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Article in English | AIM, AIM | ID: biblio-1367381


Background: Since the start of the coronavirus disease 2019 (COVID-19) pandemic, poison centres worldwide have reported an increase in exposures to chemicals used for infection prevention. Increased availability and use could lead to an increase in exposures. Potential effects on a South African Poison Information Helpline were unknown, therefore a study was performed to describe changes in call volume and profile of poison exposures. Methods: A retrospective analysis was conducted on an observational database of telephone enquiries. All human-related poisoning exposure call data collected from 01 March to 31 August during 2018, 2019 and 2020 were extracted and analyzed. Summary statistics were used to describe all variables. Results: The total number of calls were 5137, 5508, and 5181 in 2018, 2019, 2020, respectively. The monthly call number during 2020 was mostly less than in 2019. More calls were received from the public calls (39.4% vs 33.1%) and for accidental exposures (65.6% vs 62.3%) increased during 2020 compared to 2019. Exposures to pharmaceuticals decreased by 14.8% from 2019 to 2020, while exposures to eucalyptus oil more than doubled from 21 in 2019 to 43 during 2020. Exposures to antiseptics and disinfectants increased by 60.4%, mainly due to hand sanitizers exposure which showed a 26-fold increase from 2019 (n = 6) to 2020 (n = 156). Conclusion: A change in the profile of poison exposures was observed during the COVID-19 pandemic. Lockdown regulations and greater availability of antiseptics and disinfectants probably led to the increase in exposures. Although symptoms were mostly mild, the public should be educated on safe storage and proper use of all chemicals.

Humans , Male , Female , Poisons , Occupational Exposure , Pandemics , COVID-19 , Anti-Infective Agents, Local , Disinfectants
J. venom. anim. toxins incl. trop. dis ; 27: e20200179, 2021. tab, graf, ilus
Article in English | LILACS, VETINDEX | ID: biblio-1279402


Neutrophils play a pivotal role in innate immunity and in the inflammatory response. Neutrophils are very motile cells that are rapidly recruited to the inflammatory site as the body first line of defense. Their bactericidal activity is due to the release into the phagocytic vacuole, called phagosome, of several toxic molecules directed against microbes. Neutrophil stimulation induces release of this arsenal into the phagosome and induces the assembly at the membrane of subunits of the NAPDH oxidase, the enzyme responsible for the production of superoxide anion that gives rise to other reactive oxygen species (ROS), a process called respiratory burst. Altogether, they are responsible for the bactericidal activity of the neutrophils. Excessive activation of neutrophils can lead to extensive release of these toxic agents, inducing tissue injury and the inflammatory reaction. Envenomation, caused by different animal species (bees, wasps, scorpions, snakes etc.), is well known to induce a local and acute inflammatory reaction, characterized by recruitment and activation of leukocytes and the release of several inflammatory mediators, including prostaglandins and cytokines. Venoms contain several molecules such as enzymes (phospholipase A2, L-amino acid oxidase and proteases, among others) and peptides (disintegrins, mastoporan, parabutoporin etc.). These molecules are able to stimulate or inhibit ROS production by neutrophils. The present review article gives a general overview of the main neutrophil functions focusing on ROS production and summarizes how venoms and venom molecules can affect this function.(AU)

Animals , Poisons/administration & dosage , Reactive Oxygen Species , NADPH Oxidases , L-Amino Acid Oxidase , Neutrophils , Anti-Inflammatory Agents
J. venom. anim. toxins incl. trop. dis ; 27: e20200177, 2021. tab, graf
Article in English | LILACS, VETINDEX | ID: biblio-1250255


The western Russell's viper (Daboia russelii) is widely distributed in South Asia, and geographical venom variation is anticipated among distant populations. Antivenoms used for Russell's viper envenomation are, however, raised typically against snakes from Southern India. The present study investigated and compared the venom proteomes of D. russelii from Sri Lanka (DrSL) and India (DrI), the immunorecognition of Indian VINS Polyvalent Antivenom (VPAV) and its efficacy in neutralizing the venom toxicity. Methods: The venoms of DrSL and DrI were decomplexed with C18 high-performance liquid chromatography and SDS-polyacrylamide gel electrophoresis under reducing conditions. The proteins fractionated were identified through nano-ESI-liquid chromatography-tandem mass spectrometry (LCMS/MS). The immunological studies were conducted with enzyme-linked immunosorbent assay. The neutralization of the venom procoagulant effect was evaluated in citrated human plasma. The neutralization of the venom lethality was assessed in vivo in mice adopting the WHO protocol. Results: DrSL and DrI venom proteomes showed comparable major protein families, with phospholipases A2 (PLA2) being the most abundant (> 60% of total venom proteins) and diverse (six protein forms identified). Both venoms were highly procoagulant and lethal (intravenous median lethal dose in mice, LD50 = 0.24 and 0.32 µg/g, for DrSL and DrI, respectively), while lacking hemorrhagic and anticoagulant activities. VPAV was immunoreactive toward DrSL and DrI venoms, indicating conserved protein antigenicity in the venoms. The high molecular weight venom proteins were, however, more effectively immunorecognized than small ones. VPAV was able to neutralize the coagulopathic and lethal effects of the venoms moderately. Conclusion: Considering that a large amount of venom can be injected by Russell's viper during envenomation, the potency of antivenom can be further improved for optimal neutralization and effective treatment. Region-specific venoms and key toxins may be incorporated into the immunization procedure during antivenom production.(AU)

Animals , Poisons/toxicity , Antivenins/biosynthesis , Russell's Viper , Proteomics , Geographic Locations
Rev. Soc. Bras. Med. Trop ; 54: e04612020, 2021. graf
Article in English | ColecionaSUS, LILACS, ColecionaSUS, SES-SP | ID: biblio-1143887


Abstract We report a case of envenomation by Dendrobates tinctorius in the northwest of the Amazon Forest. The patients were two men, who presented with numbness in the right arm and slight numbness in the lower lip, respectively. Dendrobates tinctorius secretions contain pumiliotoxin, one of several toxins found in the dendrobatidis skin, which interferes with muscle contraction and causes locomotor difficulties. Although Dendrobatidae is a family of anurans known for their venom, few studies describe the symptoms of envenomation in humans.

