Bothrops Moojeni Snake Venom: A Source of Potential Therapeutic Agents Against Hemostatic Disorders

Abstract Hemostasis is a complex set of biological processes responsible for blood fluidity within normal vessels and for the physiological interruption of bleeding in cases of vascular injury. Bothrops moojeni snake venom is rich in bioactive compounds of pharmacological and clinical interest since its protein components are capable of interfering with many points of the hemostatic process. Here, we present the B. moojeni venom proteins that affect hemostasis and discuss their pharmacological and clinical potential. This systematic review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) protocol. Data were obtained from the CAPES Journal Portal database, using the terms "Bothrops" AND "hemostasis", in a search for scientific articles made available in the last 20 years. Many components isolated from B. moojeni snake venom are characterized for their effect on hemostasis and possible application in the diagnosis and treatment of hemostatic disorders.

First case of envenomation in humans caused by the banded cat-eyed snake Leptodeira annulata (Linnaeus, 1758) (Squamata: Dipsadidae) in Brazil

ABSTRACT A 22-year-old female researcher was bitten by a Leptodeira annulata on the index finger of the left hand during a contention activity. After removing the snake, a little bleeding and redness was observed in the bite region, accompanied by fang marks. Thirty minutes later, edema had progressed to the dorsum of the hand. After four hours, edema persisted, but the bitten area was slightly whitened. Treatment consisted of antibiotics and anti-inflammatory drugs. The edema resolved completely and disappeared after 48 hours. Overall, this report presents the first case of envenomation in humans caused by Leptodeira annulata in Brazil.

Conhecimentos sobre o manejo de vítimas do acidente botrópico no serviço de emergência / Knowledge about botropic accident victim management in emergency service / Conocimiento sobre el manejo de víctimas de accidentes botópicos en emergencia

Objetivo: identificar o conhecimento da equipe de enfermagem, no manejo do paciente vítima de acidente botrópico no serviço de emergência. Métodos: estudo descritivo, exploratório e com abordagem qualitativa. Desenvolvido em 2019, com profissionais da equipe de enfermagem do setor de emergência adulto de um Hospital Universitário. Utilizou-se entrevistas semiestruturadas, transcritas e analisadas por meio de estatística descritiva simples e análise de conteúdo. Resultados: participaram do estudo 34 profissionais da equipe de enfermagem, sendo 82% do sexo feminino, com média de idade de 37 anos. A análise de conteúdo revelou três categorias: conhecimento sobre acidentes por animais peçonhentos, trajetória acadêmica e profissional no contexto de animais peçonhentos e manejo da equipe de enfermagem do paciente vítima de acidente botrópico. Conclusão: os resultados demonstram o conhecimento e condutas da equipe de enfermagem frente ao acidente botrópico e evidenciam a necessidade de sensibilizar a equipe de enfermagem quanto ao reconhecimento do acidente ofídico, especialmente com relação às características apresentadas pelo animal peçonhento e as manifestações clínicas apresentadas pelo paciente. (AU)

Objective: to identify the knowledge of the nursing staff in dealing with bothropic accident victims in the emergency service. Methods: descriptive, exploratory study with a qualitative approach. Developed in 2019, with professionals from the nursing staff of the adult emergency sector of a University Hospital. A semi-structured interview was used, transcribed and analyzed using simple descriptive statistics and content analysis. Results: 34 professionals from the nursing team participated in the study, being 82% female, with an average age of 37 years. The content analysis revealed three categories: knowledge about accidents caused by poisonous animals, academic and professional trajectory in the context of poisonous animals and management of the nursing team to the patient victim of bothropic accidents. Conclusão: the results demonstrate the knowledge and behaviors of the nursing staff in face of bothropic accidents and highlight the need to sensitize the nursing staff regarding the recognition of the snakebite accident, especially regarding the characteristics presented by the venomous animal and the clinical manifestations presented by the patient. (AU)

Objetivo: identificar los conocimientos del equipo de enfermería en el manejo del paciente víctima de accidente botópico en el servicio de urgencias. Métodos: estudio descriptivo, exploratorio con abordaje cualitativo. Desarrollado en 2019, con profesionales del personal de enfermería del servicio de urgencias de adultos de un Hospital Universitario. Se utilizó una entrevista semiestructurada, transcrita y analizada mediante estadística descriptiva simple y análisis de contenido. Resultados: participaron en el estudio 34 profesionales del equipo de enfermería, de los cuales el 82% eran mujeres, con una edad promedio de 37 años. El análisis de contenido reveló tres categorías: conocimiento sobre accidentes causados por animales venenosos, trayectoria académica y profesional en el contexto de animales venenosos, y manejo del equipo de enfermería al paciente víctima de accidentes bottrópicos. Conclusión: los resultados demuestran el conocimiento y conducta del equipo de enfermería ante el accidente bottrópico y muestran la necesidad de sensibilizar al personal de enfermería sobre el reconocimiento del accidente de la serpiente, especialmente en lo que respecta a las características que presenta el animal venenoso y las manifestaciones clínicas que presenta el paciente. (AU)

Epidemiología y características clínicas de las mordeduras de serpientes venenosas en el norte de la Amazonía del Ecuador (2017-2021) / Epidemiology and clinical features of venomous snake bites in the Northern Amazon of Ecuador (2017-2021)

