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[PMID]:29244815
[Au] Autor:Liu CC; You CH; Wang PJ; Yu JS; Huang GJ; Liu CH; Hsieh WC; Lin CC
[Ad] Endereço:Graduate Institute of Biomedical Sciences, College of Medicine, Chang Gung University, Tao-Yuan, Taiwan.
[Ti] Título:Analysis of the efficacy of Taiwanese freeze-dried neurotoxic antivenom against Naja kaouthia, Naja siamensis and Ophiophagus hannah through proteomics and animal model approaches.
[So] Source:PLoS Negl Trop Dis;11(12):e0006138, 2017 12.
[Is] ISSN:1935-2735
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:In Southeast Asia, envenoming resulting from cobra snakebites is an important public health issue in many regions, and antivenom therapy is the standard treatment for the snakebite. Because these cobras share a close evolutionary history, the amino acid sequences of major venom components in different snakes are very similar. Therefore, either monovalent or polyvalent antivenoms may offer paraspecific protection against envenomation of humans by several different snakes. In Taiwan, a bivalent antivenom-freeze-dried neurotoxic antivenom (FNAV)-against Bungarus multicinctus and Naja atra is available. However, whether this antivenom is also capable of neutralizing the venom of other species of snakes is not known. Here, to expand the clinical application of Taiwanese FNAV, we used an animal model to evaluate the neutralizing ability of FNAV against the venoms of three common snakes in Southeast Asia, including two 'true' cobras Naja kaouthia (Thailand) and Naja siamensis (Thailand), and the king cobra Ophiophagus hannah (Indonesia). We further applied mass spectrometry (MS)-based proteomic techniques to characterize venom proteomes and identify FNAV-recognizable antigens in the venoms of these Asian snakes. Neutralization assays in a mouse model showed that FNAV effectively neutralized the lethality of N. kaouthia and N. siamensis venoms, but not O. hannah venom. MS-based venom protein identification results further revealed that FNAV strongly recognized three-finger toxin and phospholipase A2, the major protein components of N. kaouthia and N. siamensis venoms. The characterization of venom proteomes and identification of FNAV-recognizable venom antigens may help researchers to further develop more effective antivenom designed to block the toxicity of dominant toxic proteins, with the ultimate goal of achieving broadly therapeutic effects against these cobra snakebites.
[Mh] Termos MeSH primário: Antídotos/farmacologia
Antivenenos/farmacologia
Venenos Elapídicos/química
Proteoma
Mordeduras de Serpentes/tratamento farmacológico
[Mh] Termos MeSH secundário: Animais
Antídotos/química
Antivenenos/química
Cromatografia Líquida de Alta Pressão
Cromatografia Líquida
Modelos Animais de Doenças
Venenos Elapídicos/envenenamento
Liofilização
Seres Humanos
Masculino
Camundongos
Camundongos Endogâmicos C57BL
Testes de Neutralização
Taiwan
Espectrometria de Massas em Tandem
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Antidotes); 0 (Antivenins); 0 (Elapid Venoms); 0 (Proteome)
[Em] Mês de entrada:1802
[Cu] Atualização por classe:180212
[Lr] Data última revisão:
180212
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171216
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pntd.0006138


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[PMID]:29176824
[Au] Autor:Mendonça-da-Silva I; Magela Tavares A; Sachett J; Sardinha JF; Zaparolli L; Gomes Santos MF; Lacerda M; Monteiro WM
[Ad] Endereço:Escola Superior de Saúde, Universidade do Estado do Amazonas, Manaus, Amazonas, Brazil.
[Ti] Título:Safety and efficacy of a freeze-dried trivalent antivenom for snakebites in the Brazilian Amazon: An open randomized controlled phase IIb clinical trial.
[So] Source:PLoS Negl Trop Dis;11(11):e0006068, 2017 Nov.
