bluuebunny/crossref_metadata_2025_split huggingface dataset:
Measurement of Protein Synthesis by the Phenylalanine Flooding Dose Technique: Effect of Phenylalanine and Anaesthesia on Plasma Electrolyte, Enzyme and Metabolite Levels
Authors: Preedy Victor R , Hammond Barry , Bottiglieri Teodoro G , Marway Jaspaul S , Peters Timothy J 
Published: April 2011

Abstract
Ten minutes after an intravenous flooding dose of phenylalanine to rats, plasma sodium and calcium concentrations were slightly reduced (by 2–7%) but no effects on potassium or phosphate were observed. Creatine kinase activities were significantly increased by phenylalanine injection (by 39%), but alkaline phosphatase, alanine aminotransferase, lactate dehydrogenase and aspartate aminotransferase activities were unaltered. Plasma concentrations of total proteins, albumin, cholesterol, triglycerides, urea, creatinine and glucose were also unaffected. In the presence of anaesthesia, phenylalanine injection had almost identical effects, although the increase in creatine kinase activities did not reach statistical significance. Anaesthesia for 10 min reduced plasma potassium concentrations (by 27%), and calcium (by 5%), though phosphate and sodium were unaltered. The activities of lactate dehydrogenase, creatine kinase and aspartate aminotransferase were reduced by between 36–52%, but alkaline phosphatase and alanine aminotransferase activities were unaltered by anaesthesia. Plasma concentrations of total proteins and albumin were also reduced (both by 9%), but glucose concentrations were increased (by 33%). Anaesthesia had no other significant effects on cholesterol, triglycerides, urea or creatinine concentrations. The qualitative effects of anaesthesia in the presence of raised free phenylalanine concentrations were similar. It was concluded that, except for creatine kinase, determinations of plasma constituents in phenylalanine-injected rats could be made without overt interpretational errors. However, caution is required in interpreting data on plasma constituents from anaesthetized rats.
The Disposition of a Histidine Decarboxylase Inhibitor (S)-α-Fluoromethylhistidine in Rats
Authors: Sakurai Eiichi , Niwa Hiroshi , Yamasaki Seiji , Maeyama Kazutaka , Watanabe Takehiko 
Published: April 2011

Abstract
An amino acid analyser method using ninhydrin was developed for (S)-α-fluoromethylhistidine (FMH) with a minimum quantitation limit of 0.2 μg mL−1. The assay was used to study the kinetics of FMH in rat. After bolus intravenous administration of FMH hydrochloride hemihydrate (50 mg kg−1), plasma concentration decreased biexponentially with half-lives of 4.4 and 32.7 min. The distribution volumes of the central and peripheral compartments were 127.4 and 166.3 mL kg−1, respectively. The tissue concentration of FMH was highest in the kidney and also decreased biphasically. The FMH concentrations in other tissues were lower, but their tissue/plasma ratios of FMH increased continuously after FMH injection, indicating that FMH partitioned into these tissues and was lost from them very slowly.
Dose-dependent decrease in rat plasma amino acids after acute administration of ethanol
Authors: Hagman Mats , Eriksson Tomas 
Published: April 2011

Abstract
Male rats were given three different doses of ethanol in i.p. injections (0.66, 1.33 and 200 g kg−1). A dose-dependent decrease in the concentrations of most plasma amino acids was observed. For the total amino acid concentration this decrease was 5, 16 and 22%, respectively, compared with a saline-treated control group. It has previously been suggested that the oxidation of ethanol plays an important role in the amino acid decreasing effect of ethanol. In this study the lowest dose used (0.66 g kg−1) was calculated to be high enough to keep the enzyme systems involved in ethanol oxidation saturated during the 60 min course of the experiment. The observation that the ethanol-induced decrease in plasma amino acid levels was more pronounced with higher ethanol doses indicates that not only the oxidation of ethanol but also ethanol itself is important in the effect of ethanol on plasma amino acid concentrations.
Effect of gamma-irradiation on disposition of the local anaesthetic, carbisocaine in rabbits
Authors: Kállay Z , Ďurišová M , Trnovec T , Svoboda V 
Published: April 2011