Introducción. En Ecuador, las mordeduras de serpientes venenosas son un problema de salud pública. Sin embargo, no existe información hospitalaria reciente desde la Amazonía. Objetivo. Analizar retrospectivamente las características clínico-epidemiológicas de las mordeduras de serpientes en pacientes ingresados en un hospital de la Amazonía del Ecuador. Materiales y métodos. Se llevó a cabo un estudio transversal en el hospital provincial de Nueva Loja (Sucumbíos), que colinda con Colombia, 2017-2021. La información sobre las variables demográficas, epidemiológicas y clínicas, y la condición al egreso hospitalario, se obtuvieron de la ficha epidemiológica del Ministerio de Salud Pública. Resultados. En cinco años se hospitalizaron 147 pacientes (29,4 por año), sin que se presentaran muertes. Corresponden a 26, 34, 32, 29 y 26 casos, en el 2017, 2018, 2019, 2020 y 2021, respectivamente. Según el sexo, los más afectados fueron los hombres (n=99; 67,3 %), según el grupo etario, los de 21 a 30 años (n=28; 19,0 %) y, según la raza, los de etnia mestiza (n=94; 63,9 %), estudiantes y agricultores. La mediana de edad fue de 28 años (rango: 4 a 81). Hubo mayor prevalencia en abril, junio y septiembre. Todos los accidentes fueron causados por serpientes Viperidae. Veinte (13,6 %) casos fueron leves, 90 (61,2 %), moderados, y 37 (25,2 %), graves. La mordedura fue más frecuente en los pies (45 casos). El 53,1 % recibió suero antiofídico antes de la hospitalización y en el 19,8 % de los pacientes se colocó un torniquete. La mediana de tiempo de llegada al hospital fue de 5 horas (rango: 1-192), y lo más frecuente fue entre 2 y 3 horas (41 casos). No se encontraron diferencias estadísticamente significativas según la gravedad del caso. Conclusiones. Se evidenció una gran prevalencia de mordeduras de serpientes en el norte de la región amazónica-Ecuador, con mayor incidencia en la estación lluviosa y todas causadas por Viperidae. Es importante resaltar la mortalidad nula. Las campañas informativas sobre prevención y primeros auxilios, como la desmotivación del uso de torniquetes, serían fundamentales para reducir los casos, especialmente, en los grupos vulnerables.

Introduction: In Ecuador, poisonous snakebites are a public health problem. However, there is no recent hospital information from the Amazon. Objective: To retrospectively analyse the clinical-epidemiological characteristics of snakebites in patients admitted to a hospital in the Ecuadorian Amazon. Materials and methods: This is a cross-sectional study conducted at the Nueva Loja-Sucumbíos Provincial Hospital, bordering Colombia (2017-2021). Demographic, epidemiological and clinical variables, and condition at hospital discharge, were obtained from the epidemiological file of the Ministerio de Salud Pública. Results: In 5 years, 147 patients (29.4 per year) were hospitalized with no mortality. They corresponded to 26, 34, 32, 29 and 26 cases, in 2017, 2018, 2019, 2020 and 2021, respectively. Men with 99 (67.3%), aged 21-30 years with 28, mixed race with 94 cases, students, and farmers, were the most affected. The most affected (99; 67.3%) were men, people 21 to 30 years-old (28; 19.0%), mestizos (94; 63.9%), students, and farmers. The median age was 28 (range: 4-81) years. Prevalence was higher in April, June, and September. All accidents were caused by Viperidae snakes. Twenty (13.6%) cases were mild, (61.2%) were moderate and 37 (25.2%) were severe. The feet with 45 were the most bitten. Pre-hospitalization anti-venom serum was received by 53.1% and tourniquet by 19.8% patients. Median hospital arrival time was 5 (range 1-192) hours, mostly between 2-3 hours with 41 cases. No statistically significant differences were found considering the severity. Conclusions: A high prevalence of snakebites was evidenced in the north of the Amazon in Ecuador, with a higher incidence in the rainy season and all by Viperidae species. It is important to highlight the null mortality. Information campaigns on prevention and first aid, such as discouraging the use of tourniquets, especially among vulnerable groups.

Knowledge on prevention and management of snake bite among adults in rural area of West Bengal

Background: Snake bite and its consequences may be largely prevented with adequate knowledge. Better knowledge can lead to positive attitude and subsequently good practices. Hence, it is of utmost need that people should have adequate knowledge regarding snake bite and its management. Aims and Objectives: The aims of this study were to assess the knowledge regarding prevention and management of snake bite among adults in a rural area of West Bengal and to find out any association between sociodemographic profile and knowledge on prevention as well as management of snake bite among the study participants. Materials and Methods: A community-based and observational descriptive study was conducted in the rural field practice area of Medial College, Kolkata, West Bengal for of 2 months. The study participants who were willing to participate in the study and gave written informed consent were included in the study. A pre-designed, pre-tested, and semi-structured data collection form was used. It was developed based on similar type of previous studies and was modified according to the local culture. The data collection form comprised sociodemographic profile of the study participants, their knowledge regarding snake bite, and its prevention and availability of first aid management. Results: A total of 134 participants were included in the study. The mean age was 45.81 ± 8.00 years. It was observed that majority of the study subjects believed in the knowledge that all types of snakes are poisonous (93.2%) and leads to death (90.3%). First aid measures such as application of tourniquet that was seen in only 4.4% of the cases. However, more than half of the study subjects (71.6%) believed in sucking the venom out of the wound. It was noted that higher education status, improved social class had better knowledge score of snake bite prevention and management as compared to their counterparts and this association was found to be statistically significant (P < 0.001). Conclusion: Knowledge of the study subjects on snake bite and its prevention is good, but still a large number of participants have inadequate knowledge on snake bite and its prevention. Community-based awareness program on prevention and management of snake bite, use of personal protective measures, and training of peripheral health workers ware specifically recommended.

