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Aim: We test the relationship between the voluntary thermal maximum (VTMax; the temperature at which an individual actively retreats to a colder site) and geographical/environmental features in the distribution of South American pitvipers. Additionally, we explore the evolution of environmental temperatures and VTMax in species' ranges. Location: South America. Taxon: South American pitvipers of the genera Bothrops and Bothrocophias. Methods: We experimentally measured the VTMax of 15 species of South American pitvipers. We explored the relationship between VTMax and geographical/environmental features (e.g., latitude, topographic complexity and temperature) with PGLS regressions. Additionally, we explored the evolution of maximum (TMax) and minimum (TMin) environmental temperatures, as well as the Thermal Niche Breadth (TNB) and VTMax, using ancestral state reconstruction and testing for phylogenetic signal. Results: Mean VTMax values for South American pitvipers clustered primarily within the 34°C–36°C range, exhibiting little variation among species or clades. No significant correlations were found between VTMax and climatic or geographic variables. Furthermore, our analysis revealed that these snakes are absent from regions where maximum temperatures surpass their preferred thermal tolerances. Ancestral state reconstruction indicated divergent evolutionary pathways for thermal limits among species, independent of phylogenetic relationships. Main Conclusions: South American pitvipers unexpectedly exhibit similar voluntary thermal maximum values across a wide range of habitats and despite distinct phylogenetic relationships. Our results indicate that there is no strong climatic niche conservatism for South American pitvipers, with a likely weak selective pressure of VTMax. [ABSTRACT FROM AUTHOR]

Background: Bothrops venom consists primarily of metalloproteinase and phospholipase A2 toxins, which are responsible for the acute inflammatory, coagulant and hemorrhagic action following snakebite. The local effects of snakebite envenomation by Bothrops species are particularly prevalent yet poorly studied, but include pain, edema, erythema, blistering, bleeding, and ecchymosis. Methods and findings: In this study, we describe the dermatopathological findings observed in a series of 22 patients diagnosed with Bothrops envenomation treated in a tertiary hospital of Manaus, in the Brazilian Amazon. Clinically, pain and edema were observed in all patients, followed by fang marks (63.6%), secondary infection (36.3%), ecchymosis (31.8%), erythema (22.7%), blister (13.6%), and necrosis (4.5%). Regarding histopathological findings, epidermal alterations such as spongiosis, acanthosis and hyperkeratosis were the most observed characteristics in our cases series, with isolated cases of hyperplasia, hemorrhagic intraepidermal blister and severe necrosis. Changes in dermis and hypodermis consisted mainly of hemorrhage, inflammatory infiltrate, edema, congestion, and vascular damage, whereas cases of collagen damage, necrosis, abscess, and signs of tissue repair, indicated by the presence of granulation tissue, were also observed, with a persistence of inflammatory and hemostatic alterations even days after antivenom administration. Therefore, the tissue damage resulting from Bothrops envenomation could be related to both direct venom activity as well as inflammatory response or presence of infectious process. The histopathological analysis of human skin injury can enlighten the pathological and endogenous effects of local envenomation and could underpin new strategies, including novel treatments, adjuvants or changes in clinical management, that lead to better outcomes in snakebite patients. Author summary: After inoculation of the venom by a snake of the genus Bothrops, a series of changes occur around the site of the bite, as a direct effect of toxins producing tissue damage and changes in blood flow to the site associated to coagulation disorders. Current knowledge about histopathological changes resulting from snakebites is almost exclusively derived from experimental animal models. In this study, we describe the dermatopathological findings observed in a series of 22 patients diagnosed with Bothrops atrox envenomation treated in a tertiary hospital of Manaus, in the Brazilian Amazon. We found relevant changes in all strata of the skin, with emphasis on hemorrhage, inflammatory infiltrate, edema, congestion, and vascular damage. Interestingly, we observed a persistence of inflammatory and vascular alterations days after antivenom administration, suggesting that antivenom may have limited efficacy in reversing or preventing local injury mechanisms, and that inflammation following those pathological processes plays a major role in the progression of tissue damage. [ABSTRACT FROM AUTHOR]

The data on the reptilian fauna of the state of Goiás are one-off and reveal a lack of information about this group. The aim of the research was to know the composition of the reptile fauna within the area of the Anglo American mining company, evaluating the relationship of the species with the years, the types of environments and the presence of indicator species. Fieldwork was carried out during seven years, from 2007 to 2013. Sampling was performed through active search, pitfall traps, occasional encounters, and third-party records. We recorded 36 reptile species: 15 lizards and 21 snakes. The most common lizards were Anolis meridionalis, Cnemidophorus sp, and the most abundant snakes were Apostolepis cerradoensis and Bothrops moojeni. There was no relationship between the species and the years. On the other hand, there was relationship between the species and the environments or between the species and the types of habitats. The lizard Ameivula ocellifera was found as an indicator species of Cerrado areas, as well as the snake Leptotyphlops dulcis We have seen that lizards are specific to their habitat, making it essential to preserve open and forested areas for the conservation of the species that live there. [ABSTRACT FROM AUTHOR]

Snakebites inflict significant injuries on humans and animals, posing a severe global public health challenge due to high mortality and morbidity rates. This study presents results against the venoms of Bothrops jararaca and Bothrops neuwiedi using sixteen synthetic hybrid molecules containing thiophene and triazoles, designated as 6a–h and 7a–h. The compounds were assessed for their ability to inhibit proteolytic and plasma coagulant activities induced by the snake venoms, and their toxicity was analyzed. Most derivatives demonstrated nontoxicity through in silico analysis with the Osiris Property Explorer tool and in vitro cytotoxic hemocompatibility on red blood cells. Notably, only derivative 6e exhibited toxicity to erythrocytes, while 6b, 6d, 7c, and 7f displayed mutagenic, tumorigenic, or adverse effects on the reproductive system. Derivatives 6a, 6c–h, 7c–e, 7g, or 7h effectively inhibited the coagulating activity of B. jararaca venom, while 6a–b, 6d–e, 6h, or 7a–f inhibited coagulation induced by B. neuwiedi venom. All derivatives demonstrated inhibition of the proteolytic activity caused by B. jararaca venom, and derivatives 6a–d and 7e–f inhibited the activity of B. neuwiedi venom. Consequently, these derivatives exhibited varying degrees of efficacy in countering two crucial toxic effects of B. jararaca or B. neuwiedi venoms, suggesting their potential as antivenoms against both species. [ABSTRACT FROM AUTHOR]

Snake venoms are intricate mixtures of enzymes and bioactive factors that induce a range of detrimental effects in afflicted hosts. Certain Viperids, including Bothrops jararacussu, harbor C-type lectins (CTLs) known for their modulation of a variety of host cellular responses. In this study, we isolated and purified BjcuL, a CTL from B. jararacussu venom and investigated its impact on endothelial cell behavior, contrasting it with human galectin-1 (Gal-1), a prototype member of the galectin family with shared β-galactoside-binding activity. We found that BjcuL binds to human dermal microvascular endothelial cells (HMECs) in a concentration- and carbohydrate-dependent fashion and reprograms the function of these cells, favoring a pro-inflammatory and pro-coagulant endothelial phenotype. In light of the quest for universal antagonists capable of mitigating the harmful consequences of snake venoms, BjcuL emerges as a promising target to be blocked in order to regulate pathological endothelial cell responses. [ABSTRACT FROM AUTHOR]

Copyright of Biotropica is the property of Wiley-Blackwell and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Capillary leak syndrome is a unique complication characterized by extravasation of liquids in the interstitial space due to protein loss caused by snakebite envenoming. We describe the case of a 12-year-old boy from the district of Napo in the city of Iquitos in the Peruvian Amazon, who had edema and increased face volume due to the bite of a snake of the Bothrops genus in the lateral aspect of the right leg; he was the hospitalized and diagnosed with severe ophidism complicated with face edema. The patient received eight vials of antivenin, antibiotics and analgesics. Finally, the patient was discharged from the hospital after eight days of hospitalization, with favorable evolution and recovery. [ABSTRACT FROM AUTHOR]

