bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effect of a novel NSAID derivative with antioxidant moiety on oxidative damage caused by liver and cerebral ischaemia-reperfusion in rats
Authors: Kourounakis A P , Tsiakitzis K , Paramithiotis D , Kotzampassi K , Kourounakis P N 
Published: September 2002

Abstract
Tissue ischaemia-reperfusion evokes toxic and harmful biochemical processes such as oxidative stress and inflammation. The aim of this study is to investigate the indices of tissue damage in rat liver and brain after ischaemia-reperfusion injury of these organs, and to study prospective cytoprotection of molecules such as the novel anti-inflammatory N-(2-thiolethyl)-2-{2-[N′-(2,6-dichlorophenyl) amino] phenyl}acetamide (compound 1) and α-tocopherol. Two experimental models were studied: firstly, 30 min liver ischaemia via hepatoduodenal ligament clamping followed by 60 min reperfusion; and secondly, 45 min cerebral ischaemia via bilateral common carotid artery occlusion followed by 90 min reperfusion. Compound 1 and α-tocopherol were administered intraperitoneally before induction of ischaemia. We hereby report that compound 1, a molecule that combines potent in-vitro antioxidant and in-vivo anti-inflammatory activity with low gastrointestinal toxicity, offered protection in-vivo against liver or brain ischaemia-reperfusion-induced damage. Both compound 1 and α-tocopherol prevented changes in lipid peroxidation in the rat liver and brain tissue and in tumour necrosis factor (TNF-α) levels in brain. Also compound 1 attenuated glutathione depletion, evoked by ischaemia-reperfusion, in the rat brain but not in the liver. These results could be explained on the basis of the antioxidant/anti-inflammatory properties of compound 1 and suggest its beneficial effect and potential therapeutic use in post-ischaemic injury.
Effects of BDF 9198 on left ventricular contractility in advanced spontaneously hypertensive rats with heart failure
Authors: Doggrell Sheila A 
Published: September 2002

Abstract
In the first part of this study, we characterized 24-month-old Wistar Kyoto (WKY) rats and spontaneously hypertensive rats (SHRs), their heart weights, and the responses of the isolated left ventricles to electrical stimulation. In the main part of the study, we tested whether the positive inotropic effects of BDF 9198, which prevents the closure of the cardiac sodium channel, were present in senescence and heart failure. Thus, we studied the effects of BDF 9198 on the left ventricle strips of 24-month-old WKY rats (senescence) and SHRs using contractility methods. In comparison with WKY rats, the left ventricles of 24-month-old SHRs were hypertrophied and had prolonged times to peak contraction. BDF 9198 (10−8 to 10−6m) was a positive inotrope on the left ventricles of WKY rats, with a maximum augmenting effect of 122% with BDF 9198 at 10−7m. The magnitude of the augmenting effects of BDF 9198 were reduced in SHR heart failure, with a maximum augmenting effect of 26% at 10−7m. BDF 9198 at 10−6 m attenuated the responses of the SHR left ventricle to electrical stimulation. In conclusion, the potential of drugs that prevent closure of the sodium channel as positive inotropes in the treatment of heart failure should be further considered.
Effect of hr-IL2 treatment on intestinal P-glycoprotein expression and activity in Caco-2 cells
Authors: Belliard Anne-Marie , Tardivel Sylviane , Farinotti Robert , Lacour Bernard , Leroy Christine 
Published: September 2002

