1,731,372 research outputs found
BAY 41-2272 inhibits human neutrophil functions
No full textBAY 41-2272 is a guanylyl cyclase (GC) stimulator derived from YC-1 (3-[(5′-hydroxymethyl-2′-furyl)-1-benzyl indazole]). Previous studies by our group showed that BAY 41-2272 activates human monocytes via soluble guanylyl cyclase (sGC) and cGMP. In this study, we investigated the effect of BAY 41-2272 on human neutrophil function and found that 30 μM BAY 41-2272 inhibits neutrophil migration (1.82-fold lower than FMLP, P < 0.05 by one-way ANOVA followed by Tukey's test), oxidative burst (1.70-fold lower than PMA, P < 0.05 by one-way ANOVA followed by Tukey's test), and IL-8 cytokine production (1.80-fold lower than PMA, P < 0.05 by one-way ANOVA followed by Tukey's test). Our results suggest that these effects are independent of the sGC pathway but dependent instead on cGMP production, as the response induced by 30 μM BAY 41-2272 was 6.40-fold greater than that observed in our negative control (P < 0.05 by parametric t-test). 1H-[1, 2, 4] oxadiazolo [4,3-a] quinoxalin-1-one (ODQ), which is an irreversible inhibitor of sGC, was unable to reverse the effects of BAY 41-2272 on human neutrophils, indicating that this drug acts independently of sGC. Our results confirm the immunomodulatory effect of BAY 41-2272 on human neutrophils75COORDENAÇÃO DE APERFEIÇOAMENTO DE PESSOAL DE NÍVEL SUPERIOR - CAPESNão te
2272. Giraldus Cambrensis
No full text2272. Giraldus Cambrensis. In: Molinier Auguste. Les Sources de l'histoire de France - Des origines aux guerres d'Italie (1494). III. Les Capétiens, 1180-1328. Paris : A. Picard et fils, 1903. pp. 18-19
Effect of BAY 41-2272 in human T lymphocytes.
No full textNo presente trabalho avaliamos o potencial do BAY 41-2272 e sua via, como uma ferramenta para modulação da função dos linfócitos. Para isso, realizamos tratamentos farmacológicos com BAY 41-2272, avaliando a produção de citocinas e observamos que este fármaco, como ativador direto, não induz produção de IFN, IL-4 e IL-10 nos linfócitos. No entanto, o prétratamento por 24 horas com BAY 41-2272, com posterior ativação com PMA, mostrou que esta droga tem efeito inibitório na produção das citocinas. Em vista disto, avaliamos se este fármaco seria capaz de ativar estas células através da expressão de CD69. Vimos que por si só esta droga não foi capaz de aumentar a expressão de CD69, no entanto o pré-tratamento com BAY 41-2272 inibiu a ativação dos linfócitos T CD4. Assim, avaliamos se o fármaco seria capaz de inibir a expressão de fatores de transcrição FOXP3, RORT, Tbet e GATA3. Vimos que o BAY 41-2272 não induziu expressão desses fatores de transcrição e o pré-tratamento com este fármaco não alterou a expressão de FOXP3, RORT e GATA3, mas inibiu a expressão de Tbet quando comparado ao estimulado com PMA e Ionomicina sem o prétratamento. Observamos também que o pré-tratamento com BAY 41-2272 inibiu a linfoproliferação. Estes resultados sugerem que o BAY 41-2272 e sua via, têm um perfil inibitório sobre os linfócitos T CD4, e potencialmente podem ser utilizados como imunomodulador em pacientes com comprometimento do sistema imunológico e síndromes linfoproliferativas.In this work, we evaluated the potential of BAY 41-2272 and its pathway as a tool for modulating lymphocyte function. For this, we performed pharmacological treatments with BAY 41-2272, evaluating the production of cytokines and observed that this drug, as a direct activator, does not induce production of IFN, IL-4 e IL-10. However, pre-treatment for 24 hours with BAY 41-2272 and subsequente activation with PMA showed that this drug has an inhibitory effect on cytokine production. Thus, we evaluated if this drug would be able to activate these cells through the CD69 expression. We saw that alone, BAY 41-2272 was not able to increase CD69 