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[PMID]:28461065
[Au] Autor:Hu D; Bowder D; Wei W; Thompson J; Wilson MA; Xiang SH
[Ad] Endereço:Nebraska Center for Virology, University of Nebraska-Lincoln, Lincoln, NE 68583, United States; School of Veterinary Medicine and Biomedical Sciences, University of Nebraska-Lincoln, Lincoln, NE 68583, United States.
[Ti] Título:Tryptophan 375 stabilizes the outer-domain core of gp120 for HIV vaccine immunogen design.
[So] Source:Vaccine;35(23):3067-3075, 2017 05 25.
[Is] ISSN:1873-2518
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:The outer-domain core of gp120 may serve as a better HIV vaccine immunogen than the full-length gp120 because of its greater stability and immunogenicity. In our previous report, we introduced two disulfide bonds to the outer-domain core of gp120 to fix its conformation into a CD4-bound state, which resulted in a significant increase in its immunogenicity when compared to the wild-type outer-domain core. In this report, to further improve the immunogenicity of the outer-domain core based immunogen, we have introduced a Tryptophan residue at gp120 amino acid sequence position 375 (375S/W). Our data from immunized guinea pigs indeed shows a striking increase in the immune response due to this stabilized core outer-domain. Therefore, we conclude that the addition of 375W to the outer-domain core of gp120 further stabilizes the structure of immunogen and increases the immunogenicity.
[Mh] Termos MeSH primário: Vacinas contra a AIDS/imunologia
Anticorpos Anti-HIV/imunologia
Proteína gp120 do Envelope de HIV/química
Proteína gp120 do Envelope de HIV/imunologia
Imunogenicidade da Vacina
Triptofano/química
[Mh] Termos MeSH secundário: Vacinas contra a AIDS/administração & dosagem
Vacinas contra a AIDS/química
Substituição de Aminoácidos
Animais
Anticorpos Neutralizantes/imunologia
Antígenos CD4
Desenho de Drogas
Epitopos/química
Cobaias
Anticorpos Anti-HIV/sangue
HIV-1/imunologia
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (AIDS Vaccines); 0 (Antibodies, Neutralizing); 0 (CD4 Antigens); 0 (Epitopes); 0 (HIV Antibodies); 0 (HIV Envelope Protein gp120); 8DUH1N11BX (Tryptophan)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180308
[Lr] Data última revisão:
180308
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170503
[St] Status:MEDLINE


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[PMID]:29256283
[Au] Autor:Nógrádi AL; Cope I; Balogh M; Gál J
[Ad] Endereço:1 Department and Clinic of Exotic Animal and Wildlife Medicine, University of Veterinary Medicine , István u. 2, H-1078 Budapest , Hungary.
[Ti] Título:Review of gastric torsion in eight guinea pigs (Cavia porcellus).
[So] Source:Acta Vet Hung;65(4):487-499, 2017 12.
[Is] ISSN:0236-6290
[Cp] País de publicação:Hungary
[La] Idioma:eng
[Ab] Resumo:The authors present eight cases of gastric dilatation and volvulus (GDV) in guinea pigs from the Department and Clinic of Exotic Animal and Wildlife Medicine, University of Veterinary Medicine, Budapest, Hungary between 2012 and 2016. Seven animals were operated on and two survived. Gastric torsion has been noted in many mammalian species. Gastric volvulus has a high morbidity and high mortality rate with a guarded to poor prognosis in all of these species. How GDV develops is still not widely understood. Postmortem examinations, in both our cases and previously reported cases, have failed to reveal the exact causes of the gastric torsions. The aetiology of gastric torsion in guinea pigs is probably multifactorial. Feeding fewer meals per day, eating rapidly, decreased food particle size, exercise, stress after a meal, competition, age, and an aggressive or fearful temperament, are all likely and potential risk factors for GDV development in a similar fashion to dogs. Sex, breeding, dental diseases, anatomical abnormalities, pain and pregnancy may also be contributing factors.
