Prostaglandins, leukotrienes, and essential fatty acids最新文献

{"title":"Dietary arachidonic acid suppresses bone turnover in contrast to low dosage exogenous prostaglandin E(2) that elevates bone formation in the piglet.","authors":"Vienna D Lucia,&nbsp;Shirley C Fitzpatrick-Wong,&nbsp;Hope A Weiler","doi":"10.1016/s0952-3278(03)00065-6","DOIUrl":"https://doi.org/10.1016/s0952-3278(03)00065-6","url":null,"abstract":"<p><p>This study was designed to compare the effects of dietary arachidonic acid (AA) versus prostaglandin E(2) (PGE(2)) on bone cell metabolism and bone mass. Twenty-eight piglets from 7 litters were randomized to 1 of 4 treatments for 15 days: fatty acid supplemented formula (FA: 0.8% of total fatty acids as AA and 0.1% of total fatty acids as DHA)+PGE(2) injections (0.1mg/kg/day), FA+saline injections, standard formula (STD: n-6:n-3 of 8:1) + PGE(2) injections or STD+saline injections. PGE(2) resulted in elevated osteoblast activity as indicated by plasma osteocalcin and also reduced urinary calcium excretion. Dietary FA resulted in reduced bone resorption as indicated by urinary N-telopeptide and reduced bone PGE(2). Both PGE(2) and FA treatments independently lead to elevated femur mineral content, but the combined treatment caused a reduction. Thus the mechanisms by which PGE(2) and FA lead to enhanced bone mass are distinct.</p>","PeriodicalId":20659,"journal":{"name":"Prostaglandins, leukotrienes, and essential fatty acids","volume":"68 6","pages":"407-13"},"PeriodicalIF":3.0,"publicationDate":"2003-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/s0952-3278(03)00065-6","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"22430096","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Omega-3 fatty acids modulate ATPases involved in duodenal Ca absorption.","authors":"Marianne Haag,&nbsp;Olga N Magada,&nbsp;Nico Claassen,&nbsp;Linde H Böhmer,&nbsp;Marlena C Kruger","doi":"10.1016/s0952-3278(03)00067-x","DOIUrl":"https://doi.org/10.1016/s0952-3278(03)00067-x","url":null,"abstract":"<p><p>Dietary supplementation with fish oil that contains omega-3 polyunsaturated fatty acids has been shown to enhance bone density as well as duodenal calcium uptake in rats. The latter process is supported by membrane ATPases. The present in vitro study was undertaken to test the effect of omega-3 fatty acids on ATPase activity in isolated basolateral membranes from rat duodenal enterocytes. Ca-ATPase in calmodulin-stripped membranes was activated in a biphasic manner by docosahexanoic acid (DHA) (10-30 microg/ml) but not by eicosapentanoic acid (EPA). This effect was blocked partially by 0.5 microM calphostin (a protein kinase C blocker). DHA inhibited Na,K-ATPase (-49% of basal activity, [DHA]=30 microg/ml, P <0.01). This effect could be reversed partially by 50 microM genistein, a tyrosine kinase blocker. EPA also inhibited Na,K-ATPase: (-47% of basal activity, [EPA]=30 microg/ml, P <0.01), this effect was partially reversed by 100 microM indomethacin, a cyclo-oxygenase blocker. Omega-3 fatty acids are thus involved in multiple signalling effects that effect ATPases in BLM.</p>","PeriodicalId":20659,"journal":{"name":"Prostaglandins, leukotrienes, and essential fatty acids","volume":"68 6","pages":"423-9"},"PeriodicalIF":3.0,"publicationDate":"2003-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/s0952-3278(03)00067-x","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"22430098","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The effects on plasma, red cell and platelet fatty acids of taking 12 g/day of ethyl-eicosapentaenoate for 16 months: dihomogammalinolenic, arachidonic and docosahexaenoic acids and relevance to Inuit metabolism.","authors":"David Horrobin,&nbsp;M Rebecca Fokkema,&nbsp;Frits A J Muskiet","doi":"10.1016/s0952-3278(03)00007-3","DOIUrl":"https://doi.org/10.1016/s0952-3278(03)00007-3","url":null,"abstract":"<p><p>A patient with mantle cell lymphoma took 12g/day of ethyl-eicosapentaenoate for 16 months. Compared to reference values, eicosapentaenoic and docosapentaenoic acids were elevated in plasma, red cells and platelets but docosahexaenoic acid levels were in the normal range. Arachidonic acid levels were moderately reduced but dihomogammalinolenic acid levels remained in the normal range. In spite of a long chain n-3 fatty acid intake higher than in most Inuit populations, arachidonic acid levels remained considerably higher in this patient than in the Inuit. The implications for understanding of fatty acid metabolism in humans are discussed.