Toxicon: X最新文献

{"title":"Considerations for the development of a field-based medical device for the administration of adjunctive therapies for snakebite envenoming","authors":"R. Marshall Werner,&nbsp;Allison N. Soffa","doi":"10.1016/j.toxcx.2023.100169","DOIUrl":"10.1016/j.toxcx.2023.100169","url":null,"abstract":"<div><p>The timely administration of antivenom is the most effective method currently available to reduce the burden of snakebite envenoming (SBE), a neglected tropical disease that most often affects rural agricultural global populations. There is increasing interest in the development of adjunctive small molecule and biologic therapeutics that target the most problematic venom components to bridge the time-gap between initial SBE and the administration of antivenom. Unique combinations of these therapeutics could provide relief from the toxic effects of regional groupings of medically relevant snake species. The application a PRISMA/PICO literature search methodology demonstrated an increasing interest in the rapid administration of therapies to improve patient symptoms and outcomes after SBE. Advice from expert interviews and considerations regarding the potential routes of therapy administration, anatomical bite location, and species-specific venom delivery have provided a framework to identify ideal metrics and potential hurdles for the development of a field-based medical device that could be used immediately after SBE to deliver adjunctive therapies. The use of subcutaneous (SC) or intramuscular (IM) injection were identified as potential routes of administration of both small molecule and biologic therapies<strong>.</strong> The development of a field-based medical device for the delivery of adjunctive SBE therapies presents unique challenges that will require a collaborative and transdisciplinary approach to be successful.</p></div>","PeriodicalId":37124,"journal":{"name":"Toxicon: X","volume":"20 ","pages":"Article 100169"},"PeriodicalIF":0.0,"publicationDate":"2023-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/1e/7b/main.PMC10474190.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10524075","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neurologic and hematologic sequalae following a timber rattlesnake (Crotalus horridus) envenomation in a dachshund","authors":"Cory Woliver ,&nbsp;Michael Schaer","doi":"10.1016/j.toxcx.2023.100156","DOIUrl":"https://doi.org/10.1016/j.toxcx.2023.100156","url":null,"abstract":"<div><p>A 2-year-old female Dachshund had a witnessed timber rattlesnake envenomation. Although rattlesnake envenomations are a common, potentially life-threatening event in companion animals, timber rattlesnake envenomations in the dog are rarely reported. This dog described in this case report had significant hematologic and neurologic clinical derangements consistent with Types A and B rattlesnake venom and a suspected hypersensitivity reaction to the venom. This patient was treated aggressively with antivenom and fully recovered without any persistent neurologic signs at follow-up.</p></div>","PeriodicalId":37124,"journal":{"name":"Toxicon: X","volume":"18 ","pages":"Article 100156"},"PeriodicalIF":0.0,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"50172191","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A subfraction obtained from the venom of the tarantula Poecilotheria regalis contains inhibitor cystine knot peptides and induces relaxation of rat aorta by inhibiting L-type voltage-gated calcium channels","authors":"Luis Fernando Díaz-Peña ,&nbsp;Torres-Ortiz Daniela ,&nbsp;Manuel B. Aguilar ,&nbsp;Enoch Luis ,&nbsp;Fernando Lazcano-Pérez ,&nbsp;Roberto Arreguín-Espinosa ,&nbsp;Arturo Hernandez-Cruz ,&nbsp;César Ibarra-Alvarado ,&nbsp;Alejandro García-Arredondo","doi":"10.1016/j.toxcx.2023.100151","DOIUrl":"https://doi.org/10.1016/j.toxcx.2023.100151","url":null,"abstract":"<div><p>Venoms from tarantulas contain low molecular weight vasodilatory compounds whose biological action is conceived as part of the envenomation strategy due to its propagative effects. However, some properties of venom-induced vasodilation do not match those described by such compounds, suggesting that other toxins may cooperate with these ones to produce the observed biological effect. Owing to the distribution and function of voltage-gated ion channels in blood vessels, disulfide-rich peptides isolated from venoms of tarantulas could be conceived into potential vasodilatory compounds. However, only two peptides isolated from spider venoms have been investigated so far. This study describes for the first time a subfraction containing inhibitor cystine knot peptides, PrFr-I, obtained from the venom of the tarantula <em>Poecilotheria regalis</em>. This subfraction induced sustained vasodilation in rat aortic rings independent of vascular endothelium and endothelial ion channels. Furthermore, PrFr-I decreased calcium-induced contraction of rat aortic segments and reduced extracellular calcium influx to chromaffin cells by the blockade of L-type voltage-gated calcium channels. This mechanism was unrelated to the activation of potassium channels from vascular smooth muscle, since vasodilation was not affected in the presence of TEA, and PrFr-I did not modify the conductance of the voltage-gated potassium channel K_v10.1. This work proposes a new envenomating function of peptides from venoms of tarantulas, and establishes a new mechanism for venom-induced vasodilation.