[Mh] Termos MeSH primário: Cobaias
Doenças dos Roedores/cirurgia
Volvo Gástrico/veterinária
[Mh] Termos MeSH secundário: Animais
Feminino
Masculino
Doenças dos Roedores/etiologia
Doenças dos Roedores/patologia
Volvo Gástrico/etiologia
Volvo Gástrico/patologia
Volvo Gástrico/cirurgia
[Pt] Tipo de publicação:CASE REPORTS; JOURNAL ARTICLE
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180305
[Lr] Data última revisão:
180305
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171220
[St] Status:MEDLINE
[do] DOI:10.1556/004.2017.046


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[PMID]:28743763
[Au] Autor:Al-Owais MM; Hettiarachchi NT; Kirton HM; Hardy ME; Boyle JP; Scragg JL; Steele DS; Peers C
[Ad] Endereço:Division of Cardiovascular and Diabetes Research, Leeds Institute of Cardiovascular and Metabolic Medicine, Faculty of Medicine and Health, University of Leeds, Leeds, United Kingdom; and.
[Ti] Título:A key role for peroxynitrite-mediated inhibition of cardiac ERG (Kv11.1) K channels in carbon monoxide-induced proarrhythmic early afterdepolarizations.
[So] Source:FASEB J;31(11):4845-4854, 2017 11.
[Is] ISSN:1530-6860
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Exposure to CO causes early afterdepolarization arrhythmias. Previous studies in rats have indicated that arrhythmias arose as a result of augmentation of the late Na current. The purpose of the present study was to examine the basis for CO-induced arrhythmias in guinea pig myocytes in which action potentials (APs) more closely resemble those of human myocytes. Whole-cell current- and voltage-clamp recordings were made from isolated guinea pig myocytes as well as from human embryonic kidney 293 (HEK293) cells that express wild-type or a C723S mutant form of ether-a-go-go-related gene (ERG; Kv11.1). We also monitored the formation of peroxynitrite (ONOO ) in HEK293 cells fluorimetrically. CO-applied as the CO-releasing molecule, CORM-2-prolonged the APs and induced early afterdepolarizations in guinea pig myocytes. In HEK293 cells, CO inhibited wild-type, but not C723S mutant, Kv11.1 K currents. Inhibition was prevented by an antioxidant, mitochondrial inhibitors, or inhibition of NO formation. CO also raised ONOO levels, an effect that was reversed by the ONOO scavenger, FeTPPS [5,10,15,20-tetrakis-(4-sulfonatophenyl)-porphyrinato-iron(III)], which also prevented the CO inhibition of Kv11.1 currents and abolished the effects of CO on Kv11.1 tail currents and APs in guinea pig myocytes. Our data suggest that CO induces arrhythmias in guinea pig cardiac myocytes the ONOO -mediated inhibition of Kv11.1 K channels.-Al-Owais, M. M., Hettiarachchi, N. T., Kirton, H. M., Hardy, M. E., Boyle, J. P., Scragg, J. L., Steele, D. S., Peers, C. A key role for peroxynitrite-mediated inhibition of cardiac ERG (Kv11.1) K channels in carbon monoxide-induced proarrhythmic early afterdepolarizations.
