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1.
Toxicon ; 219: 106921, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36122667

RESUMO

Poisoning by avocado (Persea americana) has been confirmed in sheep, goats, dogs, rabbits and ostriches. The clinical signs and lesions are attributed to the acetogenin, persin. Little is known regarding the epidemiology, clinical signs, lesions and therapy caused by acetogenin-induced heart damage. During the two-year study, we investigated a horse farm with six horses that often fed themselves with P. americana leaves or mature fruit pulp and skin on the ground. Two horses died, and one underwent necropsy, histopathology, and immunohistochemistry using the anti-cardiac troponin C (cTnC). Grossly and histopathologically, there was severe cardiac fibroplasia. Immunohistochemically, there was a multifocal decrease or negative expression in the cTnC cardiomyocytes' cytoplasm. Persea americana leaves were confirmed in the alimentary tract using botanical anatomy and molecular techniques. The chemical investigation by (LC-ESI-MS) revealed the presence of the acetogenins, persin and avocadene 1-acetate from P. americana. Persin was present in leaves and fruits (seed and pulp), while avocadene 1-acetate was found in leaves and fruits (seed, peel, and pulp) with a higher concentration in the pulp. Four other horses have been examined by electrocardiogram, echocardiogram and serum Troponin 1 (cTnI). To establish a causal effect of consumption of P. Americana and heart fibroplasia in horses, long-time experiments must be carried out.


Assuntos
Acetogeninas , Cardiopatias , Doenças dos Cavalos , Persea , Animais , Acetogeninas/toxicidade , Cardiopatias/induzido quimicamente , Cardiopatias/patologia , Cardiopatias/veterinária , Doenças dos Cavalos/induzido quimicamente , Doenças dos Cavalos/patologia , Cavalos , Persea/envenenamento , Troponina C/análise , Fibrose
2.
Food Chem Toxicol ; 169: 113417, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36096290

RESUMO

Aflatoxins are toxic secondary metabolites produced by Aspergillus fungi. The most toxic among them is Aflatoxin B1 (AFB1) which is known to have genotoxic, immunotoxic, teratogenic, carcinogenic, and mutagenic toxic effects (amongst others). The mechanisms responsible for its toxicity include the induction of oxidative stress, cytotoxicity, and DNAdamage. Studies have found that natural anti-oxidants can reduce the damage that AFB1 inflicts on the body by alleviating oxidative stress and inhibiting the biotransformation of AFB1. Therefore, this review outlines the latest progress in research on the use of natural anti-oxidants as antidotes to aflatoxin poisoning and their detoxification mechanisms. It also considers the problems that may possibly arise from their use and their application prospects. Our aim is to provide a useful reference for the prevention and treatment of AFB1 poisoning.


Assuntos
Aflatoxina B1 , Antídotos , Antioxidantes , Desintoxicação Metabólica Fase II , Aflatoxina B1/metabolismo , Aflatoxina B1/envenenamento , Aflatoxina B1/toxicidade , Antídotos/farmacologia , Antioxidantes/farmacologia , Carcinógenos/metabolismo , Carcinógenos/toxicidade , Animais , Galinhas
3.
Toxicol Sci ; 189(2): 175-185, 2022 09 24.
Artigo em Inglês | MEDLINE | ID: mdl-35944217

RESUMO

Larval zebrafish is emerging as a new model organism for studying drug-induced liver injury (DILI) with superiorities in visual assessment, genetic engineering as well as high throughput. Metabolic bioactivation to form reactive intermediates is a common event that triggers DILI. This study first addressed the correlation between acetaminophen metabolism and hepatotoxicity in zebrafish larvae (3-day postfertilization) and demonstrated the occurrence of cytochrome P450 enzymes-mediated acetaminophen (APAP) bioactivation at early developmental stage through characterizing the dose-effect (0-1.6 mg/ml) and the time course (0-72 h) of liver injury and metabolism in the AB strain and LiPan transgenic line Tg(lfabp10a: DsRed; elaA:egfp) expressing the liver-specific fluorescent protein. APAP caused multiorgan developmental retardation and elicited dose- and time-dependent hepatotoxicity. Liver imaging revealed significant changes earlier than histological and biochemical measurements. APAP bioactivation in larval zebrafish was first confirmed by the detection of the glutathione conjugate of the reactive intermediate NAPQI (NAPQI-GSH) and subsequent mercapturate derivatives NAPQI-cysteine and NAPQI-N-acetylcysteine after even short (0.5-h postexposure) or low (0.2 mg/ml) APAP exposure. APAP overdose impaired metabolic function, in particular sulfation, whereas facilitated GSH depletion and APAP sulfate excretion. Meanwhile, APAP displayed triphasic accumulation in the larvae, agreeing with fluctuating metabolic capabilities with sulfation dominating the early larval developmental stage. Most importantly, the dose-response effects and time course of APAP accumulation and metabolism agree well with those of the liver injury development. Overall, larval zebrafish has developed mammalian-like metabolic function, enabling it an ideal model organism for high-throughput screening hepatotoxicity and mechanistic study of bioactivation-based DILI.