</p>","PeriodicalId":20659,"journal":{"name":"Prostaglandins, leukotrienes, and essential fatty acids","volume":"68 5","pages":"301-4"},"PeriodicalIF":3.0,"publicationDate":"2003-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/s0952-3278(03)00007-3","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"22354758","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Synergistic effect of D-003 and aspirin on experimental thrombosis models.","authors":"V Molina,&nbsp;M L Arruzazabala,&nbsp;D Carbajal,&nbsp;R Más","doi":"10.1016/s0952-3278(03)00020-6","DOIUrl":"https://doi.org/10.1016/s0952-3278(03)00020-6","url":null,"abstract":"<p><p>D-003 is a mixture of higher primary aliphatic saturated acids purified from sugarcane wax, with antiplatelet and antithrombotic effects experimentally demonstrated. Octacosanoic acid is the main component of D-003, followed by triacontanoic, dotriacontanoic, and tetracontanoic acids, while other acids are minor components. This work investigates the effects of combination therapy D-003+aspirin (ASA) on arachidonic acid (AA)-induced sudden death in mice and bleeding time in rats. In addition, the effects of D-003 on serum levels of two metabolites of AA: thromboxane A(2) and prostacyclin, assessed through the measurement of their stable metabolites: thromboxane B(2) (TxB(2)) and 6 keto PgF1alpha by radioimmunoassay kits, were also investigated. Combination therapy of D-003 (50mg/kg) and ASA (3mg/kg) significantly increased bleeding time in rats in a synergistic manner compared with D-003 or ASA alone. Moreover, the combined treatment of D-003 (200mg/kg) and ASA (5mg/kg) in mice protected against AA-induced sudden death (83% survivors) in a synergistic manner which was compared with each treatment alone (33% survivors). These results indicate that antiplatelet effects of D-003 are not mediated by a cyclooxygenase inhibition. D-003 and ASA monotherapies reduced serum TxB(2) levels, whereas D-003, but not ASA, significantly increased 6 keto PgF1alpha levels.</p>","PeriodicalId":20659,"journal":{"name":"Prostaglandins, leukotrienes, and essential fatty acids","volume":"68 5","pages":"305-10"},"PeriodicalIF":3.0,"publicationDate":"2003-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/s0952-3278(03)00020-6","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"22354759","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Evaluation of eicosanoids and NSAIDs as PPARgamma ligands in colorectal carcinoma cells.","authors":"J B Nixon,&nbsp;H Kamitani,&nbsp;S J Baek,&nbsp;T E Eling","doi":"10.1016/s0952-3278(03)00023-1","DOIUrl":"https://doi.org/10.1016/s0952-3278(03)00023-1","url":null,"abstract":"<p><p>The activation of peroxisome proliferator activated receptor gamma (PPARgamma) may play a role in the control of colorectal carcinogenesis. The expression of PPARgamma was examined by Western blotting in human colorectal tumors and matched normal adjacent tissues, as well as in various colorectal carcinoma cell lines. In the tissues, the expression of PPARgamma was elevated in tumors relative to the adjacent normal tissues. Each colorectal carcinoma cell line expressed PPARgamma. The ability of various eicosanoids to bind PPARgamma in colorectal carcinoma cells was investigated using luciferase reporter assays. The well-known PPARgamma ligands, troglitazone and 15-deoxy-Delta(12,14)-prostaglandin J(2) strongly induced PPARgamma binding activity. Products of lipoxygenases displayed