[Mh] Termos MeSH primário: Arritmias Cardíacas/metabolismo
Monóxido de Carbono/toxicidade
Canal de Potássio ERG1/metabolismo
Potenciais da Membrana/efeitos dos fármacos
Miócitos Cardíacos/metabolismo
Ácido Peroxinitroso/metabolismo
[Mh] Termos MeSH secundário: Animais
Arritmias Cardíacas/induzido quimicamente
Arritmias Cardíacas/genética
Arritmias Cardíacas/patologia
Canal de Potássio ERG1/genética
Cobaias
Células HEK293
Seres Humanos
Metaloporfirinas/farmacologia
Miócitos Cardíacos/patologia
Óxido Nítrico/genética
Óxido Nítrico/metabolismo
Compostos Organometálicos/farmacologia
Ácido Peroxinitroso/genética
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (5,10,15,20-tetrakis(4-sulfonatophenyl)porphyrinato iron(III) chloride); 0 (ERG1 Potassium Channel); 0 (KCNH2 protein, human); 0 (Metalloporphyrins); 0 (Organometallic Compounds); 0 (tricarbonyldichlororuthenium (II) dimer); 14691-52-2 (Peroxynitrous Acid); 31C4KY9ESH (Nitric Oxide); 7U1EE4V452 (Carbon Monoxide)
[Em] Mês de entrada:1711
[Cu] Atualização por classe:180306
[Lr] Data última revisão:
180306
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170727
[St] Status:MEDLINE
[do] DOI:10.1096/fj.201700259R


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[PMID]:29407591
[Au] Autor:Zajdel P; Kos T; Marciniec K; Satala G; Canale V; Kaminski K; Holuj M; Lenda T; Koralewski R; Bednarski M; Nowinski L; Wójcikowski J; Daniel WA; Nikiforuk A; Nalepa I; Chmielarz P; Kusmierczyk J; Bojarski AJ; Popik P
[Ad] Endereço:Department of Medicinal Chemistry, Jagiellonian University Medical College, 9 Medyczna Street, 30-688 Kraków, Poland. Electronic address: pawel.zajdel@uj.edu.pl.
[Ti] Título:Novel multi-target azinesulfonamides of cyclic amine derivatives as potential antipsychotics with pro-social and pro-cognitive effects.
[So] Source:Eur J Med Chem;145:790-804, 2018 Feb 10.
[Is] ISSN:1768-3254
[Cp] País de publicação:France
[La] Idioma:eng
[Ab] Resumo:Currently used antipsychotics are characterized by multireceptor mode of action. While antagonism of dopamine D receptors is responsible for the alleviation of "positive" symptoms of schizophrenia and the effects at other, particularly serotonergic receptors are necessary for their additional therapeutic effects, there is no consensus regarding an "ideal" target engagement. Here, a detailed SAR analysis in a series of 45 novel azinesulfonamides of cyclic amine derivatives, involving the aryl-piperazine/piperidine pharmacophore, central alicyclic amine and azinesulfonamide groups has led to the selection of (S)-4-((2-(2-(4-(benzo[b]thiophen-4-yl)piperazin-1-yl)ethyl)pyrrolidin-1-yl)sulfonyl)isoquinoline (62). The polypharmacology profile of 62, characterized by partial 5-HT R agonism, 5-HT /5-HT /D /D R antagonism, and blockade of SERT, reduced the "positive"-like, and "negative"-like symptoms of psychoses. Compound 62 produced no catalepsy, demonstrated a low hyperprolactinemia liability and displayed pro-cognitive effects in the novel object recognition task and attentional set-shifting test. While association of in vitro features with the promising in vivo profile of 62 is still not fully established, its clinical efficacy should be verified in further stages of development.
[Mh] Termos MeSH primário: Aminas/farmacologia
Antipsicóticos/farmacologia
Cognição/efeitos dos fármacos
Receptores de Dopamina D2/metabolismo
Sulfonamidas/farmacologia
[Mh] Termos MeSH secundário: Aminas/síntese química
Aminas/química
Animais
Antipsicóticos/síntese química
Antipsicóticos/química
Relação Dose-Resposta a Droga
Cobaias
Células HEK293
Seres Humanos
Masculino
Estrutura Molecular
Ratos
Ratos Wistar
Relação Estrutura-Atividade
Sulfonamidas/síntese química
Sulfonamidas/química
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Amines); 0 (Antipsychotic Agents); 0 (Receptors, Dopamine D2); 0 (Sulfonamides)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180302
[Lr] Data última revisão:
180302
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180207
[St] Status:MEDLINE


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[PMID]:29289890
[Au] Autor:Temme L; Frehland B; Schepmann D; Robaa D; Sippl W; Wünsch B
[Ad] Endereço:Institut für Pharmazeutische und Medizinische Chemie der Universität Münster, Corrensstraße 48, D-48149 Münster, Germany; Cells-in-Motion Cluster of Excellence (EXC 1003-CiM), Westfälische Wilhelms-Universität Münster, Germany.
