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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]:28732041
[Au] Autor:Yadav PK; Antonyraj CB; Basheer Ahamed SI; Srinivas S
[Ad] Endereço:Centre for Bioinformatics, Pondicherry University, Pondicherry, India.
[Ti] Título:Understanding Russell's viper venom factor V activator's substrate specificity by surface plasmon resonance and in-silico studies.
[So] Source:PLoS One;12(7):e0181216, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Blood coagulation factor V (FV) is activated either by Factor X or thrombin, cleaving at three different sites viz., Site I (Arg709-Ser710), site II (Arg1018-Thr1019), and site III (Arg1545-Ser1546). Russell's viper venom factor V activator (RVV-V) is a thrombin-like serine proteinase that activates FV with selective, single cleavage at site III. A long lasting effort is being pending in understanding the 'selective' binding specificity of the RVV-V towards site III. Here, we present the binding kinetic study of RVV-V with two designed peptides corresponding to the regions from site I (Gln699-Asn713) and site II (1008Lys-Pro1022), respectively, that include 15 amino acids. Our investigation for justifying the binding efficacy and kinetics of peptides includes SPR method, protein-peptide docking, molecular dynamics simulation, and principal component analysis (PCA). Surprisingly, the SPR experiment disclosed that the Peptide II showed a lower binding affinity with KD of 2.775 mM while the Peptide I showed none. Docking and simulation of both the peptides with RVV-V engaged either rooted or shallow binding for Peptide II and Peptide I respectively. The peptide binding resulted in global conformational changes in the native fold of RVV-V, whereas the similar studies for thrombin failed to make major changes in the native fold. In support, the PCA analysis for RVV-V showed the dislocation of catalytic triad upon binding both the peptides. Hence, RVV-V, a serine protease, is incompetent in cleaving these two sites. This study suggests a transition in RVV-V from the native rigid to the distorted flexible structure and paves a way to design a new peptide substrate/inhibitor.
[Mh] Termos MeSH primário: Fator V/metabolismo
Víbora de Russell
Serina Endopeptidases/metabolismo
Venenos de Víboras/metabolismo
[Mh] Termos MeSH secundário: Animais
Sítios de Ligação
Ligação Competitiva
Biocatálise
Fator V/química
Fator V/genética
Interações Hidrofóbicas e Hidrofílicas
Cinética
Simulação de Acoplamento Molecular
Simulação de Dinâmica Molecular
Análise de Componente Principal
Ligação Proteica
Conformação Proteica
Dobramento de Proteína
Serina Endopeptidases/química
Serina Endopeptidases/genética
Especificidade por Substrato
Ressonância de Plasmônio de Superfície
Trombina/química
Trombina/metabolismo
Venenos de Víboras/química
Venenos de Víboras/genética
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Viper Venoms); 9001-24-5 (Factor V); EC 3.4.21.- (Serine Endopeptidases); EC 3.4.21.5 (Thrombin); EC 3.4.21.95 (snake venom factor V activator)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171002
[Lr] Data última revisão:
171002
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170722
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0181216


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[PMID]:28062165
[Au] Autor:Pathan J; Mondal S; Sarkar A; Chakrabarty D
[Ad] Endereço:Department of Biological Sciences, Birla Institute of Technology and Science, Pilani, K K Birla Goa Campus, Zuarinagar, Goa, India.
[Ti] Título:Daboialectin, a C-type lectin from Russell's viper venom induces cytoskeletal damage and apoptosis in human lung cancer cells in vitro.
[So] Source:Toxicon;127:11-21, 2017 Mar 01.
[Is] ISSN:1879-3150
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:'Daboialectin', a low molecular weight C-type lectin (18.5 kDa) isolated from Russell's viper venom showed cytotoxic effects on human broncho-alveolar carcinoma derived (A549) cell lines. Daboialectin induced inhibition of A549 cell growth was time and concentration dependent with severe morphological changes by altering the functions of small GTPases such as Rac, Rho and cdc42. ROS induced DNA damage may result in apoptosis by inducing disruption of membrane integrity, blebbing and nuclear disintegration by activating caspases. Our results indicate that Daboialectin, a snake c type lectin (Snaclec) isolated from RVV alters morphology of A549 cells via regulation of cytoskeleton through RHO-GTPases. On other hand, the HSP70 and some other anti-apoptotic proteins required for the survival of cancer cells was found to be down-regulated in presence of Daboialectin. Daboialectin was also found to be inhibitory to anti-adhesive and anti-invasive to A549 cells in vitro. Daboialectin is the first Snaclec reported to induce cytoskeletal changes through regulation of RHO-GTPases and blocking anti-apoptotic pathway for a cancer cell line.
