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[PMID]:28682903
[Au] Autor:Huang J; Zhang W; Li X; Feng S; Ye G; Wei H; Gong X
[Ad] Endereço:aDepartment of Gastroenterology bDepartment of Gastrointestinal Surgery, The First Affiliated Hospital of Jinan University, Guangzhou, Guangdong, China.
[Ti] Título:Acute abrin poisoning treated with continuous renal replacement therapy and hemoperfusion successfully: A case report.
[So] Source:Medicine (Baltimore);96(27):e7423, 2017 Jul.
[Is] ISSN:1536-5964
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:RATIONALE: Abrin is a highly toxic protein obtained from the seeds of Abrus precatorius, but poisoning due to ingestion of A precatorius is extremely rare in China. PATIENT CONCERNS: A 16-year-old girl, perfectly healthy before, was admitted to the department of gastroenterology owing to intentional ingestion of 10 crushed A precatorius seeds, with multiple episodes of somnolent and anxious mental status, vomiting, abdominal pain, diarrhea, hematochezia, and hematuria. DIAGNOSIS: Acute abrin poisoning. INTERVENTIONS: We immediately took effective measures including gastric lavage, purgation, gastric acid suppression by proton pump inhibitor (PPI), liver protection, hemostasis, blood volume and electrolytes resuscitation, continuous renal replacement therapy (CRRT), and hemoperfusion (HP). OUTCOMES: Her unwell mental status was improved to the point at which she became conscious and relaxed. The symptoms of vomiting, abdominal pain, diarrhea, hematochezia, and hematuria disappeared gradually. The girl eventually made an excellent recovery with no complications at her 3-month follow-up. LESSONS: The combination of CRRT and HP is an efficient measure in the treatment of abrin poisoning for which there is no specific antidote. This is the first reported case of an abrin poisoning patient successfully treated by CRRT plus HP. Our experience will be useful to other physicians in managing patients of acute abrin poisoning in the future.
[Mh] Termos MeSH primário: Abrina/envenenamento
Abrus/envenenamento
Hemoperfusão
Terapia de Substituição Renal
[Mh] Termos MeSH secundário: Adolescente
Feminino
Seres Humanos
Intenção
Sementes/envenenamento
[Pt] Tipo de publicação:CASE REPORTS; JOURNAL ARTICLE
[Nm] Nome de substância:
1393-62-0 (Abrin)
[Em] Mês de entrada:1707
[Cu] Atualização por classe:170724
[Lr] Data última revisão:
170724
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:170707
[St] Status:MEDLINE
[do] DOI:10.1097/MD.0000000000007423


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[PMID]:28288935
[Au] Autor:Sant B; Rao PV; Nagar DP; Pant SC; Bhasker AS
[Ad] Endereço:Division of Pharmacology and Toxicology, Defence Research and Development Establishment, Jhansi Road, Gwalior 474002, India.
[Ti] Título:Evaluation of abrin induced nephrotoxicity by using novel renal injury markers.
[So] Source:Toxicon;131:20-28, 2017 Jun 01.
[Is] ISSN:1879-3150
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Abrin is a potent plant toxin analogous to ricin that is derived from the seeds of Abrus precatorius plant. It belongs to the family of type II ribosome-inactivating proteins and causes cell death by irreversibly inactivating ribosomes through site-specific depurination. In this study we examined the in vivo nephrotoxicity potential of abrin toxin in terms of oxidative stress, inflammation, histopathological changes and biomarkers of kidney injury. Animals were exposed to 0.5 and 1.0 LD50 dose of abrin by intraperitoneal route and observed for 1, 3, and 7 day post-toxin exposure. Depletion of reduced glutathione and increased lipid peroxidation levels were observed in abrin treated mice. In addition, abrin also induced inflammation in the kidneys as observed through expression of MMP-9 and MMP-9/NGAL complex in abrin treated groups by using zymography method. Nephrotoxicity was also evaluated by western blot analysis of kidney injury biomarkers including Clusterin, Cystatin C and NGAL, and their results indicate severity of kidney injury in abrin treated groups. Kidney histology confirmed inflammatory changes due to abrin. The data generated in the present study clearly prove the nephrotoxicity potential of abrin.
