European Journal of Pharmacology: Molecular Pharmacology最新文献

{"title":"Differential effects of lectins on recombinant glutamate receptors","authors":"Kay-Tsz Yue ,&nbsp;John F. MacDonald ,&nbsp;Roman Pekhletski ,&nbsp;David R. Hampson","doi":"10.1016/0922-4106(95)90062-4","DOIUrl":"10.1016/0922-4106(95)90062-4","url":null,"abstract":"<div><p>The effects of the lectins concanavalin A, succinyl concanavalin A, wheat-germ agglutinin and soybean agglutinin were studied at recombinant ionotropic glutamate receptors expressed in <em>Xenopus</em> oocytes. Homomeric and heteromeric receptors from each of the three major classes of ionotropic glutamate receptors (<span><math><mtext>N-</mtext><mtext>methyl</mtext><mtext>-</mtext><mtext>D</mtext><mtext>-</mtext><mtext>aspartate</mtext></math></span> (NMDA), α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) and kainate) were studied. The lectins potentiated homomeric configurations of kainate, AMPA and NMDA receptors to a greater degree than the corresponding heteromeric configurations although the rank order of the lectin potentiating effects was the same for both homomeric and heteromeric receptors within a given glutamate receptor class. The most profound effects of the lectins were observed with the kainate receptors; the rank order of potentiating effects of the lectins at the homo- and heteromeric kainate receptors (Glu₆ and Glu₆/KA-2) was concanavalin A &gt; succinyl concanavalin A &gt; wheat-germ agglutinin &gt; soybean agglutinin. At the recombinant Glu₃ and Glu<span><math><mtext>2</mtext><mtext>3</mtext></math></span> AMPA receptor complexes, wheat-germ agglutinin and concanavalin A produced the largest enhancements of the glutamate-activated currents followed by succinyl concanavalin A; soybean agglutinin had no significant potentiating effect. Agonist-evoked currents recorded from oocytes expressing the homo- and heteromeric NMDA receptors were only slightly enhanced by concanavalin A and succinyl concanavalin A but not by wheat-germ agglutinin or soybean agglutinin. These results demonstrate that kainate, AMPA and NMDA receptors display dramatic differences in their responses to lectins, and suggest that the receptor-bound oligosaccharide side chains may play different roles in the functional responses mediated by the three major classes of ionotropic glutamate receptors.</p></div>","PeriodicalId":100502,"journal":{"name":"European Journal of Pharmacology: Molecular Pharmacology","volume":"291 3","pages":"Pages 229-235"},"PeriodicalIF":0.0,"publicationDate":"1995-11-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/0922-4106(95)90062-4","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"19692839","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effects of benfluorex metabolites on membrane fluidity and insulin-related processes","authors":"Thierry G. Orsière,&nbsp;Michèle M. Chauvet,&nbsp;Monique H. Dell'Amico,&nbsp;Madeleine J. Bourdeaux","doi":"10.1016/0922-4106(95)90063-2","DOIUrl":"10.1016/0922-4106(95)90063-2","url":null,"abstract":"<div><p>As little work has dealt with the antihyperglycemic property of benfluorex at the hepatocyte level, we studied the effects of its main metabolites, S422 and S1475, on membrane fluidity and on insulin binding, internalization and action in healthy rat hepatocytes. Both metabolites were effective fluidizing agents. Neither one affected insulin binding. Only S422 favored the bound insulin-receptor internalization process. The metabolites produced no change in basal α-aminoisobutyric acid uptake. Only S422 promoted the insulin-stimulated α-aminoisobutyric acid uptake in a dose-dependent way. Therefore, our study demonstrated that: (i) the effects of S422 on insulin-related processes in isolated hepatocytes were direct, specific and not due to any membrane fluidizing mechanism; (ii) S422 improved hepatocyte response to insulin at a post-binding level. These results in vitro give an additional explanation, at the cellular level, of the benefit of benfluorex treatment for non insulin-dependent diabetes patients.