moderate binding activity, while other prostaglandins and fatty acids displayed little or no reporter activation. The activation of PPARgamma by 13(S)-HODE, the major metabolite of 15-lipoxygenase-1 from linoleic acid, was concentration dependent reaching maximum at 10 micro M (35-fold activation). The endogenous production of 13(S)-HODE by expression of 15-LO-1 did not activate PPARgamma. The ability of various nonsteroidal anti-inflammatory drugs (NSAIDs) to induce PPARgamma activation was also evaluated. The conventional NSAIDs that inhibit both cyclooxygenases (COX-1 and COX-2) also induced PPARgamma binding activity. In general, however, neither COX-1- nor COX-2-specific inhibitors induced the activation of PPARgamma. Taken together, the metabolites of 15-lipoxygenase and the conventional NSAIDs were confirmed as exogenous ligands for PPARgamma in colorectal carcinoma cells.</p>","PeriodicalId":20659,"journal":{"name":"Prostaglandins, leukotrienes, and essential fatty acids","volume":"68 5","pages":"323-30"},"PeriodicalIF":3.0,"publicationDate":"2003-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/s0952-3278(03)00023-1","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"22354762","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Stimulatory effect of prostaglandin F(2alpha) on Na-dependent phosphate transport in osteoblast-like cells.","authors":"I Sato,&nbsp;A Suzuki,&nbsp;A Kakita,&nbsp;Y Ono,&nbsp;Y Miura,&nbsp;M Itoh,&nbsp;Y Oiso","doi":"10.1016/s0952-3278(03)00021-8","DOIUrl":"https://doi.org/10.1016/s0952-3278(03)00021-8","url":null,"abstract":"<p><p>Prostaglandin F(2alpha) (PGF(2alpha)) has been reported to activate protein kinase C (PKC) through both phospholipase (PL) C and D, resulting in the proliferation of osteoblast-like cells. In addition, it has also been reported that Erk mitogen-activated protein kinase is also involved in the mechanism of PGF(2alpha)-induced proliferation of these cells. Recently, we have reported that several growth factors stimulate Na-dependent phosphate transport (Pi transport) activity of osteoblast-like cells, which has been recognized to play an important role in their mineralization. In the present study, we investigated the effect of PGF(2alpha) on Pi transport in MC3T3-E1 osteoblast-like cells. PGF(2alpha) stimulated Na-dependent Pi transport dose dependently in the range between 1nM and 10 micro M in MC3T3-E1 cells. The effect was time dependent up to 24h. Kinetic analysis revealed that PGF(2alpha) induces newly synthesized Pi transporter. Pretreatment with actinomycin D and cycloheximide suppressed PGF(2alpha)-induced enhancement of Pi transport. Combined effect of PMA and PGF(2alpha) was not additive in Pi transport. Calphostin C, a PKC inhibitor, dose-dependently suppressed Pi transport induced by PGF(2alpha). On the contrary, U0126, which inhibits an upstream kinase of Erk (MEK), did not affect PGF(2alpha)-induced enhancement of Pi transport. In conclusion, PGF(2alpha) stimulates Pi transport through activation of PKC in osteoblast-like cells.</p>","PeriodicalId":20659,"journal":{"name":"Prostaglandins, leukotrienes, and essential fatty acids","volume":"68 5","pages":"311-5"},"PeriodicalIF":3.0,"publicationDate":"2003-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/s0952-3278(03)00021-8","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"22354760","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Docosapentaenoic acid (22:5, n-3) suppressed tube-forming activity in endothelial cells induced by vascular endothelial growth factor.","authors":"Masako Tsuji,&nbsp;Se-itsu Murota,&nbsp;Ikuo Morita","doi":"10.1016/s0952-3278(03)00025-5","DOIUrl":"https://doi.org/10.1016/s0952-3278(03)00025-5","url":null,"abstract":"<p><p>It is generally accepted that n-3 polyunsaturated fatty acids have beneficial effects on vascular homeostasis. Among the several functions of endothelial cells, angiogenesis contributes to tumor growth, inflammation, and microangiopathy. We have already demonstrated