ABSTRACT: Present study aimed for detection, purification, quantification of Sind Krait (Bungarus sindanus) antivenom from chicken eggs and to determine extracted antivenom efficacy in mice. Hens’ three groups were immunized by sub-lethal doses of Sind Krait venom with adjuvant paraffin oil+lecithin. Booster doses were injected subcutaneously on pectorals muscles at multiple sites after every two weeks upto eight weeks. Antibodies-IgY produced against Sind Krait venom was purified form eggs’ yolk by precipitation method with PEG-6000. Purified antivenom-IgY protein contents were quantified by Nanodrop-photometer, purity accessed by SDS-PAGE, specificity checked by Ochterloneys method and titer estimated by indirect ELISA. Antivenom efficacy was assessed in albino mice. Purified antivnom-IgY exhibited single protein band 180-190 kDa on SDS-PAGE under non-reduced condition and two-bands 63 - 65 kDa and 22 - 25 kDa correspondingly under-reduced condition. Immunodiffusion exhibited sharp precipitation lines of immune-complex (venom and extracted-IgY). In all groups (G1, G2 and G3) antivenom level sharply increase from 3rd to 4th week and maintained thereafter. G2 and G3 presented high titer upto 1:2048 dilutions, while G1 showed upto 1:1024 dilutions, as tested by indirect ELISA. In neutralization assay ED50 dose of G2 and G3 obtained antivenom was 400.23 µg/mice for more than twofold LD50 dose of venom and 100% protection was at 508.84 µg/mice that completely neutralized highly lethal dose of venom. But G1 ED50 was 405.66 µg/mice and provides 100% protection at 554.21 µg/mice. Extracted antivenom, against Sind Krait venom were highly pure, and with high neutralization capacity were produced successfully from eggs yolk first time in Pakistan. ABSTRACT detection purification Bungarus sindanus mice Hens sublethal sub oillecithin oil lecithin oil+lecithin AntibodiesIgY Antibodies IgY PEG6000. PEG6000 PEG 6000. 6000 PEG-6000 antivenomIgY Nanodropphotometer, Nanodropphotometer Nanodrop photometer, photometer Nanodrop-photometer SDSPAGE, SDSPAGE SDS PAGE, PAGE ELISA antivnomIgY antivnom 180190 180 190 180-19 nonreduced non reduced twobands bands 6 2 underreduced immunecomplex immune complex extractedIgY. extractedIgY . extracted-IgY) G1, G (G1 rd th thereafter 12048 1 2048 1:204 dilutions 11024 1024 1:102 ED ED5 40023 400 23 400.2 µgmice µg LD LD5 100 50884 508 84 508.8 40566 405 66 405.6 55421 554 21 554.2 pure Pakistan PEG600 600 PEG-600 18019 18 19 180-1 extracted-IgY (G 1204 204 1:20 1102 102 1:10 4002 40 400. 10 5088 50 8 508. 4056 405. 5542 55 554. PEG60 60 PEG-60 1801 180- 120 20 1:2 110 1:1 4 5 PEG6 PEG-6 12 1: 11 PEG-