Genomic, transcriptomic, and epigenomic analysis of a medicinal snake, Bungarus multicinctus, to provides insights into the origin of Elapidae neurotoxins

The many-banded krait, Bungarus multicinctus, has been recorded as the animal resource of JinQianBaiHuaShe in the Chinese Pharmacopoeia. Characterization of its venoms classified chief phyla of modern animal neurotoxins. However, the evolutionary origin and diversification of its neurotoxins as well as biosynthesis of its active compounds remain largely unknown due to the lack of its high-quality genome. Here, we present the 1.58 Gbp genome of B. multicinctus assembled into 18 chromosomes with contig/scaffold N50 of 7.53 Mbp/149.8 Mbp. Major bungarotoxin-coding genes were clustered within genome by family and found to be associated with ancient local duplications. The truncation of glycosylphosphatidylinositol anchor in the 3'-terminal of a LY6E paralog released modern three-finger toxins (3FTxs) from membrane tethering before the Colubroidea divergence. Subsequent expansion and mutations diversified and recruited these 3FTxs. After the cobra/krait divergence, the modern unit-B of β-bungarotoxin emerged with an extra cysteine residue. A subsequent point substitution in unit-A enabled the β-bungarotoxin covalent linkage. The B. multicinctus gene expression, chromatin topological organization, and histone modification characteristics were featured by transcriptome, proteome, chromatin conformation capture sequencing, and ChIP-seq. The results highlighted that venom production was under a sophisticated regulation. Our findings provide new insights into snake neurotoxin research, meanwhile will facilitate antivenom development, toxin-driven drug discovery and the quality control of JinQianBaiHuaShe.

Fatal intracranial bleedings in a viper bite: A case report / 中华创伤杂志(英文版)

Viper bite envenomation represents a significant occupational hazard among agricultural workers in India. The viper bite envenomation is usually suspected when a patient presents with predominant local symptoms at the bitten site, including pain, swelling, and necrosis. Further, systemic findings such as diffuse intravascular coagulation, hypotension, and shock may alert physicians of viper bite envenomation rather than a neurotoxic snake bite. However, cerebral complications are rare in viper bites but may potentially fatal. Central nervous system involvement in a viper bite is either due to neurotoxins or hemorrhagins present in the venom, which may induce cerebral thrombosis, ischemia, infarction, and hemorrhage. Here we present a case of a previously healthy adult male who succumbed to extensive subarachnoid, intracerebral, and intraventricular hemorrhages involving bilateral cerebral hemispheres following viper snake bite envenomation. This report highlights the importance of anticipating cerebral complications in viper bite envenomation, a rare occurrence. It also emphasizes the need for early antisnake venom administration to prevent and control systemic envenomation and its complications.

Snakebites in Northeastern Brazil: accessing clinical-epidemiological profile as a strategy to deal with Neglected Tropical Diseases

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.

Antileishmanial effects of γCdcPLI, a phospholipase A2 inhibitor from Crotalus durissus collilineatus snake serum, on Leishmania (Leishmania) amazonensis

BACKGROUND Leishmaniasis, a neglected disease caused by the parasite Leishmania, is treated with drugs associated with high toxicity and limited efficacy, in addition to constant reports of the emergence of resistant parasites. In this context, snake serums emerge as good candidates since they are natural sources with the potential to yield novel drugs. OBJECTIVES We aimed to show the antileishmanial effects of γCdcPLI, a phospholipase A2 inhibitor from Crotalus durissus collilineatus snake serum, against Leishmania (Leishmania) amazonensis. METHODS Promastigotes forms were exposed to γCdcPLI, and we assessed the parasite viability and cell cycle, as well as invasion and proliferation assays. FINDINGS Despite the low cytotoxicity effect on macrophages, our data indicate that γCdcPLI has a direct effect on parasites promoting an arrest in the G1 phase and reduction in the G2/M phase at the highest dose tested. Moreover, this PLA2 inhibitor reduced the parasite infectivity when promastigotes were pre-treated. Also, we demonstrated that the γCdcPLI treatment modulated the host cell environment impairing early and late steps of the parasitism. MAIN CONCLUSIONS γCdcPLI is an interesting tool for the discovery of new essential targets on the parasite, as well as an alternative compound to improve the effectiveness of the leishmaniasis treatment.