Animals , Male , Anura , Poisons , Skin , Brazil
Rev. colomb. anestesiol ; 48(4): e401, Oct.-Dec. 2020. tab, graf
Article in English | LILACS, COLNAL | ID: biblio-1144319


Abstract Introduction The use of extracorporeal membrane oxygenation (ECMO) has increased exponentially in recent years and has shown to be effective in treating adult respiratory distress syndrome (ARDS) secondary to HiNi-related pneumonia. However, evidence remains controversial. This study describes a case series of ECMO in ARDS secondary to viral pneumonia. Methods A search was conducted in the ECMO database of Fundación Cardiovascular de Colombia for the 20132017 period. A case series report was written of patients diagnosed with ARDS secondary to confirmed or suspected viral pneumonia. Results Nineteen patients with ECMO support and ARDS due to viral pneumonia were included in the study. The survival rate upon discharge was 11 patients (58%) and weaning from ECMO support was successful in 13 patients (68%). Hemorrhagic complications were the most frequent: gastrointestinal bleeding, 10 patients (53%); intracranial bleeding, 2 (10%); alveolar hemorrhage, 2 (10%);' hemothorax requiring thoracostomy with chest tube drainage, 2 (10%); cannulation site bleeding, 9 patients (47%); and surgical site bleeding in 3 patients (25%) who required tracheostomy. Other complications were: pneumothorax, 1 patient (5%); sepsis, 6 patients (32%); and growth of microorganisms in bronchial lavage, 6 patients (32%). Conclusions This study supports the use of veno-venous ECMO to achieve a higher survival rate than expected in patients with severe ARDS and refractory hypoxemia secondary to viral pneumonia. Early initiation of the therapy should improve overall results.

Resumen Introducción El uso de la oxigenación por membrana extracorpórea (ECMO) ha tenido un incremento exponencial en los últimos años y ha demostrado ser efectivo en el manejo del síndrome de dificultad respiratoria del adulto (SDRA) secundario a neumonía por H1N1, si bien la evidencia sigue siendo controvertida. En este estudio describimos una serie de casos de ECMO por SDRA secundario a neumonía viral. Métodos Se realizó una búsqueda en la base de datos de ECMO de la Fundación Cardiovascular desde el año 20132017. Reportamos una serie de casos donde se incluyeron pacientes diagnosticados con SDRA secundario a neumonía viral sospechosa o confirmada. Resultados Se incluyeron en el estudio 19 pacientes con soporte de ECMO y SDRA por neumonía viral. La sobrevida al alta fue 11 pacientes (58%) y el destete del ECMO fue exitoso en 13 pacientes (68%). Las complicaciones hemorrágicas presentadas fueron: sangrado digestivo, 10 pacientes (53%), sangrado cerebral, 2 (10%), hemorragia alveolar, 2 (10%), hemotórax con requerimiento de toracostomía a drenaje cerrado, 2 (10%), sangrado activo por sitio de canulación, 9 pacientes (53%), y 3 pacientes traqueostomizados (25%) que sangraron por el sitio quirúrgico. Otras complicaciones presentadas fueron: neumotórax, 1 paciente (5%), septicemia, 6 (32%) y crecimiento de microorganismos en lavados bronquiales 6 (32%). Conclusion El presente estudio permite indicar que el uso de la ECMO VV viabiliza una sobrevida mayor a la esperada en pacientes con SDRA severo e hipoxemia refractaria secundario a neumonía viral. Su inicio tempranamente debe mejorar los resultados globales.

Humans , Male , Female , Middle Aged , Pneumonia, Viral , Poisons , Respiratory Distress Syndrome, Newborn , Extracorporeal Membrane Oxygenation , Chest Tubes , Hemothorax , Pneumothorax , Thoracostomy , Tracheostomy , Catheterization , Survival Rate , Sepsis , Bronchoalveolar Lavage , Influenza A Virus, H1N1 Subtype
Rev. colomb. nefrol. (En línea) ; 7(2): 113-118, jul.-dic. 2020. tab, graf
Article in Spanish | LILACS, COLNAL | ID: biblio-1251571


Resumen El síndrome hemolítico urémico (SHU) es una enfermedad que se caracteriza por la tríada anemia hemolítica no inmune, trombocitopenia e insuficiencia renal aguda, en la que las lesiones subyacentes están mediadas por un proceso de microangiopatía trombótica (MAT) sistêmica. Existen distintas causas que pueden desencadenar el proceso de la MAT que caracteriza el SHU. Se describe el caso de una mujer, con antecedentes de diabetes mellitus e hipertensión arterial, quién ingirió veneno de serpiente del género Bothrops con fines medicinales y 72 horas después debió ser hospitalizada por edema de miembros inferiores, dolor abdominal, equimosis e ictericia. Al ingreso, se le realizó analítica sanguínea que constató trombocitopenia, elevación de azoados y anemia; de igual forma se documentaron datos de falla renal aguda, por lo que se diagnosticó con SHU secundario a la ingesta de veneno de serpiente. En el artículo se describen aspectos del diagnóstico y el manejo clínico que se realizó y se estable que el compromiso renal por veneno de serpiente Bothrops es una entidad poco frecuente que si no se maneja de manera adecuada puede ser letal, y más aún si existen comorbilidades predisponentes.