RESUMO: O presente estudo teve como objetivo a detecção, purificação, quantificação do soro antiofídico em ovos de galinha e determinar a eficácia do soro antiofídico extraído em camundongos. Os três grupos de galinhas foram imunizados por doses subletais de veneno de cobra Sindhi krait com óleo de parafina adjuvante + lecitina. As doses de reforço foram injetadas por via subcutânea nos músculos do peito em vários locais após cada duas semanas até oito semanas. Anticorpos-IgY produzidos contra o veneno de Krait foram purificados da gema de ovo pelo método de precipitação com PEG-6000. Os conteúdos de proteína antiveneno-IgY purificada foram quantificados por fotômetro nanodrop enquanto a pureza foi acessada por SDS-PAGE. A especificidade do antiveneno-IgY foi verificada pelo método de Ochterloneys e o título foi estimado por ELISA indireto. A eficácia do antiveneno foi avaliada em camundongos albinos. A IgY purificada exibiu uma única banda de proteína 180-190 KDa em SDS-PAGE sob condição não reduzida e duas bandas 63 - 65 KDa e 22 - 25 KDa correspondentemente condição sub-reduzida. A imunodifusão exibiu linhas de precipitação nítidas de imunocomplexo (veneno e IgY extraída). Em todos os grupos (G1, G2 e G3) o nível do soro aumentou acentuadamente da 3ª para a 4ª semana e manteve-se a partir daí. G2 e G3 apresentaram títulos elevados até diluições de 1:2048, enquanto G1 apresentou diluições de até 1:1024, testado por ELISA indireto. No ensaio de neutralização, a dose ED50 de antiveneno G2 e G3 obtida foi de 400,23ug/camundongos para mais de duas vezes a LD50 e 100% de proteção foi @ 508,84ug/camundongos que neutralizam completamente a dose altamente letal de veneno. Mas G1 ED50 foi de 405,66ug/camundongos e forneceu 100% de proteção @ 554,21ug/camundongos. Antivenenos extraídos, contra veneno de Bungarus sindanus eram altamente puros, seu título de anticorpos e capacidade de neutralização foram produzidos com sucesso a partir de gemas de ovos de galinhas imunizadas pela primeira vez no Paquistão. RESUMO detecção purificação lecitina AnticorposIgY Anticorpos PEG6000. PEG6000 PEG 6000. 6000 PEG-6000 antivenenoIgY SDSPAGE. SDSPAGE SDS PAGE. PAGE indireto albinos 180190 180 190 180-19 6 2 subreduzida. subreduzida sub reduzida. sub-reduzida extraída. extraída . extraída) G1, G (G1 ª mantevese manteve se daí 12048, 12048 1 2048, 2048 1:2048 11024, 11024 1024, 1024 1:1024 ED ED5 40023ugcamundongos ugcamundongos 400 23ug ug LD LD5 100 50884ugcamundongos 508 84ug 40566ugcamundongos 405 66ug 55421ugcamundongos 554 21ug 554,21ug/camundongos extraídos puros Paquistão PEG600 600 PEG-600 18019 18 19 180-1 (G 1204 204 1:204 1102 102 1:102 40 10 50 55 PEG60 60 PEG-60 1801 180- 120 20 1:20 110 1:10 4 5 PEG6 PEG-6 12 1:2 11 1:1 PEG- 1:

ABSTRACT: Avian-derived IgY is thought to be the best therapy for scorpion bites concerning low-level side effects. The present study analyzed a hypothesis about the neutralization of scorpion venom Androcotonus australis through antibodies produced in the egg yolks of chickens. The venom used for inoculation was obtained from Androctonus australis (yellow fat-tailed scorpion) from southern Punjab, Pakistan. The lethal dose of LD50 against scorpion venom was calculated in chickens and mice. Safe doses were given to egg-laying chickens to produce IgY antibodies. The antivenom IgY antibodies were extracted from the egg yolks of immunized chicken using the polyethylene glycol (PEG) method. Moreover, IgY was confirmed through sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and the Ouchterlony double immunodiffusion assay test. The antibody titers were evaluated by the enzyme-linked immunosorbent assay (ELISA). The neutralisation capacity of extracted anti-scorpion antibodies was tested on mice. The calculated LD50 of scorpion venom for chicken and mice was 4 mg/kg and 2.5 mg/kg, respectively. SDS-PAGE and Ouchterlony double immunodiffusion confirmed the presence of IgY against scorpion venom. The maximum titer value of specific IgY produced against scorpion venom was 3.5 ug/ml. A concentration of 220 ul/LD50 was effective to neutralize 1 mg of scorpion venom. It is suggested that IgY obtained from egg yolks is safe against targeted venom and can be used as an effective alternative to equine IgG antibodies against scorpion envenoming. ABSTRACT Avianderived Avian derived lowlevel low level effects yellow fattailed fat tailed Punjab Pakistan LD LD5 egglaying laying PEG (PEG method Moreover sulfatepolyacrylamide sulfate polyacrylamide SDSPAGE SDS PAGE (SDS-PAGE test enzymelinked enzyme linked ELISA. ELISA . (ELISA) antiscorpion anti mgkg kg 25 2 5 2. respectively 35 3 3. ugml ug ml ug/ml 22 ulLD50 ulLD ul ul/LD5 envenoming (ELISA ulLD5 ul/LD