Animals are naturally exposed to several predators, and, given that a single encounter with a predator may cause prey's death, natural selection will strongly act upon its defensiveness. Therefore, defensive behavior is strongly shaped by predation pressure. Predation rate in islands tends to be relaxed due to lower abundance of predators. The aim of this study was to test the hypothesis that predation rates upon the two island pit vipers Bothrops alcatraz and B. insularis would be lower than correlated mainland B. jararaca. Additionally, we evaluated the defensive behavior of these island snakes in the field to compare with the mainland B. jararaca. Predation pressure upon the insular species was assessed utilizing plasticine replicas, and we evaluated their defensive behavior to approach. These data were compared to those previously reported for B. jararaca. We found a lower predation pressure on B. insularis (from the smaller area) than on B. alcatraz and B. jararaca from the urban mainland forest fragment (areas with intermediate size), and all of them showed lower predation pressure than B. jararaca from the continuous mainland forested area. In the field, island snakes show narrower defensive repertoire than B. jararaca , since most B. insularis fled, and B. alcatraz either fled or remained immobile on approach. Apparently, the predation pressure to which these island pit vipers are exposed shapes their defensive behavior, as well as the niches exploited by them. [ABSTRACT FROM AUTHOR]

Copyright of Revista Foco (Interdisciplinary Studies Journal) is the property of Revista Foco and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

To evaluate the effects of red and infrared wavelengths, separately and combined, on the inflammatory process and collagen deposition in muscle damage caused by B. leucurus venom. 112 mice were inoculated with diluted venom (0.6mg/kg) in the gastrocnemius muscle. The animals were divided into four groups: one control (CG) and three treatments, namely: 1) red laser (λ=660 nm) (RG), 2) infrared laser (λ=808 nm) (IG) and 3) red laser (λ=660 nm) + infrared (λ=808 nm) (RIG). Each group was subdivided into four subgroups, according to the duration of treatment application (applications every 24 hours over evaluation times of up to 144 hours). A diode laser was used (0.1 W, CW, 1J/point, ED: 10 J/cm2). Both wavelengths reduced the intensity of inflammation and the combination between them significantly intensified the anti-inflammatory response. Photobiomodulation also changed the type of inflammatory infiltrate observed and RIG had the highest percentage of mononuclear cells in relation to the other groups. Hemorrhage intensity was significantly lower in treated animals and RIG had the highest number of individuals in which this variable was classified as mild. As for collagen deposition, there was a significant increase in RG in relation to CG, in RIG in relation to CG and in RIG in relation to IG. Photobiomodulation proved to be effective in the treatment of inflammation and hemorrhage caused by B. leucurus venom and stimulated collagen deposition. Better results were obtained with the combined wavelengths. [ABSTRACT FROM AUTHOR]

Envenoming resulting from snakebites is recognized as a priority neglected tropical disease by The World Health Organization. The Bothrops genus, consisting of different pitviper species, is considered the most medically significant taxa in Central and South America. Further research into Bothrops venom composition is important to aid in the development of safer and more effective snakebite treatments. In addition, the discovery of Bothrops toxins that could potentially be used for medical or diagnostic purposes is of interest to the pharmaceutical industry. This study aimed to employ high-throughput (HT) venomics to qualitatively analyze venom composition while utilizing coagulation bioassays for identifying coagulopathic toxins and characterizing coagulopathic activity in various Bothrops venoms. Using the recently demonstrated HT venomics workflow in combination with post-column coagulopathic bioassaying, focus was placed at anticoagulant toxins. Well-known procoagulant toxins were also investigated, taking into account that using the HT venomics workflow, procoagulant toxins are especially prone to denaturation during the reversed-phase chromatographic separations performed in the workflow. The findings revealed that the venoms of B. atrox and B. jararaca harbored procoagulant toxins, whereas those of B. alternatus and B. neuwiedi contained both procoagulant and anticoagulant toxins. In general, anticoagulation was associated with phospholipases A2s, while procoagulation was associated with snake venom metalloproteinases and snake venom serine proteases. These results showed the identification of coagulopathic venom toxins in the Bothrops venoms analyzed using multiple analytical methods that complement each other. Additionally, each venom underwent qualitative characterization of its composition. [ABSTRACT FROM AUTHOR]

Snakebites result from snake bites, causing a major impact on public health in Brazil. Snakes of the genus Bothrops, popularly known as "jararacas", are responsible for the vast majority of snakebites reported in Central and South America, requiring immediate medical treatment due to the actions of their venom, which can affect the circulatory system and lead to tissue damage. and hemorrhages. Antivenom serum is effective and essential for neutralizing the effects of venom in humans, reducing the severity of symptoms and helping to save lives. The purpose of the present study was to present a literature review on the predominant clinical manifestations in cases of snakebites with the genus Bothrops, thus increasing the population's knowledge regarding the main signs and symptoms that should be given more attention in the face of such accidents. According to the results obtained, it was found that the main and most recurrent clinical manifestations involving accidents with "jararaca" are: pain, edema, erythema, ecchymosis and serious complications such as blister formation, abscess and necrosis. Early recognition and treatment of clinical manifestations aims to reduce mortality and improve the quality of life of injured patients. [ABSTRACT FROM AUTHOR]

In snakes that are known to be ambush predators, tail luring, in which the movement of a snake's tail resembles that of a worm or insect larva and is used to attract prey, has emerged as a complementary hunting strategy. In certain species, some individuals may present a conspicuously bright colour at the tail tip, which eventually disappears with age. Some authors argue that the bright colour enhances the resemblance of the snake's tail with a potential food item, increasing the success of capture. Here, we tested the influence of geographic variation, sex, and environmental factors on the probability that Common Lanceheads Bothrops jararaca (Wied-Neuwied, 1824) from southeastern Brazil were born with this contrasting tail tip and whether snakes retain this trait throughout adulthood. None of the predictors affected the probability of births with a contrasting tail tip. However, a higher proportion of individuals from the coastal populations retained this trait into adulthood. The absence of difference in the probability of being born with this trait indicates that there are other factors influencing tail tip colour, such as phylogenetic correlates, rather than intrinsic or environmental factors. A higher proportion of ectothermic prey in the diet of coastal populations may explain why this population retains tail luring throughout adulthood. [ABSTRACT FROM AUTHOR]

