bluuebunny/crossref_metadata_2025_split huggingface dataset:
The effect of intramolecular hydrogen bonding on the thermodynamics of partitioning of an isomer of the histamine H2-receptor antagonist metiamide
Authors: Mitchell R C , Dunkley D 
Published: April 2011

Abstract
The thermodynamics of transfer from water to 1−octanol of the 4 and 5 substituted N-methylimidazole isomers of the H2-receptor antagonist metiamide have been determined. The isomers have similar free energies of transfer but the enthalpy and entropy of transfer of the 4−isomer are substantially greater than those of the 5−isomer. This indicates that the 4−isomer forms an intramolecular hydrogen bond in the polar octanol phase.
Hypouricaemic effect after oral administration in chickens of polyethylene glycol-modified uricase entrapped in liposomes
Authors: Nishida Y , Kamatani N , Miyamoto T 
Published: April 2011

Abstract
Liposomal-entrapped methoxypolyethyleneglycol (PEG) modified uricase was used to study the plasma urate lowering effect after its oral administration to chickens. Plasma uric acid concentrations fell gradually and were accompanied by a rise in plasma uricolytic activity. Serum from chickens given PEG-modified uricase liposomes did not react with native uricase in immunodiffusion plates. These results suggested the clinical usefulness of liposome-entrapped PEG modified uricase in the treatment of hyperuricaemia.
Tropolone antagonism of the l−dopa-induced elevation of S-adenosylhomocysteine: S-adenosylmethionine ratio but not depletion of adrenaline in rat hypothalamus
Authors: Fuller Ray W , Perry Kenneth W , Hemrick-Luecke Susan K 
Published: April 2011

Abstract
Tropolone, an inhibitor of catechol O-methyl transferase, largely prevented the increase in SAH: SAMe ratio in rat hypothalamus following l−dopa injection. Tropolone did not prevent but instead enhanced the decrease produced by l−dopa of adrenaline concentration in rat hypothalamus. The results imply that the decrease in hypothalamic adrenaline concentration following l-dopa injection was not caused by the increase in SAH: SAMe ratio.
An in-vitro test for the duration of action of insulin suspensions
Authors: Graham D T , Pomeroy A R 
Published: April 2011

Abstract
A method is described which measures the prolongation effects of commercial insulin suspensions by monitoring the rate of solution of an insulin suspension into a phosphate buffer, pH 7·4, at 37°C. The method can rapidly categorize an insulin into the clinical classifications of either fast, intermediate or slow acting. It offers advantages of speed and sensitivity over the British Pharmacopoeial test for prolongation of insulin effect in fasted animals. Large differences between the dissolution rates of commercial samples of isophane insulin were observed which suggested a lack of bioequivalence.
Differential effects of caffeine on dihydroxyphenylacetic acid concentrations in various rat brain dopaminergic structures
Authors: Govoni S , Petkov V V , Montefusco O , Missale C , Battaini F , Spano P F , Trabucchi M 
Published: April 2011

Abstract
The behavioural and neurochemical effects of caffeine were examined in rats. The intraperitoneal administration of different doses of caffeine significantly decreased DOPAC concentrations in striatum, hypothalamus and frontal cortex, but increased them in nucleus accumbens. These observations suggest that the effects of caffeine on the central nervous system (cns) are at least partially mediated through an interaction with the dopaminergic system.
Amine oxidase activities in brown adipose tissue of the rat: identification of semicarbazide-sensitive (clorgyline-resistant) activity at the fat cell membrane
Authors: Barrand Margery A , Fox Sheila A , Callingham Brian A 
Published: April 2011

Abstract
Amine oxidase activity, previously described in homogenates of brown adipose tissue of the rat, has now been investigated in preparations of isolated fat cells. It was found that the specific activities of both monoamine oxidase A (MAO) and of the semicarbazide-sensitive clorgyline-resistant amine oxidase (SSAO) were higher in isolated fat cells than in the original whole tissue. Brown adipocytes therefore represent a major source of both these enzymes. In plasma membranes prepared from these isolated brown fat cells by borate extraction there was a similar enrichment of activity of SSAO and of the plasma membrane marker enzyme, phosphodiesterase I. However in preparations of cell membranes made by binding the cells to polycation-coated beads, enrichment of phosphodiesterase I activity was much greater than that of SSAO. It is suggested that the disposition of the enzyme within the cell membrane may account for the discrepancy in these results, i.e. the sidedness of the membrane may be important. Histochemical visualization of enzyme activity in whole tissue at the ultrastructural level was undertaken. Positive staining of mitochondria was achieved in the presence of the MAO substrate, tryptamine. Staining around the edges of the brown fat cells was observed with the SSAO substrates, tyramine and benzylamine. Staining was largely absent when substrate was omitted or after pretreatment with the irreversible SSAO inhibitor, hydralazine and the slowly reversible inhibitor, semicarbazide. It is not definitely proven that this staining represents sites of enzyme activity but the results are consistent with evidence from other studies indicating that SSAO in brown adipose tissue of the rat may be found predominantly at the fat cell surface. The significance of these findings in relation to the possible function of SSAO is discussed.
Binding of busulfan to plasma proteins and blood cells
Authors: Ehrsson Hans , Hassan Moustapha 
Published: April 2011

