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Introdução: Acidentes ofídicos são doenças negligenciadas e constituem uma parcela importante da morbidade de pessoas em idade produtiva que vivem em zonas rurais. A maior parte dos seus efeitos a curto prazo é amplamente conhecida, especialmente aqueles de natureza clínica; no entanto, ainda se observa lacuna importante do conhecimento das consequências a longo prazo de tais agravos, notadamente as de ordem psíquica. Este artigo relata um caso de adoecimento mental subsequente a um acidente crotálico e gera reflexões de âmbito cultural e fisiopatológico a respeito das sequelas de tais eventos. Apresentação do caso: Trata-se de adolescente residente no interior baiano que foi vítima de mordedura por cascavel e teve necessidade de hospitalização em unidade de terapia intensiva. Observou-se que, mesmo após melhora clínica, iniciou com sintomas psicóticos prodrômicos e progrediu para piora mental grave, que culminou em internação psiquiátrica e diagnóstico de esquizofrenia no decorrer dos meses seguintes. Conclusões: Nota-se, neste caso, correlação direta entre esses dois eventos; mas, em razão da escassez de trabalhos científicos que abordem tais questões, depreende-se que é preciso investigar e estudar com maior profundidade possíveis associações entre acidentes crotálicos e psicoses.

Introduction: Snakebites are neglected diseases and constitute an important part of the morbidity of working-age people who live in rural areas. Most of their short-term effects are widely known, especially those of a clinical nature; however, there is still an important gap in the knowledge of the long-term consequences of such injuries, notably those of a psychotic nature. This article aims to report a case of mental illness subsequent to a rattlesnake bite accident and generate cultural and pathophysiological reflections regarding the consequences of such events. Case presentation: An adolescent residing in the interior of the state of Bahia was bitten by a rattlesnake and required hospitalization in an intensive care unit. It was observed that even after clinical improvement, the case started with prodromal psychotic symptoms and progressed to severe mental deterioration that culminated in psychiatric hospitalization and diagnosis of schizophrenia over the following months. Conclusions: In this case, there was a direct correlation between these two events, but because of the scarcity of scientific works that address such issues, it is necessary to investigate and study in greater depth possible associations between snakebite accidents and psychoses.

Introducción: Las mordeduras de serpientes son enfermedades desatendidas y constituyen una parte importante de la morbilidad de las personas en edad laboral que viven en zonas rurales. La mayoría de sus efectos a corto plazo son ampliamente conocidos, especialmente los de carácter clínico; sin embargo, todavía existe un importante vacío en el conocimiento de las consecuencias a largo plazo de este tipo de lesiones, en particular las de carácter psíquico. Este artículo tiene como objetivo informar un caso de enfermedad mental posterior a un accidente crotálico y generar reflexiones culturales y fisiopatológicas sobre las consecuencias de tales eventos. Presentación del caso: Se trata de un adolescente residente en el interior de Bahía que fue mordido por una serpiente cascabel y requirió hospitalización en unidad de cuidados intensivos. Se observó que, aún después de la mejoría clínica, comenzó con síntomas psicóticos prodrómicos y progresó a un deterioro mental severo que culminó con hospitalización psiquiátrica y diagnóstico de esquizofrenia en los meses siguientes. Conclusiones: En este caso, existe una correlación directa entre estos dos eventos pero, debido a la escasez de trabajos científicos que aborden tales cuestiones, parece necesario investigar y estudiar con mayor profundidad posibles asociaciones entre accidentes crotálicos y psicosis.