Abstract Hemolytic uremic syndrome (HUS) is a disease characterized by the triad of non-immune hemolytic anemia, thrombocytopenia, and acute renal failure, in which the underlying lesions are mediated by a process of systemic thrombotic microangiopathy (TMA). There are different causes that can trigger the MAT process that characterizes HUS. The case of a woman with a history of diabetes mellitus and arterial hypertension is described, who ingested snake venom of the genus Bothrops for medicinal purposes, and 72 hours later she had to be hospitalized for edema of the lower limbs, abdominal pain, ecchymosis and jaundice. Upon admission, he underwent blood tests that found thrombocytopenia, elevated nitrogen levels and anemia; Similarly, data on acute kidney failure were documented, for which HUS was diagnosed secondary to the ingestion of snake venom. The article describes aspects of the diagnosis, and the clinical management that was carried out and it was established that renal involvement by Bothrops snake venom is a rare entity, which if not managed properly can be lethal, and even more so if there are predisposing comorbidities.

Humans , Female , Hemolytic-Uremic Syndrome , Poisons , Bothrops , Diabetes Mellitus , Ecuador , Hypertension
Cienc. tecnol. salud ; 7(2): 251-264, 2020. il 27 c
Article in Spanish | LILACS, LIGCSA, DIGIUSAC | ID: biblio-1348237


El accidente ofídico es una enfermedad tropical desatendida que ocasiona un problema de salud pública en el mundo, siendo una de las principales causas de morbilidad y mortalidad en las áreas empobrecidas de América Latina. En Guatemala se distribuyen 23 especies de serpientes venenosas de importancia médica. La composición de los venenos es compleja y diversa, resultando en una variedad de manifestaciones clínicas. Los departamentos con mayor incidencia de ofidismo son Petén, Alta Verapaz, Quiché, Escuintla e Izabal. Estos accidentes afectan más a hombres que a mujeres, siendo la mayoría agricultores; el rango de edad más comprometido es de 10-19 años y principalmente ocurren en miembros inferiores. El tiempo medio que tarda la víctima en llegar al hospital es de 5.6 h, siendo el retraso en la atención médica, un factor de riesgo para severidad y mortalidad. Los servicios de salud en ocasiones no cuentan con recursos idóneos para atender a las víctimas, brindando tratamiento sintomático. Simultáneamente, el tratamiento empírico tiene gran aceptación, sin embargo, los resultados de investigaciones realizadas con algunas plantas de uso común en casos de ofidismo, concluyeron que no es recomendable su uso aislado en el tratamiento del envenenamiento. Dada la falta de información se debe promover más investigación sobre el ofidismo en el país, siendo indispensable la elaboración de una ficha de reporte obligatoria. Además, deben elaborarse guías de tratamiento e identificación de serpientes para uso del personal médico, incluyendo programas de educación a nivel comunitario.

Snakebite envenoming is a neglected tropical disease that causes a public health problem in the world, being one of the main causes of morbidity and mortality in impoverished areas of Latin America. 23 species of poi-sonous snakes of medical importance are distributed in Guatemala. The composition of venoms is complex and diverse, resulting in a variety of clinical manifestations. The departments with the highest incidence of snakebites are Petén, Alta Verapaz, Quiché, Escuintla and Izabal. These accidents affect more men than women, the majo-rity being farmers; the most compromised age range is 10-19 years and they mainly occur in the lower limbs. The average time it takes for the victim to reach the hospital is 5.6 hours, with delay in medical care being a risk factor for severity and mortality. Health services sometimes do not have adequate resources to care for victims, providing symptomatic treatment. Simultaneously, empirical treatment is widely accepted, however, the results of research carried out with some plants commonly used in cases of envenoming concluded that their isolated use is not recommended in the treatment. Given the lack of information, more research on snakebite envenoming in the country should be promoted, making the preparation of a mandatory report form essential. In addition, snake identification and treatment guides should be developed for use by medical personnel, including education pro-grams at the community level.

Humans , Animals , Poisons/toxicity , Snake Bites/mortality , Snake Bites/drug therapy , Crotalid Venoms/poisoning , Neglected Diseases/mortality , Guatemala/epidemiology
J. venom. anim. toxins incl. trop. dis ; 26: e20200001, 2020. tab, graf
Article in English | LILACS, VETINDEX | ID: biblio-1135163


Development of antibiotic resistance that leads to resurgence of bacterial infections poses a threat to disease-free existence for humankind and is a challenge for the welfare of the society at large. Despite research efforts directed towards treatment of pathogens, antibiotics within new improved classes have not emerged for years, a fact largely attributable to the pharmacological necessities compelling drug development. Recent reversion to the use of natural products alone or in combination with standard drugs has opened up new vistas for alternative therapeutics. The success of this strategy is evident in the sudden interest in plant extracts as additives/synergists for treatment of maladies caused by drug-resistant bacterial strains. Animal venoms have long fascinated scientists as sources of pharmacologically active components that can be exploited for the treatment of specific ailments and should be promoted further to clinical trials. In the present review, we outline the scope and possible methods for the applications of animal venoms in combination with commercial antibiotics to offer a better treatment approach against antibiotic-resistant infections.(AU)

