bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effect of methotrexate on Th1 and Th2 immune responses in mice
Authors: Yamaki Kouya , Uchida Hiroyuki , Harada Yoshiki , Li Xiaojuan , Yanagisawa Rie , Takano Hirohisa , Hayashi Hideyuki , Taneda Shinji , Mori Yoki , Yoshino Shin 
Published: January 2004

Abstract
We investigated the effect of the anti-rheumatic drug methotrexate (MTX) on Th1 and Th2 immune responses in mice. For this investigation, mice were immunized subcutaneously at the base of the tail with ovalbumin (OVA) emulsified with complete Freund's adjuvant (day 0). Varying doses of MTX were orally administered daily from days 0 to 20. On day 21, anti-OVA IgG2a and interferon-γ (IFN-γ) as indicators of Th1 responses and anti-OVA IgG1 and interleukin-10 (IL-10) as those of Th2 responses were measured. The results showed that treatment with MTX was followed by decreases in OVA-specific IgG and proliferation of spleen cells to the antigen. The anti-rheumatic drug inhibited both anti-OVA IgG2a and IgG1production, although the inhibitory effect of MTX on the antigen-specific IgG2a production appeared to be greater than that on IgG1 production. IFN-γ, but not IL-10, secretion was markedly downregulated by MTX. Administration of MTX resulted in suppression of antigen (OVA)-induced arthritis in mice. The suppression of the joint inflammation by MTX was associated with inhibition of OVA-specific proliferative responses of spleen cells, anti-OVA IgG, IgG2a and IgG1 production, and IFN-γ and IL-10 secretion, although more pronounced decreases in IgG2a and IFN-γ were observed compared with those in IgG1 and IL-10 in MTX-treated mice. These results indicate that MTX appears to suppress Th1 and, to a lesser extent, Th2 immune responses and its anti-arthritic effect on human rheumatoid arthritis might be at least in part explained by down-regulation of Th1 responses involved in the disease.
Study of inhibition of CYP2A6 by some drugs derived from quinoline
Authors: Hirano Yoshie , Mizutani Takaharu 
Published: January 2004

Abstract
CYP2A6 metabolizes coumarin to 7-hydroxycoumarin showing fluorescence, as measured by fluorometry. Firstly, we measured the inhibition of coumarin 7-hydroxylase of cDNA-expressed human CYP2A6 and in bovine liver microsomes, by quinoline and fluoroquinolines (FQ). Quinoline, 5-FQ, 6-FQ and 8-FQ inhibited activity but 3-FQ showed little inhibition. This suggests that the position 3 of quinoline is a recognition site for CYP2A6. We found similar patterns of coumarin 7-hydroxylase activity with human pooled liver microsomes. The level of CYP2A6 in human and bovine microsomes is the same as that detected by immunological titration with monoclonal antibody against CYP2A6. Secondly, we studied the inhibition of CYP2A6 with clinically used drugs of quinoline compounds, such as norfloxacin as an antibacterial agent, quinidine as an antiarrhythmic agent, quinine and chloroquine as antimalaria agents and rebamipide as an anti-ulcer agent. IC50 values (concentration producing 50% inhibition in activity) of norfloxacin, rebamipide and chloroquine at mm concentrations showed them to possess almost no inhibitory activity or influence on drug interaction. Meanwhile, the IC50 value of quinidine was 1.12 mm. The IC50 value of quinine was 160 μm with weak inhibition, suggesting that quinine, at a high dose, influences the metabolism of substrates for CYP2A6 by drug–drug interaction. These results also show that CYP2A6 discriminates the structure difference between the diastereoisomers quinidine and quinine.
In-vitro and in-vivo antioxidant activity of different extracts of the leaves of Clerodendron colebrookianum Walp in the rat
Authors: Rajlakshmi D , Banerjee S K , Sood S , Maulik S K 
Published: January 2004