[Is] ISSN:1935-2735
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: In tropical areas, a major concern regarding snakebites treatment effectiveness relates to the failure in liquid antivenom (AV) distribution due to the lack of an adequate cold chain in remote areas. To minimize this problem, freeze-drying has been suggested to improve AV stability. METHODS AND FINDINGS: This study compares the safety and efficacy of a freeze-dried trivalent antivenom (FDTAV) and the standard liquid AV provided by the Brazilian Ministry of Health (SLAV) to treat Bothrops, Lachesis and Crotalus snakebites. This was a prospective, randomized, open, phase IIb trial, carried out from June 2005 to May 2008 in the Brazilian Amazon. Primary efficacy endpoints were the suppression of clinical manifestations and return of hemostasis and renal function markers to normal ranges within the first 24 hours of follow-up. Primary safety endpoint was the presence of early adverse reactions (EAR) in the first 24 hours after treatment. FDTAV thermal stability was determined by estimating AV potency over one year at 56°C. Of the patients recruited, 65 and 51 were assigned to FDTAV and SLAV groups, respectively. Only mild EARs were reported, and they were not different between groups. There were no differences in fibrinogen (p = 0.911) and clotting time (p = 0.982) recovery between FDTAV and SLAV treated groups for Bothrops snakebites. For Lachesis and Crotalus snakebites, coagulation parameters and creatine phosphokinase presented normal values 24 hours after AV therapy for both antivenoms. CONCLUSIONS/SIGNIFICANCE: Since promising results were observed for efficacy, safety and thermal stability, our results indicate that FDTAV is suitable for a larger phase III trial. TRIAL REGISTRATION: ISRCTNregistry: ISRCTN12845255; DOI: 10.1186/ISRCTN12845255 (http://www.isrctn.com/ISRCTN12845255).
[Mh] Termos MeSH primário: Antivenenos/administração & dosagem
Bothrops
Crotalus
Mordeduras de Serpentes/terapia
[Mh] Termos MeSH secundário: Adolescente
Adulto
Animais
Antivenenos/efeitos adversos
Coagulação Sanguínea
Brasil
Criança
Pré-Escolar
Feminino
Fibrinogênio/análise
Liofilização
Seres Humanos
Lactente
Recém-Nascido
Masculino
Meia-Idade
Estudos Prospectivos
Resultado do Tratamento
Adulto Jovem
[Pt] Tipo de publicação:CLINICAL TRIAL, PHASE II; JOURNAL ARTICLE; RANDOMIZED CONTROLLED TRIAL
[Nm] Nome de substância:
0 (Antivenins); 9001-32-5 (Fibrinogen)
[Em] Mês de entrada:1712
[Cu] Atualização por classe:171219
[Lr] Data última revisão:
171219
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171128
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pntd.0006068


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[PMID]:29045429
[Au] Autor:Harrison RA; Oluoch GO; Ainsworth S; Alsolaiss J; Bolton F; Arias AS; Gutiérrez JM; Rowley P; Kalya S; Ozwara H; Casewell NR
[Ad] Endereço:The Alistair Reid Venom Research Unit, Parasitology Department, Liverpool School of Tropical Medicine, Liverpool, Merseyside, United Kingdom.
[Ti] Título:Preclinical antivenom-efficacy testing reveals potentially disturbing deficiencies of snakebite treatment capability in East Africa.
[So] Source:PLoS Negl Trop Dis;11(10):e0005969, 2017 Oct.
