in the rat uterus. The calculated mean IC50 values were: 300, 147, 158, 197 and 105 μg mL−1, respectively. In the guinea-pig ileum the HE also caused graded displacement to the right of the concentration—response curves for bradykinin, histamine and carbachol, associated with pronounced inhibition of the agonist-induced maximal contractions. The calculated mean IC50 values were 165, 134 and 241 μg mL−1, respectively. The HE (100–3000 μg mL−1) caused graded relaxation (IC50 of 271 μg mL−1) of strips of guinea-pig trachea precontracted with carbachol (0.2 μM). This effect was not infuenced by propranolol (1 μM), 3-isobutyl-1-methylxanthine (1 μM) or methylene blue (10 μM), but was significantly potentiated (1.5-to 3-fold) by indomethacin (3 μM) and forskolin (1 nM). In addition, NG-monomethyl-L-arginine (L-NMMA, 100 nM) significantly reduced the HE-induced maximal relaxation, while indomethacin (3 μM) potentiated the HE response. Finally, the HE caused a concentration-dependent and long-lasting inotropic effect in the rat right atrium, contracting spontaneously with a mean EC50 value of 409 μg mL−1.
It is suggested that the effects of the HE of R. ligustrina on smooth and cardiac muscles ‘in-vitro’ may result from its ability to interact, at least partially, with the cAMP pathway.
Characteristics of Shed Snake Skin Permeability to Indomethacin and Fatty Alcohols
Authors: Kuramoto M , Tanaka T , Makita H , Nakamura Y , Yata N 
Published: April 2011

Abstract
To investigate the utilities of a shed snake skin as a model membrane for preclinical studies of transdermal drug delivery, the flux of indomethacin was determined under various conditions by using a diffusion cell. The flux of fatty alcohols was determined and compared with that in human skin reported in references. The esterase activity of shed snake skin was also determined.
It was found that the flux of indomethacin decreased with an increase of pH and the amount of ethanol in a vehicle. The flux of indomethacin increased by the addition of Azone, N-methyl−2−pyrroridone and N,N-dimethyl-m-toluamide in the cream.
The flux of fatty alcohols in shed snake skin was greater than that reported in human skin, and shed snake skin had similar esterase activity to human skin.
Kinetic Studies of N-Allenic Analogues of Tryptamine as Monoamine Oxidase Inhibitors
Authors: Perez V , Marco J L , Fernandez-Alvarez E , Unzeta M 
Published: April 2011

Abstract
A series of N-allenic analogues of tryptamine in which the side chain is located at the 2 position of the indole ring, but which differed in the ring and side-chain nitrogen substituents, were assayed kinetically as MAO A and MAO B inhibitors.
All the compounds studied were mechanism-based inhibitors. The kinetic constants of each inhibition step Ki and ki, were determined for both MAO A and B. The data obtained indicated that these allenic derivatives show a greater selectivity and potency towards MAO A as inhibitors than the corresponding acetylenic derivatives.
7−Ethoxy−3,4−dimethylcoumarin: A Substrate for a Cytochrome p450-mediated Mono-oxygenase Activity that is Highly Induced by Phenobarbitone and β-Naphthoflavone
Authors: Giurnazi Ali Mansour , Garle Michael J , Lal Kishan , Fry Jeffrey R 
Published: April 2011

Abstract
The O-dealkylation of 7−ethoxy−3,4−dimethylcournarin in rat liver microsomes was catalysed in a typical cytochrome P450−mediated reaction as judged by cofactor requirement and inhibition criteria, and displayed monophasic Michaelis-Menten kinetics. When measured at low substrate concentration, this activity was highly inducible by treatment with phenobarbitone or β-naphthoflavone (44−and 78−fold induction, respectively). These data indicate the potential usefulness of this activity as a probe for P4501A1−and P4502B-mediated activities. The O-dealkylation of 7−methoxy-and 7−propoxy−3,4−dimethylcoumarin were much less inducible.
Inhibitory Effect of Pentobarbital on Biliary Excretion of Diclofenac in a Rat Liver Perfusion System
Authors: Fukuyama Takako , Yamaoka Kiyoshi , Tabata Kenji , Nakagawa Terumichi 
Published: April 2011