Abstract
14C Labelled carbisocaine, a local anaesthetic agent, has been administered intravenously in a dose of 2 mg kg−1 to rabbits 7 days after whole-body 60Co gamma-irradiation with a dose of 5 Gy (1.9 Gy min−1) and to control rabbits. The plasma carbisocaine concentration-time courses were approximated by biexponential equations. The estimated pharmacokinetic parameters obtained when the data were fitted to an open two-compartment model were significantly different for the irradiated group relative to control animals, indicating a radiation-induced slower elimination rate of carbisocaine: AUC: 0.37 vs 0.29% dose min mL−1, CLtot: 109.8 vs 155.4 mL min−1, Vdss: 27.6 vs 33.2 mL kg−1, kel: 0.0259 vs 0.0307 min−1, MRT: 251.7 vs 214.6 min. The total excreted amount of 14C radioactivity in the irradiated group was lower in comparison with controls: 6.5 vs 8.7% in bile and 18.3 vs 23.7% in urine. However, lower carbisocaine concentrations were recorded in the heart, lungs, liver, and kidneys of irradiated rabbits compared with controls.
Evaluation of contraction time and recovery period as a parameter in the calcium antagonistic action on the K+-depolarized rat duodenum
Authors: Öztürk Yusuf , Altinkurt Orhan , Yildizoǧlu-Ari Nuray , Altan V Melih 
Published: April 2011

Abstract
Verapamil, nifedipine, phentolamine, tolazoline, gentamicin and neomycin inhibited calcium-induced contractions of K+-depolarized duodenum of the rat by shifting the concentration-response curves to the right. Non-competitive inhibitions were observed with trifluoperazine, lidoflazine, procaine and tetracaine. Lanthanum behaved as a partial agonist in this preparation, while nitroprusside was ineffective. Contraction times in the presence of the antagonists and recovery time of the Ca2+ responses after the removal of the antagonists from the bathing medium were evaluated. From the findings, it is suggested that the contraction time and the time required for tissue recovery after removal of a Ca2+ antagonist are parameters making K+-depolarized rat duodenum a potential tool for the evaluation of the pharmacological effects of Ca2+ antagonists.
1H NMR as an analytical tool for the investigation of hydrolysis rates: a method for the rapid evaluation of the shelf-life of aqueous solutions of drugs with ester groups
Authors: Ferdous Abu J , Dickinson Noel A , Waigh Roger D 
Published: April 2011

Abstract
The rate of hydrolysis of esters of primary and secondary alcohols can be determined quickly and easily by 1H NMR in aqueous solution, provided that the water signal is suppressed by the WATR (Water Attenuation by T2 Relaxation) method. To evaluate this approach, Arrhenius plots have been constructed for hydrolysis of acetylcholine, carbachol and atropine, and the effect of pH on the hydrolysis of procaine has been determined over a limited range. The results agree well with literature values for rate constants.
N
G-Monomethyl-l-arginine and NG-nitro-l-arginine inhibit endothelium-dependent relaxations in human isolated omental arteries
Authors: Vila J , Esplugues J V , Martinez-Cuesta M A , Martinez-Martinez M C , Aldasoro M , Flor B , Lluch S 
Published: April 2011

Abstract
The L-arginine analogues NG-monomethyl-l-arginine (l-NMMA, 10−4 m) and NG-nitro-L-arginine methyl ester (l-NAME, 10−4 m), which specifically inhibit the synthesis of nitric oxide from l-arginine, significantly reduced acetylcholine-induced endothelium-dependent relaxations in rings of human omental arteries. The inhibitory potency of l-NMMA and l-NAME was similar. Addition of l-NMMA or l-NAME to the organ bath did not induce any significant changes in the resting tension of the tissues. The effects of l-NMMA were reversed by l-arginine (3 × 10−4 m). The l-NMMA enantiomer, d-NMMA (10−4 m), did not influence either the basal tone of the preparation or the relaxing effects of acetylcholine. Arterial relaxations induced by sodium nitroprusside (10−6 m) were not influenced by incubation with l-NMMA or l-NAME. These results suggest that endothelium-dependent relaxations in human omental arteries are mediated by the endogenous and substrate-specific generation of nitric oxide from l-arginine.
Theophylline reduces pulmonary eosinophilia after various types of active anaphylactic shock in guinea-pigs
Authors: Tarayre J P , Aliaga M , Barbara M , Malfetes N , Vieu S , Tisne-Versailles J 
Published: April 2011

Abstract
The action of theophylline was studied on the inflammatory reaction obtained in bronchoalveolar lavage fluid 24 h after an active anaphylactic shock had been induced by ovalbumin inhalation in conscious sensitized guinea-pigs. The compound was administered twice by intraperitoneal administration after the anaphylactic reaction at a dose of 50 mg kg−1. When the guinea-pigs were sensitized by intramuscular injection of 30 mg kg−1 ovalbumin or by ovalbumin aerosol, theophylline reduced the number of eosinophils and mononuclear cells in the fluid. When animals were sensitized by intramuscular injection of 30 mg kg−1 ovalbumin mixed with Freund's complete adjuvant, treatment with the xanthine derivative decreased only the number of eosinophils. In the three models theophylline did not modify significantly the number of neutrophils. Thus theophylline always reduced pulmonary eosinophilia irrespective of the mode of sensitization used to induce anaphylactic shock.
Transport characteristics of ceftibuten, cefixime and cephalexin across human jejunal brush-border membrane
Authors: Sugawara Mitsuru , Iseki Ken , Miyazaki Katsumi , Shiroto Hiroshi , Kondo Yukifumi , Uchino Jun-Ichi 
Published: April 2011

