Toxicon: X最新文献

{"title":"Stress levels, hematological condition, and productivity of plasma-producing horses used for snake antivenom manufacture: A comparison of two industrial bleeding methods","authors":"","doi":"10.1016/j.toxcx.2024.100212","DOIUrl":"10.1016/j.toxcx.2024.100212","url":null,"abstract":"<div><div>The immunization and industrial bleeding of horses are essential stages for producing snake antivenoms. In Costa Rica, the traditional method involves stimulating the antibody response of horses by periodically injecting venoms, collecting hyperimmune plasma over three consecutive bleeding days, and repeating this process every eight weeks. While this method does not cause major physical or hematological issues in horses, the associated stress has not been evaluated. We compared this traditional method with an alternative method that involves injecting venoms, collecting hyperimmune plasma in a single bleeding day, and repeating the process every two weeks. We assessed stress (via serum and fecal cortisol levels and an ethological study), hematological parameters (hematocrit and hemoglobin concentration), and plasma productivity over eight months. Serum cortisol levels remained within the normal range for both methods throughout the immunization/bleeding cycle. However, serum and fecal cortisol levels were significantly higher in horses subjected to the traditional method compared to those in the alternative method. Neither method caused significant hematological alterations. Notably, the alternative method yielded a higher volume of plasma. We concluded that adopting the alternative method ensures horse welfare while improving industrial bleeding productivity. This approach may reduce costs and improve the availability of this essential treatment for vulnerable populations.</div></div>","PeriodicalId":37124,"journal":{"name":"Toxicon: X","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2024-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142535278","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":"Diagnosis of human envenoming by terrestrial venomous animals: Routine, advances, and perspectives","authors":"","doi":"10.1016/j.toxcx.2024.100211","DOIUrl":"10.1016/j.toxcx.2024.100211","url":null,"abstract":"<div><div>Despite the development of new and advanced diagnostic approaches, monitoring the clinical evolution of accidents caused by venomous animals is still a challenge for science. In this review, we present the state of the art of laboratory tests that are routinely used for the diagnosis and monitoring of envenomings by venomous animals, as well as the use of new tools for more accurate and specific diagnoses. While a comprehensive range of tools is outlined, comprising hematological, biochemical, immunoassays, and diagnostic imaging tools, it is important to acknowledge their limitations in predicting the onset of clinical complications, since they provide an overview of organic damage after its development. Thus, the need for discovery, validation, and use of biomarkers that have greater predictive power, sensitivity and specificity is evident. This will help in the diagnosis, monitoring, and treatment of patients envenomated by venomous animals, consequently reducing the global burden of morbidity and mortality.</div></div>","PeriodicalId":37124,"journal":{"name":"Toxicon: X","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2024-10-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142535313","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":"Supplementation of polyclonal antibodies, developed against epitope-string toxin-specific peptide immunogens, to commercial polyvalent antivenom, shows improved neutralization of Indian Big Four and Naja kaouthia snake venoms","authors":"","doi":"10.1016/j.toxcx.2024.100210","DOIUrl":"10.1016/j.toxcx.2024.100210","url":null,"abstract":"<div><div>Snakebites profoundly impact the rural population of tropical nations, leading to significant socio-economic repercussions. Polyvalent antivenom (PAV) therapy faces several limitations, including intra-specific variations and poor efficacy against some major toxins and low molecular mass, poorly immunogenic toxins, which contribute to increased mortality and morbidity rates. Innovative strategies for developing novel antivenoms are continuously explored to address these challenges. The present study focuses on designing of 17 epitope-string toxin-specific peptide immunogens from pharmacologically active major and/or poorly immunogenic toxins (snake venom metalloprotease, Kunitz-type serine protease inhibitor, phospholipase A₂, three-finger toxin) from the venom of the ‘Big Four’ venomous snakes and <em>Naja kaouthia</em> (NK) in India. These custom peptide antibodies demonstrated robust immuno-reactivity against the venoms ‘Big Four’ and NK. When these antibodies were supplemented with commercial PAV at a defined ratio (formulated polyvalent antivenom or FPAV), it significantly enhanced the neutralization of snake venom enzymes and <em>in vivo</em> neutralization of lethality and pharmacological activities such as haemorrhage, necrosis, pro-coagulant, defibrinogenation, and myotoxicity of ‘Big Four’ and NK venoms compared to PAV in mice. The present study highlights a promising strategy for developing next-generation antivenoms using synthetic peptide-based immunogens, offering a targeted approach to address the limitations of current antivenom therapy.