bluuebunny/crossref_metadata_2025_split huggingface dataset:
In-vitro Characterization of Blood-brain Barrier Permeability to Delta Sleep-inducing Peptide
Authors: Raeissi Shamsi , Audus Kenneth L 
Published: April 2011

Abstract
The diffusion of delta sleep-inducing peptide (DSIP) across the blood-brain barrier (BBB) has been investigated with an in-vitro model comprised of primary cultures of brain micro vessel endothelial cell (BMEC) monolayers. The BMEC monolayers were mounted in a side-by-side diffusion apparatus and the transendothelial flux of DSIP analysed by HPLC with UV detection at 280 nm. The transendothelial flux of the peptide was linear with time and increasing concentrations of DSIP (non-saturable), but was not altered by reduced temperature. The apparent permeability coefficient for DSIP penetration of BMEC monolayers was in a range similar to water-soluble substances (e.g. fluorescein, fluorescein isothiocyanate dextrans) that penetrate the blood-brain barrier to a limited degree based on molecular weight. DSIP flux across the BMEC monolayers was also found to be bidirectional, insensitive to metabolic inhibitors, and not altered by high concentrations of tryptophan. Little degradation (apparent t 1/2 about 10 h) of DSIP to major metabolites, tryptophan (trp) and des-trp DSIP, occurred over the time of the diffusion experiments. The results of these studies support and confirm observations in-vivo indicating that intact DSIP crosses the BBB by simple transmembrane diffusion.
Excretion of proguanil in human saliva
Authors: Onyeji C O , Ogunbona F A , Dixon P A F 
Published: April 2011

Abstract
After a single oral administration of a 300 mg dose of proguanil to six volunteers, the presence of the drug in saliva was established by chromatographic and spectrophotometric methods. The tmax and elimination half-life of proguanil derived from salivary levels were 4·0 ± 1·26 h and 15·1 ± 1·8 h, respectively. These results are in agreement with values previously reported for the drug using plasma level data. The mean saliva: plasma proguanil concentration ratio was 0·41 ± 0·17 and this was not time dependent. There was a correlation (r = 0·82) between the saliva and simultaneous plasma proguanil concentration. The results suggest that proguanil is passively secreted into saliva and that saliva levels may be useful in the determination of pharmacokinetic parameters and the therapeutic monitoring of the drug.
Physicochemical Characterization of Methotrexate—Bovine Serum Albumin Conjugates
Authors: Halbert Gavin W , Florence Alexander T 
Published: April 2011

Abstract
Physicochemical parameters have been determined for a series of methotrexate-bovine serum albumin conjugates produced using a water-soluble carbodiimide. Drug coupling produces a heterogeneous product consisting of mixtures of albumin and albumin polymers with varying quantities of covalently bound drug. Due to this heterogeneity, the measurement of absolute physicochemical values was not possible but two factors producing change were evident. The water soluble carbodiimide is responsible for major changes by producing polymers that dominate the properties of the conjugates. The changes induced by the covalently attached drug are less dramatic but still appreciable. The results emphasize that both the attached drug and the method of coupling are significant factors in altering the physicochemical properties of proteinaceous drug carriers.
On the Mechanism Involved in the Ability of Meptazinol to Potentiate the Effects of Sympathetic Nerve Stimulation
Authors: El-Mas M , Goodall J , Hughes I E 
Published: April 2011

Abstract
Mouse isolated vas deferens responded to field stimulation (0.1 Hz) with twitch responses which were abolished by ag-methyleneadenosine 5′-triphosphate (0.5 p μM) and were potentiated 2 to 3 fold by meptazinol(5–300 p μM). Exogenous adenosine 5′-triphosphate (4–30 p μM) also caused a twitch response but was unaffected by meptazinol(30 p μM) as was the response to phenylephrine. The effect of meptazinol on the electrically-induced twitch was reproducible, fast in onset, easily reversed by washing and was still seen in the presence of prazosin (1 p μM), yohimbine (1 p μM), propranolol(O.1 p μM), atropine (0.1 p μM), physostigmine (1 p μM), cocaine (1 p μM) or desmethylimipramine (0.3 p μM) indicating that the mechanism involved does not depend on adrenoceptors, cholinergic mechanisms or blockade of uptake,. Mouse isolated atria responded to stimulation (1, 2 or 5 Hz) of their sympathetic nerves via transmural electrodes with chronotropic responses which were abolished by atenolol(5 and 50 p μM) but were unaffected by ag-methyleneadenosine 5′-triphosphate (0.5 p μM). Meptazinol (100 p μM) failed to potentiate the responses. It is suggested that meptazinol potentiates the effects of the non-adrenergic non-cholinergic transmitter thought to be involved in the response of the mouse vas deferens to electrical stimulation.
The Effect of Hydrotropic Agents on the Heat Coagulation of Bovine Serum Albumin
Authors: Saleh A M , Florence A T , Whateley T L , El-Khordagui L K 
Published: April 2011

