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1.
Toxicon ; 188: 11-15, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33039367

RESUMO

Vipers include approximately 300 species and usually feed on vertebrates, but over 30 species of them occasionally eat centipedes. Centipedes have been also known to occur in stomach contents of a Japanese pit viper, mamushi, Gloydius blomhoffii. Toxicity of the venom of mamushi to small mammals has been well studied, but there is no information concerning its toxicity to arthropods. Here, we studied the toxicity of the raw venom to the red-headed centipede, Scolopendra subspinipes mutilans, by comparing with the toxicity to two other common prey animals, a house mouse, Mus musclus, and a pond frog, Pelophylax nigromaculatus. The lethal doses for mice weighing around 21.5 g and frogs weighing around 3.78 g were less than 5 µl (equivalent to ca. 0.23 and 1.32 µl/g, respectively), which presumably corresponds to an approximate dose of mamushi's one envenomation. On the other hand, centipedes weighing around 1.86 g needed 10-36 µl of venom to die (16.0 µl/g on average). This result suggests that the centipedes are much more resistant to the venom than other prey animals, and it is difficult for mamushi to kill or incapacitate centipedes by the venom of a single envenomation.


Assuntos
Agkistrodon , Venenos de Crotalídeos/toxicidade , Sequência de Aminoácidos , Animais , Artrópodes/fisiologia , Crotalinae , Transcriptoma
2.
Toxicon ; 185: 188-192, 2020 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-32712023

RESUMO

Malayan pit vipers (Calloselasma rhodostoma) are major health hazard in Southern Thailand causing systemic bleeding by defibrination and thrombocytopenia. Twenty minute whole blood clotting test (20WBCT) is a useful and informative bedside test recommended by WHO for diagnosis of significant coagulopathy following snakebite envenoming since it to some extent predicts the need for anti-venom therapy. Prothrombin time (PT), international normalized ratio (INR) and activated partial thromboplastin time (APTT) are standard clotting assays that are widely used for diagnosis of coagulopathy. The purpose of this study is to compare 20WBCT with the standard clotting assays (PT, INR, APTT, fibrinogen) in management of Malayan pit viper bitten-patients. We studied 296 victims prospectively during a 3-year period. In total, 115 (38.9%) cases showed a positive 20WBCT (un-clot) suggesting systemic envenomation. Thrombocytopenia (platelet count less than 100,000/µL), prolonged PT, prolonged APTT, INR ≥ 1.2, and fibrinogen level <100 mg/dl were found in 12.2%, 47.6%, 18.9%, 34.8% and 40.9%, respectively. Significant predictors for thrombocytopenia by multivariate analysis included systemic bleeding (p < 0.001), higher INR (p < 0.001), 20WBCT showing unclotted blood (p = 0.049), and longer bite-to-hospital time (p = 0.031). When a fibrinogen level below 100 mg/dl was determined as hypofibrinogenemic condition, INR had the highest area under ROC curve followed by 20WBCT and APTT, respectively, to identify such as hypofibrinogenemic condition. The diagnostic accuracy of 20WBCT and INR at or more than 1.155 were better than APTT at any cut-off points. INR >1.155 had a sensitivity of 78.5% and specificity of 90.3% while 20WBCT had sensitivity of 81.0% and specificity of 90.3%. CONCLUSIONS: Both 20WBCT and INR are useful to assess coagulation abnormality in Malayan pit viper-bitten patients.


Assuntos
Mordeduras de Serpentes/diagnóstico , Venenos de Víboras/toxicidade , Agkistrodon , Animais , Transtornos da Coagulação Sanguínea , Testes de Coagulação Sanguínea , Fibrinogênio , Coeficiente Internacional Normatizado , Tempo de Tromboplastina Parcial , Tempo de Protrombina , Sensibilidade e Especificidade , Tailândia
3.
South Med J ; 113(5): 232-239, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32358618