Abstract
The reversible and non-reversible binding of busulfan to plasma proteins and to blood cells has been evaluated in man. The reversible binding to plasma proteins was insignificant in both healthy subjects and in patients with chronic myelocytic leukaemia. The percentage of busulfan irreveribly bound to plasma ligands was 32·4. Busulfan was distributed evenly between blood cells and plasma. The fraction of busulfan irreversibly bound to the blood cells was 46·9%. The major portion of busulfan that is degraded in whole blood reacts with the blood cells and the main part of that binds to macromoelcular components in the cells.
Role of vagus in the antagonism of ouabain induced arrhythmias in dogs by β-adrenoceptor antagonists and related drugs
Authors: Alkondon M , Ray A , Sen P 
Published: April 2011

Abstract
The effects of propranolol and related drugs were investigated on ouabain-induced ventricular tachycardia (VT) in dogs with intact and ablated vagi. Propranolol and UM-272 completely antagonized the ouabain VT in dogs with intact vagi, whereas timolol was ineffective. Bilateral vagotomy completely abolished the effect of UM-272 and reduced the effect of propranolol. Diphenylhydantoin, however, reversed ouabain VT in dogs with both intact and ablated vagi. It is inferred that the vagus plays a significant role in the arrhythmolytic effect of propranolol and UM-272.
Improvement in the percutaneous absorption of beclomethasone dipropionate by γ-cyclodextrin complexation
Authors: Uekama K , Otagiri M , Sakai A , Irie T , Matsuo N , Matsuoka Y 
Published: April 2011

Abstract
Inclusion complex formation of beclomethasone dipropionate (BMDP) with γ-cyclodextrin (γ-CyD) in water and in solid state was assessed by solubility analysis and X-ray diffractometry. The solid complex of BMDP with γ-CyD in a molar ratio of 1:2 was prepared and its in-vitro release behaviour was investigated using an ointment release simulator. The release of BMDP from hydrophilic ointment was significantly improved by the γ-CyD complexation. Permeation and uptake studies indicated that the enhanced release of BMDP from the ointment may be due to the faster dissolution and the lower binding affinity of the complex in the ointment base. The vasoconstrictor activity of BMDP in man was found to be increased by γ-CyD complexation, suggesting an improvement in the percutaneous absorption of BMDP.
Enhanced delivery of mitomycin C derivatives through hairless mouse and rat skins
Authors: Hashida M , Mukai E , Kimura T , Sezaki H 
Published: April 2011

Abstract
The percutaneous permeation characteristics of two lipophilic mitomycin C derivatives with aromatic moieties were determined using excised hairless mouse and rat skins and compared with those of mitomycin C (MMC). 1a-N-Benzylmitomycin C penetrated more readily through both kinds of skin than MMC without metabolic conversion. 1a-N-Benzyloxycarbonylmitomycin C effected a 4-fold increase in the delivery of MMC through the rat skin and was completely converted to MMC by an enzyme in rat skin. However, saturation of the metabolic conversion activity was observed in the hairless mouse skin.
Promoting effect of the new chymotrypsin inhibitor FK-448 on the intestinal absorption of insulin in rats and dogs
Authors: Fujii Setsuro , Yokoyama Toru , Ikegaya Koji , Sato Fumiyasu , Yokoo Nobuo 
Published: April 2011

