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1.
PLoS Negl Trop Dis ; 14(3): e0008060, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-32163415

RESUMO

The northeast (NE) region of Brazil commonly goes through drought periods, which favor cyanobacterial blooms, capable of producing neurotoxins with implications for human and animal health. The most severe dry spell in the history of Brazil occurred between 2012 and 2016. Coincidently, the highest incidence of microcephaly associated with the Zika virus (ZIKV) outbreak took place in the NE region of Brazil during the same years. In this work, we tested the hypothesis that saxitoxin (STX), a neurotoxin produced in South America by the freshwater cyanobacteria Raphidiopsis raciborskii, could have contributed to the most severe Congenital Zika Syndrome (CZS) profile described worldwide. Quality surveillance showed higher cyanobacteria amounts and STX occurrence in human drinking water supplies of NE compared to other regions of Brazil. Experimentally, we described that STX doubled the quantity of ZIKV-induced neural cell death in progenitor areas of human brain organoids, while the chronic ingestion of water contaminated with STX before and during gestation caused brain abnormalities in offspring of ZIKV-infected immunocompetent C57BL/6J mice. Our data indicate that saxitoxin-producing cyanobacteria is overspread in water reservoirs of the NE and might have acted as a co-insult to ZIKV infection in Brazil. These results raise a public health concern regarding the consequences of arbovirus outbreaks happening in areas with droughts and/or frequent freshwater cyanobacterial blooms.


Assuntos
Morte Celular/efeitos dos fármacos , Microcefalia/patologia , Envenenamento/complicações , Envenenamento/patologia , Saxitoxina/toxicidade , Infecção por Zika virus/complicações , Infecção por Zika virus/patologia , Animais , Toxinas Bacterianas/análise , Toxinas Bacterianas/toxicidade , Encéfalo/patologia , Brasil/epidemiologia , Células Cultivadas , Modelos Animais de Doenças , Surtos de Doenças , Feminino , Humanos , Incidência , Toxinas Marinhas/análise , Toxinas Marinhas/toxicidade , Camundongos Endogâmicos C57BL , Microcistinas/análise , Microcistinas/toxicidade , Modelos Teóricos , Neurotoxinas/análise , Neurotoxinas/toxicidade , Saxitoxina/análise , Água/química
2.
Microb Pathog ; 136: 103679, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31437578

RESUMO

Lipopolysaccharide (LPS) is an endotoxin composed of a polysaccharide and lipid component. It is intrinsically responsible for the pathogenicity of Gram-negative bacteria and is involved in the development of bacterial sepsis. Atmospheric pressure non-thermal plasma is proposed as a potential new approach for the treatment of infected tissue such as chronic wounds, with both antibacterial and wound-healing activities extensively described. Using both the RAW264.7 murine macrophage cell line in vitro assays and the Galleria mellonella insect in vivo toxicity model, the effect non-thermal plasma exposure on LPS-mediated toxicity has been characterised. Short (60 s) non-thermal plasma exposures of Pseudomonas aeruginosa conditioned growth media, membrane lysates and purified P. aeruginosa LPS, resulted in a substantial detoxification and reduction of LPS-induced cytotoxicity in RAW264.7 murine macrophages. Non-thermal plasma exposure (60 s) of purified P. aeruginosa LPS led to a significant (p < 0.05) improvement in the G. mellonella health index (GHI) score, a measure of in vivo toxicity. These findings demonstrate the ability of short plasma exposures to significantly reduce LPS-induced cytotoxicity both in vitro and in vivo; attenuating the toxicity of this important virulence factor intrinsic to the pathogenicity of Gram-negative bacteria.


Assuntos
Antídotos/farmacologia , Pressão Atmosférica , Endotoxinas/toxicidade , Lipopolissacarídeos/toxicidade , Gases em Plasma/farmacologia , Envenenamento/patologia , Pseudomonas aeruginosa/efeitos dos fármacos , Animais , Modelos Animais de Doenças , Lepidópteros , Camundongos , Modelos Teóricos , Envenenamento/prevenção & controle , Células RAW 264.7
3.
Anaerobe ; 59: 76-91, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31145997

RESUMO

Epsilon toxin (ETX) is the major virulence determinant of C. perfringens type B or type D strains, causing diseases in animals, besides being a listed biological and toxin warfare (BTW) agent. Keeping in mind the high lethality and the rapid onset of clinical manifestations, early diagnosis of epsilon toxin exposure is of paramount importance for implementation of appropriate medical countermeasures. Using a 2DE-MS approach, the present study is the first comprehensive proteomic elucidation of ETX-induced protein markers in the mouse model, providing putative targets for early diagnosis of ETX exposure. A total of 52 unique proteins showing ETX-induced modulations were identified in plasma and urine samples. Fibrinogen, apolipoprotein, serum amyloid protein, plasminogen, serum albumin, glutathione peroxidase, transferrin, major urinary protein 2, haptoglobin, transthyretin, and vitamin D-binding protein were among the proteins observed in more than one dataset with altered abundance after the ETX-intoxication. The predicted localization, function, and interaction of the ETX-modulated proteins in the plasma and urine indicated involvement of multiple pathways; extracellular proteins, followed by macromolecular complexes associated with blood coagulation and plasminogen activating cascade, being the most prominent among others. The putative markers elucidated here warrants further validation and can be of immense value for the early diagnosis of ETX exposure.


