Cat snakes (Genus: Boiga) are considered to be of lesser medical important in Sri Lanka, as their bites are known to cause only mild local effects such as local pain and swelling at the site of the bite. Five species of cat snakes are found in Sri Lanka, of which three are endemic. They are widely distributed all over the country. Out of seven cases of cat snake bites, including six adults and one child, five developed only mild local effects and two did not have any symptoms. Any of them did not develop systemic manifestations. The snakes responsible were the Sri Lanka cat snake (Boiga ceylonensis), Forsten's cat snake (Boiga forsteni), and also Ranawana's cat snake (Boiga ranawanei) which is the first report in Sri Lanka.

The cururu toad (Rhinella jimi) is an anuran belonging to the fauna of the Brazilian northeast region, which releases a secretion with toxins from your parotoid glands. Although it has some information about secondary metabolites and proteins, the elemental composition of the released secretion is unknown. Therefore, this is the first report on the ionome of the secretion of the parotoid glands from R. jimi, investigating the influences of abiotic factors such as biome, seasonality, and gender. ICP-MS was used for measurements combined with principal component analysis (PCA). A screening of the secretion sample detected 68 elements which the total concentration of 18 elements was determined. PCA revealed that biome and seasonality factors have a greater influence on the ionomic profile of parotoid secretion. The presence of toxic metals in the secretion samples indicates that the R. jimi toad can be considered a potential bioindicator. These findings may contribute to understanding the metabolism, lifestyle, and interaction of the R. jimi toad with environmental factors as well as open new perspectives to investigate the relationships of the ionome with other biomolecules, for example, metalloproteins and their physiological functions.

Kratom is a mixture of compounds that are present in the leaves of the tropical tree Mitragyna speciosa. It is used as a psychoactive agent with both opiate and stimulant-like effects. In this case series we describe the signs, symptoms, and the management of kratom overdose in the prehospital setting and in intensive care. We retrospectively searched for cases in the Czech Republic. Over 36 months we found 10 cases of kratom poisoning, which healthcare records were analyzed and reported as per CARE guidelines. The dominant symptoms in our series were neurological and included quantitative (n = 9) or qualitative (n = 4) disorder of consciousness. Signs and symptoms of vegetative instability [hypertension (n = 3) and tachycardia (n = 3) vs. bradycardia/cardiac arrest (n = 2), mydriasis (n = 2) vs. miosis (n = 3)] were noticed. Prompt response to naloxone in two cases and lack of response in one patient were observed. All patients survived and the effect of intoxication wore off within two days. Kratom overdose toxidrome is variable and, in keeping with its receptor physiology, consists of signs and symptoms of opioid-like overdose, sympathetic overactivation and serotonin-like syndrome. Naloxone can help to avoid intubation in some cases.

The receptor protein CLEC-2 on platelet membranes is the target of the endogenous ligand podoplanin found on cancer cells and of rhodocytin, a snake venom component of the Malayan pit viper Calloselasma rhodostoma. Ligand binding results in platelet activation, increased blood coagulation and thrombosis. In an effort to isolate rhodocytin, we have purified CLEC-2 as bait from E. coli. Affinity captured rhodocytin interacted with mammalian CLEC-2 and stimulated platelet aggregation in a dose dependent manner.

Micrurus surinamensis is a semi-aquatic coral snake found in primary forest region and can cause relevant human accidents. In this work we investigated the toxic and antigenic activities of the Peruvian Micrurus surinamensis venom (MsV). We found that MsV show hyaluronidase activity but lack LAAO and PLA2 enzymatic activities. Interestingly, MsV induce edematogenic responses but cannot cause nociceptive effects. Furthermore, MsV can reduce in vitro cell viability in MGSO-3 cell line derived from human breast cancer tissue. To evaluate its antigenic potential, rabbits were immunized with MsV, which proved to be immunogenic. ELISA, immunobloting and in vivo neutralization assays demonstrated that the specific rabbit anti-MsV antivenom is more efficient than the therapeutic Brazilian antivenom in recognizing and neutralizing the lethal activity of MsV. MsV differs in protein profile and biological activities from M. frontalis venom (MfV), used as control, which impairs its recognition and neutralization by Brazilian therapeutic anti-elapidic antivenom. We performed a SPOT immunoassay for the identification of B-cell linear epitopes in the main toxins described for MsV targeted by the elicited neutralizing antibodies previously produced. A membrane containing 15-mer peptides representing the sequences of five 3TFxs and five PLA2s was produced and probed with anti- MsV antibodies. Results revealed important regions in 3FTx toxins for venom neutralization. Identifying the main MsV components and its biological activities can be helpful in guiding the production of antivenoms and in the optimization of treatment for coral snake envenomation in Brazil.

