bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effect of Age on the Gastrointestinal Absorption of Acyclovir in Rats
Authors: Fujioka Yūko , Mizuno Nobuyasu , Morita Emiko , Motozono Hitomi , Takahashi Koichi , Yamanaka You , Shinkuma Denji 
Published: April 2011

Abstract
Drug elimination from the body after intravenous administration of acyclovir (20 mg kg−1) was delayed in 1-week-old rats but the pharmacokinetic data for 2–5-week-old rats were the same as those for 8-week-old rats. The areas under the plasma concentration-time curves at 0–∞ h (AUC) after oral administration of acyclovir (20 mg kg−1) decreased with increasing age. The absolute bioavailabilities for 1-, 2·5-, 3- and 8-week-old rats were 77·59, 51·52, 14·61 and 7·30%, respectively. The gastrointestinal absorption of poorly absorbed acyclovir was good for rats younger than 2·5 weeks but dropped abruptly between 2·5 and 3 weeks of age. The intestinal membrane permeability of acyclovir was studied using the everted sac method. The rate of transfer of an initial concentration of 10 μm acyclovir from the mucosal to the serosal side was constant until 60 min in rats of different ages while the rate in 2–5-week-old rats was significantly greater than that in 3-, 4- and 8-week-old rats. Abrupt in-vivo and in-vitro changes were observed in the experimental results between 2·5- and 3-week-old rats; this period coincided with the weaning period of the rat. The membrane transport mechanism of acyclovir in 2·5- and 8-week-old rats was also studied. Cumulative transferred amounts of acyclovir were linear (r = 0·99) over the range 5 μm–1 min and dose-independent. The influence of metabolic inhibitors (sodium azide, 2,4-dinitrophenol, ouabain), purine and pyrimidine analogues (2-deoxyguanosine, guanine, adenine, uridine) and temperature on the permeation of acyclovir was studied. The permeation of acyclovir was inhibited only by 2-deoxyguanosine and guanine in 2·5-week-old rats. These results suggest that throughout the maturation period, the gastrointestinal absorption mechanism of acyclovir is predominantly via passive diffusion with little or no active or facilitated transport. The abrupt change that occurs during the weaning period is attributable not to facilitated transport but to a change in the factors regarding passive transport.
The Effect of Aminoguanidine Treatment, With or Without Food Restriction on the Liver, Stomach and Small Intestine of the Rat
Authors: Marway Jaspaul S , Preedy Victor R 
Published: April 2011

Abstract
A comparative investigation has been made into the effects of aminoguanidine treatment (60 mg kg−1 day−1) with or without dietary restriction (i.e. 50% reduction in food intake) on the protein, RNA and DNA composition of the liver, small intestine and stomach of young rats (0·1 kg body weight). After 3 weeks of dietary restriction the wet weights of the liver and small intestine decreased by 56 and 52%, respectively. There were significant reductions (approx 50%) in total hepatic and intestinal protein, RNA and DNA. Changes in ratios of RNA/protein, RNA/DNA and protein/DNA were only significant for intestinal RNA/DNA, where a 15% reduction was observed. In contrast, stomach wet weight and total protein content were unaltered by dietary deprivation. Stomach RNA and DNA contents were reduced by only 18–21%, and the protein/DNA ratio increased by 22%. Similar responses of liver, small intestine and stomach to dietary deprivation were observed in aminoguanidine-treated rats. Aminoguanidine-treatment of rats on an unrestricted diet for three weeks had no effect on the wet weights, total protein, RNA or DNA contents of the liver, stomach or small intestine. In dietary-restricted rats, the liver and stomach were unaffected by the treatment. However, aminoguanidine treatment of dietary-restricted rats caused significant increases in the amounts of intestinal protein, RNA and DNA by approximately 15%. The treatment abolished the dietary restriction-induced decrease in total intestinal DNA/body weight. The wet weights of the lung, diaphragm, kidney, spleen and testes of both fed and dietary-restricted rats were also unaffected by aminoguanidine. It was concluded that the stomach is protected against the deleterious effects of nutritional deprivation; the data derived from the small intestine of dietary-restricted rats suggests aminoguanidine may have some potential therapeutic properties as a trophic agent.
Effect of Hydroxyethyl Rutosides and Related Compounds on Lipid Peroxidation and Free Radical Scavenging Activity. Some Structural Aspects
Authors: Rekka Eleni , Kourounakis Panos N 
Published: April 2011