Peptides , Poisons/chemistry , Bacterial Infections , Pharmaceutical Preparations , Anti-Bacterial Agents , Biological Products , Drug Resistance, Microbial
J. venom. anim. toxins incl. trop. dis ; 26: e20200128, 2020. ilus
Article in English | LILACS, VETINDEX | ID: biblio-1135154


As in previous contributions to the JVATiTD, the aim of this note is to bring some general information on a particular aspect of the scorpion biology. An attempt is made to explain the possible coevolution of telson morphology and venom glands, which took place during several hundred million years and in particular since scorpions migrated from aquatic to terrestrial environments. Three components can be directly associated with predation and defensive behaviours: (1) morphology of the chelae and structure of the chelae fingers granulations; (2) morphology of the metasoma and in particular of the telson; (3) evolution of tegumentary glands in the telson toward different types of venom glands. Since a number of recent contributions already treated some of these aspects, I will limit my comments to the possible evolution of the telson in relation to the evolution of venom glands. As in previous contributions, the content of this article is basically addressed to non-specialists on scorpions whose research embraces scorpions in several fields such as venom toxins and public health.(AU)

Animals , Poisons , Predatory Behavior , Scorpions , Biological Coevolution
Article in English | WPRIM | ID: wpr-829020


Objective@#This study aimed to explore the protective effect of procyanidin B2 (PCB2) on acute liver injury induced by aflatoxin B (AFB ) in rats.@*Methods@#Forty Sprague Dawley rats were randomly divided into control, AFB , AFB + PCB2, and PCB2 groups. The latter two groups were administrated PCB2 intragastrically (30 mg/kg body weight) for 7 d, whereas the control and AFB groups were given the same dose of double distilled water intragastrically. On the sixth day of treatment, the AFB and AFB + PCB2 groups were intraperitoneally injected with AFB (2 mg/kg). The control and PCB2 groups were intraperitoneally administered the same dose of dimethyl sulfoxide (DMSO). On the eighth day, all rats were euthanized: serum and liver tissue were isolated for further examination. Hepatic histological features were assessed by hematoxylin and eosin-stained sections. Weight, organ coefficient (liver, spleen, and kidney), liver function (serum alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, total bilirubin, and direct bilirubin), oxidative index (catalase, glutathione, superoxide dismutase, malondialdehyde, and 8-hydroxy-2'-deoxyguanosine), inflammation factor [hepatic interleukin-6 (IL-6) mRNA expression and serum IL-6], and bcl-2/bax ratio were measured.@*Results@#AFB significantly caused hepatic histopathological damage, abnormal liver function, oxidative stress, inflammation, and bcl-2/bax ratio reduction compared with DMSO-treated controls. Our results indicate that PCB2 treatment can partially reverse the adverse liver conditions induced by AFB .@*Conclusion@#Our findings indicate that PCB2 exhibits a protective effect on acute liver injury induced by AFB .

Aflatoxin B1 , Toxicity , Animals , Biflavonoids , Pharmacology , Catechin , Pharmacology , Chemical and Drug Induced Liver Injury , Drug Therapy , Male , Poisons , Toxicity , Proanthocyanidins , Pharmacology , Protective Agents , Pharmacology , Random Allocation , Rats , Rats, Sprague-Dawley
Rev. med. Risaralda ; 25(2): 65-72, jul.-dic. 2019. graf
Article in Spanish | LILACS, COLNAL | ID: biblio-1115749


Resumen Los escorpiones del género Tityus presentan la mayor distribución mundial, de mayor importancia clínica, epidemiológica y más peligrosa del continente americano. Las toxinas de su veneno producen perturbación severa de los procesos de excitación y conducción del impulso nervioso. Desde el punto de vista histopatológicos se han observado cambios estructurales en diferentes tejidos de ratones, con el veneno de varias especies de Tityus venezolanos. Objetivo: Describir los efectos clínicos e histopatológicos agudos y subagudos del veneno de escorpión (Buthidae: T. breweri) en el miocardio de hámster. Método: Estudio experimental, exploratoria, descriptivo, analítica y correlacional. Se utilizaron hámsteres de ambos sexos del genero Cricetus y se obtuvo el veneno de 26 escorpiones T. breweri, se escogieron 6 hámster al azar, inyectándoles vía intraperitonial (VIP) veneno de Tityus breweri, 3 sacrificados a los 30 minutos y los otros 3 a los 60 minutos, 3 inyectados con agua destilada constituyeron el grupo control. Resultados: La mayoría de los animales expuestos presentaron manifestaciones de tipo colinérgicas y adrenérgicas. Las alteraciones histopatológicas agudas observadas fueron edema interfascicular y congestión vascular, infiltrado linfohistiocítico perivascular. Al transcurrir 12, 24, 48 y 72 horas de exposición del veneno, no se evidenciaron cambios histopatológicos, lo que hace presumir que se activaron los procesos de reparación de los tejidos dañados. Conclusión: el veneno de T. breweri produjo alteración histológicas agudas y subagudas en el tejido miocárdico en los hámsteres sin evidencia de alteración en el grupo control.