Abstract
Caco-2 cells were used to investigate the effect of human recombinant interleukin-2 (IL2) on intestinal P-glycoprotein (P-gp) transporter activity in-vitro. More specifically the efflux function of P-gp was studied by measuring the transepithelial transport of rhodamine-123, a fluorescent substrate of P-gp. Its transport was completely inhibited by two specific P-gp inhibitors, ciclosporin A and GG918, in our experiments. Conversely, these two specific P-gp inhibitors inhibited only 50% of transepithelial transport when [3H]vincristine was used as substrate. After Caco-2 cells were treated with 100 IU mL−1 (6.1 ng mL−1) IL2 for 24 h, a significant diminution (21%) of P-gp transporter function was observed with rhodamine-123 substrate. This effect was also confirmed after 48 and 72 h of exposure to IL2. However, for higher concentrations of IL2 (1000 and 5000 IU mL−1), diminution of P-gp function only occurred after a longer treatment period (48 h and more). The inhibitory effect of IL2 on P-gp activity was found to be independent of tight junction function as demonstrated by constant transepithelial electrical resistance (TEER) measurements for all experimental conditions encountered in this study (time and concentration of IL2 exposure). Furthermore, the MDR1 mRNA level was found to be strongly repressed in Caco-2 cells exposed with 1000 IU mL−1 IL2 for 72 h while the amount of MRP1 mRNA remained unchanged. In conclusion, acute incubation of Caco-2 cells with IL2 induced a decrease of P-gp transporter expression and activity.
Tachykinin-independent activity of capsaicin on in-vitro lamb detrusor
Authors: Tucci Paolo , Evandri Maria Grazia , Bolle Paola 
Published: September 2002

Abstract
The capsicum alkaloid capsaicin is an afferent fibre exciter. In the vesical bladder, capsaicin acts by releasing peptides stored in afferent fibres. The aim of this work was to verify the activity of capsaicin on in-vitro lamb urinary bladder and to ascertain whether this alkaloid evokes peptide release. Capsaicin relaxed about 80 % of the lamb detrusor muscle preparations tested and contracted about 20%. Whereas neurokinin A and substance P antagonists, administered alone or together, left the contractile responses to capsaicin unchanged, atropine and tetrodotoxin totally inhibited contraction. Ruthenium red and indometacin abolished contractions and relaxation. The substance P and neurokinin A antagonists and the NO-synthesis inhibitor Nω-nitro-l-arginine methyl ester (L-NAME) left relaxation unchanged; conversely, the calcitonin gene-related peptide antagonist αh-CGRP (8–37) abolished this response. These results suggest that capsaicin relaxes lamb detrusor muscle not through tachykinins but by releasing CGRP from afferent fibres. Our observation that indometacin blocks the capsaicin response in in-vitro lamb urinary bladder also suggests a role of prostanoids.
Causative agent of vascular pain among photodegradation products of dacarbazine
Authors: Asahi Mariko , Matsushita Ryo , Kawahara Masami , Ishida Tomoyuki , Emoto Chie , Suzuki Nagao , Kataoka Osamu , Mukai Chisato , Hanaoka Miyoji , Ishizaki Junko , Yokogawa Koichi , Miyamoto Ken'ichi 
Published: September 2002

Abstract
The photodegradation products of the anticancer drug, dacarbazine, cause adverse reactions including local venous pain when injected intravenously. In this study, we attempted to identify which of these products is responsible. We synthesized or purchased five photodegradation products of dacarbazine (dimethylamine, 5-diazoimidazole-4-carboxamide (Diazo-IC), 4-carbamoylimidazolium-5-olate, 5-carbamoyl-2-(4-carbamoylimidazol-5-ylazo) imidazolium-5-olate and 2-azahypoxanthine) and examined the pain reaction induced by their intraperitoneal administration in mice using an abdominal stretching or constriction assay. Only Diazo-IC clearly induced pain reaction in mice in a dose-dependent manner, the other products caused no pain reaction. The threshold concentration for pain reaction in mice was estimated to be about 0.1 mg mL−1. While diclofenac sodium significantly reduced acetic-acid-induced pain reaction in mice, it did not influence those induced by Diazo-IC. This result suggests that the mechanism of Diazo-IC-induced pain is different from that of acetic-acid-induced inflammatory pain. Dacarbazine itself produced marked relaxation of rat thoracic aorta strips in a concentration-dependent manner, but there was no difference between the activity of dacarbazine and its photo-exposed solution, so constriction or relaxation of blood vessels is unlikely to be a factor in the pain reaction. In conclusion, Diazo-IC generated by photodegradation of dacarbazine solution causes the side-effect of venous pain. Dacarbazine solution that has turned pink should not be used, because Diazo-IC is an intermediate in the formation of the reddish product, 5-carbamoyl-2-(4-carbamoylimidazol-5-ylazo) imidazolium-5-olate. Drip infusion preparations of dacarbazine should be shielded from light.
AT-1015, a newly synthesized 5-HT2 receptor antagonist, dissociates slowly from the 5-HT2 receptor sites in rabbit cerebral cortex membrane
Authors: Rashid Mamunur , Watanabe Masatomo , Nakazawa Mikio , Nagatomo Takafumi 
Published: September 2002