Based on its phylogenetic relationship to monitor lizards (Varanidae), Gila monsters (Heloderma spp.), and the earless monitor Lanthanotus borneesis, the Chinese crocodile lizard, Shinisaurus crocodilurus, has been assigned to the Toxicofera clade, which comprises venomous reptiles. However, no data about composition and biological activities of its oral secretion have been reported. In the present study, a proteomic analysis of the mandibular gland of S. crocodilurus and, for comparison, of the herbivorous Solomon Island skink Corucia zebrata, was performed. Scanning electron microscopy (SEM) of the teeth from S. crocodilurus revealed a sharp ridge on the anterior surface, but no grooves, whereas those of C. zebrata possess a flattened crown with a pointed cusp. Proteomic analysis of their gland extracts provided no evidence of venom-derived peptides or proteins, strongly supporting the non-venomous character of these lizards. Data are available via ProteomeXchange with identifier PXD039424.

The Azorean dairy industry is based on a semi-intensive model. Due to the few storage facilities and the large climatic fluctuations that characterize the Azores, the complete feed mixture (total mixed ration - TMR) is susceptible to the proliferation of a variety of fungi and mycotoxin contamination. Thus, chronic ingestion of these xenobiotics may lead to increased susceptibility to disease, loss of reproductive performance and, in the case of dairy cattle, decreased productivity and quality of milk produced. Since it is impossible to eliminate completely the presence of mycotoxins, it is essential to ensure the implementation of strategies to reduce their concentration in products intended for food and feed, as well as to monitor and control the levels present in food. This study aimed to evaluate the occurrence zearalenone (ZEA) in feed (TMR) in four dairy cattle farms on the Azorean Island of São Miguel and relate it to the occurrence of this mycotoxin in the milk produced, by associating several production and health indicators translated by the monthly milk contrast. To this end, the monthly milk contrast data, the determination of ZEA in the ingested feed and the (individual) milk samples from the four farms included in the study were used. Eighty-three (98.8%) of the milk samples under study had detectable ZEA levels (1.56 ± 1.36 μg/L), higher than reported in previous similar studies. Although ZEA concentration was not significantly associated with any production indicator analyzed (days in milk, age at calving, milk yield, protein content, butyrate content, somatic cell concentration and urea), it was found that the production regime and type of feed management is a major factor in the exposure of animals to high mycotoxin contents. Further studies are recommended to ensure continued monitoring and reduction of the risk associated with exposure of animals and humans to ZEA.

Fumonisin B1 (FB1) is etiologically linked to cancer, yet the underlying mechanisms remain largely unclear. It is also not known if mitochondrial dysfunction is involved as a contributor to FB1-induced metabolic toxicity. This study investigated the effects of FB1 on mitochondrial toxicity and its implications in cultured human liver (HepG2) cells. HepG2 cells poised to undergo oxidative and glycolytic metabolism were exposed to FB1 for 6 h. We determined mitochondrial toxicity, reducing equivalent levels and mitochondrial sirtuin activity using luminometric, fluorometric and spectrophotometric methods. Molecular pathways involved were determined using western blots and PCR. Our data confirm that FB1 is a mitochondrial toxin capable of disrupting the stability of complexes I and V of the mitochondrial electron transport and decreasing the NAD:NADH ratio in galactose supplemented HepG2 cells. We further showed that in cells treated with FB1, p53 acts as a metabolic stress-responsive transcription factor that induces the expression of lincRNA-p21, which plays a crucial role in stabilising HIF-1α. The findings provide novel insights into the impact of this mycotoxin in the dysregulation of energy metabolism and may contribute to the growing body of evidence of its tumor promoting effects.

The cDNAs encoding the Zn+2-metalloproteases (SVMPs) of Trimeresurus gracilis (abbreviated as Tgc), a pitviper endemic to Taiwan, were cloned from venom glands and sequenced. The amino-acid sequences of five novel SVMPs, including one P-III, three P-II and one P-I class enzymes, were thus deduced and subjected to BLAST-analyses. The P-III enzyme (designated as Tgc-PIII) is structurally most similar to the PIII-SVMPs of New World pitvipers but not similar to the PIII-SVMP of Ovophis okinavensis. Sequence-similarity analysis of 22 homologous PIII-SVMPs reveal three major structural subtypes of the pitviper PIII-SVMPs, which possibly have different substrate specificities. In addition, Tgc-PIII and the PI-class SVMP (named Tgc-MP) were isolated from the venom and verified by mass spectrometry. All the three deduced sequences of PII-SVMPs (Tgc-PIIs) contain an abnormal Zn+2-binding-site in their catalytic-domain, and an identical "long-disintegrin" domain. The predicted 85-residues disintegrin, gracilisin, bears high similarities to some long-disintegrins of the New-World pitvipers and salmosin3. By BLAST search and comparison, Tgc-MP is 96% similar to okinalysin, the hemorrhagic PI-SVMP of O. okinavensis, rather than any other PI-SVMPs in the databanks. Our results confirm the fast evolution of Tgc-SVMPs as well as their structural similarities to different SVMP-classes of the New-World pitvipers and of O. okinavensis, respectively. The implications of our findings are discussed along with our previous sequence comparisons of venom phospholipases A2 and ten venom serine proteases of Tgc.