Background: Photobiomodulation has exhibited promise in mitigating the local effects induced by Bothrops snakebite envenoming; however, the mechanisms underlying this protection are not yet fully understood. Herein, the effectiveness of photobiomodulation effects on regenerative response of C2C12 myoblast cells following exposure to Bothrops jararacussu venom (BjsuV), as well as the mechanisms involved was investigated. Methodology/Principal findings: C2C12 myoblast cells were exposed to BjsuV (12.5 μg/mL) and irradiated once for 10 seconds with laser light of 660 nm (14.08 mW; 0.04 cm2; 352 mW/cm2) or 780 nm (17.6 mW; 0.04 cm2; 440 mW/ cm2) to provide energy densities of 3.52 and 4.4 J/cm2, and total energies of 0.1408 and 0.176 J, respectively. Cell migration was assessed through a wound-healing assay. The expression of MAPK p38-α, NF-Кβ, Myf5, Pax-7, MyoD, and myogenin proteins were assessed by western blotting analysis. In addition, interleukin IL1-β, IL-6, TNF-alfa and IL-10 levels were measured in the supernatant by ELISA. The PBM applied to C2C12 cells exposed to BjsuV promoted cell migration, increase the expression of myogenic factors (Pax7, MyF5, MyoD and myogenin), reduced the levels of proinflammatory cytokines, IL1-β, IL-6, TNF-alfa, and increased the levels of anti-inflammatory cytokine IL-10. In addition, PBM downregulates the expression of NF-kB, and had no effect on p38 MAKP. Conclusion/Significance: These data demonstrated that protection of the muscle cell by PBM seems to be related to the increase of myogenic factors as well as the modulation of inflammatory mediators. PBM therapy may offer a new therapeutic strategy to address the local effects of snakebite envenoming by promoting muscle regeneration and reducing the inflammatory process. Author summary: Photobiomodulation (PBM) therapy, a technique using light to influence cell behavior, has shown promising results in reducing the damage caused by snakebites from Bothrops species, a common venomous snake in Latin America. This study explores how PBM aids in the recovery of muscle cells after exposure to Bothrops jararacussu venom. Our research focused on C2C12 myoblast cells, a type of muscle cell, treated with PBM following venom exposure. We observed that PBM not only helped these cells move and close wounds faster but also increased the production of proteins essential for muscle formation and recovery. Interestingly, it also shifted the balance towards less inflammation by decreasing pro-inflammatory signals and increasing anti-inflammatory ones. This work sheds light on the potential of PBM as a novel treatment approach for snakebite victims. By promoting muscle repair and reducing inflammation, PBM therapy could improve recovery outcomes following envenoming. Our findings suggest that, with further development, PBM could become a valuable tool in the medical response to snakebites, offering a ray of hope for faster, more effective recovery processes. [ABSTRACT FROM AUTHOR]

The head is the most important element in trophic ecology among snakes. Head shape is affected by several factors, both intrinsic, such as size and sex, and extrinsic, such as geographical variation. Often, different populations are subject to different environmental conditions that are reflected in different phenotypes adapted to local conditions. Here, we investigate sexual dimorphism, ontogenetic allometry and environmental effects on head shape in two populations of Bothrops jararaca. We have found a significant effect of sex and population, with females from the highland population having a large braincase region and a more arrow-shaped head. Size increase accounted for a considerable amount of variation in shape, but the coefficient of correlation diverged between populations. Sexual dimorphism in head shape was not found in juveniles, but the ontogenetic trajectory was non-parallel between populations. Rainfall was most associated with a larger snout and reduced braincase. In the genus Bothrops , except in early stages, females often grow faster and attain larger sizes than males, which might affect head shape. Also, possible differences in diet, behaviour and ontogenetic variations between populations might be a reasonable cause of specific allometric trajectories. [ABSTRACT FROM AUTHOR]

Accidents caused by Bothrops jararaca (Bj) snakes result in several local and systemic manifestations, with pain being a fundamental characteristic. The inflammatory process responsible for hyperalgesia induced by Bj venom (Bjv) has been studied; however, the specific roles played by the peripheral and central nervous systems in this phenomenon remain unclear. To clarify this, we induced hyperalgesia in rats using Bjv and collected tissues from dorsal root ganglia (DRGs) and spinal cord (SC) at 2 and 4 h post-induction. Samples were labeled for Iba-1 (macrophage and microglia), GFAP (satellite cells and astrocytes), EGR1 (neurons), and NK1 receptors. Additionally, we investigated the impact of minocycline, an inhibitor of microglia, and GR82334 antagonist on Bjv-induced hyperalgesia. Our findings reveal an increase in Iba1 in DRG at 2 h and EGR1 at 4 h. In the SC, markers for microglia, astrocytes, neurons, and NK1 receptors exhibited increased expression after 2 h, with EGR1 continuing to rise at 4 h. Minocycline and GR82334 inhibited venom-induced hyperalgesia, highlighting the crucial roles of microglia and NK1 receptors in this phenomenon. Our results suggest that the hyperalgesic effects of Bjv involve the participation of microglial and astrocytic cells, in addition to the activation of NK1 receptors. [ABSTRACT FROM AUTHOR]

Background: Snakebite envenomation (SBE) causes diverse toxic effects in humans, including disability and death. Current antivenom therapies effectively prevent death but fail to block local tissue damage, leading to an increase in the severity of envenomation; thus, seeking alternative treatments is crucial. Methods: This study analyzed the potential of two fucoidan sulfated polysaccharides extracted from brown seaweeds Fucus vesiculosus (FVF) and Undaria pinnatifida (UPF) against the fibrinogen or plasma coagulation, proteolytic, and phospholipase A2 (PLA2) activities of Bothrops jararaca, B. jararacussu, and B. neuwiedi venom. The toxicity of FVF and UPF was assessed by the hemocompatibility test. Results: FVF and UPF did not lyse human red blood cells. FVF and UPF inhibited the proteolytic activity of Bothrops jararaca, B. jararacussu, and B. neuwiedi venom by approximately 25%, 50%, and 75%, respectively, while all venoms led to a 20% inhibition of PLA2 activity. UPF and FVF delayed plasma coagulation caused by the venoms of B. jararaca and B. neuwiedi but did not affect the activity of B. jararacussu venom. FVF and UPF blocked the coagulation of fibrinogen induced by all these Bothropic venoms. Conclusion: FVF and UPF may be of importance as adjuvants for SBE caused by species of Bothrops, which are the most medically relevant snakebite incidents in South America, especially Brazil. [ABSTRACT FROM AUTHOR]

In recent years, extensive research has delved into the pathophysiology of local reactions triggered by Bothrops snake venoms. Even though antivenom works well at reducing death and systemic effects, it is still not very effective in treating local reactions because it cannot counteract damage that has already been triggered. This limitation might be attributed to certain molecules that amplify the venom-induced innate response. While evidence suggests endogenous mediators at the venom site play a role in this envenomation, in Brazil, the concurrent use of anti-inflammatory agents or other drugs alongside antivenom remains uncommon. This study evaluated the pharmacological mediation of alterations in leukocyte–endothelium interactions following the experimental envenomation of mice with Bothrops jararaca venom, the main culprit of snake-related accidents in Southeast Brazil. We treated envenomed mice with inhibitors of different pharmacological pathways and observed the cremaster muscle microcirculation with intravital microscopy. We found that eicosanoids related to cyclooxygenase pathways and nitric oxide significantly contributed to B. jararaca venom-induced alterations in leukocyte–endothelium interactions. Conversely, lipoxygenase-mediated eicosanoids, histamine, and serotonin had minimal participation. Notably, dexamethasone and antivenom treatment diminished B. jararaca venom–induced alterations in leukocyte–endothelium interactions. The limited efficacy of the antivenom in managing Bothrops venom-induced local reactions emphasizes the critical need for supplementary treatments to enhance therapeutic outcomes. [ABSTRACT FROM AUTHOR]

The Viperidae is the most speciose family of Brazilian venomous snakes, with 33 known species. Although the family is well defined cladistically, there are few studies concerning the postcranial skeletal morphology, and only a single vertebral synapomorphy has been proposed. The paucity of knowledge on postcranial morphology poses challenges for the study of the Brazilian viper fossil record since most fossils consist of disarticulated and isolated vertebrae. Currently, Bothrops and Crotalus are the only vipers recognized in the Brazilian fossil record. Nonetheless, interspecific differentiation based on vertebral material is hampered due to the lack of comprehensive detailed anatomical data. We compared the trunk vertebrae of extant specimens of Crotalus and Bothrops using two-dimensional geometric morphometrics to obtain discriminant data about their vertebral morphology. We examined the trunk vertebrae of 20 vipers, 10 Crotalus, and 10 Bothrops and performed macroscopic analyses and measurements and landmark-based, two-dimensional geometric morphometric analyses. We sought to identify structural differences between the genera and to assess morphological variation along the spine. Most differences in the trunk vertebrae between Crotalus and Bothrops occurred in the length of the neural spine, the parapophyseal processes, the prezygapophyseal processes, and in the angle on the prezygapophyses. However, when we accounted for intracolumnar variation, differentiation is hampered. We expect our results will serve as a starting point for future studies of viperid vertebrae and aid paleontologists in accurately identifying fossil vipers. [ABSTRACT FROM AUTHOR]