Abstract
The in-vitro antioxidant activities of different concentrations of the water, alcoholic, petroleum ether and ethyl acetate extracts of the dried leaves of Clerodendron colebrookianum Walp, and in-vivo antioxidant activity of the water extract was studied in experimental rat models. The results obtained from in-vitro lipid peroxidation induced by FeSO4-ascorbate in rat liver homogenate showed a significant inhibition of lipid peroxidation by different extracts of C. colebrookianum leaf. Water extracts at concentrations (w/v) of 1:30, 1:50, 1:200 and 1:1000 showed the strongest inhibitory activity over the other organic extracts, suggesting maximum antioxidant effect. Chronic feeding of the water extract to Wistar albino rats (both sexes, 150–200g) in 1 or 2g kg−1/day doses for 14 days significantly increased the ferric reducing ability of plasma by 19% and 40% on the seventh day, and by 45% and 57% on the fourteenth day of treatment, respectively. Thiobarbituric acid reactive substances (TBARS), as a marker of lipid peroxidation, and some cellular antioxidants (superoxide dismutase, catalase and reduced glutathione) were estimated in heart, liver and kidney. There was a significant reduction in hepatic and renal TBARS with both the doses, without any change in myocardial TBARS. There was no change in the level of antioxidants in heart, liver and kidney, except for the hepatic superoxide dismutase. The findings of this study showed that the leaf extract of C. colebrookianum increased the antioxidant capacity of blood and had an inhibitory effect on the basal level of lipid peroxidation of liver and kidney. This lends scientific support to the therapeutic use of the plant leaves, as claimed by the tribal medicine of North-East India.
Medicinal cannabis: is Δ9–tetrahydrocannabinol necessary for all its effects?
Authors: Wilkinson J D , Whalley B J , Baker D , Pryce G , Constanti A , Gibbons S , Williamson E M 
Published: January 2004

Abstract
Cannabis is under clinical investigation to assess its potential for medicinal use, but the question arises as to whether there is any advantage in using cannabis extracts compared with isolated Δ9-trans-tetrahydrocannabinol (Δ9THC), the major psychoactive component. We have compared the effect of a standardized cannabis extract (SCE) with pure Δ9THC, at matched concentrations of Δ9THC, and also with a Δ9THC-free extract (Δ9THC-free SCE), using two cannabinoid-sensitive models, a mouse model of multiple sclerosis (MS), and an in-vitro rat brain slice model of epilepsy. Whilst SCE inhibited spasticity in the mouse model of MS to a comparable level, it caused a more rapid onset of muscle relaxation, and a reduction in the time to maximum effect compared with Δ9THC alone. The Δ9THC-free extract or cannabidiol (CBD) caused no inhibition of spasticity. However, in the in-vitro epilepsy model, in which sustained epileptiform seizures were induced by the muscarinic receptor agonist oxotremorine-M in immature rat piriform cortical brain slices, SCE was a more potent and again more rapidly-acting anticonvulsant than isolated Δ9THC, but in this model, the Δ9THC-free extract also exhibited anticonvulsant activity. Cannabidiol did not inhibit seizures, nor did it modulate the activity of Δ9THC in this model. Therefore, as far as some actions of cannabis were concerned (e.g. anti-spasticity), Δ9THC was the active constituent, which might be modified by the presence of other components. However, for other effects (e.g. anticonvulsant properties) Δ9THC, although active, might not be necessary for the observed effect. Above all, these results demonstrated that not all of the therapeutic actions of cannabis herb might be due to the Δ9THC content.
In-vitro and in-vivo anti-inflammatory effect of oxyresveratrol from Morus alba L
Authors: Chung Kyung-Ook , Kim Bo-Young , Lee Myung-Hee , Kim Yeo-Ryun , Chung Hae-Young , Park Jong-Hee , Moon Jeon-Ok 
Published: January 2004

Abstract
The antioxidative effects of mulberroside A and oxyresveratrol obtained from Mori Cortex were examined. Mulberroside A and oxyresveratrol showed an inhibitory effect against FeSO4/H2O2-induced lipid peroxidation in rat microsomes and a scavenging effect on 1,1-diphenyl-2-picrylhydrazyl radical. The anti-inflammatory effects of mulberroside A and oxyresveratrol using the carrageenin-induced model of inflammation were investigated in rats. Mulberroside A and oxyresveratrol significantly reduced paw edema. To investigate the mechanism of the anti-inflammatory action of these compounds, we examined the effects of oxyresveratrol on lipopolysaccharide (LPS)-induced responses in murine macrophage cell line RAW 264.7. Exposure of LPS-stimulated cells to oxyresveratrol inhibited nitrite accumulation in the culture medium. Oxyresveratrol also inhibited the LPS-stimulated increase of inducible nitric oxide synthase (iNOS) expression in a concentration-dependent manner; however, it had little effect on iNOS enzyme activity, suggesting that the inhibitory activity of oxyresveratrol is mainly due to the inhibition of iNOS expression rather than iNOS enzyme activity. Oxyresveratrol significantly inhibited LPS-evoked nuclear translocation of NF-kB and cyclooxygenase-2 (COX-2) activity in RAW 264.7 cells. The results suggest that the anti-inflammatory properties of oxyresveratrol might be correlated with inhibition of the iNOS expression through down-regulation of NF-kB binding activity and significant inhibition of COX-2 activity.
Chitosan salts as nasal sustained delivery systems for peptidic drugs
Authors: Cerchiara T , Luppi B , Bigucci F , Zecchi V 
Published: January 2004

