bluuebunny/crossref_metadata_2025_split huggingface dataset:
Intra-articular therapy of experimental arthritis with a derivative of triamcinolone acetonide incorporated in liposomes
Authors: LóPez-García Francisco , Vázquez-Autón Iosé M , Oil Francisco , Latoore Rafael , Moreno Francisco , Villalaín José , Gómez-Fernández Juan C 
Published: April 2011

Abstract
Triamcinolone acetonide-21-palmitate was synthesized and incorporated into liposomes for intra-articular treatment of an experimentally-induced arthritis in the knee joints of rabbits. The liposomal formulation was more efficient than free triamcinolone acetonide in solution in suppressing the arthritis. Using radioactive tracers, it was found that triamcinolone acetonide-21-palmitate incorporated into liposomes was retained in the articular cavity, together with the liposomal lipids, for a much longer period than free triamcinolone acetonide, and this correlated with its anti-inflammatory effect.
Effect of Alginate and Alginate-cimetidine Combination Therapy on Stimulated Postprandial Gastro-oesophageal Reflux
Authors: Washington N , Denton G 
Published: April 2011

Abstract
This randomized, single-blind cross-over study compared the effectiveness of a conventional alginate reflux barrier formulation (20 mL single dose of Liquid Gaviscon; sodium alginate, sodium bicarbonate, calcium carbonate) with a 20 mL single dose of an alginate-cimetidine combination formulation (Algitec Suspension; sodium alginate, cimetidine) in the suppression of food and acid reflux into the oesophagus after a test meal in 12 healthy volunteers.
Subjects were fasted overnight before the study. A pH electrode and gamma detector were accurately positioned 5 cm above the cardia. The volunteers received a 99mTc-labelled meal designed to provoke reflux and then either remained untreated, or 30 min later were given either Algitec Suspension or Liquid Gaviscon. Reflux of both food and acid into the oesophagus was measured for 3 h. There was a seven day wash-out period between each treatment.
Food reflux in the control group was 22 878 ± 14 385 counts × 103 and this was significantly suppressed by both Liquid Gaviscon (174 ± 128 (s.e.) counts × 103; P = 0.003); however, although the reduction of food reflux to 3812 ± 2322 counts × 103 observed after Algitec treatment was considerable, this did not reach statistical significance (P&gt;0.05) due to the large intersubject variation. Liquid Gaviscon was significantly better at reducing food reflux than Algitec (P = 0.001). Gaviscon also significantly reduced acid reflux when compared with the control group (1.08 ± 0.73 vs 5.87 ± 3.27% recording time oesophageal pH &lt; 4, respectively) (P = 0.03). The slight reduction in acid reflux after Algitec treatment (3.25 ± 1.82% recording time oesophageal pH &lt; 4) also did not reach statistical significance. The difference between Algitec and Gaviscon treatment was also not significant.
Percutaneous Absorption of Salicylates from Some Commercially Available Topical Products Containing Methyl Salicylate or Salicylate Salts in Rats
Authors: Megwa S A , Benson H A E , Roberts M S 
Published: April 2011

Abstract
Studies to determine the extent of local tissue penetration of topically applied, commercially available salicylate esters and salts were conducted in male Wistar rats.
The salicylate concentrations in the deeper tissues approached concentrations observed in the contralateral tissues suggesting that salicylate present in these tissues was due to the systemic blood supply.
The salicylate concentration in plasma, tissues underlying the site of drug application, and similar tissues on the contralateral (control) side were measured. The plasma and tissue salicylate levels suggest that direct penetration of salicylate was predominant to the top muscle level on the treated site. Results also suggest that the drugs were first absorbed into the bloodstream and subsequently distributed to both the deeper tissues on the treated site and the contralateral tissues. The topical application of formulations of ester methyl salicylate and salts triethanolamine salicylate and diethylamine salicylate containing comparable salicylate concentrations yielded similar salicylate concentrations in the various tissues.
Effect of 2-Hydroxypropyl-β-cyclodextrin on Percutaneous Absorption of Methyl Paraben
Authors: Tanaka Muneo , Iwata Yuhei , Kouzuki Yuichi , Taniguchi Kazuyo , Matsuda Hajime , Arima Hidetoshi , Tsuchiya Seishi 
Published: April 2011

