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1.
PLoS Negl Trop Dis ; 18(9): e0012516, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39288194

RESUMO

BACKGROUND: Human-snake conflicts are common worldwide, often resulting in snakebites. Snakebite envenoming causes over 125,000 deaths and 400,000 permanent disabilities worldwide every year. India alone accounts for an average of ~58,000 annual snakebite-induced deaths. As human developments rapidly expand into suburban and rural areas, snakes are being displaced and incidences of residents finding snakes within their dwellings are increasing. Most people have an innate fear of snakes, compounded by centuries of negative influence from culture and mythology manifesting in people often attempting to kill snakes. Snake rescuers are volunteers who remove and relocate snakes to safe areas. This is a risky job that poses potentially fatal implications if bitten. These volunteers mostly receive no financial compensation for their time or transportation costs, but they choose to do it for their love of snakes, conservation, and for the altruistic nature of helping others. Snake rescuers often receive no formal training and are unfunded resulting in removing snakes improperly without adequate safety equipment or the required skill set to safely complete the task. Therefore, it is critical to determine their challenges and requirements to promote the safe rescue of snakes while protecting human lives. METHODOLOGY/PRINCIPAL FINDINGS: In this study, we developed an online questionnaire and interviewed 152 snake rescuers in Tamil Nadu, India following written informed consent to determine their challenges and needs for rescuing snakes safely. The results demonstrate that most rescuers are males, and they conduct snake rescues for varying lengths of time. They mostly receive no formal training and are bitten by snakes. They spend their own money on the purchase of snake-handling equipment and on treatments if bitten or injured during a rescue. CONCLUSIONS/SIGNIFICANCE: The rescuers highlighted the urgent need for formal training, safety equipment and standard protocols for rescuing snakes in Tamil Nadu. Overall, this study demonstrates that snake rescuing should be appropriately regulated by the authorities, in particular the Wildlife Division of State Forest Departments in India, and formal training along with necessary equipment, medical insurance and appropriate recognition should be provided to them to safely remove snakes from human dwellings and manage the safety of both snakes and humans. They can also act as educators to disseminate information about the preventive and first aid measures for snakebites as well as the ecological importance of snakes.


Assuntos
Mordeduras de Serpentes , Serpentes , Índia , Humanos , Mordeduras de Serpentes/prevenção & controle , Animais , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Adulto Jovem , Adolescente , Conservação dos Recursos Naturais , Inquéritos e Questionários , Idoso , Voluntários/psicologia
2.
Toxins (Basel) ; 16(5)2024 May 11.
Artigo em Inglês | MEDLINE | ID: mdl-38787074

RESUMO

Snakebite envenoming and its resulting complications are serious threats to the health of vulnerable people living in rural areas of developing countries. The knowledge of the heterogeneity of symptoms associated with snakebite envenoming and their management strategies is vital to treat such life-threatening complications to save lives. Russell's viper envenomation induces a diverse range of clinical manifestations from commonly recognised haemotoxic and local effects to several rare conditions that are often not reported. The lack of awareness about these unusual manifestations can affect prompt diagnosis, appropriate therapeutic approaches, and positive outcomes for patients. Here, we report pulmonary thromboembolism that developed in three patients following Russell's viper envenomation and demonstrate their common clinical features and diagnostic and therapeutic approaches used. All patients showed clinical signs of local (oedema) and systemic (blood coagulation disturbances) envenomation, which were treated using polyvalent antivenom. They exhibited elevated heart rates, breathlessness, and reduced oxygen saturation, which are non-specific but core parameters in the diagnosis of pulmonary embolism. The recognition of pulmonary embolism was also achieved by an electrocardiogram, which showed sinus tachycardia and computed tomography and echocardiogram scans further confirmed this condition. Anti-coagulant treatment using low-molecular-weight heparin offered clinical benefits in these patients. In summary, this report reinforces the broad spectrum of previously unreported consequences of Russell's viper envenomation. The constant updating of healthcare professionals and the dissemination of major lessons learned in the clinical management of snakebite envenoming through scientific documentation and educational programs are necessary to mitigate the adverse impacts of venomous snakebites in vulnerable communities.