[Is] ISSN:1935-2735
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Antivenom is the treatment of choice for snakebite, which annually kills an estimated 32,000 people in sub-Saharan Africa and leaves approximately 100,000 survivors with permanent physical disabilities that exert a considerable socioeconomic burden. Over the past two decades, the high costs of the most polyspecifically-effective antivenoms have sequentially reduced demand, commercial manufacturing incentives and production volumes that have combined to create a continent-wide vacuum of effective snakebite therapy. This was quickly filled with new, less expensive antivenoms, many of which are of untested efficacy. Some of these successfully marketed antivenoms for Africa are inappropriately manufactured with venoms from non-African snakes and are dangerously ineffective. The uncertain efficacy of available antivenoms exacerbates the complexity of designing intervention measures to reduce the burden of snakebite in sub-Saharan Africa. The objective of this study was to preclinically determine the ability of antivenoms available in Kenya to neutralise the lethal effects of venoms from the most medically important snakes in East Africa. METHODS: We collected venom samples from the most medically important snakes in East Africa and determined their toxicity in a mouse model. Using a 'gold standard' comparison protocol, we preclinically tested the comparative venom-neutralising efficacy of four antivenoms available in Kenya with two antivenoms of clinically-proven efficacy. To explain the variant efficacies of these antivenoms we tested the IgG-venom binding characteristics of each antivenom using in vitro IgG titre, avidity and venom-protein specificity assays. We also measured the IgG concentration of each antivenom. FINDINGS: None of the six antivenoms are preclinically effective, at the doses tested, against all of the most medically important snakes of the region. The very limited snake polyspecific efficacy of two locally available antivenoms is of concern. In vitro assays of the abilities of 'test' antivenom IgGs to bind venom proteins were not substantially different from that of the 'gold standard' antivenoms. The least effective antivenoms had the lowest IgG content/vial. CONCLUSIONS: Manufacture-stated preclinical efficacy statements guide decision making by physicians and antivenom purchasers in sub-Saharan Africa. This is because of the lack of both clinical data on the efficacy of most of the many antivenoms used to treat patients and independent preclinical assessment. Our preclinical efficacy assessment of antivenoms available in Kenya identifies important limitations for two of the most commonly-used antivenoms, and that no antivenom is preclinically effective against all the regionally important snakes. The potential implication to snakebite treatment is of serious concern in Kenya and elsewhere in sub-Saharan Africa, and underscores the dilemma physicians face, the need for clinical data on antivenom efficacy and the medical and societal value of establishing independent preclinical antivenom-efficacy testing facilities throughout the continent.
[Mh] Termos MeSH primário: Antivenenos/imunologia
Antivenenos/uso terapêutico
Mordeduras de Serpentes/terapia
Venenos de Serpentes/antagonistas & inibidores
[Mh] Termos MeSH secundário: África Oriental
Animais
Antivenenos/química
Antivenenos/metabolismo
Avaliação Pré-Clínica de Medicamentos
Seres Humanos
Imunoglobulina G/análise
Imunoglobulina G/metabolismo
Quênia
Dose Letal Mediana
Camundongos
Ligação Proteica
Venenos de Serpentes/química
Venenos de Serpentes/imunologia
Venenos de Serpentes/toxicidade
Serpentes
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antivenins); 0 (Immunoglobulin G); 0 (Snake Venoms)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171031
[Lr] Data última revisão:
171031
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171019
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pntd.0005969


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[PMID]:28830630
[Au] Autor:Sundar K; Venkatasubramanian S; Shanmugam S; Arthur P; Subbaraya R; Hazeena P
[Ad] Endereço:Department of Neurology, Sri Ramachandra University, India. Electronic address: drkaushiksundar@rediffmail.com.
[Ti] Título:False positive immunoassay for acetyl choline receptor antibody (AChR Ab) in patients exposed to polyvalent antisnake venom.
[So] Source:J Neuroimmunol;311:68-70, 2017 Oct 15.
[Is] ISSN:1872-8421
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:Acute flaccid paralysis is a neuromuscular emergency characterized by rapidly worsening weakness that evolves quickly to cause diaphragmatic failure. The challenge for the treating physician is to stabilize the patient, generate the differential diagnosis and determine the management; all in quick time. Neurotoxic snake bites have inadequate signs of inflammation and are easily missed. Myasthenic crisis, on the other hand, could be the first sign of myasthenia gravis in up to 20% of patients. Both present with acute respiratory failure and inadequate history. Two of our patients presented with similar clinical picture, and received polyvalent anti-snake venom obtained from hyperimmunised horses (Equus caballus). Both tested positive for anti-acetyl choline receptor antibody. After recovery, both patients narrated a history suggestive of neurotoxic envenomation. We later discovered that patients, who are exposed to polyvalent anti-snake venom (Equus caballus) prior to radioimmunoassay, demonstrate high titers of Anti-AChR Ab in their serum erroneously.