Assuntos
Acetaminofen , Doença Hepática Induzida por Substâncias e Drogas , Acetaminofen/envenenamento , Acetilcisteína/farmacologia , Animais , Benzoquinonas , Doença Hepática Induzida por Substâncias e Drogas/metabolismo , Sistema Enzimático do Citocromo P-450/metabolismo , Glutationa/metabolismo , Iminas , Larva/metabolismo , Fígado , Mamíferos/metabolismo , Sulfatos/metabolismo , Sulfatos/farmacologia , Peixe-Zebra/metabolismo
7.
Artigo em Chinês | MEDLINE | ID: mdl-35785891

RESUMO

Objective: To investigate the predictive value of the product of first plasmacolchicine concentration and poisoning time for the prognosis of colchicine poisoning patients, and to provide a basis for early prognosis assessment. Methods: October 2021, patients with colchicine poisoning admitted in the First Affiliated Hospitol of Wenzhou Medical University from January 2017 to September 2021 were collected, including general information such as patient gender, age, oral colchicine dose, poisoning time, the first laboratory test index andplasma colchicine concentration after admission. The patients were divided into survival group and death group according to their prognosis. The differences in clinical indicators such as admission plasma colchicine concentration, blood routine, blood biochemistry, coagulation function, and blood gas analysis were compared between the two groups, and their predictive value for the prognosis of patients were analyzed. Results: A total of 23 patients with colchicine poisoning, aged 20-85 years, were included in this study, of which 15 cases (65.22%) survived and 8 cases (34.78%) died. The first plasma colchicine concentration at admision were 0.42-53.61 ng/ml. The plasma colchicine concentration and the concentration-time product were 10.08-2147.04 h·ng/ml.Compared with the survival group, the plasma colchicine concentration and the concentration-time product in the death group were significantly increased, and the differences were statistically significant (P<0.05). Univariate logistic regression analysis showed that first plasma concentration and poisoning time>132.48 h·ng/ml, high C-reactive protein, high D-dimer, high absolute value of BE were the risk factors for the prognosis of patients with colchicine poisoning (OR=12.000, 95%CI: 1.1181-128.836; OR=1.053, 95%CI: 1.009-1.098; OR=1.219, 95%CI: 1.039-1.429; OR=1.360, 95%CI: 1.1.044-1.773; P<0.05). High prothrombin time activity was protective factor affecting the prognosis of colchicine poisoning patients (OR=0.941, 95%CI: 0.892~0.993; P<0.05). ROC curve analysis showed that the areas under the curves of first plasma concentration and poisoning time, C-reactive protein, absolute value of BE, D-dimer for predicting the prognosis of patients with colchicine poisoning were 0.918, 0.888, 0.867, 0.837, respectively, and the areas under the curves of prothrombin time activityfor predicting the prognosis of patients with colchicine poisoning was 0.788 (P<0.05) . Conclusion: The product of the first plasma colchicine concentration at admission and poisoning time is closely related to the prognosis of patients with colchicine poisoning, it can be used as a predictor for early evaluation of the prognosis of poisoned patients.


Assuntos
Proteína C-Reativa , Colchicina , Colchicina/sangue , Colchicina/farmacocinética , Colchicina/envenenamento , Humanos , Prognóstico , Curva ROC , Fatores de Risco , Fatores de Tempo
8.
J Vet Emerg Crit Care (San Antonio) ; 32(6): 824-829, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-35869756

RESUMO

OBJECTIVE: To describe the rapid diagnosis, treatment, and clinical course of a dog that ingested an amanitin-containing mushroom. CASE SUMMARY: A 2-month-old female intact Australian Shepherd presented with diarrhea and vomiting, along with a possible mushroom exposure. Upon presentation, the dog's urine was collected and tested positive by a point-of-care rapid diagnostic test specific for detecting amanitins, the causative agents of amatoxicosis. NEW OR UNIQUE INFORMATION PROVIDED: This is the first reported case of amatoxicosis that was diagnosed using a point-of-care test prior to starting treatment. An early diagnosis helps to guide early treatment decisions in this frequently fatal toxicosis.