[Mh] Termos MeSH primário: Antineoplásicos/farmacologia
Apoptose/efeitos dos fármacos
Citoesqueleto/efeitos dos fármacos
Lectinas Tipo C
Víbora de Russell
Venenos de Víboras/farmacologia
[Mh] Termos MeSH secundário: Células A549
Animais
Proliferação Celular/efeitos dos fármacos
Sobrevivência Celular/efeitos dos fármacos
Citoesqueleto/ultraestrutura
Dano ao DNA/efeitos dos fármacos
Seres Humanos
Proteínas Monoméricas de Ligação ao GTP/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antineoplastic Agents); 0 (Lectins, C-Type); 0 (Viper Venoms); EC 3.6.5.2 (Monomeric GTP-Binding Proteins)
[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:170108
[St] Status:MEDLINE


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[PMID]:27936776
[Au] Autor:Kalita B; Patra A; Mukherjee AK
[Ad] Endereço:Microbial Biotechnology and Protein Research Laboratory, Department of Molecular Biology and Biotechnology, Tezpur University , Tezpur 784028, Assam, India.
[Ti] Título:Unraveling the Proteome Composition and Immuno-profiling of Western India Russell's Viper Venom for In-Depth Understanding of Its Pharmacological Properties, Clinical Manifestations, and Effective Antivenom Treatment.
[So] Source:J Proteome Res;16(2):583-598, 2017 Feb 03.
[Is] ISSN:1535-3907
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:The proteome composition of western India (WI) Russell's viper venom (RVV) was correlated with pharmacological properties and pathological manifestations of RV envenomation. Proteins in the 5-19 and 100-110 kDa mass ranges were the most predominate (∼35.1%) and least abundant (∼3.4%) components, respectively, of WI RVV. Non-reduced SDS-PAGE indicated the occurrence of multiple subunits, non-covalent oligomers, self-aggregation, and/or interactions among the RVV proteins. A total of 55 proteins belonging to 13 distinct snake venom families were unambiguously identified by ESI-LC-MS/MS analysis. Phospholipase A (32.5%) and Kunitz-type serine protease inhibitors (12.5%) represented the most abundant enzymatic and non-enzymatic proteins, respectively. However, ATPase, ADPase, and hyaluronidase, detected by enzyme assays, were not identified by proteomic analysis owing to limitations in protein database deposition. Several biochemical and pharmacological properties of WI RVV were also investigated. Neurological symptoms exhibited by some RV-bite patients in WI may be correlated to the presence of neurotoxic phospholipase A enzymes and Kunitz-type serine protease inhibitor complex in this venom. Monovalent antivenom was found to be better than polyvalent antivenom in immuno-recognition and neutralization of the tested pharmacological properties and enzyme activities of WI RVV; nevertheless, both antivenoms demonstrated poor cross-reactivity and neutralization of pharmacological activities shown by low-molecular-mass proteins (<18 kDa) of this venom.