[Mh] Termos MeSH primário: Abrina/toxicidade
Biomarcadores/sangue
Nefropatias/patologia
Rim/efeitos dos fármacos
[Mh] Termos MeSH secundário: Abrus/química
Animais
Glutationa/sangue
Inflamação/induzido quimicamente
Inflamação/patologia
Rim/patologia
Nefropatias/induzido quimicamente
Peroxidação de Lipídeos/efeitos dos fármacos
Lipocalina-2/genética
Lipocalina-2/metabolismo
Metaloproteinase 9 da Matriz/genética
Metaloproteinase 9 da Matriz/metabolismo
Camundongos
Camundongos Endogâmicos BALB C
Estresse Oxidativo/efeitos dos fármacos
Sementes/química
Toxinas Biológicas/toxicidade
Fator de Necrose Tumoral alfa/genética
Fator de Necrose Tumoral alfa/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Biomarkers); 0 (Lipocalin-2); 0 (Toxins, Biological); 0 (Tumor Necrosis Factor-alpha); 126469-30-5 (Lcn2 protein, mouse); 1393-62-0 (Abrin); EC 3.4.24.35 (Matrix Metalloproteinase 9); EC 3.4.24.35 (Mmp9 protein, mouse); GAN16C9B8O (Glutathione)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170928
[Lr] Data última revisão:
170928
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170315
[St] Status:MEDLINE


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[PMID]:28088476
[Au] Autor:Tiwari V; Bagaria S; Karande AA
[Ad] Endereço:Department of Biochemistry, Indian Institute of Science, Bangalore, Karnataka, 560012, India.
[Ti] Título:A chimeric protein of abrin and Abrus precatorius agglutinin that neutralizes abrin mediated lethality in mice.
[So] Source:Toxicon;127:122-129, 2017 Mar 01.
[Is] ISSN:1879-3150
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Abrin, a type II ribosome inactivating protein from the Abrus precatorius plant, is extremely toxic. It has been shown to be 75 times more potent than its infamous sister toxin, ricin and their potential use in bio-warfare is a cause of major concern. Although several vaccine candidates are under clinical trials for ricin, none are available against abrin. The present study proposes a chimeric protein, comprising of 1-123 amino acids taken from the A chain of abrin and 124-175 amino acids from Abrus precatorius agglutinin A chain, as a vaccine candidate against abrin intoxication. The design was based on the inclusion of the immunogenic region of the full length protein and the minimal essential folding domains required for inducing neutralizing antibody response. The chimera also contains the epitope for the only two neutralizing antibodies; D6F10 and A7C4, reported against abrin till now. Active immunization with the chimera protected all the mice challenged with 45 X LD of abrin. Also, passive transfer of antibodies raised against the chimera rescued all mice challenged with 50 X LD of toxin. Hence the chimeric protein appears to be a promising vaccine candidate against abrin induced lethality.
[Mh] Termos MeSH primário: Abrina/toxicidade
Abrus/química
Aglutininas/imunologia
Lectinas de Plantas/imunologia
Intoxicação por Plantas/prevenção & controle
Proteínas Recombinantes de Fusão/imunologia
[Mh] Termos MeSH secundário: Abrina/genética
Abrus/imunologia
Abrus/envenenamento
Animais
Anticorpos Neutralizantes/genética
Anticorpos Neutralizantes/imunologia
Epitopos
Feminino
Seres Humanos
Células Jurkat
Camundongos Endogâmicos BALB C
Lectinas de Plantas/genética
Intoxicação por Plantas/imunologia
Conformação Proteica
Coelhos
Proteínas Recombinantes de Fusão/genética
Vacinas Sintéticas/genética
Vacinas Sintéticas/imunologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Agglutinins); 0 (Antibodies, Neutralizing); 0 (Epitopes); 0 (Plant Lectins); 0 (Recombinant Fusion Proteins); 0 (Vaccines, Synthetic); 0 (abrus agglutinin); 1393-62-0 (Abrin)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170926
[Lr] Data última revisão:
170926
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170116
[St] Status:MEDLINE


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[PMID]:27834872
[Au] Autor:Sarkes DA; Hurley MM; Stratis-Cullum DN
[Ad] Endereço:Biotechnology Branch, Sensors and Electron Devices Directorate, US Army Research Laboratory, Adelphi, MD 20783, USA. deborah.a.sarkes.civ@mail.mil.