Abstract
The transport characteristics of orally active cephalosporins, ceftibuten, cefixime and cephalexin have been examined using brush border membrane vesicles isolated from human jejunum. In the initial uptake of ceftibuten, the stimulation and overshoot phenomena were observed in the presence of an inward H+ gradient. Effects of H+ gradient on the uptake of cefixime and cephalexin were low and no overshoot was observed. These transport characteristics, especially uphill transport phenomena, were in agreement with previous results obtained from rat intestinal brush-border membrane vesicles and suggest that these β-lactam antibiotics are absorbed by different transport systems, despite their similar molecular structures.
A novel bradykinin antagonist with improved properties
Authors: Lammek Bernard , Wang Yi-Xin , Gavras Irene , Gavras Haralambos 
Published: April 2011

Abstract
Acylation of the N-terminus of [d-Arg0, Hyp3, Thi5.8, d-Phe7] bradykinin with 1-adamantanecarboxylic acid results in an analogue with enhanced potency of at least 33-fold. The new antagonist has potential as a pharmacological tool in the investigation of the role of endogenous bradykinin in cardiovascular regulation.
The Site of Inversion of R(–)-Ibuprofen: Studies Using Rat In-situ Isolated Perfused Intestine/liver Preparations
Authors: Jeffrey Phillip , Tucker Geoffrey T , Bye Alan , Crewe H Kim , Wright Paul A 
Published: April 2011

Abstract
The site of metabolic inversion of R(–)-ibuprofen to the pharmacologically active S(+)-enantiomer has been investigated using an array of in-situ rat perfused organ preparations allowing vascular perfusion (55–60 min) of the separate or combined intestine and liver. After addition of R(–)-ibuprofen (20 mg kg−1 body weight) to the closed (static) lumen of isolated 25 cm lengths of duodenum, jejunum or ileum, and single-pass vascular perfusion, both isomers were measured in the lumen and in vascular perfusate plasma (mean plasma AUC values (±s.d., μg mL−1 min, n = 5) R(–)-ibuprofen: 1669±115 (duodenum), 1687 ± 203 (jejunum), 2061 ±188 (ileum); S(+)-ibuprofen: 23 ± 6 (duodenum), 14 ±5 (jejunum), 26±1 (ileum)). Addition of the same dose of 5(+)-ibuprofen to the jejunum (n = 5) resulted in AUC values of 1864 ± 238 for 5(+)-ibuprofen and 6±3 for R(–)-ibuprofen. After addition of R(–)-ibuprofen (30 μg mL−1) to the recirculating vascular perfusate (100 mL) of the entire small intestine (n = 6) AUC values were 1647 ± 34 for R(–)-ibuprofen and 13 ± 3 for S(+)-ibuprofen. The same dose of R(–)-ibuprofen to combined intestine/liver (n = 6) and liver only preparations (n = 6) gave AUC values of 1011 ± 25 and 1021 ± 49 for R(–)-ibuprofen and 220 ± 28 and 238 ± 22 for 5(+)-ibuprofen, respectively. In all experiments, except those involving perfusion of the combined intestine/liver and the liver, the concentrations of the isomer opposite to that administered could be accounted for solely by the level of enantiomeric impurity (1·3% for R(–)-ibuprofen and 0·6% for S(+)-ibuprofen). We conclude that inversion of R(–)-ibuprofen to the S(+) antipode occurs in the liver but does not occur on either mucosal or serosal sides of the small intestine of the rat.
Rectal Bioavailability of Water-Soluble Drugs: Sodium Valproate
Authors: Margarit María Victoria , Rodriguez Inés Carmen , Cerezo Antonio 
Published: April 2011