expression, however, pre-treatment inhibited activation of CD4 T lymphocytes. Then, we evaluated if this chemical compound would be able to inhibite the expression of transcription factors FOXP3, RORT, Tbet and GATA3. We have seen that BAY 41-2272 did not induce expression of these transcription factors and pretreatment with this drug did not alter expression of FOXP3, RORT and GATA3, but inhibited Tbet expression. We also observed that pre-treatment with BAY 41-2272 inhibited lymphoproliferation. These results suggest that BAY 41-2272 and its pathway have an inhibitory profile on CD4 T lymphocytes and can potentially be used as an immunomodulator in patients with impaired imune system and lymphoproliferative syndromes
Block Card 2272 Kneer Drive
No full textThis image was produced by the Auditor's Office in Lucas County, Ohio for tax assessment purposes. Associated dates are approximate. Descriptive terms related to this photograph include: 2272 Kneer Drive (Toledo, Ohio) | Heatherwoods (Toledo, Ohio) | South Toledo Area (Toledo, Ohio) | Split-Level Style | Dwellin
Block Card 2272 Forrer Street
No full textThis image was produced by the Auditor's Office in Lucas County, Ohio for tax assessment purposes. Associated dates are approximate. Descriptive terms related to this photograph include: Shotgun houses | 2272 Forrer Street (Toledo, Ohio) | Dwelling | Morfoot's Addition (Toledo, Ohio) | Scott Park Area (Toledo, Ohio
Stimulation of soluble guanylyl cyclase by BAY 41-2272 relaxes anococcygeus muscle: interaction with nitric oxide
No full textFAPESP - FUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULOThe compound BAY 41-2272 stimulates the soluble guanylyl cyclase in a nitric oxide (NO)-independent manner. We have investigated the potency and efficacy of BAY 41-2272 in the rat anococcygeus muscle, as well as the effects of BAY 41-2272 on NO-mediated anococcygeus relaxations. BAY 41-2272 (0.01-10 mu M) potently relaxed precontracted anococcygeus muscle strips, with a pEC(50) value of 6.44 +/- 0.03 and maximum response of 100 +/- 2%. The soluble guanylyl cyclase inhibitor H-1-[1,2,4]-oxidiazolo[4,3-a] quinoxalin-1-one (ODQ, 1 mu M) and the NO inhibitor N-omega-nitro-L-arginine methyl ester (L-NAME, 100 mu M) caused significant rightward shifts in the concentration-response curves to BAY 41-2272. The phosphodiesterase type-5 inhibitor tadalafil (0.1 mu M) markedly enhanced the relaxations evoked by BAY 41-2272. In addition, BAY 41-2272 increased the duration of nitrergic relaxations by approximately 55%. The relaxations induced by glyceryl trinitrate were also significantly potentiated by BAY 41-2272. In conclusion, BAY 41-2272 interacts with endogenous and exogenous NO causing a potent relaxation of rat anococcygeus muscleElsevier5301-2157165FAPESP - FUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULOFAPESP - FUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULOsem informaçãoAmsterd
Block Card 2272 Ashland Avenue
No full textThis image was produced by the Auditor's Office in Lucas County, Ohio for tax assessment purposes. Associated dates are approximate. Descriptive terms related to this photograph include: Queen Anne style | 2272 Ashland Avenue (Toledo, Ohio) | dwelling | Ashland Avenue (Toledo, Ohio) | Machen's Suburban Addition (Toledo, Ohio) | Machen's Addition (Toledo, Ohio) | Old West End (Toledo, Ohio) | Southeast Quarter 7-9-2
Evaluation of relaxant effect of BAY 41-2272 in rabbit isolated detrusor
