bluuebunny/crossref_metadata_2025_split huggingface dataset:
Human Calcitonin Delivery in Rats by Iontophoresis
Authors: Thysman Sophie , Hanchard Cecile , Préat Veronique 
Published: April 2011

Abstract
In-vitro iontophoresis (0·33 mA cm−2) of calcitonin (50 μg mL−1, pH 4) was performed with the hairless rat skin model. Direct current was as potent as pulse current (2·5 kHz on/off 1/1) iontophoresis in promoting transdermal permeation of calcitonin. Increase in duration of current application from 20 min to 1 h did not increase calcitonin flux. Results suggest that calcitonin can be blocked in the skin pores through which it travels or can accumulate in the skin and be progressively released from the depot. Invivo experiments showed that transdermal iontophoretic administration of calcitonin induced a hypocalcaemic effect in rats.
Effects of ZCR-2060 on Allergic Airway Inflammation and Cell Activation in Guinea-pigs
Authors: Abe Tooru , Yoshida Kenji , Omata Takeshi , Segawa Yoshihide , Matsuda Kazuo , Nagai Hiroichi 
Published: April 2011

Abstract
The effects of 2-(2-(4-(diphenylmethyl)-1-piperadinyl) ethoxy) benzoic acid malate (ZCR-2060) on allergic airway inflammation and inflammatory cell activation in guinea-pigs were studied. Allergic airway inflammation was induced by inhalation of antigen into actively-sensitized animals and the increase in inflammatory cells into bronchoalveolar lavage fluid (BALF) was measured. Aeroantigen-induced infiltration of inflammatory cells, especially eosinophils and neutrophils, in BALF gradually increased, and reached a peak at 6 or 9 h after the challenge. ZCR-2060 (1 mg kg−1 p.o.) clearly inhibited the increase of eosinophil numbers in BALF. Moreover, the effect of ZCR-2060 on inflammatory cell activation in terms of chemotaxis and superoxide generation in-vitro was studied. ZCR-2060 (10−6-10−4 m) inhibited the platelet-activating factor (PAF)-induced chemotaxis of eosinophils and neutrophils, but did not inhibit the leukotriene B4-induced chemotaxis of eosinophils and the formyl-Met-Leu-Phe-induced chemotaxis of neutrophils. PAF-induced superoxide anion generation by eosinophils, neutrophils and alveolar macrophages was inhibited by ZCR-2060 (10−6-10−4 m). However, ZCR-2060 did not affect phorbol myristate acetate-induced superoxide anion generation by eosinophils, neutrophils and alveolar macrophages. These results indicate that ZCR-2060 inhibits allergic airway inflammation, and PAF-induced inflammatory cell activation in guinea-pigs. ZCR-2060 may prove useful for the treatment of allergic airway inflammation or allergic disorders, especially inflammatory cell infiltration and activation.
Flavanones with Potent Antibacterial Activity against Methicillin-resistant Staphylococcus aureus
Authors: Iinuma Munekazu , Tsuchiya Hironori , Sato Masaru , Yokoyama Junji , Ohyama Masayoshi , Ohkawa Yasutoshi , Tanaka Toshiyuki , Fujiwara Syuu , Fujii Teruhisa 
Published: April 2011

Abstract
With the therapeutic concept of using the defensive ability of plants against microbial infections, phytoalexin, an antimicrobial phytochemical was studied for its ability to inhibit the growth of methicillin-resistant Staphylococcus aureus (MRSA). Extracts from Sophora exigua (Leguminosae) were fractionated by serial chromatography and the anti-MRSA activity of each fraction was determined by the agar-plate method. Among the active isolates, 5,7,2′,6′-tetrahydroxy-6-isoprenyl-8-lavandulyl-4′-methoxyflavanone (exiguaflavanone D) completely inhibited the growth of all the MRSA strains examined at the concentration of 1·56–6·25 μg mL−1, and 5, 2′,6′-trihydroxy-8-lavandulyl-7-methoxy-flavanone (exiguaflavanone B) inhibited at a concentration of 50 μg mL−1. This former compound is expected to be a phytotherapeutic agent for MRSA infections as an alternative to conventional antibiotics with unwanted side-effects or the appearance of antibiotic-resistant bacteria.
Does α1-Acid Glycoprotein Act as a Non-functional Receptor for α1-Adrenergic Antagonists?
Authors: Qin Mingsheng , Øie Svein 
Published: April 2011