</p></div>","PeriodicalId":37124,"journal":{"name":"Toxicon: X","volume":"18 ","pages":"Article 100151"},"PeriodicalIF":0.0,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"50172274","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The safety of botulinum neurotoxin type A's intraarticular application in experimental animals","authors":"Ana Dugonjić Okroša ,&nbsp;Victor Ricardo Manuel Muñoz-Lora ,&nbsp;Ivica Matak ,&nbsp;Lidija Bach-Rojecky ,&nbsp;Mikhail Kalinichev ,&nbsp;Zdravko Lacković","doi":"10.1016/j.toxcx.2023.100155","DOIUrl":"10.1016/j.toxcx.2023.100155","url":null,"abstract":"<div><p>In vivo studies of botulinum neurotoxin type A (BoNT-A) enabled characterization of its activity in the nociceptive sensory system separate from its preferred action in motor and autonomic nerve terminals. However, in the recent rodent studies of arthritic pain which employed high intra-articular (i.a.) doses (expressed as a total number of units (U) per animal or U/kg), possible systemic effects have not been conclusively excluded. Herein we assessed the effect of two pharmaceutical preparations, abobotulinumtoxinA (aboBoNT-A, 10, 20, and 40 U/kg corresponding to 0.05, 0.11, and 0.22 ng/kg neurotoxin) and onabotulinumtoxinA (onaBoNT-A, 10 and 20 U/kg corresponding to 0.09 and 0.18 ng/kg, respectively) injected into the rat knee, on safety-relevant readouts: digit abduction, motor performance and weight gain during 14 days post-treatment.</p><p>The i. a. toxin produced dose-dependent impairment of the toe spreading reflex and rotarod performance, which was moderate and transient after 10 U/kg onaBoNT-A and ≤20 U/kg aboBoNT-A doses, and severe and long-lasting (examined up to 14 days) after ≥20 U/kg of onaBoNT-A and 40 U/kg aboBoNT-A. In addition, lower toxin doses prevented the normal weight gain compared to controls, while higher doses induced marked weight loss (≥20 U/kg of onaBoNT-A and 40 U/kg aboBoNT-A).</p><p>Commonly employed BoNT-A formulations, depending on the doses, cause local relaxation of the surrounding muscles and systemic adverse effects in rats. Thus, to evade possible toxin unwanted local or systemic spread, careful dosing and motor testing should be mandatory in preclinical behavioral studies, irrespective of the sites and doses of toxin application.</p></div>","PeriodicalId":37124,"journal":{"name":"Toxicon: X","volume":"18 ","pages":"Article 100155"},"PeriodicalIF":0.0,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10121478/pdf/main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9447373","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Availability, accessibility and use of antivenom for snakebite envenomation in Africa with proposed strategies to overcome the limitations","authors":"Mahmood Muazu Dalhat ,&nbsp;Julien Potet ,&nbsp;Abdulaziz Mohammed ,&nbsp;Nafiisah Chotun ,&nbsp;Hanna Amanuel Tesfahunei ,&nbsp;Abdulrazaq Garba Habib","doi":"10.1016/j.toxcx.2023.100152","DOIUrl":"10.1016/j.toxcx.2023.100152","url":null,"abstract":"<div><p>Africa remains one of the regions with the highest incident and burden of snakebite. The goal of the World Health Organization to halve the global burden of snakebite by 2030 can only be achieved if sub-optimal access to antivenoms in the most affected regions is addressed. We identified upstream, midstream, and downstream factors along the antivenom value chain that prevent access to antivenoms in the African region. We identified windows of opportunities that could be utilized to ensure availability, accessibility, and affordability for snakebite endemic populations in Africa. These include implementation of multicomponent strategies such as intensified advocacy, community engagement, healthcare worker trainings, and leveraging the institutional and governance structure provided by African governments to address the challenges identified.</p></div>","PeriodicalId":37124,"journal":{"name":"Toxicon: X","volume":"18 ","pages":"Article 100152"},"PeriodicalIF":0.0,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/71/62/main.PMC10015232.