[Ti] Título:Hydroxymethyl bioisosteres of phenolic GluN2B-selective NMDA receptor antagonists: Design, synthesis and pharmacological evaluation.
[So] Source:Eur J Med Chem;144:672-681, 2018 Jan 20.
[Is] ISSN:1768-3254
[Cp] País de publicação:France
[La] Idioma:eng
[Ab] Resumo:Antagonists addressing selectively NMDA receptors containing the GluN2B subunit are of particular interest for the treatment of various neurological disorders including neurodegenerative diseases. With the aim to bioisosterically replace the metabolically labile phenol of 7-amino-6,7,8,9-tetrahydro-5H-benzo[7]annulen-2-ols, several analogs were docked into the ifenprodil binding site leading to the hydroxymethyl derivatives 4 as promising candidates. They display the same binding pose as Ro 25-6981 and the same H-bond interactions with Gln110 and Glu236 within the GluN2B subunit. The phenylalkyl moieties occupy the hydrophobic pocket formed predominantly by Pro78 (GluN2B), Phe114 (GluN2B), and Tyr109 (GluN1b). Starting from o-phthalaldehyde, the hydroxymethyl derivatives 4 were prepared in a 7-step synthesis with a haloform reaction of trichloroacetophenone 7 as key step. In receptor binding studies, the phenylpropyl derivative 4a shows promising GluN2B affinity (K = 101 nM) and high selectivity over the PCP binding site and both σ receptor subtypes. 4a was able to inhibit the glutamate/glycine induced cytotoxicity at mouse fibroblasts with an IC value of 5.2 µM. It is assumed that the hydroxymethyl moiety of 4a stabilizes the closed channel conformation by an H-bond with Glu236 as does the phenolic OH moiety of 3, Ro 25-6981 and ifenprodil.
[Mh] Termos MeSH primário: Desenho de Drogas
Receptores de N-Metil-D-Aspartato/antagonistas & inibidores
o-Ftalaldeído/farmacologia
[Mh] Termos MeSH secundário: Animais
Células Cultivadas
Relação Dose-Resposta a Droga
Fibroblastos/efeitos dos fármacos
Cobaias
Seres Humanos
Camundongos
Simulação de Acoplamento Molecular
Estrutura Molecular
Ratos
Relação Estrutura-Atividade
o-Ftalaldeído/síntese química
o-Ftalaldeído/química
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Receptors, N-Methyl-D-Aspartate); 643-79-8 (o-Phthalaldehyde)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180302
[Lr] Data última revisão:
180302
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180101
[St] Status:MEDLINE


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[PMID]:29412172
[Au] Autor:Hull JD; Lyon RA
[Ad] Endereço:Procter & Gamble, Greater London Innovation Centre, Egham, Surrey TW20 9NW, UK.
[Ti] Título:In vitro pharmacology of ambroxol: Potential serotonergic sites of action.
[So] Source:Life Sci;197:67-72, 2018 Mar 15.