Abstract
Four hydroxyethyl rutosides, 7,3′,4′-trihydroxyethyl quercetin, quercetin and a commercial standardized mixture of hydroxyethyl rutosides were investigated on non-enzymatic lipid peroxidation, for hydroxyl radical scavenging activity and interaction with 1,1-diphenyl-2-picrylhydrazyl stable free radical (DPPH). It was found that the tested compounds exhibited a considerable inhibition of microsomal lipid peroxidation. They were less active than the reference compound quercetin, and this was attributed to their structural characteristics. They were also found to be potent hydroxyl radical scavengers and to interact with DPPH. As hydroxyl radical scavengers, they were more potent than the known hydroxyl radical scavengers mannitol and dimethyl sulphoxide. These properties could be considered as a useful and exploitable combination.
The lipid peroxidation product 4-hydroxy-2,3-trans-1 nonenal decreases rat intestinal smooth muscle function in-vitro by alkylation of sulphydryl groups
Authors: Van Der Vliet A , Van Der Aar E M , Bast A 
Published: April 2011

Abstract
The effects of the lipid peroxidation product 4-hydroxy-2,3-trans-1 nonenal (HNE) on intestinal smooth muscle function have been studied. Exposure of rat isolated small intestinal segments to HNE (0·1–0·5 Mm) led to decreased muscarinic and β-adrenergic responses. The maximal response to the muscarinic agonist methacholine and its pEC50 decreased in a dose dependent manner. The response to the β-adrenoceptor agonist isoprenaline was affected in a similar manner, but at slightly higher concentrations of HNE. As HNE has been described to be sulphydryl-reactive these effects were compared with the effects of the sulphydryl-reactive agent N-ethylmaleimide (NEM). Incubation of intestinal segments with NEM had similar effects on pharmacological responses to methacholine, indicating that the effects of HNE like that of NEM are likely to be caused by alkylation of sulphydryl groups. Dithiothreitol, a compound which reduces oxidized sulphydryl groups, was unable to restore the effects of HNE or NEM, which suggests that the effects of HNE and NEM are irreversible.
Toxicity of amphotericin B emulsion to cultured canine kidney cell monolayers
Authors: Lamb K A , Washington C , Davis S S , Denyer S P 
Published: April 2011

Abstract
The effect of amphotericin B in an emulsion formulation on the integrity of monolayers of kidney cells has been studied. Whereas a conventional solubilized amphotericin formulation (Fungizone, Squibb) caused a loss in monolayer integrity at concentrations above 1 μg mL−1, the emulsion formulation had no measurable effect on confluence at amphotericin concentrations up to 100 μg mL−1. The emulsion retained a comparable antifungal activity to that of Fungizone against Saccharomyces cerevisiae in suspension culture. These results parallel the observed erythrocyte lysis data obtained previously using amphotericin B emulsions, and suggest that the emulsion formulation may have a lower toxicity and improved therapeutic potential over existing formulations.
Thromboxane-mimetic U46619 causes depressor responses in anaesthetized rats
Authors: Hui S-C G , Ogle C W 
Published: April 2011