RESUMO: Acredita-se que a IgY derivada de aves seja a melhor terapia para picadas de escorpião em relação aos efeitos colaterais. O presente estudo teve como objetivo analisar uma hipótese sobre a neutralização do veneno do escorpião Androcotonus australis através de anticorpos produzidos na gema de ovos de galinhas. O veneno usado para inoculação foi obtido de Androctonus australis (escorpião amarelo de cauda gorda) do sul de Punjab, Paquistão. A dose letal de LD50 contra veneno de escorpião foi calculada em galinhas e camundongos. Doses seguras foram dadas a galinhas poedeiras para produzir anticorpos IgY. Os anticorpos antiveneno IgY foram extraídos das gemas de ovos de galinhas imunizadas pelo método do polietilenoglicol (PEG). Além disso, a IgY foi confirmada por eletroforese em gel de poliacrilamida e dodecil sulfato de sódio (SDS-PAGE) e pelo teste de imunodifusão dupla de Ouchterlony. Os títulos de anticorpos foram avaliados pelo ensaio imunoenzimático (ELISA). A capacidade de neutralização dos anticorpos anti-escorpião extraídos foi testada em camundongos. A LD50 calculada do veneno de escorpião para galinhas e camundongos foi de 4 mg/kg e 2,5 mg/kg, respectivamente. SDS-PAGE e imunodifusão dupla Ouchterlony confirmaram a presença de IgY contra veneno de escorpião. O valor máximo do título de IgY específico produzido contra veneno de escorpião foi de 3,5 ug/ml. Uma concentração de 220 ul/LD50 foi considerada eficaz para neutralizar 1 mg de veneno de escorpião. Sugere-se que a IgY obtida da gema do ovo seja segura contra o veneno direcionado e possa ser usada como uma alternativa eficaz aos anticorpos IgG equinos contra o envenenamento por escorpiões. RESUMO Acreditase Acredita se colaterais gorda Punjab Paquistão LD LD5 PEG. PEG . (PEG) disso SDSPAGE SDS PAGE (SDS-PAGE ELISA. ELISA (ELISA) antiescorpião anti mgkg kg 25 2 5 2, respectivamente 35 3 3, ugml ug ml ug/ml 22 ulLD50 ulLD ul ul/LD5 Sugerese Sugere escorpiões (PEG (ELISA ulLD5 ul/LD

Abstract Tityus serrulatus scorpion is responsible for a significant number of envenomings in Brazil, ranging from mild to severe, and in some cases, leading to fatalities. While supportive care is the primary treatment modality, moderate and severe cases require antivenom administration despite potential limitations and adverse effects. The remarkable proliferation of T. serrulatus scorpions, attributed to their biology and asexual reproduction, contributes to a high incidence of envenomation. T. serrulatus scorpion venom predominantly consists of short proteins acting as neurotoxins (α and β), that primarily target ion channels. Nevertheless, high molecular weight compounds, including metalloproteases, serine proteases, phospholipases, and hyaluronidases, are also present in the venom. These compounds play a crucial role in envenomation, influencing the severity of symptoms and the spread of venom. This review endeavors to comprehensively understand the T. serrulatus scorpion venom by elucidating the primary high molecular weight compounds and exploring their potential contributions to envenomation. Understanding these compounds' mechanisms of action can aid in developing more effective treatments and prevention strategies, ultimately mitigating the impact of scorpion envenomation on public health in Brazil. Brazil fatalities modality effects T scorpions reproduction α β, β , β) channels Nevertheless metalloproteases proteases phospholipases hyaluronidases strategies