Abstract
The effect of two hydrotropic solubilizers on the heat coagulation of bovine serum albumin (BSA) has been investigated. Photon correlation spectroscopy indicated possible unfolding of BSA molecules in solutions of sodium benzoate and sodium salicylate at 25°C. The effect of these hydrotropes on the heat coagulation of BSA was concentration-dependent. Relatively low concentrations stabilized the protein structure as indicated by the increase in the transition temperature (Tm) and induced gelation at temperatures and BSA concentrations lower than those required in the absence of hydrotropes. Higher concentrations of the hydrotropes considerably reduced Tm and inhibited gelation of BSA, the effect of sodium salicylate being more pronounced, as was the lower aggregation rate of BSA. The behaviour of these hydrotropes as protein denaturants differs from that of neutral electrolytes but is similar to that of concentrated solutions of urea.
Comparative Effects of Azapropazone on Cellular Events at Inflamed Sites. Influence on Joint Pathology in Arthritic Rats, Leucocyte Superoxide and Eicosanoid Production, Platelet Aggregation, Synthesis of Cartilage Proteoglycans, Synovial Production and Actions of Interleukin-1 in Cartilage Resorption Correlated with Drug Uptake into Cartilage In-vitro
Authors: Rainsford K D , Davies Alison , Mundy Linda , Ginsburg I 
Published: April 2011

Abstract
Azapropazone (APZ) has been compared with standard NSAIDs in title systems to establish aspects of its mode of action on cellular events at inflamed sites. APZ (150 mg kg−1 day−1) given for 10–13 days exhibited a reduction in joint pathology in established adjuvant arthritis in rats comparable with that of indomethacin (2 mg kg−1 day−1) and clobuzarit (20 mg kg−1 day−1). APZ was shown to be a potent inhibitor of the production of leucocyte superoxide and synovial interleukin-1 (IL-1)-like activity and stimulated articular cartilage proteoglycan synthesis, but was ineffective as an inhibitor of platelet aggregation or IL-1 induced cartilage degradation in-vitro. These in-vitro effects may have relevance to the mode of action of this weak inhibitor of prostaglandin synthesis.
Conformational Analysis of 9-Substituted Adenines in Relation to Their Microsomal N1-Oxidation
Authors: Lam Siu Ping , Barlow David John , Gorrod John William 
Published: April 2011

Abstract
Metabolic TV-oxidation of adenine, 9-methyladenine, 9-benzyladenine, 9-benzhydryladenine and 9-trityladenine has been investigated using hepatic microsomes from hamster, guinea-pig, rabbit, mouse, rat, and dog. N1-Oxide formation occurs with 9-benzyladenine and 9-benzhydryladenine using liver preparations of all species examined, although to different extents. The N-oxidase activity was found, amongst rodents, in the order hamster &gt; mouse &gt; rabbit &gt; rat &gt; guinea-pig. Microsomal preparations from dog liver contained a small quantity of P-450 and yet produced a relatively large amount of the N-oxides, possibly indicating that other cytochromes in addition to P-450 may be involved in the TV-oxidation of these compounds. The most favourable conformations of these 9-substituted analogues have been established using computer graphics modelling and 1H NMR techniques. Results obtained confirmed the importance of the stereochemical properties of these compounds in relation to N1-oxidation. These observations substantiate and extend our previous findings on the electronic, lipophilic, and stereochemical factors affecting the TV-oxidation of adenine derivatives.
Kinetics and Mechanism of the Facile Cyclization of Histidyl-prolineamide to Cyclo (His-Pro) in Aqueous Solution and the Competitive Influence of Human Plasma
Authors: Møss Judi , Bundgaard Hans 
Published: April 2011