Abstract
FK-448 is a potent and specific inhibitor of chymotrypsin, which enhances the intestinal absorption of insulin in rats and dogs resulting in a decrease in blood glucose levels in these animals. In dogs, the immunoreactive insulin (IRI) level of plasma rose proportionally to the decrease in blood glucose level. From in-vitro data, insulin was inactivated by pancreatic enzymes or the supernatants of intestine or liver homogenates. FK-448 suppressed the digestion of insulin by pancreatic enzymes and its enhancement of the intestinal absorption of insulin was found to be related to its inhibition of digestive enzymes, especially chymotrypsin.
Acute effects of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine on dopamine metabolism in mouse and rat striatum
Authors: Pileblad E , Fornstedt B , Clark D , Carlsson A 
Published: April 2011

Abstract
Monoamines and metabolites in mouse striatum were measured at intervals (0-6 h) after injection of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP; 50 mg kg-1 subcutaneously). In addition, the accumulation of 3,4-dihydroxyphenylalanine (dopa), induced by inhibition of the aromatic amino acid decarboxylase by 3-hydroxybenzylhydrazihe (NSD 1015), was assessed during every 15 min (0-135 min) after MPTP administration. The alterations induced by MPTP during the first hour after injection were a transient acceleration followed by a marked retardation of dopa synthesis, a decrease in 3,4-dihydroxyphenylacetic acid (DOPAC; −55%) and an increase in 3-methoxytyramine (3-MT; +400%). Between 60 and 75 min after administration, some dramatic changes took place: a 40% reduction of dopamine (DA), a marked additional increase in 3-MT (to 1300% of control) and an increase in homovanillic acid (HVA; +50%). The period after 75 min was characterized by a further depletion of DA, a decrease in 3-MT and a transient increase in HVA (max. 240% of control). Six hours after the administration, all concentrations of DA and its metabolites were subnormal, i.e. DA (30% of control), 3-MT (10%), DOPAC (10%) and HVA (65%). The MPTP-induced retardation of dopa synthesis was not antagonized by haloperidol or by reserpine pretreatment. MPTP (25 or 50 mg kg−1 s.c.) produced similar acute changes in the levels of DA and its metabolites in rat as in mouse striatum, though much less pronounced. Fourteen days after injection of MPTP (2 times 50 mg kg−1; 16 h interval) in mice, significant reductions in the striatal levels of NA, DA, 3-MT, DOPAC, HVA and 5-HT were observed. In rat striatum, no changes in the levels of monoamines and metabolites were noted 14 days after injection of MPTP (2 times 25 mg kg−1; 16 h interval). The possible mechanisms underlying the rather dramatic acute biochemical changes induced by MPTP as well as their relationship to the neurotoxic effect are discussed.
Assessment of the contribution of α1-acid glycoprotein to the serum binding of basic drugs using serum treated with sulphosalicylic acid and DEAE-cellulose
Authors: Suzuki Yasuyuki , Sugiyama Yuichi , Sawada Yasufumi , Iga Tatsuji , Hanano Manabu 
Published: April 2011

Abstract
Treatment of human serum with DEAE-cellulose in acid conditions almost completely removed α1-acid glycoprotein (α1-AG) with little change in the concentration of albumin and β-lipoprotein, while treatment with sulphosalicylic acid removed almost all the proteins except α1-AG. The binding of various drugs to serum treated as above was measured by equilibrium dialysis and the contribution of α1-AG to drug binding by human serum was assessed. Sulphosalicylic acid-treated serum exhibited a saturable binding for propranolol, which was considered to be due to the binding to α1-AG while DEAE-cellulose-treated serum mostly exhibited non-saturable binding, for which albumin and β-lipoprotein may be responsible. With this treated serum, α1-AG was estimated to contribute approximately 40% to the binding of therapeutic concentrations of propranolol, 15% to that of imipramine and 15-20% to that of desipramine, respectively, in serum samples pooled from healthy adults. However, no contribution of α1-AG was observed in the binding of salicylic acid to the serum. Dissociation constants of the propranolol binding to the high affinity site in control serum, sulphosalicylic acid-treated serum and purified α1-AG showed similar values (3.7-6.7 μM). These results suggest that treatment of serum with sulphosalicylic acid and DEAE cellulose is useful in assessing the contribution of α1-AG to the serum binding of basic drugs.
The pharmacokinetics and dynamics of Oxprenolol: a simulation study with six subjects
Authors: Saunders L , Ingram D , Warrington S J 
Published: April 2011