RESUMO

OBJECTIVES: Injuries resulting from contact with animals are a significant public health concern. This study quantifies and updates nonfatal bite and sting injuries by noncanine sources using the most recent data available (2011-2015) from the National Electronic Injury Surveillance System-All Injury Program with the purpose of using these updates to better understand public health consequences and prevention techniques. Increased rates of bites and stings can be expected in this study's time frame, possibly caused by the increasing human population expanding into animal territories, as well as changes in animal geographic distribution and pet ownership. METHODS: The National Electronic Injury Surveillance System-All Injury Program is an ongoing nationally representative surveillance system used to monitor all types and causes of injuries treated in US hospital emergency departments (EDs). Cases were coded by trained hospital coders using information from medical records on animal sources of bite and sting injuries being treated. Data from 2011-2015 were weighted to produce national annualized estimates, percentages, and rates based on the US population. RESULTS: An estimated 1.17 million people visited EDs for noncanine bite and sting injuries annually. This translates to a rate of 371.3/100,000 people. Insects accounted for 71.0% of noncanine bite and sting injuries, followed by arachnids (19.2%) and mammals (7.8%). The estimated annual total lifetime medical and work cost of unintentional noncanine injuries was $5,755,581,000. CONCLUSIONS: Various sources of bite and sting injuries had an outsized effect on injury rates and identify potential areas of focus for education and prevention programs to reduce the burden of these injuries on health and healthcare costs. The study describes the diversity of animal exposures based on a national sample of EDs. Noncanine bite and sting injuries significantly affect public health and healthcare resources. Priorities can be focused on animal sources with the most impact on bite and sting injury rates, healthcare costs, and disease burden.


Assuntos
Mordeduras e Picadas/epidemiologia , Serviço Hospitalar de Emergência , Adolescente , Adulto , Idoso , Agkistrodon , Animais , Viúva Negra , Aranha Marrom Reclusa , Gatos , Criança , Pré-Escolar , Crotalus , Feminino , Humanos , Himenópteros , Lactente , Recém-Nascido , Mordeduras e Picadas de Insetos/epidemiologia , Masculino , Pessoa de Meia-Idade , Roedores , Mordeduras de Serpentes/epidemiologia , Picaduras de Aranhas/epidemiologia , Picadas de Carrapatos/epidemiologia , Estados Unidos/epidemiologia , Adulto Jovem
4.
Int J Clin Pharmacol Ther ; 58(6): 351-353, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32194023

RESUMO

Hemocoagulase is often used for hemostasis in patients with bleeding and hemorrhagic diseases, and to avoid or stanch bleeding after surgery. Herein, three patients with hepatic diseases suffering from hypofibrinogenemia were treated with hemocoagulase agkistrodon (HCA) in Peking University People's Hospital during September 2018. All the 3 patients were chronic hepatitis B patients: Patient 1 presented with hepatic carcinoma and chronic hepatitis B, and right hepatectomy was performed; patient 2 presented with chronic hepatitis B and gastrointestinal bleeding; patient 3 presented with chronic hepatitis B, acute liver failure with hematemesis, and was awaiting liver transplantation. All three patients were percutaneously injected with HCA to prevent late-onset bleeding. After HCA was discontinued, coagulation was restored to > 60 mg/dL on day 6, without injection of fibrinogen. HCA significantly reduced the need for fibrinogen in patients with hepatic diseases, and the level of fibrinogen should be carefully monitored in clinical applications.


Assuntos
Afibrinogenemia , Agkistrodon , Batroxobina/uso terapêutico , Hemostáticos/uso terapêutico , Hepatopatias/tratamento farmacológico , Animais , Fibrinogênio , Humanos
5.
PLoS One ; 15(2): e0229102, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32059022

RESUMO

Hematology, plasma biochemistry, and blood gas analysis were performed on venous samples obtained from free-ranging Eastern Copperheads (Agkistrodon contortrix) and Eastern Ratsnakes (Pantherophis alleghaniensis) in central North Carolina during a mark-recapture study conducted from April to October 2015 at the North Carolina Zoo. Blood samples were collected from 31 (15 male and 16 female) free-ranging copperheads and 34 (20 male and 14 female) free-ranging ratsnakes at the beginning and end of restraint. Restraint was performed for morphometric measurements, sex determination, and identification via placement of intracelomic passive integrated transponder (PIT) tags and marking of ventral scutes with a handheld electrocautery unit. Blood gas analytes were measured at the beginning of restraint and compared to analytes measured at the end to evaluate for changes secondary to handling. Total restraint time prior to the first blood sampling was 1.4 ± 0.4 mins (mean ± SD) and 1.0 ± 0.2 mins (mean ± SD) and restraint time prior to second blood sampling was 12.5 ± 2.4 mins (mean ± SD) and 13.5 ± 3.4 mins (mean ± SD) for copperheads and ratsnakes, respectively. Blood lactate concentrations at the beginning of restraint were similar for both species. Lactate concentrations increased significantly and pH decreased significantly for both species at the end of restraint when compared to the beginning of restraint. Furthermore, lactate concentrations at the end of restraint were significantly elevated in ratsnakes compared to copperheads. This study provides guidelines for interpretation of venous hematology, plasma biochemistry, and blood gas values for free-ranging copperheads and ratsnakes in central North Carolina and demonstrates the physiological response to venous blood gas analytes secondary to capture and restraint.