Abstract
A crucial point in the biosynthesis of cyclo (His-Pro), an endogenous and biologically active cyclic dipeptide, is the spontaneous cyclization of its precursor L-histidyl-L-prolineamide (His-ProNH2). In this study the kinetics and mechanism of the cyclization process has been investigated. His-ProNH2 was found to be converted quantitatively to cyclo(His-Pro) in aqueous solution at pH 2–10 and 37°C, the rate of cyclization being maximal at pH 6–7. Buffer substances such as phosphate (pH 6–7.4) were found to catalyse the cyclization. The bell-shaped pH-rate profile observed was accounted for by assuming spontaneous and specific acid- and base-catalysed reactions of the His-ProNH2 species in which the imidazole group is protonated and the primary amino group unprotonated. The much more rapid rate of cyclization of His-ProNH2 (t 1/2 of 140 min at pH 6–7 and 37°C) relative to other proline-containing di- and tripeptides studied was suggested to be due to an intramolecular general acid catalytic effect by the protonated imidazole group. In the presence of human plasma enzymatic hydrolysis of His-ProNH2 competed with the cyclization and predominated greatly at 80% plasma concentration.
Relaxant Effects of α-Adrenoceptor Agonists in the Rat Isolated Gastric Fundus
Authors: Kelly J , Macdonald A 
Published: April 2011

Abstract
In rat gastric fundus preparations with tone raised by the addition of barium chloride or carbachol, and in the presence of propranolol (2 μM) to prevent β-adrenoceptor mediated effects, the adrenoceptor agonists noradrenaline, adrenaline, α-methylnoradrenaline, isoprenaline, cirazoline and phenylephrine all caused concentration-related relaxant responses. Relaxations to the catecholamines were poorly antagonized by prazosin (0.01-1 μM) resulting in the slopes of Schild plots being less than unity, low pA2 values for prazosin against the catecholamines and a clear relaxant effect of the catecholamines even in the presence of 1 μM prazosin. The prazosin-resistant relaxations were unaffected by higher concentrations of prazosin (2 μM) and propranolol (30 μM) or by further additions of idazoxan (1 μM) or haloperidol (30 μM). The relaxations were not due to a non-specific effect of the catechol nucleus since neither dihydroxyphenylethylene glycol (DOPEG) nor dihydroxyphenylacetic acid (DOPAC) produced relaxant effects at concentrations upto 300 μM. In contrast to the results with the catecholamines, prazosin was a potent antagonist of the relaxant effect of cirazoline and phenylephrine, although the antagonism was difficult to quantify due to a lowering of the slope of the concentration response curves to cirazoline and phenylephrine with the higher concentrations of prazosin (0.1 and 1.0 μM). In conclusion postjunctional relaxatory effects of catecholamines in the rat gastric fundus are mediated partly via α1-adrenoceptors and partly via an atypical adrenoceptor.
Failure of σ-receptor ligands to reduce the excitatory actions of N-methyl-DL-aspartate on rat spinal neurons in-vivo
Authors: Church John , Lodge David 
Published: April 2011

Abstract
Haloperidol and (+)-3-PPP, compounds with known affinity for the σ-receptor, have been examined for their ability to reduce the excitatory actions of N-methyl-DL-aspartate (NMDLA), quisqualate and kainate on rat spinal neurons in-vivo. The actions of (-)-3-PPP were also tested. Haloperidol was injected intravenously whereas the 3-PPP enantiomers were administered by microelectrophoresis. Haloperidol had little effect on excitations evoked by NMDLA, quisqualate or kainate whereas both (+)- and (-)-3-PPP usually enhanced, non-selectively, responses to all three excitatory amino acid analogues. The results support suggestions that phencyclidine (PCP)-like compounds with affinity for both PCP and σ-receptors reduce neuronal excitations mediated by the N-methyl-D-aspartate (NMDA) receptor via a selective effect at the PCP site.
Effects of Intra-accumbens Administration of Dopamine Agonists on Stress-induced Behavioural Deficit
Authors: Plaźnik Adam , Stefański Roman , Pucilowski Olgierd , Kostowski Wojciech 
Published: April 2011