Completude das notificações dos acidentes por animais peçonhentos no Sistema de Informação de Agravos de Notificação: estudo descritivo, Brasil, 2007-2019 / Completeness of notifications of accidents involving venomous animals in the Information System for Notifiable Diseases: a descriptive study, Brazil, 2007-2019 / Completitud de las notificaciones de accidentes por animales ponzoñosos en el Sistema de Información de Agravamientos de Notificación: estudio descriptivo, Brasil, 2007-2019

Objective: to describe the completeness of notifications of accidents involving venomous animals held on the Notifiable Health Conditions Information System (SINAN), in Brazil and its macro-regions, from 2007 to 2019. Methods: we analyzed essential and non-mandatory fields for snakebite, spider bite and scorpion sting notifications, considering the following completeness categories: Excellent (≤ 5.0% incompleteness), Good (5.0% to 10.0%), Regular (10.0% to 20.0%), Poor (20.0% ≤ 50.0%) and Very Poor (> 50.0%). Proportional change in completeness between 2007 and 2019 was estimated. Results: 1,871,462 notifications were investigated. The "localized manifestations", "systemic manifestations", "case classification", "case progression" and "zone of occurrence" fields had excellent or good completeness. Completeness was regular or poor for the "schooling" and "race/color" fields. The "occupation" field was predominantly poorly or very poorly filled in. There was a proportional worsening in completeness ((VP < 0) in most regions for the "zone of occurrence", "case progression" and "schooling" fields. Conclusion: completeness of most fields improved, although socioeconomic and occupational fields require more attention.

Objetivo: describir la completitud de las notificaciones de envenenamiento por serpientes, arañas y escorpiones en el Sistema de Información de Enfermedades de Declaración - Sinan, en Brasil y regiones, de 2007 a 2019. Métodos: se analizaron campos esenciales y no obligatorios para las notificaciones de ofidismo, aracneismo y escorpionismo, considerando las categorías de completitud: Excelente (≤ 5,0% de incompletitud), Buena (5,0% a 10,0%), Regular (10,0% a 20,0%), Mala (20,0% ≤ 50,0%) y Muy mala (> 50,0%). Se estimó el cambio proporcional en la completitud entre 2007-2019. Resultados: se investigaron 1.871.462 notificaciones. Los campos "manifestaciones locales y sistémicas", "zona de ocurrencia", "clasificación y evolución de casos" presentaron excelente o buena completitud. "Escolaridad" y "raza/color de piel" regular o mala completitud. "Ocupación" fue predominantemente mala/muy mala completitud. "Zona","evolución" y "escolaridad" mostraron empeoramiento proporcional en la completitud en la mayoría de las regiones ((VP < 0). Conclusión: hay mejoría y completitud en la mayoría de los campos, aunque los campos socioeconómico y ocupacional demandan atención.

Objetivo: descrever a completude das notificações de acidentes causados por animais peçonhentos no Sistema de Informação de Agravos de Notificação, no Brasil e macrorregiões, em 2007-2019. Métodos: analisou-se a completude de campos de preenchimento essenciais e não obrigatórios das notificações de ofidismo, araneísmo e escorpionismo, utilizando-se a classificação de "Excelente" (≤ 5,0% de incompletude), "Bom" (5,0% a 10,0%), "Regular" (10,0% a 20,0%), "Ruim" (20,0% e ≤ 50,0%) e "Muito ruim" (> 50,0%); estimou- -se a variação proporcional (VP) da completude. Resultados: foram investigadas 1.871.462 notificações; os campos "manifestações locais", "sistêmicas", "classificação do caso", "evolução do caso" e "zona de ocorrência" apresentaram completude excelente ou boa; "escolaridade" e "raça/cor da pele", completude regular ou ruim; ocupação, completude ruim ou muito ruim; "zona", "evolução do caso" e "escolaridade" apresentaram piora proporcional na completude, na maioria das regiões ((VP < 0). Conclusão: melhorou a completude na maioria dos campos, exceto socioeconômicos e ocupacionais, que demandam maior atenção.

Compartment Syndrome Secondary to Bothrops spp. Envenomation in Triângulo Mineiro, Region, Minas Gerais, Brazil

ABSTRACT Background: Snakebite is a neglected global health problem with high morbidity. We describe compartment syndrome (CS) cases related to snakebites by Bothrops spp. Methods: The medical records of patients admitted with snakebites envenomation were reviewed. Results: Of 47 patients with Bothrops spp. envenomation (4 male; mean age: 42 years), 7 (15%) developed CS. The mean time to antivenom administration was 9.5 hours. The time to fasciotomy was variable. Seven patients developed infection and four had acute kidney injury. Conclusions: The incidence of CS is higher than that reported previously. This may be due to the clinical severity and long delay before administering antivenom.

Snake venom disintegrins update: insights about new findings

ABSTRACT Snake venom disintegrins are low molecular weight, non-enzymatic proteins rich in cysteine, present in the venom of snakes from the families Viperidae, Crotalidae, Atractaspididae, Elapidae, and Colubridae. This family of proteins originated in venom through the proteolytic processing of metalloproteinases (SVMPs), which, in turn, evolved from a gene encoding an A Disintegrin And Metalloprotease (ADAM) molecule. Disintegrins have a recognition motif for integrins in their structure, allowing interaction with these transmembrane adhesion receptors and preventing their binding to proteins in the extracellular matrix and other cells. This interaction gives disintegrins their wide range of biological functions, including inhibition of platelet aggregation and antitumor activity. As a result, many studies have been conducted in an attempt to use these natural compounds as a basis for developing therapies for the treatment of various diseases. Furthermore, the FDA has approved Tirofiban and Eptifibatide as antiplatelet compounds, and they are synthesized from the structure of echistatin and barbourin, respectively. In this review, we discuss some of the main functional and structural characteristics of this class of proteins and their potential for therapeutic use.