Abstract
Intravenous (i.v.) or intra-arterial injections of U46619, a thromboxane A2 (TxA2)-mimetic agent, into chloralose-anaesthetized rats dose-dependently decreased the arterial blood pressure. Indomethacin (8 mg kg−1) or atropine (1 mg kg−1), given i.v. 30 min beforehand, attenuated the hypotensive effect of U46619 i.v. whereas methysergide pretreatment (5 mg kg−1 i-v.) was without action. Pretreatment with AH23848 (5 mg kg−1 i.v.), a specific TxA2-receptor antagonist, completely abolished the depressor responses to U46619. The findings suggest that the vasodepressor effect of U46619 appears to be mediated via TxA2-receptor activation, with the release of prostacyclin and/or acetylcholine both of which produce vasodilatation.
Pharmacological characterization of the inhibitory activity of βh-endorphin (βh-EP),[Arg9,19,24,28,29]-)βh-EP,[Gln8,Gly31]-βh-EP-Gly-Gly-NH2, in the neuroeffector junction of the mouse vas deferens
Authors: Valenzuela Raúl , Li Choh Hao , Huidobro-Toro J Pablo 
Published: April 2011

Abstract
The inhibitory opioid activities of βh-endorphin (βh-EP), its structurally related peptide analogues [Gln8, Gly31]-βh-EP-Gly-Gly-NH2 (Gly-Gly-βh-EP), [Arg9,19,24,28,29]-βh-EP (Arg-βh-EP) and methionine enkephalin have been examined in the electrically stimulated mouse vas deferens bioassay. All four peptides behaved as full agonists; methionine enkephalin was the most potent followed by Arg-βh-EP, βh-EP and Gly-Gly-βh-EP. Neither Gly-Gly-βh-EP nor Arg-βh-EP antagonized the inhibitory action of βh-EP or methionine enkephalin. An hour of tissue exposure to 30 Nm β-funaltrexamine followed by thorough washing, displaced to the right, in a parallel fashion, the concentration-response curves of βh-EP and analogues. Whereas the displacement of the concentration response curves was 8 to 10-fold for βh-EP and Arg-βh-EP, it was only about 3-fold for Gly-Gly-βh-EP and methionine enkephalin. Naltrindole was the most potent antagonist of methionine enkephalin with an apparent pA2 of 9·4; its potency as an antagonist of βh-EP and related analogues was approximately one-tenth of this with pA2 values approximately 8·5. Norbinaltorphimine also antagonized the action of the opioid peptides with pA2 values close to 7·8.
Permeability of the blood-brain barrier for atenolol studied by positron emission tomography
Authors: Agon Philippe , Goethals Patrick , Van Haver Dirk , Kaufman Jean-Marc 
Published: April 2011

Abstract
The permeability of the blood-brain barrier for atenolol, a hydrophilic β-adrenergic blocking agent, has been assessed in dogs, by studying the distribution of [11C]atenolol in brain tissue with positron emission tomography. The passage of atenolol into the brain was very limited, but a measurable small net influx into the brain tissues did occur. Osmotic opening of the blood-brain barrier resulted in a marked increase of the atenolol concentrations in brain tissue. The approach described, with sequential non-invasive measurements in brain tissue, is applicable to pharmacokinetic studies of atenolol in man.
Salt Formation of Lactic Acid Oligomers as Matrix for Sustained Release of Drugs
Authors: Wada Ryoichi , Hyon Suong-Hyu , Ikada Yoshito 
Published: April 2011

Abstract
The calcium and sodium salts of l- and d, l-lactic acid oligomers were obtained by immersion of the oligomer powders (weight average mol. wt 3000–10000) in aqueous solutions of CaCl2 and NaCl, respectively, at room temperature (22°C). The salt formation was analysed by atomic absorption measurement. The thermal properties, including glass transition temperature, melting temperature, and softening temperature, were altered by conversion of the terminal free acid of the oligomer to its salt. An in-vitro release test of an anti-cancer drug from the oligomer beads showed that the drug was released more rapidly from the beads prepared from the non-converted oligomers than those prepared from the salts when the release test was carried out in media containing no calcium and no sodium ions.
Effect of Cigarette Smoking on Theophylline Pharmacokinetics in Rats
Authors: Gomita Yutaka , Furuno Katsushi , Eto Kohei , Okazaki Masatoshi , Suemaru Katsuya , Araki Yasunori 
Published: April 2011