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This study investigated crotamine (CTA), a peptide derived from the venom of the South American rattlesnake Crotalus durissus terrificus, known for its exceptional cell penetration potential. The objective was to explore the antibacterial and antifungal activity of CTA, its ability to inhibit efflux pumps and evaluate the effectiveness of its pharmacological combination with antibiotics and antifungals. In microbiological assays, CTA in combination with antibiotics was tested against strains of S. aureus and the inhibition of NorA, Tet(K) and MepA efflux pumps was also evaluated. CTA alone did not present clinically relevant direct antibacterial action, presenting MIC > 209.7 µM against strains S. aureus 1199B, IS-58, K2068. The standard efflux pump inhibitor CCCP showed significant effects in all negative relationships to assay reproducibility. Against the S. aureus 1199B strain, CTA (20.5 µM) associated with norfloxacin diluted 10 × (320.67 µM) showed a potentiating effect, in relation to the control. Against the S. aureus IS-58 strain, the CTA associated with tetracycline did not show a significant combinatorial effect, either with 2304 or 230.4 µM tetracycline. CTA at a concentration of 2.05 µM associated with ciprofloxacin at a concentration of 309.4 µM showed a significant potentiating effect. In association with EtBr, CTA at concentrations of 2.05 and 20.5 µM potentiated the effect in all strains tested, reducing the prevention of NorA, Tet(K) and MepA efflux pumps. In the C. albicans strain, a potentiating effect of fluconazole (334.3 µM) was observed when combined with CTA (2.05 µM). Against the C. tropicalis strain, a significant effect was also observed in the association of fluconazole 334.3 µM, where CTA 2.05 µM considerably reduced fungal growth and decreased the potentiation of fluconazole. Against the C. krusei strain, no significant potentiating effect of fluconazole was obtained by CTA. Our results indicate that CTA in pharmacological combination potentiates the effects of antibiotics and antifungal. This represents a new and promising antimicrobial strategy for treating a wide variety of infections.

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The presence of cardiac shunts in ectothermic tetrapods is thought to be consistent with active vascular modulations for proper hemodynamic support. Local control of blood flow modulates tissue perfusion and thus systemic conductance (Gsys) is assumed to increase with body temperature (Tb) to accommodate higher aerobic demand. However, the general increase of Gsys presses for a higher right-to-left (R-L) shunt, which reduces arterial oxygen concentration. In contrast, Tb reduction leads to a Gsys decrease and a left-to-right shunt, which purportedly increases pulmonary perfusion and plasma filtration in the respiratory area. This investigation addressed the role of compensatory vascular adjustments in the face of the metabolic alterations caused by Tb change in the South American rattlesnake (Crotalus durissus). Cardiovascular recordings were performed in decerebrated rattlesnake preparations at 10, 20 and 30°C. The rise in Tb increased metabolic demand, and correlated with an augmentation in heart rate. Although cardiac output increased, systemic stroke volume reduced while pulmonary stroke volume remained stable. Although that resulted in a proportionally higher increase in pulmonary blood flow, the R-L shunt was maintained. While the systemic compliance of large arteries was the most relevant factor in regulating arterial systemic blood pressure, peripheral conductance of pulmonary circulation was the major factor influencing the final cardiac shunt. Such dynamic adjustment of systemic compliance and pulmonary resistance for shunt modulation has not been demonstrated before and contrasts with previous knowledge on shunt control.

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Mexico has the highest diversity of snake species in the world, following Australia when considering just venomous snakes. Specifically, in Sonora, the second largest state in the country, more than 15 highly venomous species occur, including the northern black-tailed rattlesnake (Crotalus molossus). This specie's venom has not been as thoroughly researched in contrast with other Mexican vipers, nevertheless some studies report its biological activity and even pharmacological potential with antibacterial and cytotoxic activity. In this study we identified the main protein components from a pool of C. molossus venom through a gel-free proteomics approach, reporting ∼140 proteins belonging to the SVMP (38.76%), PLA2 (28.75%), CTL (11.93%), SVSP (6.03%) and LAAO (5.67%) toxin families. To study its biological activities, we evaluated its hemolytic, antibacterial, and cytotoxic activity in red blood cells, Gram positive and negative bacteria and a luminal A breast carcinoma cell line (T47D), respectively, in vitro. We report that concentrations <100 µg/mL are potentially not hemolytic and reduced the bacteria viability of E. coli and S. aureus with an IC50 of 10.27 and 11.51 µg/mL, respectively. Finally, we determined the C. molossus venom as cytotoxic against the T47D breast carcinoma cell line, with an IC50 of 1.55 µg/mL. We suggest that the evaluated cytotoxicity was due to a high abundance of SVMPs and PLA2s, since it's been reported that they affect the extracellular matrix and membrane permeation. This may provide a useful tool for pharmaceutical screening in the future.