[Ti] Título:Unraveling the Roots of Selectivity of Peptide Affinity Reagents for Structurally Similar Ribosomal Inactivating Protein Derivatives.
[So] Source:Molecules;21(11), 2016 Nov 09.
[Is] ISSN:1420-3049
[Cp] País de publicação:Switzerland
[La] Idioma:eng
[Ab] Resumo:Peptide capture agents have become increasingly useful tools for a variety of sensing applications due to their ease of discovery, stability, and robustness. Despite the ability to rapidly discover candidates through biopanning bacterial display libraries and easily mature them to Protein Catalyzed Capture (PCC) agents with even higher affinity and selectivity, an ongoing challenge and critical selection criteria is that the peptide candidates and final reagent be selective enough to replace antibodies, the gold-standard across immunoassay platforms. Here, we have discovered peptide affinity reagents against abrax, a derivative of abrin with reduced toxicity. Using on-cell Fluorescence Activated Cell Sorting (FACS) assays, we show that the peptides are highly selective for abrax over RiVax, a similar derivative of ricin originally designed as a vaccine, with significant structural homology to abrax. We rank the newly discovered peptides for strongest affinity and analyze three observed consensus sequences with varying affinity and specificity. The strongest (Tier 1) consensus was FWDTWF, which is highly aromatic and hydrophobic. To better understand the observed selectivity, we use the XPairIt peptide-protein docking protocol to analyze binding location predictions of the individual Tier 1 peptides and consensus on abrax and RiVax. The binding location profiles on the two proteins are quite distinct, which we determine is due to differences in pocket size, pocket environment (including hydrophobicity and electronegativity), and steric hindrance. This study provides a model system to show that peptide capture candidates can be quite selective for a structurally similar protein system, even without further maturation, and offers an in silico method of analysis for understanding binding and down-selecting candidates.
[Mh] Termos MeSH primário: Abrina/antagonistas & inibidores
Abrina/química
Simulação de Acoplamento Molecular
Peptídeos/química
Ricina/antagonistas & inibidores
Ricina/química
[Mh] Termos MeSH secundário: Homologia Estrutural de Proteína
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Peptides); 1393-62-0 (Abrin); 9009-86-3 (Ricin)
[Em] Mês de entrada:1704
[Cu] Atualização por classe:170407
[Lr] Data última revisão:
170407
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161112
[St] Status:MEDLINE


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[PMID]:27298272
[Au] Autor:Falach R; Sapoznikov A; Gal Y; Israeli O; Leitner M; Seliger N; Ehrlich S; Kronman C; Sabo T
[Ad] Endereço:Department of Biochemistry and Molecular Genetics, Israel Institute for Biological Research, Ness-Ziona, Israel.
[Ti] Título:Quantitative profiling of the in vivo enzymatic activity of ricin reveals disparate depurination of different pulmonary cell types.
[So] Source:Toxicol Lett;258:11-19, 2016 Sep 06.