Abstract
A potential use of 2-hydroxypropyl-β-cyclodextrin (HP-β-CyD) to solubilize methyl paraben and to suppress its percutaneous absorption was examined, and compared with nonionic surfactant HCO-60.
HP-β-CyD significantly increased the solubility of methyl paraben in water, where the apparent 1:1 stability constant of the soluble complex was determined to be 2150 M−1. The in-vitro cutaneous permeability of methyl paraben through an isolated skin of hairless mouse was suppressed by HP-β-CyD, thus promoting the bioconversion of methyl paraben to the less toxic metabolite, p-hydroxybenzoic acid (p-HBA) in the epidermis. These effects of HP-β-CyD were greater than those of HCO-60. HP-β-CyD (2% w/v) reduced the in-vivo percutaneous absorption of methyl paraben by 66% 24 h after the topical application of a solution containing [14C]methyl paraben to hairless mouse skin. Additionally, the percutaneous absorption of [14C]HP-β-CyD was confirmed to be extremely low.
These results suggest that HP-β-CyD is useful in liquid preparations of methyl paraben for topical application.
Involvement of NK1 and NK2 Receptors in Pulmonary Responses Elicited by Non-adrenergic, Non-cholinergic Vagal Stimulation in Guinea-pigs
Authors: Savoie Chantal , Tousignant Christine , Rodger Ian W , Chan Chi-Chung 
Published: April 2011

Abstract
Previous studies from our laboratory using exogenously administered neurokinin (NK) agonists have shown that both NK1- and NK2-receptor subtypes are involved in plasma extravasation in the guinea-pig airways. In the present study, we have extended these observations using antidromic vagal stimulation to stimulate sensory c-fibres as a means of eliciting the release of endogenous tachykinins in propranolol- and atropine-treated guinea-pigs.
Antidromic vagal stimulation (5 ms, 30 s) induced frequency-dependent (1–10 Hz) bronchoconstriction that was completely abolished by co-administration of the NK1-selective antagonist CP-99,994 ((2s-methoxy-benzyl)-(2-phenyl-piperidin-3s-yl)-amine), and the NK2-selective antagonist SR-48,968 ((S)-N-methyl-N-[4-(4-acetylamino-4-phenyl piperidino)-2-(3,4-dichlorophenyl) butyl]benzamide), each at a dose sufficient to block NK1 and NK2 receptors, respectively (each at 0.3 mg kg−1, i.v.). In contrast, SR-48,968 when given alone only partially blocked the vagal stimulation-induced bronchospasm, whereas CP-99,994 had no effect. Significant increases (2–3-fold) in plasma extravasation of [125I]fibrinogen in the trachea, main bronchi, distal airways and oesophagus following vagal stimulation (5 Hz, 5 min, 10 V, 5 ms) were observed. Pretreatment with the neutral endopeptidase inhibitor, thiorphan (1 mg kg−1, i.v.), and the angiotensin-converting enzyme inhibitor, enalapril (1 mg kg−1, i.v.), potentiated both vagal stimulation-induced bronchoconstriction and plasma leakage in all tissues examined. This potentiation was due to reduced metabolism of endogenously released tachykinins since enhanced plasma overflow of immuno-reactive substance P was observed following vagal stimulation in thiorphan- and enalapril-treated guinea-pigs. CP-99,994 substantially blocked plasma leakage in all parts of the airways and in the oesophagus. In comparison, SR-48,968 had no significant effect in the trachea and the oesophagus but partially inhibited plasma leakage in the main bronchi and distal airways. Co-administration of both CP-99,994 and SR-48,968 abolished the residual plasma leakage in these two regions.
These results support the hypothesis that both NK1 and NK2 receptors are involved in tachykinin-induced pulmonary responses in the airways.
Pre- and Postjunctional Effects of Diadenosine Polyphosphates in the Guinea-pig Vas Deferens
Authors: Hoyle Charles H V , Postorino Alessandra , Burnstock Geoffrey 
Published: April 2011