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9152446","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Clinical effects of immunization, bleeding, and albumin-based fluid therapy in horses used as immunoglobulin source to produce a polyspecific antivenom (Echitab-plus-ICP) towards venoms of African snakes","authors":"Rose Mary Huertas ,&nbsp;Mauricio Arguedas ,&nbsp;Juan Manuel Estrada ,&nbsp;Edwin Moscoso ,&nbsp;Deibid Umaña ,&nbsp;Gabriela Solano ,&nbsp;Mariángela Vargas ,&nbsp;Álvaro Segura ,&nbsp;Andrés Sánchez ,&nbsp;María Herrera ,&nbsp;Mauren Villalta ,&nbsp;Cynthia Arroyo-Portilla ,&nbsp;José María Gutiérrez ,&nbsp;Guillermo León","doi":"10.1016/j.toxcx.2023.100158","DOIUrl":"10.1016/j.toxcx.2023.100158","url":null,"abstract":"<div><p>During the production of snake antivenoms, the animals used as immunoglobulin source are subjected to processes that could deteriorate their physical condition. Therefore, these conditions must be carefully designed and validated. In this work, the immunization and bleeding protocols applied to horses used to produce the African polyspecific antivenom EchiTAb-plus-ICP were evaluated regarding their effects on the horses' health. The study focused on horses that had been previously immunized with venoms and then received periodic booster venom injections for antivenom production. It was found that the periodic immunization with 5 mg of a mixture of venoms of <em>Bitis arietans</em>, <em>Echis ocellatus</em>, <em>Dendroaspis polylepis,</em> and <em>Naja nigricollis</em> did not induce systemic signs of envenomation, and only caused mild swelling at the injection site, which did not evolve to abscesses, fistulas, or fibrosis. Three consecutive days of bleeding, collecting 6–8 L of blood per day, and self-transfusing the red blood cells (RBC) in the second and third days, did not induce evident cardiorespiratory alterations. However, this procedure caused significant reductions in RBC, hematocrit, hemoglobin, and total plasma protein values. Seven weeks after bleeding, these parameters were recovered, and horses were ready for the next immunization/bleeding cycle. The intravenous administration of equine albumin, at a dose of 2 g/kg body weight, increased the apparent plasma volume and the albumin concentration. However, this procedure induced early adverse reactions and transient alterations of the serum levels of the enzyme gamma-glutamyl transferase (GGT), thus suggesting some degree of hepatic injury. It was concluded that immunization and bleeding as described in this work do not cause significant clinical alterations in the horse's health, except for a transient drop in some hematological parameters. The albumin-based fluid therapy used does not hasten the recovery after bleeding but instead induces adverse events in the animals.</p></div>","PeriodicalId":37124,"journal":{"name":"Toxicon: X","volume":"18 ","pages":"Article 100158"},"PeriodicalIF":0.0,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10172988/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9473447","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Special issue editorial: Resource mapping for the management of snakebite envenomation","authors":"Wuelton M. Monteiro ,&nbsp;Hui Wen Fan ,&nbsp;Abdulrazaq G. Habib ,&nbsp;Kalana Maduwage ,&nbsp;João Ricardo Nickenig Vissoci ,&nbsp;José María Gutiérrez","doi":"10.1016/j.toxcx.2023.100154","DOIUrl":"10.1016/j.toxcx.2023.100154","url":null,"abstract":"","PeriodicalId":37124,"journal":{"name":"Toxicon: X","volume":"18 ","pages":"Article 100154"},"PeriodicalIF":0.0,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/c2/cf/main.PMC10031530.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9192495","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Snakebite care through the first two waves of COVID-19 in West Bengal, India: a qualitative study","authors":"Soumyadeep Bhaumik ,&nbsp;Deepti Beri ,&nbsp;Anthony B. Zwi ,&nbsp;Jagnoor Jagnoor","doi":"10.1016/j.toxcx.2023.100157","DOIUrl":"10.1016/j.toxcx.2023.100157","url":null,"abstract":"<div><p>Snakebite is a public health problem in many countries, with India having the highest number of deaths. Not much is known about the effect of the COVID-19 pandemic on snakebite care. We conducted 20 in-depth interviews with those bitten by venomous snakes through the two waves of COVID-19 (March–May 2020; May–November 2021), their caregivers, health care workers and social workers in two areas (Sundarbans and Hooghly) of West Bengal, India. We used a constructivist approach and conducted a thematic analysis. We identified the following themes: 1. Snakebite continued to be recognised as an acute emergency during successive waves of COVID-19; 2. COVID-19 magnified the financial woes of communities with high snakebite burden; 3. The choice of health care provider was driven by multiple factors and consideration of trade-offs, many of which leaned toward use of traditional providers during COVID-19; 4. Rurality, financial and social disadvantage and cultural safety, in and beyond the health system, affected snakebite care; 5. There is strong and shared felt need for multi-faceted community programs on snakebite.