[Mh] Termos MeSH primário: Antivenenos/uso terapêutico
Autoanticorpos/sangue
Receptores Colinérgicos/imunologia
Insuficiência Respiratória/tratamento farmacológico
Mordeduras de Serpentes/tratamento farmacológico
Peçonhas/imunologia
[Mh] Termos MeSH secundário: Adulto
Seres Humanos
Masculino
Radioimunoensaio
Insuficiência Respiratória/etiologia
Mordeduras de Serpentes/complicações
Mordeduras de Serpentes/imunologia
[Pt] Tipo de publicação:CASE REPORTS; JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antivenins); 0 (Autoantibodies); 0 (Receptors, Cholinergic); 0 (Venoms)
[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:170824
[St] Status:MEDLINE


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[PMID]:28827807
[Au] Autor:Shahmy S; Kularatne SAM; Rathnayake SS; Dawson AH
[Ad] Endereço:South Asian Clinical Toxicology Research Collaboration, Faculty of Medicine, University of Peradeniya, Peradeniya, Sri Lanka.
[Ti] Título:A prospective cohort study of the effectiveness of the primary hospital management of all snakebites in Kurunegala district of Sri Lanka.
[So] Source:PLoS Negl Trop Dis;11(8):e0005847, 2017 Aug.
[Is] ISSN:1935-2735
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:INTRODUCTION: Sri Lanka records substantial numbers of snakebite annually. Primary rural hospitals are important contributors to health care. Health care planning requires a more detailed understanding of snakebite within this part of the health system. This study reports the management and epidemiology of all hospitalised snakebite in the Kurunegala district in Sri Lanka. METHODOLOGY: The district has 44 peripheral/primary hospitals and a tertiary care hospital-Teaching Hospital, Kurunegala (THK). This prospective study was conducted over one year. All hospitals received copies of the current national guidelines on snakebite management. Clinical and demographic details of all snakebite admissions to primary hospitals were recorded by field researchers and validated by comparing with scanned copies of the medical record. Management including hospital transfers was independently assessed against the national guidelines recommendation. Population rates were calculated and compared with estimates derived from recent community based surveys. RESULTS: There were 2186 admissions of snakebites and no deaths in primary hospitals. An additional 401 patients from the district were admitted directly to the teaching hospital, 2 deaths were recorded in this group. The population incidence of hospitalized snakebite was 158/100,000 which was significantly lower than community survey estimates of 499/100,000. However there was no significant difference between the incidence of envenomation of 126/100,000 in hospitalised patients and 184/100,000 in the community survey. The utilisation of antivenom was appropriate and consistent with guidelines. Seventy patients received antivenom. Anaphylactic reactions to antivenom occurred in 22 patients, treatment reactions was considered to be outside the guidelines in 5 patients. Transfers from the primary hospital occurred in 399(18%) patients but the majority (341) did not meet the guideline criteria. A snake was identified in 978 cases; venomous snakebites included 823 hump-nosed viper (Hypnalespp), 61 Russell's viper, 14 cobra, 13 common krait, 03 saw scaled viper. CONCLUSIONS: Primary hospitals received a significant number of snakebites that would be missed in surveys conducted in tertiary hospitals. Adherence to guidelines was good for the use of antivenom but not for hospital transfer or treatment of anaphylaxis. The large difference in snakebite incidence between community and hospital studies could possibly be due to non-envenomed patients not presenting. As the majority of snakebite management occurs in primary hospitals education and clinical support should be focused on that part of the health system.
[Mh] Termos MeSH primário: Anafilaxia/epidemiologia
Antivenenos/uso terapêutico
Hospitais Rurais/normas
Mordeduras de Serpentes/mortalidade
Mordeduras de Serpentes/terapia
[Mh] Termos MeSH secundário: Adulto
Anafilaxia/induzido quimicamente
Animais
Antivenenos/efeitos adversos
Bungarus
Feminino
Fidelidade a Diretrizes
Seres Humanos
Incidência
Masculino
Meia-Idade
Guias de Prática Clínica como Assunto
Estudos Prospectivos
Víbora de Russell
Sri Lanka/epidemiologia
Resultado do Tratamento
[Pt] Tipo de publicação:JOURNAL ARTICLE; MULTICENTER STUDY
[Nm] Nome de substância:
0 (Antivenins)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170917
[Lr] Data última revisão:
170917
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170823
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pntd.0005847


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[PMID]:28764620
[Au] Autor:Johnston CI; Ryan NM; Page CB; Buckley NA; Brown SG; O'Leary MA; Isbister GK
[Ad] Endereço:NSW Poisons Information Centre, Sydney Children's Hospitals Network, Sydney, NSW geoff.isbister@gmail.com.