Assuntos
Agkistrodon/sangue , Animais Selvagens/sangue , Colubridae/sangue , Restrição Física/efeitos adversos , Estresse Fisiológico , Agkistrodon/fisiologia , Animais , Animais Selvagens/fisiologia , Gasometria , Colubridae/fisiologia , Feminino , Concentração de Íons de Hidrogênio , Ácido Láctico/sangue , Masculino , North Carolina , Veias
8.
Clin Toxicol (Phila) ; 58(4): 262-265, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-31342795

RESUMO

Background: Copperhead snakes (Agkistrodon contortrix) are considered as the least toxic of the North American pit vipers. The reported incidence of coagulopathy from copperhead envenomation is variable, possibly secondary to regional variation in subspecies and venom potency. Coagulation studies are often obtained when evaluating for the coagulopathic effects of copperhead venom, but the clinical utility of these indices is unclear. The aim of this study was to determine the prevalence of hematologic toxicity due to copperhead envenomation in hospitalized patients.Methods: This was a multi-center retrospective chart review study using electronic hospital data between January 1, 2006 and December 31, 2016 evaluating prevalence of coagulopathy following copperhead envenomation. Patients presenting to one of three major academic tertiary care centers in Virginia with suspected copperhead envenomation were identified using medical billing codes. The primary outcome was to summarize the prevalence of hematologic toxicity including thrombocytopenia, elevated prothrombin or partial thromboplastin times, or hypofibrinogenemia.Results: There were 244 cases used for final analysis. Hematologic toxicity occurred in 14% (95% CI 10-18%) of patients. Specific indices included thrombocytopenia in 1.2% (95% CI 0.4-3.6%), hypofibrinogenemia in 0.7% (95% CI 0.0-3.8%), elevated PT in 10.0% (95% CI 6.8-14.5%), and aPTT in 3.9% (95% CI 2.1-7.2%) of patients. There was no clinically significant bleeding reported in any case.Conclusions: Subtle hematologic abnormalities due to copperhead envenomation in patients treated in the Commonwealth of Virginia were relatively common, but do not appear to be clinically significant in this study population.


Assuntos
Agkistrodon , Transtornos da Coagulação Sanguínea/etiologia , Venenos de Crotalídeos/toxicidade , Mordeduras de Serpentes/complicações , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Animais , Transtornos da Coagulação Sanguínea/epidemiologia , Transtornos da Coagulação Sanguínea/fisiopatologia , Criança , Pré-Escolar , Feminino , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , Prevalência , Estudos Retrospectivos , Adulto Jovem
9.
Clin Toxicol (Phila) ; 58(3): 178-182, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31190571

RESUMO

Introduction: The majority of venomous snake exposures in the United States are due to snakes from the subfamily Crotalinae (pit vipers). There are three types of US pit vipers: rattlesnakes (Crotalus and Sisturus spp.) copperheads (Agkistrodon contortrix), and cottonmouths (Agkistrodon piscivorus) also known as water moccasins. Cottonmouth bites are reported less frequently than other pit viper envenomations, and data on cottonmouth envenomation are limited. Our objective was to describe the epidemiology, clinical manifestations, and management of cottonmouth envenomations using prospective data reported to the Toxicology Investigators Consortium's (ToxIC) North American Snakebite Registry (NASBR)Methods: Cottonmouth envenomation cases reported to NASBR for the period from January 1, 2013, through December 31, 2017 were reviewed. Variables collected included patient demographics, bite location, clinical manifestations, and management.Results: Thirty-one cottonmouth envenomations were reported. Most bites occurred in children aged 7-12 (39%). Most bites involved the lower extremity (72%). Intentional interaction with the snake occurred in three cases (10%). Swelling was the most reported clinical effect and occurred in all patients. Gastrointestinal symptoms were reported in 19% of patients, and 19% developed coagulopathy. Antivenom treatment was used in 84% of patients. Nineteen patients (61%) required hospital stays of >24 hours.Discussion: Our study represents the first systematic prospective data collection on cottonmouth bites. Our data demonstrate that cottonmouth envenomations cause primarily local effects and, occasionally, systemic toxicity. Our study also demonstrates that antivenom is often indicated for these envenomations per published guidelines and recommendations.Conclusions: Cottonmouth envenomations are relatively infrequent. However, they can cause significant local and systemic toxicity. Most cottonmouth envenomations in this series were treated with antivenom and were hospitalized beyond 24 hours.