T-2 toxin is part of the most toxic fungal secondary metabolites contaminating different kinds of grains. Previous studies have demonstrated that T-2 toxin can influence the survival of chondrocytes and extracellular matrix (ECM) composition. MiR-214-3p is essential for the homeostasis of chondrocytes and ECM. However, the molecular machinery underlying T-2 toxin-induced chondrocyte apoptosis and ECM degradation remain to be elucidated. The present study aimed to investigate the mechanism of miR-214-3p's involvement in T-2 toxin-induced chondrocyte apoptosis and ECM degradation. Meanwhile, the role of the NF-κB signaling pathway was scrutinized. C28/I2 chondrocytes were treated with 8 ng/ml of T-2 toxin for 24 h, after the pretreatment of miR-214-3p interfering RNAs for 6 h. Gene and protein levels involved in chondrocyte apoptosis and ECM degradation were assessed through RT-PCR and Western blotting. The apoptosis rate of chondrocyte was measured by flow cytometry. Results and data indicated that miR-214-3p was decreased in a dose-dependent manner at different concentrations of T-2 toxin. The enhancement of miR-214-3p could alleviate chondrocyte apoptosis and ECM degradation due to T-2 toxin exposure. The upregulation of miR-214-3p was associated with the decreased expression of apoptosis-promoting genes such as Bax and Cleaved-caspase3/caspase3 as well as the increased expression of anti-apoptotic genes such as Bcl2 and Survivin. Furthermore, miR-214-3p stimulated the relative protein expression of collagen Ⅱ but inhibited the expression of MMP13. Overexpressing miR-214-3p could suppress the relative protein expression of IKKβ and phospho-p65/p65, thus blocking the activation of the NF-κB signaling pathway. The study suggested that the miR-214-3p attenuates T-2 toxin-induced chondrocyte apoptosis and ECM degradation through a potential NF-κB signaling pathway.

AIM: to evaluate the effects of visible and invisible wavelengths, individually and combined, on local edematogenic activity, serum and muscle enzymes, and clinical response in mice inoculated with B. leucurus snake venom. METHODS: 112 male mice were inoculated with diluted B. leucurus snake venom in the right gastrocnemius muscle, the same volume of saline solution was applied in the contralateral muscle. The animals were divided into four groups, one control and three treated with: 1) red laser (λ = 660 nm), 2) infrared laser (λ = 808 nm) and 3) red laser (λ = 660 nm) + infrared (λ = 808 nm). Each group was subdivided into four subgroups, according to the duration of treatment application (applications every 24 h over evaluation times of up to 144 h). A diode laser was used (0.1 W, CW, 1J/point, DE: 10 J/cm2). RESULTS: the treatments prevented the loss of the proprioception reflex, accelerated the reestablishment of the damaged area, and reduced claudication, local hemorrhage, and edematogenic activity caused by bothropic venom. Both wavelengths reduced serum concentrations of creatine kinase (CK) and aspartate aminotransferase (AST) and increased muscle concentration of CK. The combined wavelengths caused a significant reduction in serum enzyme concentrations and a better clinical response when compared to the isolated treatments. CONCLUSION: Laser photobiomodulation proved to be effective in the treatment of the disorders evaluated and the interaction between red and infrared wavelengths potentiated the therapy effects.

In this work, a novel electrochemical biosensor was fabricated based on modification of a glassy carbon electrode (GCE) with nafion-DNA/gold nanoparticles/poly-ethylenedioxy pyrrole/multi-walled carbon nanotubes-ionic liquid (NF-DNA/Au NPs/PEDOP/MWCNTs-IL/GCE) with the aim of amperometric detection of the DNA damage induced by thiram (TH). By incubation of the biosensor with the TH, the TH was intercalated within DNA, and the exposed DNA released negative charges at the surface of the biosensor which repelled the probe molecules and caused the amperometric response of the biosensor to be decreased. Protective effects of extra virgin olive oil (EVOO) on the DNA damage induced by the TH were investigated by recording amperometric responses of the biosensor in the presence of EVOO, and the results confirmed that the response of the biosensor didn't change to confirm the protective effects of the EVOO on preventing the DNA damage induced by the TH. A novel and sensitive electroanalytical method was developed for determination of the TH in two linear ranges including 1-6 pM and 7-10 pM based on amperometric detection of the DNA damage induced by the TH which gave a LOD of 0.31 pM. The developed methodology in this work was successful in detection of the DNA damage induced by TH, detection of protective effects of EVOO on preventing DNA damage and determination of the TH in real matrices.