[Ti] Título:The Australian Snakebite Project, 2005-2015 (ASP-20).
[So] Source:Med J Aust;207(3):119-125, 2017 Aug 07.
[Is] ISSN:1326-5377
[Cp] País de publicação:Australia
[La] Idioma:eng
[Ab] Resumo:OBJECTIVE: To describe the epidemiology, treatment and adverse events after snakebite in Australia. DESIGN: Prospective, multicentre study of data on patients with snakebites recruited to the Australian Snakebite Project (2005-2015) and data from the National Coronial Information System. Setting, participants: Patients presenting to Australian hospitals with suspected or confirmed snakebites from July 2005 to June 2015 and consenting to participation. MAIN OUTCOME MEASURES: Demographic data, circumstances of bites, clinical effects of envenoming, results of laboratory investigations and snake venom detection kit (SVDK) testing, antivenom treatment and adverse reactions, time to discharge, deaths. RESULTS: 1548 patients with suspected snakebites were enrolled, including 835 envenomed patients (median, 87 per year), for 718 of which the snake type was definitively established, most frequently brown snakes (41%), tiger snakes (17%) and red-bellied black snakes (16%). Clinical effects included venom-induced consumption coagulopathy (73%), myotoxicity (17%), and acute kidney injury (12%); severe complications included cardiac arrest (25 cases; 2.9%) and major haemorrhage (13 cases; 1.6%). There were 23 deaths (median, two per year), attributed to brown (17), tiger (four) and unknown (two) snakes; ten followed out-of-hospital cardiac arrests and six followed intracranial haemorrhages. Of 597 SVDK test results for envenomed patients with confirmed snake type, 29 (4.9%) were incorrect; 133 of 364 SVDK test results for non-envenomed patients (36%) were false positives. 755 patients received antivenom, including 49 non-envenomed patients; 178 (24%), including ten non-envenomed patients, had systemic hypersensitivity reactions, of which 45 (6%) were severe (hypotension, hypoxaemia). Median total antivenom dose declined from four vials to one, but median time to first antivenom was unchanged (4.3 hours; IQR, 2.7-6.3 hours). CONCLUSIONS: Snake envenoming is uncommon in Australia, but is often severe. SVDKs were unreliable for determining snake type. The median antivenom dose has declined without harming patients. Improved early diagnostic strategies are needed to reduce the frequently long delays before antivenom administration.
[Mh] Termos MeSH primário: Antivenenos/administração & dosagem
Mordeduras de Serpentes/epidemiologia
Mordeduras de Serpentes/terapia
Serpentes/classificação
[Mh] Termos MeSH secundário: Lesão Renal Aguda/epidemiologia
Adolescente
Adulto
Idoso
Idoso de 80 Anos ou mais
Animais
Antivenenos/efeitos adversos
Austrália/epidemiologia
Criança
Pré-Escolar
Coagulação Intravascular Disseminada/epidemiologia
Feminino
Hemorragia/epidemiologia
Seres Humanos
Hipersensibilidade/epidemiologia
Lactente
Masculino
Meia-Idade
Parada Cardíaca Extra-Hospitalar/epidemiologia
Estudos Prospectivos
Mordeduras de Serpentes/mortalidade
Venenos de Serpentes
Adulto Jovem
[Pt] Tipo de publicação:JOURNAL ARTICLE; MULTICENTER STUDY; OBSERVATIONAL STUDY
[Nm] Nome de substância:
0 (Antivenins); 0 (Snake Venoms)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:170807
[Lr] Data última revisão:
170807
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170803
[St] Status:MEDLINE


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[PMID]:28719273
[Au] Autor:Mao YC; Liu PY; Chiang LC; Liao SC; Su HY; Hsieh SY; Yang CC
[Ad] Endereço:Division of Clinical Toxicology and Occupational Medicine, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan.
[Ti] Título: Snakebite in Taiwan.
[So] Source:Am J Trop Med Hyg;96(6):1497-1504, 2017 Jun.