[Is] ISSN:1879-3169
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:The plant-derived toxins ricin and abrin, operate by site-specific depurination of ribosomes, which in turn leads to protein synthesis arrest. The clinical manifestation following pulmonary exposure to these toxins is that of a severe lung inflammation and respiratory insufficiency. Deciphering the pathways mediating between the catalytic activity and the developing lung inflammation, requires a quantitative appreciation of the catalytic activity of the toxins, in-vivo. In the present study, we monitored truncated cDNA molecules which are formed by reverse transcription when a depurinated 28S rRNA serves as template. We found that maximal depurination after intranasal exposure of mice to 2LD50 ricin was reached 48h, where nearly 40% of the ribosomes have been depurinated and that depurination can be halted by post-exposure administration of anti-ricin antibodies. We next demonstrated that the effect of ricin intoxication on different cell types populating the lungs differs greatly, and that outstandingly high levels of damage (80% depurination), were observed in particular for pulmonary epithelial cells. Finally, we found that the magnitude of depurination induced by the related plant-derived toxin abrin, was significantly lower in comparison to ricin, and can be attributed mostly to reduced depurination of pulmonary epithelial cells by abrin. This study provides for the first time vital information regarding the scope and timing of the catalytic performance of ricin and abrin in the lungs of intact animals.
[Mh] Termos MeSH primário: Citotoxinas/toxicidade
Pulmão/efeitos dos fármacos
Envenenamento/metabolismo
Inibidores da Síntese de Proteínas/toxicidade
Mucosa Respiratória/efeitos dos fármacos
Ribossomos/efeitos dos fármacos
Ricina/toxicidade
[Mh] Termos MeSH secundário: Abrina/administração & dosagem
Abrina/isolamento & purificação
Abrina/metabolismo
Abrina/toxicidade
Abrus/enzimologia
Administração Intranasal
Animais
Antitoxinas/uso terapêutico
Citotoxinas/administração & dosagem
Citotoxinas/antagonistas & inibidores
Citotoxinas/metabolismo
DNA Complementar/metabolismo
Feminino
Citometria de Fluxo
Dose Letal Mediana
Pulmão/metabolismo
Pulmão/patologia
Camundongos
Pneumonia/etiologia
Pneumonia/prevenção & controle
Envenenamento/tratamento farmacológico
Envenenamento/patologia
Envenenamento/fisiopatologia
Inibidores da Síntese de Proteínas/administração & dosagem
Inibidores da Síntese de Proteínas/química
Inibidores da Síntese de Proteínas/metabolismo
Purinas/metabolismo
RNA Ribossômico 28S/metabolismo
Insuficiência Respiratória/etiologia
Insuficiência Respiratória/prevenção & controle
Mucosa Respiratória/metabolismo
Mucosa Respiratória/patologia
Ribossomos/enzimologia
Ribossomos/metabolismo
Ricina/administração & dosagem
Ricina/antagonistas & inibidores
Ricina/metabolismo
Ricinus/enzimologia
[Pt] Tipo de publicação:COMPARATIVE STUDY; JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antitoxins); 0 (Cytotoxins); 0 (DNA, Complementary); 0 (Protein Synthesis Inhibitors); 0 (Purines); 0 (RNA, Ribosomal, 28S); 1393-62-0 (Abrin); 9009-86-3 (Ricin)
[Em] Mês de entrada:1702
[Cu] Atualização por classe:170926
[Lr] Data última revisão:
170926
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160615
[St] Status:MEDLINE


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[PMID]:27055473
[Au] Autor:Yu Y; Yang R; Zhao X; Qin D; Liu Z; Liu F; Song X; Li L; Feng R; Gao N
[Ad] Endereço:Pharmacology and Toxicology Research Center, Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing 100193, China Center of Research on Life Sciences and Environmental Sciences, Harbin University of Commerce, Harbin 150076, China.
[Ti] Título:Abrin P2 suppresses proliferation and induces apoptosis of colon cancer cells via mitochondrial membrane depolarization and caspase activation.
[So] Source:Acta Biochim Biophys Sin (Shanghai);48(5):420-9, 2016 May.