Abstract
The ability of a variety of α1-acid glycoproteins (AAG) to affect the intrinsic activity of the α1, -adrenergic antagonist prazosin was studied in rabbit aortic strip preparations. From these studies, the activity of AAG appears to be linked to their ability to bind the antagonist. However, a capability to bind prazosin was not the only requirement for this effect. The removal of sialic acid and partial removal of the galactose and mannose residues by periodate oxidation of human AAG all but eliminated the ability of AAG to affect the intrinsic pharmacologic activity of prazosin, although the binding of prazosin was not significantly affected. The presence of bovine AAG, a protein that has a low ability to bind prazosin, reduced the effect of human AAG on prazosin activity. Based upon these results, we propose that AAG is able to bind in the vicinity of the α1-adrenoceptors, therefore extending the binding region for antagonists in such a way as to decrease the ability of the antagonist to interact with the receptor. The carbohydrate side-chains are important for the binding of AAG in the region of the adrenoceptor.
Characterization of the Prejunctional Adenosine Receptors in the Rat Anococcygeus Muscle
Authors: Coates Jill , Green Mark A , Sheehan Michael J , Strong Peter 
Published: April 2011

Abstract
Adenosine receptor agonists inhibited electrically-evoked contractions of the rat isolated anococcygeus muscle. The compounds tested were: N6-cyclopentyladenosine (CPA), N((S, trans)-2-hydroxycyclopentyl)adenosine (GR79236), the R- and S-isomers of phenylisopropyladenosine (PIA), 5′-N-ethylcarboxamidoadenosine (NECA), ((2-(4-(2-carboxyethyl)phenyl)ethyl)amino)-N-ethylcarbox-amidoadenosine (CGS 21680) and N-((2-methylphenyl)methyl)adenosine (metrifudil). The rank order of agonist potency was: CPA = R-PIA = GR79236 = NECA » S-PIA &gt; metrifudil &gt; CGS 21680, which is consistent with an effect mediated by adenosine A1 receptors. A similar rank order of potency was obtained for inhibition of electrically-evoked contractions of the guinea-pig ileum. However, there may be a lower receptor reserve in rat anococcygeus compared with the guinea-pig ileum, since higher concentrations of agonists were necessary to produce effects in the anococcygeus than in the guinea-pig ileum and S-PIA behaved as a partial agonist. The effect of NECA was antagonized in rat anococcygeus and guinea-pig ileum by the mixed A1/A2 receptor antagonist, 8-phenyltheophylline (pA2 values of 6·8 and 6·9, respectively). The selective A1-receptor antagonist, 8-cyclopentyl-l,3-dipropylxanthine (DPCPX), also blocked the inhibitory response to NECA in both tissues. Here, however, the pA2 values (9·6 and 8·6, respectively) were slightly but significantly different. These values confirm that the prejunctional adenosine receptors of the rat anococcygeus are of the A1 type, and suggest that they are similar but not necessarily identical to those of the guinea-pig ileum. The differing potencies of DPCPX as an antagonist of NECA between the preparations may reflect a tissue-dependent variation in sensitivity to this antagonist.
Studies on the Synthesis of Some Xanthonoid Derivatives Possessing Antiplatelet Effects
Authors: Lin Chun-Nan , Fang Song-Chwan , Lin Hsien-Cheng , Ko Feng-Nien , Shieh Bor-Jinn , Liu Hong-Wen , Teng Che-Ming 
Published: April 2011