</p></div>","PeriodicalId":100502,"journal":{"name":"European Journal of Pharmacology: Molecular Pharmacology","volume":"291 3","pages":"Pages 237-243"},"PeriodicalIF":0.0,"publicationDate":"1995-11-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/0922-4106(95)90063-2","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"19692840","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Impairment of adenylyl cyclase signal transduction in mecobalamin-deficient rats","authors":"Shinichi Hatta ,&nbsp;Masayuki Watanabe ,&nbsp;Hiroshi Ikeda ,&nbsp;Hiroki Kamada ,&nbsp;Toshikazu Saito ,&nbsp;Hideyo Ohshika","doi":"10.1016/0922-4106(95)90076-4","DOIUrl":"10.1016/0922-4106(95)90076-4","url":null,"abstract":"<div><p>This study examined alterations in the β-adrenoceptor-G_s-adenylyl cyclase system in cerebral cortex membranes from vitamin B₁₂-deficient rats fed a diet lacking vitamin B₁₂ (mecobalamin) for 15 weeks. Basal, 5'-guanylylimidodiphosphate (GppNHp)-, isoproterenol-, and forskolin-stimulated adenylyl cyclase activities were significantly reduced in mecobalamin-deficient rats compared with those in control rats. However, no significant differences were observed in the amount and function of G_s, estimated by immunoblotting and guanine nucleotide photoaffinity labeling, respectively, or in the densities and the dissociation constants of β-adrenoceptors, estimated by [¹²⁵I] pindolol binding, between control and the deficient rats. These results indicate that vitamin B₁₂ deficiency results in the impairment of the coupling among the β-adrenoceptor, G_s, and the catalytic subunit of adenylyl cyclase, and in dysfunction of the catalytic subunit of the enzyme, suggesting that vitamin B₁₂ participates in the regulation of neuronal adenylyl cyclase signal transduction.</p></div>","PeriodicalId":100502,"journal":{"name":"European Journal of Pharmacology: Molecular Pharmacology","volume":"291 3","pages":"Pages 351-358"},"PeriodicalIF":0.0,"publicationDate":"1995-11-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/0922-4106(95)90076-4","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"19693373","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pre-incubation of synaptosomes with arachidonic acid potentiates inhibition of [3H]D-aspartate transport","authors":"Denise F. Lundy,&nbsp;Gethin J. McBean","doi":"10.1016/0922-4106(95)90067-5","DOIUrl":"10.1016/0922-4106(95)90067-5","url":null,"abstract":"<div><p>The ability of low micromolar concentrations of the polyunsaturated fatty acid, arachidonic acid (cis-5,8,11,14-eicosatetraenoic acid) to inhibit the high-affinity, sodium-dependent transport of [³H]<span>D</span>-aspartate into purified synaptosomes of rat brain has been examined. Pre-incubation of the synaptosomes with arachidonic acid for 10–60 min produced a marked potentiation of the response to 10 μM arachidonic acid compared to co-incubation, and the threshold for inhibition of [³H]<span>D</span>-aspartate transport occurred at a concentration of 1 μM. Minimal inhibition of transport was seen with the unsaturated fatty acids, cis-oleic (cis-9-octadecenoic acid) and cis-linolenic (cis-9,12,15-octadecatrienoic acid),nor with the 20-carbon saturated fatty acid, arachidic acid (<em>n</em>-eicosanoic acid). Inclusion of the cyclo-oxygenase inhibitor, nor-dihydroguaretic acid (NDGA), in the presence of 5 μM arachidonic acid did not alter the inhibition of [³H]<span>D</span>-aspartate transport between 0–10 min, but did enhance the response at longer pre-incubation times. Inhibition of [³H]<span>D</span>-aspartate transport by arachidonic acid persisted during addition of the calcium ionophore, A23187, whereas removal of calcium ions from the incubation medium potentiated the response to arachidonic acid. The results are discussed in terms of the physiological relevance of the inhibition of glutamate transport by arachidonic acid, and suggest that regulation of inhibition of the glutamate transporter by arachidonic acid may be achieved by changes in the extracellular, as well as the intracellular, concentration of calcium ions.