[Is] ISSN:1476-1645
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:AbstractAlthough specific antivenom is available in Taiwan, respiratory failure and general pain frequently accompany envenomation and there have been few reports on the management of envenomation. We retrospectively analyzed 44 cases of bite admitted to Taichung Veterans General Hospital (VGH) or to Taipei VGH. Demographic data, treatment, and outcome of patients with and without respiratory failure were compared. In this study, 20.5% patients had bites without noticeable signs or symptoms of significant envenoming, 27.3% developed respiratory failure, and 27.3% experienced general pain. Bivalent specific antivenom for and was administered in all envenomed cases. Respiratory failure occurred 1.5-6.5 hours post-bite and general pain occurred 1-12 hours post-bite. Specific antivenom for and at the recommended dose (i.e., 2-4 vials) might not effectively prevent respiratory failure and pain. Respiratory failure, general pain, and autonomic effects after bite were probably caused, at least partly, by ß-bungarotoxin. Although general weakness, ptosis, dysarthria, and dilated pupils were significantly associated with respiratory failure, their predictive value could not be accurately determined in such a retrospective study. Due to the rapid onset of respiratory failure, every suspected envenomed case thus should be closely monitored in the first few hours. We recommend the initial administration of four vials of antivenom in all envenomation cases, and a subsequent four vials be considered if the patient's condition is deteriorating. Prospective evaluation of the antivenom dosing regimen is urgently needed to improve envenomation treatment.
[Mh] Termos MeSH primário: Bungarus
Insuficiência Respiratória/epidemiologia
Mordeduras de Serpentes/epidemiologia
[Mh] Termos MeSH secundário: Adulto
Idoso
Idoso de 80 Anos ou mais
Animais
Antivenenos/uso terapêutico
Relação Dose-Resposta a Droga
Feminino
Seguimentos
Seres Humanos
Masculino
Meia-Idade
Insuficiência Respiratória/tratamento farmacológico
Insuficiência Respiratória/etiologia
Estudos Retrospectivos
Mordeduras de Serpentes/complicações
Mordeduras de Serpentes/tratamento farmacológico
Taiwan/epidemiologia
Resultado do Tratamento
Adulto Jovem
[Pt] Tipo de publicação:JOURNAL ARTICLE; OBSERVATIONAL STUDY
[Nm] Nome de substância:
0 (Antivenins)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:170823
[Lr] Data última revisão:
170823
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:170719
[St] Status:MEDLINE
[do] DOI:10.4269/ajtmh.17-0005


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[PMID]:28708892
[Au] Autor:Engmark M; Lomonte B; Gutiérrez JM; Laustsen AH; De Masi F; Andersen MR; Lund O
[Ad] Endereço:Department of Bio and Health Informatics, Technical University of Denmark, Kgs. Lyngby, Denmark.
[Ti] Título:Cross-recognition of a pit viper (Crotalinae) polyspecific antivenom explored through high-density peptide microarray epitope mapping.
[So] Source:PLoS Negl Trop Dis;11(7):e0005768, 2017 Jul.
[Is] ISSN:1935-2735
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Snakebite antivenom is a 120 years old invention based on polyclonal mixtures of antibodies purified from the blood of hyper-immunized animals. Knowledge on antibody recognition sites (epitopes) on snake venom proteins is limited, but may be used to provide molecular level explanations for antivenom cross-reactivity. In turn, this may help guide antivenom development by elucidating immunological biases in existing antivenoms. In this study, we have identified and characterized linear elements of B-cell epitopes from 870 pit viper venom protein sequences by employing a high-throughput methodology based on custom designed high-density peptide microarrays. By combining data on antibody-peptide interactions with multiple sequence alignments of homologous toxin sequences and protein modelling, we have determined linear elements of antibody binding sites for snake venom metalloproteases (SVMPs), phospholipases A2s (PLA2s), and snake venom serine proteases (SVSPs). The studied antivenom antibodies were found to recognize linear elements in each of the three enzymatic toxin families. In contrast to a similar study of elapid (non-enzymatic) neurotoxins, these enzymatic toxins were generally not recognized at the catalytic active site responsible for toxicity, but instead at other sites, of which some are known for allosteric inhibition or for interaction with the tissue target. Antibody recognition was found to be preserved for several minor variations in the protein sequences, although the antibody-toxin interactions could often be eliminated completely by substitution of a single residue. This finding is likely to have large implications for the cross-reactivity of the antivenom and indicate that multiple different antibodies are likely to be needed for targeting an entire group of toxins in these recognized sites.