Abstract
Experimental results of plasma concentration determinations and lowering of exercise heart rate for six subjects taking a conventional tablet and a sustained release preparation of Oxprenolol have been analysed by a comprehensive computer simulation model. Individual plasma values were simulated using a least squares procedure and the results were applied to evaluate individual release patterns following dosage with the sustained release preparation. Application of the model to the lowering of exercise heart rate indicated that the response is in a steady state with the plasma values and that the response-concentration relation is of the saturable, Emax, type. The parameters for this were evaluated for each subject for the results after a dose of a conventional tablet. These parameters were applicable to the results after dosage with a sustained release preparation. The method should be applicable to other sustained release preparations.
Deviating central hypotensive activity of Urapidil in the cat
Authors: van Zwieten P A , Mathy M J , Thoolen M J M C 
Published: April 2011

Abstract
Urapidil, a novel antihypertensive drug, as well as possessing a peripheral α1-adrenoceptor antagonistic effect, also has a significant degree of central hypotensive activity. When injected into the left vertebral artery of ***chloralose-anaesthetized cats the dose-dependent hypotensive effect of the drug was much stronger than after its systemic administration. Prior treatment, also via the vertebral artery, with various receptor antagonists (yohimbine, prazosin, diphenhydramine, metiamide, sulpiride, pirenzepine, R 56413, naloxone) did not antagonize the central hypotensive effect of Urapidil administered subsequently. Accordingly, the central hypotensive action of Urapidil is not mediated by central receptors of the following types: α2- or α1-adrenoceptors; H1- and H2-histamine; dopaminergic; muscarinic; 5-hydroxytryptamine; opiate. As such the mechanism of the central hypotensive action remains unexplained. It obviously deviates from that of classical centrally acting antihypertensive drugs like Clonidine, guanfacine and α-methyldopa, which are agonists of central α2-adrenoceptors.
Effect of dantrolene sodium on [3H]nitrendipine binding to rat cardiac plasma membranes
Authors: Pong S F , Demuth S M , White R L 
Published: April 2011

Abstract
Dantrolene sodium (Dantrium) has antiarrhythmic activity in addition to its direct-acting skeletal muscle relaxant activity. Dantrolene sodium exerts its skeletal muscle relaxant action by reducing Ca2+ release for sarcoplasmic reticulum. The mechanism by which dantrolene sodium produces its antiarrhythmic effects is not well defined. The effects of dantrolene sodium on [3H]nitrendipine binding to rat cardiac plasma membranes were, therefore, investigated to determine whether the antiarrhythmic action involves an interaction with calcium channels. Whereas 1,4-dihydropyridines maximally inhibited [3H]nitrendipine binding with IC50 values less than 1 nM, verapamil and gallopamil (D 600) inhibited the binding not more than 70% with IC50 values at μM concentrations. Dantrolene sodium caused only minimal inhibition at concentrations up to 100 μM. Thus, the antiarrhythmic action of the drug probably involves a mechanism(s) other than an interaction with the nitrendipine binding site of the slow inward calcium channel.
Correlation of thermodynamic activity and vapour diffusion through human skin for the model compound, benzyl alcohol
Authors: Barry B W , Harrison S M , Dugard P H 
Published: April 2011

Abstract
This work tested the potential for predicting percutaneous absorption rates of a volatile penetrant from any vehicle by using thermodynamic activity measurements. Benzyl alcohol was chosen as a non-ideal, hydrogen bonding, volatile model penetrant. A manual headspace gas chromatography method measured benzyl alcohol vapour concentrations and thermodynamic activities above binary mixtures with vehicles: butanol, butyl acetate, isopropyl myristate, isophorone, toluene and propylene carbonate. Benzyl alcohol vapour diffusion through human, abdominal skin was also measured in-vitro for these mixtures. The benzyl alcohol vapour flux was linearly related to the activity, suggesting that percutaneous absorption is controlled by thermodynamic activity when the vehicle has no effect on the stratum corneum barrier.
Morphine inhibits the carrageenan-induced oedema and the chemoluminescence of leucocytes stimulated by zymosan
Authors: Gyires Klñra , Budavñri I , Fürst S , Molnñr I 
Published: April 2011