Abstract
2,3- and 3,4-Dihydroxyxanthone react with ethyl 2,3-dibromopropanoate to form the new, substituted 1,4-benzodioxanes 3 and 4, respectively. The regioisomers 3a and 3b; 4a and 4b were separated by column chromatography and characterized for evaluation of the antiplatelet effects in rabbit washed platelets and human platelet-rich plasma. The ethoxycarbonyl derivatives 3a (20 μm) and 3b (20 μm) strongly inhibited the aggregation of rabbit washed platelets induced by arachidonic acid and collagen. The compound 4b showed the most potent inhibition of rabbit washed-platelet aggregation induced by arachidonic acid (IC50 = 8·3 μm). Of the compounds tested in human platelet-rich plasma, compound 4b exhibited the most potent inhibition of primary and secondary aggregation induced by adrenaline (IC50 = 8·6 μm). We conclude that the antiplatelet effects of these four ethoxycarbonyl derivatives are mainly due to an inhibitory effect on thromboxane formation and interference in the adrenaline-receptor interaction.
Anti-complement activity of oleanolic acid: an inhibitor of C3-convertase of the classical complement pathway
Authors: Kapil Aruna , Sharma Shalini 
Published: April 2011

Abstract
Oleanolic acid is a naturally occurring compound, isolated from Luffa cylindrica, which inhibits the in-vitro immuno-haemolysis of antibody-coated sheep erythrocytes by guinea-pig serum. In further experiments this reduced immunohaemolysis was found to be due to inhibition of the C3-convertase of the classical complement pathway. The threshold concentration for inhibition of C3-convertase was 100 μg mL−1. However, higher concentrations of oleanolic acid showed constant inhibitory effects on immunohaemolysis. Oleanolic acid also exhibited weak inhibitory effects on individual components of the complement system.
Buspirone and 1-(2-pyrimidinyl)-piperazine attenuate xylazine-induced antinociception in the mouse
Authors: Cao Bo-Jin , Li Wei-Ping 
Published: April 2011

Abstract
The effects of subcutaneous pretreatment with buspirone and its major metabolite 1-(2-pyrimidinyl)-piperazine (1-PP) on the antinociceptive effect of xylazine were examined using the mouse acetic acid assay. Both buspirone and 1-PP dose-dependently attenuated the antinociceptive action of subcutaneously administered xylazine (0·8 mg kg−1), with ED50 values of 7·3 mg kg−l for buspirone and 3·4 mg kg−1 for 1-PP. Pretreatment with either buspirone (8 mg kg−1) or 1-PP (4 mg kg−1) increased the antinociceptive ED50 of xylazine 3–4-fold. These data support the involvement of α2-adrenoceptor and 1-PP in the pharmacological activity of buspirone.
Improvement of Transdermal Delivery of Tetragastrin by Lipophilic Modification with Fatty Acids
Authors: Setoh Kazunari , Murakami Masahiro , Araki Naoko , Fujita Takuya , Yamamoto Akira , Muranishi Shozo 
Published: April 2011

Abstract
The in-vitro permeability of chemically modified tetragastrin with fatty acids through the rat skin was studied. The permeability of these compounds through intact skin and stripped skin of rat was determined with a Franz-type diffusion cell. The permeation of tetragastrin across the intact skin was improved by chemical modification with acetic acid and butyric acid. However, tetragastrin and caproyl-tetragastrin did not permeate across the intact skin up to the end of experiment. The permeation of tetragastrin across the stripped skin was improved by chemical modification, the skin flux of these acyl derivatives being in the order: acetyl &gt; butyroyl &gt; caproyl. The stability of tetragastrin in skin homogenate was also significantly improved by chemical modification with fatty acids.
These results suggest that chemical modification of tetragastrin with fatty acids increases its lipophilicity, which makes it permeable across the stratum corneum. Moreover, the chemical modification reduced the degradation of tetragastrin in the viable skin, resulting an increase in permeation of tetragastrin across the skin.
Permeability of NS-3, a Thyrotropin-releasing Hormone Analogue, into the Brain After Its Systemic Administration in Rats: A Microdialysis Study
Authors: Itoh Yoshinori , Sugimoto Taketoshi , Ukai Yojiro , Morino Akira , Kimura Kiyoshi 
Published: April 2011