[Mh] Termos MeSH primário: Antivenenos/imunologia
Venenos de Crotalídeos/imunologia
Mapeamento de Epitopos
Epitopos de Linfócito B/imunologia
Metaloproteases/imunologia
Fosfolipases A2/imunologia
[Mh] Termos MeSH secundário: Animais
Antivenenos/uso terapêutico
Reações Cruzadas
Seres Humanos
Análise em Microsséries
Alinhamento de Sequência
Mordeduras de Serpentes/terapia
Homologia Estrutural de Proteína
Viperidae
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antivenins); 0 (Crotalid Venoms); 0 (Epitopes, B-Lymphocyte); EC 3.1.1.4 (Phospholipases A2); EC 3.4.- (Metalloproteases)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:170808
[Lr] Data última revisão:
170808
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170715
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pntd.0005768


  9 / 3774 MEDLINE  
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Romero, Gustavo Adolfo Sierra
Wen, Fan Hui
Texto completo
[PMID]:28692641
[Au] Autor:Sachett JAG; da Silva IM; Alves EC; Oliveira SS; Sampaio VS; do Vale FF; Romero GAS; Dos Santos MC; Marques HO; Colombini M; da Silva AMM; Wen FH; Lacerda MVG; Monteiro WM; Ferreira LCL
[Ad] Endereço:Diretoria de Ensino e Pesquisa, Fundação de Medicina Tropical Dr. Heitor Vieira Dourado, Manaus, Brazil.
[Ti] Título:Poor efficacy of preemptive amoxicillin clavulanate for preventing secondary infection from Bothrops snakebites in the Brazilian Amazon: A randomized controlled clinical trial.
[So] Source:PLoS Negl Trop Dis;11(7):e0005745, 2017 Jul.
[Is] ISSN:1935-2735
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Secondary bacterial infections from snakebites contribute to the high complication rates that can lead to permanent function loss and disabilities. Although common in endemic areas, routine empirical prophylactic use of antibiotics aiming to prevent secondary infection lacks a clearly defined policy. The aim of this work was to estimate the efficacy of amoxicillin clavulanate for reducing the secondary infection incidence in patients bitten by Bothrops snakes, and, secondarily, identify risk factors for secondary infections from snakebites in the Western Brazilian Amazon. METHODS AND FINDINGS: This was an open-label, two-arm individually randomized superiority trial to prevent secondary infection from Bothrops snakebites. The antibiotic chosen for this clinical trial was oral amoxicillin clavulanate per seven days compared to no intervention. A total of 345 patients were assessed for eligibility in the study period. From this total, 187 accomplished the inclusion criteria and were randomized, 93 in the interventional group and 94 in the untreated control group. All randomized participants completed the 7 days follow-up period. Enzyme immunoassay confirmed Bothrops envenoming diagnosis in all participants. Primary outcome was defined as secondary infection (abscess and/or cellulitis) until day 7 after admission. Secondary infection incidence until 7 days after admission was 35.5% in the intervention group and 44.1% in the control group [RR = 0.80 (95%CI = 0.56 to 1.15; p = 0.235)]. Survival analysis demonstrated that the time from patient admission to the onset of secondary infection was not different between amoxicillin clavulanate treated and control group (Log-rank = 2.23; p = 0.789).Secondary infections incidence in 7 days of follow-up was independently associated to fibrinogen >400 mg/dL [AOR = 4.78 (95%CI = 2.17 to 10.55; p<0.001)], alanine transaminase >44 IU/L [AOR = 2.52 (95%CI = 1.06 to 5.98; p = 0.037)], C-reactive protein >6.5 mg/L [AOR = 2.98 (95%CI = 1.40 to 6.35; p = 0.005)], moderate pain [AOR = 24.30 (95%CI = 4.69 to 125.84; p<0.001)] and moderate snakebites [AOR = 2.43 (95%CI = 1.07 to 5.50; p = 0.034)]. CONCLUSIONS/SIGNIFICANCE: Preemptive amoxicillin clavulanate was not effective for preventing secondary infections from Bothrops snakebites. Laboratorial markers, such as high fibrinogen, alanine transaminase and C-reactive protein levels, and severity clinical grading of snakebites, may help to accurately diagnose secondary infections. TRIAL REGISTRATION: Brazilian Clinical Trials Registry (ReBec): RBR-3h33wy; UTN Number: U1111-1169-1005.