Assuntos
Antivenenos , Daboia , Embolia Pulmonar , Mordeduras de Serpentes , Mordeduras de Serpentes/complicações , Mordeduras de Serpentes/tratamento farmacológico , Embolia Pulmonar/etiologia , Embolia Pulmonar/tratamento farmacológico , Humanos , Animais , Masculino , Antivenenos/uso terapêutico , Venenos de Víboras/toxicidade , Adulto , Feminino , Pessoa de Meia-Idade , Anticoagulantes/uso terapêutico
4.
Sci Rep ; 14(1): 3184, 2024 02 07.
Artigo em Inglês | MEDLINE | ID: mdl-38326450

RESUMO

Local tissue damage following snakebite envenoming remains a poorly researched area. To develop better strategies to treat snakebites, it is critical to understand the mechanisms through which venom toxins induce envenomation effects including local tissue damage. Here, we demonstrate how the venoms of two medically important Indian snakes (Russell's viper and cobra) affect human skeletal muscle using a cultured human myoblast cell line. The data suggest that both venoms affect the viability of myoblasts. Russell's viper venom reduced the total number of cells, their migration, and the area of focal adhesions. It also suppressed myogenic differentiation and induced muscle atrophy. While cobra venom decreased the viability, it did not largely affect cell migration and focal adhesions. Cobra venom affected the formation of myotubes and induced atrophy. Cobra venom-induced atrophy could not be reversed by small molecule inhibitors such as varespladib (a phospholipase A2 inhibitor) and prinomastat (a metalloprotease inhibitor), and soluble activin type IIb receptor (a molecule used to promote regeneration of skeletal muscle), although the antivenom (raised against the Indian 'Big Four' snakes) has attenuated the effects. However, all these molecules rescued the myotubes from Russell's viper venom-induced atrophy. This study demonstrates key steps in the muscle regeneration process that are affected by both Indian Russell's viper and cobra venoms and offers insights into the potential causes of clinical features displayed in envenomed victims. Further research is required to investigate the molecular mechanisms of venom-induced myotoxicity under in vivo settings and develop better therapies for snakebite-induced muscle damage.


Assuntos
Daboia , Mordeduras de Serpentes , Humanos , Animais , Naja naja , Mordeduras de Serpentes/tratamento farmacológico , Venenos de Víboras/toxicidade , Elapidae , Venenos Elapídicos/farmacologia , Venenos Elapídicos/uso terapêutico , Mioblastos , Atrofia
5.
Antibiotics (Basel) ; 13(1)2024 Jan 14.
Artigo em Inglês | MEDLINE | ID: mdl-38247637

RESUMO

Antimicrobial peptides have been developed based on plant-derived molecular scaffolds for the treatment of infectious diseases. Chenopodin is an abundant seed storage protein in quinoa, an Andean plant with high nutritional and therapeutic properties. Here, we used computer- and physicochemical-based strategies and designed four peptides derived from the primary structure of Chenopodin. Two peptides reproduce natural fragments of 14 amino acids from Chenopodin, named Chen1 and Chen2, and two engineered peptides of the same length were designed based on the Chen1 sequence. The two amino acids of Chen1 containing amide side chains were replaced by arginine (ChenR) or tryptophan (ChenW) to generate engineered cationic and hydrophobic peptides. The evaluation of these 14-mer peptides on Staphylococcus aureus and Escherichia coli showed that Chen1 does not have antibacterial activity up to 512 µM against these strains, while other peptides exhibited antibacterial effects at lower concentrations. The chemical substitutions of glutamine and asparagine by amino acids with cationic or aromatic side chains significantly favoured their antibacterial effects. These peptides did not show significant hemolytic activity. The fluorescence microscopy analysis highlighted the membranolytic nature of Chenopodin-derived peptides. Using molecular dynamic simulations, we found that a pore is formed when multiple peptides are assembled in the membrane. Whereas, some of them form secondary structures when interacting with the membrane, allowing water translocations during the simulations. Finally, Chen2 and ChenR significantly reduced SARS-CoV-2 infection. These findings demonstrate that Chenopodin is a highly useful template for the design, engineering, and manufacturing of non-toxic, antibacterial, and antiviral peptides.