The protein profile of Bothrops rhombeatus venom was compared to Bothrops asper and Bothrops atrox, and the effectiveness of antivenoms from the National Institute of Health of Colombia (INS) and Antivipmyn-Tri (AVP-T) of Mexico were analyzed. Protein profiles were studied with sodium dodecyl sulfate–polyacrylamide gel electrophoresis (SDS-PAGE) and reverse-phase high-performance liquid chromatography (RP-HPLC). The neutralizing potency and the level of immunochemical recognition of the antivenoms to the venoms were determined using Western blot, affinity chromatography, and enzyme-linked immunosorbent assay (ELISA). Bands of phospholipase A2 (PLA2), metalloproteinases (svMPs) I, II, and III as well as serine proteinases (SPs) in the venom of B. rhombeatus were recognized by SDS-PAGE. With Western blot, both antivenoms showed immunochemical recognition towards PLA2 and svMP. INS showed 94% binding to B. rhombeatus venom and 92% to B. asper while AVP-T showed 90.4% binding to B. rhombeatus venom and 96.6% to B. asper. Both antivenoms showed binding to PLA2 and svMP, with greater specificity of AVP-T towards B. rhombeatus. Antivenom neutralizing capacity was calculated by species and mL of antivenom, finding the following for INS: B. asper 6.6 mgV/mL, B. atrox 5.5 mgV/mL, and B. rhombeatus 1.3 mgV/mL. Meanwhile, for AVP-T, the following neutralizing capacities were found: B. asper 2.7 mgV/mL, B. atrox 2.1 mgV/mL, and B. rhombeatus 1.4 mgV/mL. These results show that both antivenoms presented similarity between calculated neutralizing capacities in our trial, reported in a product summary for the public for the B. asper species; however, this does not apply to the other species tested in this trial. [ABSTRACT FROM AUTHOR]

Bothrofav, a monospecific antivenom, was introduced in June 1991 and has shown excellent effectiveness against life-threatening and thrombotic complications of Bothrops lanceolatus envenoming. Because of the reoccurrence of cerebral stroke events despite the timely administration of antivenom, new batches of Bothrofav were produced and introduced into clinical use in January 2011. This study's aim was to evaluate the effectiveness of Bothrofav generations at treating B. lanceolatus envenoming. During the first period of the study (2000–2010), 107 patients were treated with vials of antivenom produced in June 1991, while 282 envenomed patients were treated with vials of antivenom produced in January 2011 in the second study period (2011–2023). Despite timely antivenom administration, thrombotic complications reoccurred after an interval free of thrombotic events, and a timeframe analysis suggested that the clinical efficacy of Bothrofav declined after it reached its 10-year shelf-life. In of the case of an antivenom shortage due to the absence of regular batch production, no adverse effects were identified before the antivenom reached its 10-year shelf-life, which is beyond the accepted shelf-life for a liquid-formulation antivenom. While our study does not support the use of expired antivenom for potent, life-threatening B. lanceolatus envenoming, it can be a scientific message to public entities proving the necessity of new antivenom production for B. lanceolatus envenoming. [ABSTRACT FROM AUTHOR]

Copyright of Boletín Latinoamericano y del Caribe de Plantas Medicinales y Aromáticas is the property of Universidad de Santiago de Chile and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

In Brazil, the genus Bothrops is responsible for most ophidian accidents. Snake venoms have a wide variety of proteins and peptides exhibiting a broad repertoire of pharmacological and toxic effects that elicit systemic injury and characteristic local effects. The snakes' natural resistance to envenomation caused by the presence of inhibitory compounds on their plasma have been extensively studied. However, the presence of these inhibitors in different developmental stages is yet to be further discussed. The aim of this study was to evaluate the ontogeny of Bothrops jararaca plasma inhibitor composition and, to this end, plasma samples of B. jararaca were obtained from different developmental stages (neonates, youngs, and adults) and sexes (female and male). SDS-PAGE, Western blotting, affinity chromatography, and mass spectrometry were performed to analyze the protein profile and interaction between B. jararaca plasma and venom proteins. In addition, the presence of γBjPLI, a PLA2 inhibitor previously identified and characterized in B. jararaca serum, was confirmed by Western blotting. According to our results, 9–17% of plasma proteins were capable of binding to venom proteins in the three developmental stages. The presence of different endogenous inhibitors and, more specifically, different PLA2 inhibitor (PLI) classes and antihemorrhagic factors were confirmed in specimens of B. jararaca from newborn by mass spectrometry. For the first time, the αPLI and βPLI were detected in B. jararaca plasma, although low or no ontogenetic and sexual correlation were found. The γPLI were more abundant in adult female, than in neonate and young female, but similar to neonate, young and adult male according to the results of mass spectrometry analysis. Our results suggest that there are proteins in the plasma of these animals that can help counteract the effects of self-envenomation from birth. [ABSTRACT FROM AUTHOR]

Snake venoms have evolved in several families of Caenophidae, and their toxins have been assumed to be biochemical weapons with a role as a trophic adaptation. However, it remains unclear how venom contributes to the success of venomous species for adaptation to different environments. Here we compared the venoms from Bothrocophias hyoprora, Bothrops taeniatus, Bothrops bilineatus smaragdinus, Bothrops brazili, and Bothrops atrox collected in the Amazon Rainforest, aiming to understand the ecological and toxinological consequences of venom composition. Transcriptomic and proteomic analyses indicated that the venoms presented the same toxin groups characteristic from bothropoids, but with distinct isoforms with variable qualitative and quantitative abundances, contributing to distinct enzymatic and toxic effects. Despite the particularities of each venom, commercial Bothrops antivenom recognized the venom components and neutralized the lethality of all species. No clear features could be observed between venoms from arboreal and terrestrial habitats, nor in the dispersion of the species throughout the Amazon habitats, supporting the notion that venom composition may not shape the ecological or toxinological characteristics of these snake species and that other factors influence their foraging or dispersal in different ecological niches. [ABSTRACT FROM AUTHOR]

Os acidentes ofídicos apresentam grande incidência no Brasil, sendo considerados doença tropical negligenciada e podem cursar com complicações potencialmente fatais. Este artigo é um estudo epidemiológico observacional, retrospectivo, transversal sobre os dados registrados pelo DATATOX-2. Foram analisados 1.738 acidentes botrópicos, popularmente conhecidos como jararacas, registrados entre 2014 e 2021. Através de tais dados foi possível construir um perfil epidemiológico dos acidentes no Paraná em consonância com levantamentos realizados em âmbito nacional. Houve predominância dos acidentes no verão e primavera, que acometeram homens, na faixa dos 39 anos e moradores de área rural. Tais resultados podem auxiliar na implementação de medidas de saúde pública e enfrentamento desses acidentes, considerando-se a população mais afetada e municípios acometidos, de forma a auxiliar profissionais da saúde e reduzir a morbimortalidade associada a esses agravos.

Background: Snake envenomation is a medical condition with high morbidity and mortality in southwestern Colombia. Objectives: To describe the characteristics of the envenomation caused by Viperidae snakes view in a highly complex hospital in Southwestern Colombia. Methods: A cross-sectional study was carried out. Patients treated for Viperidae snake envenomation from 2001 to 2020 in a Hospital Fundación Valle del Lili, Cali, Colombia, were studied. Results: Twenty-eight patients were included. Envenomation was caused by the genera Bothrops, Bothriechis, Porthidium, and Bothrocophias. The median age was 37.7 (±20.6), and they were predominantly male (19, 68%). Bites occurred on the upper extremities in 16 (57%) patients. Pain (23, 81%) and edema (22, 78%) were the most common clinical symptoms. Thirteen (46%) patients presented coagulopathy. Prolonged prothrombin and activated partial thromboplastin times were common: (22, 78% and 15, 53%, respectively). Twenty (71%) patients were treated with polyvalent antivenom (median dose of 6 (2–15) vials). The median time between the accident and antivenom administration was 9 h (5.5–17). Door-to-needle time was 37.5 (0–62) min. Eighteen (64%) patients were admitted to the intensive care unit. Three (11%) patients had serum sickness. Seven (25%) developed infectious complications, four (14%) had surgery, one (3%) had compartment syndrome, one (3%) underwent amputation of the affected limb, and one (3%) patient died. Conclusions: Local manifestations and coagulopathy were common clinical features. Polyvalent antivenom was an effective treatment for disease control. Significant complications were associated with delays in seeking medical care.