[Mh] Termos MeSH primário: Antivenenos/farmacologia
Fosfolipases A2/isolamento & purificação
Subunidades Proteicas/isolamento & purificação
Proteoma/isolamento & purificação
Inibidores de Serino Proteinase/isolamento & purificação
Venenos de Víboras/química
[Mh] Termos MeSH secundário: Animais
Antivenenos/isolamento & purificação
Fracionamento Químico
Eletroforese em Gel de Poliacrilamida
Ontologia Genética
Cavalos
Seres Humanos
Soros Imunes/química
Anotação de Sequência Molecular
Peso Molecular
Fosfolipases A2/química
Agregados Proteicos
Subunidades Proteicas/antagonistas & inibidores
Subunidades Proteicas/química
Proteoma/antagonistas & inibidores
Proteoma/química
Víbora de Russell/fisiologia
Inibidores de Serino Proteinase/química
Espectrometria de Massas por Ionização por Electrospray
Venenos de Víboras/antagonistas & inibidores
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antivenins); 0 (Immune Sera); 0 (Protein Aggregates); 0 (Protein Subunits); 0 (Proteome); 0 (Serine Proteinase Inhibitors); 0 (Viper Venoms); EC 3.1.1.4 (Phospholipases A2)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171016
[Lr] Data última revisão:
171016
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161213
[St] Status:MEDLINE
[do] DOI:10.1021/acs.jproteome.6b00693


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[PMID]:27871786
[Au] Autor:Namal Rathnayaka RM; Kularatne SA; Kumarasinghe KD; Ranaweera J; Nishanthi Ranathunga PE
[Ad] Endereço:Intensive Care Unit, Provincial General Hospital, Ratnapura, Sri Lanka; Department of Veterinary Pathobiology, Faculty of Veterinary Medicine and Animal Science, University of Peradeniya, Sri Lanka. Electronic address: namalrath10@yahoo.com.
[Ti] Título:Ischemic brain infarcts and intracranial haemorrhages following Russell's viper (Daboia russelii) bite in Sri Lanka.
[So] Source:Toxicon;125:70-73, 2017 Jan.
[Is] ISSN:1879-3150
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Snakebite is an important medical problem in Sri Lanka. Of the deadly venomous snakes, Russell's viper (Daboia russelii) is widely distributed and responsible for most of the fatalities of snakebite in the country. It is not uncommon to see atypical manifestations in Russell's viper bite. We report the events of intracranial haemorrhages and multiple ischemic brain infarcts following Russell's viper (Daboia russelii) bite of a previously healthy 43-years-old male who succumbed to envenoming.
[Mh] Termos MeSH primário: Infarto Encefálico/etiologia
Hemorragias Intracranianas/etiologia
Víbora de Russell
Mordeduras de Serpentes/complicações
Venenos de Víboras/envenenamento
[Mh] Termos MeSH secundário: Adulto
Animais
Infarto Encefálico/patologia
Seres Humanos
Hemorragias Intracranianas/patologia
Masculino
Mordeduras de Serpentes/patologia
Sri Lanka
[Pt] Tipo de publicação:CASE REPORTS; JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Viper Venoms)
[Em] Mês de entrada:1707
[Cu] Atualização por classe:170724
[Lr] Data última revisão:
170724
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161123
[St] Status:MEDLINE


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[PMID]:27806970
[Au] Autor:Jayakrishnan MP; Geeta MG; Krishnakumar P; Rajesh TV; George B
[Ad] Endereço:Government Medical College, Kozhikode, Kerala, India.
[Ti] Título:Snake bite mortality in children: beyond bite to needle time.
[So] Source:Arch Dis Child;102(5):445-449, 2017 May.
[Is] ISSN:1468-2044
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:OBJECTIVE: To study the clinical characteristics and predictors of mortality from snake bite envenomation in children. DESIGN: Prospective observational study with a one-group cohort design. SETTING: Paediatric intensive care unit of a tertiary care hospital in South India. SUBJECTS: The study cohort consisted of 145 children (55 girls and 90 boys) <12 years of age with snake bite envenomation. METHODS: Demographic and clinical details were recorded in a semistructured pro forma. Children were treated with polyvalent antisnake venom (ASV) as per WHO protocol. Details of treatment, complications and outcomes were recorded. Univariate analysis was done to identify statistical significance, and those variables found to be significant were analysed using binary logistic regression. RESULTS: Russell's viper was the most common offending snake followed by hump-nosed pit viper. Features of haemotoxicity, neurotoxicity and combined haemotoxicity and neurotoxicity occurred in 68 (47%), 39 (26.9%) and 9 (6%) children, respectively. Acute kidney injury (AKI) occurred in 36 (25%) children. The mortality rate was 10.3%. On univariate analysis, nocturnal bites, severe leucocytosis on day 1, AKI, capillary leak syndrome and a need for more than 20 vials of ASV were significantly associated with mortality. On multivariate analysis, only severe leucocytosis on day 1 (OR 35.29; 95% CI 1.37 to 911.89) and AKI (OR 35.05 95% CI 1.74 to 706.93) were found to be independent predictors of mortality. CONCLUSIONS: This study has identified two hitherto unrecognised risk factors-severe leucocytosis on day 1 and capillary leak syndrome. These findings need to be taken into consideration when planning management strategies for snake bite envenomation in children.