Abstract
The effect of pentobarbital on the biliary excretion of diclofenac was investigated in a rat liver perfusion system following a pulse input of the drug.
Without albumin in the perfusate, a trace amount of diclofenac was detected in the outflow from the liver (&lt; 0.1%). The total biliary excretion of diclofenac (intact diclofenac plus its glucuronide) decreased from 23.8% (diclofenac 6.01, glucuronide 17.8%) to 16.3% (diclofenac 5.09, glucuronide 11.2%) with an increase in the perfusate concentration of pentobarbital from 0 to 2.5 μg mL−1. At pentobarbital concentrations exceeding 2.5 μg mL−1, the biliary excretion of diclofenac and its glucuronide (14% total diclofenac) was not reduced further. The mean local excretion times of both diclofenac and its glucuronide were approximately 17 min and were unchanged at all pentobarbital concentrations tested. The ratios of biliary excreted diclofenac and its glucuronide to total diclofenac were 22 and 78%, respectively, and these values were virtually constant at all concentrations of pentobarbital in the perfusate.
These results suggest that the glucuronidation of diclofenac and the biliary excretion of its glucuronide are rapid processes and that pentobarbital blocks a step before glucuronidation.
Interaction between Fenbendazole and Piperonyl Butoxide: Pharmacokinetic and Pharmacodynamic Implications
Authors: Benchaoui H A , Mckellar Q A 
Published: April 2011

Abstract
The effect of the cytochrome P450 inhibitor, piperonyl butoxide on the pharmacokinetics and anthelmintic efficacy of the benzimidazole compound fenbendazole was studied in sheep and goats.
Pretreatment of goats with the inhibitor caused a greater than three-fold increase in the relative bioavailability of fenbendazole and fenbendazole sulphoxide. A pharmacokinetic dose titration study was carried out in sheep with fenbendazole (5 mg kg−1) and piperonyl butoxide administered orally at 0, 15, 31, 63, 125 and 250 mg kg−1. The AUC of fenbendazole and the sulphoxide were significantly increased when fenbendazole was co-administered with piperonyl butoxide at dose rates equal to or higher than 31 mg kg−1. Peak plasma concentrations (Cmax) and mean residence time (MRT) were also significantly increased.
The efficacy of the combination was assessed in sheep against two species of benzimidazole-resistant abomasal nematodes; Ostertagia circumcincta and Haemonchus contortus. The percentage reduction in the total number of O. circumcincta worms was 7.9% (fenbendazole) and 97.8% (fenbendazole-piperonyl butoxide). For H. contortus, the percentage reduction was 84.8% (fenbendazole) and 99.0% (fenbendazole-piperonyl butoxide).
The in-vitro S-oxidation of fenbendazole and fenbendazole sulphoxide was studied using microsomal preparations from rat liver. Piperonyl butoxide inhibited significantly the sulphoxidation and sulphonation of fenbendazole.
It was concluded that piperonyl butoxide inhibited the oxidative conversion of fenbendazole into inactive metabolites and this resulted in a potentiated anthelmintic action.
Antidiarrhoeal Activity of New Thiazolidinones Related to Loperamide
Authors: Diurno M V , Izzo A A , Mazzoni O , Bolognese A , Capasso F 
Published: April 2011

Abstract
A series of thiazolidinones related to loperamide was synthesized and evaluated for antidiarrhoeal activity in mice, using the castor oil test.
Of five compounds tested, antidiarrhoeal activity was found only for 2−(p-nitrophenyl)−3−{3−[(4−(p-chloro-phenyl)-4−hydroxy)piperidino]ethyl}-1,3−thiazolidin−4−one. The compound was less active than loperamide (ED50 values = 48.7 (24.8−95.6) and 0.91 (0.24−3.40) mg kg−1, respectively), but was also less toxic (LD50 values = 745.9 (545.2−929.8) and 108.9 (85.5−138.7) mg kg−1, respectively). Its antidiarrhoeal activity was counteracted by naloxone.
Our results support the hypothesis that this compound, like loperamide, is an opiate-receptor agonist.
Comparative Cardiovascular Effects of the Angiotensin II Type 1 Receptor Antagonists ZD 7155 and Losartan in the Rat
Authors: Junggren Inga-Lill , Zhao Xiaohe , Sun Xiangying , Hedner Thomas 
Published: April 2011