[Is] ISSN:1879-0631
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:AIMS: Ambroxol is a muco-active agent with multiple, clinically relevant effects in the airway. Despite its widespread use and well documented clinical efficacy, there are few data on its mechanism of action and receptor pharmacology beyond sodium channel blockade and inhibition of guanylate cyclase. Accordingly, in vitro studies were conducted to determine its overall receptor pharmacology and possible sites of action. MATERIALS AND METHODS: In vitro radioligand binding/enzyme inhibition studies were conducted at 62 receptors, ion channels and enzymes using standard techniques. Additional in vitro studies were conducted to establish the potency of ambroxol at selected sites. KEY FINDINGS: These studies indicate that ambroxol has affinity for the 5-HT serotonin receptor, as well as affinity for the 5-HT serotonin transporter (SERT), with IC values of 17,600 nM and 19,500 nM respectively. In vitro functional studies in isolated guinea pig colon indicate that ambroxol is a 5-HT serotonin receptor antagonist with an IC value of 36,000 nM. SIGNIFICANCE: Together, these studies indicate that ambroxol may exert its beneficial properties via antagonism of the 5-HT serotonin receptor and/or inhibition of serotonin uptake (5-HT transport: SERT), in addition to its reported effects at the sodium channel and guanylate cyclase.
[Mh] Termos MeSH primário: Ambroxol
Receptores 5-HT3 de Serotonina/metabolismo
Antagonistas do Receptor 5-HT3 de Serotonina
[Mh] Termos MeSH secundário: Ambroxol/farmacocinética
Ambroxol/farmacologia
Animais
Linhagem Celular Tumoral
Cobaias
Seres Humanos
Camundongos
Proteínas de Ligação a RNA/metabolismo
Ratos
Antagonistas do Receptor 5-HT3 de Serotonina/farmacocinética
Antagonistas do Receptor 5-HT3 de Serotonina/farmacologia
Proteínas da Membrana Plasmática de Transporte de Serotonina/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (RNA-Binding Proteins); 0 (Receptors, Serotonin, 5-HT3); 0 (SERT protein, rat); 0 (SLC6A4 protein, human); 0 (Serotonin 5-HT3 Receptor Antagonists); 0 (Serotonin Plasma Membrane Transport Proteins); 0 (Slc6a4 protein, mouse); 200168S0CL (Ambroxol)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180301
[Lr] Data última revisão:
180301
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180208
[St] Status:MEDLINE


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[PMID]:28451640
[Au] Autor:Horikawa J; Ojima H
[Ad] Endereço:Department of Computer Science and Engineering Graduate School of Engineering, Toyohashi University of Technology, Hibarigaoka 1-1, Tempaku, Toyohashi, Aichi 441-8580, Japan.
[Ti] Título:Cortical Activation Patterns Evoked by Temporally Asymmetric Sounds and Their Modulation by Learning.
[So] Source:eNeuro;4(2), 2017 Mar-Apr.
[Is] ISSN:2373-2822
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:When complex sounds are reversed in time, the original and reversed versions are perceived differently in spectral and temporal dimensions despite their identical duration and long-term spectrum-power profiles. Spatiotemporal activation patterns evoked by temporally asymmetric sound pairs demonstrate how the temporal envelope determines the readout of the spectrum. We examined the patterns of activation evoked by a temporally asymmetric sound pair in the primary auditory field (AI) of anesthetized guinea pigs and determined how discrimination training modified these patterns. Optical imaging using a voltage-sensitive dye revealed that a forward ramped-down natural sound (F) consistently evoked much stronger responses than its time-reversed, ramped-up counterpart (revF). The spatiotemporal maximum peak ( ) of F-evoked activation was always greater than that of revF-evoked activation, and these s were significantly separated within the AI. Although discrimination training did not affect the absolute magnitude of these s, the revF-to-F ratio of the activation peaks calculated at the location where hemispheres were maximally activated (i.e., F-evoked ) was significantly smaller in the trained group. The F-evoked activation propagated across the AI along the temporal axis to the ventroanterior belt field (VA), with the local activation peak within the VA being significantly larger in the trained than in the naïve group. These results suggest that the innate network is more responsive to natural sounds of ramped-down envelopes than their time-reversed, unnatural sounds. The VA belt field activation might play an important role in emotional learning of sounds through its connections with amygdala.