Abstract
The influence of adjuvants in suppository formulations on the release and absorption of sodium valproate, a water soluble anti-epileptic, was analysed in order to determine the optimal formula for rectal administration. Three formulations were prepared with Suppocire AS2(formula I), Aerosil R 972 (formula II) or Span 80 (formula III). In-vivo and in-vitro release-diffusion studies were performed using white laboratory rabbits as the experimental model. The adjuvants decreased the percentage release of valproic acid to 96·7% (formula I) and 84·1% (formula II), and delayed peak release-diffusion concentration (210 and 150min, respectively, with formulas II and III in comparison with 120 min with formula I). Their effect on bioavailability was observed as an increase in plasma levels of the active substance, with areas under the plasma concentration/time curve of 396·26 and 306·64 μg h mL−1 (formulas II and III, respectively) and 243·28 μg h mL−1 (formula I). The time to peak plasma concentration was also delayed with peaks at 30, 55 and 50 min with formulas I, II and III, respectively.
The influence of sampling chamber dimensions on aerosol particle size measurement by cascade impactor and twin impinger
Authors: Fults K , Cyr T D , Hickey A J 
Published: April 2011

Abstract
The influence of the sampling chamber dimensions upon particle size estimation by cascade impaction has been investigated and compared with measurements by the twin impinger. Aerosols of salbutamol and disodium fluorescein (DF) were generated from pressurized metered dose inhalers. The mass median aerodynamic diameter (MMAD) by the Andersen Impactor for salbutamol ranged from 2·0 to 2·8 μm with geometric standard deviations (g.s.d.) of 1·7 to 2·4. These observations were independent of the distance travelled to the first impaction surface of the impactor and volume of the sampling chamber. The DF MMAD ranged from 5·0 to 6·9 μm with g.s.d. values of 1·7 to 1·8. Changes in droplet size within the sampling chamber may cause significant differences in particle size estimates as indicated by the cascade impaction data for DF. The respirable fraction of the salbutamol samples was similar whether determined by impaction or using the impinger. The latter device has previously been indicated to give clinically relevant estimates of respirable fraction for commercial inhalation aerosol devices.
The effect of the uptake of particles on the chemotaxis of polymorphonuclear leucocytes in-vitro
Authors: Hyde R , Lewis D A , Taylor P W 
Published: April 2011

Abstract
The relationship between the phagocytic uptake of latex microspheres (11 μm diam.) and the mobility of rat polymorphonuclear leucocytes (PMNLs) has been investigated in-vitro. The movement of PMNLs was found to be independent of the uptake of particles but about half of the PMNLs were not receptive to the chemo-attractant N-formylmethionyleucylphenylalanine. However, the uptake of particles was greater when particle/cell ratios were high and the greatest number of particles were carried into a cellulose nitrate filter by chemotaxis at the highest particle/cell ratio of 30:1.
Studies on antiparasitic agents: effect of the lactam nucleus substitution in the 2-position on the in-vitro activity of new 5-nitroimidazoles
Authors: Vanelle P , Maldonado J , Gasquet M , Delmas F , Timon-David P , Jentzer O , Crozet M P 
Published: April 2011

Abstract
The in-vitro antiprotozoal activity of a series of new 5-nitroimidazoles substituted in the 2-position via a lactam nucleus was studied. All these compounds exhibited a better effect than metronidazole and structure-activity relationships are discussed.
Endothelin-induced contractions of rat pulmonary artery are not affected by drugs acting on potassium channels
Authors: Wanstall Janet C , O'Donnell Stella R 
Published: April 2011

Abstract
The effects of the potassium channel opening drug, pinacidil, and the potassium channel closing drug, tetraethylammonium (TEA), on concentration-response (contraction) curves to spasmogens on rat pulmonary artery were examined. Pinacidil (3 μM) decreased, and TEA (2 Mm) increased contractions to 5-hydroxytryptamine (5-HT) more than it did to noradrenaline but contractions to endothelin −1 were only minimally affected. It is concluded that the mechanism whereby endothelin-1 contracts rat pulmonary artery differs from that of noradrenaline or 5-HT in that it does not involve membrane depolarization or calcium entry through voltage operated calcium channels.
Synthesis, Biological Evaluation and Quantitative Structure Activity Relationship Analysis of Nuclear-substituted Pargylines as Competitive Inhibitors of MAO-A and MAO-B
Authors: Ali Anmar , Robinson J B 
Published: April 2011