Abstract
Binding experiments show that ZD 7155 is a potent angiotensin II type 1 receptor antagonist. In this study this novel substance was studied in normotensive and hypertensive rats.
The relative potency and duration of the antihypertensive effects of ZD 7155 were compared with those of the reference substance, losartan. The inhibitory effects of both compounds on angiotensin II-induced pressor actions were studied in the conscious normotensive Sprague-Dawley (SD) rat and in the conscious, spontaneously hypertensive rat (SHR). Arterial blood pressure and heart rate (HR) were obtained by direct intraarterial recording. Angiotensin II infusion was administered intravenously in the dose range 53.3 ng—12.8 μg kg−1 min−1 to the conscious rats. ZD 7155 was administered in a bolus dose of 1.082 μmol kg−1 (0.51 mg kg−1) and losartan in bolus doses of 2.165 and 6.495 μmol kg−1 (1.0 and 3.0 mg kg−1). In conscious SD rats, ZD 7155 and losartan behaved as competitive antagonists and the pressor response curve to angiotensin II was shifted to the right. Experiments in conscious SD rats also showed that ZD 7155 was approximately ten times as potent as losartan in suppressing the angiotensin II-induced pressor response (240 ng kg−1; 10 min infusion). In addition, experiments with conscious rats demonstrated that ZD 7155 could suppress the angiotensin II-induced pressor response for approximately 24 h when ZD 7155 was administered intravenously in a 1.082 μmol kg−1 bolus dose and angiotensin II was given at 240 ng kg−1 (in a 10−min infusion). Experiments in conscious SHRs using ZD 7155 (1.082 μmol kg−1) and losartan (6.495 μmol kg−1) as intravenous boluses indicated that both ZD 7155 and the reference compound losartan exhibited a significant antihypertensive effect. These results demonstrate that ZD 7155 is a potent angiotensin II-type 1 antagonist which is approximately ten times as potent as losartan in suppressing the angiotensin II-induced pressor response. Furthermore, ZD 7155 may suppress the angiotensin II-induced pressor response for 24 h and in the SHR ZD 7155 induces a pronounced and persistent antihypertensive effect.
Synthesis and Anticonvulsant Activity of Some 1,2,3,3a-Tetrahydropyrrolo[2,1-b]-benzothiazol-, -thiazol-or -oxazol−1−ones in Rodents
Authors: Trapani Giuseppe , Franco Massimo , Latrofa Andrea , Carotti Angelo , Cellamare Saverio , Serra Mariangela , Ghiani Cristina A , Tuligi Graziella , Biggio Giovanni , Liso Gaetano 
Published: April 2011

Abstract
To identify more potent anticonvulsant agents and to gain insights into the structural properties determining the potency of a new class of anticonvulsants, some 3a-substituted tetrahydropyrrolo[2,1-b]benzothiazol-1−ones (1a-d) and the thiazole and oxazole analogues (2a-c and 3a-c, respectively) have been synthesized and tested for anticonvulsant activity against isoniazid-induced seizures in rodents.
The most active compound, 2a, with a median effective dose (ED50, i.p.) of 24.3 mg kg−1 and 15.9 mg kg−1 in mice and in rats, respectively, was more extensively investigated and found to strengthen the effects of diazepam. No clear correlation was observed between the anticonvulsant activity and molecular lipophilicity descriptors of compounds 1−3. Structural similarity between the antiepileptic drug phenobarbital and compounds 1−3 was evidenced by molecular modelling studies and used to derive preliminary structure-activity relationships.
The results demonstrate that 2a is an attractive candidate as an anticonvulsant agent worthy of further study and may help the design of other anticonvulsant drugs.