Assuntos
Amanitinas , Doenças do Cão , Intoxicação Alimentar por Cogumelos , Animais , Cães , Feminino , Amanitinas/envenenamento , Austrália , Doenças do Cão/induzido quimicamente , Doenças do Cão/diagnóstico , Diagnóstico Precoce , Intoxicação Alimentar por Cogumelos/diagnóstico , Intoxicação Alimentar por Cogumelos/veterinária , Testes Imediatos , Urinálise/veterinária
9.
Leg Med (Tokyo) ; 59: 102111, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-35802996

RESUMO

Recently, 2-aminothiazoline-4-carboxylic acid (ATCA), a cyanide (CN) metabolite, has been proposed as a stable diagnostic marker of CN poisoning. In this study, liquid chromatography coupled with electrospray ionization - tandem mass spectrometry was used to quantify ATCA concentrations in human postmortem blood samples, and differences in ATCA concentrations according to age and sex were determined. Both age and sex had significant effects on blood ATCA concentrations. Although ATCA concentrations exhibited an inverted U shape with increasing age in men, in women ATCA concentrations plateaued at around 40-59 years of age. There were significant differences between the sexes in ATCA concentrations for the 20-39 and 40-59 year age groups (P < 0.05 and P < 0.01, respectively). Correlations between ATCA concentrations and carboxyhemoglobin (CO-Hb) saturation were also examined in fire victims. ATCA concentrations increased significantly with increasing CO-Hb saturation (r = 0.382, P < 0.01). In addition, ATCA concentrations were also correlated to CN concentrations (r = 0.309, P < 0.05). The results of our study may provide novel information about the contribution of CN poisoning to the cause of death at fire scenes.


Assuntos
Carboxihemoglobina , Cianetos , Incêndios , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Carboxihemoglobina/análise , Ácidos Carboxílicos , Cianetos/envenenamento , Caracteres Sexuais , Adulto Jovem , Autopsia
11.
Emergencias (Sant Vicenç dels Horts) ; 34(3): 190-195, Jun. 2022. tab, graf
Artigo em Espanhol | IBECS | ID: ibc-203722

RESUMO

Objetivo. Conocer los aspectos clínicos relacionados con el tratamiento del antídoto N-acetilcisteína (NAC) en las intoxicaciones por paracetamol. Método. Estudio observacional y retrospectivo de los pacientes atendidos por intoxicación por paracetamol en cuatro servicios de urgencias durante 3 años (2017-2019). Se analizan variables epidemiológicas, clínicas y asistenciales, así como la idoneidad y seguridad en el empleo del tratamiento antidótico. Resultados. Se incluyeron 332 intoxicaciones: 260 casos (78%) tenían más de 16 años y 242 (73%) fueron mujeres. Doscientos sesenta y ocho intoxicaciones (81%) fueron de causa voluntaria y la semivida de eliminación se determinó en 20 ocasiones (6%). La descontaminación digestiva se indicó de forma incorrecta en 39 ocasiones (28%). Se inició tratamiento con antídoto en 195 casos (58,7%). En 282 casos (85%) no hubo ninguna clínica de gravedad. La correlación entre la dosis referida ingerida y la paracetamolemia en los casos de ingesta voluntaria (R2 = 0,23) fue más fuerte que en los casos de ingesta accidental (R2 = 0,007). Existieron diferencias estadísticamente significativas al relacionar los criterios de gravedad con la dosis referida ajustada al peso (p = 0,001) y el intervalo desde la ingesta y la primera asistencia médica (p = 0,008). Conclusiones. Existe variabilidad en aspectos fundamentales del tratamiento antidótico en las intoxicaciones por paracetamol, a pesar de estar claramente protocolizado su manejo.


Objective. To identify the most common problems related to use of N-acetylcysteine to reverse the toxic effects of paracetamol poisoning. Methods. Retrospective descriptive observational study of clinical records for patients treated for paracetamol poisoning in 4 emergency departments during 3 years (2017-2019). We analyzed epidemiologic, clinical, and care variables, especially those related to the suitability and safety of using N-acetylcysteine as an antidote. Results. We included 332 cases of poisoning of 260 patients (78%) were over the age of 16 years, and 242 (73%) were female. Two hundred sixty-eight poisonings (81%) were the result of voluntary intake. The elimination half-life was determined in 20 cases (6%). Gastrointestinal decontamination was incorrectly prescribed on 39 occasions (28%). Treatment with the antidote was begun in 195 cases (58.7%). No serious clinical signs or symptoms were present in 282 cases (85%). The correlation of paracetamol levels in urine was stronger with the amount of drug ingested voluntarily (R2 = 0.23) than with accidental intake (R2 = 0.007). Predefined severity criteria were significantly related to reported dose ingested per body weight (P = .001) and the interval between intake and first medical assistance (P = .008). Conclusions. Even though clear protocols are available to guide the use of antidote treatment in cases of paracetamol poisoning, variability in fundamental aspects of management is excessive.