Network meta-analysis of the effectiveness and safety of 3 kinds of snake venom hemocoagulase drugs for hemostasis in abdominal surgery / 中国药房

OBJECTIVE To systematically evaluate the hemostatic effect and safety of snake venom hemocoagulase drugs in abdominal surgery， so as to provide evidence-based evidence for clinic. METHODS Retrieved from Embase， Cochrane Library， PubMed， China Biomedical Literature Database， CNKI and Wanfang database， randomized controlled trials （RCTs） about 3 kinds of snake venom hemocoagulase drugs （Hemocoagulase injection， Hemocoagulase Bothrops atrox for injection， Haemocoagulase Agkistrodon for injection） in abdominal surgery were collected from the establishment of the database to Aug. 2023. Screening， quality evaluation， and data extraction were conducted on literature according to the inclusion and exclusion criteria， and Cochrane 5.1 was used for literature quality evaluation. The risk bias diagram and network diagram were drawn by Stata 15.1 software， and the Bayesian network meta-analysis was carried out by using R 3.6.2 software and Markov chain-Monte Carlo method. RESULTS A total of 11 studies were included， involving 1 401 patients， 852 in the study group， and 549 in the control group. In terms of hemostatic effect， Hemocoagulase injection was significantly superior to Haemocoagulase Agkistrodon for injection [MD＝－2.45， 95%CI （－4.39，－0.24）， P＜0.05]， and the probability of reducing intraoperative bleeding was ranked as follows： Hemocoagulase injection＞hemocoagulase B. atrox for injection＞Haemocoagulase Agkistrodon for injection； in terms of safety， there was no statistically significant difference between the three snake venom hemocoagulase drugs and placebo （P＞0.05）. CONCLUSIONS The hemostatic effect of Hemocoagulase injection in abdominal surgery is significantly better than that of Haemocoagulase Agkistrodon for injection； all three snake venom hemocoagulase drugs have good safety.

Efficacy of galantamine combined with Fufang Haishe Jiaonang in the treatment of Alzheimer's disease in 52 patients / 中国基层医药

Objective:To investigate the efficacy of galantamine combined with Fufang Haishe Jiaonang in the treatment of Alzheimer's disease and its effects on serum levels of inflammatory factors, Aβ1-42 protein, and Tau protein. Methods:A total of 104 patients with Alzheimer's disease who received treatment in Jiaozhou People's Hospital from January 2019 to January 2021 were included in this study. They were randomly divided into a control group and an observation group ( n = 52/group). The control group was given galantamine treatment. The observation group was given galantamine combined with Fufang Haishe Jiaonang. All patients were treated for 3 months. Clinical efficacy was compared between the two groups. Before and after treatment, serum inflammatory factor, Aβ1-42 protein, Tau protein, Mini-Mental State Examination score, and The Quality of Life in Alzheimer's Disease Seale score were compared between the two groups. Adverse reactions were observed during the treatment. Results:Total response rate in the observation group was significantly higher than that in the control group [92.31% (48/52) vs. 76.92% (40/52), χ2 = 4.73, P < 0.05]. After treatment, serum levels of interleukin-6, interleukin-8, tumor necrosis factor-alpha, and Tau protein in the observation group were significantly lower than those in the control group, and Aβ1-42 protein level in the observation group was significantly higher than that in the control group ( t = 16.78, 6.94, 5.16, 2.91, 2.55, all P < 0.05). After treatment, Mini-Mental State Examination score and The Quality of Life in Alzheimer's Disease (QOL-AD) Seale score were increased in each group ( t = 13.48, 6.34, 18.58, 14.45, all P < 0.001), and they were significantly higher in the observation group than the control group ( t = 5.86, 7.25, both P < 0.05). There was no significant difference in the incidence of adverse reactions between the two groups ( P > 0.05). Conclusion:Galantamine combined with Fufang Haishe Jiaonang for the treatment of Alzheimer's disease can better reduce clinical symptoms and signs, regulate serum levels of inflammatory factors, Aβ1-42 protein, and Tau protein, and improve the mental state and quality of life.

Renal and hepatic changes in a case of envenomation by snake bite: Case report and review of literature

Snake bite is a major health hazard, moreover in tropical countries where the density of snakes, frequent human contact, lack of diagnostic and treatment facilities further add-on to the high morbidity and mortality. No organ escapes the effect of envenomation from Heart to liver and kidney, CNS to local bite site. While the effect of snake venom on kidney has been documented, the literature available on the pathological effects of envenomation in human liver is lacking. We present a case of an elderly male with renal and hepatic manifestations of envenomation.