The clinical management of snakebite envenomation (SBE) is challenging in many tropical and subtropical regions of developing countries due to the complex clinical manifestations and inadequate medical infrastructure. Some venomous snakes, such as the Indian Russell's viper (Daboia russelii) cause a wide range of rare complications in addition to their classical envenomation effects. In general, these uncommon complications are often misdiagnosed or not treated promptly due to a lack of awareness about these conditions. Thus, it is critical to report such complications to draw the attention of the healthcare and research communities to improve the clinical management and scientific research of SBE, respectively. Here, we report bilateral adrenal and pituitary haemorrhages in an SBE patient following a bite by Russell's viper in India. The initial symptoms included gum bleeding, swelling, axillary lymphadenopathy and clotting abnormalities. Despite the administration of antivenom, the patient presented palpitation, nausea, and abdominal pain, which were not recovered by combinational therapy with epinephrine and dexamethasone. Further infusion of antivenom did not address these issues and the patient displayed persistent hypotension, hypoglycaemia and hyperkalaemia suggesting an adrenal crisis. Inadequate secretion of corticosteroids was confirmed by laboratory tests, and imaging investigations revealed haemorrhages in both the adrenal and pituitary glands. The patient made a full recovery after treatment with hydrocortisone and thyroxine. This report adds to the growing evidence of rare complications induced by Russell's viper envenomations and it provides relevant guidance to diagnose and treat such complications in SBE victims.

Warnings of neurotoxic respiratory paralysis following envenomation by rattlesnakes (Crotalus sp.) have been included in numerous scholarly publications over the past 60 years, resulting in fear and anxiety in the public and among clinicians. We examine the validity of the widespread belief that rattlesnakes in the arid southwestern United States, and particularly the Mohave Rattlesnake (Crotalus scutulatus), pose a significant risk of medically relevant respiratory weakness and paralysis in humans. A retrospective review of 3440 suspected rattlesnake bites reported to the Arizona Poison and Drug Information Center between 1999 and 2020 produced no evidence of respiratory weakness in a region with three species known to express significant amounts of neurotoxin in their venoms: Crotalus concolor, C. tigris, and the more widely distributed C. scutulatus. A literature review produced numerous warnings regarding respiratory paralysis following envenomation by rattlesnakes in our region that either lacked references or cited sources that did not contain strong supportive data. We found no case reports of neurotoxic respiratory weakness following Arizona rattlesnake bites in the literature and such reports in surrounding states were scant. We conclude that neurotoxic respiratory failure in this region following rattlesnake envenomation is extraordinarily rare. All rattlesnake bites should receive the same consideration and critical care, and warnings about significant risk of respiratory failure are unwarranted, regardless of species involved.

Botulinum neurotoxin-producing species of Clostridium are highly diverse. Clostridium botulinum could represent at least four different species of Clostridium. In addition, strains that do not produce botulinum neurotoxin are closely related to toxigenic strains, probably representing the same species. Although reclassification of these organisms has been proposed in the past, their species names have remained unchanged, mainly because of the premise that changing names of medically relevant organisms might cause confusion in the healthcare and scientific community. In this review, we discuss the possible unintended consequences of reclassifying botulinum neurotoxin-producing species of Clostridium, which are of public health, medical, and biodefense interest.

Muscle necrosis is a potential clinical complication of snakebite envenomings, which in severe cases can lead to functional or physical sequelae such as disability or amputation. Snake venom proteins with the ability to directly damage skeletal muscle fibers are collectively referred to as myotoxins, and include three main types: cytolysins of the "three-finger toxin" protein family expressed in many elapid venoms, the so-called "small" myotoxins found in a number of rattlesnake venoms, and the widespread secreted phospholipase A2 (sPLA2) molecules. Among the latter, protein variants that conserve the sPLA2 structure, but lack such enzymatic activity, have been increasingly found in the venoms of many viperid species. Intriguingly, these sPLA2-like proteins are able to induce muscle necrosis by a mechanism independent of phospholipid hydrolysis. They are commonly referred to as "Lys49 myotoxins" since they most often present, among other substitutions, the replacement of the otherwise invariant residue Asp49 of sPLA2s by Lys. This work comprehensively reviews the historical developments and current knowledge towards deciphering the mechanism of action of Lys49 sPLA2-like myotoxins, and points out main gaps to be filled for a better understanding of these multifaceted snake venom proteins, to hopefully lead to improved treatments for snakebites.