Abstract
The effect of post-footshock injections of (+)-amphetamine, the selective D2-receptor agonist quinpirole (LY 171555), and the D2-receptor antagonist metoclopramide, into the nucleus accumbens, on the formation of the open field deficit, has been studied in rats. Microinjections of (+)-amphetamine (10 μg) stimulated rat locomotor activity tested 5 min later, while quinpirole (10 μg) significantly inhibited animal motility in the test. The open field behaviour was not changed 24 h after injection of either drug. Amphetamine applied immediately after inescapable footshock did not modify stress-induced locomotor depression, when the rats' behaviour was examined 24 h later. On the other hand, post-shock injections of quinpirole significantly attenuated the long-term effects of the stressor, in the open field. Metoclopramide (10 μg) inhibited rat locomotor activity 5 min, but not 24 h, after local injection. Administration of a solution containing both quinpirole (10 μg) and metoclopramide (1 μg) decreased motor activity of unstressed rats to a smaller degree than did quinpirole (10 μg) alone. Post-footshock injection of metoclopramide did not affect stress-induced hypomotility. It is concluded that the present data support the hypothesis that local depletion of brain dopaminergic stores causes some behavioural effects of stressors.
Reproducible Withdrawal Contractions of Isolated Guinea-pig Ileum after Brief Morphine Exposure: Effects of Clonidine and Nifedipine
Authors: Valeri P , Martinelli B , Morrone L A , Severini C 
Published: April 2011

Abstract
Guinea-pig ileum stored for 30 min in Krebs solution and then mounted in Tyrode solution gave reproducible contracture responses to naloxone after brief exposure to morphine. The preparation lasted for several hours and a variety of pharmacological tests could be made. Clonidine, an α2-adrenoceptor agonist, and nifedipine, a calcium channel antagonist, both known to interfere with tolerance and physical dependence, inhibited naloxone withdrawal contractures in a dose related way. Their action seemed to be receptor-mediated since yohimbine and Bay k 8644, respectively, reversed their inhibitory effect.
An observation of polymorphism in pentamidine isethionate
Authors: Steele G 
Published: April 2011

Abstract
Two forms of pentamidine isethionate have been identified from two commercial samples of the compound. The lower melting form was produced by freeze drying and has a melting point of 133.4°C whilst the higher melting form has a melting point of 192°C. Powder x-ray diffraction studies showed that each modification was crystalline and the infra-red spectra showed differences that could be attributed to polymorphism. It was noted that when the freeze dried material was exposed to the atmosphere it converted to the higher melting form and was hygroscopic. Examination of this compound in a formal polymorphism screen was advocated.
Resistance of myenteric neurons in the rat's colon to depletion by 1,8-dihydroxyanthraquinone
Authors: Heinicke E A , Kiernan J A 
Published: April 2011

Abstract
Earlier reports have suggested that anthraquinone purgatives in excessive amounts cause degeneration of neurons in the nteric nervous system. Danthron (1,8-dihydroxyanthraquinone) was administered to rats in their drinking water for four months. The effects of the drug on the total number of neurons and on the immunoreactivity of eight putative neurotransmitters in the myenteric plexus of the colon have been assessed. No differences were found between the treated animals and their controls, indicating that the drug does not kill myenteric neurons. These results agree with recent observations on the effects of senna in rats and mice, and do not support earlier claims that myenteric neurons are killed by anthraquinone purgatives.
Arecoline, but not haloperidol, induces changes in the permeability of the blood-brain barrier in the rat
Authors: Saija A , Princi P , De Pasquale R , Costa G 
Published: April 2011

Abstract
The aim of the present study was to investigate the existence of alterations of the blood-brain barrier (BBB) permeability in rats injected with centrally acting drugs, by calculating a unidirectional blood-to-brain transfer constant (Ki) for the circulating tracer [14C]-α-aminoisobutyric acid. The intraperitoneal (i.p.) injection of the dopaminergic antagonist haloperidol (1 mg kg−1) did not modify the regional BBB permeability. When the cholinomimetic agent arecoline hydrobromide (6.25 mg kg−1) was injected i.p. into methylatropine-pretreated rats, it induced a significant decrease of Kj values within the frontal cortex, parietal cortex, striatum and brain-stem. Our findings emphasize two concepts: (1) centrally acting drugs, such as arecoline, can induce changes in the BBB permeability, through several mechanisms; (2) there is no predictable correlation of drug stimulation of specific brain neuronal pathways and changes in the permeability of the BBB.
Serum protein binding of noscapine: Influence of a reversible hydrolysis
Authors: Karlsson Mats O , Dahlström Bengt 
Published: April 2011