Assuntos
Agkistrodon , Sistema de Registros , Mordeduras de Serpentes/epidemiologia , Adolescente , Adulto , Fatores Etários , Idoso , Animais , Criança , Pré-Escolar , Feminino , Hospitalização/estatística & dados numéricos , Humanos , Lactente , Masculino , Pessoa de Meia-Idade , América do Norte/epidemiologia , Sistema de Registros/estatística & dados numéricos , Adulto Jovem
10.
Gen Comp Endocrinol ; 287: 113324, 2020 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-31733208

RESUMO

There is growing interest in the use of glucocorticoid (GC) hormones to understand how wild animals respond to environmental challenges. Blood is the best medium for obtaining information about recent GC levels; however, obtaining blood requires restraint and can therefore be stressful and affect GC levels. There is a delay in GCs entering blood, and it is assumed that blood obtained within 3 min of first disturbing an animal reflects a baseline level of GCs, based largely on studies of birds and mammals. Here we present data on the timing of changes in the principle reptile GC, corticosterone (CORT), in four reptile species for which blood was taken within a range of times 11 min or less after first disturbance. Changes in CORT were observed in cottonmouths (Agkistrodon piscivorus; 4 min after first disturbance), rattlesnakes (Crotalus oreganus; 2 min 30 s), and rock iguanas (Cyclura cychlura; 2 min 44 s), but fence lizards (Sceloporus undulatus) did not exhibit a change within their 10-min sampling period. In both snake species, samples taken up to 3-7 min after CORT began to increase still had lower CORT concentrations than after exposure to a standard restraint stressor. The "3-min rule" appears broadly applicable as a guide for avoiding increases in plasma CORT due to handling and sampling in reptiles, but the time period in which to obtain true baseline CORT may need to be shorter in some species (rattlesnakes, rock iguanas), and may be unnecessarily limiting for others (cottonmouths, fence lizards).


Assuntos
Coleta de Amostras Sanguíneas/veterinária , Corticosterona/sangue , Répteis/sangue , Restrição Física/fisiologia , Agkistrodon/sangue , Animais , Coleta de Amostras Sanguíneas/métodos , Coleta de Amostras Sanguíneas/psicologia , Coleta de Amostras Sanguíneas/normas , Corticosterona/análise , Crotalus/sangue , Técnicas de Diagnóstico Endócrino/normas , Técnicas de Diagnóstico Endócrino/veterinária , Manobra Psicológica , Iguanas/sangue , Lagartos/sangue , Restrição Física/psicologia , Estresse Psicológico/sangue , Estresse Psicológico/etiologia , Fatores de Tempo
11.
Zhongguo Zhong Yao Za Zhi ; 44(22): 4820-4829, 2019 Nov.
Artigo em Chinês | MEDLINE | ID: mdl-31872588

RESUMO

Agkistrodon acutus is a traditional Chinese herb medicine which has immunological regulation,anti-tumor,anti-inflammatory and analgesic effects,which is mainly used for the treatment of rheumatoid arthritis,ankylosing spondylitis,sjogren's syndrome and tumors. In order to excavate more important functional genes from A. acutus,the transcriptome of the venom gland was sequenced by the Illumina Hi Seq 4000,and 32 862 unigenes were assembled. Among them,26 589 unigenes were mapped to least one public database. 2 695 unigenes were annotated and assigned to 62 TF families,and 5 920 SSR loci were identified. The majority of mapped unigenes was from Protobothrops mucrosquamatus in the NR database,which revealed their closest homology. Three secretory phospholipase A_2 with different amino acid sequences showed similar spatial structures and all had well-conserved active sites. The 3 D structural models of C-type lectin showed conserved glycosylation binding sites( Asn45). This study will lay the foundation for the further study of the function of snake venom protein,and promoting the development and utilization of genome resources from A. acutus.