Assuntos
Toxinas Bacterianas/toxicidade , Biomarcadores/sangue , Biomarcadores/urina , Envenenamento/patologia , Proteínas/análise , Animais , Modelos Animais de Doenças , Eletroforese em Gel Bidimensional , Feminino , Espectrometria de Massas , Camundongos Endogâmicos BALB C , Plasma/química , Urina/química
4.
Basic Clin Pharmacol Toxicol ; 125(1): 62-74, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30712291

RESUMO

Aluminium phosphide (AlP) is a highly toxic substance with a high mortality rate and no effective antidote. Once exposed to the moisture and acidic conditions of the stomach, AlP releases toxic phosphine (PH3 ) gas, which results in severe toxicity in poisoned subjects. Selegiline is a monoamine oxidase inhibitor with antioxidant and anti-apoptotic properties, which is mostly prescribed for the treatment of mood disorders and Parkinson's disease. Since AlP has detrimental effects on cardiac physiology and mitochondrial function, we tested the protective effects of acute selegiline treatment on cardiac mitochondrial function, redox status and electrocardiographic parameters in rats after AlP poisoning. To do this, AlP was given to rats by gavage to induce toxicity. Selegiline was injected intraperitoneally in the treatment groups 1 hour after AlP poisoning. Selegiline treatment after AlP intoxication was not associated with a significant difference in the mortality rate of animals. However, selegiline reduced oxidative stress (decreased the reactive oxygen species and malondialdehyde) and increased glutathione in the cardiac tissue of rats exposed to AlP. Further, the mitochondrial membrane potential (ΔΨm) collapse reversed after treatment with selegiline. Selegiline also improved the electrocardiographic (ECG) parameters and enhanced heart rate. The histopathological evaluation revealed that selegiline eliminated the inflammation and injuries induced by AlP in the stomach and duodenum, as well as cardiac tissue. In conclusion, selegiline treatment can ameliorate the AlP-induced cardiac and gastrointestinal injuries in rats via boosting redox status and mitochondrial function with no significant effect on survival. We suggest that using selegiline, apart from other clinical treatments, may improve the quality of treatment process for AlP toxicity.


Assuntos
Compostos de Alumínio/envenenamento , Antídotos/administração & dosagem , Praguicidas/envenenamento , Fosfinas/envenenamento , Envenenamento/tratamento farmacológico , Selegilina/administração & dosagem , Animais , Modelos Animais de Doenças , Avaliação Pré-Clínica de Medicamentos , Duodeno/efeitos dos fármacos , Duodeno/patologia , Coração/efeitos dos fármacos , Humanos , Injeções Intraperitoneais , Masculino , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/patologia , Miocárdio/patologia , Estresse Oxidativo/efeitos dos fármacos , Envenenamento/etiologia , Envenenamento/patologia , Ratos , Espécies Reativas de Oxigênio/metabolismo , Estômago/efeitos dos fármacos , Estômago/patologia , Resultado do Tratamento
5.
Elife ; 82019 02 12.
Artigo em Inglês | MEDLINE | ID: mdl-30747102

RESUMO

The fish-hunting marine cone snail Conus geographus uses a specialized venom insulin to induce hypoglycemic shock in its prey. We recently showed that this venom insulin, Con-Ins G1, has unique characteristics relevant to the design of new insulin therapeutics. Here, we show that fish-hunting cone snails provide a rich source of minimized ligands of the vertebrate insulin receptor. Insulins from C. geographus, Conus tulipa and Conus kinoshitai exhibit diverse sequences, yet all bind to and activate the human insulin receptor. Molecular dynamics reveal unique modes of action that are distinct from any other insulins known in nature. When tested in zebrafish and mice, venom insulins significantly lower blood glucose in the streptozotocin-induced model of diabetes. Our findings suggest that cone snails have evolved diverse strategies to activate the vertebrate insulin receptor and provide unique insight into the design of novel drugs for the treatment of diabetes.