Abstract Scorpions of the genus Tityus present the largest distribution of the world, of greater clinical, epidemiological and more dangerous importance of the American continent. The toxins from its venom produce severe disturbance of the excitation and conduction processes of the nerve impulse. From the histopathological point of view structural changes have been observed in different tissues of mice, with the venom of several species of Venezuelan Tityus. Objective: To describe the acute and subacute clinical and histopathological effects of scorpion venom (Buthidae: T. breweri) on the hamster myocardium. Method: Experimental, exploratory, descriptive, analytical and correlational study. Hersters of both sexes of the genus Cricetus were obtained and venom of 26 T. breweri scorpions were obtained, 6 random hamsters were chosen, injecting intravenously (VIP) venom of Tityus breweri, 3 sacrificed at 30 minutes and the other 3 a The 60 minutes, 3 injected with distilled water constituted the control group. Results: Most of the exposed animals presented cholinergic and adrenergic type manifestations. The acute histopathological alterations observed were interfascicular edema and vascular congestion, perivascular lymphohistiocytic infiltrate. At the end of 12, 24, 48 and 72 hours of exposure of the venom, no histopathological changes were evidenced, which suggests that the repair processes of the damaged tissues were activated. Conclusion: T. breweri venom caused acute and subacute histological alterations in myocardial tissue in hamsters with no evidence of alteration in the control group.

Humans , Animals , Scorpion Venoms , Scorpions , Cholinergic Agents , Adrenergic Agents , Edema , Myocardium , Poisons , Venoms , Distilled Water
J. venom. anim. toxins incl. trop. dis ; 25: e147418, 2019. graf, ilus
Article in English | LILACS | ID: biblio-984697


Background: Pore-forming proteins (PFP) are a class of toxins abundant in the venom of sea anemones. Owing to their ability to recognize and permeabilize cell membranes, pore-forming proteins have medical potential in cancer therapy or as biosensors. In the present study, we showed the partial purification and sequencing of a pore-forming protein from Anthopleura dowii Verrill (1869). 17. Methods: Cytolytic activity of A. dowii Verrill (1869) venom was determined via hemolysis assay in the erythrocytes of four mammals (sheep, goat, human and rabbit). The cytotoxic activity was analyzed in the human adherent lung carcinoma epithelial cells (A549) by the cytosolic lactate dehydrogenase (LDH) assay, and trypan blue staining. The venom was fractionated via ammonium sulfate precipitation gradient, dialysis, and ion exchange chromatography. The presence of a pore-forming protein in purified fractions was evaluated through hemolytic and cytotoxic assays, and the activity fraction was analyzed using the percent of osmotic protections after polyethylene glycol (PEG) treatment and mass spectrometry. 18. Results: The amount of protein at which the venom produced 50% hemolysis (HU50) was determined in hemolysis assays using erythrocytes from sheep (HU50 = 10.7 ± 0.2 µg), goat (HU50 = 13.2 ± 0.3 µg), rabbit (HU50 = 34.7 ± 0.5 µg), and human (HU50 = 25.6 ± 0.6 µg). The venom presented a cytotoxic effect in A549 cells and the protein amount present in the venom responsible for producing 50% death (IC50) was determined using a trypan blue cytotoxicity assay (1.84 ± 0.40 µg/mL). The loss of membrane integrity in the A549 cells caused by the venom was detected by the release of LDH in proportion to the amount of protein. The venom was fractionated; and the fraction with hemolytic and cytotoxic activities was analyzed by mass spectrometry. A pore-forming protein was identified. The cytotoxicity in the A549 cells produced by the fraction containing the pore-forming protein was osmotically protected by PEG-3350 Da molecular mass, which corroborated that the loss of integrity in the plasma membrane was produced via pore formation. 19. Conclusion: A. dowii Verrill (1869) venom contains a pore-forming protein suitable for designing new drugs for cancer therapy.(AU)

Humans , Animals , Sea Anemones , Cnidarian Venoms/isolation & purification , Lung Neoplasms/therapy , Poisons/toxicity , Mass Spectrometry/methods , A549 Cells
Campinas; s.n; 2019. ilus, graf, tab.
Thesis in Portuguese | LILACS | ID: biblio-1118162