Abstract
The purpose of this study was to investigate the association and dissociation kinetics of [3H]AT-1015 from 5-HT2 receptors in rabbit cerebral cortex membranes using a radioligand binding assay method and to make a comparison with those of [3H]ketanserin binding. Scatchard analysis of [3H]AT-1015 binding in rabbit cerebral cortex membranes indicated the existence of a single class of binding sites (dissociation constant, Kd = 2.18 nm). The specific binding of [3H]AT-1015 increased slowly with time and the association rate constant of [3H]AT-1015 binding (k1 = 0.1229 min−1 nm−1) was two times slower than that of [3H]ketanserin binding (k1 = 0.2451 min−1 nm−1). The dissociation rate constant of [3H]AT-1015 binding (t1/2 = 37.03 min) was six times slower than that of [3H]ketanserin binding (t1/2 = 6.29 min), when the addition of excess unlabelled ligands were AT-1015 and ketanserin, respectively. The dissociation rate constant of [3H]AT-1015 was slowed to a greater degree (t1/2 = 163.40 min and t1/2 = 198.12 min) by the addition of ketanserin and sarpogrelate as excess unlabelled ligands than was that of [3H]ketanserin (t1/2. = 17.76 min and t1/2. = 18.45 min) by the addition of AT-1015 and sarpogrelate as an excess unlabelled ligand, respectively. These findings on the dissociation kinetics of [3H]AT-1015 have confirmed and supported previously reported evidence of the slower dissociation of AT-1015 from 5-HT2 receptors.
Synthesis and properties of a naproxen polymeric prodrug
Authors: Wang L F , Chiang H N , Chen W B 
Published: September 2002

Abstract
A water-soluble polymeric prodrug containing a naproxen moiety was synthesized. The carboxylic groups of naproxen were condensed with the hydroxyl groups of 2-hydroxyethyl methacrylate (HEMA) to produce a drug-linked monomer, denoted HN. The polymeric prodrug was prepared by copolymerization of HN with methacrylic acid. The molar percentage of HN in the polymeric prodrug was 26 mol%, as determined by 1H NMR. To investigate the pertinence of this polymeric prodrug, the hydrolysis was studied in-vitro with or without esterase or lipase. The kinetics of enzymatic catalysis was calculated from a Lineweaver-Burk plot. The anti-inflammatory activity was evaluated using the carrageenan-induced oedema test. The polymeric prodrug released a major fraction of the free naproxen and a significant fraction of the hydroxyethyl ester derived-naproxen. The maximum hydrolysis rate Vmax, and the Michaelis constant Km were calculated to be 2.16 times 10−5 equiv. mol L−1 min−1 and 5.11 times 10−2 equiv. mol L−1. The maximum anti-inflammatory inhibition of free naproxen appeared at 2 h and quickly decreased thereafter. In contrast, the polymeric prodrug showed a maximum at around 2∼3 h and then slowly decreased. This indicates that the polymeric prodrug displays greater potency than free naproxen in the inhibition of acute inflammatory processes over long periods.
Topical anti-inflammatory activity of extracts and compounds from Thymus broussonettii
Authors: Ismaili H , Sosa S , Brkic D , Fkih-Tetouani S , Ilidrissi A , Touati D , Aquino R P , Tubaro A 
Published: September 2002