Abstract
The aim of this study was to describe a sustained drug release system based on chitosan salts for vancomycin hydrochloride delivery. Chitosan lactate, chitosan aspartate, chitosan glutamate and chitosan hydrochloride were prepared by spray-drying technique. Vancomycin hydrochloride was used as a model peptidic drug, the nasal sustained release of which should avoid first-pass metabolism in the liver. This in-vitro study evaluated the influence of chitosan salts on the release behaviour of vancomycin hydrochloride from the physical mixtures at pH 5.5 and 7.4. In-vitro release of vancomycin was retarded by chitosan salts and, in particular, chitosan hydrochloride provided the lowest release of vancomycin.
Effects of microcrystalline plant sterol suspension and a powdered plant sterol supplement on hypercholesterolemia in genetically obese Zucker rats
Authors: Summanen Jari , Yrjönen Teijo , Christiansen Leena , Mervaala Eero , Vaskonen Timo , Lassila Markus , Ahotupa Markku , Yliruusi Jouko , Karppanen Heikki , Hiltunen Raimo 
Published: January 2004

Abstract
Because dietary fat appears to be an effective vehicle for dispensing plant sterols into the diet, a special plant-sterol-containing ingredient has recently been developed. This ingredient is a plant sterol suspension in oil in which the sterols are in microcrystalline form. The objective of the present study was to analyse the cholesterol-lowering effects and safety of two different plant sterol preparations, an orally administered microcrystalline plant sterol suspension (MPS) in rapeseed oil and a powdered plant sterol supplement, in obese Zucker rats. Dietary plant sterol supplements (0.5%, w/w) were given concurrently with a high cholesterol diet (HCD, 1% cholesterol and 18% fat, w/w). No significant changes in serum triglyceride, blood glucose, serum glutamate oxaloacetic transaminase and glutamic pyruvic transaminase values or body and liver weights were observed. The powdered plant sterol supplement lowered the serum cholesterol by 25% (P&lt; 0.05) and the MPS diet by 35% (P&lt; 0.001) compared with HCD by the end of the 12-week experiment. Interestingly, the plant sterol supplements also produced a marked reduction in serum ubiquinone levels, suggesting a possible effect on isoprene synthesis. Unlike the powdered plant sterol, both MPS and plain rape-seed oil decreased the serum baseline diene conjugation values, suggesting that they protect against oxidative stress-induced lipid peroxidation in rats. This lipid peroxidation diminishing effect is probably due to some antioxidative components in rapeseed oil. These findings indicate that an unesterified plant sterol, such as the microcrystalline suspension in oil, effectively prevents cholesterol absorption in obese Zucker rats.
Absorption, distribution and excretion of 14C-chloroquine after single oral administration in albino and pigmented rats: binding characteristics of chloroquine-related radioactivity to melanin in-vivo
Authors: Ono Chiho , Yamada Masayoshi , Tanaka Makoto 
Published: January 2004

Abstract
Chloroquine is an antimalarial agent that has been reported to have distinct affinity to melanin. After single oral administration of 14C-chloroquine at a dose of 20 mg kg−1 under non-fasting conditions, the absorption, distribution and excretion of 14C-chloroquine-related radioactivity were studied in albino and pigmented rats. The objectives of the study were to investigate differences in the disposition of chloroquine between albino and pigmented rats and to define its in-vivo binding characteristics to melanin-containing ocular tissues. Extensive uptake of radioactivity into tissues was indicated by higher concentrations in most tissues compared with serum and there was no quantitative differences in the distribution of radioactivity found between albino and pigmented rats except for melanin-containing tissues, such as the uveal tract of the eye and perhaps hair follicles. There was selective and strong binding of drug-related compounds to these tissues in pigmented rats. The uveal tract concentrations reached the maximum value of 158.42 + 7.86 μg equiv g−1 (mean + s.e.) at 1 week and decreased very slowly with a terminal half life of 4476h (187 day). The uveal tract concentrations at 24 weeks were still high (67.75 + 6.19 μg equiv g−1). The AUC for uveal tract was 842.3 mg h g−1. A relatively high concentration was still determined in the uveal tract even at 48 weeks after single oral dosing by whole-body autoradiography. The uveal tracts separated from one eye of each rat were extracted with 0.067 m phosphate buffer (pH 7.4) and 1 m HCl–EtOH (30:70) successively. In pigmented rats, almost all radioactivity was released from the tissue with 1 m HCl–EtOH (30:70), indicating that the strong binding by melanin was reversible, and that hydrophobic or electrostatic interaction would play a critical role in the binding of chloroquine and its metabolites with the melanin-containing ocular tissues. Approximately 70% of the radioactivity given was recovered in urine and faeces up to 144h after dosing both in pigmented and albino rats. The excretion pattern in pigmented rats was similar to that seen in albino rats.
Exposure of the yeast Candida albicans to the anti-neoplastic agent adriamycin increases the tolerance to amphotericin B
Authors: O'Keeffe Joseph , Doyle Sean , Kavanagh Kevin 
Published: January 2004