Resumo: O veneno da aranha Phoneutria nigriventer (PNV) contém neuropeptídeos que afetam canais iônicos e a neurotransmissão, induzindo a quebra da barreira hematoencefálica (BHE) no hipocampo de ratos, o que ocorre paralelamente ao aumento do fator de crescimento endotelial vascular (VEGF). Sabe-se que a resposta biológica do VEGF é desencadeada através da regulação transcricional promovida pelo domínio tirosina-quinase de receptores transmembranares do VEGF, dos quais o VEGFR-2 (Flk-1) é considerado o principal mediador e ativador de várias vias de sinalização. O trabalho propõe investigar o possível papel neuroprotetor do VEGF após inibir sua ligação ao receptor Flk-1 pelo itraconazol (ITZ). Para isso, examinamos o status bioquímico do hipocampo por espectroscopia no Infravermelho com Transformada de Fourier (FT-IR), bem como avaliamos as proteínas envolvidas nas rotas paracelular e transcelular da BHE e quais vias de sinalização, relacionadas à neuroproteção do VEGF, foram ativadas. Os ratos receberam PNV ou foram pré-tratados com ITZ (30 min) seguido de PNV pela veia da cauda e depois sacrificados em 1 e 2 h (intervalos com maiores sinais de intoxicação), 5 h (intervalo com sinais incipientes de recuperação) e 24 h (intervalo sem sinal visual detectável de envenenamento), sendo comparados aos controles, salina e ITZ. O pré-tratamento com o antifúngico agravou os efeitos do veneno e aumentou danos à BHE. Os espectros FT-IR do veneno, hipocampo dos controles, PNV e ITZ-PNV mostraram as bandas de 1400 cm-1 (carboxilato) e de 1467 cm-1 (flexão de CH2: principalmente lipídios), que foram considerados bandas biomarcadora e referência, respectivamente. A inibição da ligação VEGF/Flk-1 produziu mudanças marcantes na estabilidade lipídios/proteínas em 1-2 h. As maiores diferenças ocorreram nas regiões espectrais atribuídas à lípides simétricos (2852 cm-1) e assimétricos (2924 e 2968 cm-1). As análises quantitativas mostraram maiores aumentos na razão 1400 cm-1/1467 cm-1 no período de intoxicação grave (1 h), e referem-se à região espectral de 3106 cm-1 a 687 cm-1. Ademais, a desativação da ligação VEGF/Flk-1 pelo itraconazol (ITZ) aumentou o fator indutor de hipóxia (H1F1-?), VEGF, Flk-1, Flt-1, Neu-N e caspase-3 às 5 horas após a injeção do PNV. No mesmo intervalo, a permeabilidade transcelular da BHE aumentou (caveolina-1?, dinamina-2 e família Src de não receptores tirosina-quinase (SKFs)), enquanto laminina e a via paracelular (occludina, ?-catenina) foram reforçadas e a proteína de efluxo glicoproteína-P (P-gp) aumentou. Ao mesmo tempo (5 h), ocorreu auto-fosforilação da via pró-proliferação celular (p38-fosforilada). Às 24 h, apesar da ausência de sinais de intoxicação, a via pró-sobrevivência celular (Akt-fosforilada) diminuiu nos animais pré-tratados com ITZ, enquanto aumentou nos tratados com PNV apenas. Os dados indicam ativação de mecanismos de neuroproteção relacionados ao VEGF envolvendo o receptor Flk-1 e principalmente à serina-treonina-quinase Akt, provavelmente via PI3K. ERK-fosforilada (2 h) e p38-fosforilada (5 h) sugerem interação entre as vias de sinalização com o objetivo de restabelecer a homeostase do hipocampo. O intervalo de 5 h parece ser o ponto de virada orquestrando respostas biológicas variadas. Os dados permitem concluir sobre o papel neuroprotetor do VEGF e que o mesmo pode ser explorado como possível alvo terapêutico no envenenamento por P. nigriventer.(AU)

Abstract: Phoneutria nigriventer spider venom (PNV) contains ion channels-acting neuropeptides that affect neurotransmission and induces transitory blood-brain barrier (BBB) breakdown in rat¿s hippocampus, which run in parallel with (vascular endothelial growth factor) VEGF upregulation. It is known that VEGF biological response is triggered through transcriptional regulation promoted by transmembrane tyrosine kinase receptors, being VEGFR-2 (Flk-1) considered the major mediator of VEGF effect through activation of a number of signaling pathways. The purpose of this work is to investigate a putative neuroprotective role of VEGF by inhibiting its binding to receptor Flk-1 by itraconazole (ITZ). To do this, we examined the biochemical status of the hippocampus by Infrared Spectroscopy and Fourier Transform (FT-IR), as well as evaluated the proteins involved in the BBB paracellular and transcellular routes and which signaling pathways related to VEGF neuroprotection were activated. Rats were administered PNV alone or were pre-treated with ITZ (30 min) followed by PNV through the tail vein, and then euthanized at 1 and 2 h (intervals with greatest signs of intoxication), 5 h (interval with incipient signs of animals¿ recovery) and 24 h (interval with no visually detectable envenomation sign) and compared to saline and ITZ controls. The antifungal pre-treatment aggravated PNV toxic effects and increased BBB damage. FT-IR spectra of venom and from hippocampi of controls, PNV and ITZ-PNV showed a 1400 cm-1 band linked to symmetric stretch of carboxylate and 1467 cm-1 band (CH2 bending: mainly lipids), which were considered biomarker and reference bands, respectively. Inhibition of VEGF/Flk-1 binding produced marked changes in lipid/protein stability at 1-2 h. The largest differences were observed in spectra regions assigned to lipids, both symmetric (2852 cm-1) and asymmetric (2924 and 2968 cm-1). Quantitative analyses showed greatest increases in the 1400 cm-1/1467 cm-1 ratio also at 1 h. Such changes at period of rats¿ severe intoxication referred to wavenumber region from 3106 cm-1 to 687 cm-1. Furthermore, the deactivation of Flk-1 receptor by VEGF through itraconazole (ITZ) showed increased hypoxia inducible factor (H1F-1?), VEGF, Flk-1, Flt-1, Neu-N and caspase-3 at 5 h after PNV injection. At same interval, BBB transcellular permeability increased (caveolin-1?, dynamin-2 and Src family of non-receptor tyrosine kinases (SKFs)), while laminin and paracellular route (occludin, ?-catenin) were reinforced and P-glycoprotein (P-gp) efflux protein was increased. Such effects were timely followed by upregulation of auto-phosphorylation of the pro-proliferation (phosphorylated-p38) pathway. At 24 h, despite absence of intoxication signs, the pro-survival (p-Akt) pathway was downregulated in animals underwent inhibition of VEGF-Flk-1 binding, whereas it was upregulated in PNV rats non-treated with ITZ. The data indicate triggering of VEGF-related mechanisms involving Flk-1 receptor and serine-threonine kinase Akt, probably via PI3K, as the main mechanism of neuroprotection. Phosphorylated ERK (2 h) and p-p38 (5 h) indicates interplay among transduction pathways likely aiming at re-establishment of hippocampal homeostasis. The findings suggest 5 h interval as the turning point that orchestrates varied biological responses. Taking together the data of the present study allow concluding that VEGF expression exerts neuroprotective role and can be explored as a possible therapeutic target in P. nigriventer envenomation.(AU)