Assuntos
Agkistrodon/genética , Venenos de Crotalídeos , Venenos de Serpentes/genética , Animais , Perfilação da Expressão Gênica , Serpentes , Transcriptoma
12.
Wilderness Environ Med ; 30(4): 446-449, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31699647

RESUMO

Snake envenomation during pregnancy is an uncommon emergency with several potential complications associated with the poisoning and its treatment. This case discusses a 27-y-old gravida 3, para 1102 (3 total pregnancies, 1 term birth, 1 premature birth, 0 abortions, 2 living births, twins) at 36 wk gestation who was bitten by a presumed Agkistrodon contortrix (copperhead snake). She had worsening pain and swelling in the right lower limb. Crotalidae polyvalent immune Fab was administered. The patient felt significantly better with improvement in swelling. She had a reactive nonstress test and reassuring coagulation studies. She gave birth to a healthy female infant 12 d later. This case supports the use of Crotalidae polyvalent immune Fab for venomous snakebites in pregnant patients to prevent possible maternal and fetal morbidity and mortality.


Assuntos
Agkistrodon , Antivenenos/uso terapêutico , Fragmentos Fab das Imunoglobulinas/uso terapêutico , Mordeduras de Serpentes/terapia , Adulto , Animais , Antivenenos/administração & dosagem , Venenos de Crotalídeos/envenenamento , Feminino , Humanos , Fragmentos Fab das Imunoglobulinas/administração & dosagem , Gravidez , Resultado da Gravidez
13.
Toxins (Basel) ; 11(11)2019 11 14.
Artigo em Inglês | MEDLINE | ID: mdl-31739403

RESUMO

This work reports the purification and biochemical and functional characterization of ACP-TX-I and ACP-TX-II, two phospholipases A2 (PLA2) from Agkistrodon contortrix pictigaster venom. Both PLA2s were highly purified by a single chromatographic step on a C18 reverse phase HPLC column. Various peptide sequences from these two toxins showed similarity to those of other PLA2 toxins from viperid snake venoms. ACP-TX-I belongs to the catalytically inactive K49 PLA2 class, while ACP-TX-II is a D49 PLA2, and is enzymatically active. ACP-TX-I PLA2 is monomeric, which results in markedly diminished myotoxic and inflammatory activities when compared with dimeric K49 PLA2s, confirming the hypothesis that dimeric structure contributes heavily to the profound myotoxicity of the most active viperid K49 PLA2s. ACP-TX-II exhibits the main pharmacological actions reported for this protein family, including in vivo local myotoxicity, edema-forming activity, and in vitro cytotoxicity. ACP-TX-I PLA2 is cytotoxic to A549 lung carcinoma cells, indicating that cytotoxicity to these tumor cells does not require enzymatic activity.


Assuntos
Venenos de Crotalídeos/metabolismo , Fosfolipases A2/metabolismo , Agkistrodon , Sequência de Aminoácidos , Animais , Fosfolipases A2/química , Homologia de Sequência de Aminoácidos
14.
Sci Rep ; 9(1): 15499, 2019 10 29.
Artigo em Inglês | MEDLINE | ID: mdl-31664072

RESUMO

Human-induced global climate change is exerting increasingly strong selective pressures on a myriad of fitness traits that affect organisms. These traits, in turn, are influenced by a variety of environmental parameters such as temperature and precipitation, particularly in ectothermic taxa such as amphibians and reptiles. Over the past several decades, severe and prolonged episodes of drought are becoming commonplace throughout North America. Documentation of responses to this environmental crisis, however, is often incomplete, particularly in cryptic species. Here, we investigated reproduction in a population of pitviper snakes (copperhead, Agkistrodon contortrix), a live-bearing capital breeder. This population experienced a severe drought from 2012 through 2016. We tested whether declines in number of progeny were linked to this drought. Decline in total number offspring was significant, but offspring length and mass were unaffected. Reproductive output was positively impacted by precipitation and negatively impacted by high temperatures. We hypothesized that severe declines of prey species (e.g., cicada, amphibians, and small mammals) reduced energy acquisition during drought, negatively impacting reproductive output of the snakes. Support for this view was found using the periodical cicada (Magicicada spp.) as a proxy for prey availability. Various climate simulations, including our own qualitative analysis, predict that drought events will continue unabated throughout the geographic distribution of copperheads which suggests that long-term monitoring of populations are needed to better understand geographic variation in drought resilience and cascading impacts of drought phenomena on ecosystem function.