[Mh] Termos MeSH primário: Amoxicilina/administração & dosagem
Antibacterianos/administração & dosagem
Infecções Bacterianas/prevenção & controle
Bothrops
Coinfecção/prevenção & controle
Mordeduras de Serpentes/diagnóstico
[Mh] Termos MeSH secundário: Adolescente
Adulto
Alanina Transaminase/sangue
Animais
Brasil
Proteína C-Reativa/análise
Criança
Pré-Escolar
Feminino
Fibrinogênio/análise
Seres Humanos
Lactente
Masculino
Meia-Idade
Dor
Análise de Regressão
Mordeduras de Serpentes/complicações
Análise de Sobrevida
Centros de Atenção Terciária
Resultado do Tratamento
Adulto Jovem
[Pt] Tipo de publicação:JOURNAL ARTICLE; RANDOMIZED CONTROLLED TRIAL
[Nm] Nome de substância:
0 (Anti-Bacterial Agents); 804826J2HU (Amoxicillin); 9001-32-5 (Fibrinogen); 9007-41-4 (C-Reactive Protein); EC 2.6.1.2 (Alanine Transaminase)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:170808
[Lr] Data última revisão:
170808
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170711
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pntd.0005745


  10 / 3774 MEDLINE  
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[PMID]:28683119
[Au] Autor:Kasturiratne A; Pathmeswaran A; Wickremasinghe AR; Jayamanne SF; Dawson A; Isbister GK; de Silva HJ; Lalloo DG
[Ad] Endereço:Faculty of Medicine, University of Kelaniya, Ragama, Sri Lanka.
[Ti] Título:The socio-economic burden of snakebite in Sri Lanka.
[So] Source:PLoS Negl Trop Dis;11(7):e0005647, 2017 Jul.
[Is] ISSN:1935-2735
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Snakebite is a major problem affecting the rural poor in many of the poorest countries in the tropics. However, the scale of the socio-economic burden has rarely been studied. We undertook a comprehensive assessment of the burden in Sri Lanka. METHODS: Data from a representative nation-wide community based household survey were used to estimate the number of bites and deaths nationally, and household and out of pocket costs were derived from household questionnaires. Health system costs were obtained from hospital cost accounting systems and estimates of antivenom usage. DALYs lost to snakebite were estimated using standard approaches using disability weights for poisoning. FINDINGS: 79% of victims suffered economic loss following a snakebite with a median out of pocket expenditure of $11.82 (IQR 2-28.57) and a median estimated loss of income of $28.57 and $33.21 for those in employment or self-employment, respectively. Family members also lost income to help care for patients. Estimated health system costs for Sri Lanka were $ 10,260,652 annually. The annual estimated total number of DALYS was 11,101 to 15,076 per year for envenoming following snakebite. INTERPRETATION: Snakebite places a considerable economic burden on the households of victims in Sri Lanka, despite a health system which is accessible and free at the point of care. The disability burden is also considerable, similar to that of meningitis or dengue, although the relatively low case fatality rate and limited physical sequelae following bites by Sri Lankan snakes means that this burden may be less than in countries on the African continent.
[Mh] Termos MeSH primário: Custos de Cuidados de Saúde
Mordeduras de Serpentes/economia
Mordeduras de Serpentes/terapia
[Mh] Termos MeSH secundário: Animais
Antivenenos/economia
Antivenenos/uso terapêutico
Seres Humanos
Renda
Mordeduras de Serpentes/epidemiologia
Sri Lanka/epidemiologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antivenins)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:170804
[Lr] Data última revisão:
170804
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170707
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pntd.0005647



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