No full textOrientador: Edson AntunesDissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Ciencias MedicasResumo: A síndrome da bexiga hiperativa atinge grande parte da população mundial, e gera sintomas que prejudicam a qualidade de vida dos portadores. Está associada com a hiperatividade do detrusor que se dá por um aumento das contrações espontâneas. Alguns estudos têm mostrado que a deficiência de NO é um dos fatores responsáveis por gerar estas contrações espontâneas. É sabido que o mecanismo de sinalização do NO envolve a ativação da guanilil ciclase solúvel e produção de GMPc. Atualmente, algumas drogas têm sido sintetizadas para mimetizar o efeito exercido pelo NO, tal como o BAY 41-2272, um potente estimulador da guanilil ciclase solúvel independente de NO. Vários trabalhos mostraram que o BAY 41-2272 causa relaxamento de vários tipos de musculatura lisa, podendo ser um composto com grande potencial terapêutico em doenças onde a via do NO/GMPc está prejudicada. O objetivo deste trabalho é investigar a capacidade do BAY 41-2272 de relaxar detrusor isolado de camundongo, coelho e rato in vitro e os mecanismos farmacológicos envolvidos na resposta relaxante. Camundongos C57b6 machos (30-40 g), coelhos New Zealand machos (2-3 kg) e ratos Wistar machos (250-300 g) foram anestesiados e mortos. As bexigas foram removidas e fragmentos de detrusor foram montados em banho para órgãos isolados contendo 10 ml de solução de Krebs. Curvas concentração-resposta ao BAY 41-2272 (10-9 - 10-4 M) foram construídas em tecidos précontraídos com carbacol (10 µM) ou KCl (80 mM), na ausência ou na presença de LNAME (inibidor da óxido nítrico sintase; 100 µM), ODQ (inibidor da guanilato ciclase solúvel; 100 µM), Sildenafil (inibidor da fosfodiesterase tipo-5; 10 µM), ou inibidores de canais de potássio (0,1 µM charibdotoxina + 1 µM apamina; 1µM tetraetilamônio; ou 10 µM glibenclamida). Curvas concentração-resposta ao nitroprussiato de sódio (SNP; 10-8 - 10-4 M), gliceril trinitrato (GTN; 10-8 - 10-4 M) e 8Br-GMPc (10-8 - 10-4 M) foram também construídas. Contrações induzidas por CaCl2 extracelular foram avaliadas na presença do BAY 41-2272, bem como o efeito no influxo de cálcio em plaquetas isoladas de coelho. Níveis de GMPc e AMPc foram avaliados após a estimulação do detrusor com BAY 41- 2272 (10 e 100 µM) e SNP (100 µM) na ausência ou na presença de ODQ (100 µM), através de imunoensaio enzimático (ELISA). O BAY 41-2272 produziu relaxamento de detrusor isolado de camundongos, ratos e coelhos de maneira concentração-dependente, com valores de resposta máxima de 61,3 ± 6,6%, 91,7 ± 5,9% e 95,1 ± 9,9%, respectivamente. Detrusor de coelhos foram selecionados para os experimentos subseqüentes. Os doadores de NO, SNP e GTN, bem com o 8Br-GMPc produziram um discreto relaxamento comparado ao BAY 41-2272. O tratamento dos tecidos com L-NAME (100 µM) ou sildenafil (10 µM) não afetou de maneira significativa o relaxamento induzido pelo BAY 41-2272. Entretanto, o ODQ (100 µM), reduziu significativamente a resposta ao BAY 41-2272. Os bloqueadores de canais de K+ (apamin + charibdotoxina, glibenclamida ou tetraetilamônio) também não afetaram a resposta relaxante do BAY 41-2272. O BAY 41-2272 (10 e 100 µM) elevou os níveis de GMPc em cerca de 14 e 20 vezes respectivamente, sem afetar os níveis de AMPc. Na menor concentração do BAY 41-2272 (10 µM), o ODQ aboliu a elevação dos níveis de GMPc, ao passo que na maior concentração do BAY 41-2272 (100 µM), o ODQ inibiu parcialmente a elevação dos níveis
de GMPc. A adição de CaCl2 (0,01-30 mM) extracelular em detrusor isolado de coelhos causou contração de maneira concentração-dependente que foi significativamente reduzida pelo tratamento prévio com BAY 41-2272 (1 e 10 µM), sendo que este efeito não foi prevenido pelo ODQ. O BAY 41-2272 reduziu significativamente o aumento dos níveis intracelulares de cálcio em plaquetas de coelho induzido por trombina. Em resumo, o BAY 41-2272 produz relaxamento em detrusor isolado de camundongos, coelhos e ratos através da produção de GMPc e da inibição do influxo de cálcio que independe de GMPcAbstract: Overactive bladder (OAB) is a highly prevalent condition that affects millions