Abstract
The pre- and postjunctional activities of a number of diadenosine polyphosphates were examined in the guinea-pig isolated vas deferens at the level of the membrane-potential, using a modified sucrose-gap technique.
P1,P3-Di(adenosine 5′)triphosphate (Ap3A), P1,P4-di(adenosine 5′)tetraphosphate (Ap4A) and P1,P5-di(adenosine 5′)pentaphosphate (Ap5 A) all caused concentration-dependent depolarization of the smooth muscle membrane. The potency order was: Ap5A &gt; Ap4A. Ap3A. P1, P2-Di(adenosine 5′)pyrophosphate (Ap2A) did not evoke depolarization even at the highest concentration tested (1 mM). All the dinucleotides caused a reduction in the amplitude of evoked excitatory junction potentials (e.j.ps). The potency order was: Ap5A = Ap4A &gt; Ap3A &gt; Ap2A. The depolarizations evoked by the dinucleotides were markedly reduced by the selective P2X-purinoceptor antagonist, pyridoxalphosphate-6-azophenyl-2′,4′-disulphonic acid (PPADS, 10 μM), as was the amplitude of the fully facilitated e.j.p. The inhibition of the e.j.p. evoked by Ap3A and Ap2A was reduced by the P1-purinoceptor antagonist, 8-p-sulphophenyltheophylline (8-pSPT, 50 μM), but that evoked by Ap5A and Ap4A was not.
Thus, Ap3A, Ap4A and Ap5 A evoke depolarization of the guinea-pig vas deferens via P2X-purinoceptors, and additionally Ap2A and Ap3A exert a prejunctional effect via P1-purinoceptors. The prejunctional activity of Ap4A and Ap5A is mediated via an undefined purinoceptor, which is neither P1 nor P2X.
The Effect of Co-administered Drugs on Oxaprozin Binding to Human Serum Albumin
Authors: Aubry Anne-Françoise , Markoglou Nektaria , Adams Marijke H , Longstreth James , Wainer Irving W 
Published: April 2011

Abstract
The binding of the non-steroidal anti-inflammatory drug oxaprozin to human serum albumin was studied by bioaffinity high-performance liquid chromatography using a column based on immobilized human serum albumin.
Displacement studies using marker compounds for the major drug binding sites showed that oxaprozin has a high affinity for the benzodiazepine/indole site and binds to the warfarin site but with a significantly lower affinity.
Biochromatography and ultrafiltration techniques were used to screen for possible competition and allosteric interactions between oxaprozin and potential co-administered drugs including non-steroidal anti-inflammatory drugs, antipyretics, hypoglycaemics, inhibitors of angiotensin-converting enzyme, anaesthetics, metal ions and anticancer agents. Competition occurred mainly with drugs bound at the benzodiazepine site (benzodiazepines, various non-steroidal anti-inflammatories).
Bioavailability of Phenytoin Following Oral Administration of Phenytoin-lipid Conjugates to Rats
Authors: Scriba Gerhard K E , Lambert Didier M , Poupaert Jacques H 
Published: April 2011

Abstract
The bioavailability of phenytoin was evaluated in rats upon oral administration of phenytoin-lipid conjugates obtained by covalent binding of 3-hydroxymethylphenytoin to 1,3-dimyristoylglyceride via a succinidyl linkage, to 2-(1,3-dimyristoyl-2-glyceryl)butyric acid and to 3-myristoyloxy-2-myristoyloxy-methylpropionic acid.
Despite differences of the phenytoin plasma concentrations all three compounds approximately doubled the AUC compared with the dosing of phenytoin itself. The early onset and the long duration of the anticonvulsant activity after administration of the triglyceride-derived conjugate could be correlated to the increased phenytoin plasma levels.
It is concluded that drug-lipid conjugates may be useful prodrugs for the oral delivery of poorly watersoluble drugs.
Metabolism of Quinine in Man: Identification of a Major Metabolite, and Effects of Smoking and Rifampicin Pretreatment
Authors: Wanwimolruk Sompon , Wong Suk-Ming , Zhang Hu , Coville Peter F , Walker Robert J 
Published: April 2011

Abstract
Our previous studies have shown that cigarette smoking and rifampicin pretreatment enhance the elimination of quinine, metabolism assumed, by analogy with quinidine, to be carried out by CYP3A (P450IIIA). This finding is unexpected since it has been shown that smoking induces the CYP1A rather than the CYP3A enzyme family, suggesting that the metabolism of quinine may be catalysed by CYP1A. Therefore, we conducted this study to identify possible quinine metabolites in human urine and to determine which metabolic pathway is induced by cigarette smoking and rifampicin pretreatment. A specific HPLC procedure was employed to identify metabolites of quinine in urine samples collected from healthy volunteers after an oral dose of 600 mg quinine sulphate.
The results showed that there were at least seven possible metabolites of quinine detected in human urine. Three of these were identified as 2′-oxoquininone, quinine glucuronide and 3-hydroxyquinine. The 3-hydroxyquinine appeared to be a major metabolite of quinine in urine samples from every subject who took an oral dose of quinine.
Although cigarette smoking and rifampicin pretreatment were shown to cause a marked increase in the elimination of quinine there were no significant changes in the formation of 3-hydroxyquinine as measured in the urine samples. This suggests that the effects of smoking and rifampicin are more complicated than we expected and require further investigation.
A Clinical Study to Evaluate the Efficacy of the Antihistamine Doxylamine Succinate in the Relief of Runny Nose and Sneezing Associated with Upper Respiratory Tract Infection
Authors: Eccles R , Van Cauwenberge P , Tetzloff W , Borum P 
Published: April 2011