</p></div>","PeriodicalId":100502,"journal":{"name":"European Journal of Pharmacology: Molecular Pharmacology","volume":"291 3","pages":"Pages 273-279"},"PeriodicalIF":0.0,"publicationDate":"1995-11-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/0922-4106(95)90067-5","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"19693424","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Amidines are potent inhibitors of nitric oxide synthases: preferential inhibition of the inducible isoform","authors":"Garry J. Southan ,&nbsp;Csaba Szabó ,&nbsp;Michael P. O'Connor ,&nbsp;Andrew L. Salzman ,&nbsp;Christoph Thiemermann","doi":"10.1016/0922-4106(95)90071-3","DOIUrl":"10.1016/0922-4106(95)90071-3","url":null,"abstract":"<div><p>We evaluated the ability of simple alkyl amidines to inhibit the activity of the inducible isoform of nitric oxide (NO) synthase in vitro. In immunostimulated J774 macrophages, 2-iminopiperidine (EC₅₀ = 10 <em>μ</em>M) and butyramidine (EC₅₀ = 60 <em>μ</em>M) were more potent than N^G-methyl-<span>L</span>-arginine (EC₅₀ = 70 <em>μ</em>M) in inhibiting nitrite formation. The five amidines tested for their ability to inhibit the conversion of <span>L</span>-arginine to <span>L</span>-citrulline by bovine endothelial cell homogenates (a source of the constitutive, endothelial NO synthase isoform) were less effective than N^G-nitro-<span>L</span>-arginine or N^G-methyl-<span>L</span>-arginine. The rank-order of the potencies of the amidines against the en endothelial NO synthase was, in general, similar to the rank-order of the pressor effects of these agents in anesthetized rats. Thus, certain amidines are potent inhibitors of NO synthase, and are more selective towards the inducible NO synthase than the commonly used <span>L</span>-arginine based NO synthase inhibitors.</p></div>","PeriodicalId":100502,"journal":{"name":"European Journal of Pharmacology: Molecular Pharmacology","volume":"291 3","pages":"Pages 311-318"},"PeriodicalIF":0.0,"publicationDate":"1995-11-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/0922-4106(95)90071-3","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"19693428","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Carazolol: a potent, selective β3-adrenoceptor agonist","authors":"Annick Méjean,&nbsp;Jean-Luc Guillaume,&nbsp;A.Donny Strosberg","doi":"10.1016/0922-4106(95)90077-2","DOIUrl":"https://doi.org/10.1016/0922-4106(95)90077-2","url":null,"abstract":"<div><p>Carazolol is a β₁/β₂ adrenoceptor antagonist of high potency used in the treatment of hypertension. Its affinity for the β₃-adrenoceptor was determined in Chinese hamster ovary cells transfected with the gene of the human or the murine β₃-adrenoceptor. Carazolol is recognized with a nanomolar affinity, which position it among the best ligands for <em>β</em>₃-adrenoceptors. The adenylyl cyclase stimulation was measured in transfected cells where carazolol acted as a full agonist on both murine and human receptor subtypes. Furthermore, in murine adipocyte-like 3T3-F442A cells, which express <em>β</em>₃-adrenoceptor naturally, carazolol induced lipolysis. This compound also appeared to be a useful tool for molecular characterization of the <em>β</em>₃-adrenoceptor : unlike the classical <em>β</em>₃-adrenoceptor agonists, carazolol conferred an appreciable protection of receptor binding sites against inactivation by the reducing agent dithiothreitol. The major iodinated analog of carazolol retained its binding characteristics for the <em>β</em>₃-adrenoceptor and remained an efficient adenylyl cyclase stimulator in cells expressing human <em>β</em>₃-adrenoceptor.