Rats , Spider Venoms , Blood-Brain Barrier , Vascular Endothelial Growth Factor A , Poisoning , Poisons/administration & dosage , Central Nervous System , Itraconazole , Neuroprotection , Ion Channels
Article in English | LILACS, VETINDEX | ID: biblio-1002500


Studies on toad poison are relevant since they are considered a good source of toxins that act on different biological systems. Among the molecules found in the toad poison, it can be highlighted the cardiotonic heterosides, which have a known mechanism that inhibit Na+/K+-ATPase enzyme. However, these poisons have many other molecules that may have important biological actions. Therefore, this work evaluated the action of the low molecular weight components from Rhinella schneideri toad poison on Na+/K+-ATPase and their anticonvulsive and / or neurotoxic effects, in order to detect molecules with actions of biotechnological interest. Methods: Rhinella schneideri toad (male and female) poison was collected by pressuring their parotoid glands and immediately dried and stored at -20 °C. The poison was dialysed and the water containing the low molecular mass molecules (< 8 kDa) that permeate the dialysis membrane was collected, frozen and lyophilized, resulting in the sample used in the assays, named low molecular weight fraction (LMWF). Na+/K+ ATPase was isolated from rabbit kidneys and enzyme activity assays performed by the quantification of phosphate released due to enzyme activity in the presence of LMWF (1.0; 10; 50 and 100 µg/mL) from Rhinella schneideri poison. Evaluation of the L-Glutamate (L-Glu) excitatory amino acid uptake in brain-cortical synaptosomes of Wistar rats was performed using [3H]L-glutamate and different concentration of LMWF (10-5 to 10 µg/µL). Anticonvulsant assays were performed using pentylenetetrazole (PTZ) and N-methyl-D-aspartate (NMDA) to induce seizures in Wistar rats (n= 6), which were cannulated in the lateral ventricle and treated with different concentration of LMWF (0.25; 0.5; 1.0; 2.0; 3.0 and 4.0 µg/µL) 15 min prior to the injection of the seizure agent. Results: LMWF induced a concentration-dependent inhibition of Na+/K+-ATPase (IC50% = 107.5 μg/mL). The poison induces an increased uptake of the amino acid L-glutamate in brain-cortical synaptosomes of Wistar rats. This increase in the L-glutamate uptake was observed mainly at the lowest concentrations tested (10-5 to 10-2 µg/µL). In addition, this fraction showed a very relevant central neuroprotection on seizures induced by PTZ and NMDA. Conclusions: LMWF from Rhinella schneideri poison has low molecular weight compounds, which were able to inhibit Na+/K+-ATPase activity, increase the L-glutamate uptake and reduced seizures induced by PTZ and NMDA. These results showed that LMWF is a rich source of components with biological functions of high medical and scientific interest.(AU)

Animals , Poisons , Synaptosomes , Bufo rana , Neuroprotection , Anticonvulsants , Glutamic Acid , Molecular Weight
Rev. bras. ciênc. saúde ; 23(3): 263-272, 2019. Tab
Article in Portuguese | LILACS | ID: biblio-1045964


Objetivo: Foi realizado estudo transversal com objetivo de descrever as práticas de uso de inseticidas utilizados no controle dos vetores no ambiente doméstico. Material e Métodos: Foram aplicados questionários em 122 residências no município de Niterói, na Região Oceânica em 2010. Destes, 61 foram realizados em condomínio de classe média alta e 61 em Comunidade de baixa renda. Resultados: Os resultados demonstraram que 92% do grupo Condomínio e 77,7% do grupo Colônia de Pescadores usam inseticidas. Em relação aos cuidados com manuseio de inseticidas, 62,2% dos entrevistados do Grupo Condomínio e 35,6% dos entrevistados do Grupo Colônia de Pescadores, disseram que não tomavam nenhum cuidado ao usar estes produtos. Os dados sugerem que pessoas com menor escolaridade têm mais chances de não usar adequadamente os inseticidas que são produtos potencialmente tóxicos. Conclusão: Conclui-se que aspectos relacionados ao nível educacional e local de moradia estão relacionados ao uso mais adequado de inseticidas domésticos. (AU)

Objetive: Cross-sectional study was performed in order to describe practices with insecticides used in the control of insect vectors in the household. Methods: Questionnaires were applied in 154 households in Niterói City, in the Oceanic Region of Rio de Janeiro ́s State, in 2010. Of these, 77 were performed in upper middle class Apartament Complexes and 61 in the low-income community both in the Oceanic Region of Niterói. Results:The results showed that 92% of Apartment Complexes and 77.7% of Fishermen Colony use insecticides. Regarding care handling insecticides, 62.2% of the respondents of the Apartment Complex Group and 35.6% of the respondents from the Fishermen Colony Group said they were not taking any care when using these products. Data suggests that people with low education are more likely to not properly use potentially toxic pesticides. Conclusion: We conclude that aspects related to educational level and residential location are associated to more appropriate use of household insecticides. (AU)

Humans , Male , Female , Pest Control , Poisons , Environmental Health
Med. Afr. noire (En ligne) ; 65(02): 103-110, 2018. ilus
Article in French | AIM, AIM | ID: biblio-1266286