Abstract
A series of nuclear substituted derivatives of pargyline has been prepared and tested (under controlled conditions designed to measure the competitive component of the inhibition) as competitive inhibitors of MAO-A and -B. Adequate correlation of the biological data with the physicochemical constants of substituent groups was obtained only when the m- and p-substituted derivatives were considered separately. Due to the narrow range of activity displayed by the p-substituted derivates when inhibiting MAO-B, meaningful correlations were not found. However, the inhibition of MAO-B by the m-substituted derivatives required the inclusion of the Verloop L parameter for adequate correlation, suggesting that the inhibitor binding site of MAO-B is present within a cavity of more limited lateral dimensions than that present on the MAO-A surface. Inhibition of both MAO-A and -B demonstrated a parabolic relationship between inhibitory activity and π. Whereas this parabolic relationship showed a maximal value for inhibition of MAO-A (mean πo = 0·86), inhibition of MAO-B demonstrated a minimal value of π (πmin= −0·5) i.e. the optimal value of π for inhibition of MAO-B has not been achieved for this series of compounds but such would be greater than that demonstrated for MAO-A. The Hammett σ function was important or significant only in the inhibition of MAO-A by the p-substituted derivatives.
An Investigation into the Haematological Toxicity of Structural Analogues of Dapsone In-vivo and In-vitro
Authors: Coleman M D , Tingle M D , Hussain F , Storr R C , Park B K 
Published: April 2011

Abstract
With microsomes prepared from a single human liver, 4,4′-diaminodiphenyl sulphone (DDS), 4-acetyl-4-aminodiphenyl sulphone (MADDS), 4-acetyl-4-aminodiphenyl thioether (MADDT) and 4,4′-diacetyldiphenyl thioether (DADDT) caused significantly greater methaemoglobin formation compared with control. In-vitro in the rat, the pattern of toxicity was slightly different: DADDT was not haemotoxic, whilst 3,4′-diaminodiphenyl sulphone (3,4′DDS) and 3,3′-diaminodiphenyl sulphone (3,3′DDS) as well as DDS, MADDS and MADDT were significantly greater than control. 4,4′ Acetyl diphenyl sulphone (DADDS), 4,4′ diaminodiphenyl thioether (DDT), 4,4′-diaminodiphenyl ether (DDE) and 4,4′ diamino-octofluorodiphenyl sulphone (F8DDS) did not cause significant methaemoglobinaemia in either human or rat liver microsomes. DDS, MADDS, and MADDT were not significantly different in haemotoxicity generation in-vitro in the presence of human microsomes. In the rat in-vitro, DDS, MADDS, and 3,4′DDS did not differ significantly in red cell toxicity, and were the most potent methaemoglobin formers. The 3,3′ DDS and MADDT derivatives were both significantly less toxic compared with DDS. None of the compounds tested caused haemoglobin oxidation in the absence of NADPH in-vitro. In the whole rat, DDS, MADDS and MADDT caused significantly higher levels of methaemoglobin compared with control. None of the remaining compounds caused methaemoglobin formation which was significantly greater than control. DDS and MADDS were the most potent methaemoglobin formers tested, in-vivo and in-vitro. The 3,3′ and 3,4′DDS analogues caused no detectable haemotoxicity in-vivo. However, the plasma elimination of the 3,4′ analogue was much more rapid compared with that of DDS. Overall, there was no correlation between log k0 and increasing haemotoxicity. The use of the two-compartment system together with in-vivo studies may be applied to the evaluation of the structural features required for bioactivation of candidate antiparasitic compounds to haemotoxic metabolites by cytochrome P450 enzymes.
Importance of Two Arginine Residues in Lapemis Postsynaptic Neurotoxins: Re-examination using Acetylcholine Receptor-neurotoxin Complex Instead of Free Toxin
Authors: Mori Nobuhiro , Tu Anthony T 
Published: April 2011

Abstract
The role of the three arginine residues in Lapemis neurotoxin has been re-examined using an acetylcholine receptor-toxin complex. The receptor-bound neurotoxin was treated with phenylglyoxal to modify available arginine residues. The positions of the modified arginine residues were then identified from the amino acid sequences of proteolytically digested fragments of the detached neurotoxin. The result was compared with the result from modification of the free Lapemis toxin (unbound). Arg-31 and Arg-34 were not modified when Lapemis toxin was bound to receptor although they were modified when the toxin was not bound to receptor. It was concluded that Arg-31 and Arg-34 residues are involved in the toxin-receptor interaction.
In-vitro interaction of mitomycin C and streptomycin A with collagen
Authors: Ramesh D Vijaya , Sehgal Praveen K 
Published: April 2011

Abstract
Mitomycin C and streptomycin A were studied for their interaction with soluble collagens from sepia, fish and rat skins using UV absorption spectroscopy at pH 7·4 and 3·0 and equilibrium dialysis. Both the drugs bound to collagen as shown from association constants and could be quantitatively recovered by prolonged dialysis against water showing formation of dissociable bonds between drug and collagen. At pH 7·4, mitomycin C showed greater binding affinity than streptomycin A with collagen from all three species. The reverse trend was seen at pH 3·0. Binding capacity of sepia and fish skin collagens for streptomycin A at pH 3·0 was found to be significantly greater than for mitomycin C.