</p></div>","PeriodicalId":100502,"journal":{"name":"European Journal of Pharmacology: Molecular Pharmacology","volume":"291 3","pages":"Pages 359-366"},"PeriodicalIF":0.0,"publicationDate":"1995-11-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/0922-4106(95)90077-2","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71828781","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A long-term receptor stimulation is requisite for angiotensin II-dependent DNA synthesis in vascular smooth muscle cells from spontaneously hypertensive rats","authors":"Kohji Itazaki ,&nbsp;Mariko Hara ,&nbsp;Nobuyuki Itoh ,&nbsp;Masafumi Fujimoto","doi":"10.1016/0922-4106(95)90084-5","DOIUrl":"10.1016/0922-4106(95)90084-5","url":null,"abstract":"<div><p>Angiotensin II stimulates DNA synthesis in aortic smooth muscle cells prepared from spontaneously hypertensive rats, with maximal levels detected 20 h after stimulation. Angiotensin II receptor antagonists inhibited the angiotensin II-induced DNA synthesis. In particular, the noncompetative antagonist 2-ethoxy-1-[[2′(1<em>H</em>-tetrazol-5-yl)biphenyl-4-yl]methyl-1]<em>H</em>-benzimidazole-7-carboxylic] acid (CV11974) was more effective than expected from its affinity for the angiotensin II receptor and its potency for inhibiting angiotensin II-induced increase in cytosolic free Ca²⁺ concentration. 2-<em>n</em>-Butyl-4-chloro-5-hydroxymethyl-1-[(2′-(1 <em>H</em>-tetrazol-5-yl)biphenyl-4-yl)methyl]imidazole, potassium salt (losartan), one of the antagonists, inhibited angiotensin II-induced DNA synthesis by 92% and 79%, even when added 2 and 4 h after angiotensin II stimulation, respectively. Angiotensin II also increases the mRNA of platelet-derived growth factor-A chain and basic fibroblast growth factor. The increase was observed within 4 h after angiotensin II stimulation. In this case, the addition of losartan at 4 h after angiotensin II stimulation hardly influenced the time course of the mRNA level of growth factors. Also, conditioned media of cells stimulated with angiotensin II did not influence DNA synthesis in the presence of CV11974. These results suggest that sustained receptor stimulation with angiotensin II is required for DNA synthesis in addition to the early intracellular signaling following phospholipase C activation in a manner independent of the induction of growth factors such as platelet-derived growth factor-AA and basic fibroblast growth factor.</p></div>","PeriodicalId":100502,"journal":{"name":"European Journal of Pharmacology: Molecular Pharmacology","volume":"291 3","pages":"Pages 417-425"},"PeriodicalIF":0.0,"publicationDate":"1995-11-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/0922-4106(95)90084-5","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"19692556","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"GABA θ1 receptor: inhibition by protein kinase C activators","authors":"Tadashi Kusama ,&nbsp;Manabu Sakurai ,&nbsp;Yasuo Kizawa ,&nbsp;George R. Uhl ,&nbsp;Hajime Murakami","doi":"10.1016/0922-4106(95)90086-1","DOIUrl":"https://doi.org/10.1016/0922-4106(95)90086-1","url":null,"abstract":"<div><p>The effects of protein kinase C (PKC) activators on γ-aminobutyric acid (GABA) <em>θ</em>₁ receptor function were studied in <em>θ</em>₁-expressing<em>Xenopus</em> oocytes. The PKC activator phorbol 12-myristate 13-acetate (PMA) but not the inactive analog phorbol 12-mono-myristate inhibited the GABA-gated chloride currents. Mezerein, a non-phorbol ester type PKC activator, also inhibited the θ₁ responses, but 8-chlorophenylthio-cyclic AMP, a protein kinase A activator, had no effect. The effect of PMA was significantly reduced by a PKC inhibitor, staurosporine. These results suggest that GABA <em>θ</em>₁ receptor function can be regulated by PKC-mediated phosphorylation events.