Abstract
The concentration of NS-3 (montirelin hydrate, CG 3703), a thyrotropin-releasing hormone (TRH) analogue, in the cerebral cortex of urethane-anaesthetized rats was measured after its systemic administration (1 mgkg−1, i.v.), using in-vivo microdialysis coupled with a radioimmunoassay.
The concentration in microdialysates was highest (24nM) during the first 20 min after injection, and it fell below the detection limit (3.5 nM) 100 min after treatment. The maximal interstitial concentration was estimated to be 0.51 μM.
From these results, it is suggested that NS-3 can readily penetrate into the brain.
Tableting Characteristics of Micro-aggregated Egg Albumin Particles Containing Paracetamol
Authors: Torrado-DurÁn Juan J , Torrado Santiago , CadÓrniga Rafael , Augsburger Larry L 
Published: April 2011

Abstract
The tableting characteristics of micro-aggregated egg albumin particles containing paracetamol were evaluated and compared with non-micro-encapsulated paracetamol and coagulated egg albumin particles.
Mean yield pressure values of micro-aggregated egg albumin particles containing paracetamol and coagulated egg albumin particles were 30·5 and 49·3 MPa, respectively, which were lower than the mean yield pressure obtained for paracetamol (97-5 MPa). Paracetamol tablets obtained with micro-aggregated egg albumin particles did not show the capping characteristic of conventional paracetamol tablets. Crushing strength of paracetamol tablets obtained with egg micro-aggregated particles was similar to that obtained using paracetamol granulated with povidone and gelatin as binders at 3 and 6% (w/w) concentrations. Drug release from the paracetamol tablets depends on the choice of excipients. Crospovidone showed good protective characteristics for the tableting of micro-aggregated particles.
Crushing strength of paracetamol tablets formed from egg albumin-coated particles could be increased using crospovidone or microcrystalline cellulose as fillers and was decreased by the use of magnesium stearate. Nevertheless, magnesium stearate was useful to decrease the ejection force.
In-vivo and In-vitro Correlation for Delayed-release Behaviour of a Molsidomine/O-carboxymethyl-O-ethyl-β-cyclodextrin Complex in Gastric Acidity-controlled Dogs
Authors: Horikawa Takashi , Hirayama Fumitoshi , Uekama Kaneto 
Published: April 2011

Abstract
The in-vivo absorption behaviour of molsidomine from the delayed-release tablets of an O-carboxy-methyl-O-ethyl-β-cyclodextrin complex was investigated using gastric acidity-controlled dogs under fasted and non-fasted conditions.
The in-vitro release profiles were generated by changing the pH of the dissolution medium at different rotation paddle speeds. The absorptivity of molsidomine in the high acidity dog was correlated with the pH-changed release profile (pH 1·2 to 7·0 after 2 h), whereas that in the low acidity dog was correlated with the release profile at a constant pH of 7·0. The absorption in fasted dogs was well correlated with the in-vitro release at the low-rotation paddle speed (&lt; 5 rev min−1), whereas that in the non-fasted dogs was correlated with that of high rotation (100 rev min−1).
The present results suggested that the in-vivo delayed-release behaviour of the complex is predictable from the in-vitro release profiles generated using pH-variable dissolution testing apparatus at different rotation speeds of the paddle.
Interaction Between Fibronectin-bearing Surfaces and Bacillus Calmette-Guérin (BCG) or Gelatin Microparticles
Authors: Lou Y , Olson W P , Tian X X , Klegerman M E , Groves M J 
Published: April 2011