[Mh] Termos MeSH primário: Antivenenos/administração & dosagem
Mordeduras de Serpentes/mortalidade
[Mh] Termos MeSH secundário: Lesão Renal Aguda/etiologia
Lesão Renal Aguda/mortalidade
Animais
Antivenenos/uso terapêutico
Síndrome de Vazamento Capilar/etiologia
Síndrome de Vazamento Capilar/mortalidade
Criança
Pré-Escolar
Esquema de Medicação
Feminino
Seres Humanos
Índia/epidemiologia
Lactente
Unidades de Terapia Intensiva Pediátrica
Leucocitose/etiologia
Leucocitose/mortalidade
Masculino
Prognóstico
Víbora de Russell
Mordeduras de Serpentes/complicações
Mordeduras de Serpentes/terapia
Viperidae
[Pt] Tipo de publicação:JOURNAL ARTICLE; OBSERVATIONAL STUDY
[Nm] Nome de substância:
0 (Antivenins)
[Em] Mês de entrada:1705
[Cu] Atualização por classe:170509
[Lr] Data última revisão:
170509
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:161104
[St] Status:MEDLINE
[do] DOI:10.1136/archdischild-2016-311142


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[PMID]:27401825
[Au] Autor:Silva A; Kuruppu S; Othman I; Goode RJ; Hodgson WC; Isbister GK
[Ad] Endereço:Monash Venom Group, Department of Pharmacology, Biomedicine Discovery Institute, Monash University, Melbourne, VIC, 3800, Australia. anjana.silva@monash.edu.
[Ti] Título:Neurotoxicity in Sri Lankan Russell's Viper (Daboia russelii) Envenoming is Primarily due to U1-viperitoxin-Dr1a, a Pre-Synaptic Neurotoxin.
[So] Source:Neurotox Res;31(1):11-19, 2017 Jan.
[Is] ISSN:1476-3524
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Russell's vipers are snakes of major medical importance in Asia. Russell's viper (Daboia russelii) envenoming in Sri Lanka and South India leads to a unique, mild neuromuscular paralysis, not seen in other parts of the world where the snake is found. This study aimed to identify and pharmacologically characterise the major neurotoxic components of Sri Lankan Russell's viper venom. Venom was fractionated using size exclusion chromatography and reverse-phase high-performance liquid chromatography (RP-HPLC). In vitro neurotoxicities of the venoms, fractions and isolated toxins were measured using chick biventer and rat hemidiaphragm preparations. A phospholipase A (PLA ) toxin, U1-viperitoxin-Dr1a (13.6 kDa), which constitutes 19.2 % of the crude venom, was isolated and purified using HPLC. U1-viperitoxin-Dr1a produced concentration-dependent in vitro neurotoxicity abolishing indirect twitches in the chick biventer nerve-muscle preparation, with a t of 55 ± 7 min only at 1 µM. The toxin did not abolish responses to acetylcholine and carbachol indicating pre-synaptic neurotoxicity. Venom, in the absence of U1-viperitoxin-Dr1a, did not induce in vitro neurotoxicity. Indian polyvalent antivenom, at the recommended concentration, only partially prevented the neurotoxic effects of U1-viperitoxin-Dr1a. Liquid chromatography mass spectrometry analysis confirmed that U1-viperitoxin-Dr1a was the basic S-type PLA toxin previously identified from this venom (NCBI-GI: 298351762; SwissProt: P86368). The present study demonstrates that neurotoxicity following Sri Lankan Russell's viper envenoming is primarily due to the pre-synaptic neurotoxin U1-viperitoxin-Dr1a. Mild neurotoxicity observed in severely envenomed Sri Lankan Russell's viper bites is most likely due to the low potency of U1-viperitoxin-Dr1a, despite its high relative abundance in the venom.