</p><p>We mapped factors affecting snakebite care in the three-delay model (decision to seek care, reaching appropriate health facility, receiving appropriate care), originally developed for maternal mortality. The result of our study contextualises and brings forth evidence on impact of COVID-19 on snakebite care in West Bengal, India. Multi-faceted community programs, are needed for addressing factors affecting snakebite care, including during disease outbreaks - thus improving health systems resilience. Community programs for increasing formal health service usage, should be accompanied by health systems strengthening, instead of an exclusive focus on awareness against traditional providers.</p></div>","PeriodicalId":37124,"journal":{"name":"Toxicon: X","volume":"18 ","pages":"Article 100157"},"PeriodicalIF":0.0,"publicationDate":"2023-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10091724/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9423096","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Snakebite envenoming at MSF: A decade of clinical challenges and antivenom access issues","authors":"Julien Potet ,&nbsp;Saschveen Singh ,&nbsp;Koert Ritmeijer ,&nbsp;Kasaye Sisay ,&nbsp;Gabriel Alcoba ,&nbsp;Fabienne Jouberton ,&nbsp;Yannick Wilson Henko Kinding ,&nbsp;Alexandra Kruse ,&nbsp;Aboubacar Bengaly ,&nbsp;Malwal Sabino ,&nbsp;Narcisse Patrice Komas ,&nbsp;Matthew Coldiron","doi":"10.1016/j.toxcx.2022.100146","DOIUrl":"10.1016/j.toxcx.2022.100146","url":null,"abstract":"<div><p>The medical humanitarian organization Médecins Sans Frontières (MSF) provides medical care in more than 70 countries and admits more than 7000 cases of snakebite in its facilities each year.</p><p>We describe our activities against snakebite in three African countries: Central African Republic, South Sudan and Ethiopia, in which different models of care have been developed. A standard protocol using two different antivenoms depending on the patient's syndrome has been introduced, and a simple blood coagulation test is performed to detect venom-induced coagulopathy. Other services, including surgery for necrotizing wounds, are offered in the facilities where MSF admits a large number of snakebite patients. All services, including provision of antivenom, are offered free-of-charge in MSF-supported facilities. Community-based activities focusing on preventive measures and prompt transport to hospital have been developed in a few MSF projects.</p><p>The provision of quality care and treatment, including effective antivenoms, without out-of-pocket payments by the patients, probably explains why MSF has admitted an increasing number of snakebite victims over the last years. This model requires significant resources and monitoring, including regular training of healthcare workers on treatment protocols and a considerable budget for antivenom procurement.</p></div>","PeriodicalId":37124,"journal":{"name":"Toxicon: X","volume":"17 ","pages":"Article 100146"},"PeriodicalIF":0.0,"publicationDate":"2023-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/f8/fe/main.PMC9813776.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10508683","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Antivenom availability, delays and use in Australia","authors":"Geoffrey K. Isbister","doi":"10.1016/j.toxcx.2022.100145","DOIUrl":"10.1016/j.toxcx.2022.100145","url":null,"abstract":"<div><p>Antivenom is the main treatment for snake envenoming and there are ongoing concerns about availability in resource poor regions of the world. However, effective antivenom treatment for snake envenoming requires more than improved availability of safe and efficacious antivenoms. Most importantly, antivenom must be administered as early as possible, and within 2–6 h of the bite in Australia. At the same time, it is also important that antivenom not be given to all patients indiscriminately with a suspected snakebite, because of the risk of anaphylaxis. Delays in the administration of antivenom are a significant impediment to effective antivenom treatment and can be divided into pre-hospital and in-hospital delays. These range from delays due to remoteness of snakebite, to delays in diagnosis and administration of antivenom once in hospital. In Australia, antivenom is readily available in most hospitals, and a large portion of patients present to hospital within 2 h of the bite. However, there is on average a further delay of 2.5 h before antivenom is administered. Early diagnosis with accurate bedside tests and rapid clinical assessment of patients with snakebite are key to improving the effective use of antivenom.</p></div>","PeriodicalId":37124,"journal":{"name":"Toxicon: X","volume":"17 ","pages":"Article 100145"},"PeriodicalIF":0.0,"publicationDate":"2023-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9747507/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10363128","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}