</div></div>","PeriodicalId":37124,"journal":{"name":"Toxicon: X","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2024-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142417299","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":"Bioprospection of rattlesnake venom peptide fractions with anti-adipose and anti-insulin resistance activity in vitro","authors":"","doi":"10.1016/j.toxcx.2024.100209","DOIUrl":"10.1016/j.toxcx.2024.100209","url":null,"abstract":"<div><div>Animal venoms are natural products that have served as a source of novel molecules that have inspired novel drugs for several diseases, including for metabolic diseases such as type-2 diabetes and obesity. From venoms, toxins such as exendin-4 (<em>Heloderma suspectum</em>) and crotamine (<em>Crotalus durissus terrificus</em>) have demonstrated their potential as treatments for obesity. Moreover, other toxins such as Phospholipases A₂ and Disintegrins have shown their potential to modulate insulin secretion in vitro. This suggests an unexplored diversity of venom peptides with a potential anti-obesogenic in Mexican rattlesnake venoms. For that reason, this study explored the in vitro effect of Crotalus venom peptide-rich fractions on models for insulin resistance, adipocyte lipid accumulation, antioxidant activity, and inflammation process through nitric oxide production inhibition. Our results demonstrated that the peptide-rich fractions of <em>C. aquilus, C. ravus</em>, and <em>C. scutulatus scutulatus</em> were capable of reverting insulin resistance, enhancing glucose consumption to normal control; <em>C. culminatus, C. molossus oaxacus</em>, and <em>C. polystictus</em> diminished the lipid accumulation on adipocytes by 20%; <em>C. aquilus, C. ravus</em>, and <em>C. s. salvini</em> had the most significant cellular antioxidant activity, having nearly 80% of ROS inhibition. <em>C. aquilus, C. pyrrhus,</em> and <em>C. s. salvini</em> inhibited nitric oxide production by about 85%. We demonstrated the potential of these peptides from <em>Crotalus</em> venoms to develop novel drugs to treat type-2 diabetes and obesity. Moreover, we described for the first time that <em>Crotalus</em> venom peptide fractions have antioxidant and inflammatory properties in vitro models.</div></div>","PeriodicalId":37124,"journal":{"name":"Toxicon: X","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2024-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142417300","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":"A probabilistic hazard assessment for cyanobacterial toxins accounting for regional geography and water body trophic status","authors":"","doi":"10.1016/j.toxcx.2024.100208","DOIUrl":"10.1016/j.toxcx.2024.100208","url":null,"abstract":"<div><p>Under climate change scenarios freshwater eutrophication is expected to increase, and with it the occurrence of cyanobacterial toxin-producing harmful algal blooms. In the current study, microcystin toxin occurrence data from literature sources and a long-term provincial monitoring program were used to conduct a probabilistic hazard assessment for Alberta, Canada. The large temporal and spatial range of data makes Alberta a model system for identifying regional geography and water body trophic status factors driving toxin concentrations. Environmental exposure distributions of microcystin concentrations were plotted and used to identify the likelihood of a given sample exceeding water guideline values as a function of regional geography, total phosphorus and chlorophyll-a concentration. This process identified regions with intensive cultivation and those most prone to water deficits associated with climate change to be most associated with exceedances of regulatory guideline values. Elevated phosphorus and chlorophyll-a concentrations were also drivers of toxin occurrence. This assessment can be used to identify water bodies of greatest risk to human and animal populations from cyanotoxins and thereby inform regulators as to most effective monitoring strategies.</p></div>","PeriodicalId":37124,"journal":{"name":"Toxicon: X","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2024-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2590171024000250/pdfft?md5=1961cadfcb6242435fa5bac611f967ba&pid=1-s2.0-S2590171024000250-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142272916","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":"Plug and play virus-like particles for the generation of anti-toxin antibodies","authors":"","doi":"10.1016/j.toxcx.2024.100204","DOIUrl":"10.1016/j.toxcx.2024.100204","url":null,"abstract":"<div><p>Snakebite is a major global health concern, for which antivenom remains the only approved treatment to neutralise the harmful effects of the toxins. However, some medically important toxins are poorly immunogenic, resulting in reduced efficacy of the final product. Boosting the immunogenicity of these toxins in the commercial antivenom immunising mixtures could be an effective strategy to improve the final dose efficacy, and displaying snake antigens on Virus-like particles (VLPs) is one method for this. However, despite some applications in the field of snakebite, VLPs have yet to be explored in methods that could