that eicosapentaenoic acid (EPA, 20:5, n-3) suppressed angiogenesis. In this paper, we examined the effect of docosapentaenoic acid (DPA, 22:5, n-3), an elongated metabolite of EPA, on tube-forming activity in bovine aortic endothelial cells (BAE cells) incubated between type I collagen gels. The pretreatment of BAE cells with DPA suppressed tube-forming activity induced by vascular endothelial growth factor (VEGF). The effect of DPA was stronger than those of EPA and docosahexaenoic acid (22:6, n-3). The migrating activity of endothelial cells stimulated with VEGF was also suppressed by DPA pretreatment. The treatment of BAE cells with DPA caused the suppression of VEGF receptor-2 (VEGFR-2, the kinase insert domain-containing receptor, KDR) expression in both plastic dish and collagen gel cultures. These data indicate that DPA has a potent inhibitory effect on angiogenesis through the suppression of VEGFR-2 expression.</p>","PeriodicalId":20659,"journal":{"name":"Prostaglandins, leukotrienes, and essential fatty acids","volume":"68 5","pages":"337-42"},"PeriodicalIF":3.0,"publicationDate":"2003-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/s0952-3278(03)00025-5","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"22354764","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The effects of nitric oxide and peroxynitrite on the formation of prostaglandin and arachidonoyl-CoA formed from arachidonic acid in rabbit kidney medulla microsomes.","authors":"Satoru Sakuma,&nbsp;Yohko Fujimoto,&nbsp;Yuhsuke Katoh,&nbsp;Tadashi Fujita","doi":"10.1016/s0952-3278(03)00026-7","DOIUrl":"https://doi.org/10.1016/s0952-3278(03)00026-7","url":null,"abstract":"<p><p>Under physiological conditions, small amounts of free arachidonic acid (AA) are released from membrane phospholipids, and cyclooxygenase (COX) and acyl-CoA synthetase (ACS) competitively act on this fatty acid to form prostaglandins (PGs) and arachidonoyl-CoA (AA-CoA). To clarify factors deciding the metabolic fate of free AA into these two pathways, we investigated the effects of a nitric oxide (NO) donor 1-hydroxyl-2-oxo-3-(N-methyl-3-aminopropyl)-3-methyl-1-triazene (NOC7), and peroxynitrite (ONOO(-)) on the formation of PG and AA-CoA from high and low concentrations of AA (60 and 5 micro M) in rabbit kidney medulla microsomes. The kidney medulla microsomes were incubated with 60 or 5 micro M [14C]-AA in 0.1M Tris/HCl buffer (pH 8.0) containing cofactors of COX (reduced GSH and hydroquinone) and cofactors of ACS (ATP, MgCl(2) and CoA). After incubation, PG (as total PGs) and AA-CoA were separated by selective extraction using petroleum ether and ethyl acetate. When 60 micro M AA was used as the substrate concentration, NOC7 stimulated the PG formation at 0.5 micro M, and inhibited it at 50 and 100 micro M, without affecting the AA-CoA formation. When 5 micro M AA was used as the substrate concentration, NOC7 showed no effect on the PG and AA-CoA formation up to 10 micro M or below, but enhanced the AA-CoA formation with a coincident decrease in the PG formation at 50 micro M or over. Experiments utilizing a NO antidote, carboxy-2-phenyl-4,4,5,5-tetramethylimidazoline-1-oxyl 3-oxide, revealed that the observed effects of NOC7 using 60 and 5 micro M AA are caused by NO. On the other hand, ONOO(-) stimulated the PG formation from 60 micro M AA, with no alteration in the AA-CoA formation at a concentration of 100 micro M, but when 5 micro M AA was used as the substrate concentration, it was without effect on the PG and AA-CoA formation. These findings indicate that actions of NO and ONOO(-) on the PG and AA-CoA formation by the kidney medulla microsomes may change depending on the substrate concentration. The effects of NO using 5 micro M AA were reversed by the addition of the superoxide generating system (xanthine-xanthine oxidase plus catalase), indicating that superoxide is a vital modulator of the action of NO. These results suggest that NO, but not ONOO(-), can be a regulator of the PG and AA-CoA formation at low substrate concentrations (close to the physiological concentration of AA), and that superoxide may play an important role in the action of NO.