of people worldwide with a profound effect on quality of life. The bladder overactivity is related to spontaneous contractions of the detrusor smooth muscle causing an increase in the intravesical pressure and consequently stimulation of the micturirion reflex. Evidences suggest that impairment of nitric oxide (NO) signaling pathway may account for OAB. It is well established that NO signaling pathways involves soluble guanylate cyclase (sGC) stimulation and cyclic GMP production. Recently, pharmacological agents capable of directly stimulating soluble guanylate cyclase independenly of NO, such as BAY 41-2272 has been reported to produce relaxation of different types of smooth muscle, showing great therapeutic potential in disturbs which NO pathway is impaired. The present study aimed to evaluate the capacity of BAY 41-2272 to relax isolated mouse, rat and rabbit DSM and the mechanism underlying these response. C57b6 male mice, Wistar male rats and New Zealand male rabbits were anesthetized, and urinary bladder removed. DSM was transferred to 10-mL organ baths containing oxygenated and warmed Krebs-Henseleit solution. Tissues were connected to force-displacement transducers and changes in isometric force were recorded. Concentration-response curves to BAY 41-2272 (10-9 - 10-4M) were constructed, in previously contracted tissues with carbachol (10 µM) or KCl (80 mM), in the absence and in the presence of L-NAME (Nitric Oxide Synthase inhibitor; 100 µM), ODQ (sGC inhibitor; 100 µM), Sildenafil (phosphodiesterase type-5 inhibitor; 10 µM), or potassium channel blockers (0.1 µM charybdotoxin + 1 µM apamin; 1 µM tetraethylammonium; or 10 µM glybenclamide). Concentration-response curves to sodium nitroprusside (SNP; 10-8 - 10-4 M), glyceryl trinitrate (GTN; 10-8 - 10-4 M) and 8Br-cGMP (10-8 - 10-4 M) were also constructed. CaCl2-induced contractions in DSM and calcium influx in rabbit isolated platelets were evaluated in the presence of BAY 41-2272. Levels of cAMP and cGMP in DSM strips were determined after treatment with BAY 41-2272 (10 and 100 µM), SNP (100 µM) in the absence or in the presence of ODQ (100 µM) using specific EIA kit. BAY 41-2272 (0.001-100 µM) produced concentration-dependent DSM relaxations in mouse, rat and rabbit with maximal responses of 61.3 ± 6.6%, 95.1 ± 9.9% and 91.7 ± 5.9%, respectively. The NO-donors sodium nitroprusside and glyceryl trinitrate, as well as 8-bromo-cGMP also produced concentration-dependent rabbit DSM relaxations, but to a lesser extent than BAY 41-2272. Pretreatment with L-NAME (NO synthesis inhibitor) or sildenafil (phosphodiesterase-5 inhibitor) had no effect in BAY 41-2272- induced responses. However, the soluble guanylyl cyclase inhibitor ODQ significantly reduced BAY 41-2272-induced relaxantions. BAY 41-2272 (10 and 100 µM) increased the bladder cGMP levels by about of 14- and 20-fold, respectively, without affecting the cAMP levels. The cGMP increases in response to BAY 41-2272 and SNP were markedly reduced by ODQ. CaCl2 caused a concentration-dependent contraction in DSM strips and BAY 41- 2272 significantly reduced the contractile responses to extracellular Ca2+ in an ODQinsensitive manner. BAY 41-2272 also significantly reduced the increase of intracellular calcium levels induced by thrombin. This inhibitory effect was completely reverted after the treatment with ODQ. BAY 41-2272 relaxes DSM of the three animal species studied. BAY 41-2272-induced DSM relaxation involves mainly cGMP production, but an additional mechanism involving Ca2+ influx blockade independently of cGMP production appears to be involvedMestradoFarmacologiaMestre em Farmacologi
Going Beyond Counting First Authors in Author Co-citation Analysis
Get PDFThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
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