Assuntos
Agkistrodon/fisiologia , Secas , Fertilidade , Reprodução , Animais , Mudança Climática , Ecossistema , Feminino , Masculino , Viviparidade não Mamífera
15.
Mo Med ; 116(3): 201-205, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31527942

RESUMO

The past two decades have seen changes to the management of copperhead snakebites. We review the current use of antivenom, analgesics, and laboratory testing as well as the declining role of surgical management.


Assuntos
Agkistrodon , Antivenenos/uso terapêutico , Mordeduras de Serpentes , Animais , Transtornos da Coagulação Sanguínea , História do Século XX , História do Século XXI , Humanos , Missouri , Mordeduras de Serpentes/história , Mordeduras de Serpentes/terapia
16.
Artigo em Inglês | MEDLINE | ID: mdl-31454702

RESUMO

Phospholipase A2 toxins present in snake venoms interact with biological membranes and serve as structural models for the design of small peptides with anticancer, antibacterial and antiparasitic properties. Oligoarginine peptides are capable of increasing cell membrane permeability (cell penetrating peptides), and for this reason are interesting delivery systems for compounds of pharmacological interest. Inspired by these two families of bioactive molecules, we have synthesized two 13-mer peptides as potential antileishmanial leads gaining insights into structural features useful for the future design of more potent peptides. The peptides included p-Acl, reproducing a natural segment of a Lys49 PLA2 from Agkistrodon contortrix laticinctus snake venom, and its p-AclR7 analogue where all seven lysine residues were replaced by arginines. Both peptides were active against promastigote and amastigote forms of Leishmania (L.) amazonensis and L. (L.) infantum, while displaying low cytotoxicity for primary murine macrophages. Spectrofluorimetric studies suggest that permeabilization of the parasite's cell membrane is the probable mechanism of action of these biomolecules. Relevantly, the engineered peptide p-AclR7 was more active in both life stages of Leishmania and induced higher rates of ethidium bromide incorporation than its native template p-Acl. Taken together, the results suggest that short peptides based on phospholipase toxins are potential scaffolds for development of antileishmanial candidates. Moreover, specific amino acid substitutions, such those herein employed, may enhance the antiparasitic action of these cationic peptides, encouraging their future biomedical applications.


Assuntos
Venenos de Crotalídeos/farmacologia , Leishmania infantum/efeitos dos fármacos , Leishmaniose Visceral/tratamento farmacológico , Macrófagos/efeitos dos fármacos , Peptídeos/farmacologia , Fosfolipases A2/farmacologia , Agkistrodon/metabolismo , Animais , Células Cultivadas , Venenos de Crotalídeos/síntese química , Macrófagos/citologia , Camundongos , Camundongos Endogâmicos BALB C , Peptídeos/síntese química
17.
BMC Complement Altern Med ; 19(1): 176, 2019 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-31315617

RESUMO

BACKGROUND: Snake venoms contain various bioactive constituents which possess potential therapeutic effects. The aim of this work was to investigate the effect of the extract from Agkistrodon halys venom on lipopolysaccharide (LPS)-induced myocardial injury. METHODS: Thirty male Sprague-Dawley rats were randomly assigned to three groups (10 rats per group): control group, LPS group and LPS + extract group. Rats in control and the LPS groups were intravenously injected with sterile saline solution, and rats in the LPS + extract group with the extract. After 2 h, rats of the control group were intraperitoneally injected sterile saline solution, and rats in the LPS and the LPS + extract groups were treated with LPS (20 mg per kg body weight). Levels of creatine kinase (CK) and lactate dehydrogenase (LDH) in serum were determined. Anti-inflammation of the extract was analyzed via determination of TNF-α and IL-6 in serum, and expression of TNF-α, IL-6, COX-2 and p-ERK protein in hearts. Heme oxygenase-1 (HO-1) and p-NF-κB protein expression in hearts, superoxide dismutase (SOD) activity and malondialdehyde (MDA) level in serum were used to evaluate the anti-oxidative properties of the extract. RESULTS: Extract pretreatment significantly decreased the level of serum CK and LDH, reduced the generation of inflammatory cytokines such as TNF-α and IL-6, and also reduced serum level of MDA in the LPS + extract group compared with the LPS group. In addition, the extract increased SOD activity in serum, HO-1 protein expression in hearts, and decreased TNF-α, IL-6, COX-2, p-NF-κB and p-ERK1/2 protein expression. CONCLUSION: Our results suggested that beneficial effect of this extract might be associated with an improved anti-oxidation and anti-inflammatory effect via downregulation of NF-κB/COX-2 signaling by activating HO-1/CO in hearts.