Snakebite management is largely driven by expert opinion and consensus. However, there are a few large retrospective studies and randomised controlled trials that have improved the quality of medical guidance currently available. South African snakes are different in venomous potential to snakes in other parts of the world, and it behoves the hospital provider and the average medical practitioner to know the current best practice concepts concerning assessment, treatment and antivenom use. The recent South African Snakebite Symposium meeting in July 2022 provided an update and national consensus from which this Hospital Care document is derived.

The coastal regions of Africa are endowed with indigenous wild fruit plants rich in nutritional and medicinal phytochemicals and micronutrients. South African wild fruit plants complement the diet and health needs of rural poor households by providing vital dietary nutrients and remedies for various health concerns, and alleviating food insecurity. Milk plum, Natal plum, wild custard apple, and wild medlar medicinal plants are found mainly in the coastal provinces of South Africa. Studies have established that these plants are good sources of vitamins, essential elements, and bioactive phytocompounds such as flavonoids, phenolic acids, and terpenoids, which demonstrate significant antioxidant, antimicrobial and anti-inflammatory activities. The plants studied possess anti-epileptic, antiplasmodial, and snake antivenom qualities. Here we highlight the views of different reports on ethnopharmacological relevance, phytochemistry, and bioactivity of the selected South African indigenous medicinal plants. We found a research gap in the phytochemical composition and phytopharmacological activity evaluation of Carissa macrocarpa and Englerophytum magalismontanum. SIGNIFICANCE: South African indigenous medicinal plants augment the dietary and other health needs of the rural populace. The phytochemistry and phytopharmacological activities of C. macrocarpa and E. magalismontanum have been only partially studied, hence the need for further studies to examine their worth and possible use in cosmetic product enrichment

Abstract Background: Bivalent freeze-dried neurotoxic (FN) antivenom has been the primary treatment since the 1980s for Taiwan cobra (Naja atra) envenomation in Taiwan. However, envenomation-related wound necrosis is a significant problem after cobra snakebites. In the present study, we analyzed the changes in serum venom concentration before and after antivenom administration to discover their clinical implications and the surgical treatment options for wound necrosis. Methods: The patients were divided into limb swelling and wound necrosis groups. The clinical outcome was that swelling started to subside 12 hours after antivenom treatment in the first group. Serum venom concentrations before and after using antivenoms were measured to assess the antivenom's ability to neutralize the circulating cobra venom. The venom levels in wound wet dressing gauzes, blister fluids, and debrided tissues were also investigated to determine their clinical significance. We also observed the evolutional changes of wound necrosis and chose a better wound debridement timing. Results: We prospectively enrolled 15 Taiwan cobra snakebite patients. Males accounted for most of this study population (n = 11, 73%). The wound necrosis group received more antivenom doses than the limb swelling group (4; IQR:2-6 vs 1; IQR:1-2, p = 0.05), and less records of serum venom concentrations changed before/after antivenom use (p = 0.0079). The necrotic wound site may release venom into circulation and cause more severe envenomation symptoms. Antivenom can efficiently diminish limb swelling in cobra bite patients. However, antivenom cannot reduce wound necrosis. Patients with early debridement of wound necrosis had a better limb outcome, while late or without debridement may have long-term hospital stay and distal limb morbidity. Conclusions: Antivenom can efficiently eliminate the circulating cobra venom in limb swelling patients without wound necrosis. Early debridement of the bite site wound and wet dressing management are suggestions for preventing extended tissue necrosis and hospital stay. Background freezedried freeze dried FN (FN s Naja atra However envenomationrelated related snakebites Methods groups 1 gauzes fluids significance timing Results n 11 73%. 73 73% . 73%) 4 (4 IQR26 IQR 2 6 IQR:2- IQR12, IQR12 2, IQR:1-2 0.05, 005 0.05 , 0 05 0.05) beforeafter 0.0079. 00079 0.0079 0079 0.0079) symptoms longterm long term morbidity Conclusions 7 ( IQR2 IQR:2 IQR1 IQR:1- 00 0.0 0007 0.007 007 IQR: IQR:1 0. 000 0.00