</p>","PeriodicalId":20659,"journal":{"name":"Prostaglandins, leukotrienes, and essential fatty acids","volume":"68 5","pages":"343-9"},"PeriodicalIF":3.0,"publicationDate":"2003-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/s0952-3278(03)00026-7","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"22355287","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prostaglandin E2 induced the differentiation of osteoclasts in mouse osteoblast-depleted bone marrow cells.","authors":"D Fujita,&nbsp;N Yamashita,&nbsp;S Iita,&nbsp;H Amano,&nbsp;S Yamada,&nbsp;K Sakamoto","doi":"10.1016/s0952-3278(03)00027-9","DOIUrl":"https://doi.org/10.1016/s0952-3278(03)00027-9","url":null,"abstract":"<p><p>Prostaglandin (PG) E(2) is a known bone absorbing agent that acts on osteoblasts to facilitate osteoclastogenesis by increasing the secretion of RANKL. In the present study, we investigated the direct action of PGE(2) on osteoclastic progenitors that differentiate into TRAP-positive multinucleated cells. The hematopoietic stem cell obtained from murine bone marrow was purified by a Sephadex G-10 column, and cultured in the presence of CSF-1 and RANKL to facilitate cell differentiation. The introduction of low-density PGE(2) into the culture resulted in a drastic increase of TRAP-positive multinucleated cells, whereas the addition of high-density PGE(2) had the opposite effect. PCR analysis revealed increased level of EP3 mRNA in undifferentiated cells and reduced level after the development of osteoclast; EP1, EP2 and EP4 were constitutively expressed throughout the differentiation. Investigation of intracellular signaling verified that low-density PGE(2) suppressed PKA activity in undifferentiated cells, suggesting that PGE(2) acts on the osteoclastic cell lineage to facilitate cell differentiation by suppressing PKA in the presence of RANKL.</p>","PeriodicalId":20659,"journal":{"name":"Prostaglandins, leukotrienes, and essential fatty acids","volume":"68 5","pages":"351-8"},"PeriodicalIF":3.0,"publicationDate":"2003-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/s0952-3278(03)00027-9","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"22355288","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effects of essential fatty acids on mediators of mast cells in culture.","authors":"T Gueck,&nbsp;A Seidel,&nbsp;H Fuhrmann","doi":"10.1016/s0952-3278(03)00022-x","DOIUrl":"https://doi.org/10.1016/s0952-3278(03)00022-x","url":null,"abstract":"<p><p>The objective of this study was to investigate the effects of alpha-linolenic acid (18:3n-3) and linoleic acid (18:2n-6) on the fatty acid composition and the activity and release of mast cell mediators in the canine mastocytoma cell line C2. Cells were cultured in Dulbecco's modified Eagle's medium mixed with 50% Ham's F12 (containing linoleic acid 0.14 micro M). The basic medium (DEH) was supplemented with 0.14 micro M alpha-linolenic acid. 14.0 micro M alpha-linolenic acid (DEH-n-3) or 14.0 micro M linoleic acid (DEH-n-6) was added. Eight days after culturing of C2 in DEH-n-3 we measured elevated levels of n-3 fatty acids up to 22:3. The tryptase activity and the stimulated PGE2 production and histamine release were reduced. In contrast, after culturing of C2 in DEH-n-6 we determined elevated levels of n-6 fatty acids up to 20:3, increased tryptase activity and stimulated histamine release. Thus 18:3n-3 has anti-inflammatory effects in cultured canine mastocytoma cells.</p>","PeriodicalId":20659,"journal":{"name":"Prostaglandins, leukotrienes, and essential fatty acids","volume":"68 5","pages":"317-22"},"PeriodicalIF":3.0,"publicationDate":"2003-05-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/s0952-3278(03)00022-x","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"22354761","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}