Mordeduras de ofidios en mano pediátrica y sus complicaciones locales / Snake bites in pediatric hand and their local complications / Mordidas de serpentes de mão pediátricas e suas complicações locais

Introducción: el envenenamiento por mordedura de ofidios es reconocido como un problema de salud pública según la Organización Mundial de la Salud. La baja incidencia sumada a la diversidad de presentaciones clínicas, edades, topografías afectadas, así como los diferentes protocolos en la bibliografía existente sobre algunos aspectos del tratamiento, hacen difícil el manejo sistematizado de estos pacientes. El objetivo de este trabajo es realizar una revisión sistemática de la literatura sobre mordedura de serpientes en pacientes pediátricos con afectación en mano y miembro superior, haciendo hincapié en la conducta frente las complicaciones loco-regionales. Por importancia y frecuencia destacamos al síndrome compartimental, las flictenas y las infecciones. Metodología: se realizó una búsqueda bibliográfica en MedLine/PubMed con las palabras clave: "Snake Bite hand Children" y "Snake Bite compartimental syndrome". Se incluyeron los artículos publicados en los últimos 10 años (2012 al 2022). Resultados: la búsqueda de artículos ante las palabras "Snake Bite hand Children" resultó en 20 articulos y la busqueda ante las palabras "Snake Bite compartimental syndrome" derivó en 34. Luego de aplicar los criterios de inclusión y exclusión se obtuvieron 30 artículos para el análisis. Conclusiones: la población pediátrica se encuentra más expuesta a las mordeduras por serpientes y a su vez a presentar lesiones más severas. El tratamiento del síndrome compartimental continúa siendo un tema de debate. El veneno inoculado puede simular un síndrome compartimental que puede revertir sin fasciotomías con el tratamiento adecuado. Igualmente, ante síntomas y signos claros de síndrome compartimental se sugiere realizar fasciotomías frente a las graves secuelas potenciales. Ante la aparición de flictenas, el destechado cuidadoso de la misma es un tratamiento adecuado. La mayoría de los autores coinciden con el tratamiento profiláctico con antibioticoterapia.

Introduction: Ophidian bite poisoning is recognized as a public health problem by the World Health Organization. The low incidence added to the diversity of clinical presentations, ages, affected topographies, as well as the different protocols in the existing literature on some aspects of treatment, make the systematized management of these patients difficult. The aim of this work is to carry out a systematic review of the literature on snakebite in pediatric patients with hand and upper limb involvement, with emphasis on the management of loco-regional complications. In terms of importance and frequency, we highlight compartment syndrome, phlyctenas and infections. Methodology: a literature search was carried out in MedLine/PubMed with the keywords: "Snake Bite hand Children" and "Snake Bite compartment syndrome". Articles published in the last 10 years (2012 to 2022) were included. Results: the search for articles with the words "Snake Bite hand Children" resulted in 20 articles and the search for the words "Snake Bite compartment syndrome" resulted in 34 articles. After applying the inclusion and exclusion criteria, 30 articles were obtained for the analysis. Conclusions: the pediatric population is more exposed to snake bites and in turn to present more severe lesions. The treatment of compartment syndrome continues to be a subject of debate. Inoculated venom can simulate a compartment syndrome that can be reversed without fasciotomies with proper treatment. Likewise, in the presence of clear symptoms and signs of compartment syndrome, fasciotomies are suggested because of the serious sequelae generated. In the event of the appearance of phlyctenas, careful unroofing of the phlyctenas would be an appropriate treatment. Most authors agree with prophylactic treatment with antibiotic therapy.

Introdução: O envenenamento por mordidas ofídias é reconhecido como um problema de saúde pública pela Organização Mundial da Saúde. A baixa incidência, juntamente com a diversidade de apresentações clínicas, idades, topografias afetadas, bem como os diferentes protocolos da literatura existente sobre alguns aspectos do tratamento, tornam difícil o gerenciamento sistemático desses pacientes. O objetivo deste trabalho é realizar uma revisão sistemática da literatura sobre mordida de cobra em pacientes pediátricos com envolvimento de mãos e membros superiores, com ênfase no gerenciamento de complicações loco-regionais. Em termos de importância e freqüência, destacamos a síndrome compartimental, as flectenas e as infecções. Metodologia: foi realizada uma pesquisa bibliográfica no MedLine/PubMed com as palavras-chave: "Snake Bite hand Children" e "Snake Bite compartment syndrome". Os artigos publicados nos últimos 10 anos (2012 a 2022) foram incluídos. Resultados: a busca de artigos usando as palavras "Snake Bite hand Children" resultou em 20 artigos e a busca das palavras "Snake Bite compartment syndrome" resultou em 34 artigos. Após a aplicação dos critérios de inclusão e exclusão, foram obtidos 30 artigos para análise. Conclusões: a população pediátrica está mais exposta às picadas de cobra e, por sua vez, a lesões mais graves. O tratamento da síndrome compartimental continua a ser motivo de debate. O veneno inoculado pode simular uma síndrome de compartimento que pode ser revertida sem fasciotomias com tratamento apropriado. Da mesma forma, se houver sinais e sintomas claros de síndrome compartimental, são sugeridas fasciotomias por causa das severas seqüelas. Se as flectenas aparecerem, o desenrolamento cuidadoso das flectenas seria um tratamento apropriado. A maioria dos autores concorda com o tratamento profilático com a antibioticoterapia.