</p></div>","PeriodicalId":100502,"journal":{"name":"European Journal of Pharmacology: Molecular Pharmacology","volume":"291 3","pages":"Pages 431-434"},"PeriodicalIF":0.0,"publicationDate":"1995-11-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/0922-4106(95)90086-1","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71785495","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Implication of dopamine transporter system on 1-methyl-4-phenylpyridinium and rotenone effect in striatal synaptosomes","authors":"Mohammed Bougria,&nbsp;Javier Vitorica,&nbsp;Josefina Cano,&nbsp;Alberto Machado","doi":"10.1016/0922-4106(95)90083-7","DOIUrl":"10.1016/0922-4106(95)90083-7","url":null,"abstract":"<div><p>The neurotoxic effect of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) seems to be produced by the inhibition of the respiratory chain by its metabolite 1-methyl-4-phenylpyridinium ion (MPP⁺). At the same time, its specific selectivity seems to be related especially to the dopamine uptake system. However, it is possible that other specific different in dopaminergic neurons at the nigrostriatal system, such as constitutive metabolic deficiencies or other differences related to the energy capacity, could determine the greater vulnerability to MPP⁺. We have addressed this point by studying the effect of MPP⁺ and different inhibitors of the respiratory chain (rotenone, antimycin A and KCN) on the maximal respiratory rate from both synaptosomes and isolated synaptosomal mitochondria from different brain areas, i.e. cortex, hippocampus and striatum, and in isolated liver mitochondria. The results demonstrate the absence of differences in the effect of the inhibitors in isolated mitochondria. In contrast, a greater inhibition was found in striatal synaptosomes than in cortical or hippocampal synaptosomes when MPP⁺ and retenone were used. Moreover, nomifensine or 1-[2-[bis(4-fluorophenyl)methoxy]ethyl] 4-(3-phenylpropyl) piperazine dihydrochloride (GBR-12909), inhibitor of the dopamine uptake system, has a protective effect in both cases. Our study indicates the great importance of the dopamine uptake system in the vulnerability of the dopamine striatum system. Moreover, our results show the low selectivity of this dopamine uptake system that is able to transport actively compounds with different chemical structures such as dopamine, MPP⁺ and rotenone.</p></div>","PeriodicalId":100502,"journal":{"name":"European Journal of Pharmacology: Molecular Pharmacology","volume":"291 3","pages":"Pages 407-415"},"PeriodicalIF":0.0,"publicationDate":"1995-11-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/0922-4106(95)90083-7","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"19692555","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mevalonate pathway and isoprenoids regulate human bronchial myocyte proliferation","authors":"Teresa Viganò ,&nbsp;Alicia Hernandez ,&nbsp;Alberto Corsini ,&nbsp;Agnese Granata ,&nbsp;Pierangelo Belloni ,&nbsp;Remo Fumagalli ,&nbsp;Rodolfo Paoletti ,&nbsp;Giancarlo Folco","doi":"10.1016/0922-4106(95)90143-4","DOIUrl":"10.1016/0922-4106(95)90143-4","url":null,"abstract":"<div><p>The role of mevalonate and geranylgeraniol in the control of cellular proliferation of cultured human bronchial myocytes was examined by investigating the effect of simvastatin, an inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A reductase, the rate-limiting enzyme in mevalonate synthesis. Simvastatin inhibited the rate of growth of human bronchial smooth muscle cells in a concentration-dependent manner, with an IC₅₀ value of 0.97±0.1 <em>μ</em>M. Mevalonate (100 μM), as well as geranylgeraniol (5 μM), at their highest non-toxic concentrations, restored cell proliferation to control levels.</p></div>","PeriodicalId":100502,"journal":{"name":"European Journal of Pharmacology: Molecular Pharmacology","volume":"291 2","pages":"Pages 201-203"},"PeriodicalIF":0.0,"publicationDate":"1995-10-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1016/0922-4106(95)90143-4","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"19547034","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}