be practical at an antivenom manufacturing scale. Here we describe the utilisation of a “plug and play” VLP system to display immunogenic linear peptide epitopes from three finger toxins (3FTxs) and generate anti-toxin antibodies. Rabbits were immunised with VLPs displaying individual consensus linear epitopes and their antibody responses were characterised by immunoassay. Of the three experimental consensus sequences, two produced antibodies capable of recognising the consensus peptides, whilst only one of these could also recognise native whole toxins. Further characterisation of antibodies raised against this peptide demonstrated a sub-class specific response, and that these were able to elicit partially neutralising antibody responses, resulting in increased survival times in a murine snakebite envenoming model.</p></div>","PeriodicalId":37124,"journal":{"name":"Toxicon: X","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2590171024000213/pdfft?md5=ba01fce4aaed7e7545df55c4bc9a9c0d&pid=1-s2.0-S2590171024000213-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142099558","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":"Design, development and preclinical assessment of MENAVip-ICP, a new snake antivenom with potential coverage of species in the Middle East and North Africa regions","authors":"","doi":"10.1016/j.toxcx.2024.100206","DOIUrl":"10.1016/j.toxcx.2024.100206","url":null,"abstract":"<div><p>Snakebite in the Middle East and North Africa (MENA) is a public health problem whose magnitude is not fully known. Several antivenoms are available in these regions, but these formulations are designed for restricted geographical settings. Many countries do not have local production of antivenoms and must access products whose clinical performance has not been demonstrated. We hypothesize that it is possible to unify the treatment for viperid snakebites of MENA in a single antivenom formulation. Hereby we describe the design, development and preclinical evaluation of an antivenom of broad geographical coverage for this region (MENAVip-ICP). We produced this antivenom from the plasma of horses immunized with eight medically important venoms of viperid snake species from MENA. For this, we used a strategy based on two stages: first, immunization of horses with North African (NA) venoms, followed by a second immunization stage, on the same horses, with MENA venoms. We purified antivenoms from both stages: the Anti-NA and the final product Anti-MENA (MENAVip-ICP). Anti-NA was considered as intermediate formulation and was purified with the intention to study the progression of the immunoglobulin immune response of the horses. Antivenoms from both stages neutralized lethal, hemorrhagic, and procoagulant activities of homologous venoms. Compared to Anti-NA, MENAVip-ICP improved the neutralization profile of intravenous lethality and <em>in vitro</em> procoagulant activities of venoms. A notable finding was the difference in the neutralization of lethality when MENAVip-ICP was assessed intraperitoneally versus intravenously in the murine model. Intraperitoneally, MENAVip-ICP appears more effective in neutralizing the lethality of all venoms. Furthermore, MENAVip-ICP neutralized the lethal activity of venoms of species from other regions of MENA, Central/East Asia, and Sub-Saharan Africa that were not included in the immunization protocol. Our results showed that MENAVip-ICP neutralizes the main toxic activities induced by viperid MENA venoms at the preclinical level. Consequently, it is a promising product that could be clinically assessed for the treatment of snakebite envenomings in this region.</p></div>","PeriodicalId":37124,"journal":{"name":"Toxicon: X","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2024-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2590171024000237/pdfft?md5=ec6d45a05b83dcdfb12958b3bde3d8de&pid=1-s2.0-S2590171024000237-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142130117","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":"Stroke as a rare complication of scorpion stings: A systematic review and analysis","authors":"","doi":"10.1016/j.toxcx.2024.100205","DOIUrl":"10.1016/j.toxcx.2024.100205","url":null,"abstract":"<div><p>Approximately 1 million scorpion stings are recorded annually worldwide, resulting in 3000 deaths. Scorpion venom has various effects on the human body, with neurological complications occurring in about 2% of cases. Among these complications, stroke—whether ischemic or hemorrhagic—is particularly significant. A systematic literature review was conducted through a bibliographic search using key terms in the PubMed, Scopus, Scielo, Latin American and Caribbean Literature in Health Sciences (LILACS) and Google Schoolar databases without date restrictions. Articles related to stroke due to scorpion stings in Spanish, English, and Portuguese were included. Our protocol was registered in PROSPERO. A total of 24 articles met the inclusion criteria for this review. The primary neurological symptoms caused by scorpion stings include hemiplegia, hemiparesis, seizures, and limb weakness. Stroke should be suspected in the presence of these symptoms, as scorpion stings can lead to both hemorrhagic and ischemic strokes in both adults and pediatric populations. While stroke is a rare complication of scorpion stings, it is crucial to consider this diagnosis in patients presenting with neurological symptoms, necessitating the use of computed tomography or magnetic resonance imaging if stroke is suspected.