Assuntos
Caramujo Conus/química , Insulina/metabolismo , Venenos de Moluscos/metabolismo , Venenos/metabolismo , Receptor de Insulina/agonistas , Animais , Antígenos CD/química , Modelos Animais de Doenças , Humanos , Hipoglicemia/patologia , Insulina/química , Insulina/genética , Camundongos , Simulação de Dinâmica Molecular , Envenenamento/patologia , Receptor de Insulina/química , Peixe-Zebra
6.
J Antibiot (Tokyo) ; 72(4): 210-217, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30635615

RESUMO

To find novel amphotericin B (AmB) derivatives with high therapeutic potential, low toxicity, and water solubility, a series of nine N-substituted AmB derivatives were evaluated for their antifungal activity using the broth dilution method and for their hemolytic toxicity with sterile defibrinated sheep blood. Qualitative screening of the effect of the derivatives on two reference Candida albicans strains and of their solubility was performed based on the value of n (n is a positive integer), resulting in the identification of an optimal compound, NH2-(AEEA)5-AmB (DMR005; AEEA is 8-amino-3,6- dioxaoctanoic acid). Preliminary safety assessments of DMR005 were carried out via the MTT cell viability assay in vitro and acute toxicity assay in vivo. In general, DMR005 not only has higher water solubility and less toxicity than the parent polyene but also retains antifungal potency.


Assuntos
Anfotericina B/síntese química , Anfotericina B/farmacologia , Antifúngicos/síntese química , Antifúngicos/farmacologia , Candida albicans/efeitos dos fármacos , Anfotericina B/análogos & derivados , Anfotericina B/toxicidade , Animais , Antifúngicos/toxicidade , Sobrevivência Celular , Técnicas Citológicas , Modelos Animais de Doenças , Eritrócitos/efeitos dos fármacos , Células HEK293 , Hemólise/efeitos dos fármacos , Humanos , Testes de Sensibilidade Microbiana , Envenenamento/patologia , Ovinos , Solubilidade
7.
Praxis (Bern 1994) ; 107(22): 1211-1217, 2018.
Artigo em Alemão | MEDLINE | ID: mdl-30376777

RESUMO

Cause of Death: 'Intoxication' - a Matter of the Concentration? Abstract. Elucidation of the cause of death is one of the main reasons for medico-legal investigations. In clinical toxicology, the severity of a given poisoning is typically assessed with the blood concentration of a pharmacologically or toxicologically active compound. Such an interpretation proves to be difficult or even impossible in postmortem toxicology. Numerous biochemical and biological processes beginning immediately after death may render the calculated drug concentration unreliable. Concentrations obtained from postmortem samples do not necessarily reflect the blood concentration at the time of death. A prediction if and to what extent such postmortem changes might have occurred is still impossible for individual cases. Interpretation therefore needs to be done with care, considering case circumstances and all available information.


Assuntos
Causas de Morte , Envenenamento/sangue , Relação Dose-Resposta a Droga , Toxicologia Forense , Humanos , Envenenamento/diagnóstico , Envenenamento/patologia , Venenos/farmacocinética
8.
Mycotoxin Res ; 34(4): 297-305, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30117108

RESUMO

The Ascomycete fungus Claviceps gigantea infects maize kernels and synthetizes several alkaloids, mostly dihydrolysergamides. There is limited information on the damage these toxins cause in mammals, despite reports from infested areas with 90% presence of the fungus sclerotia. With this background, it was decided to determine the biological activity of chemical compounds present in sclerotia of C. gigantea in rabbits 38 days after weaning. Sclerotia of C. gigantea were collected in fields with high incidence of the disease, ground and analysed for nutrients. Experimental diets were prepared with four treatments, where sclerotial powder was added, substituting for alfalfa flour in increasing proportions [C. gigantea/alfalfa flour (0:100, 5:95, 15:85 and 25:75)]. Total ergot alkaloid content was analysed by high-performance liquid chromatography. Male juvenile rabbits were utilised and distributed in completely randomised design with four replications. Initial weight was recorded in each animal, and experimental diet was offered. In this study, weight of animals, feed consumption and feed conversion were evaluated in individual animals. Blood samples were taken for haemograms, and finally euthanasia was practiced. The consumption of C. gigantea had a negative effect on body weight and feed consumption. The necropsies showed anomalies proportional to the consumption of feed contaminated with the fungus.