In this study, we describe the isolation of a new isoform, l-Amino acid oxidase (LAAO), referred to as Balt-LAAO-II, from Bothrops alternatus snake venom, which was highly purified using a combination of molecular exclusion (Sephadex G-75) and RP-HPLC chromatographic steps. SDS-PAGE analysis showed that purified Balt-LAAO-II had a molecular weight of ∼ 66 kDa. The N-terminal amino acid sequence and internal peptide sequences showed close structural homology to those of other snake venom l-Amino acid oxidases. This enzyme induces in vitro cytotoxicity in cultured human leukemic HL60 cells. Cells were grown in RPMI medium and incubated with the isoform Balt-LAAO-II (1, 10, and 100 μ g/mL) for up to 72 h. All three concentrations of venom markedly decreased cell viability from 6 h onwards based on staining with propidium iodide, the reduction of 3-(4,5-dimethylthazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT), and the uptake of neutral red. Flow cytometry showed that all isoforms of Balt-LAAO-II and whole venom concentrations induced apoptosis after 2–6 h of incubation. Morphological analysis of cells incubated with the isoform Balt-LAAO-II and whole venom showed cell rounding and lysis, which increased with venom concentration and duration of incubation. These results show that the isoform Balt-LAAO-II from venom Bothrops alternatus is cytotoxic to cultured HL60 cells, suggesting that this damage may involve the apoptotic and oxidative stress pathways. [ABSTRACT FROM AUTHOR]

Snake venoms are primarily composed of proteins and peptides, which selectively interact with specific molecular targets, disrupting prey homeostasis. Identifying toxins and the mechanisms involved in envenoming can lead to the discovery of new drugs based on natural peptide scaffolds. In this study, we used mass spectrometry-based peptidomics to sequence 197 peptides in the venom of Bothrops cotiara , including a novel 7-residue peptide derived from a snake venom metalloproteinase. This peptide, named Bc-7a, features a pyroglutamic acid at the N-terminal and a PFR motif at the C-terminal, homologous to bradykinin. Using FRET (fluorescence resonance energy transfer) substrate assays, we demonstrated that Bc-7a strongly inhibits the two domains of angiotensin converting enzyme (K i < 1 μM). Our findings contribute to the repertoire of biologically active peptides from snake venoms capable of inhibiting angiotensin-converting enzyme (ACE), beyond current known structural motifs and precursors. In summary, we report a novel snake venom peptide with ACE inhibitory activity, suggesting its potential contribution to the hypotensive effect observed in envenomation. [Display omitted] • A total of 197 peptides were identified in the venom of Bothrops cotiara. • A novel peptide is an angiotensin converting enzyme inhibitor. • This peptide inhibitor is a fragment of a snake venom metalloproteinase. [ABSTRACT FROM AUTHOR]

Hemostasis impairment represents the most threatening consequence of Viperidae envenoming, notably with Bothrops genus. In the French departments of America, B. atrox envenomation in French Guiana may lead to bleeding while B. lanceolatus envenomation in Martinique to thrombosis. Bleeding related to B. atrox envenomation is attributed to vascular damage mediated by venom metalloproteinases and blood uncoagulable state resulting from thrombocytopenia and consumptive coagulopathy. Thrombosis related to B. lanceolatus envenomation are poorly understood. We aimed to compare the effects of B. atrox and B. lanceolatus venoms in the rat to identify the determinants of the hemorrhagic versus thrombotic complications. Viscoelastometry (ROTEM), platelet count, plasma fibrinogen, thrombin generation assay, fibrinography, endothelial (von Willebrand factor, ADAMTS13 activity, ICAM-1, and soluble E-selectin), and inflammatory biomarkers (IL-1β, IL-6, TNF-α, MCP-1, and PAI-1) were determined in blood samples obtained at H3, H6, and H24 after the subcutaneous venom versus saline injection. In comparison to the control, initial fibrinogen consumption was observed with the two venoms while thrombocytopenia and reduction in the clot amplitude only with B. atrox venom. Moreover, we showed an increase in thrombin generation at H3 with the two venoms, an increase in fibrin generation accompanied with hyperfibrinogenemia at H24 and an increase in inflammatory biomarkers with B. lanceolatus venom. No endothelial damage was found with the two venoms. To conclude, our data support two-sided hemostasis complications in Bothrops envenoming with an initial risk of hemorrhage related to platelet consumption and hypocoagulability followed by an increased risk of thrombosis promoted by the activated inflammatory response and rapid-onset fibrinogen restoration. Author summary: Bothrops venoms contain toxins targeting hemostasis, a physiological process aiming stopping bleeding in case of injury. Envenomation by B. atrox in French Guiana leads to hemorrhage while envenomation by B. lanceolatus in Martinique results in thrombosis. To understand the mechanisms involved in these opposite manifestations related to the two venoms, we designed a comparative rat study of hemostasis based on a comprehensive approach including blood measurement of initiation time and size of the clot, platelet count, plasma fibrinogen, thrombin and fibrin generation, and various inflammatory and endothelial biomarkers. We showed that B. atrox venom induces more marked platelet and fibrinogen consumption, promoting the risk of hemorrhage, while B. lanceolatus venom induces an initial fibrinogen consumption followed by a secondary increase in combination to an enhanced inflammatory reaction resulting in increased thrombosis risk. Interestingly, the two venoms exhibited no endothelial toxicity. [ABSTRACT FROM AUTHOR]

Snake venom protein synthesis undergoes finely regulated processes in the specialized secretory epithelium within the venom gland. Such processes occur within a defined period in the cell and at specific cellular locations. Thus, the determination of subcellular proteomes allows the characterization of protein groups for which the site may be relevant to their biological roles, thereby allowing the deconvolution of complex biological circuits into functional information. In this regard, we performed subcellular fractionation of proteins from B. jararaca venom gland, focusing on nuclear proteins since this cellular compartment comprises key effectors that shape gene expression. Our results provided a snapshot of B. jararaca's subcellular venom gland proteome and pointed to a 'conserved' proteome core among different life stages (newborn and adult) and between sexes (adult male and female). Overall, the top 15 highly abundant proteins identified in B. jararaca venom glands mirrored the panel of highly expressed genes in human salivary glands. Therefore, the expression profile observed for such a protein set could be considered a conserved core signature of salivary gland secretory epithelium. Moreover, the newborn venom gland displayed a unique expression signature of transcription factors involved in regulating transcription and biosynthetic processes and may mirror biological constraints of the ontogenetic development of B. jararaca , contributing to venom proteome diversity. • Venom protein synthesis undergoes finely regulated processes within the venom gland. • Subcellular proteome analysis allows the deconvolution of biological circuits. • B. jararaca's subcellular venom gland proteome pointed to a 'conserved' proteome core. • The findings reported may mirror biological features of B. jararaca's natural history. [ABSTRACT FROM AUTHOR]