[Mh] Termos MeSH primário: Neurotoxinas/toxicidade
Víbora de Russell
Venenos de Víboras/toxicidade
[Mh] Termos MeSH secundário: Acetilcolina/farmacologia
Sequência de Aminoácidos
Animais
Antivenenos/farmacologia
Carbacol/farmacologia
Galinhas
Relação Dose-Resposta a Droga
Feminino
Masculino
Músculos/efeitos dos fármacos
Junção Neuromuscular/efeitos dos fármacos
Neurotoxinas/química
Neurotoxinas/genética
Neurotoxinas/isolamento & purificação
Neurotransmissores/farmacologia
Nervos Periféricos/efeitos dos fármacos
Terminações Pré-Sinápticas/efeitos dos fármacos
Ratos
Mordeduras de Serpentes
Técnicas de Cultura de Tecidos
Venenos de Víboras/química
Venenos de Víboras/genética
Venenos de Víboras/isolamento & purificação
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antivenins); 0 (Neurotoxins); 0 (Neurotransmitter Agents); 0 (U1-viperitoxin-Dr1a, Daboia russelii); 0 (Viper Venoms); 8Y164V895Y (Carbachol); N9YNS0M02X (Acetylcholine)
[Em] Mês de entrada:1707
[Cu] Atualização por classe:171110
[Lr] Data última revisão:
171110
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160713
[St] Status:MEDLINE
[do] DOI:10.1007/s12640-016-9650-4


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[PMID]:27940955
[Au] Autor:Phinikaridou A; Andia ME; Lavin B; Smith A; Saha P; Botnar RM
[Ad] Endereço:From the Division of Imaging Science and Biomedical Engineering (A.P., M.E.A., B.L., R.M.B.), Academic Department of Surgery, Cardiovascular Division (A.S., P.S.), BHF Centre of Excellence, Cardiovascular Division (A.S., R.M.B.), and Wellcome Trust and EPSRC Medical Engineering Center (P.S., R.M.B.)
[Ti] Título:Increased Vascular Permeability Measured With an Albumin-Binding Magnetic Resonance Contrast Agent Is a Surrogate Marker of Rupture-Prone Atherosclerotic Plaque.
[So] Source:Circ Cardiovasc Imaging;9(12), 2016 Dec.
[Is] ISSN:1942-0080
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Compromised structural integrity of the endothelium and higher microvessel density increase vascular permeability. We investigated whether vascular permeability measured in vivo by magnetic resonance imaging using the albumin-binding contrast agent, gadofosveset, is a surrogate marker of rupture-prone atherosclerotic plaque in a rabbit model. METHODS AND RESULTS: New Zealand white rabbits (n=10) were rendered atherosclerotic by cholesterol-diet and endothelial denudation. Plaque rupture was triggered with Russell's viper venom and histamine. Animals were imaged pre-triggering, at 3 and 12 weeks, to quantify plaque area, vascular permeability, vasodilation, and stiffness and post-triggering to identify thrombus. Plaques identified on the pretrigger scans were classified as stable or rupture-prone based on the absence or presence of thrombus on the corresponding post-trigger magnetic resonance imaging, respectively. All rabbits had developed atherosclerosis, and 60% had ruptured plaques. Rupture-prone plaques had higher vessel wall relaxation rate (R ; 2.30±0.5 versus 1.86±0.3 s ; P<0.001), measured 30 minutes after gadofosveset administration, and higher R /plaque area ratio (0.70±0.06 versus 0.47±0.02, P= 0.01) compared with stable plaque at 12 weeks. Rupture-prone plaques had higher percent change in R between the 3 and 12 weeks compared with stable plaque (50.80±7.2% versus 14.22±2.2%; P<0.001). Immunohistochemistry revealed increased vessel wall albumin and microvessel density in diseased aortas and especially in ruptured plaque. Electron microscopy showed lack of structural integrity in both luminal and microvascular endothelium in diseased vessels. Functionally, the intrinsic vasodilation of the vessel wall decreased at 12 weeks compared with 3 weeks (18.60±1.0% versus 23.43±0.8%; P<0.001) and in rupture-prone compared with stable lesions (16.40±2.0% versus 21.63±1.2%; P<0.001). Arterial stiffness increased at 12 weeks compared with 3 weeks (5.00±0.1 versus 2.53±0.2 m/s; P<0.001) both in animals with stable and rupture-prone lesions. CONCLUSIONS: T1 mapping using an albumin-binding contrast agent (gadofosveset) could quantify the changes in vascular permeability associated with atherosclerosis progression and rupture-prone plaques.