Abstract
The topical anti-inflammatory activity of four extracts from Thymus broussonetii Boiss (Labiatae) leaves, a herbal drug used in Moroccan traditional medicine, has been studied using the croton oil ear test in mice. A bioassay-oriented fractionation revealed that the pharmacological activity is mainly in the chloroform extract. Fractionation and analysis of this extract allowed the identification of ursolic acid and oleanolic acid as the main anti-inflammatory principles. Some flavonoids (luteolin, eriodictyol, thymonin) and glycosides (luteolin-7-O-glucoside, luteolin-3′-O-glucuronide, eriodictyol-7-O-glucoside) were also isolated from the methanol extract.
Discovery of novel inhibitors of inducible nitric oxide synthase
Authors: Kita Yasuhiro , Muramoto Masakazu , Fujikawa Akihiko , Yamazaki Takao , Notsu Yoshitada , Nishimura Shintaro 
Published: September 2002

Abstract
We have discovered three compounds, 5-chloro-1,3-dihydro-2H-benzimidazol-2-one (FR038251), 1,3(2H,4H)-isoquinolinedione (FR038470) and 5-chloro-2,4(1H,3H)-quinazolonedione (FR191863), which show inhibition of inducible nitric oxide synthase (iNOS). The iNOS inhibitory activity of the compounds was examined in comparison with that of aminoguanidine, a representative iNOS inhibitor. FR038251, FR038470 and FR191863 inhibited mouse iNOS, with IC50 values of 1.7, 8.8 and 1.9 μM, respectively, in an in-vitro enzyme assay. These inhibitory activities are comparable with that of aminoguanidine (IC50 = 2.1 μm). The three compounds had iNOS selectivity 38- and 8-times, &gt;11- and 3-times, and 53- and 3-times compared with rat neuronal NOS and bovine endothelial NOS, respectively. These compounds concentration-dependently inhibited NO production in intact RAW264.7 mouse macrophages stimulated by lipopolysaccharide (LPS)/interferon-γ. At 100μM, FR038251, FR038470, FR191863 and aminoguanidine showed 81, 44, 54 and 78% inhibition of NO production, respectively. In an in-vivo experiment, FR038251, FR038470, FR191863 and aminoguanidine inhibited NO production in LPS-treated mice by 68, 40, 5 and 68% at an oral dose of 100 mg kg−1. The in-vivo inhibitory activity of FR038251 was almost identical to that of aminoguanidine. In conclusion, the three FR compounds are iNOS inhibitors with novel structures and may be candidate compounds leading to discovery of more iNOS inhibitors in the future.
Effect of the flavonoid galangin on urinary bladder rat contractility in-vitro
Authors: Capasso Raffaele , Tavares Ignatius A 
Published: September 2002

Abstract
Galangin is a flavanol with several biological activities. We have evaluated the effect of galangin on the contractile response elicited by electrical field stimulation (EFS) in the rat isolated urinary bladder. Galangin (10−8- 10−4m) produced a concentration-dependent inhibition of the EFS contractile response without modifying the contractions produced by exogenous acetylcholine (10−6 m). Blockade of adrenergic and cholinergic nerves with a combination of atropine (10−6 m), phentolamine (10−6 m) and propranolol (10−6 m) or blockade of tachykinin NK1 and NK2 receptors with SR140333 (10−7 m) and SR48968 (10−6 m) did not modify the inhibitory effect of galangin. However, verapamil (10−7 m) significantly reduced the inhibitory effect of galangin. It is concluded that the galangin inhibits EFS-induced contractions of the rat urinary bladder by acting on L-type calcium channels on presynaptic nerves.
1-Oxides and 1,1-Dioxides of Thiophenes and Selenophenes and Related Compounds
Authors: Nakayama Juzo 
Published: September 2002

Abstract
The first topic of the present article involves recent advances in the chemistry of thiophene 1-oxides. Next is the chemistry of the parent thiophene 1,1-dioxide, which is followed by that of congested thiophene 1,1-dioxides, where emphasis is placed on their syntheses and synthetic applications. The chemistry of 1-imino, 1,1-diimino, and 1-imino-1-oxo derivatives of thiophenes is then described. Finally, the newborn chemistry of selenophene 1-oxides and 1,1-dioxides is discussed.
Preparation of 2-Propanol Dehydrogenation Catalysts for Chemical Heat Pump System
Authors: Lee Hwaung , Song Hyung Keun , Na Byung-Ki 
Published: September 2002