Vocalization, visual and chemical signals are courtship behaviours of anurans that may expose them to the risk of predation. Here, we described a predation event in which a population of the torrent frog Hylodes cardosoi was in intense courtship behaviour and one individual was caught by a specimen of the pitviper Bothrops jararaca. The predation event was recorded in a region of Atlantic Forest, Paraná, Brazil. We hypothesized that the pitviper was ambush hunting and captured a female frog that was attracted by the vocalization of a nearby male. Predatory interactions are important ecological factors driving the evolution and population size of both prey and predator. This report increases the prey richness described for B. jararaca and also extends the known geographic distribution of H. cardosoi. Our observation contributes to knowledge of the natural history of the species involved. [ABSTRACT FROM AUTHOR]

Fossils of amphibians and squamates are relatively common in Pliocene–Pleistocene sediments in the southeastern Atlantic coast of Buenos Aires Province (Argentina), particularly in the southern slope of the Tandilia mountain system. These taxa are less known in the northern slope, which in the county of Mar Chiquita are solely represented by one anuran record. Here, new herpetofaunal material is described from Mar Chiquita county in the northern slope of the Tandilia mountain system. These specimens, while few, present an interesting taxonomical and morphological diversity. From the Ensenadan outcrops, amphibians are represented by cf. Rhinella. On the other hand, Stenocercus, an indeterminate tropidurid, Colubroides, and an indeterminate snake account for the Ensenadan squamates. In the Bonaerian outcrops, squamates are represented by the viperid Bothrops and an indeterminate Pleurodont. These latter taxa are also present in the Lujanian with an indeterminate snake. These are the first fossil records of squamates from Mar Chiquita and together with the new and previous amphibian records constitute a herpetological assemblage (Ceratophrys ornata, cf. Rhinella, Stenocercus, and Bothrops) that suggests that the paleoclimatic conditions during the Pleistocene of the Pampean region would have been similar to those of the present day. This inference should be considered with caution, since it contradicts those suggested by the mammalian record, which is richer and presents taxonomic identifications that are more precise. Mammalian fossil records indicate a cold and dry glacial Pleistocene interspersed with short, warmer, and more humid periods.

The reduction of predation is a potentially important factor for the evolution of the traits of an island animal species. By relaxed selection, insular animals tend to lose their antipredator behaviors. A monophyletic group of pitvipers (genus Bothrops) in southeastern Brazil, which have high genetic affinity and dwell on the mainland and adjacent islands, provide an appropriate setting to study the evolution of antipredator behavior and how different predatory stimuli can influence this behavior. The mainland Bothrops jararaca has several terrestrial and aerial predators, whereas B. insularis and B. alcatraz, restricted to two small islands, Queimada Grande and Alcatrazes, respectively, have a smaller range of aerial predators. Terrestrial predators are absent on Queimada Grande, but one potential snake predator occurs on Alcatrazes. We observed that the defensive repertoire of island snakes has not been lost, but they display different frequencies of some antipredator behaviors. The type of predatory stimuli (terrestrial and aerial) influenced the defensive response. Bothrops insularis most often used the escape strategies, especially against terrestrial predatory stimuli. Bothrops alcatraz displayed the highest rate of strike for both terrestrial and aerial stimuli. Our results indicate that even though relaxed selection may occur in island environments as compared to mainland environments, these pitvipers still retain their antipredator behaviors but with different response degrees to the two predator types. [ABSTRACT FROM AUTHOR]

Snakebite envenoming represents an important Neglected Tropical Disease (NTD) that mainly affects tropical and subtropical developing countries according to the World Health Organization (WHO). As a priority issue in the tropics, it is estimated that accidental encounter between snakes and humans is the leading cause of morbidity and mortality among all NTDs in the world. In Brazil, an extremely diverse country with continental dimensions, snakebite envenoming is the second leading cause of reported human envenoming. Treating the disease has been an unprecedented challenge for Brazilian Health Systems for decades. Despite access to Antivenom therapy and distributing it free of charge across the country, Brazil faces numerous issues regarding the notification process and accurate treatment targeting for at-risk populations. Thus, this study aimed to identify the temporal epidemiological dynamics of accidents caused by Bothrops snakes in Brazil, the country's major group of venomous snakes, based on secondary information from the online database provided by The Brazilian Notifiable Diseases Information System (SINAN). For this purpose, reported Bothrops snakebites between 2012 and 2021 were counted, then the data were analyzed. We looked at the frequency, occurrence, mortality rates, case fatality rate (CFR), age and gender distribution, and the time lapse between the incident and the initiation of Antivenom therapy. The data were also organized considering regional variations of the country. Throughout the studied period, a total of 202,604 cases of envenoming caused by Bothrops spp. were notified, resulting in 766 fatalities. These accidents were found to occur in variable proportions across different regions in Brazil, with notable concentrations observed in the North, Northeast, and Southeast regions. The epidemiological profile of patients varied greatly between the regions, revealing that snake envenoming is much more a social, economic, and ecological problem than a medical one. In conclusion, our study provides an overview of the clinical and epidemiological profile of envenoming by Bothrops snakes in Brazil. Notably, this is the first study to present such information in a country as vast and diverse as Brazil, encompassing a comparative analysis of its regions using SINAN data, that proves to be a very useful national tool to improve the control and management of envenoming. Author summary: Snakebite envenoming it is a health challenge worldwide. In Brazil, the largest country in Latin America, Bothrops snakebites represents the main cause of envenoming by venomous snakes. Every year, at least 20,000 accidents with Bothrops snakes are notified by The Brazilian Information System for Notifiable Diseases (SINAN). However, it is well known that these numbers do not represent reality in many cases, since a significant portion of envenoming patients continue to dispense specialized medical care or are unable to arrive in time at the reference medical centers. Therefore, in our comprehensive study with secondary data made available online by SINAN, we decided to understand the temporal dynamics of Bothrops snakebites over a ten-year period across the five regions of Brazil. According to our results, which evaluated variables such as occurrence, incidence, mortality and lethality, envenoming by Bothrops snakes remains an important neglected public health problem in our country. Currently, the high rates of occurrence and incidence in certain regions are due to socioeconomic problems found in a vast and developing country such as Brazil. Despite this, lethality and mortality rates remain low at all regions of the country, a fact that can be associated with the effectiveness of the Antivenom therapy treatment provided free of charge by The Brazilian National Health System (SUS). [ABSTRACT FROM AUTHOR]

Bothrops venoms are rich in enzymes acting on platelets and coagulation. This action is dependent on two major co-factors, i.e., calcium and phospholipids, while antivenoms variably neutralize venom-related coagulopathy effects. Our aims were (i) to describe the composition of B. atrox and B. lanceolatus venoms; (ii) to study their activity on the whole blood using rotational thromboelastometry (ROTEM); (iii) to evaluate the contribution of calcium and phospholipids in their activity; and (iv) to compare the effectiveness of four antivenoms (Bothrofav™, Inoserp™ South America, Antivipmyn™ TRI, and PoliVal-ICP™) on the procoagulant activity of these two venoms. Venom composition was comparable. Both venoms exhibited hypercoagulant effects. B. lanceolatus venom was completely dependent on calcium but less dependent on phospholipids than B. atrox venom to induce in vitro coagulation. The four antivenoms neutralized the procoagulant activity of the two venoms; however, with quantitative differences. Bothrofav™ was more effective against both venoms than the three other antivenoms. The relatively similar venom-induced effects in vitro were unexpected considering the opposite clinical manifestations resulting from envenomation (i.e., systemic bleeding with B. atrox and thrombosis with B. lanceolatus). In vivo studies are warranted to better understand the pathophysiology of systemic bleeding and thrombosis associated with Bothrops bites. [ABSTRACT FROM AUTHOR]