Assuntos
Humanos , Acetilcisteína/administração & dosagem , Intoxicação , Administração Oral , Doença Hepática Induzida por Substâncias e Drogas , Mortalidade , Estudos Multicêntricos como Assunto , Acetaminofen , Antídotos/envenenamento , Serviços Médicos de Emergência
12.
Oxid Med Cell Longev ; 2022: 7832983, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35707280

RESUMO

Paraquat (PQ), a highly toxic herbicide and primary attack for lung, results in severe acute lung injury (ALI) appeared as evident oxidative stress, inflammation, and apoptosis. Increasing evidence elucidates that nuclear factor erythroid-2-related factor 2 (Nrf2) and its associated nuclear factor-κB (NF-κB) exhibit many merits for protection of ALI by coordinating a fine-turned response to oxidative stress, inflammation, and apoptosis. Ginkgolide C (GC) has been reported to be a safe and potent therapeutic agent against ALI. However, whether GC could protect ALI induced by PQ poisoning and the possible underlining mechanisms have remained not to be fully elucidated. A rat model of ALI and a model of acute type II alveolar epithelial cell (RLE-6TN) injury constructed by exposure to PQ were applied to discuss the protective effect of GC. Furthermore, Nrf2 gene silencing RLE-6TN cells were used to discuss the exact mechanism. We confirmed that GC significantly ameliorated the histopathological damages, ultrastructural changes, lung injury score, W/D ratio, and Hyp activity of lung tissue and inhibited polymorphonuclear neutrophil (PMN) infiltration after PQ poisoning. Further results revealed that GC remarkably activated Nrf2-based cytoprotective system and inhibited NF-κB-induced inflammatory injury as well as apoptosis. Taken together, we concluded that GC preserved protection of PQ-induced ALI via the Nrf2-NF-κB dependent signal pathway, which may provide us novel insights into the treatment strategies for PQ poisoning.


Assuntos
Lesão Pulmonar Aguda , Ginkgolídeos , Fator 2 Relacionado a NF-E2 , NF-kappa B , Paraquat , Lesão Pulmonar Aguda/induzido quimicamente , Lesão Pulmonar Aguda/tratamento farmacológico , Lesão Pulmonar Aguda/metabolismo , Animais , Fator de Transcrição de Proteínas de Ligação GA/metabolismo , Ginkgolídeos/farmacologia , Inflamação/patologia , Lactonas , Pulmão/patologia , Fator 2 Relacionado a NF-E2/metabolismo , NF-kappa B/metabolismo , Estresse Oxidativo , Paraquat/envenenamento , Ratos , Transdução de Sinais
13.
Sci Signal ; 15(740): eabn4395, 2022 06 28.
Artigo em Inglês | MEDLINE | ID: mdl-35763560

RESUMO

Ligands of the transforming growth factor-ß (TGF-ß) superfamily, including TGF-ßs, activins, and bone morphogenetic proteins (BMPs), have been implicated in hepatic development, homeostasis, and pathophysiology. We explored the mechanisms by which hepatocytes decode and integrate injury-induced signaling from TGF-ßs and activins (TGF-ß/Activin) and BMPs. We mapped the spatiotemporal patterns of pathway activation during liver injury induced by acetaminophen (APAP) in dual reporter mice carrying a fluorescent reporter of TGF-ß/Activin signaling and a fluorescent reporter of BMP signaling. APAP intoxication induced the expression of both reporters in a zone of cells near areas of tissue damage, which showed an increase in autophagy and demarcated the borders between healthy and injured tissues. Inhibition of TGF-ß superfamily signaling by overexpressing the inhibitor Smad7 exacerbated acute liver histopathology but eventually accelerated tissue recovery. Transcriptomic analysis identified autophagy as a process stimulated by TGF-ß1 and BMP4 in hepatocytes, with Trp53inp2, which encodes a rate-limiting factor for autophagy initiation, as the most highly induced autophagy-related gene. Collectively, these findings illustrate the functional interconnectivity of the TGF-ß superfamily signaling system, implicate the coordinated activation of TGF-ß/Activin and BMP pathways in balancing tissue reparatory and regenerative processes upon APAP-induced hepatotoxicity, and highlight opportunities and potential risks associated with targeting this signaling system for treating hepatic diseases.