Abstract
The effect of acute cigarette smoke inhalation on the plasma levels of theophylline administered orally and parenterally to rats has been studied. The animals were exposed to smoke containing low- or high-nicotine/tar concentration for 10 min immediately after oral, intraperitoneal (i.p.) or intravenous (i.v.) administration of theophylline. The plasma levels of theophylline when administered orally (20 mg kg−1) were lower in the two cigarette smoke-inhaling groups than in the non-smoking restrained control group, with the lowest values in the high-nicotine/tar group. The plasma levels (8 and 12 h after administration) in the high-nicotine/tar group when theophylline was administered i.p. (10 mg kg−1), were also slightly lower than in the non-smoking restrained control group but this was not significant. When theophylline was administered i.v. (5 mg kg−1), there was no difference between the high-nicotine/tar group and the nonsmoking restrained control group. These data indicate that cigarette smoke inhalation causes suppression or delay of theophylline absorption from the gastrointestinal tract.
Development of Tolerance to the Plasma Amino Acid-Decreasing Effect of Ethanol in the Rat
Authors: Hagman Mats , Eriksson Tomas 
Published: April 2011

Abstract
Male Sprague-Dawley rats were treated for one month with daily intraperitoneal injections of ethanol (2 g kg−1), or saline. After this pretreatment, animals from each group were given acute doses of ethanol (2 g kg−1) or saline. Plasma amino acid concentrations and brain tyrosine, tryptophan, dopamine, 5-HT and 5-HIAA concentrations were measured in samples collected 1 h after the injections. Acute administration of ethanol induced a dramatic fall in the concentrations of 18 out of 20 plasma amino acids in animals pretreated with saline. In animals chronically pretreated with ethanol this decrease was much smaller. Furthermore, the decrease was significantly lower for 6 of the measured amino acids in the chronic ethanol group compared with the saline-treated control group. Tolerance to the plasma amino acid decreasing effect of ethanol had thus developed. This acquired tolerance might be explained by both pharmacokinetic and pharmacodynamic mechanisms. Chronic administration of ethanol induced increased concentrations of tyrosine and dopamine in the brain, probably due to increased transport of tyrosine into the brain caused by an increase in the ratio of tyrosine to large neutral amino acids in plasma.
The Synthesis, and Structure-activity Relationships of some Long Chain Acyl Carnitine Esters on the Coronary Circulation of the Rat Isolated Heart
Authors: Criddle D N , Dewar G H , Radniknam M , Wathey W B , Woodward B 
Published: April 2011

Abstract
The synthesis of the isopropyl ester of carnitine and a series of fatty acid derivatives with fatty acid lengths C8-C30 is described. Bolus doses of these compounds (0·03–300 nmol) showed coronary vasodilator activity in the rat isolated heart. Increasing fatty acid chain length from C8 to C16 resulted in an increased vasodilator potency. Longer lasting vasodilation was observed with the C20 compound. Increasing fatty acid chain length to C30 was associated with a small dilator response preceded by vasoconstriction.
M3-Muscarinic Receptor Mediates Prejunctional Inhibition of Noradrenaline Release and the Relaxation in Cat Femoral Artery
Authors: Fernándes Filomena A , Alonso María J , Marín Jesús , Salaices Mercedes 
Published: April 2011