Assuntos
Ração Animal/microbiologia , Claviceps/química , Dieta/métodos , Alcaloides de Claviceps/toxicidade , Contaminação de Alimentos , Envenenamento/patologia , Animais , Peso Corporal , Cromatografia Líquida de Alta Pressão , Modelos Animais de Doenças , Alcaloides de Claviceps/análise , Masculino , Coelhos , Desmame
9.
Microb Pathog ; 124: 82-88, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30138754

RESUMO

It has been recognized that oxidative stress is implicated in the initiation and progression of diseases due to the excessive formation of free radicals and impairment of the antioxidant defense system, contributing to the mortality of affected animals. The occurrence of a disequilibrium between the antioxidant/oxidant status in serum and liver of freshwater fish fed with aflatoxin B1 (AFB1) remains poorly understood and limited to only a few oxidant variables. Thus, the aim of this study was to evaluate whether an AFB1-contaminated diet causes disturbance on the antioxidant and oxidant status in silver catfish (Rhamdia quelen) of freshwater. Serum and hepatic reactive oxygen species (ROS), metabolites of nitric oxide (NOx), and lipid hydroperoxide increased on days 14 and 21 post-feeding in animals that received AFB1 contaminated diet compared to the control group (basal diet), while protein carbonylation levels increased on day 21 post-feeding. On the other hand, serum and hepatic antioxidant capacity against peroxyl radical and vitamin C levels, as well as glutathione peroxidase and catalase activities were lower on days 14 and 21 post-feeding in animals that received AFB1 contaminated diet compared to the control group. No difference was observed between groups regarding the superoxide dismutase activity and glutathione levels. Based on these evidences, an AFB1-contaminated diet causes a disturbance on serum and hepatic antioxidant/oxidant system due to lipid and protein damage elicited by excessive ROS and NOx production. Also, the antioxidant defense system was unable to avoid or minimize ROS and NOx deleterious effects, and consequently, the oxidative damage. In summary, this disturbance can contribute to understand the pathophysiology and mortality of fish after the consumption of AFB1-contaminated diets.


Assuntos
Aflatoxina B1/toxicidade , Peixes-Gato , Doenças dos Peixes/patologia , Fígado/patologia , Envenenamento/veterinária , Venenos/toxicidade , Soro/química , Administração Oral , Aflatoxina B1/administração & dosagem , Experimentação Animal , Animais , Antioxidantes/análise , Peróxidos Lipídicos/análise , Fígado/efeitos dos fármacos , Óxido Nítrico/análise , Estresse Oxidativo , Envenenamento/patologia , Venenos/administração & dosagem , Carbonilação Proteica , Espécies Reativas de Oxigênio/análise , Fatores de Tempo
10.
Mycotoxin Res ; 34(4): 241-255, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-29971579

RESUMO

The presence of the mycotoxin ochratoxin A (OTA) in cereal grains is due to the growth of toxigenic Penicillium mold on stored crops. Human exposure to OTA is higher in infants, toddlers, and children than in adolescents and adults, based on exposure assessments of ng OTA consumed/kg body weight/day. Ochratoxin A is nephrotoxic and teratogenic in animals, but its effects on juveniles exposed during the reproduction and development period have not been studied. To address this, Fischer rats were exposed to 0, 0.16, 0.4, 1.0, or 2.5 mg OTA/kg diet throughout breeding, gestation, and lactation and its adverse effects were assessed in adult rats and their offspring on postnatal day (PND) 21. There were no effects on implantation but post-implantation fetotoxicity was observed in the 2.5 mg/kg dose group, corresponding to a calculated dose of 167.0 µg/kg bw/day in dams. Adverse effects on body and kidney weights and on clinical parameters indicative of renal toxicity were significant in adult rats exposed to 1.0 mg OTA/kg diet (55.2 and 73.3 µg/kg bw/day in adult males and females, respectively) and in PND21 rats at the 0.4 mg/kg dose (33.9 µg/kg bw/day in dams), suggesting that weanling rats were more sensitive to OTA than adults. Overall, nephrotoxicity was the primary effect of OTA in weanling rats exposed throughout gestation and lactation at sub-fetotoxic concentrations in diet.


Assuntos
Ocratoxinas/toxicidade , Envenenamento/patologia , Complicações na Gravidez/patologia , Insuficiência Renal/patologia , Teratogênios/toxicidade , Anormalidades Induzidas por Medicamentos/epidemiologia , Anormalidades Induzidas por Medicamentos/patologia , Administração Oral , Animais , Modelos Animais de Doenças , Feminino , Ocratoxinas/administração & dosagem , Gravidez , Ratos Endogâmicos F344 , Insuficiência Renal/induzido quimicamente
11.
Toxicol Mech Methods ; 28(7): 475-487, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-29685079

RESUMO

Humans accumulate large numbers of inorganic particles in their lungs over a lifetime. Whether this causes or contributes to debilitating disease over a normal lifespan depends on the type and concentration of the particles. We developed and tested a protocol for in situ characterization of the types and distribution of inorganic particles in biopsied lung tissue from three human groups using field emission scanning electron microscopy (FE-SEM) combined with energy dispersive spectroscopy (EDS). Many distinct particle types were recognized among the 13 000 particles analyzed. Silica, feldspars, clays, titanium dioxides, iron oxides and phosphates were the most common constituents in all samples. Particles were classified into three general groups: endogenous, which form naturally in the body; exogenic particles, natural earth materials; and anthropogenic particles, attributed to industrial sources. These in situ results were compared with those using conventional sodium hypochlorite tissue digestion and particle filtration. With the exception of clays and phosphates, the relative abundances of most common particle types were similar in both approaches. Nonetheless, the digestion/filtration method was determined to alter the texture and relative abundances of some particle types. SEM/EDS analysis of digestion filters could be automated in contrast to the more time intensive in situ analyses.