Abstract
Antihistamines are widely used in common cold medications, although the role of histamine in the development of common cold symptoms is unclear and the use of antihistamines for the treatment of common cold is controversial. It is clear that antihistamines do not offer a cure for common cold but they may alleviate symptoms of sneezing and runny nose. The present study was designed to investigate the efficacy of an antihistamine, doxylamine, on the symptoms of runny nose and sneezing associated with common cold.
We conducted a randomized double-blind study in cold sufferers. One thousand and one volunteers with cold symptoms were screened in four centres (UK, Denmark, Belgium, Germany) and 688 satisfied the entry criteria of the study. The main reasons for excluding subjects were a low nasal secretion weight (secretion weight &lt; 0.2 g, 72%) and a low subjective rhinorrhoea score (24%). Volunteers were randomized to receive either doxylamine succinate 7.5 mg by mouth four times a day up to nine doses (n = 345) or placebo (n = 343). The principal measurements were prospectively defined as runny nose and sneezing symptom scores. Data were analysed on an intention-to-treat basis, using Cochran-Mantel-Haenszel statistics controlling for baseline symptom scores.
A between-group comparison showed that doxylamine-treated volunteers benefited from a significantly greater reduction in runny nose scores (P &lt; 0.01) and sneezing scores (P &lt; 0.001), than those volunteers in the placebo group. Doxylamine therapy was well tolerated; the incidence of unexpected side-effects was comparable with placebo. Of the expected side-effects, 13.3% of doxylamine-treated patients reported drowsiness. The incidence of sedative effects was lower than has been reported for other commonly used first-generation antihistamines.
Effects of Amitriptyline on Rat Plasma and Brain Content of Monoamine Precursors and Other Large Neutral Amino Acids
Authors: Eriksson Tomas , Eriksson Thomas E 
Published: April 2011

Abstract
Amitriptyline caused decreased concentrations in rat plasma of the amino acids tyrosine and tryptophan, which are precursors to monoaminergic neurotransmitters, and also of those other large neutral amino acids (LNAAs) (valine, phenylalanine, leucine and isoleucine) with which tyrosine and tryptophan compete for the carrier-mediated transport from plasma into the brain.
The various LNAAs were, however, not decreased to the same extent. Thus, the relative concentrations, calculated as the ratio of each one of them to the total concentration of LNAAs, were also influenced by amitriptyline. The relative concentrations of tryptophan were decreased while the relative concentrations of phenylalanine and leucine were increased. Those of tyrosine, valine and isoleucine were not influenced by amitriptyline. The relative concentrations of the LNAAs in plasma are considered to be of importance to how much of each of them that will be transported into the brain. Based on this assumption one would have expected that the amitriptyline-induced changes in the relationships between different LNAAs would have caused changes in their brain concentrations in accordance with their relative concentrations in plasma. However, amitriptyline caused decreased concentrations of all LNAAs in rat whole brain.
This finding cannot be explained by altered relationships between the LNAAs but must be explained by other mechanisms. Nevertheless, this effect of amitriptyline on brain LNAA concentrations might be of importance to monoamine function.
In-vitro Platelet Responses to Arachidonic Acid in the Rat
Authors: Rodríguez-Liñares Belén , Cano Ernesto 
Published: April 2011

Abstract
Using both the turbidimetric and the conductive methods to study aggregation of platelets, we found that arachidonic acid stimulated rat washed platelets in a dose-dependent manner (40 μM-0.5mM).
Although a high concentration of arachidonic acid (0.5 mM) produced an increase in light transmission both in the presence of 2 mM CaCl2 and EGTA (45.8 ± 2.8 and 50.4 ± 0.8% respectively) no changes in impedance were detected. Lysis caused by this concentration of arachidonic acid was very high at all the concentrations of calcium used (mean of 81.3%). In addition, the turbidimetric response induced by 0.5 mM arachidonic acid implied an initial decrease in light transmission but did not correlate with a real shape change. Forty micromolar arachidonic acid induced a calcium-dependent aggregation measured both by aggregometry and impedance. Morphology of aggregates induced by both concentrations was also studied.
These results suggest that the optimal concentration for studying rat platelet activation by arachidonic acid is 40 μM; high concentrations (0.5 mM) cause aspecific effects not correlated to a physiological activation response.
Mechanisms in Inhibitory Action of Aclarubicin on Contractility of Rat Aorta
Authors: Wakabayashi Ichiro , Hatake Katsuhiko , Masui Hidehisa , Sakamoto Kunihiro 
Published: April 2011