Abstract
Morphine inhibited the oedema formation induced by carrageenan. The anti-inflammatory activity developed 120 min after carrageenan injection, suggesting that inhibition of the kinin phase might be partly responsible. This assumption is supported by the findings that morphine inhibited bradykinin oedema but did not influence oedema formation induced by histamine, 5-HT or PGE2. The anti-inflammatory activity of morphine was partially inhibited by naloxone (0.5−1 mg kg−1) in the carrageenan oedema test. Zymosanstimulated chemoluminescence of neutrophils of the rat was inhibited both by morphine (0.1-10 μM) and naloxone (1-100 μM). When morphine and naloxone were administered simultaneously (10 μM) their inhibitory effects were additive. Naloxone also failed to antagonize the inhibitory action of morphine in lower dose (0.1 μM). These results suggest that the effect of morphine in inflammation might be mediated either by one of the opiate receptor subtypes insensitive to naloxone or a non-opiate mechanism might be involved.
Repeated treatment with amitriptyline reduces immobility in the behavioural ‘despair’ test in rats by activating dopaminergic and β-adrenergic mechanisms
Authors: Borsini F , Nowakowska E , Pulvirenti L , Samanin R 
Published: April 2011

Abstract
Seven days of treatment with amitriptyline 10 mg kg−1 day−1, reduced the immobility time in the behavioural ‘despair’ test in rats. 0.5, but not 0.25 mg kg−1 haloperidol significantly counteracted the reduction of immobility caused by amitriptyline. Its anti-immobility effect was reduced by 50 and 100 mg kg−1 sulpiride, another blocker of dopamine receptors, and 5 mg kg−1 (±)-propranolol, a β-adrenolytic drug. Prazosin, 3 mg kg−1, an antagonist of post-synaptic α-adrenoceptors, had no effect. It is suggested that dopaminergic and β-adrenoceptors mediate the anti-immobility effect of repeated amitriptyline treatment in rats.
Effects of phenobarbitone and 6-methylprednisolone pretreatment on pressure/flow relations in the superior mesenteric and iliac arterial beds of the rat
Authors: Hiley C R , Nichols A J , Wilson A C 
Published: April 2011

Abstract
The in-situ blood perfused rat superior mesenteric arterial and right iliac arterial preparations were used to investigate the effects of pretreatment for 5 days with either phenobarbitone (80 mg kg−1 daily) or 6−methylprednisolone (17 mg kg−1 daily) on regional vascular resistances. The elevation of the regression of perfusion pressure on perfusion rate in the superior mesenteric arterial bed was significantly decreased by both phenobarbitone and 6−methylprednisolone over the range of flow rates used. Neither phenobarbitone nor 6−methylprednisolone had a significant effect on hepatic portal venous pressure nor was there any significant effect on the regression of perfusion pressure on flow rate in the in-situ iliac arterial bed. It is concluded that pretreatment with either phenobarbitone or 6−methylprednisolone lowers vascular resistance in the superior mesenteric arterial by approximately 9 and 8% respectively but does not affect vascular resistance in the iliac arterial bed.
Pyrimethamine pharmacokinetics and its tissue localization in mice: effect of dose size
Authors: Coleman M D , Mihaly G W , Edwards G , Ward S A , Howells R E , Breckenridge A M 
Published: April 2011

Abstract
The plasma pharmacokinetics and mass fate of [14 C]pyrimethamine were investigated in the mouse, following dosage with 12.5, 25, 50, and 75 mg kg−1 (i.p.). Peak plasma concentrations of pyrimethamine were reached between 1 and 2 h and then declined monoexponentially. The mean values for AUC 0 → 30 h increased linearly in relation to the administered dose of pyrimethamine (r = 0.979, P &lt; 0.001). The mean values for intraperitoneal clearance and half-life were not significantly different between dose groups, indicating that the plasma pharmacokinetics of pyrimethamine were independent of dose. The percentage of the administered dose excreted in urine as pyrimethamine (1.3−3.5%) and 14 C-radioactivity (21.7−29.1%) did not change with increasing dose. In contrast, the cumulative percentage of the dose excreted as 14 C-radioactivity in faeces (16.7−22.8%) after the three highest doses 25, 50 and 75 mg kg−1 was significantly less than that seen with the lowest dose of 12.5 mg (50.3%). This suggests extensive biliary excretion of radioactivity, and that the capacity of this process may have been exceeded with the highest doses. Seven days after the administration of each of the three highest doses, a significantly greater percentage of [14 C]pyrimethamine was localized in the soft tissues; i.e. heart, lung and kidney (7.8−13.8%), gut (5.4−9.4%) and particularly the liver (25.0−27.9%) when compared with the lowest dose of the drug (1.2, 1.0, 0.3% respectively). Following each dose, between 85 and 97% of the administered radioactivity was accounted for. These studies indicate, that with higher doses of pyrimethamine, the parent drug and/or metabolites may accumulate in soft tissue, particularly the liver, but without appreciable effects on the plasma disposition and urinary excretion of the drug.