Assuntos
Doença Ambiental/patologia , Compostos Inorgânicos/análise , Pulmão/química , Material Particulado/análise , Envenenamento/patologia , Adulto , Biópsia , Doença Ambiental/induzido quimicamente , Doença Ambiental/diagnóstico , Humanos , Indicadores e Reagentes/química , Exposição por Inalação/efeitos adversos , Compostos Inorgânicos/química , Compostos Inorgânicos/toxicidade , Pulmão/patologia , Pulmão/ultraestrutura , Metais/análise , Metais/química , Metais/toxicidade , Microscopia Eletrônica de Varredura , Medicina Militar/métodos , Militares , Tamanho da Partícula , Material Particulado/química , Material Particulado/toxicidade , Envenenamento/diagnóstico , Hipoclorito de Sódio/química , Solo/química , Espectrometria por Raios X , Estados Unidos
12.
J Nutr Biochem ; 51: 80-90, 2018 01.
Artigo em Inglês | MEDLINE | ID: mdl-29107825

RESUMO

The burden and morbidity of environmental nephrosis is increasing globally. Atrazine (ATR) and degradation products in the environment are considered key determinants of nephrosis. However, the lack of highly effective treatments for environmental nephrosis creates an urgent need to better understand the preventive strategies and mechanisms. This study aimed to highlight the mechanism of ATR-induced environmental nephrosis and the chemoprotective potential of lycopene (LYC) against the renal injury and nephrosis. Male mice were treated with LYC (5 mg/kg) and/or ATR (50 mg/kg or 200 mg/kg) by gavage administration for 21 days. Histopathological changes and biochemical function, cytochrome P450 enzymes system (CYP450s), nuclear xenobiotic receptors (NXRs) response and the transcription of CYP isoforms (CYPs) were detected. ATR exposure caused the changes of the histopathological and biochemical function, activated the NXR response and disturbed the CYP450s homeostasis. Supplementary LYC significantly prevented ATR-induced nephrotoxicity and alleviated the alternation of histopathological and biochemical function via modulating the CYP450s homeostasis and the NXR response. The results demonstrated AHR, CAR, PXR, PPAR (α, γ), CYP1, CYP2, CYP3 and CYP4 superfamily play a vital role in LYC-ATR interaction. Our findings provide new evidence that ATR exposure can cause the environmental nephrosis via inducing the kidney injury. Supplementary LYC showed significant chemoprotective potential against ATR-induced renal injury and environmental nephrosis via regulating the NXR response and the CYP450s homeostasis.


Assuntos
Antioxidantes/uso terapêutico , Atrazina/toxicidade , Carotenoides/uso terapêutico , Herbicidas/toxicidade , Nefrose/prevenção & controle , Envenenamento/fisiopatologia , Receptores de Esteroides/antagonistas & inibidores , Transporte Ativo do Núcleo Celular/efeitos dos fármacos , Animais , Animais não Endogâmicos , Atrazina/administração & dosagem , Núcleo Celular/efeitos dos fármacos , Núcleo Celular/metabolismo , Núcleo Celular/patologia , Sistema Enzimático do Citocromo P-450/química , Sistema Enzimático do Citocromo P-450/genética , Sistema Enzimático do Citocromo P-450/metabolismo , Suplementos Nutricionais , Relação Dose-Resposta a Droga , Perfilação da Expressão Gênica , Regulação da Expressão Gênica/efeitos dos fármacos , Herbicidas/administração & dosagem , Rim/efeitos dos fármacos , Rim/metabolismo , Rim/patologia , Rim/fisiopatologia , Licopeno , Masculino , Camundongos , Nefrose/etiologia , Envenenamento/metabolismo , Envenenamento/patologia , Receptor de Pregnano X , Análise de Componente Principal , Receptores Citoplasmáticos e Nucleares/agonistas , Receptores Citoplasmáticos e Nucleares/antagonistas & inibidores , Receptores Citoplasmáticos e Nucleares/genética , Receptores Citoplasmáticos e Nucleares/metabolismo , Receptores de Esteroides/agonistas , Receptores de Esteroides/genética , Receptores de Esteroides/metabolismo
13.
Fa Yi Xue Za Zhi ; 33(1): 48-51, 2017 Feb.
Artigo em Chinês | MEDLINE | ID: mdl-29231010