Abstract
The aim of the present study was to analyse the muscarinic receptors involved in the vasodilation elicited by acetylcholine (ACh) and the carbachol inhibition of electrically-evoked [3H]noradrenaline (NA) release in cat femoral artery. For this purpose, the following receptor antagonists were used, atropine, pirenzepine (M1-antagonist), AF-DX 116 (M2-antagonist) and 4-diphenylacetoxy-N-methylpiperidine methobromide (4-DAMP; M3-antagonist). The order of potency (pA2 values) of these drugs at postjunctional level was: atropine (9·7) ≥ 4-DAMP (9·6) &gt; pirenzepine (7·2) &gt; AF-DX 116 (6·0), and at prejunctional level (pIC50 values) was: 4-DAMP (9·3) &gt; atropine (8·5) &gt; AF-DX 116 (7·1) &gt; pirenzepine (5·9). These findings indicate that the muscarinic receptors mediating the vasodilation induced by ACh and the carbachol inhibition of NA release are of the M3-subtype.
The Influence of α1-Acid Glycoprotein on Quinine and Quinidine Disposition in the Rat Isolated Perfused Liver Preparation
Authors: Mansor S M , Ward S A , Edwards G , Hoaksey P E , Breckenridge A M 
Published: April 2011

Abstract
We have studied the effect of 0·5 and 2·0 g L−1 of α1-acid glycoprotein (AAG) on the disposition of quinine and quinidine in the rat isolated perfused liver preparation. The higher concentration of AAG (2·0 g L−1) resulted in a significant decrease in clearance [quinine study (control: 9·6 ±2·9 vs test: 31 ± 1·2 mL min−1); quinidine study (control: 9·8 ± 2·4 vs test: 3·5±1·1 mL min−1)] and volume of distribution [quinine study (control: 1198 ± 416 vs test: 466 ± 95 mL); quinidine study (control: 1352 ± 459 vs test: 317 ± 24 mL)] but not the elimination half-life compared with control. At the lower concentration (0·5 g L−1) of AAG there was no significant difference in clearance, volume of distribution and elimination half-life for either drug compared with control. By increasing the concentration of AAG from 0·5 to 2·0 g L−1 both the hepatic extraction ratio and the fraction of drug unbound when compared with controls significantly decreased by about 66 and 60% for quinine, and by 65 and 58% for its diastereoisomer quinidine, respectively. The consequence of these changes is a substantial increase in the total quinine (or quinidine) concentrations without any change in the free quinine (or quinidine) concentrations. However, at 0·5 g L−1 AAG compared with control, no significant difference was observed in fraction of drug unbound, extraction ratio, total drug concentration or free drug concentration for either drug. In summary, changing concentrations of AAG, an important binding protein for quinine and quinidine, can affect the hepatic disposition of both drugs.
Acoustic emission during the deformation of α-lactose monohydrate and anhydrous α-lactose monocrystals
Authors: Wong D Y T , Waring M J , Wright P , Aulton M E 
Published: April 2011

Abstract
During the deformation of single crystals of α-lactose monohydrate and anhydrous α-lactose in a crushing strength rig, their acoustic activity was monitored using a portable activity meter. The acoustic parameters measured were the average signal level (ASL), count rates and total acoustic counts. Both types of lactose, even though deformed by fragmentation, differed fundamentally in the degree and nature of this fragmentation. Close correlation was observed between the ASL, count rate profiles and the force-displacement profiles. The monohydrate form is acoustically more active than the anhydrous form during deformation. Small internal fractures which were neither visually observed nor detected in the force-displacement profiles (in particular the anhydrous α-lactose) were detected by monitoring the acoustic signals during the deformation of these crystals. This work illustrates the potential of using the acoustic emission technique as an aid in the assessment of the deformation characteristics of pharmaceutical materials during single crystal compression studies.
Antihaemostatic and antithrombotic effect of some antiplatelet agents isolated from Chinese herbs
Authors: Teng Che-Ming , Ko Feng-Nien , Wang Jih-Pyang , Lin Chun-Nan , Wu Tian-Shung , Chen Chien-Chih , Huang Tur-Fu 
Published: April 2011