6.
PLoS Negl Trop Dis ; 17(10): e0011699, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37844081

RESUMO

BACKGROUND: India suffers ~58,000 annual deaths due to snakebites. The 'Big Four' snakes (Russell's viper, Indian cobra, common krait, and saw-scaled viper) that are responsible for most bites cause diverse clinical effects. Delayed treatment increases the risk of serious complications and treatment costs. Although government hospitals offer free treatment for snakebites in India, most patients opt for private healthcare, which is an out-of-pocket expense as they often lack health insurance coverage. This study aims to analyse snakebite treatment costs in private tertiary care hospitals in Tamil Nadu, India and identifies the key factors contributing to treatment costs. METHODOLOGY/PRINCIPAL FINDINGS: The treatment cost details for 913 snakebite victims were collected from 10 private tertiary care hospitals across Tamil Nadu. The data were classified into hospital, pharmacy, investigation, and laboratory costs, and analysed to determine various factors that contribute to the costs. The results demonstrate that the average treatment costs vary widely for different snakes. The hospital and pharmacy costs are higher than investigation and laboratory costs for all snakebites. Notably, Russell's viper bites cost significantly more than the bites from other snakes. Overall, the type of snake, nature of complications, specialist treatments required, and arrival time to hospitals were identified as some of the key factors for higher treatment costs. CONCLUSIONS/SIGNIFICANCE: These data demonstrate that ~80% of snakebite patients can be treated with INR 100,000 (~GBP 1000 or USD 1200) or less. This study emphasises the urgent need to improve rural medical care by providing appropriate training for healthcare professionals and essential resources to facilitate early assessment of patients, administer the initial dose of antivenom and refer the patients to tertiary care only when needed. Moreover, the outcome of this study forms a basis for developing appropriate policies to regulate snakebite treatment costs and provide affordable medical insurance for vulnerable communities.


Assuntos
Daboia , Mordeduras de Serpentes , Viperidae , Animais , Humanos , Mordeduras de Serpentes/tratamento farmacológico , Atenção Terciária à Saúde , Índia/epidemiologia , Antivenenos/uso terapêutico , Custos de Cuidados de Saúde
7.
Toxicon ; 234: 107307, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37783315

RESUMO

Despite the considerable global impact of snakebite envenoming, available treatments remain suboptimal. Here, we report the discovery of a broadly-neutralizing human monoclonal antibody, using a phage display-based cross-panning strategy, capable of reducing the cytotoxic effects of venom phospholipase A2s from three different snake genera from different continents. This highlights the potential of utilizing monoclonal antibodies to develop more effective, safer, and globally accessible polyvalent antivenoms that can be widely used to treat snakebite envenoming.


Assuntos
Mordeduras de Serpentes , Animais , Humanos , Peçonhas , Anticorpos Monoclonais , Antivenenos/farmacologia , Serpentes , Fosfolipases A2 , Venenos de Serpentes
8.
Toxins (Basel) ; 15(9)2023 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-37755956