Lesión renal aguda secundaria a mordedura de serpiente del género bothrops: a propósito de un caso

Introducción: el accidente ofídico es una intoxicación ocasionada por la inoculación de veneno a través de la mordedura de una serpiente, la cual genera alteraciones locales y sistémicas. Dicho evento representa un importante problema de salud pública en los países en vía de desarrollo debido a su alta frecuencia y gravedad. Las serpientes del género Bothrops son responsables de la mayoría de los accidentes y esto se debe, en parte, a su amplia distribución geográfica y comportamiento agresivo cuando se sienten amenazadas. La lesión renal aguda es una causa importante de mortalidad en pacientes con mordedura de serpientes de este género. Objetivo: describir el caso de un paciente femenino con lesión renal aguda inducida por mordedura de serpiente del género Bothrops. Simultáneamente se detallan los datos epidemiológicos más relevantes de dicha entidad, sus factores de riesgo, los posibles mecanismos fisiopatológicos que explican la génesis de la misma, su diagnóstico y manejo clínico. Se resalta la importancia de su identificación precoz y tratamiento oportuno. Presentación del caso: se presenta el caso de una paciente de 40 años que ingresa a una institución de cuarto nivel de complejidad por presentar lesión renal aguda y coagulopatía por consumo secundario a mordedura de serpiente del género Bothrops, con presencia de sangrado vaginal y hematuria que progresa a anuria y hematemesis, requiriendo transfusión de hemoderivados y terapia de reemplazo renal, medidas con las cuales presentó una evolución clínica favorable. Discusión y conclusión: la lesión renal aguda asociada a la mordedura de serpientes del género Bothrops es una complicación clínica común y potencialmente mortal que no debe ser olvidada. Los eventos fisiopatológicos responsables de esta complicación incluyen mecanismos inmunológicos, trastornos de la coagulación, pigmenturia, nefrotoxicidad directa y la respuesta inflamatoria con efectos hemodinámicos sistémicos y renales. Se hace imprescindible el conocimiento de dicha entidad en aras de reconocerla de forma precoz e instaurar su tratamiento oportuno con el fin de reducir sus complicaciones potencialmente fatales.

Introduction: The ophidian accident is an intoxication caused by the inoculation of venom through the bite of a snake, which generates local and systemic alterations. This event represents an important public health problem in developing countries due to its high frequency and severity. Snakes of the genus Bothrops are responsible for the majority of accidents, and this is partly due to their wide geographic distribution and aggressive behavior when threatened. Acute kidney injury is an important cause of mortality in patients with snake bites of this genus. Purpose: To describe the case of a female patient with bothrops snakebite-induced acute kidney injury. Simultaneously, the most relevant epidemiological data of said entity, its risk factors, the possible pathophysiological mechanisms that explain its genesis, its diagnosis and clinical management are detailed. The importance of its early identification and timely treatment is highlighted. Case presentation: We present the case of a 40-year-old female patient who was admitted to a fourth level of complexity institution due to acute kidney injury and consumption coagulopathy secondary to bothrops snakebite, with the presence of vaginal bleeding and hematuria that progressed to anuria. and hematemesis; requiring transfusion of blood products and renal replacement therapy, measures with which she presented a favorable clinical evolution. Conclusion and discussion: Acute kidney injury associated with the bite of bothrops snakes is a common and life-threatening clinical complication that should not be overlooked. The pathophysiological events responsible for this complication include immunological mechanisms, coagulation disorders, pigmenturia, direct nephrotoxicity, and the inflammatory response with systemic and renal hemodynamic effects. Knowledge of this entity is essential in order to recognize it early and establish its timely treatment in order to reduce its potentially fatal complications.

Massive acute ischemic stroke after Bothrops spp. envenomation in southwestern Colombia: Case report and literature review / Accidente cerebrovascular isquémico agudo masivo por veneno de Bothrops spp. en el suroccidente de Colombia: reporte de caso y revisión de la literatura

Bothrops spp. envenomation and its relationship with ischemic stroke has complex pathogenesis. Local effects such as edema, pain, redness, necrosis, and systemic manifestations like coagulation disorders, thrombosis, renal failure, and hemorrhage have been reported. Hemorrhagic stroke is a common neurological complication but ischemic stroke is poorly understood. We present here the case of a 50-year-old male with no comorbidities referred from a rural area in southwest Colombia with a Bothrops spp. snakebite on the left hand. On admission, the patient presented with a deterioration of consciousness and required mechanical ventilation assistance. The MRI showed multiple ischemic areas in the bilateral frontal- temporal and occipital regions. Two months later, the patient had a favorable resolution, although central paresis in the III and VI cranial nerves and positive Babinski's sign persisted. As already mentioned, the pathophysiology of ischemic stroke due to snakebite is complex but the procoagulant activity of the venom components, the hypovolemic shock, the endothelial damage, and the thromboinflammation can explain it, and although it rarely occurs, it should be considered as a complication of ophidian accidents caused by Bothrops spp.