Abstract
Gelatin, prepared commercially by degradation of animal collagen, was studied to see whether it had an affinity for fibronectin, which has a known affinity for collagen, and whether gelatin-based drugs could be used to target fibronectin-excreting tumours.
Bacillus Calmette-Guérin (BCG) vaccine, an attenuated strain of Mycobacterium bovis, is currently the most effective treatment for superficial transitional cell carcinoma of the bladder. The living cells of the BCG vaccine associate with the fibronectin-bearing surfaces of the tumour.
Using a multi-well culture plate technique, gelatin microparticles were shown to be adsorbed onto murine S180 sarcoma cells and this reaction was substantially inhibited by the addition of human plasma fibronectin.
The avidities of various BCG substrains and gelatin microparticles for glass-bound fibronectin were measured and the association constants determined. The gelatin microparticles associated with the fibronectin with equal avidity as the BCG cells.
The results suggest that this model system may allow the investigation of gelatin-based drug delivery devices capable of targeting fibronectin-bearing surfaces associated with some tumours.
Calorimetric Evaluation of Hydration of Cholestyramine
Authors: Joshi H N , Wilson T D 
Published: April 2011

Abstract
We have investigated the mechanism of hydration of cholestyramine, a water-insoluble resin used pharmaceutically.
Two types of water of hydration (freezing and non-freezing) and the amounts of heat evolved or absorbed during the hydration of cholestyramine were determined. From differential scanning calorimetry, 0·57 g water was observed to be tightly bound per gram of resin (non-freezing water). The hydration of dry cholestyramine was found to be exothermic. The heats of hydration of cholestyramine with chloride or nitrate counter-anions were found to be −6·05 and −3·46 cal g−1, respectively. Some of the partially hydrated cholestyramine samples showed absorption of heat during hydration.
The data generated in the study were utilized to better understand the mechanism of hydration and swelling of cholestyramine.
Anticonvulsant Activity of Phenytoin-lipid Conjugates, a New Class of Phenytoin Prodrugs
Authors: Scriba Gerhard K E , Lambert Didier M , Poupaert Jacques H 
Published: April 2011

Abstract
The anticonvulsant activity of phenytoin-lipid conjugates obtained by covalent binding of 3-hydroxy-methylphenytoin to dimyristoylglycerides via a succinidyl linkage, to 2-(1,3-dimyristoylglyceryl)butyric acid and to 3-myristoyl-2-myristoylmethylpropionic acid was evaluated in the maximal electroshock (MES) test and the seizure threshold test with subcutaneous pentetrazol.
The phenytoin-lipid conjugates were less active than the parent drug in the MES test after intraperitoneal administration as suspensions, but exhibited comparable activity when injected as a solution in dimethysulphoxide. They also protected mice from MES-induced seizures following oral administration of aqueous suspensions of the compounds or when incorporated into emulsions. The anticonvulsant activity could be correlated to in-vitro pancreatic lipase-mediated hydrolysis. The bis-deacyl derivatives were at least as active but in some cases also more toxic than phenytoin. Oral administration of two of the lipid conjugates resulted in a faster onset of the anticonvulsant activity compared with the administration of an equimolar dose of phenytoin itself. All compounds were inactive in the subcutaneous pentetrazol test.
It is concluded that the lipids act as prodrugs of phenytoin, which is generated by lipolysis upon oral administration.
Mechanism for Drug Absorption from Rat-liver Surface Membrane: Effect of Dose and Transport Inhibitors on the Pharmacokinetics of Phenol Red
Authors: Nishida Koyo , Sato Norihito , Sasaki Hitoshi , Nakamura Junzo 
Published: April 2011