Nerium oleander L. is a medicinal plant, used for the treatment of cancers and hyperglycemia across the world, especially in Indian sub-continent, Turkey, Morocco, and China. Although clinical studies supporting its pharmacological effects remain critically underexplored, accidental and intentional consumption of any part of the plant causes fatal toxicity in animals and humans. While the polyphenolic fraction of oleander leaves has been attributed to its pre-clinical pharmacological activities, the presence of diverse cardiac glycosides (especially oleandrin) causes apoptosis to cancer cells in vitro and results in clinical signs of oleander poisoning. Thus, the dual pharmacological and toxicological role of oleander is a perplexing dichotomy in phytotherapy. The current investigative review, therefore, intended to analyze the intrinsic and extrinsic factors that likely contribute to this conundrum. Especially by focusing on gut microbial diversity, abundance, and metabolic functions, oleander-associated pharmacological and toxicological studies have been critically analyzed to define the dual effects of oleander. Electronic databases were extensively screened for relevant research articles (including pre-clinical and clinical) related to oleander bioactivities and toxicity. Taxonomic preference was given to the plant N. oleander L. and synonymous plants as per 'The World Flora Online' database (WCSP record #135196). Discussion on yellow oleander (Cascabela thevetia (L.) Lippold) has intentionally been avoided since it is a different plant. The review indicates that the gut microbiota likely plays a key role in differentially modulating the pharmacological and toxicological effects of oleander. Other factors identified influencing the oleander bioactivities include dose and mode of treatment, cardiac glycoside pharmacokinetics, host-endogenous glycosides, plant material processing and phytochemical extraction methods, plant genotypic variations, environmental effects on the phytochemical quality and quantity, gene expression variations, host dietary patterns and co-morbidity, etc. The arguments proposed are also relevant to other medicinal plants containing toxic cardiac glycosides.

Snakebite envenomation causes systemic and local manifestations, which result from the individual or synergistic actions of multiple venom components. The pathological hallmarks of medically important venomous snakes such as the Indian Russell's viper (Daboia russelii) are well known. Envenomation by Russell's viper is typically characterised by coagulopathies, muscular damage, nephrotoxicity, and neurotoxicity. However, recent reports have revealed several unusual complications that provide a better understanding of Russell's viper envenomation effects. To further strengthen this, here, we report a case of Russell's viper bite that induced acute abdominal pain, which was intensified on day two and conservatively treated under medical supervision. Both Fothergill and Carnett signs were positive for this patient. An ultrasound imaging revealed a dissimilar dense mass, and the abdominal computed tomography scan confirmed rectus sheath haematoma. The clinical management involved the administration of polyvalent antivenom, packed red blood cells, fresh frozen plasma, and platelets. The patient recovered gradually and was discharged from the hospital eight days after the bite. Overall, this case presentation shares an uncommon experience and adds new insights into the complex series of rare pathological events associated with Russell's viper bites in India. The scientific documentation of relatively infrequent entities based on an ongoing living assessment of medical experiences, for example, this rectus sheath haematoma, constitutes valuable guidance for an adequate diagnosis and timely treatment. Essential awareness among clinicians and further research on understanding the molecular relationship between Russell's viper venom and rectus sheath haematoma will improve patient outcomes and understanding of this condition, respectively.

The purpose of this study was to investigate the efficacy and safety of intra-articular Botulinum Toxin type A (BTA) injection in the management of patients with knee osteoarthritis (KOA). The literature retrieval was conducted based on PRISMA guidelines. Databases including Pubmed, Web of science, EMBASE, and Cochrane Library were searched to identify RCTs that comparing the effects of intra-articular BTA injection with control interventions on patients with KOA. The primary outcomes involved pain and function improvements as well as the occurrence of adverse events. Seven RCTs comprising 548 participants were included in this meta-analysis. Compared with the control group, BTA injection exhibited greater pain reduction at 4 weeks posttreatment (SMD = -0.86, 95% CI [-1.52, -0.19], p = 0.011), but not 8-24 weeks posttreatment (wk 8, SMD = -0.53, 95% CI [-1.21, 0.15], p = 0.127; wk 12, SMD = -0.34, 95% CI [-0.73, 0.04], p = 0.081; wk 24, SMD = -0.65, 95% CI [-1.52, 0.22], p = 0.144). Additionally, no differences were found between BTA injection versus control intervention on functional improvement at all time points assessed (wk 4, WMD = -5.16, 95% CI [-12.31, 2.00], p = 0.158; wk 8, WMD = -0.98, 95% CI [-5.66, 3.71], p = 0.683; wk 12, WMD = -2.52, 95% CI [-7.54, 2.50], p = 0.325); wk 24, WMD = -3.66, 95% CI [-14.09, 6.76], p = 0.491). There was no significant difference in adverse event rate between the BTA and control group (OR = 0.88, 95% CI [0.24, 3.18], p = 0.843). This meta-analysis suggests that intra-articular BTA injection could be an efficious and safe strategy for analgesic treatment of KOA. However, evidence is limited due to the small number and heterogeneity of included studies, this urges further and stronger trials to confirm our findings.