Abstract Many biological activities are described for the Clusiaceae family. Clusia fluminensis, a species from Brazilian flora, is mainly employed for ornamental purposes. This review aimed to depict the current knowledge of C. fluminensis from a bioprospecting standpoint. “Clusia fluminensis” search term was applied in Scopus, Web of Science, PubMed and Bireme databases according to PRISMA-ScR statement. Selected papers on Phytochemistry or Bioactivity followed hand searching procedures. Bioactivity preclinical studies considered in vitro or in vivo biological systems, treated with plant extracts or isolated compounds. The outcomes were compared with standard or no treatment control groups. Critical appraisal of individual trials considered completeness in the research fields. Our results showed that 81% of the selected papers presented high level of completeness, 69% revealed phytochemical parameters and 31% biological applications of plant extracts and isolated compounds. Polyisoprenylated benzophenones, terpenoids, sterols and phenolic compounds were identified. Antiviral, insecticidal and snake antivenom activities were reported. In conclusion, the phytochemical data reinforce the reported activities. Potential applications in personal care, nutritional supplementation and pharmaceutical, food, chemical or textile industries were also identified. Toxicological and phytochemical complementary studies may be required. family flora purposes C standpoint Scopus Science PRISMAScR PRISMA ScR statement procedures systems groups fields 81 69 31 benzophenones terpenoids identified Antiviral conclusion care pharmaceutical food required 8 6 3

ABSTRACT Venomous fish are commonly found in Brazilian waters. The most important marine venomous fish species are stingrays (Dasyatidae, Gimnuridae, Myliobatidae, and Rhinopteridae families), catfish (Ariidae family), scorpionfish and lionfish (both Scorpaenidae family), and toadfish (Batrachoididae family). Meanwhile, Potamotrygonidae stingrays and Pimelodidae catfish are the most important venomous freshwater fish. The mechanisms of envenomation vary and involve various venomous apparatuses and glands. Despite not being highly developed, these venomous apparatuses in fish appear rudimentary, using structures such as fins and rays to inoculate toxins and rarely presenting with specialized structures. Toxins are produced by glandular tissue made up of proteinaceous cells, lacking true glands, and are positioned along the inoculation structures. However, systemic manifestations are rare. No antivenom serum has been developed for any species of American venomous fish. Brazilian venomous fish and their venoms have only recently attracted attention, leading to new studies not only addressing clinical issues in humans, but also exploring the discovery of new active substances with immense pharmacological potential. waters Dasyatidae, Dasyatidae (Dasyatidae Gimnuridae Myliobatidae families, families , families) Ariidae family, family family) both Batrachoididae family. . Meanwhile glands rudimentary cells However rare attention humans potential

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. Background morbidity (CS spp Methods reviewed Results 4 ( male age years, years , years) 15% 15 (15% 95 9 5 9. hours variable injury Conclusions previously 1 (15 (1