RESUMO

The interactions between specific snake venom toxins and muscle constituents are the major cause of severe muscle damage that often result in amputations and subsequent socioeconomic ramifications for snakebite victims and/or their families. Therefore, improving our understanding of venom-induced muscle damage and determining the underlying mechanisms of muscle degeneration/regeneration following snakebites is critical to developing better strategies to tackle this issue. Here, we analysed intramuscular bleeding and thrombosis in muscle injuries induced by two different snake venom toxins (CAMP-Crotalus atrox metalloprotease (a PIII metalloprotease from the venom of this snake) and a three-finger toxin (CTX, a cardiotoxin from the venom of Naja pallida)). Classically, these toxins represent diverse scenarios characterised by persistent muscle damage (CAMP) and successful regeneration (CTX) following acute damage, as normally observed in envenomation by most vipers and some elapid snakes of Asian, Australasian, and African origin, respectively. Our immunohistochemical analysis confirmed that both CAMP and CTX induced extensive muscle destruction on day 5, although the effects of CTX were reversed over time. We identified the presence of fibrinogen and P-selectin exposure inside the damaged muscle sections, suggesting signs of bleeding and the formation of platelet aggregates/microthrombi in tissues, respectively. Intriguingly, CAMP causes integrin shedding but does not affect any blood clotting parameters, whereas CTX significantly extends the clotting time and has no impact on integrin shedding. The rates of fibrinogen clearance and reduction in microthrombi were greater in CTX-treated muscle compared to CAMP-treated muscle. Together, these findings reveal novel aspects of venom-induced muscle damage and highlight the relevance of haemostatic events such as bleeding and thrombosis for muscle regeneration and provide useful mechanistic insights for developing better therapeutic interventions.


Assuntos
Crotalus , Mordeduras de Serpentes , Trombose , Serpentes Peçonhentas , Humanos , Cardiotoxinas/toxicidade , Venenos Elapídicos/farmacologia , Venenos de Serpentes/farmacologia , Hemorragia/induzido quimicamente , Metaloproteases/farmacologia , Fibrinogênio , Músculo Esquelético , Integrinas , Mordeduras de Serpentes/complicações
9.
Toxicon ; 234: 107284, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37683700

RESUMO

Snakebite envenoming (SBE) is common in rural communities living in tropical regions that often have fragile and/or overwhelmed healthcare systems. The complex scenarios around SBE lead to a high number of deaths, disabilities, and long-term consequences in patients. Russell's viper (Daboia russelii) is one of the most medically important snake species in India, which causes devastating pathological conditions characterised by a wide range of clinical manifestations. This broad spectrum of symptoms requires additional therapeutic interventions beyond the classical antivenom administration. Hence, positive outcomes for patients affected by SBE can be achieved with a better understanding of previous experiences describing clinical manifestations and various therapeutic interventions including for rare and underreported conditions. Here, we report an SBE victim who developed partial segmental thrombosis in the corpus cavernosum following Russell's viper envenomation and its diagnostic and treatment approaches. The patients received 180 ml of antivenom to resolve the abnormalities in their haematological parameters. Despite antivenom treatment, they developed severe pain in their genital region, and subsequent ultrasound and magnetic resonance imaging confirmed segmental thrombosis in the corpus cavernosum, which required supportive measures. The treatment using low molecular weight heparin, rivaroxaban and non-steroidal anti-inflammatory drugs resolved segmental thrombosis. In conclusion, this case report exemplifies the development of a rare segmental thrombosis in corpus cavernosum and how the medical, scientific, and general community can benefit from documenting clinical manifestations, medically relevant insights into patient care and the management of underreported complications.