Acting as microRNA (miRNA) sponges, circular RNAs (circRNAs) have been discovered to be critical modulators of inflammatory processes. Ricin Toxin (RT) is highly toxic to mammalian cells and low doses of RT can induce acute inflammation. However, current researches on the underlying mechanism and function of circRNA/miRNA network in RT-induced inflammation are limited. Previously, we found miR-221-5p was aberrant and associated with the inflammation of RT induction. In this study, based on the circRNA high-throughput sequencing (circRNA-seq), we obtained a novel circRNA termed circNLRP3 and revealed that circNLRP3 can sponge miR-221-5p, release its target mRNA A20, and further suppress NF-κB signaling pathway to alleviated RT-induced TNF-α production. Our findings elucidated a possible mechanistic link between the circNLRP3/miR-221-5p/A20 axis and RT-induced inflammatory response, which may broaden our understanding of RT poisoning.

Snakebite envenoming in Sub-Saharan Africa present a significant public health problem. An investigation into how often species responsible for envenomation were correctly identified, as well as which venomous species caused the most frequent and problematic envenomation symptomatology were conducted to establish severity of this problem from a South African context. Descriptive statistics were used to quantitatively describe the variables in snakebite related Telelog call records reported to the Poison Information Helpline of the Western Cape (PIHWC) over a five-year period. A total of 1411 snakebite related calls were received. In 44% of all snakebite calls the bite was inflicted by an unidentified snake specie. The most snakebites occurred during the summer months from December-March. The most bites occurred in males (20-39 years). The incidence of snakebite in South Africa was 2.39 per 100 000 population, with the highest incidence of snakebite in North-West province of South Africa. In sub-Saharan Africa there is a major underestimation of the incidence of snakebite due to under reporting and absence of physical attendance to health care facilities. The PIHWC provides an invaluable service in assisting and in-forming medical personnel and the public on the management of snakebites. Data collected by centers provides a source of information on the prevalence of snakebites and medically important species that research should be aimed towards.

Herein, we report three new separate cases of human envenomations by Micrurus hemprichii for the Amazon, which is a biome where envenomations by Micrurus are seldom reported. Two women were bitten after stepping on the snakes and one man was bitten while handling the animal. All cases occurred in the peridomicile, in rural areas. The first case evolved mainly to local symptoms, but the patient was discharged before the identification of the snake and had to be called back for observation before being eventually discharged. In the second case, the patient presented transitory dyspnea and she was discharged after four days in hospital. In the third case, the patient showed only local symptoms, but he was about to receive unnecessary antivenom against coral snakes. Cases like these show the importance of educational problems regarding local venomous snakes in order to avoid bites and to provide the correct hospital treatment. For this, trained professionals in cases involving venomous animals are needed.

BACKGROUND: In the late nineties, Bond and Burkhardt described a severe thrombocytopenic phenomenon from envenomation by Crotalus horridus. This thrombocytopenia persisted despite administration of platelets and antivenom. Questions remain regarding the clinical significance and time to resolution of this thrombocytopenia. In addition, as new antivenoms are available in North America, the response to current treatment is not well reported. The purpose of this study is to provide further insight into the approach to treatment of Crotalus horridus envenomation. METHODS: This is a retrospective chart review of 21 cases of presumed envenomation by C. horridus. Data collected included age, sex, antivenom administration, laboratory data, length of hospital stay, blood products administered, and general clinical course. We also evaluated platelet response to antivenom, bleeding outcomes, and complications from envenomation. RESULTS: Patients' ages ranged from 19 to 71 years. All patients were men. Most patients presented with thrombocytopenia and all had limb swelling. Patients responded initially to antivenom treatment, however subsequently developed a profound thrombocytopenia, including fourteen with platelet counts less than 20 × 109/L. Abnormalities in thromboelastography (TEG) were noted in conjunction with thrombocytopenia. Patients displayed persistent thrombocytopenia despite administration of Crotalidae polyvalent immune Fab or Crotalidae immune F(ab')2. Median time to rebound platelet count greater than 20 × 109/L was ten days (range 6-12 days) from envenomation. Complications included a partial finger amputation in one patient, bleeding gums in four patients, bloody stools in two patients, bloody nasogastric output in one patient. No patients required red blood cell transfusion and no deaths occurred. CONCLUSION: Practitioners treating C. horridus should recognize the possibility of severe thrombocytopenia and its persistence despite antivenom. They should counsel patients on appropriate abstention from activities that could lead to trauma, as well as the importance of follow up for repeat laboratory studies to ensure the resolution of thrombocytopenia.