Abstract Snakebite envenoming is a major global health problem that kills or disables half a million people in the world’s poorest countries. Identifying the biting snake and its habitat use is key to understanding snakebite eco-epidemiology and optimizing its clinical management. To prevent and combat the neglected snakebite disease, we characterize the morphology, geographic distribution, habitat use, and snakebites of medically important venomous snakes in the state of Rio de Janeiro (Brazil). Despite Philodryas spp. not being considered of medical importance by the Brazilian Ministry of Health, we also explore their data once the bites may require medical intervention, may cause death, and their consequences are underestimated. Methods: We assessed taxonomy and geographic data from specimens housed in scientific collections, the literature, and the Notifiable Diseases Information System. Our data revealed fragility in the morphological characters recommended to distinguish Bothrops jararaca from B. jararacussu, identify the subspecies of Crotalus durissus and distinguish the species of Philodryas. To help identify these species, we present an identification key to the venomous snake species from Rio de Janeiro based on the morphological data collected. We record the genera Bothrops and Micrurus in all mesoregions of the state. Here, we provide the first record of C. durissus in the Serrana region, supporting the hypothesis of geographic expansion of the species in the state. The crotalic antivenom must not be missing in Médio Paraíba, Centro-Sul Fluminense, and Serrana, where the rattlesnake C. durissus occurs. Bothrops bilineatus and Lachesis muta have historical records presented for the first time herein. However, these species are likely endangered or extinct in the state. There were 7,483 snakebites reported between 2001 and 2019, with an annual average of 393.8 cases. The Bothrops genus is responsible for the majority of accidents. The highest number of cases occurred in the Serrana region, the largest pole of family agriculture in Rio de Janeiro. We improve the identification of venomous snake species, better delimit their distribution, and update the number of cases of snakebites, thus providing greater precision in the attention to this problem in Rio de Janeiro. We emphasize the importance of clinical studies to test using bothropic-crotalic antivenom and heparin in all mesoregions to treat B. jararacussu envenomation; and mechanical ventilation, atropine, and anticholinesterases in the emergency health centers in the Metropolitana and Norte Fluminense regions due to the occurrence of the coral M. lemniscatus in these areas. worlds world s countries ecoepidemiology eco epidemiology management disease morphology distribution Brazil. Brazil . (Brazil) spp Health intervention death underestimated Methods collections literature System B collected Here C region Paraíba CentroSul Centro Sul occurs herein However 7483 7 483 7,48 200 2019 3938 393 8 393. accidents bothropiccrotalic bothropic envenomation ventilation atropine M areas (Brazil 748 48 7,4 20 201 39 74 4 7, 2 3

Resumo O envenenamento com serpentes de importância médica é um grande problema de saúde global que mata ou incapacita meio milhão de pessoas nos países mais pobres do mundo. A identificação de serpentes de importância médica e aspectos de sua história de vida é fundamental para compreender a eco-epidemiologia dos acidentes ofídicos e otimizar seu manejo clínico. Para prevenir e combater a doença negligenciada do ofidismo, caracterizamos os dados de morfologia, distribuição, uso de habitat e acidentes ofídicos das serpentes peçonhentas de importância médica no estado do Rio de Janeiro, Brasil. Apesar de Philodryas spp. não serem consideradas de importância médica pelo Ministério da Saúde do Brasil, também apresentamos seus dados porque suas picadas podem exigir intervenção médica, causar morte e suas consequências são subestimadas. Foram avaliados dados morfológicos e de habitat de espécimes pertencentes a coleções cientificas, literatura e dados do Sistema de Informação de Agravos de Notificação. Nossos dados revelaram caracteres morfológicos frágeis recomendados para distinguir Bothrops jararaca e B. jararacussu, para identificar as subespécies de cascavel Crotalus durissus e para distinguir as serpentes cipó Philodryas spp. Para auxiliar na identificação dessas espécies apresentamos uma chave de identificação para as mesmas com base nos dados morfológicos coletados. Registramos os gêneros Bothrops e Micrurus em todas as mesorregiões do estado. Já o soro anticrotálico não pode faltar no Médio Paraíba, Centro-Sul Fluminense e Serrana, onde encontramos a cascavel Crotalus durissus. Aqui estendemos o registro da cascavel pela primeira vez para a região Serrana, corroborando a hipótese da expansão da espécie no estado. Bothrops bilineatus e Lachesis muta possuem registros históricos aqui apresentados pela primeira vez. Essas espécies provavelmente estão ameaçadas ou extintas no estado. Foram 7,483 acidentes entre 2001-2019, com média anual de 393.8. O gênero Bothrops é responsável pela maioria dos acidentes. O maior número de casos ocorreu na região Serrana, maior polo da agricultura familiar do Rio de Janeiro. Aperfeiçoamos a identificação das espécies de serpentes de importância médica, delimitamos melhor sua distribuição e atualizamos os acidentes ofídicos, proporcionando maior precisão na atenção ao ofidismo no estado do Rio de Janeiro. Ressaltamos a importância de estudos clínicos para testar o uso de soro antibotrópico-crotálico e heparina em todas as mesorregiões para o tratamento do ofidismo B. jararacussu e ventilação mecânica, atropina e anticolinesterásicos nos prontos-socorros das regiões Metropolitana e Norte Fluminense pela ocorrência do coral M. lemniscatus. mundo ecoepidemiologia eco epidemiologia clínico morfologia Janeiro Brasil spp subestimadas cientificas Notificação B coletados Paraíba CentroSul Centro Sul Serrana 7483 7 483 7,48 20012019, 20012019 2001 2019, 2019 2001-2019 3938 393 8 393.8 antibotrópicocrotálico antibotrópico crotálico mecânica prontossocorros prontos socorros M lemniscatus 748 48 7,4 2001201 200 201 2001-201 39 393. 74 4 7, 200120 20 2001-20 3 20012 2 2001-2 2001-