Assuntos
Agkistrodon/metabolismo , Traumatismos Cardíacos/prevenção & controle , Lipopolissacarídeos/efeitos adversos , Substâncias Protetoras/administração & dosagem , Venenos de Serpentes/administração & dosagem , Animais , Coração/efeitos dos fármacos , Traumatismos Cardíacos/induzido quimicamente , Traumatismos Cardíacos/genética , Traumatismos Cardíacos/metabolismo , Heme Oxigenase-1/genética , Heme Oxigenase-1/metabolismo , Humanos , Interleucina-6/genética , Interleucina-6/metabolismo , Masculino , Malondialdeído/metabolismo , NF-kappa B/genética , NF-kappa B/metabolismo , Ratos , Ratos Sprague-Dawley , Superóxido Dismutase/genética , Superóxido Dismutase/metabolismo
18.
West J Emerg Med ; 20(3): 497-505, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31123552

RESUMO

Introduction: Copperhead envenomation causes local tissue destruction, leading people to seek treatment for the pain and swelling. First-line treatment for the pain is opioid medications. There is rising concern that an initial opioid prescription from the emergency department (ED) can lead to long-term addiction. This analysis sought to determine whether use of Fab antivenom (FabAV) for copperhead envenomation affected opioid use. Methods: We performed a secondary analysis using data from a randomized clinical trial designed to determine the effect of FabAV on limb injury recovery following mild to moderate copperhead envenomation. Opioid use was a defined secondary outcome in the parent trial. Patients were contacted after discharge, and data were obtained regarding medications used for pain and the patients' functional status. This analysis describes the proportion of patients in each treatment group reporting opioid use at each time point. It also assesses the interaction between functional status and use of opioids. Results: We enrolled 74 patients in the parent trial (45 received FabAV, 29 placebo), of whom 72 were included in this secondary analysis. Thirty-five reported use of any opioids after hospital discharge. A smaller proportion of patients treated with FabAV reported opioid use: 40.9% vs 60.7% of those in the placebo group. The proportion of patients using opioids remained smaller in the FabAV group at each follow-up time point. Controlling for confounders and interactions between variables, the model estimated that the odds ratio of using opioids after hospital discharge among those who received placebo was 5.67 times that of those who received FabAV. Patients who reported higher baseline pain, those with moderate as opposed to mild envenomation, and females were more likely to report opioid use at follow-up. Patients with ongoing limitations to functional status had an increased probability of opioid use, with a stronger association over time. Opioid use corresponded with the trial's predefined criteria for full recovery, with only two patients reporting opioid use in the 24 hours prior to achieving full limb recovery and no patients in either group reporting opioid use after full limb recovery. Conclusion: In this study population, the proportion of patients using opioids for pain related to envenomation was smaller in the FabAV treatment group at all follow-up time points.


Assuntos
Agkistrodon , Analgésicos Opioides/uso terapêutico , Antivenenos/administração & dosagem , Transtornos Relacionados ao Uso de Opioides/prevenção & controle , Dor , Mordeduras de Serpentes , Animais , Feminino , Humanos , Fatores Imunológicos/administração & dosagem , Masculino , Pessoa de Meia-Idade , Dor/tratamento farmacológico , Dor/etiologia , Mordeduras de Serpentes/complicações , Mordeduras de Serpentes/tratamento farmacológico , Resultado do Tratamento
19.
J Exp Biol ; 222(Pt 9)2019 05 07.
Artigo em Inglês | MEDLINE | ID: mdl-30975741