Abstract
Five antiplatelet agents have been isolated from Chinese herbs. Apigenin and magnolol are inhibitors of thromboxane synthesis, while osthole, protopine and norathyriol are inhibitors of phosphoinositide breakdown. Thirty min after intraperitoneal (i.p.) administration of these drugs, tail bleeding time of mice was prolonged markedly in a dose-dependent manner by norathyriol, protopine, osthole and magnolol, but not by apigenin. However, the antiplatelet agents (up to 200 mg kg−1, i.p.) could not prevent acute thromboembolic death in mice. In endotoxin-induced experimental disseminated intravascular coagulation in rats, norathyriol (50–100 mg kg−1, i.p.) prevented the decrease in platelet counts and fibrinogen, and the prolongation of plasma prothrombin time. Norathyriol (100 mg kg−1, i.p.) also suppressed ex-vivo platelet aggregation induced by collagen and ADP in rat plasma.
α-Methyl analogues of acetylenic amines as striatal muscarinic antagonists
Authors: Sethy Vimala H , Heier Richard F , Moon Malcolm W 
Published: April 2011

Abstract
The effect of acetylenic amines, with or without α-methyl substitution, on striatal acetylcholine (ACh) concentration in rats was investigated. Oxotremorine, oxotremorine-1, and U-77053 (trimethyl (4-(1-pyrrolidinyl)-2 butynyl)-urea), the unsubstituted amines, increased striatal ACh concentration. On the other hand, the corresponding α-methyl substituted analogues, α-methyl-oxotremorine, BM-5, and α-methyl U-77053, decreased the concentration of ACh in the striatum. The results indicate that substitution of α-methyl in acetylenic amines converts compounds from agonists to antagonists for striatal muscarinic receptors.
The Effect of Site of Administration in the Gastrointestinal Tract on the Absorption of Insulin from Nanocapsules in Diabetic Rats
Authors: Michel C , Aprahamian M , Defontaine L , Couvreur P , Damgé C 
Published: April 2011

Abstract
Isobutylcyanoacrylate nanocapsules have been used as drug carriers for the enteral absorption of insulin. Their absorption has been studied by measuring fasted glycaemia in streptozotocin-induced diabetic rats after a single administration of encapsulated insulin (100 units kg−1) at various sites along the gastrointestinal tract. Glycaemia decreased from the second day, the intensity and duration depending on the site of administration (65% ileum, 59% stomach, 52% duodenum and jejunum, 34% colon). This hypoglycaemic effect lasted up to the 18th day after administration for ileum and jejunum, the 15th day for stomach and duodenum, and the 13th day for colon. In-vitro, nanocapsules protect insulin against proteolysis from pepsin, chymotrypsin and trypsin. These results suggest (i) that insulin is protected by nanocapsules in the gastrointestinal tract, (ii) that it is absorbed in an active form, and (iii) that ileum is he most potent site of absorption.
Orally Active Carbamate Prodrugs of the Selective Dopamine Agonist N-0437: In-vivo Activities in the 6-OHDA Turning Model and In-vitro Activities
Authors: den Daas Izaak , De Boer Peter , Tepper Pieter G , Rollema Hans , Horn Alan S 
Published: April 2011

Abstract
The in-vivo activities of eight carbamate prodrugs of the D2-agonist N-0437 were determined by examining the effects of the prodrugs, after their oral administration in rats with unilateral 6-OHDA lesions of the striatum. The resulting contralateral turning was used as an index of the activity of the compounds. A comparison of the area under the curve of the time-effect curves of the prodrugs, revealed a significantly improved duration of action compared with N-0437 during the period 11–15 h after administration, for the propylcarbamate and the dimethoxyphenylcarbamate derivatives. The 2,4-dimethylphenylcarbamate showed a significantly enhanced turning behaviour over the whole 15 h time interval in comparison with N-0437. Three of the nine carbamates were virtually unhydrolysed in rat serum at 37°C, while the other test compounds were hydrolysed relatively slowly, with t 1/2 values ranging from 1.5–6 h. The test compounds differed greatly in partition coefficients, which were estimated by RP-HPLC (1–12 times more lipophilic than N-0437). The potential Cholinesterase inhibiting properties of the carbamate prodrugs were assessed by a simple in-vitro incubation assay, which showed that only two carbamates were very weak Cholinesterase inhibitors.