Abstract
2-Propanol dehydrogenation catalysts were prepared using three types of preparation methods. The catalytic activities of these catalysts were compared through reaction experiments. A Ru catalyst, prepared by an incipient-wetness method followed by NaBH4 reduction, had the predominant reaction rate, and a Pt catalyst, prepared by an incipient-wetness method with H2 reduction at 400 °C, showed high activity. The Ru catalysts with high temperature reduction and Pt catalysts with NaBH4 reduction showed negligible reaction rates; Also, a catalyst supported on activated carbon had a better activity than that on alumina. The Ru on activated carbon was proper for a chemical heat-pump system because of higher activity and a lower reduction temperature than the Pt catalyst.
3,4′-Bis[bis(t-butyl- and methoxy-phenyl)amino]stilbene Bis(cation radical)s and Their Electrochemical and Magnetic Properties
Authors: Michinobu Tsuyoshi , Tsuchida Eishun , Nishide Hiroyuki 
Published: September 2002

Abstract
3,4′-Bis[bis(p-t-butylphenyl)amino]stilbene 1a and 3,4′-bis[bis(p-methoxyphenyl)amino]stilbene 1b were synthesized. The oxidation of 1 was analyzed by electrochemical measurements, which revealed the reversible formation of the bis(cation radical) 2 via a two-electron transfer reaction. The chemical oxidation of 1 with NOBF4 also gave the bis(cation radical) 2; UV/vis and ESR spectroscopies supported aminium radical formation without any side reaction. Magnetization, magnetic susceptibility, and the ESR ΔMs = ±2 signal of the biradicals indicated triplet ground states with a large triplet-singlet energy gap.
Characteristics of MoO3 Reduced with H2 at the Different Flow Rates of H2
Authors: Matsuda Takeshi , Hirata Yasuyoshi , Uchijima Fumiko , Itoh Hidenobu , Takahashi Nobuo 
Published: September 2002

Abstract
MoO3 was treated with H2 at 623 K for 12 h. The degree of reduction and the specific surface area of H2-reduced MoO3 were dependent on the flow rate of H2 in the reduction process. MoO3 with a surface area of about 5 m2 g-1 was transformed to a porous MoOx with a surface area of 180 m2 g-1 after reduction at a flow rate of H2 larger than 600 ml min-1 g-1. The MoOx was found to be stable at 623 K, even in the presence of H2O vapor. A study of reduction with a mixture of H2 and H2O showed that the degree of reduction and the surface area decreased with increasing partial pressure of H2O in the reduction process. We conclude from these results that the reduction of MoO3 to porous MoOx with a large surface area was prohibited by the action of H2O produced by the reduction.
Structures and Photodimerizations of 1-Alkylthymine Crystals Obtained from N,N-Dimethylformamide
Authors: Mochizuki Eiko , Yasui Nobuyoshi , Kai Yasushi , Inaki Yoshiaki , Tohnai Norimitsu , Miyata Mikiji 
Published: September 2002

Abstract
Single crystals of 1-alkylthymine (carbon numbers of the alkyl chain were 8, 11, 12, 13, 14, and 16) were obtained from N,N-dimethylformamide (DMF) solution as plates, and the crystal structures were determined by X-ray crystal analysis. The terminal methyl group of the alkyl chain was found to approach to the double bond of the thymine base in the crystal. The thymine bases in these crystals did not give the photodimer by UV irradiation, while the crystals obtained from ethyl acetate and acetonitrile gave the photodimer as reported previously. The terminal methyl group of the alkyl chain was concluded to inhibit the rotation of the thymine bases in crystal, which made the crystal from DMF inactive for the photodimerization.
Thiamine as a Cationic Host in Anion Coordination Chemistry. Crystal Structures of Five Anion Salts of Thiamine Monophosphate
Authors: Hu Ning-Hai , Liu Wen , Aoki Katsuyuki 
Published: September 2002