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. Background America planning 200 2019 Methods Results 17658 17 658 17,65 period Bothrops bite recovered however 13 2039 20 39 20-3 years workers pain edema ecchymosis neuroparalysis syndrome myolysis March 936 (93 cases, , cases) 705 (70 627 (62 cases. . Conclusions However envenomation attendance 201 1765 1 65 17,6 203 2 3 20- 93 (9 70 (7 62 (6 176 6 17, 9 ( 7

ABSTRACT Crotalic envenomation is responsible for approximately 8%-13% of ophidism cases in Brazil, yet it is associated with the highest mortality among snakes. We describe the case of a patient bitten by a rattlesnake who developed ventilatory muscle paralysis within hours after envenomation. While diaphragmatic paralysis is a rare late neurotoxic event following crotalic envenomation, in this case, paralysis occurred early but was rapidly reversed after antivenom administration. This report discusses potential contributing factors based on a comprehensive literature review. 8%13% 813 8% 13% 8 13 8%-13 Brazil snakes administration review 8%13 81 1 8%-1 8%1 8%-

Acute limb compartment syndrome can occur with cytotoxic snake envenomation. Ultrasound (US) assessment of the affected limb has been suggested as an adjunct to the administration of snakebite polyvalent antivenom to ameliorate the systemic and local effects. US may also aid in the diagnosis of compartment syndrome and the need for fasciotomy to prevent limb loss. This report presents an adult male who had severe soft tissue swelling from a puff adder bite to the wrist and highlights the use of US in assessing and monitoring the degree of swelling in subcutaneous and fascial compartments of the arm. This US monitoring in conjunction with frequent physical examination avoided the need for a fasciotomy and its attendant morbidity, resulting in complete resolution of the swelling and full recovery of limb function.

Abstract Snakebite envenoming is a significant global health challenge, and for over a century, traditional plasma-derived antivenoms from hyperimmunized animals have been the primary treatment against this infliction. However, these antivenoms have several inherent limitations, including the risk of causing adverse reactions when administered to patients, batch-to-batch variation, and high production costs. To address these issues and improve treatment outcomes, the development of new types of antivenoms is crucial. During this development, key aspects such as improved clinical efficacy, enhanced safety profiles, and greater affordability should be in focus. To achieve these goals, modern biotechnological methods can be applied to the discovery and development of therapeutic agents that can neutralize medically important toxins from multiple snake species. This review highlights some of these agents, including monoclonal antibodies, nanobodies, and selected small molecules, that can achieve broad toxin neutralization, have favorable safety profiles, and can be produced on a large scale with standardized manufacturing processes. Considering the inherent strengths and limitations related to the pharmacokinetics of these different agents, a combination of them might be beneficial in the development of new types of antivenom products with improved therapeutic properties. While the implementation of new therapies requires time, it is foreseeable that the application of biotechnological advancements represents a promising trajectory toward the development of improved therapies for snakebite envenoming. As research and development continue to advance, these new products could emerge as the mainstay treatment in the future. challenge century plasmaderived plasma derived infliction However patients batchtobatch batch variation costs outcomes crucial efficacy profiles focus goals species antibodies nanobodies molecules neutralization processes properties time advance future