RESUMO

Colonization of novel habitats often requires plasticity or adaptation to local conditions. There is a critical need to maintain hydration in terrestrial environments having limited water. Atypical populations of Florida cottonmouth snakes, Agkistrodon conanti, inhabit continental islands with no permanent sources of fresh water. Here, we report investigations related to how these insular snakes maintain water balance considering the mainland conspecifics are semi-aquatic and typically associate with freshwater mesic habitats. We tested three hypotheses related to water relations of insular populations of cottonmouth snakes compared with those on the mainland. (1) Voluntary drinking of fresh water in free-ranging insular snakes should reflect a relationship to recency of rainfall more strongly than in mainland snakes. (2) Insular snakes will tolerate greater dehydration before drinking than will mainland snakes. (3) Insular snakes will avoid drinking seawater more strongly than will those from the mainland. Between 2001 and 2018, we quantitatively estimated the hydration status of 337 individual cottonmouth snakes from insular populations and 30 cottonmouth snakes from mainland Florida, as judged by the tendency of wild-caught snakes to drink fresh water immediately following capture. We found that insular cottonmouth snakes had a higher incidence of dehydration than did mainland cottonmouth snakes (64% versus 23%), and the hydration status of the insular snakes correlated with patterns of precipitation. We also determined experimentally the dehydration threshold for drinking fresh water in insular (mean±s.d. -5.64±4.3%, n=34) and mainland cottonmouth snakes (-5.74±4.5%, n=21), and these were not significantly different. Discrimination tests for drinking serially from a graded series of brackish water showed that mainland snakes did not discriminate against the highest brackish value (10.5 ppt or 30% seawater), whereas insular snakes showed a preference for <15% seawater. Naive neonates from insular and mainland cohorts behaved similarly. The preference of insular snakes for fresh water represents an important aspect of the maintenance of water balance that differs from the mainland conspecifics and is likely a habituated or adaptive response to dependence on rainfall.


Assuntos
Agkistrodon/fisiologia , Ingestão de Líquidos , Água/fisiologia , Animais , Dessecação , Feminino , Florida , Masculino
20.
JAMA Surg ; 154(4): 346-354, 2019 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-30758508

RESUMO

Importance: Venomous snakebite severity ranges from an asymptomatic dry bite to severe envenomation and death. The clinical evaluation aids in prognosis and is essential to determine the risks and potential benefits of antivenom treatment. Objectives: To identify historical features, clinical examination findings, basic laboratory testing, and clinical grading scales that will risk-stratify patients with pit viper snake envenomation for severe systemic envenomation, severe tissue injury, and/or severe hematologic venom effects. Data Sources: We conducted a structured search of PubMed (1966-October 3, 2017) and Embase database (1980-October 3, 2017) to identify English-language studies that evaluated clinical features predictive of severe envenomation. Study Selection: We included studies that evaluated the test performance of at least 1 clinical finding with an acceptable reference standard of severe envenomation for venomous snakes of the Western Hemisphere. Only studies involving the most common subfamily, Crotalinae (pit vipers), were evaluated. Seventeen studies with data were available for abstraction. Data Extraction and Synthesis: The clinical features assessed and severity outcome measures were extracted from each original study. We assessed severity in 3 categories: systemic toxicity, tissue injury, and hematologic effects. Differences were resolved by author consensus. Results: The pooled prevalence of severe systemic envenomation was 14% (95% CI, 9%-21%). The pooled prevalence of severe tissue injury and severe hematologic venom effects were 14% (95% CI, 12%-16%) and 18% (95% CI, 8%-27%), respectively. Factors increasing the likelihood of severe systemic envenomation included the time from bite to care of 6 or more hours (likelihood ratio [LR], 3.4 [95% CI, 1.1-6.4]), a patient younger than 12 years (LRs, 3.2 [95% CI, 1.5-7.1] and 2.9 [95% CI, 1.3-6.2]), large snake size (LR, 3.1 [95% CI, 1.5-5.7]), and ptosis (LRs, 1.4 [95% CI, 1.0-2.1] and 3.8 [95% CI, 1.8-8.3]). Envenomation by the genus Agkistrodon (copperhead and cottonmouth), as opposed to rattlesnakes, decreased the likelihood of severe systemic envenomation (LR, 0.28 [95% CI, 0.10-0.78]). Initial hypofibrinogenemia (LR, 5.1 [95% CI, 1.7-15.0]) and thrombocytopenia (LR, 3.7 [95% CI, 1.9-7.3]) increased the likelihood of severe hematologic venom effects. Other clinical features from history, physical examination, or normal laboratory values were not discriminative. Conclusions: Clinical features can identify patients at increased risk of severe systemic envenomation and severe hematologic venom effects, but there are few features that are associated with severe tissue injury or can confidently exclude severe envenomation. Physicians should monitor patients closely and be wary of progression from nonsevere to a severe envenomation and have a low threshold to escalate therapy as needed.


Assuntos
Agkistrodon , Crotalus , Testes Hematológicos , Exame Físico , Mordeduras de Serpentes/complicações , Mordeduras de Serpentes/diagnóstico , Animais , Humanos , Índice de Gravidade de Doença , Mordeduras de Serpentes/epidemiologia , Fatores de Tempo
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