10.
Cells ; 12(16)2023 08 15.
Artigo em Inglês | MEDLINE | ID: mdl-37626884

RESUMO

Envenomation by the Indian ornamental tarantula (Poecilotheria regalis) is medically relevant to humans, both in its native India and worldwide, where they are kept as pets. Muscle-related symptoms such as cramps and pain are commonly reported in humans following envenomation by this species. There is no specific treatment, including antivenom, for its envenomation. Moreover, the scientific knowledge of the impact of this venom on skeletal muscle function is highly limited. Therefore, we carried out this study to better understand the myotoxic properties of Poecilotheria regalis venom by determining its effects in cultured myoblasts and in the tibialis anterior muscle in mice. While there was no effect found on undifferentiated myoblasts, the venom affected differentiated multinucleated myotubes resulting in the reduction of fusion and atrophy of myotubes. Similarly, intramuscular administration of this venom in the tibialis anterior muscle in mice resulted in extensive muscle damage on day 5. However, by day 10, the regeneration was evident, and the regeneration process continued until day 20. Nevertheless, some tissue abnormalities including reduced dystrophin expression and microthrombi presence were observed on day 20. Overall, this study demonstrates the ability of this venom to induce significant muscle damage and affect its regeneration in the early stages. These data provide novel mechanistic insights into this venom-induced muscle damage and guide future studies to isolate and characterise individual toxic component(s) that induce muscle damage and their significance in developing better therapeutics.


Assuntos
Mioblastos , Peçonhas , Humanos , Animais , Camundongos , Músculo Esquelético , Causalidade , Fibras Musculares Esqueléticas
11.
TH Open ; 7(2): e168-e183, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-37333023

RESUMO

Envenomings by Russell's viper ( Daboia russelii ), a species of high medical importance in India and other Asian countries, commonly result in hemorrhage, coagulopathies, necrosis, and acute kidney injury. Although bleeding complications are frequently reported following viper envenomings, thrombotic events occur rarely (reported only in coronary and carotid arteries) with serious consequences. For the first time, we report three serious cases of peripheral arterial thrombosis following Russell's viper bites and their diagnostic, clinical management, and mechanistic insights. These patients developed occlusive thrombi in their peripheral arteries and symptoms despite antivenom treatment. In addition to clinical features, computed tomography angiography was used to diagnose arterial thrombosis and ascertain its precise locations. They were treated using thrombectomy or amputation in one case that presented with gangrenous digits. Mechanistic insights into the pathology through investigations revealed the procoagulant actions of Russell's viper venom in standard clotting tests as well as in rotational thromboelastometry analysis. Notably, Russell's viper venom inhibited agonist-induced platelet activation. The procoagulant effects of Russell's viper venom were inhibited by a matrix metalloprotease inhibitor, marimastat, although a phospholipase A 2 inhibitor (varespladib) did not show any inhibitory effects. Russell's viper venom induced pulmonary thrombosis when injected intravenously in mice and thrombi in the microvasculature and affected skeletal muscle when administered locally. These data emphasize the significance of peripheral arterial thrombosis in snakebite victims and provide awareness, mechanisms, and robust strategies for clinicians to tackle this issue in patients.

12.
Toxicon ; 228: 107111, 2023 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-37060927

RESUMO

Snakebite envenomation is regarded as a high-priority neglected tropical disease by the World Health Organisation, as it results in significant loss of lives and permanent disabilities. Russell's viper is one of the important venomous snakes that causes morbidities, mortalities and disabilities in India. The clinical presentation of Russell's viper envenomation is characterised by local envenoming effects including tissue damage, venom-induced coagulopathy, neurotoxicity, and kidney injury. However, venom composition and its mechanisms of toxicity are highly variable even within snakes of the same species including Russell's viper. This variation in venom composition results in a broad range of clinical complications. Here, we present a previously undocumented case of neutrophil-mediated erythrophagocytosis in a healthy 28-year-old female following Russell's viper bite. Systemic envenomation effects and bleeding abnormalities in this patient were corrected by the administration of polyvalent antivenom. Two days later, the patient developed progressive swelling and ecchymosis in the bitten limb. Observed abnormal limits within blood testing were followed up by a peripheral blood smear where it was found that 30% of neutrophils had phagocytosed erythrocytes as they were found within the cytoplasm. The patient underwent a fasciotomy for compartmental syndrome and received packed red cells and a course of corticosteroids. Following this treatment, the patient made a full recovery. This case report outlines a previously undocumented pathological event induced by Russell's viper envenomation, guiding diagnosis and treatment. Clinicians' knowledge of the mechanisms of toxicity of Russell's viper envenomation and its clinical manifestations are essential for improving the treatment of snakebites to achieve positive outcomes.