Abstract Background: The genus Randia L. (Rubiaceae) is native to Americas and highly distributed in tropical areas. Some Randia species are used in traditional medicine in some countries to treat diverse illnesses/symptoms of kidney, circulatory system, lungs, diabetes, cancer, inflammation, and against the bites/stings of snakes and other poisonous animals. Questions: What are the phytochemical compounds previously identified in Randia? What biological activities do they present? Data description: Twenty-eight studies on chemical composition and biological activities of Randia were reviewed. Species names were corroborated in Plants of the World Online and World Flora Online. The site and studied years: Studies of Randia of Americas from 1991 to 2021. Methods: Database reviewed were PubMed, Scopus, Scielo, BVS, DAOJ, Science Direct, Springer Link, Web of Science, and Google Scholar, employing the keywords Randia and its synonym Basanacantha. Results: Six species are the most studied (R. aculeata, R. echinocarpa, R. ferox, R. hebecarpa, R. matudae, and R. monantha). Ethnopharmacology information of 12 species was recovered. One hundred compounds in Randia have been identified (phenolic acids, terpenes, sterols, and others), and diverse biological activities reported in 24 studies (e.g., antimutagenic, antioxidant, and antivenom) have demonstrated for nine species. Conclusions: Biological activities found in some species of Randia support their traditional uses, but only the antivenom effect of Randia aculeata has been demonstrated. Randia species could be a source of bioactive compounds; however, knowledge must be expanded to demonstrate their traditional uses and contribute to the development of strategies for their preservation and rational use.

Resumen Antecedentes: El género Randia L. (Rubiaceae) es originario de América y está altamente distribuido en zonas tropicales. Algunas de sus especies son utilizadas en la medicina tradicional de algunos países para tratar diversos padecimientos/síntomas: renales, circulatorios, pulmonares, diabetes, cáncer, inflamación y contra las mordeduras/picaduras de serpientes y animales ponzoñosos. Preguntas: ¿Cuáles son los compuestos fitoquímicos identificados en Randia? ¿Qué actividades biológicas presentan? Descripción de datos: Se revisaron 28 estudios sobre composición química y actividades biológicas de Randia. La nomenclatura se corroboró en Plants of the World Online y World Flora Online. Sitio y años de estudio: Estudios de Randia de América desde 1991 a 2021. Métodos: Las bases de datos revisadas fueron PubMed, Scopus, Scielo, BVS, DAOJ, Science Direct, Springer Link, Web of Science y Google académico, empleando las palabras clave Randia y su sinónimo Basanacantha. Resultados: Seis especies de Randia son las más estudiadas (R. aculeata, R. echinocarpa, R. ferox, R. hebecarpa, R. matudae y R. monantha). Se recuperó información etnofarmacológica de 12 especies. Cien compuestos han sido identificados en Randia (ácidos fenólicos, terpenos, esteroles y otros) y demostrado diversas actividades biológicas en 24 estudios (e.g., antimutagénica, antioxidante, antiveneno) para nueve especies. Conclusiones: Las actividades biológicas de especies de Randia soportan sus usos tradicionales, pero solo está demostrada la actividad antiveneno de R. aculeata. Especies de Randia podrían ser fuente de compuestos bioactivos, pero su conocimiento debe incrementarse para demonstrar sus usos tradicionales y contribuir al desarrollo de estrategias para su preservación y uso racional.