Abstract
The binding of the antitussive drug noscapine to human serum, pure albumin and α1-acid glycoprotein has been investigated by ultrafiltration and equilibrium dialysis, using radiolabelled noscapine. The binding in serum pooled from volunteers was 93 ± 0.2% (at 100 ng mL−1). After incubation for 24 h the binding decreased to about 85% (ultrafiltration 87.0 ± 1.0%; equilibrium dialysis 84.3 ± 1.2%), because of the conversion of noscapine to noscapinic acid. Only unbound drug underwent this hydrolysis, and as noscapine is extensively bound in healthy volunteers, this elimination process is probably unimportant. The major binding protein of noscapine was albumin (K = 3060 M−1, n = 5.62), but the binding to ai-acid glycoprotein was also substantial (K = 31500 M−1, n = 1.73). The interindividual variation in binding was low and binding was linear at the concentrations observed after therapeutic doses (0–500 ng mL−1).
Design of a polyvinyl alcohol hydrogel containing phospholipid as controlled-release vehicle for rectal administration of (±)-propranolol HCl
Authors: Morimoto Kazuhiro , Fukanoki Shinichi , Hatakeyama Yoko , Nagayasu Atsushi , Morisaka Katsuaki , Hyuhyon Suong , Ikada Yoshito 
Published: April 2011

Abstract
Polyvinyl alcohol hydrogels which contained phospholipid, egg yolk lecithin or hydrogenated soya lecithin were designed as a transrectal delivery system for propranolol hydrochloride. The hydrogel preparations containing phospholipid were prepared by a low-temperature crystallization method. The release profile of propranolol from hydrogel preparations containing phospholipid complied with Fickian diffusion (Higuchi model). The release of propranolol from the hydrogel preparation decreased with higher contents of phospholipid (∼ 2% w/w). In rats plasma concentrations of propranolol after rectal administration of hydrogel preparations containing phospholipid (1 and 2% w/w) were prolonged compared with those of rats receiving preparations without phospholipid.
Effect of naproxen sodium on the net synthesis of glycosaminoglycans and protein by normal canine articular cartilage in-vitro
Authors: Brandt Kenneth D , Albrecht Marjorie 
Published: April 2011

Abstract
The effects of the non-steroidal anti-inflammatory drug, naproxen sodium, on the metabolism of normal canine articular cartilage has been examined. At a concentration approaching that achieved in synovial fluid of patients treated with the drug (i.e. 30 μg mL−1) naproxen sodium had no significant effect on net synthesis of either glycosaminoglycans or protein in organ cultures of femoral condylar cartilage, nor did it increase the proportion of newly synthesized glycosaminoglycans recovered from the culture medium, suggesting that it had no direct effect on the integrity of the extracellular matrix.
Effect of Compression Speed on the Tensile Strength of Tablets of Binary Mixtures Containing Aspirin
Authors: Cook Graham D , Summers Malcolm P 
Published: April 2011

Abstract
Mixtures of aspirin with sodium chloride, sucrose, Starch 1500 or Emcompress have been compressed to two maximum upper punch pressures at two compression speeds. Non-linear relationships between tensile strength and composition, and tablet porosity and composition were found in all cases. Tablets of the individual materials compressed at fast speed showed either little change or a reduction in tensile strength when compared with those compressed at slow speed. For mixtures of aspirin with Starch 1500, tablets compressed at fast speed were weaker and more porous than those compressed at slow speed. However, some mixtures of aspirin with sodium chloride, sucrose or Emcompress gave tablets with greater tensile strength and lower porosity when prepared at fast compression speed compared with tablets prepared at slow speed. This behaviour was attributed to the modification of the consolidation behaviour of the aspirin by the second material.
The interaction of orally administered iron with levodopa and methyldopa therapy
Authors: Greene R J , Hall A D , Hider R C 
Published: April 2011

Abstract
The ability of methyldopa and levodopa to interact with both ferrous and ferric iron under a variety of conditions likely to be encountered physiologically has been examined. Spectrophotometric studies of ferrous sulphate in the presence of methyldopa indicate that no complexation occurs below pH 2, whilst between pH 4–9, a variety of iron-methyldopa complexes is formed. The formation of these complexes is fast at high pH (pH 9: t 1/2 &lt; 5 s), whilst the rate slows as the pH is lowered (pH 4: t 1/2 &gt; 30 min). These complexes are characteristic of iron-catecholate species, indicating that in the presence of methyldopa (and levodopa) ferrous iron undergoes autoxidation to the ferric form. The tight binding of ferric iron to methyldopa is predicted to alter the biodistribution characteristics of the complex with respect to the unchelated components. Furthermore, under the acid conditions of the stomach, redox cycling can occur. This will result in both catechol oxidation and production of the toxic hydroxyl radical. The findings suggest that care should be exercised when simultaneous administration of either methyldopa or levodopa with ferrous sulphate is indicated.