[Mh] Termos MeSH primário: Aorta/diagnóstico por imagem
Doenças da Aorta/diagnóstico por imagem
Aterosclerose/diagnóstico por imagem
Permeabilidade Capilar
Meios de Contraste/metabolismo
Gadolínio/metabolismo
Imagem por Ressonância Magnética
Microvasos/diagnóstico por imagem
Compostos Organometálicos/metabolismo
Placa Aterosclerótica
Albumina Sérica/metabolismo
[Mh] Termos MeSH secundário: Animais
Aorta/metabolismo
Aorta/fisiopatologia
Doenças da Aorta/etiologia
Doenças da Aorta/metabolismo
Doenças da Aorta/fisiopatologia
Área Sob a Curva
Aterosclerose/etiologia
Aterosclerose/metabolismo
Aterosclerose/fisiopatologia
Colesterol na Dieta
Modelos Animais de Doenças
Progressão da Doença
Endotélio Vascular/diagnóstico por imagem
Endotélio Vascular/metabolismo
Endotélio Vascular/fisiopatologia
Histamina
Masculino
Microvasos/metabolismo
Microvasos/fisiopatologia
Valor Preditivo dos Testes
Ligação Proteica
Curva ROC
Coelhos
Ruptura Espontânea
Víbora de Russell
Fatores de Tempo
Rigidez Vascular
Vasodilatação
Venenos de Víboras
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Cholesterol, Dietary); 0 (Contrast Media); 0 (Organometallic Compounds); 0 (Serum Albumin); 0 (Viper Venoms); 820484N8I3 (Histamine); AU0V1LM3JT (Gadolinium); XM33Q67UVH (gadofosveset trisodium)
[Em] Mês de entrada:1705
[Cu] Atualização por classe:170922
[Lr] Data última revisão:
170922
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161213
[St] Status:MEDLINE


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[PMID]:27911900
[Au] Autor:Silva A; Johnston C; Kuruppu S; Kneisz D; Maduwage K; Kleifeld O; Smith AI; Siribaddana S; Buckley NA; Hodgson WC; Isbister GK
[Ad] Endereço:Monash Venom Group, Department of Pharmacology, Biomedicine Discovery Institute, Monash University, Melbourne, Victoria, Australia.
[Ti] Título:Clinical and Pharmacological Investigation of Myotoxicity in Sri Lankan Russell's Viper (Daboia russelii) Envenoming.
[So] Source:PLoS Negl Trop Dis;10(12):e0005172, 2016 Dec.
[Is] ISSN:1935-2735
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Sri Lankan Russell's viper (Daboia russelii) envenoming is reported to cause myotoxicity and neurotoxicity, which are different to the effects of envenoming by most other populations of Russell's vipers. This study aimed to investigate evidence of myotoxicity in Russell's viper envenoming, response to antivenom and the toxins responsible for myotoxicity. METHODOLOGY AND FINDINGS: Clinical features of myotoxicity were assessed in authenticated Russell's viper bite patients admitted to a Sri Lankan teaching hospital. Toxins were isolated using high-performance liquid chromatography. In-vitro myotoxicity of the venom and toxins was investigated in chick biventer nerve-muscle preparations. Of 245 enrolled patients, 177 (72.2%) had local myalgia and 173 (70.6%) had local muscle tenderness. Generalized myalgia and muscle tenderness were present in 35 (14.2%) and 29 (11.8%) patients, respectively. Thirty-seven patients had high (>300 U/l) serum creatine kinase (CK) concentrations in samples 24h post-bite (median: 666 U/l; maximum: 1066 U/l). Peak venom and 24h CK concentrations were not associated (Spearman's correlation; p = 0.48). The 24h CK concentrations differed in patients without myotoxicity (median 58 U/l), compared to those with local (137 U/l) and generalised signs/symptoms of myotoxicity (107 U/l; p = 0.049). Venom caused concentration-dependent inhibition of direct twitches in the chick biventer cervicis nerve-muscle preparation, without completely abolishing direct twitches after 3 h even at 80 µg/ml. Indian polyvalent antivenom did not prevent in-vitro myotoxicity at recommended concentrations. Two phospholipase A2 toxins with molecular weights of 13kDa, U1-viperitoxin-Dr1a (19.2% of venom) and U1-viperitoxin-Dr1b (22.7% of venom), concentration dependently inhibited direct twitches in the chick biventer cervicis nerve-muscle preparation. At 3 µM, U1-viperitoxin-Dr1a abolished twitches, while U1-viperitoxin-Dr1b caused 70% inhibition of twitch force after 3h. Removal of both toxins from whole venom resulted in no in-vitro myotoxicity. CONCLUSION: The study shows that myotoxicity in Sri Lankan Russell's viper envenoming is mild and non-life threatening, and due to two PLA2 toxins with weak myotoxic properties.