</p></div>","PeriodicalId":37124,"journal":{"name":"Toxicon: X","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2024-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2590171024000225/pdfft?md5=179dfdf271603b577c9a070d3ce41e14&pid=1-s2.0-S2590171024000225-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142122586","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":"Development of a gold nanoparticle-based novel diagnostic prototype for in vivo detection of Indian red scorpion (Mesobuthus tamulus) venom","authors":"","doi":"10.1016/j.toxcx.2024.100203","DOIUrl":"10.1016/j.toxcx.2024.100203","url":null,"abstract":"<div><p>Indian red scorpion <em>Mesobuthus tamulus</em> is responsible for substantial mortality in India and Sri Lanka; however, no specific diagnostic method is available to detect the venom of this scorpion in envenomed plasma or body fluid. Therefore, we have proposed a novel, simple, and rapid method for detecting <em>M. tamulus</em> venom (MTV) in the plasma of envenomed animals using polyclonal antibodies (PAb) raised against three modified custom peptides representing the antigenic epitopes of K⁺ (Tamapin) and Na⁺ (α-neurotoxin) channel toxins, the two major MTV toxins identified by proteomic analysis. The optimum PAb formulation containing PAb 1, 2, and 3 in proportion (1:1:1, w/w/w) acted synergistically, demonstrating significantly higher immunological recognition of MTV than anti-scorpion antivenom (developed against native toxins) and individual antibodies against peptide immunogens. The PAb formulation could detect MTV optimally in envenomed rat plasma (intravenous and subcutaneous routes) at 30–60 min post-injection. The acetonitrile precipitation method developed in this study to augment the MTV detection sensitivity enriched the low molecular mass peptide toxins in envenomed rat plasma, which was ascertained by mass spectrometry analysis. The gold nanoparticles conjugated PAb formulation, characterised by biophysical techniques such as Fourier transform infrared spectroscopy (FTIR) and transmission electron microscopy (TEM), demonstrated their interaction with low molecular mass MTV peptide toxins in envenomed rat plasma. This interaction results in the accumulation of the gold nanoparticles, thus leading to signal change in absorbance spectra that can be discerned within 10 min. From a standard curve of MTV spiked plasma, the quantity of MTV in envenomed rat plasma could be determined by gold nanoparticle-PAb formulation conjugate.</p></div>","PeriodicalId":37124,"journal":{"name":"Toxicon: X","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2024-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2590171024000201/pdfft?md5=8238eec18bed45328ca818b6d09a6e67&pid=1-s2.0-S2590171024000201-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142041260","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":"Pilot-scale evaluation of a dynamic body-feed filtration system for primary clarification of snake antivenoms produced by the caprylic acid method","authors":"","doi":"10.1016/j.toxcx.2024.100202","DOIUrl":"10.1016/j.toxcx.2024.100202","url":null,"abstract":"<div><p>The performance of dynamic body-feed filtration (DBF) in the removal of bulky solids produced during the manufacturing of snake antivenoms using the caprylic acid method was evaluated. For this purpose, diatomites with different filterability properties were compared in a bench-scale study to assess their effectiveness in removing the precipitated material formed after the addition of caprylic acid to equine hyperimmune plasma. C1000 diatomite at a concentration of 90 g/L of precipitated plasma showed the best performance. Then, the process was scaled up to three batches of 50 L of hyperimmune horse plasma. At this pilot scale, 108 ± 4% of the immunoglobulins present following plasma precipitation were recovered after DBF. The antivenoms generated using this procedure met quality specifications. When compared to open filtration systems commonly used at an industrial scale by many antivenom manufacturers, DBF has a similar yield and produces filtrates with comparable physicochemical characteristics. However, DBF ensures the microbiological quality of the primary clarification in a way that open systems cannot. This is because: 1) DBF is performed in a single-use closed device of depth filters which prevents microbial contamination, and 2) DBF removes bulky material in few minutes instead of the more than 24 h needed by open filtration systems, thus reducing the risk of contamination. It was concluded that DBF is a cost-effective, easily validated, and GMP-compliant alternative for primary clarification following caprylic acid precipitation of plasma in snake antivenom production.</p></div>","PeriodicalId":37124,"journal":{"name":"Toxicon: X","volume":null,"pages":null},"PeriodicalIF":3.6,"publicationDate":"2024-08-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2590171024000195/pdfft?md5=3dd29b384f64d71414bc636ba033eb5f&pid=1-s2.0-S2590171024000195-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141993675","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}