Assuntos
Daboia , Mordeduras de Serpentes , Animais , Feminino , Neutrófilos , Venenos de Víboras/toxicidade , Mordeduras de Serpentes/tratamento farmacológico , Antivenenos/uso terapêutico , Antivenenos/farmacologia
13.
PLoS Negl Trop Dis ; 17(4): e0011264, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-37099489

RESUMO

With the continued growth of human populations, rural urbanisation and habitat degradation are on the rise, resulting in the displacement of native wildlife and an increase in human-wildlife conflicts. The presence of human habitation and waste often attracts rodents and thereby, snakes, leading to increased snake sightings in homes. To address this problem, snake handlers, who are volunteers that remove and relocate snakes away from human development areas, are called upon. However, snake removal is a high-risk task that poses a risk of envenomation, particularly when dealing with spitting snakes. Several cobra species have the ability to spit venom. If the venom enters a person's eye, it can result in ophthalmic envenomation, which can have serious consequences for their eyesight. Therefore, snake handlers should take precautions, wear suitable eye protection, and use appropriate tools to ensure their safety and that of the snake. In this case, an experienced snake handler was called to remove a spitting cobra, but they were ill-equipped. During the removal, the venom was sprayed across the handler's face, and some of it entered their eye, resulting in ophthalmic envenomation. The handler promptly irrigated their eye, but medical treatment was still necessary. This report highlights the risks and consequences of ophthalmic injury and the importance of wearing appropriate eye protection and taking due care when dealing with venomous species, particularly those that can spit venom. It serves as a reminder that accidents can happen at any time and experienced snake handlers are not exempt from the risks.


Assuntos
Mordeduras de Serpentes , Animais , Humanos , Mordeduras de Serpentes/terapia , Elapidae , Venenos Elapídicos , Antivenenos , Venenos de Serpentes
14.
Toxins (Basel) ; 15(3)2023 03 03.
Artigo em Inglês | MEDLINE | ID: mdl-36977081

RESUMO

Snakebite envenomation (SBE) is a life-threatening medical emergency with a high mortality rate. Common secondary complications following SBE, such as wound infections, are significant due to their impact on worsening local tissue damage and causing systemic infection. Antivenoms are not effective to treat wound infections following SBE. Moreover, in several rural clinical settings, broad-spectrum antibiotics are often used without clear guidelines or based on limited laboratory data, resulting in undesirable side effects and exacerbated treatment costs. Therefore, robust antibiotic strategies should be developed to tackle this critical issue. Currently, there is limited information available on the bacterial profiles of SBE-induced infections and antibiotic susceptibility. Hence, it is essential to improve the knowledge of bacterial profiles and their antibiotic sensitivity in SBE victims to develop better treatment strategies. This study aimed to address this issue by examining the bacterial profiles of SBE victims with a specific focus on Russell's viper envenomation. The most frequently found bacteria in the bites of SBE victims were Staphylococcus aureus, Klebsiella sp., Escherichia coli, and Pseudomonas aeruginosa. Linezolid, clindamycin, colistin, meropenem, and amikacin were some of the most effective antibiotics for commonly grown bacteria in SBE victims. Similarly, ciprofloxacin, ampicillin, amoxiclave, cefixime, and tetracyclin were the least effective antibiotics for common bacteria found in the wound swabs of SBE victims. These data provide robust guidance for infection management following SBE and offer useful insights to aid in designing effective treatment protocols for SBE with serious wound infections in rural areas where laboratory facilities may not be readily available.