• BjV decreases CD1d, CD83, and CD86 expression on BMDCs. • BjV did not promote the release of IL-1β, IL-6, or TNF-α. • BjV affects the maturation of DCs. This study was designed to characterize mice bone marrow (BM) and bone marrow-derived dendritic cells (BMDC) and to compare the surface markers expression and inflammatory cytokine liberation in response to LPS and Bothrops jararacussu venom (BjV) stimulation. Typical morphology was observed in BM and BMDCs from the 4th up to the 8th day of culture using recombinant mouse GM-CSF and IL-4. A high basal level of MHC-II, CD1d, CD83, CD11c, CD80, and low CD86 was expressed by BM cells. After stimulation with GM-CSF/IL-4 for BMDCs differentiation, the BM cells differentiated into BMDCs presented MHC-II, CD1d, CD83, CD11c, CD86, and CD80 expression on the 4th – 8th day accompanied with high levels of TNF-α liberated. The difference between the surface markers' expression was observed in this time course in which CD1d, CD11c, and CD80 remained in high levels of expression, while MHC-II and CD83 showed moderate expression during the differentiation period. Also, cytokines liberation was monitored over the period of the BMDCs culture, and on the 6th day, low levels of IL-6 and IL-1β were found, while high levels of TNF-α on the 4th and 8th days, both of which contributed to the maturity of the BMDCs. Maturation of DCs with LPS showed significant upregulation of surface markers (MHC-II, CD1d, CD83, CD86, CD80) and pro-inflammatory cytokines (IL-1β, IL-6, TNF-α) liberation. On the other hand, BjV induced a decrease in CD1d, CD11c, CD83, and CD86 expression in mature BMDCs which was not observed when LPS was used to stimulate BMDCs which probably induces impairment in T-cell activation. [ABSTRACT FROM AUTHOR]

Bothrops snakebite envenomation (SBE) is consider an important health problem in Brazil, where Bothrops atrox is mainly responsible in the Brazilian Amazon. Local effects represent a relevant clinical issue, in which inflammatory signs and symptoms in the bite site represent a potential risk for short and long-term disabilities. Among local complications, secondary infections (SIs) are a common clinical finding during Bothrops atrox SBE and are described by the appearance of signs such as abscess, cellulitis or necrotizing fasciitis in the affected site. However, the influence of SI in the local events is still poorly understood. Therefore, the present study describes for the first time the impact of SBE wound infection on local manifestations and inflammatory response from patients of Bothrops atrox SBE in the Brazilian Amazon. This was an observational study carried out at the Fundação de Medicina Tropical Dr. Heitor Vieira Dourado, Manaus (Brazil), involving victims of Bothrops SBE. Clinical and laboratorial data were collected along with blood samples for the quantification of circulating cytokines and chemokines before antivenom administrations (T0) and 24 h (T1), 48 h (T2), 72 h (T3) and 7 days after (T4). From the 94 patients included in this study, 42 presented SI (44.7%) and 52 were without SI (NSI, 55.3%). Patients classified as moderate envenoming presented an increased risk of developing SI (OR = 2.69; CI 95% = 1.08–6.66, p = 0.033), while patients with bites in hands showed a lower risk (OR = 0.20; CI 95% = 0.04–0.96, p = 0.045). During follow-up, SI patients presented a worsening of local temperature along with a sustained profile of edema and pain, while NSI patients showed a tendency to restore and were highlighted in patients where SI was diagnosed at T2. As for laboratorial parameters, leukocytes, erythrocyte sedimentation ratio, fibrinogen and C-reactive protein were found increased in patients with SI and more frequently in patients diagnosed with SI at T3. Higher levels of circulating IL-2, IL-10, IL-6, TNF, INF-γ and CXCL-10 were observed in SI patients along with marked correlations between these mediators and IL-4 and IL-17, showing a plurality in the profile with a mix of Th1/Th2/Th17 response. The present study reports for the first time the synergistic effects of local infection and envenoming on the inflammatory response represented by local manifestations, which reflected on laboratorial parameters and inflammatory mediators and thus help improve the clinical management of SI associated to Bothrops SBE. [ABSTRACT FROM AUTHOR]

Not surprisingly, Vane asked Sérgio to use the BBOT technique to analyse the pharmacokinetics of bradykinin in the circulation. In 1965, Sérgio Ferreira had completed his PhD programme under the supervision of Prof Rocha e Silva, his thesis had been accepted, and he was preparing to go to England for his first post-doctoral fellowship at the Pharmacology Department at Oxford University. For physiology, because all the blood passes through the pulmonary circulation, such passage would inactivate the vasodilator peptide bradykinin and convert the inactive angiotensin I to the potent vasoconstrictor angiotensin II. 4317874 14 Ferreira S.H., Greene L.J., Alabaster V.A., Bakhle Y.S., Vane J.R. Activity of Various Fractions of Bradykinin Potentiating Factor against Angiotensin I Converting Enzyme. [Extracted from the article]

ABSTRACT Background: Brazil ranks first in the number of snakebites in South America. A detailed analysis of these cases is required to improve the public health planning. In this study, we retrospectively examined the clinical and epidemiological profiles of snakebites in Maranhão between January 2009 and December 2019. Methods: Data were obtained from the compulsory notification forms provided by the Health Department of Maranhão. Results: A total of 17,658 cases were recorded during the study period. Most of the bites were from snakes belonging to the genus Bothrops. Medical care was mostly within three hours after the bite. Most cases were classified as mild and most victims recovered; however, 139 deaths were recorded. Most bites occurred among people aged 20-39 years, mainly among rural workers. The most frequent local clinical manifestations were pain, edema, and ecchymosis. The most common systemic clinical manifestations include neuroparalysis, vagal syndrome, and myolysis. Most snakebites occurred between January and March. The municipalities with the highest number of notifications were Buriticupu (936 cases), Arame (705 cases), and Grajaú (627 cases). Conclusions: The clinical profile of snakebites in Maranhão is similar to that observed in other states of Northeast Brazil. However, we found that some systemic manifestations are not compatible with the etiology of snakebites, which leads us to believe that the problem could be the lack of knowledge of the health professionals at the site of envenomation, who may not be ready for attendance, and an important lack of health centers with snake antivenom to treat snakebites.

Snakebite envenoming represents a major health problem in tropical and subtropical countries. Considering the elevated number of accidents and high morbidity and mortality rates, the World Health Organization reclassified this disease to category A of neglected diseases. In Latin America, Bothrops genus snakes are mainly responsible for snakebites in humans, whose pathophysiology is characterized by local and systemic inflammatory and degradative processes, triggering prothrombotic and hemorrhagic events, which lead to various complications, organ damage, tissue loss, amputations, and death. The activation of the multicellular blood system, hemostatic alterations, and activation of the inflammatory response are all well-documented in Bothrops envenomings. However, the interface between inflammation and coagulation is still a neglected issue in the toxinology field. Thromboinflammatory pathways can play a significant role in some of the major complications of snakebite envenoming, such as stroke, venous thromboembolism, and acute kidney injury. In addition to exacerbating inflammation and cell interactions that trigger vaso-occlusion, ischemia–reperfusion processes, and, eventually, organic damage and necrosis. In this review, we discuss the role of inflammatory pathways in modulating coagulation and inducing platelet and leukocyte activation, as well as the inflammatory production mediators and induction of innate immune responses, among other mechanisms that are altered by Bothrops venoms. [ABSTRACT FROM AUTHOR]

An mRNA transcript that codes for a Disintegrin and a Metalloprotease from a venom gland of the viper Bothrops ammodytoides was isolated. Vector pCR®2.1-TOPO was used to clone the Disintegrin transcript and then subcloned in the pET-28a vector to express the protein in the E. coli strain BL21. The recombinant disintegrin, HisrDisintegrin, comprises 38 residues at the N-terminal and 75 residues of the Disintegrin, including 14 cysteines or 7 disulfide bonds. HisrDisintegrin was obtained soluble in the intracellular fraction and separated by affinity chromatography. The experimental molecular mass of HisrDisintegrin, 11,750.8 Da, agreed with its theoretical value, including the cleavage of a Met residue caused by a bacterial post-translational modification. HisrDisintegrin was folded in in vitro conditions and then purified, finding a main fraction with a comparable molecular mass. The HisrDisintegrin contains an alpha/beta structure, as observed by circular dichroism. Its biological activity demonstrated the growth reduction of the human endothelial (HMEC-1) cells and the human mammary gland adenocarcinoma (MDA-MB-231). Furthermore, HisrDisintegrin inhibits the adhesion of HMEC-1 and MDA-MB-231 cells to the proteins of the extracellular matrix (laminin (LN), fibronectin (FN), and vitronectin (VN)). [ABSTRACT FROM AUTHOR]