[Mh] Termos MeSH primário: Córtex Auditivo/fisiologia
Percepção Auditiva/fisiologia
Potenciais Evocados Auditivos
Aprendizagem
[Mh] Termos MeSH secundário: Estimulação Acústica
Animais
Discriminação (Psicologia)
Cobaias
Masculino
Imagem Óptica
Processamento de Sinais Assistido por Computador
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Em] Mês de entrada:1801
[Cu] Atualização por classe:180228
[Lr] Data última revisão:
180228
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170429
[St] Status:MEDLINE


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[PMID]:29370235
[Au] Autor:Li X; Wu GY; Yao J; Yang Y; Ye JN; Sui JF
[Ad] Endereço:Department of Physiology, College of Basic Medical Science, Third Military Medical University, Chongqing, P.R. China.
[Ti] Título:Time-limited involvement of caudal anterior cingulate cortex in trace eyeblink conditioning retrieval is dependent on conditioned stimulus intensity.
[So] Source:PLoS One;13(1):e0191320, 2018.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:The medial prefrontal cortex (mPFC) has been widely investigated for its roles in learning and memory. The present study investigated the time-limited involvement of the caudal anterior cingulate cortex (cACC) of the mPFC in the retrieval process for a simple associative motor learning, trace eyeblink conditioning (tEBC), using a 75 dB or 100 dB tone as the conditioned stimulus (CS). The GABAA receptor agonist muscimol was injected into the cACC of guinea pigs at 1 day or 4 weeks after tEBC acquisition. When muscimol was administered 1 day after tEBC acquisition, the conditioned response (CR) of the 75 dB group was severely impaired, whereas the CR of the 100 dB group exhibited no significant change relative to the control. When muscimol was administered 4 weeks after tEBC acquisition, the CR was impaired in both the 75 dB and 100 dB groups. This study indicate that the cACC of the mPFC is necessary for recent retrieval of tEBC with a low-intensity CS but not of tEBC with a high-intensity CS, whereas for remote retrieval of tEBC, the cACC of the mPFC is essential regardless of whether the CS intensity is high or low. These results support a conditional role for the mPFC in modulating recent retrieval of tEBC and a persistent role for its involvement in remote retrieval of tEBC.
[Mh] Termos MeSH primário: Condicionamento Palpebral
Córtex Pré-Frontal/fisiologia
[Mh] Termos MeSH secundário: Animais
Agonistas de Receptores de GABA-A/farmacologia
Cobaias
Masculino
Muscimol/farmacologia
Córtex Pré-Frontal/efeitos dos fármacos
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (GABA-A Receptor Agonists); 2763-96-4 (Muscimol)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180226
[Lr] Data última revisão:
180226
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180126
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0191320


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[PMID]:29352276
[Au] Autor:Osadchii OE
[Ad] Endereço:Department of Biomedical Sciences, University of Copenhagen, Copenhagen, Denmark.
[Ti] Título:Arrhythmogenic drugs can amplify spatial heterogeneities in the electrical restitution in perfused guinea-pig heart: An evidence from assessments of monophasic action potential durations and JT intervals.
[So] Source:PLoS One;13(1):e0191514, 2018.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Non-uniform shortening of the action potential duration (APD90) in different myocardial regions upon heart rate acceleration can set abnormal repolarization gradients and promote arrhythmia. This study examined whether spatial heterogeneities in APD90 restitution can be amplified by drugs with clinically proved proarrhythmic potential (dofetilide, quinidine, procainamide, and flecainide) and, if so, whether these effects can translate to the appropriate changes of the ECG metrics of ventricular repolarization, such as JT intervals. In isolated, perfused guinea-pig heart preparations, monophasic action potentials and volume-conducted ECG were recorded at progressively increased pacing rates. The APD90 measured at distinct ventricular sites, as well as the JTpeak and JTend values were plotted as a function of preceding diastolic interval, and the maximum slopes of the restitution curves were determined at baseline and upon drug administration. Dofetilide, quinidine, and procainamide reverse rate-dependently prolonged APD90 and steepened the restitution curve, with effects being greater at the endocardium than epicardium, and in the right ventricular (RV) vs. the left ventricular (LV) chamber. The restitution slope was increased to a greater extent for the JTend vs. the JTpeak interval. In contrast, flecainide reduced the APD90 restitution slope at LV epicardium without producing effect at LV endocardium and RV epicardium, and reduced the JTpeak restitution slope without changing the JTend restitution. Nevertheless, with all agents, these effects translated to the amplified epicardial-to-endocardial and the LV-to-RV non-uniformities in APD90 restitution, paralleled by the increased JTend vs. JTpeak difference in the restitution slope. In summary, these findings suggest that arrhythmic drug profiles are partly attributable to the accentuated regional heterogeneities in APD90 restitution, which can be indirectly determined through ECG assessments of the JTend vs. JTpeak dynamics at variable pacing rates.