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It is well known that C. d. terrificus venom causes pathophysiological effects such as neuropathies, coagulopathies, and even death. Previous studies have reported that ASC16 can interact with monomeric phospholipases A2 from the venom of various snake species (e.g., Vipera russelli and Echis carinatus). As a result, ASC16 has been proposed as an inhibitor of the toxic effects induced by the heterodimeric complex (crotoxin) and other components of the venom of C. d. terrificus. To investigate this further, in silico studies were designed using the crotoxin (CTX) protein complex as a model, and experimental assays were conducted to evaluate the inhibitory effect of ASC16 on CTX, as well as on other venom enzymes such as thrombin-like enzyme (TLE), phosphodiesterase (PDE) and l-aminoxidase (LAAO). For in vitro assays, specific substrates were used, and lethal activity was measured over 48 h using an in vivo murine experimental model (CF01). In silico studies have indicated that the hydrophilic portion of ASC16 adopts a stable conformation while interacting with the catalytic site of crotoxin. At the highest concentrations, ASC16 significantly inhibited the activities of PLA2 (40.89 ± 0.09 %), TLE (11.03 ± 0.69 %), PDE (51.33 ± 2.83 %), and LAAO (56.79 ± 2.91 %). Furthermore, ASC16 neutralized the 2 LD50 lethality of crotalic venom. These findings lay the groundwork for designing promising adjuvants that can facilitate the incorporation of a larger quantity of proteins in immunization schemes. Consequently, this approach aims to achieve higher antibody titers, reduce the number of required immunizations, and minimize local damage in the producer animal.

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The impact of temperature on reptile physiology has been examined through two main parameters: locomotor performance and metabolic rates. Among reptiles, different species may respond to environmental temperatures in distinct ways, depending on their thermal sensitivity. Such variation can be linked to the ecological lifestyle of the species and needs to be taken into consideration when assessing the thermal influence on physiology. This is particularly relevant for snakes, which are a very functionally diverse group. In this study, our aim was to analyze the thermal sensitivity of locomotor performance and resting metabolic rate (RMR) in three snake species from central Mexico (Crotalus polystictus, Conopsis lineata, and Thamnophis melanogaster), highlighting how it is influenced by their distinctive behavioral and ecological traits. We tested both physiological parameters in five thermal treatments: 15 °C, 25 °C, 30 °C, 33 °C, and 36 °C. Using the performance data, we developed thermal performance curves (TPCs) for each species and analyzed the RMR data using generalized linear mixed models. The optimal temperature for locomotion of C. polystictus falls near its critical thermal maximum, suggesting that it can maintain performance at high temperatures but with a narrow thermal safety margin. T. melanogaster exhibited the fastest swimming speeds and the highest mass-adjusted RMR. This aligns with our expectations since it is an active forager, a high energy demand mode. The three species have a wide performance breadth, which suggests that they are thermal generalists that can maintain performance over a wide interval of temperatures. This can be beneficial to C. lineata in its cold habitat, since such a characteristic has been found to allow some species to maintain adequate performance levels in suboptimal temperatures. RMR increased along with temperature, but the proportional surge was not uniform since thermal sensitivity measured through Q10 increased at the low and high thermal treatments. High Q10 at low temperatures could be an adaptation to maintain favorable performance in suboptimal temperatures, whereas high Q10 at high temperatures could facilitate physiological responses to heat stress. Overall, our results show different physiological adaptations of the three species to the environments they inhabit. Their different activity patterns and foraging habits are closely linked to these adaptations. Further studies of other populations with different climatic conditions would provide valuable information to complement our current understanding of the effect of environmental properties on snake physiology.