Abstract
Cancer patients experience a high incidence of fungal infections due to their immuno-suppressed condition. This work has investigated the interaction of an anti-neoplastic agent, adriamycin (doxorubicin), with the yeast Candida albicans and examined whether this drug altered the susceptibility of the yeast to amphotericin B – an anti-fungal agent used for the treatment of systemic fungal infections in cancer patients. Exposure to adriamycin for 24 h increased the growth of C. albicans and increased the tolerance to amphotericin B by a small, but statistically significant, extent. Growth in adriamycin-supplemented medium suppressed the respiration rate of C. albicans, which resulted in a decrease in the ergosterol content of the fungal cell membrane. The tolerance to amphotericin B was lost after exposure to adriamycin for 48 h, which coincided with a restoration in the respiration rate and the ergosterol content of the fungal cell membrane. This work demonstrated that short-term exposure (24 h) to adriamycin increased the tolerance of C. albicans for amphotericin B, which may be mediated by a decrease in the ergosterol content as a result of an adriamycin-induced disruption of oxidative phosphorylation.
Rational design of powder formulations for tamp filling processes
Authors: Hardy Ian J , Fitzpatrick Shaun , Booth Steven W 
Published: January 2004

Abstract
Tamp filling processes are widely used for the filling of powders into hard gelatin capsules, whereby capsule fill weight is controlled by the formation of a loosely packed plug of material that is dispensed into the capsule shell. To rationally design formulations for tamp filling processes the formulator must have an intimate knowledge of the synergy between machine parameters and powder properties and the corresponding effect on product quality. However, despite ubiquitous use throughout the pharmaceutical industry, relatively little is understood about the design of powders for tamp filling processes. The aim of the following review is to summarize the published literature to date from a formulation design perspective and to provide a framework for future scientific research.
On the Reaction Mechanism of “Higher-Order Cuprate”, Alias “Lipshutz Cuprate”
Authors: Nakamura Eiichi , Yoshikai Naohiko 
Published: January 2004

Abstract
An organocuprate reagent of the R2Cu(CN)Li composition introduced by Lipshutz has been frequently used in organic synthesis because its reactivity in some reactions is higher than that of the standard Gilman reagent R2CuLi. The higher reactivity of the Lipshutz cuprate was once ascribed to a dianionic tri-coordinated copper(I) (“higher-order”) structure, but numerous structural studies over the last ten years have shown that the Lipshutz cuprate exists as a “cyano-Gilman” (R2CuLi·LiCN) cuprate. This conclusion notwithstanding, our recent theoretical study indicated that a minor and undetectable species such as R(CN)CuLi·LiR may play some roles in the substitution and the addition reactions of the Lipshutz cuprate. The high reactivity of the minor species originates from the anisotropic and multi-coordination capability of the cyanide ligand to metals. Our result accounts for the higher or anomalous reactivity of the Lipsthuz cuprate in some reactions, and further demonstrates the importance of computational study on poly-metallic reaction pathways, where experimental mechanistic information may be difficult to obtain.
Surface Tension of Barium Chlorapatite Crystals Grown from Flux
Authors: Suzuki Takaomi , Nakayama Kazuhito , Oishi Shuji 
Published: January 2004