Abstract
The effects of aclarubicin on vasocontractile response and 45Ca2+ influx were investigated using rat isolated aorta.
KCl-induced contractile force in medium containing 2.5 mM calcium and calcium-induced contractile force in high K+ (60 mM)-depolarized aorta were both markedly attenuated by aclarubicin (70 μM) pretreatment. 45Ca2+ influx stimulated by 60 mM KCl was significantly lower in the aclarubicin (70 μM)-pretreated aorta compared with the control. Aclarubicin pretreatment attenuated phorbol 12, 13-dibutyrate (1 μM)-induced contraction both in the presence and absence of calcium in the medium. Aclarubicin pretreatment also attenuated caffeine (20 mM)-induced transient contraction.
These results suggest that aclarubicin attenuates vasoconstriction by inhibiting both Ca2+ entry through the voltage-dependent calcium channel and the intracellular contractile pathway after elevation of intracellular free calcium in vascular smooth muscle, in addition to the known mechanism of inhibition of phosphoinositides hydrolysis.
Inhibition of In-vitro Lymphocyte Transformation by the Isoquinoline Alkaloid Berberine
Authors: Ckless K , Schlottfeldt J L , Pasqual M , Moyna P , Henriques J A P , Wajner M 
Published: April 2011

Abstract
Berberine is an isoquinoline alkaloid with multiple pharmacological actions, including an anti-inflammatory activity. The effects of berberine on in-vitro cellular proliferation of human peripheral lymphocytes stimulated with phytohaemagglutinin, concanavalin A and pokeweed mitogen were studied. Mononuclear cells were cultured in flat-bottomed 96-well microplates at 37°C for 96–144 h in the presence of one mitogen at different concentrations and the alkaloid at doses of 2.5 to 20 μgmL−1. The mitogen-induced response of lymphocytes was evaluated from the extent of the incorporation of [3H]thymidine into cells in-vitro.
A consistent and progressive inhibitory influence of berberine with increasing concentrations in culture was identified with all mitogens and was more pronounced with pokeweed mitogen. The effect of berberine was observed in phytohaemagglutinin (PHA)- and concanavalin A-activated lymphocytes when the drug was added during the first 24 h of culture, whereas the same effect occurred throughout the incubation period in pokeweed mitogen-stimulated cells. The viability of lymphocytes following treatment with the drug, as assessed by the trypan blue exclusion test, revealed no change when compared with the same untreated lymphocytes, indicating no lymphocytotoxic activity.
We conclude that some effects of berberine, especially its anti-inflammatory action, may arise in part from the inhibition of DNA-synthesis in activated lymphocytes.
Absorption and Excretion of Paeoniflorin in Rats
Authors: Takeda Shuichi , Isono Tomoko , Wakui Yoko , Matsuzaki Yutaka , Sasaki Hiromi , Amagaya Sakae , Maruno Masao 
Published: April 2011

Abstract
The absorption and excretion of paeoniflorin after intravenous and oral administration was studied in rats to evaluate the significance of paeoniflorin in the pharmacological action of Paeony root.
The plasma concentration of paeoniflorin after intravenous administration at the doses of 0.5, 2.0 and 5.0 mg kg−1 rapidly decreased, simulated by a biexponential curve, with mean terminal half-lives of 11.0, 9.9 and 12. 6 min, respectively. The Vdss values were 0.332, 0.384 and 0.423 L kg−1 and the CLtot values were 26.1, 31.2 and 30.3 mL min−1 kg−1 at each dose. When given orally at the same doses, the absolute bioavailability values (F) determined by the AUC were 0.032, 0.033 and 0.038, respectively. The cumulative urinary and faecal excretions of paeoniflorin at the dose of 5 mg kg−1 after intravenous administration were 50.5 and 0.22% of the dose within 72 h, and 1.0 and 0.08% of the dose after oral administration within 48 h, respectively. Cumulative biliary excretion after intravenous or oral administration at a dose of 0.5 mg kg−1 was 6.9 and 1.3% of the dose within 24 h, respectively. The total CLR and CLB value after intravenous dosing was less than the CLtot value. These findings suggest that paeoniflorin is metabolized in other organs as well as in the liver.
We conclude that paeoniflorin absorbed is excreted mainly in urine, it has a low bioavailability and the metabolites may be involved in the pharmacological action of Paeony root.