RESUMO

Insulin as a common clinical hypoglycemic agent can effectively control serves to lower the concentration of blood glucose. However, insulin overdose can lead to death. In the whole fatal cases of insulin overdose, medical accident is the most common, followed by suicide. Though insulin homicide is extremely rare, it deserves great attention. Though there are some researches about insulin poisoning on forensic toxicology and pathology, it is still a difficult task in forensic practice. In this paper, the mechanism of death, pathological changes, detection methods and diagnose criteria of insulin overdose will be discussed in the view of forensic toxicology and pathology. We hope that this paper could enhance relative knowledges of insulin poisoning for medical examiners.


Assuntos
Overdose de Drogas , Toxicologia Forense , Hipoglicemiantes/envenenamento , Insulinas/envenenamento , Envenenamento/patologia , Acidentes , Morte , Homicídio , Humanos , Hipoglicemiantes/uso terapêutico , Insulinas/uso terapêutico , Suicídio
14.
Vet Ital ; 53(3): 251-254, 2017 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-29152707

RESUMO

Ethylene glycol (EG) is a well known toxic compound, the assumption of which can be fatal to pet animals as well as to humans. Limited information is available on the pathological features of EG poisoning in pet animals, with special emphasis on cats. Twenty-five cats with histologically confirmed EG intoxication were retrospectively investigated, in order to define more precisely the gross pathological findings and improve the diagnostic process. Furthermore, a brief comparison with the lesions reported in EG-poisoned human patients and dogs was also made.


Assuntos
Etilenoglicol/envenenamento , Animais , Gatos , Etilenoglicol/toxicidade , Humanos , Envenenamento/patologia , Estudos Retrospectivos
15.
J Am Vet Med Assoc ; 251(6): 689-695, 2017 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-28857697

RESUMO

OBJECTIVE To establish the minimum toxic dose of isoniazid in dogs, characterize the clinical signs and outcomes for dogs following isoniazid ingestion, and determine whether IV administration of pyridoxine to dogs with isoniazid toxicosis is protective against death. DESIGN Retrospective case series. ANIMALS 137 dogs with isoniazid toxicosis. PROCEDURES The electronic database of the American Society for the Prevention of Cruelty to Animals Animal Poison Control Center was reviewed from January 2004 through December 2014 to identify dogs with isoniazid toxicosis. For each dog identified, information extracted from the medical record included signalment, estimated dose of isoniazid ingested, clinical signs, treatment, and outcome. Follow-up communication with pet owners or primary care veterinarians was performed when necessary to obtain missing information. RESULTS Clinical signs of isoniazid toxicosis were observed in 134 of 137 (98%) dogs and included seizures (n = 104), CNS signs without seizures (94), and gastrointestinal (41), cardiovascular (19), urogenital (4), and respiratory (1) abnormalities. Of the 87 dogs for which the outcome was available, 61 survived, 18 died, and 8 were euthanized. Probability of survival was positively associated with body weight and IV administration of pyridoxine and negatively associated with dose of isoniazid ingested and presence of seizures. Dogs that received pyridoxine IV were 29 times as likely to survive as dogs that did not receive pyridoxine IV. CONCLUSIONS AND CLINICAL RELEVANCE Results indicated rapid diagnosis of isoniazid toxicosis and prompt treatment of affected dogs with pyridoxine and other supportive care were imperative for achieving a successful outcome.


Assuntos
Antituberculosos/toxicidade , Doenças do Cão/induzido quimicamente , Isoniazida/toxicidade , Envenenamento/veterinária , Animais , Cães , Feminino , Masculino , Envenenamento/patologia , Piridoxina/uso terapêutico , Estudos Retrospectivos , Complexo Vitamínico B/uso terapêutico
16.
Sci Rep ; 7(1): 7912, 2017 08 11.
Artigo em Inglês | MEDLINE | ID: mdl-28801624