Abstract
Large, well-formed crystals of barium chlorapatite [Ba5Cl(PO4)3] were grown from a sodium chloride flux. The prismatic crystals of Ba5Cl(PO4)3 were bordered by {(101-0)} and {(101-1)} faces. The crystals have a tendency to elongate in the &lt;0001&gt; directions. Contact angles of water, formamid, ethylene glycol, and diethylene glycol droplets on the Ba5Cl(PO4)3 crystals were observed. The surface tension, that is, the surface free energy of the grown crystals, was calculated in order to study the relationship between the morphology and the surface tension of the crystal. The contact angles of water, formamid, ethylene glycol, and diethylene glycol droplets on the ((101-0) ) face of a Ba5Cl(PO4)3 crystal were 40°, 37°, 30°, and 26°, respectively, and the contact angles of those liquids on the ((101-1) ) face were 20°, 18°, 16°, and 14°, respectively. The surface tension of the crystal faces were calculated from the observed contact angles using harmonic mean and geometric mean equations. The calculated surface tensions of the crystal faces were 58 ± 1 and 69 ± 1 mN/m for the ((101-0) ) and ((101-1) ) faces of a Ba5Cl(PO4)3 crystal, respectively. The fact that the surface tension of the ((101-0) ) face is smaller than that of the ((101-1) ) face indicates that the ((101-0) ) face is more stable than the ((101-1) ) face. The energetic stability of the ((101-0) ) face corresponds to the morphology of the Ba5Cl(PO4)3 crystal, which elongates in the &lt;0001&gt; directions.
Density Functional Studies of [{Mo(η5-Cp)(CO)2}2(μ-H)(μ-PMe2)], [{Mo(η5-Cp)(CO)2}2(μ-PMe2)]− and [{Mo(η5-Cp)(CO)3}2]: Do the Metal–Metal Bonds Exist?
Authors: Hong Fung-E , Chang Yu-Chang 
Published: January 2004

Abstract
Computational methods employing the Kohn–Sham description of density functional theory with the hybrid B3LYP-DFT means were used to investigate the nature of the metal–metal interactions of [{Mo(η5-Cp)(CO)2}2(μ-H)(μ-PMe2)] 1 and its deprotonated form, [{Mo(η5-Cp)(CO)2}2(μ-PMe2)]−4 as well as a dimeric compound, [{Mo(η5-Cp)(CO)3}2] 3. Both the Boys localization procedures as well as NBO analysis were performed to probe the character of the localized orbitals for all the three compounds. Consequently, a direct molybdenum–molybdenum bond was found in compound 3 and 4. However, there is neither a direct metal–metal bond found in 1 at its singlet ground state nor any unpaired electron around each metal center.
Ammonia Absorption on Alkaline Earth Halides as Ammonia Separation and Storage Procedure
Authors: Liu Chun Yi , Aika Ken-ichi 
Published: January 2004

Abstract
For the low pressure ammonia synthesis (∼1 MPa, 573–623 K), 40–80 kPa of ammonia produced must be separated. For this purpose, the absorption behavior of five kinds of alkaline earth metal halides (MgCl2, CaCl2, CaBr2, SrCl2, and SrBr2) and their hydrated forms were studied under 0 to 80 kPa of ammonia at 298 to 473 K. Although the equilibrium data of the ammine complex formation of these materials are known, the absorption started at higher pressure than the equilibrium data, due to the presence of enough chemical potential Δμ for ammonia absorption. Initial absorption (to low numbers of coordinated ammonia) was slow and depended on the sample specific surface area. The successive absorption (beyond 1 or 2 of ammonia coordination) occurs easily and reversibly. The “quasi” absorption and desorption isotherms studied here were useful for the design of ammonia separation materials. MgCl(OH), CaCl2, and CaBr2 were found to be practical for TSA (Temperature Swing Absorption) material working between 298 and 473 K at 40 kPa. Especially, the ammonia separation capacity of MgCl(OH) (26.1 mmol g−1) was 5.5 times as high as that of Na exchanged Y-zeolite.
Rhodium-Catalyzed Asymmetric Addition of Organo-Boron and -Titanium Reagents to Electron-Deficient Olefins
Authors: Hayashi Tamio 
Published: January 2004

Abstract
Asymmetric 1,4-arylation and -alkenylation was achieved by use of organoboronic acids or their derivatives in the presence of a rhodium catalyst coordinated with binap or its related ligands. The scope of this asymmetric addition is very broad, α,β-unsaturated ketones, esters, amides, 1-alkenylphosphonates, and 1-nitroalkenes being efficiently converted into the corresponding 1,4-addition products with over 95% enantioselectivity. The catalytic cycle of the reaction in water is proposed to involve three intermediates (aryl- or alkenyl-rhodium, (oxa-π-allyl)rhodium, and hydroxo-rhodium), as suggested by NMR studies on the rhodium intermediates. The asymmetric addition of B-aryl-9BBN and ArTi(OPr-i)3 in aprotic solvents proceeded with high enantioselectivity under mild conditions to give the corresponding metal enolates as the 1,4-addition products.