Abstract
We examined the effect of dose and transport inhibitors on the pharmacokinetics of phenol red as a model drug after application to rat liver surface in-vivo, employing a cylindrical glass cell (i.d. 9 mm, area 0·64 cm2), to elucidate the mechanism for drug absorption from liver surface membrane.
Absorption ratios of phenol red in 6 h were determined to be 91·1, 91·8 and 89·9% at a dose of 0·3, 1 and 3 mg, respectively. The AUC value for plasma concentration profile of phenol red was proportional to the dose. It is thus suggested that the absorption process of phenol red from rat liver surface does not approach saturability. The time course of the remaining amount of phenol red in the glass cell obeyed first-order kinetics at a dose of 0·3 mg, and its rate constant Ka was calculated to be 0·0069 min−1. Moreover, no significant difference was seen in the Ka value within the dose range of 0·3-3 mg, which was estimated by curve fitting of the plasma concentration profile of phenol red after application to rat liver surface in the two-compartment model with first-order absorption. 2,4-Dinitrophenol (0·3 mg) and probenecid (0·5 and 1 mg), inhibitors of metabolic energy and anion transport, respectively, had no significant effect on the pharmacokinetics of phenol red after application to rat liver surface.
These data demonstrate that a specific transport mechanism such as active transport is not involved in phenol red absorption from rat liver surface membrane.
Phenyl-substituted Normethadones: Synthesis and Pharmacology
Authors: Mbela T K N , Poupaert J H , Cumps J , Moussebois C , Haemers A , Borloo M , Dumont P 
Published: April 2011

Abstract
Phenyl-substituted normethadone derivatives were synthesized and their affinity (IC50) for opioid receptors was determined by displacement of the specific binding sites of [3H]sufentanyl on rat brain preparations.
Substitution resulted in a decrease of affinity in-vitro.
These results suggest that normethadone-like compounds may interact with the P subsite of the μ-opioid receptor and that the P subsite has a well-defined cavity shape of stringent dimensions.
The Peristaltic Reflex in the Rat Ileum: Evidence for Functional μ- and δ-Opiate Receptors
Authors: Coupar Ian M 
Published: April 2011

Abstract
The potency order of opiate agonists at decreasing the rate of peristalsis in the rat isolated ileum was: difenoxin &gt; loperamide &gt; DADLE (d-Ala2-d-Leu5-enkephalin) &gt; morphine &gt; DSLET (d-Ser2, Leu5-Thr6-enkephalin). U-50488 (trans 3,4-dichloro-N-methyl-N-(2-(1-pyrrolidinyl) cyclohexyl) benzeneacet-amide methane sulphonate) was inactive at 300 nm. Naloxone (400 nm) caused a significant 1·52-fold increase in the rate of peristaltic contractions and inhibited the effects of the active opiate agonists. The apparent pA2 values of naloxone were similar using difenoxin, loperamide and morphine as agonists, but the value was slightly, though significantly lower when DADLE was the agonist.
It is suggested that the previously identified δ-opiate receptors of the rat small intestine have a functional role in suppressing the peristaltic reflex. The same response is subserved by μ-opiate receptors and either of these opiate-receptor subtypes could be activated by endogenous enkephalins.
Dihydroetorphine is a μ-Receptor-selective Ligand
Authors: Wang Dan-Xin , Lu Xin-Qiang , Qin Bo-Yi 
Published: April 2011

Abstract
The selectivity to opioid receptors of dihydroetorphine, a potent analgesic with only mild physical dependence, was investigated using radioligand binding assay and its analgesic activity in mice determined.
The relative affinity ratio of dihydroetorphine to μ-, δ- and κ- opioid receptors was 333:1:1. The analgesic effect of intracerebro-ventricular injection in mice could be antagonized by the μ-antagonist β-funaltrexamine but could not be antagonized by δ- and κ-selective antagonists naltrindole and nor-binaltorphimine.
We conclude that dihydroetorphine is a selective ligand for the μ-opioid receptor.
Gel Chromatographic Analysis of Cyclosporin and Its Metabolites in Human Blood Compartments
Authors: Kadobayashi M , Yamamoto K , Takahara S , Okuyama A , Takashima N , Sawada M , Yanaihara C , Kurokawa N 
Published: April 2011

Abstract
Gel chromatography combined with specific and non-specific cyclosporin radioimmunoassays was adopted for quantitative analysis of cyclosporin and metabolites in free and protein-bound forms in blood compartments of kidney transplant patients. The analytical method was proved to be useful for the purpose, although plasma protein-bound forms of neither cyclosporin nor metabolites could be quantitated in the system. The present study also provided, by gel chromatographic analysis, additional examples to prove that concentrations of cyclosporin metabolites in blood compartments may not be deduced or inferred simply from those of cyclosporin.