Introduction : L'objectif de cette étude était de déterminer les paramètres épidémiologiques et médico-légaux des morts toxiques à Abidjan.Patients et méthode : Il s'agissait d'une étude rétrospective descriptive sur les morts toxiques de diagnostic post mortem sur une période de 14 ans (de 2002 à 2015) dans le service d'anatomo-pathologie et de médecine légale du CHU de Treichville sis à Abidjan.Résultats : Neuf-cent-soixante-dix (970) autopsies judiciaires ont été pratiquées sur la période d'étude, parmi lesquelles 204 ont fait l'objet d'une expertise toxicologique sur des prélèvements biologiques réalisées en cours d'autopsies. Parmi ces expertises toxicologiques, 40 ont mis en évidence une intoxication mortelle. La majorité de ces cas d'intoxications mortelles était des adultes jeunes appartenant à la tranche des 25-34 ans (30%), de sexe masculin (82,5%). Ils exerçaient pour la plupart dans le secteur moderne (57,5%). Les prélèvements post-autopsiques étaient généralement effectués dans les deux jours qui suivaient le décès (25%) avec comme motifs d'expertise un accident de travail (25%) ou une catastrophe collective (30%). La voie d'intoxication était essentiellement respiratoire (28 cas sur 40) et les xénobiotiques le plus souvent retrouvés concernaient le monoxyde de carbone (10 cas sur 40) et l'hydrogène sulfuré (12 cas sur 40). L'accident était la circonstance de survenue la plus fréquente au cours des morts toxiques (55%).Conclusion : Les morts toxiques représentent une faible part de l'ensemble des décès pris en charge par la Médecine légale à Abidjan en Côte d'Ivoire. Le diagnostic de ces morts requiert une autopsie judiciaire et une expertise toxicologique qui sont incontournables mais malheureusement rarement financées par les autorités judiciaires. Nous insistons sur l'implication effective de ces autorités dans le financement de ces expertises pour une plus juste appréciation de ces décès dans nos régions

Autopsy , Cote d'Ivoire , Death , Forensic Medicine , Poisons/toxicity
Article in Korean | WPRIM | ID: wpr-718682


PURPOSE: The Korean government has tried to decrease the suicide death rate over the last decade. Suicide attempts, particularly non-fatal attempts, are the most powerful known risk factor for a completed suicide. An analysis of suicide attempt methods will help establish the effective preventive action of suicide. Fit prevention according to the method of suicide attempt may decrease the incidence of suicide death. Self-poisoning is suggested as a major method of both suicide attempts and suicide death. The aim of this study was to determine if a self-poisoning patient is a suitable target for the prevention of the suicide. METHODS: This was retrospective analysis of a prospective cohort, which included patients who presented to the emergency department (ED) after a self-harm or suicide attempt from Jan 2013 to Dec 2017. The proportion of methods in suicide attempts, psychological consultation, and fatality according to the suicide attempt method were analyzed. The types of poison were also analyzed. RESULTS: Poisoning was the most common method of suicide attempts (52.1%). The rate of psychological consultations were 18.8% for all patients and 29.1% for poison patients (p < 0.001). The rate of mortality in poisoning was 0.6%. Psychological consultation was performed more frequently in admission cases than discharged cases. The most common materials of poisons was psychological medicines and sedatives that had been prescribed at clinics or hospital. CONCLUSION: Self-poisoning is a major method of suicide attempt with a high rate of psychiatric consultation, low mortality rate, versus others methods. The prevention of suicide death for suicide attempts may focus on self-poisoning, which is the major method of suicide attempts. A suitable aftercare program for self-poisoning may be an effective method for preventing suicide if an early diagnosis and management of psychiatric disorders through psychiatric consultation can be made, and early connection to social prevention program for non-fatal patients are possible.

Aftercare , Cohort Studies , Early Diagnosis , Emergency Service, Hospital , Humans , Hypnotics and Sedatives , Incidence , Methods , Mortality , Poisoning , Poisons , Prospective Studies , Referral and Consultation , Retrospective Studies , Risk Factors , Suicide
J. venom. anim. toxins incl. trop. dis ; 24: 36, 2018. tab, graf, ilus
Article in English | LILACS, VETINDEX | ID: biblio-976026


Animal poisons and venoms are sources of biomolecules naturally selected. Rhinella schneideri toads are widespread in the whole Brazilian territory and they have poison glands and mucous gland. Recently, protein from toads' secretion has gaining attention. Frog skin is widely known to present great number of host defense peptides and we hypothesize toads present them as well. In this study, we used a RNA-seq analysis from R. schneideri skin and biochemical tests with the gland secretion to unravel its protein molecules. Methods: Total RNA from the toad skin was extracted using TRizol reagent, sequenced in duplicate using Illumina Hiseq2500 in paired end analysis. The raw reads were trimmed and de novo assembled using Trinity. The resulting sequences were submitted to functional annotation against non-redundant NCBI database and Database of Anuran Defense Peptide. Furthermore, we performed caseinolytic activity test to assess the presence of serine and metalloproteases in skin secretion and it was fractionated by fast liquid protein chromatography using a reverse-phase column. The fractions were partially sequenced by Edman's degradation. Results: We were able to identify several classes of antimicrobial peptides, such as buforins, peroniins and brevinins, as well as PLA2, lectins and galectins, combining protein sequencing and RNA-seq analysis for the first time. In addition, we could isolate a PLA2 from the skin secretion and infer the presence of serine proteases in cutaneous secretion. Conclusions: We identified novel toxins and proteins from R. schneideri mucous glands. Besides, this is a pioneer study that presented the in depth characterization of protein molecules richness from this toad secretion. The results obtained herein showed evidence of novel AMP and enzymes that need to be further explored.(AU)

Anura/physiology , Poisons , Metalloproteases , Serine Proteases , Bodily Secretions , Sequence Analysis, Protein