[Mh] Termos MeSH primário: Antiarrítmicos/efeitos adversos
Arritmias Cardíacas/induzido quimicamente
Arritmias Cardíacas/fisiopatologia
[Mh] Termos MeSH secundário: Potenciais de Ação/efeitos dos fármacos
Potenciais de Ação/fisiologia
Animais
Fenômenos Eletrofisiológicos
Feminino
Flecainida/efeitos adversos
Cobaias
Técnicas In Vitro
Perfusão
Fenetilaminas/efeitos adversos
Procainamida/efeitos adversos
Quinidina/efeitos adversos
Sulfonamidas/efeitos adversos
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Anti-Arrhythmia Agents); 0 (Phenethylamines); 0 (Sulfonamides); ITX08688JL (Quinidine); K94FTS1806 (Flecainide); L39WTC366D (Procainamide); R4Z9X1N2ND (dofetilide)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180226
[Lr] Data última revisão:
180226
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180121
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0191514


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[PMID]:29374509
[Au] Autor:Jin J; Park C; Cho SH; Chung J
[Ad] Endereço:Department of Biochemistry and Molecular Biology, Seoul National University College of Medicine, Seoul 00380, Republic of Korea; Department of Biomedical Science, Seoul National University College of Medicine, Seoul 00380, Republic of Korea.
[Ti] Título:The level of decoy epitope in PCV2 vaccine affects the neutralizing activity of sera in the immunized animals.
[So] Source:Biochem Biophys Res Commun;496(3):846-851, 2018 02 12.
[Is] ISSN:1090-2104
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Viral pathogens have evolved a wide range of tactics to evade host immune responses and thus propagate effectively. One efficient tactic is to divert host immune responses toward an immunodominant decoy epitope and to induce non-neutralizing antibodies toward this epitope. Therefore, it is expected that the amount of decoy epitope in a subunit vaccine can affect the level of neutralizing antibody in an immunized animal. In this study, we tested this hypothesis by generating an antibody specific to the decoy epitope on the capsid protein of porcine circovirus type 2 (PCV2). Using this antibody, we found that two commercial vaccines contained statistically different amounts of the decoy epitope. The vaccine with lower levels of decoy epitope induced a significantly higher level of neutralizing antibody after immunization. This antibody can be used as an analytical tool to monitor the quality of a vaccine from batch to batch.
[Mh] Termos MeSH primário: Vacinas contra Adenovirus/administração & dosagem
Anticorpos Neutralizantes/imunologia
Infecções por Circoviridae/imunologia
Infecções por Circoviridae/prevenção & controle
Circovirus/imunologia
Vacinas Virais/imunologia
Vacinas Virais/toxicidade
[Mh] Termos MeSH secundário: Animais
Anticorpos Neutralizantes/sangue
Circovirus/efeitos dos fármacos
Epitopos/imunologia
Cobaias
Resultado do Tratamento
Vacinação/métodos
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Adenovirus Vaccines); 0 (Antibodies, Neutralizing); 0 (Epitopes); 0 (Viral Vaccines)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180222
[Lr] Data última revisão:
180222
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180129
[St] Status:MEDLINE



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