A multi-disciplinary team surveyed ranchers at the Kalunga Historical and Cultural Heritage Site, in the Cerrado region of west central Brazil, to determine impacts promoted by toxic plants on cattle. The expedition to the Kalunga region was carried out by Brazilian and American researchers. Previously selected cattle ranch properties from "Vão das Almas", "Engenho II" and "Vão do Moleque" were visited. Twenty-four interviews were carried out with cattle ranchers and a questionnaire was applied to obtain information about outbreaks of native plant poisoning and their effects on livestock, and the use of local plants in phytotherapy. We classified problematic plants into three distinct categories. First, the toxic plants most cited by residents causing cattle losses were the flowers of Caryocar brasiliense Cambess ("pequi"), the fruits of Terminalia corrugata (Ducke) Gere & Boatwr. (Buchenavia tomentosa Eichler - "mirindiba" or "pau-pilão"), Eugenia dysenterica (Mart.) DC ("cagaita"), and Palicourea marcgravii A. St. Hil ("erva-café" or "cafezinho"). Secondly, other plants considered toxic, but causing less severe losses were Emmotum nitens (Benth.) Miers ("casco d'anta"), Indigofera lespedezioides (Kunth) ("timbozinho"), Ricinus communis L. ("mamona"), Pteridium esculentum (G. Forst.) Cockayne ("samambaia"), Stryphnodendron adstringens (Mart.) Coville ("barbatimão"), and Actinocladum verticillatum (Nees) McClure ex Soderstr. ("cambaúba"). The most important finding was the identification of the C. brasiliense flower as potentially toxic to cattle, which must be subject for future research. Further, we confirmed the toxicity and importance of P. marcgravii, E. dysenterica, and Terminalia corrugata. The survey highlighted phytotherapy plants used by the community, and greatly increased awareness by local livestock producers of poisonous plants for management purposes. We conclude that ethnobotanical knowledge, especially from the traditional community, is essential to understand livestock losses to toxic plants, and should be valued not only for reducing livestock losses, but also for cultural importance to the Kalunga communities in the Cerrado.

One natural antimicrobial peptide (EpVP2a, Eumenes pomiformis Venom Peptide 2a) found in the venom of a potter wasp (Eumenes pomiformis) and six analogs were synthesized and tested to compare their antimicrobial, antifungal, pesticide, and hemolytic activity with the wild type. Our results indicated that while the original peptide and the synthetic analogs had no antifungal activity or anti-bacterial activity against Pseudomonas aeruginosa, the original peptide and the analog with substitution of the aspartic acid on the sequence by a lysine (EpVP2a-D2K2) had activity against Escherichia coli, Staphylococcus aureus and Bacillus subtilis. This same analog also shows significant insecticide activity. The analog with substitution of lysine with a slightly smaller ornithine had activity against E. coli and B. subtilis. All analogs show low hemolytic activity compared to the natural peptide. The peptide with a reverse sequence to the natural one (EpVp2a Retro) shows low helix structure which can also explain why it has no antibacterial activity and low hemolytic activity. Circular dichroism spectra show that these peptides form an alpha helix structure and their amino acid positions predict an amphipathic nature.

The Puff Adder (Bitis arietans) is a viper native to Africa and the Middle East. Envenomation by this species often requires the administration of appropriate antivenom in order to achieve a favorable outcome. A patient was bitten in both hands by a captive B. arietans presented to a teaching hospital in Malaysia. The patient developed painful progressive swelling on both limbs that extended to the chest, hypotension, hypokalemia with worsening anemia, thrombocytopenia, coagulopathy, and severe metabolic acidosis. The patient was managed supportively while waiting for the appropriate antivenom, Antivipmyn-Africa, from the Singapore Zoo. The patient developed cardiorespiratory arrest twice and did not recover from the second. The patient was pronounced dead 23 hours post-incident. The local unavailability of the appropriate antivenom may be the most important factor that contributed to the patient's death. There is also a need to amend the Malaysian Wildlife Act in order to prevent such cases from recurring.

The 20 minutes Whole Blood Clotting Test (20WBCT) was evaluated in 1541 snakebite patients at 3 hospitals in Nigeria. It was useful in detection, monitoring, guiding antivenom therapy and prognostication of coagulopathy, with initial sensitivity of 84.7% (95%CI:82.7-86.5%) and specificity of 64.3% (95%CI:50.4-76.7%) compared to clinical envenoming. It led to correct decisions regarding administration or withholding antivenom in 97.93% of patients. The proportion of carpet viper (Echis romani) envenomed patients who restored clotting rose steadily following effective antivenom therapy. Patients with positive 20WBCT had severer envenoming, required more blood transfusion, had longer hospital stay and derived higher antivenom protection against death from carpet viper. However, there was no association between positive 20WBCT and fatality or complications.