Abstract
Five anion salts of thiamine monophosphate {(TMP), TMP+·Cl-·2H2O (1), TMP+·NO3-·2H2O (2), TMP+·ClO4-·2H2O (3), TMP+·ClO4-·H2O (4), and TMP2+·2CF3SO3- (5)} have been prepared and structurally characterized by X-ray diffraction in order to examine the host-guest-like anion binding in TMP compounds. In each salt, the TMP molecule adopts the usually observed F conformation and, as a cationic host, captures anionic or electronegative guests ( = A) through three kinds of anion-bridging interactions: C2-H…A…pyrimidinium-ring, N4′1-H…A…thiazolium-ring, and C6′-H…A…thiazolium-ring. Compared with the thiamine system, the TMP system displays more varieties of self-assembled and higher-ordered structures, due to an additional involvement of the phosphate group: a dimeric structure is formed through both `head-to-tail' and `tail-to-tail' hydrogen bonds in 1, where `head' and `tail' refer to the pyrimidinium ring and the phosphate group, respectively; a `head-to-head' hydrogen-bonded dimer forms in 2; each TMP molecule being linked to two other TMP molecules to form a `head-to-tail' cyclic dimer for each neighbor, thus creating an infinite columnar structure in 3; each TMP molecule is linked to two neighbors, to one in the `head-to-head' fashion and to the other in the `tail-to-tail' fashion, producing an infinite chain structure in 4; and an anion-bridged `head-to-tail' macrocycle, [TMP-A-]2, is formed and linked to two neighboring macrocycles in the `tail-to-tail' fashion to generate an infinite columnar structure in 5.
Molecular Design of Prostaglandin Probes in Brain Research: High, Specific Binding to a Novel Prostacyclin Receptor in the Central Nervous System
Authors: Suzuki Masaaki , Noyori Ryoji , Långström Bengt , Watanabe Yasuyoshi 
Published: September 2002

Abstract
Molecular design to develop a stable biochemical probe for a study of the role of prostacyclin (PGI2) in the brain led to the discovery of (15R)-16-m-tolyl-17,18,19,20-tetranorisocarbacylin (referred to as 15R-TIC), that selectively bind to a novel PGI2 receptor, IP2, expressed in the central nervous system (CNS). This artificial prostaglandin with the 15R configuration exhibits high binding affinity for the IP2 receptor in the thalamus (IC50 = 32 nM) and weak affinity for the peripheral-type PGI2 receptor, IP1, in the NTS (IC50 = 1.2 μM). The length of the ω side-chain and the position of the methyl substituent on the aromatic ring strongly influence the binding characteristics. The features of the IP2 receptor were elucidated by quantitative mapping, specificity studies, and Scatchard analysis, as well as by a study using knockout mice with a tritium-labeled 15R-TIC and related radioligands. In order to conduct in vivo PET studies, a rapid methylation reaction using methyl iodide and an excess amount of an aryltributylstannane has been developed. This has successfully been applied to the synthesis of short-lived 11C-incorporated PET tracers, 15R-[11C]TIC and its methyl ester. The PET experiments accomplished the imaging of the IP2 receptor in the brain of living rhesus monkeys through intravenous administration. The elimination of the C(15) chirality results in 15-deoxy-TIC with ten-fold higher affinity and selectivity for the IP2 receptor than original 15R-TIC. Neither 15R-TIC nor 15-deoxy-TIC inhibit platelets aggregation, up to 400 nM, while PGI2 derivatives which bind with the IP1 receptor show a very potent inhibitory effect at a several nM level. Notably, these artificial CNS-specific PGI2 ligands, like the unstable natural PGI2 itself, prevent the apoptotic cell death of hippocampal neurons induced under high (50%) oxygen atmosphere and by xanthine and xanthine oxidase or serum deprivation. The difference in the binding potency between 15R-TIC and 15-deoxy-TIC for the IP2 receptor correlates well with the extent of the prevention of the neuronal cell death (IC50 values of 300 and 30 nM, respectively, under high oxygen atmosphere). 15R-TIC protects CA1 pyramidal neurons against ischemic damage in gerbils. Thus the designed TICs have neuronal survival-promoting activity both in vitro and in vivo, providing the possibility as a new type of chemotherapeutic agents for applications in neurodegeneration.