RESUMO

One of the hallmarks of acute inflammation is neutrophil infiltration of tissues. We investigated molecular mechanisms implicated in acute neutrophilic inflammation induced by the venom of a freshwater stingray (Potamotrygon cf. henlei) in mice. Ray venom induced early mobilization of neutrophil in the microvasculature of cremaster mice and infiltration of the peritoneal cavity 2 hours after injury, in a dose-response manner. IL-1ß, IL-6, TNF-α, and KC were produced. The neutrophilic infiltration did not occur in mice with ST2 receptor and MyD88 adapters neutralized, or in those with PI3K and p38 MAPK signaling blocked. Drastic reduction of neutrophil infiltration to peritoneal cavities was observed in ST2-/-, TLR2/TLR4-/-, MyD88-/-, TRIF-/- and IL-17A-/- mice, and a partial reduction was observed in IL-18R-/- mice. Mast cell Kit W(sh)/W(sh)-, AHR-, NLRP3-, ICE-, IL-1ß-, P2RX7-, CD39-, IL-17RA-, and TBX21 KO mice retain the ability to induce neutrophilia in peritoneal cavity after ray venom injection. IL-6 and TNF-α alone were insufficient for promote neutrophilia in the absence of ST2 signaling. Finally, abundant production of IL-33 by cardiomyocytes was observed. These results refine our understanding of the importance of the IL-33/ST2 axis and IL-33-producing cardiomyocytes in the early acute neutrophilia induced by freshwater stingray venoms.


Assuntos
Interleucina-33/metabolismo , Mastócitos/efeitos dos fármacos , Miócitos Cardíacos/efeitos dos fármacos , Miócitos Cardíacos/metabolismo , Neutrófilos/imunologia , Venenos/toxicidade , Peçonhas/toxicidade , Animais , Citocinas/genética , Citocinas/metabolismo , Proteína 1 Semelhante a Receptor de Interleucina-1/genética , Proteína 1 Semelhante a Receptor de Interleucina-1/metabolismo , Camundongos , Camundongos Knockout , Cavidade Peritoneal/patologia , Envenenamento/patologia , Venenos/administração & dosagem , Transdução de Sinais , Rajidae , Peçonhas/administração & dosagem
17.
Toxicol Mech Methods ; 27(7): 511-517, 2017 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-28463034

RESUMO

Aniline exposure is associated with toxicity to the spleen, however, early molecular events in aniline-induced cell cycle progression in the spleen remain unknown. MicroRNAs (miRNAs) have been implicated in tumor development by modulating key cell cycle regulators and controlling cell proliferation. This study was, therefore, undertaken on the expression of miRNAs, regulation of cyclins and cyclin-dependent kinases (CDKs) in an experimental condition that precedes a tumorigenic response. Male SD rats were treated with aniline (1 mmol/kg/day by gavage) for 7 days, and expression of miRNAs, cyclins and CDKs in rat spleens were analyzed. Microarray and/or qPCR analyses showed that aniline exposure led to significantly decreased miRNA expression of let-7a, miR-24, miR-34c, miR-100, miR-125b, and greatly increased miR-181a. The aberrant expression of miRNAs was associated with significantly increased protein expression of cyclins A, B1, D3 and E. Furthermore, remarkably enhanced expression of CDKs like CDK1, CDK2, CDK4, CDK6, especially p-CDK1 and p-CDK2 as well as alternations in the expression of pRB, p27, and CDC25A in the spleens of aniline-treated rats was also observed. The data suggest that aniline exposure leads to aberrant expression of miRNAs in the spleen which could be important in the regulation of cell cycle proteins. Our findings, thus, provide new insight into the role of miRNAs in cell cycle progression, which may contribute to aniline-induced tumorigenic response in the spleen.


Assuntos
Compostos de Anilina/toxicidade , Carcinógenos Ambientais/toxicidade , Ciclo Celular/efeitos dos fármacos , Regulação da Expressão Gênica/efeitos dos fármacos , MicroRNAs/antagonistas & inibidores , Envenenamento/metabolismo , Baço/efeitos dos fármacos , Animais , Análise por Conglomerados , Quinases Ciclina-Dependentes/química , Quinases Ciclina-Dependentes/genética , Quinases Ciclina-Dependentes/metabolismo , Ciclinas/agonistas , Ciclinas/genética , Ciclinas/metabolismo , Indução Enzimática/efeitos dos fármacos , Perfilação da Expressão Gênica , Masculino , MicroRNAs/metabolismo , Envenenamento/patologia , RNA Mensageiro/metabolismo , Distribuição Aleatória , Ratos Sprague-Dawley , Reprodutibilidade dos Testes , Baço/metabolismo , Baço/patologia
18.
J Am Anim Hosp Assoc ; 53(4): 236-241, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28535134

RESUMO

Five dogs were presented with clinical signs compatible with upper airway obstruction, including stridor, stertor, coughing, gagging, and varying degrees of respiratory distress. All dogs had radiographic findings of soft tissue opacity in the area of the pharynx, larynx, or trachea, and several had narrowing of the tracheal lumen. Coagulation abnormalities (prolonged prothrombin time, activated partial thromboplastin time) were present in the four dogs that underwent testing. Four of five dogs were treated for the coagulopathy, presumably due to anticoagulant rodenticide toxicosis, and survived to discharge.Upper airway obstruction is an unusual presentation for anticoagulant rodenticide toxicosis in dogs. Raising the index of suspicion for this treatable condition may help clinicians to identify this sooner.