Consumption coagulopathy and hemorrhagic syndrome exacerbated by blood anticoagulability remain the most important causes of lethality associated with Bothrops snake envenomation. Bothrops venom also engages platelet aggregation on the injured endothelium via von Willebrand factor (vWF) interactions. Besides platelet aggregation, some Bothrops venom toxins may induce qualitative thrombopathy, which has been in part related to the inhibition of vWF activation. We tested whether B. lanceolatus venom impaired vWF to collagen(s) binding (vWF:CB) activity. Experiments were performed with B. lanceolatus crude venom, in the presence or absence of Bothrofav, a monospecific B. lanceolatus antivenom. Venom of B. lanceolatus fully inhibited vWF to collagen type I and III binding, suggesting venom interactions with the vWF A3 domain. In contrast, B. lanceolatus venom increased vWF to collagen type VI binding, suggesting the enhancement of vWF binding to collagen at the vWF A1 domain. Hence, B. lanceolatus venom exhibited contrasting in vitro effects in terms of the adhesive properties of vWF to collagen. On the other hand, the antivenom Bothrofav reversed the inhibitory effects of B. lanceolatus venom on vWF collagen binding activity. In light of the respective distribution of collagen type III and collagen type VI in perivascular connective tissue and the sub-endothelium, a putative association between an increase in vWF:CB activity for collagen type VI and the onset of thrombotic events in human B. lanceolatus envenomation might be considered. [ABSTRACT FROM AUTHOR]

RNA purification and cDNA synthesis represents the starting point for molecular analyses of snake venom proteins-enzymes. Usually, the sacrifice of snakes is necessary for venom gland extraction to identify protein-coding transcripts; however, the venom can be used as a source of transcripts. Although there are methods for obtaining RNA from venom, no comparative analysis has been conducted in the Bothrops genus. In the present study, we compared four commercial methods for RNA purification and cDNA synthesis from venom (liquid, lyophilized, or long-term storage) of four clinically relevant species of Peruvian Bothrops. Our results show that the TRIzol method presents the highest yield of RNA purified from venom (59 ± 11 ng/100 µL or 10 mg). The SuperScript First-Strand Synthesis System kit produced high amounts of cDNA (3.2 ± 1.2 ng cDNA/ng RNA), and the highest value was from combination with the Dynabeads mRNA DIRECT kit (4.8 ± 2.0 ng cDNA/ng RNA). The utility of cDNA was demonstrated with the amplification of six relevant toxins: thrombin-like enzymes, P-I and P-III metalloproteinases, acid and basic phospholipases A2, and disintegrins. To our knowledge, this is the first comparative study of RNA purification and cDNA synthesis methodologies from Bothrops genus venom. [ABSTRACT FROM AUTHOR]

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The systemic increase in inflammatory mediator levels can induce diverse pathological disorders, including potentially thrombus formation, which may be lethal. Among the clinical conditions in which the formation of thrombi dictates the patient's prognosis, envenomation by Bothrops lanceolatus should be emphasized, as it can evolve to stroke, myocardial infarction and pulmonary embolism. Despite their life-threatening potential, the immunopathological events and toxins involved in these reactions remain poorly explored. Therefore, in the present study, we examined the immunopathological events triggered by a PLA2 purified from B. lanceolatus venom, using an ex vivo human blood model of inflammation. Our results showed that the purified PLA2 from the venom of B. lanceolatus damages human erythrocytes in a dose dependent way. The cell injury was associated with a decrease in the levels of CD55 and CD59 complement regulators on the cell surface. Moreover, the generation of anaphylatoxins (C3a and C5a) and the soluble terminal complement complex (sTCC) indicates that human blood exposure to the toxin activates the complement system. Increased production of TNF-α, CXCL8, CCL2 and CCL5 followed complement activation. The venom PLA2 also triggered the generation of lipid mediators, as evidenced by the detected high levels of LTB4, PGE2 and TXB2. The scenario here observed of red blood cell damage, dysfunctions of the complement regulatory proteins, accompanied by an inflammatory mediator storm, suggests that B. lanceolatus venom PLA2 contributes to the thrombotic disorders present in the envenomed individuals. [ABSTRACT FROM AUTHOR]

From the venom of the Bothrops pictus snake, an endemic species from Peru, we recently have described toxins that inhibited platelet aggregation and cancer cell migration. In this work, we characterize a novel P-III class snake venom metalloproteinase, called pictolysin-III (Pic-III). It is a 62 kDa proteinase that hydrolyzes dimethyl casein, azocasein, gelatin, fibrinogen, and fibrin. The cations Mg2+ and Ca2+ enhanced its enzymatic activity, whereas Zn2+ inhibited it. In addition, EDTA and marimastat were also effective inhibitors. The amino acid sequence deduced from cDNA shows a multidomain structure that includes a proprotein, metalloproteinase, disintegrin-like, and cysteine-rich domains. Additionally, Pic-III reduces the convulxin- and thrombin-stimulated platelet aggregation and in vivo, it has hemorrhagic activity (DHM = 0.3 µg). In epithelial cell lines (MDA-MB-231 and Caco-2) and RMF-621 fibroblast, it triggers morphological changes that are accompanied by a decrease in mitochondrial respiration, glycolysis, and ATP levels, and an increase in NAD(P)H, mitochondrial ROS, and cytokine secretion. Moreover, Pic-III sensitizes to the cytotoxic BH3 mimetic drug ABT-199 (Venetoclax) in MDA-MB-231 cells. To our knowledge, Pic-III is the first SVMP reported with action on mitochondrial bioenergetics and may offer novel opportunities for promising lead compounds that inhibit platelet aggregation or ECM–cancer-cell interactions. [ABSTRACT FROM AUTHOR]

The tongue has a series of functions that can be related to feeding, such as transporting food to the back of the mouth, sensory function and capturing prey. The tongue of the reptiles has great morphological and functional variations between orders. This study aimed to described the morphological characteristics of the tongue of the snake Bothrops jararaca, relating them to the habitat and eating habits of this species. This work used five adult animals which were collected in the municipality of Viçosa, in the Zona da Mata Mineira region. The animals were euthanized, with anesthetic overdose, for the removal of the tongue, which was used for histological processing and scanning electron microscopy. The tongue had stratified epithelium with an extensive degree of keratinization and pigmentation. It was shown to be strongly muscular, innervated and vascularized. Keratinization and pigmentation is an important protection mechanism, due to the protrability of this organ, which is exposed to the environment to capture odors and locate prey. Mucous secretion was present as an important tool for lubrication and protection of the lingual lining. The tongue of the B. jararaca has no papillae and taste buds, being its function strictly olfactory, in association with the vomeronasal organ. [ABSTRACT FROM AUTHOR]

Botropic accidents are the most common among snake accidents in Brazil. The species Bothrops jararaca, the popular jararaca, predominantly inhabits the south and southeast regions, and thus is the most relevant venomous snake in the region, being responsible for most accidents. Its poison causes important clinical repercussions, with proteolytic, coagulant and hemorrhagic actions, which cause an exuberant clinical picture. In addition to the pain, local manifestations and coagulation disorders, the jararaca sting can present complications such as infections and tissue necrosis. Thus, this case report aims to describe the approach and evolution of a botropic accident involving a previously healthy 5-year-old pediatric patient.