The World Health Organization has listed Snakebite Envenoming (SBE) as a priority neglected tropical disease, with a worldwide annual snakebite affecting 5.4 million people and injuring 2.7 million lives. In many parts of rural areas of Africa and Asia, medicinal plants have been used as alternatives to conventional antisnake venom (ASV) due in part to inaccessibility to hospitals. Systemic reviews (SR) of laboratory-based preclinical studies play an essential role in drug discovery. We conducted an SR to evaluate the relationship between interventional medicinal plants and their observed effects on venom-induced experiments. This SR was reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses. The Modified collaborative approach to meta-analysis and review of animal data from experimental studies (CAMARADES) and SYRCLE's risk of bias tools were used to appraise the included studies. Data were searched online in Medline via PubMed, Embase via OVID, and Scopus. Studies reporting in vivo and in vitro pharmacological activities of African medicinal plants/extracts/constituents against venom-induced pathologies were identified and included for screening. Data from the included studies were extracted and synthesized. Ten studies reported statistically significant percentage protection (40-100%) of animals against venom-induced lethality compared with control groups that received no medicinal plant intervention. Sixteen studies reported significant effects (p ≤ 0.05) against venom-induced pathologies compared with the control group; these include hemolytic, histopathologic, necrotic, and anti-enzymatic effects. The plant family Fabaceae has the highest number of studies reporting its efficacy, followed by Annonaceae, Malvaceae, Combretaceae, Sterculiaceae, and Olacaceae. Some African medicinal plants are preclinically effective against venom-induced lethality, hematotoxicity, and cytotoxicity. The evidence was extracted from three in vitro studies, nine in vivo studies, and five studies that combined both in vivo and in vitro models. The effective plants belong to the Fabaceae family, followed by Malvaceae, and Annonaceae.

The Alto Juruá region has a rich diversity of venomous snakes, and snakebites represent an important cause of morbidity. The present study was carried out in five communities in the Alto Juruá region, and aimed to evaluate the history of snakebites in terms of which snakes were involved and what was the victims' conduct in relation to first aid and prevention. Between 2017 and 2019, semi-structured interviews were applied to 260 residents, 56 (21.53%) of whom had a history of snakebites. The profile of the victims is 73.2% male, a resident of rural areas who develops activities mainly in agriculture and extractivism and who has a low level of education. Just over half of the snakebites occurred during the rainy season (52.8%) and the majority during the day (77%). Bothrops bites were the most frequently reported (90.3%) and B. atrox was the most mentioned snake (jararaca and surucucu) for being responsible for snakebites (80.8%). Approximately 87.5% of the bites occurred to the lower limbs, and 48.2% of the victims were barefoot at the time of the bite. Inadequate first-aid procedures were reported, such as using tourniquets and consuming the drink known as "Específico Pessoa", not drinking water, and treatment with traditional therapy (phytotherapics, zootherapeutics and faith healers), as well as not seeking hospital care. Thus, the need to facilitate access to hospital units in these communities and health education (prevention and first aid) are essential in order to minimize this situation.

A high diversity of rattlesnake species can be found in the Baja California peninsula and the island of the Gulf of California, nevertheless, their venom has been poorly evaluated. The aim of this work was to present the first characterization of endemic Crotalus mitchellii, micro endemic C. polisi and C. thalassoporus venoms. All samples provoke human plasma coagulation showing doses in the rank of 2.3-41.0 μg and also produce rapid hydrolysis of the alpha chain of bovine fibrinogen while the beta chain is attacked at larger incubation periods by C. polisi and especially by C. thalassoporus. Phospholipase activity ranging from 23.2 to 173.8 U/mg. The venoms of C. thalassoporus and C. polisi show very high hemorrhagic activity (from 0.03 to 0.31 μg). A total of 130 toxin-related proteins were identified and classified into ten families. Crotalus mitchellii venom was characterized by high abundance of crotoxin-like and other phospholipase proteins (34.5%) and serine proteinases (29.8%). Crotalus polisi showed a similar proportion of metalloproteinases (34%) and serine proteinases (22.8%) components with important contribution of C-type lectins (14.3%) and CRiSP (14.0%) proteins. Venom of C. thalassoporus is dominated by metalloproteases that amount to more than 66% of total toxin proteins. These results provide a foundation for comprehending the biological, ecological and evolutionary significance of venom composition of speckled rattlesnake from the Baja California peninsula.

In the present study, the antibacterial property of the organophilic bentonite (Bent-ODA) and organophilic bentonite incorporated with geranyl acetate ester (Bent-ODA-GA) was evaluated against bacteria Staphylococcus aureus, Escherichia coli and Salmonella typhimurium. Oral acute toxicity of Bent-ODA-GA was evaluated in mice, by a single oral dose of 300 and 2000 mg kg-1. Animals were observed for any toxicity clinical signs or mortality for 15 days according to OECD 423 guidelines. The release assay of GA presents in Bent-ODA in simulated gastric fluid, pH 3.5 and pH 6.5 was also performed. Bent-ODA-GA composite presented antibacterial activity against S. aureus and S. typhimurium bacteria with 10.7 ± 0.6 mm and 2.2 ± 0.1 mm inhibition halo, respectively, which make it possible to associate the composite antimicrobial feature due to the ester presence. The composite did not reveal any toxicity signs or mortality in any animal for acute toxicity treatment during the 15 days observation period. The LD50 of Bent-ODA-DA was estimated to be greater than 2000 mg kg-1. It was also observed that geranyl acetate is released from Bent-ODA in concentrations lower than 0.03 mg kg-1 for pH 3.5 and 0.004 mg kg-1 for pH 6.5, which are lower than those that could cause some toxic effects in animals.