[Is] ISSN:1745-7270
[Cp] País de publicação:China
[La] Idioma:eng
[Ab] Resumo:To explore the cytotoxic mechanism of abrin P2 on human colon cancer HCT-8 cells, abrin P2 was isolated from the seed of Abrus precatorius L. It was found that abrin P2 exhibited cytotoxicity toward 12 different human cancer cell lines. Our results demonstrated that abrin P2 suppressed the proliferation of human colon cancer cells (HCT-8 cells) and induced cell cycle arrest at the S and G2/M phases. The mechanism by which abrin P2 inhibited cell proliferation was via the down-regulation of cyclin B1, proliferating cell nuclear antigen and Ki67, as well as the up-regulation of P21. In addition, abrin P2 induced a dose- and time-dependent increase in the rate of HCT-8 cell apoptosis. Treatment with both Z-VAD-FMK, a broad-spectrum caspase inhibitor, and abrin P2 demonstrated that abrin P2 induced HCT-8 cell apoptosis via the activation of caspases. Together, our results revealed that abrin P2-induced apoptosis in HCT-8 cells was associated with the activation of caspases-3/-8/-9, the reduction in the Bcl-2/Bax ratio, the loss of mitochondrial membrane potential, and the increase in cytochrome c release. We further showed that abrin P2 administration effectively suppressed the growth of colon cancer xenografts in nude mice. This is the first report that abrin P2 effectively inhibits colon cancer cell growth in vivo and in vitro by suppressing proliferation and inducing apoptosis.
[Mh] Termos MeSH primário: Abrina/farmacologia
Antineoplásicos Fitogênicos/farmacologia
Neoplasias do Colo/tratamento farmacológico
[Mh] Termos MeSH secundário: Animais
Apoptose/efeitos dos fármacos
Caspases/metabolismo
Pontos de Checagem do Ciclo Celular/efeitos dos fármacos
Pontos de Checagem do Ciclo Celular/genética
Linhagem Celular Tumoral
Proliferação Celular/efeitos dos fármacos
Neoplasias do Colo/metabolismo
Neoplasias do Colo/patologia
Ativação Enzimática/efeitos dos fármacos
Seres Humanos
Masculino
Potencial da Membrana Mitocondrial/efeitos dos fármacos
Camundongos
Camundongos Nus
RNA Mensageiro/genética
RNA Neoplásico/genética
Ensaios Antitumorais Modelo de Xenoenxerto
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antineoplastic Agents, Phytogenic); 0 (RNA, Messenger); 0 (RNA, Neoplasm); 1393-62-0 (Abrin); EC 3.4.22.- (Caspases)
[Em] Mês de entrada:1702
[Cu] Atualização por classe:170501
[Lr] Data última revisão:
170501
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160409
[St] Status:MEDLINE
[do] DOI:10.1093/abbs/gmw023


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[PMID]:26379120
[Au] Autor:Kumar MS; Karande AA
[Ad] Endereço:a Undergraduate Studies and Department of Biochemistry ; Indian Institute of Science ; Bangalore , Karnataka , India.
[Ti] Título:A monoclonal antibody to an abrin chimera recognizing a unique epitope on abrin A chain confers protection from abrin-induced lethality.
[So] Source:Hum Vaccin Immunother;12(1):124-31, 2016.
[Is] ISSN:2164-554X
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Abrin, obtained from the seeds of Abrus precatorius plant, is a potent toxin belonging to the family of type II ribosome-inactivating proteins. Recently, a recombinant vaccine consisting of the A subunits of abrin and its homolog Abrus precatorius agglutinin (APA) was demonstrated to protect mice from abrin lethality. Toward identifying neutralizing epitopes recognized during this response, we generated monoclonal antibodies against the proposed vaccine candidate. One antibody, namely A7C4, the corresponding epitope of which was found to be distal to the active site of the enzymatic A chain, prevented abrin-mediated toxicity on cells and abrin-induced lethality in mice but did not inhibit the catalytic activity of the A chain. The in vivo protection conferred by monoclonal antibody A7C4 highlights the potential use of this antibody as a promising immunotherapeutic.