Assuntos
Obstrução das Vias Respiratórias/veterinária , Doenças do Cão/induzido quimicamente , Hemorragia/veterinária , Envenenamento/veterinária , Rodenticidas/toxicidade , Obstrução das Vias Respiratórias/induzido quimicamente , Animais , Antídotos/administração & dosagem , Antídotos/uso terapêutico , Cães , Evolução Fatal , Feminino , Hemorragia/induzido quimicamente , Hemorragia/complicações , Hemorragia/tratamento farmacológico , Masculino , Envenenamento/patologia , Vitamina K 1/administração & dosagem , Vitamina K 1/uso terapêutico
19.
Toxicol Lett ; 271: 20-25, 2017 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-28237808

RESUMO

Chlorine (Cl2) gas exposure and toxicity remains a concern in military and industrial sectors. While post-Cl2 exposure damage to the lungs and other tissues has been documented and major underlying mechanisms elucidated, no targeted therapeutics that are effective when administered post-exposure, and which are amenable to mass-casualty scenarios have been developed. Our recent studies show nitrite administered by intramuscular (IM) injection post-Cl2 exposure is effective in preventing acute lung injury and improving survival in rodent models. Our goal in this study was to develop a rabbit model of Cl2 toxicity and test whether nitrite affords protection in a non-rodent model. Exposure of New Zealand White rabbits to Cl2 gas (600ppm, 45min) caused significant increases in protein and neutrophil accumulation in the airways and ∼35% mortality over 18h. Nitrite administered 30min post Cl2 exposure by a single IM injection, at 1mg/kg or 10mg/kg, prevented indices of acute lung injury at 6h by up to 50%. Moreover, all rabbits that received nitrite survived over the study period. These data provide further rationale for developing nitrite as post-exposure therapeutic to mitigate against Cl2 gas exposure injury.


Assuntos
Lesão Pulmonar Aguda/prevenção & controle , Cloro , Pulmão/efeitos dos fármacos , Nitritos/farmacologia , Envenenamento/prevenção & controle , Substâncias Protetoras/farmacologia , Lesão Pulmonar Aguda/etiologia , Lesão Pulmonar Aguda/metabolismo , Lesão Pulmonar Aguda/patologia , Animais , Líquido da Lavagem Broncoalveolar/química , Citoproteção , Modelos Animais de Doenças , Gases , Injeções Intramusculares , Interleucina-8/metabolismo , Pulmão/metabolismo , Pulmão/patologia , Masculino , Infiltração de Neutrófilos/efeitos dos fármacos , Nitritos/administração & dosagem , Envenenamento/etiologia , Envenenamento/metabolismo , Envenenamento/patologia , Substâncias Protetoras/administração & dosagem , Coelhos , Fatores de Tempo
20.
Microb Pathog ; 104: 340-347, 2017 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-28126667

RESUMO

Lipopolysaccharide (LPS) of P. multocida B:2, a causative agent of haemorrhagic septicaemia (HS) in cattle and buffaloes, is considered as the main virulence factor and contribute in the pathogenesis of the disease. Recent studies provided evidences about the involvement of the nervous system in pathogenesis of HS. However, the role of P. multocida B:2 immunogens, especially the LPS is still uncovered. Therefore, this study was designed to investigate the role of P. multocida B:2 LPS to induce pathological changes in the nervous system. Nine eight-month-old, clinically healthy buffalo calves were used and distributed into three groups. Calves of Group 1 and 2 were inoculated orally and intravenously with 10 ml of LPS broth extract represent 1 × 1012 cfu/ml of P. multocida B:2, respectively, while calves of Group 3 were inoculated orally with 10 ml of phosphate buffer saline as a control. Significant differences were found in the mean scores for clinical signs, post mortem and histopathological changes especially in Group 2, which mainly affect different anatomic regions of the nervous system, mainly the brain. On the other hand, lower scores have been recorded for clinical signs, gross and histopathological changes in Group 1. These results provide for the first time strong evidence about the ability of P. multocida B:2 LPS to cross the blood brain barrier and induce pathological changes in the nervous system of the affected buffalo calves.


Assuntos
Septicemia Hemorrágica/microbiologia , Lipopolissacarídeos/toxicidade , Sistema Nervoso/microbiologia , Pasteurella multocida/química , Envenenamento/patologia , Animais , Encéfalo/patologia , Búfalos , Septicemia Hemorrágica/patologia , Histocitoquímica , Lipopolissacarídeos/isolamento & purificação , Microscopia , Sistema Nervoso/patologia , Medula Espinal/patologia
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