La mordedura de serpientes Bothrops spp. y el ataque cerebrovascular isquémico tienen una patogenia compleja. Se reconocen efectos locales como edema, dolor, enrojecimiento y necrosis, así como manifestaciones sistémicas como trastornos de la coagulación, trombosis, insuficiencia renal y hemorragia, por lo que el accidente cerebrovascular hemorrágico es una complicación neurológica común, pero, en cambio, el accidente cerebrovascular isquémico es poco conocido. Se presenta el caso de un paciente de 50 años, sin comorbilidades, remitido de una zona rural del suroccidente de Colombia debido a la mordedura de una serpiente Bothrops spp. en su mano izquierda. En el momento del ingreso, el paciente presentaba deterioro de la conciencia y requirió asistencia respiratoria mecánica. Mediante resonancia magnética, se observaron múltiples áreas isquémicas bilaterales en la región fronto-temporal y en la occipital. Dos meses después, el paciente había evolucionado favorablemente, pero persistían la paresia en los pares craneales III y VI y el signo de Babinski. La fisiopatología del accidente cerebrovascular isquémico por mordedura de serpiente es compleja. La actividad procoagulante de los componentes del veneno, el choque hipovolémico, el daño endotelial y la tromboinflamación pueden explicar el accidente cerebrovascular isquémico que, aunque raro, debe considerarse como una complicación del accidente ofídico causado por serpientes Bothrops spp.

Venomous animals in Pernambuco: children at risk / Animais peçonhentos em Pernambuco: crianças em risco

Abstract Objectives: to analyze the epidemiological and clinical aspects of accidents caused by venomous animals in children under 15 years old. Methods: a cross-sectional study with an analytical component using secondary data from Centro de Informação e Assistência Toxicológica de Pernambuco (CIATox-PE), (Poison Center in Pernambuco)), in 2017 to 2019. Notifications of accidents caused were included in the studied age group and evaluated the characteristics of poisoning (animal classification, exposure zone, place and time of the occurrence and specific use of serum therapy), and of the patient (sociodemographic variables, clinical condition and evolution). The analysis performed in STATA® 13.1 presents frequency distribution tables and Pearson's chi-square for comparison. Results: of the 2678 notifications, 82,8% were scorpionism and 10, 8% snakebite. The age group of1 to 9 years old (70.5%) and being male (54.1%) were predominant. Most of the cases occurred in urban area (80.9%), in Recife (67.3%), inside the victim's residence (83.9%) and at night (47.3%). The majority (87.1%) were classified as 'mild severity', 10% received antivenom therapy and one died (by scorpionism). Two cases of snakebite in the workplace were registered. Conclusion: there was a high frequency of accidents caused in the urban area, which may be related to the lack of urban planning and sanitary education. The accidents caused among children in the household environment and the suspicion of child labor in the age group of 10 to 14 years old were also highlighted which favors the development and habits of the venomous animal.

Resumo Objetivos: analisar aspectos epidemiológicos e clínicos dos acidentes por animais peçonhentos em menores de 15 anos. Métodos: estudo transversal com componente analítico utilizando dados secundários do Centro de Informação e Assistência Toxicológica de Pernambuco (CIATox-PE), no período de 2017 a 2019. Foram incluídas as notificações dos acidentes na faixa etária estudada e avaliadas características do envenenamento (classe do animal, zona de exposição, local/turno da ocorrência e uso soroterapia específica) e do paciente (variáveis sociodemográficas, gravidade clínica e evolução). A análise realizada no STATA® 13.1 apresenta tabelas de distribuição de frequência e qui-quadrado de Pearson para comparação. Resultados: das 2678 notificações, 82,8% foram de escorpionismo e 10,8% de ofidismo. Predominaram na faixa etária de 1a 9 anos (70,5%) e sexo masculino (54,1%);ocorreram principalmente na zona urbana (80,9%),no Recife(67,3%), na residência da vítima (83,9%), durante horário noturno (47,3%). A maioria (87,1%) foi classificada como de gravidade leve, 10% receberam soroterapia e ocorreu um óbito (escorpionismo). Registraram-se dois casos de ofidismo em ambiente de trabalho. Conclusão: ressaltam-se os acidentes intradomiciliares entre crianças e a suspeita de trabalho infantil na faixa etária de 10 a 14anos.Os acidentes ocorreram sobretudo na zona urbana provavelmente associado à falta de planejamento e educação sanitária que favorece o desenvolvimento e hábitos do animal peçonhento.

New multienzymatic complex formed between human cathepsin D and snake venom phospholipase A2

Background Cathepsin D (CatD) is a lysosomal proteolytic enzyme expressed in almost all tissues and organs. This protease is a multifunctional enzyme responsible for essential biological processes such as cell cycle regulation, differentiation, migration, tissue remodeling, neuronal growth, ovulation, and apoptosis. The overexpression and hypersecretion of CatD have been correlated with cancer aggressiveness and tumor progression, stimulating cancer cell proliferation, fibroblast growth, and angiogenesis. In addition, some studies report its participation in neurodegenerative diseases and inflammatory processes. In this regard, the search for new inhibitors from natural products could be an alternative against the harmful effects of this enzyme. Methods An investigation was carried out to analyze CatD interaction with snake venom toxins in an attempt to find inhibitory molecules. Interestingly, human CatD shows the ability to bind strongly to snake venom phospholipases A2 (svPLA2), forming a stable muti-enzymatic complex that maintains the catalytic activity of both CatD and PLA2. In addition, this complex remains active even under exposure to the specific inhibitor pepstatin A. Furthermore, the complex formation between CatD and svPLA2 was evidenced by surface plasmon resonance (SPR), two-dimensional electrophoresis, enzymatic assays, and extensive molecular docking and dynamics techniques. Conclusion The present study suggests the versatility of human CatD and svPLA2, showing that these enzymes can form a fully functional new enzymatic complex.