[Mh] Termos MeSH primário: Abrina/imunologia
Abrina/toxicidade
Anticorpos Monoclonais/imunologia
Antitoxinas/imunologia
Epitopos/imunologia
Envenenamento/prevenção & controle
[Mh] Termos MeSH secundário: Animais
Anticorpos Monoclonais/administração & dosagem
Antitoxinas/administração & dosagem
Camundongos Endogâmicos BALB C
Análise de Sobrevida
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Antibodies, Monoclonal); 0 (Antitoxins); 0 (Epitopes); 1393-62-0 (Abrin)
[Em] Mês de entrada:1612
[Cu] Atualização por classe:170220
[Lr] Data última revisão:
170220
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:150918
[St] Status:MEDLINE
[do] DOI:10.1080/21645515.2015.1067741


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[PMID]:26492622
[Au] Autor:Xu C; Li X; Liu G; Xu C; Xia C; Wu L; Zhang H; Yang W
[Ad] Endereço:1 College of Animal Science And Veterinary Medicine, Heilongjiang Bayi Agricultural University , China .
[Ti] Título:Development of ELISA and Colloidal Gold-PAb Conjugate-Based Immunochromatographic Assay for Detection of Abrin-a.
[So] Source:Monoclon Antib Immunodiagn Immunother;34(5):341-5, 2015 Oct.
[Is] ISSN:2167-9436
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:When abrin-a was combined with several polyclonal antibodies (PAb), the detection limit could be increased. In this way, a monoclonal antibody (capture) and polyclonal antibody (detection) sandwich enzyme-linked immunosorbent assay (ELISA) and a colloidal gold-PAb conjugate-based immunochromatographic assay for detection of abrin-a were developed. The ELISA had a detection limit of 3.9 ng/mL for abrin-a in standard solution and 7.8 ng/mL in soybean milk, and was more sensitive than polyclonal antibody (capture) and monoclonal antibody (detection) ELISA, which had a detection limit of 15.6 ng/mL. The test strip had a detection range of 50 to 500 ng/mL for abrin-a and a detection limit in standard solution or soybean milk samples of 50 ng/mL. However, the test strip had a reduced detection capability compared with a colloidal gold-monoclonal antibody conjugate-based immunochromatographic assay test strip, which had a lower detection limit of 10 ng/mL. The developed ELISAs and test strip show the specificity towards abrin-a and have no cross-reactivity towards abrin-b, -c, -d, ricin, or the agglutinins from either castor beans or rosary peas.
[Mh] Termos MeSH primário: Abrina/imunologia
Anticorpos Monoclonais/imunologia
Ensaio de Imunoadsorção Enzimática/métodos
Coloide de Ouro/imunologia
[Mh] Termos MeSH secundário: Reações Cruzadas/imunologia
Imunocromatografia/métodos
Limite de Detecção
Sensibilidade e Especificidade
Feijão de Soja/imunologia
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Antibodies, Monoclonal); 0 (Gold Colloid); 1393-62-0 (Abrin)
[Em] Mês de entrada:1608
[Cu] Atualização por classe:151023
[Lr] Data última revisão:
151023
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:151023
[St] Status:MEDLINE
[do] DOI:10.1089/mab.2014.0100


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[PMID]:26475386
[Au] Autor:Chaturvedi K; Jadhav SE; Bhutia YD; Kumar O; Kaul RK; Shrivastava N
[Ad] Endereço:Defence Research and Development Establishment Division of Pharmacology and Toxicology Gwalior India.
[Ti] Título:Purification and dose-dependent toxicity study of abrin in swiss albino male mice.
[So] Source:Cell Mol Biol (Noisy-le-grand);61(5):36-44, 2015 Oct 16.