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Camelid immunoglobulins represent a unique facet of antibody biology, challenging conventional understandings of antibody diversification. IgG2 and IgG3 in particular are composed solely of heavy chains and exhibit a reduced molecular weight (90 kDa); their elongated complementarity determining region (CDR) loops play a pivotal role in their functioning, delving deep into enzyme active sites with precision. Serum therapy stands as the primary venom-specific treatment for snakebite envenomation, harnessing purified antibodies available in diverse forms such as whole IgG, monovalent fragment antibody (Fab), or divalent fragment antibody F (ab')2. This investigation looks into the intricacies of IgGs derived from camelid serum previously immunized with crotamine and crotoxin, toxins predominantly in Crotalus durissus venom, exploring their recognition capacity, specificity, and cross-reactivity to snake venoms and its toxins. Initially, IgG purification employed affinity chromatography via protein A and G columns to segregate conventional antibodies (IgG1) from heavy chain antibodies (IgG2 and IgG3) of camelid isotypes sourced from Lama glama serum. Subsequent electrophoretic analysis (SDS-PAGE) revealed distinct bands corresponding to molecular weight profiles of IgG's fractions representing isotypes in Lama glama serum. ELISA cross-reactivity assays demonstrated all three IgG isotypes' ability to recognize the tested venoms. Notably, IgG1 exhibited the lowest interactivity in analyses involving bothropic and crotalic venoms. However, IgG2 and IgG3 displayed notable cross-reactivity, particularly with crotalic venoms and toxins, albeit with exceptions such as PLA2-CB, showing reduced reactivity, and C. atrox, where IgGs exhibited insignificant reactivity. In Western blot assays, IgG2 and IgG3 exhibited recognition of proteins within molecular weight (≈15 kDa) of C. d. collilineatus to C. d. terrificus, with some interaction observed even with bothropic proteins despite lower reactivity. These findings underscore the potential of camelid heavy-chain antibodies, suggesting Lama glama IgGs as prospective candidates for a novel class of serum therapies. However, further investigations are imperative to ascertain their suitability for serum therapy applications.

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Rattlesnakes belonging to the genus Crotalus are widely distributed throughout the Americas. In Brazil, symptoms commonly associated with envenomation by Crotalus durissus collilineatus include myalgia, rhabdomyolysis, renal failure, neurotoxicity, and progressive paralysis, which are related to the protein composition of this venom. Snake venom composition exhibits compositional variability that may reflect geographic distribution, age, captivity, diet, sex, and even individual genetics. Although seasonality is also considered a possible source of variation, there are few reports of such variability in snake venom. In this work, venoms of the same eight C. durissus collilineatus were extracted every three months for two years, to analyze seasonal changes in composition and activities. To this end, venom composition was analyzed by protein quantification, SDS-PAGE, and HPLC, and the LAAO, PLA2 and coagulant activities were measured. Venoms of these C. d. collilineatus showed minor seasonal differences in venom activities and no composition differences were found. LAAO and coagulant activities displayed a pattern of seasonal change, while PLA2 activity seemed to have no seasonality tendency. Also, there are sexual differences, in which males seem to be more stable than females in regard to some activities. Individual variability occurs even in seasonal variation of activities, highlighting the importance of controlling circumstances of venom extraction before comparing results between groups of snakes.

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Despite a recent surge in high-throughput venom research that has enabled many species to be studied, some snake venoms remain understudied. The long-tailed rattlesnakes (Crotalus ericsmithi, C. lannomi, and C. stejnegeri) are one group where such research lags, largely owing to the rarity of these snakes and the hazardous areas, ripe with drug (marijuana and opium) production, they inhabit in Mexico. To fill this knowledge gap, we used multiple functional assays to examine the coagulotoxic (including across different plasma types), neurotoxic, and myotoxic activity of the venom of the long-tailed rattlesnakes. All crude venoms were shown to be potently anticoagulant on human plasma, which we discovered was not due to the destruction of fibrinogen, except for C. stejnegeri displaying minor fibrinogen destruction activity. All venoms exhibited anticoagulant activity on rat, avian, and amphibian plasmas, with C. ericsmithi being the most potent. We determined the mechanism of anticoagulant activity by C. ericsmithi and C. lannomi venoms to be phospholipid destruction and inhibition of multiple coagulation factors, leading to a net disruption of the clotting cascade. In the chick biventer assay, C. ericsmithi and C. lannomi did not exhibit neurotoxic activity but displayed potential weak myotoxic activity. BIRMEX® (Faboterápico Polivalente Antiviperino) antivenom was not effective in neutralising this venom effect. Overall, this study provides an in-depth investigation of venom function of understudied long-tailed rattlesnakes and provides a springboard for future venom and ecology research on the group.

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Our study presents the anticancer potential of crotamine from Crotalus durissus terrificus in human prostate cancer cell line DU-145. Crotamine isolation was conducted through RP-FPLC, its molecular mass analyzed by MALDI-TOF was 4881.4 kDa, and N-terminal sequencing confirmed crotamine identity. Crotamine demonstrated no toxicity and did not inhibit migration in HUVEC cells. Although no cell death occurred in DU-145 cells, crotamine inhibited their migration. Thus, crotamine presented potential to be a prototype of anticancer drug.

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