[Mh] Termos MeSH primário: Víbora de Russell/fisiologia
Mordeduras de Serpentes/parasitologia
Venenos de Víboras/toxicidade
[Mh] Termos MeSH secundário: Adolescente
Adulto
Idoso
Animais
Embrião de Galinha
Creatina Quinase/sangue
Feminino
Seres Humanos
Masculino
Meia-Idade
Peso Molecular
Fosfolipases A2/química
Fosfolipases A2/toxicidade
Ratos
Ratos Sprague-Dawley
Mordeduras de Serpentes/sangue
Mordeduras de Serpentes/enzimologia
Sri Lanka
Venenos de Víboras/química
Venenos de Víboras/enzimologia
Adulto Jovem
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Viper Venoms); EC 2.7.3.2 (Creatine Kinase); EC 3.1.1.4 (Phospholipases A2)
[Em] Mês de entrada:1706
[Cu] Atualização por classe:170613
[Lr] Data última revisão:
170613
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161203
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pntd.0005172


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[PMID]:27752013
[Au] Autor:Weerakkody RM; Lokuliyana PN; Lanerolle RD
[Ad] Endereço:Renal Services, University Medical Unit, National Hospital of Sri Lanka, Colombo, Sri Lanka.
[Ti] Título:Transient distal renal tubular acidosis following hump nosed viper bite: Two cases from Sri Lanka.
[So] Source:Saudi J Kidney Dis Transpl;27(5):1018-1020, 2016 Sep-Oct.
[Is] ISSN:1319-2442
[Cp] País de publicação:Saudi Arabia
[La] Idioma:eng
[Ab] Resumo:Hump-nosed viper (Hypnale hypnale; HNV) is one of the six major snake species in Sri Lanka that cause envenomation. Nephrotoxicity, coagulopathy, and neurotoxicity are wellrecognized features of its envenomation. Type 4 renal tubular acidosis (RTA4) has only once been described previously in this condition, and we report two further cases. Two patients aged 53 and 51 presented following HNV bites with acute kidney injury and microangiopathic hemolytic anemia. Both underwent multiple cycles of hemodialysis until the polyuric phase was reached. Despite polyuria, both patients developed resistant hyperkalemia that needed further hemodialysis. The urinary pH, arterial pH, delta ratio, and transtubular potassium gradient confirmed RTA4. HNV venom has been shown to damage the proximal convoluted tubules in animal studies, but not the distal convoluted tubule, and hence the mechanism of our observation in these two patients is unclear. Unexplained hyperkalemia in recovery phase of HNV bite should raise suspicions of RTA4.
[Mh] Termos MeSH primário: Acidose Tubular Renal
Mordeduras de Serpentes
[Mh] Termos MeSH secundário: Animais
Transtornos da Coagulação Sanguínea
Seres Humanos
Meia-Idade
Víbora de Russell
Sri Lanka
Venenos de Víboras
Viperidae
[Pt] Tipo de publicação:CASE REPORTS
[Nm] Nome de substância:
0 (Viper Venoms)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:170831
[Lr] Data última revisão:
170831
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161019
[St] Status:MEDLINE
[do] DOI:10.4103/1319-2442.190879



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