[Is] ISSN:1165-158X
[Cp] País de publicação:France
[La] Idioma:eng
[Ab] Resumo:Abrin, a phytotoxin obtained from the seeds of the Abrus precatorius plant, is highly toxic with an estimated human fatal dose of 0.1­1 µg/kg. In this study, abrin was purified and characterized through SDS PAGE and mass spectrometry analysis; further study on toxicity was carried out to investigate the alteration in biochemical, and hematological variables through histopathological observations in mice. The intraperitoneal LD50 value of purified abrin for mice was found to be 0.91µg/kg of body weight. Mice were exposed to 0.4 and 1.0 LD50 abrin doses intraperitoneally and observed on days 1, 3, and 7. Plasma GOT and GPT levels increased significantly at both doses. At 1.0 LD50 dose, alkaline phosphatase, bilirubin, urea, uric acid, and creatinine levels increased, whereas albumin, total protein, glucose and cholesterol levels decreased significantly. Abrin intoxication also altered the hemoglobin, WBC, and RBC counts significantly at 1.0 LD50 dose. Liver GSH levels decreased while lipid peroxidation increased significantly in a dose­dependent manner. Biochemical changes were supported by the histological investigation, which also showed the degenerative changes in organs. In conclusion, abrin intoxication caused toxic effects and severe damages on studied organs mediated through alteration in biochemical and hematological variables, lipid peroxidation, and degeneration.
[Mh] Termos MeSH primário: Abrina/toxicidade
Peroxidação de Lipídeos/fisiologia
Fígado/patologia
Estresse Oxidativo/efeitos dos fármacos
[Mh] Termos MeSH secundário: Abrus/metabolismo
Animais
Peso Corporal/efeitos dos fármacos
Glutationa/metabolismo
Dose Letal Mediana
Masculino
Espectrometria de Massas
Camundongos
Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz
Substâncias Reativas com Ácido Tiobarbitúrico/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Thiobarbituric Acid Reactive Substances); 1393-62-0 (Abrin); GAN16C9B8O (Glutathione)
[Em] Mês de entrada:1608
[Cu] Atualização por classe:151017
[Lr] Data última revisão:
151017
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:151018
[St] Status:MEDLINE


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[PMID]:26086588
[Au] Autor:Wang J; Gao S; Xin W; Kang L; Xu N; Zhang T; Liu W; Wang J
[Ad] Endereço:a State Key Laboratory of Pathogen and Biosecurity; Beijing Institute of Microbiology and Epidemiology ; Beijing , PR China.
[Ti] Título:A novel recombinant vaccine protecting mice against abrin intoxication.
[So] Source:Hum Vaccin Immunother;11(6):1361-7, 2015.
[Is] ISSN:2164-554X
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Abrin toxin (AT) consisting of an A chain and a B chain is a potential agent for bioterrorism and an effective vaccine against AT poisoning is urgently required. In this study, AT B chain (ATB) was successfully expressed in the Escherichia coli (E. coli) and assessed the protection capacity against AT intoxication. The recombinant ATB (rATB) subunit induces a good immune response after 4 immunizations. All BALB/c mice immunized intraperitoneally (i.p.) with the purified rATB protein survived after challenged with 5 × LD50 of AT. Transfusion of sera from immunized mice provided passive protection in naive mice. Furthermore, histological findings showed that immunization with rATB decreased the severity of toxin-related tissue damage. This work indicates that the rATB protein may be a promising vaccine candidate against human exposure to AT.
[Mh] Termos MeSH primário: Abrina/imunologia
Abrina/toxicidade
Envenenamento/prevenção & controle
Vacinas Sintéticas/imunologia
[Mh] Termos MeSH secundário: Animais
Modelos Animais de Doenças
Feminino
Imunização Passiva
Injeções Intraperitoneais
Camundongos Endogâmicos BALB C
Envenenamento/patologia
Análise de Sobrevida
Vacinas Sintéticas/administração & dosagem
Vacinas Sintéticas/genética
Vacinas Sintéticas/isolamento & purificação
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Vaccines, Synthetic); 1393-62-0 (Abrin)
[Em] Mês de entrada:1603
[Cu] Atualização por classe:160204
[Lr] Data última revisão:
160204
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:150619
[St] Status:MEDLINE
[do] DOI:10.1080/21645515.2015.1008879



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