Assuntos
Infecções Bacterianas , Mordeduras de Serpentes , Humanos , Antibacterianos/uso terapêutico , Antibacterianos/farmacologia , Antivenenos/uso terapêutico , Infecções Bacterianas/tratamento farmacológico , Mordeduras de Serpentes/complicações , Venenos de Víboras/uso terapêutico
15.
Int J Mol Sci ; 24(5)2023 Feb 22.
Artigo em Inglês | MEDLINE | ID: mdl-36901790

RESUMO

Infections caused by multi-drug-resistant (MDR) bacteria are a global threat to human health. As venoms are the source of biochemically diverse bioactive proteins and peptides, we investigated the antimicrobial activity and murine skin infection model-based wound healing efficacy of a 13 kDa protein. The active component PaTx-II was isolated from the venom of Pseudechis australis (Australian King Brown or Mulga Snake). PaTx-II inhibited the growth of Gram-positive bacteria in vitro, with moderate potency (MICs of 25 µM) observed against S. aureus, E. aerogenes, and P. vulgaris. The antibiotic activity of PaTx-II was associated with the disruption of membrane integrity, pore formation, and lysis of bacterial cells, as evidenced by scanning and transmission microscopy. However, these effects were not observed with mammalian cells, and PaTx-II exhibited minimal cytotoxicity (CC50 > 1000 µM) toward skin/lung cells. Antimicrobial efficacy was then determined using a murine model of S. aureus skin infection. Topical application of PaTx-II (0.5 mg/kg) cleared S. aureus with concomitant increased vascularization and re-epithelialization, promoting wound healing. As small proteins and peptides can possess immunomodulatory effects to enhance microbial clearance, cytokines and collagen from the wound tissue samples were analyzed by immunoblots and immunoassays. The amounts of type I collagen in PaTx-II-treated sites were elevated compared to the vehicle controls, suggesting a potential role for collagen in facilitating the maturation of the dermal matrix during wound healing. Levels of the proinflammatory cytokines interleukin-1ß (IL-1ß), interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α), cyclooxygenase-2 (COX-2) and interleukin-10 (IL-10), factors known to promote neovascularization, were substantially reduced by PaTx-II treatment. Further studies that characterize the contributions towards efficacy imparted by in vitro antimicrobial and immunomodulatory activity with PaTx-II are warranted.


Assuntos
Anti-Infecciosos , Venenos de Cnidários , Colubridae , Humanos , Animais , Camundongos , Staphylococcus aureus , Austrália , Cicatrização , Anti-Infecciosos/farmacologia , Venenos de Cnidários/farmacologia , Colágeno/farmacologia , Peptídeos/farmacologia , Citocinas/farmacologia , Mamíferos
16.
Toxicon ; 225: 107068, 2023 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-36863530

RESUMO

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


Assuntos
Daboia , Mordeduras de Serpentes , Animais , Antivenenos/uso terapêutico , Venenos de Víboras , Mordeduras de Serpentes/tratamento farmacológico , Índia
17.
Int J Mol Sci ; 24(4)2023 Feb 08.
Artigo em Inglês | MEDLINE | ID: mdl-36834844

RESUMO

Annexin A1 (ANXA1) is an endogenous protein, which plays a central function in the modulation of inflammation. While the functions of ANXA1 and its exogenous peptidomimetics, N-Acetyl 2-26 ANXA1-derived peptide (ANXA1Ac2-26), in the modulation of immunological responses of neutrophils and monocytes have been investigated in detail, their effects on the modulation of platelet reactivity, haemostasis, thrombosis, and platelet-mediated inflammation remain largely unknown. Here, we demonstrate that the deletion of Anxa1 in mice upregulates the expression of its receptor, formyl peptide receptor 2/3 (Fpr2/3, orthologue of human FPR2/ALX). As a result, the addition of ANXA1Ac2-26 to platelets exerts an activatory role in platelets, as characterised by its ability to increase the levels of fibrinogen binding and the exposure of P-selectin on the surface. Moreover, ANXA1Ac2-26 increased the development of platelet-leukocyte aggregates in whole blood. The experiments carried out using a pharmacological inhibitor (WRW4) for FPR2/ALX, and platelets isolated from Fpr2/3-deficient mice ascertained that the actions of ANXA1Ac2-26 are largely mediated through Fpr2/3 in platelets. Together, this study demonstrates that in addition to its ability to modulate inflammatory responses via leukocytes, ANXA1 modulates platelet function, which may influence thrombosis, haemostasis, and platelet-mediated inflammation under various pathophysiological settings.


Assuntos
Anexina A1 , Animais , Humanos , Camundongos , Anexina A1/metabolismo , Plaquetas/metabolismo , Inflamação/metabolismo , Neutrófilos/metabolismo , Peptídeos/farmacologia , Receptores de Formil Peptídeo/metabolismo , Receptores de Lipoxinas/metabolismo
18.
Toxicon ; 224: 107037, 2023 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-36690089

RESUMO

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


Assuntos
Daboia , Síndromes Neurotóxicas , Mordeduras de Serpentes , Animais , Mordeduras de Serpentes/tratamento farmacológico , Antivenenos/uso terapêutico , Venenos de Víboras , Síndromes Neurotóxicas/tratamento farmacológico
19.
Toxicon X ; 17: 100147, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36632238

RESUMO

Snakebite envenoming (SBE) predominantly affects rural impoverished communities that have limited access to immediate healthcare. These communities often hold numerous myths/misbeliefs about snakes and SBE. Moreover, healthcare professionals who practice in rural regions often work in unstable situations with limited medical infrastructure and therefore, lack sufficient knowledge/experience and confidence in the clinical management of SBE. Due to the lack of reliable statistics on the true burden of SBE, developing health policies for this condition by relevant authorities may be difficult. Hence, it is critical to improve awareness about SBE among rural communities, healthcare professionals and health authorities using robust multifaceted community health education approaches. Here, we describe the design, development, implementation, and impact of distinctive community health education approaches that we used in India and Brazil. A wide range of educational tools including information leaflets, posters, pocket guides, learning materials for healthcare professionals and short/long video documentaries were developed in local languages and used to engage with target communities through direct assemblies as well as mass/traditional and social media. Notably, we used diverse methods to determine the impact of our programs in improving awareness, treatment-seeking behaviour, and clinical practice. The people-centred approaches that we used were inclusive and highly impactful in instigating fundamental changes in the management of SBE among rural communities. The resources and approaches presented in this article can be easily adapted for wider use in other countries in order to collectively reduce SBE-induced deaths, disabilities and socioeconomic ramifications.

20.
Toxins (Basel) ; 14(12)2022 11 22.
Artigo em Inglês | MEDLINE | ID: mdl-36548714

RESUMO

India suffers the highest incidence of snakebite envenomation (SBE) in the world. Rural communities within India and other countries have long-held cultural beliefs surrounding snakes and SBE treatments, with snake statues present in numerous Hindu temples. While most cultural beliefs are well respected and do not affect anyone, some people worship live venomous snakes without any safety precautions. Moreover, they practice various inappropriate first aid and traditional treatments that exacerbate SBE-induced complications. We report an unusual case of SBE on the tongue of a patient who was bitten while worshipping Russell's viper following the advice of an astrologer based on the appearance of a snake in the patient's dream. Following the bite, the tongue was deeply incised by the priest as a first aid to mitigate SBE-induced complications. The patient suffered profuse bleeding and swelling of the tongue resulting in difficulties in intubating them. The patient regained consciousness after antivenom administration, intranasal ventilation, and blood removal from the mouth. The tongue underwent extensive surgery to restore movement and function. This report advises caution to those undertaking the extremely risky practice of worshipping live snakes and emphasises the urgent need to develop and enforce policies to mitigate such actions and educate rural communities.


Assuntos
Daboia , Mordeduras de Serpentes , Animais , Primeiros Socorros , Mordeduras de Serpentes/complicações , Mordeduras de Serpentes/terapia , Mordeduras de Serpentes/epidemiologia , Antivenenos/uso terapêutico , Língua , Venenos de Víboras
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