Assuntos
Acetaminofen , Proteínas Morfogenéticas Ósseas , Doença Hepática Induzida por Substâncias e Drogas , Fator de Crescimento Transformador beta , Acetaminofen/envenenamento , Ativinas/metabolismo , Animais , Autofagia , Proteínas Morfogenéticas Ósseas/genética , Proteínas Morfogenéticas Ósseas/metabolismo , Doença Hepática Induzida por Substâncias e Drogas/etiologia , Doença Hepática Induzida por Substâncias e Drogas/genética , Doença Hepática Induzida por Substâncias e Drogas/metabolismo , Fígado/efeitos dos fármacos , Fígado/metabolismo , Camundongos , Transdução de Sinais/efeitos dos fármacos , Fator de Crescimento Transformador beta/genética , Fator de Crescimento Transformador beta/metabolismo
14.
Biomed Pharmacother ; 151: 113152, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35594712

RESUMO

BACKGROUND: Although some studies have shown the average side effects of cardiovascular medication, the short-term effect after newly initiated cardiovascular medications has not been studied in any detail. We aim to determine the effect of newly initiated cardiovascular medications resulting in unintentional poisoning and to identify those at high risk. METHODS: A case-crossover design was used. From the Swedish National Patient Register, a total of 9,354 persons aged ≥ 50 and hospitalized with a first event of unintentional poisoning between July 2006 and September 2018 were identified. Through linkage to the Prescribed Drug Register, exposure to newly initiated cardiovascular medication during the case period (1-28 days prior to the onset date of unintentional poisoning) was compared with that in a corresponding control period (113-140 days prior to the onset date). Conditional logistic regression was used to determine the associations in total, for different time periods as well as by age, sex, underlying comorbidity, and use of other medications. RESULTS: Newly initiated cardiovascular medications were associated with a higher risk of unintentional poisoning, especially during the first week after initiation (odds ratio [OR]=1.39), (95% confidence interval [CI]=1.08-1.79). The risk of unintentional poisoning was comparable across age groups, sex, underlying comorbidities, and medications with OR (95% CI) ranging from 1.15 (0.75-1.74) to 2.00 (1.15-3.47). CONCLUSION: This large population-based case-crossover study showed that newly initiated cardiovascular medication is associated with an increased risk of unintentional poisoning, particularly during the first week after initiation. The risk is comparable across age, sex, underlying comorbidity, and medications.


Assuntos
Fármacos Cardiovasculares , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Idoso , Fármacos Cardiovasculares/envenenamento , Estudos de Casos e Controles , Estudos Cross-Over , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Razão de Chances , Sistema de Registros , Medição de Risco , Suécia/epidemiologia
15.
Leg Med (Tokyo) ; 58: 102084, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-35561504

RESUMO

The purpose of this study is to show a very rare complication of acute cocaine poisoning, namely heart rupture. In the present case report, acute cocaine intoxication caused massive myocardial infarction, resulting in heart rupture and cardiac tamponade. A crime scene investigation found a dead body on the street in a drug dealing district. Examination of the body showed no external injuries. A thorough autopsy was performed showing massive cardiac tamponade with 510 ml of blood within the pericardium and full-thickness tissue lesion at the posterior wall of the left ventricle of 3.5 × 3 cm. Histological examination in hematoxylin and eosin was performed and confirmed the interruption of the posterior wall of the left ventricle with the presence of blood. In fact, although the correlation between cocaine and myocardial damage is well established, the relationship between heart rupture and acute cocaine intoxication is an extremely rare event. Moreover, since there are, to date, few reports of similar deaths, our report provides useful information regarding sudden death in a cocaine abuser. It is, therefore, of crucial importance to report this case to the scientific community.


Assuntos
Cocaína/envenenamento , Ruptura Cardíaca , Infarto do Miocárdio , Vasoconstritores , Autopsia , Transtornos Relacionados ao Uso de Cocaína , Morte Súbita , Toxicologia Forense , Ruptura Cardíaca/induzido quimicamente , Humanos , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/induzido quimicamente , Vasoconstritores/envenenamento
16.
Hum Exp Toxicol ; 41: 9603271221094008, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35442113

RESUMO

BACKGROUND: Acute paraquat poisoning-induced multiple organ dysfunction syndrome (MODS) leads to the high mortality. This study aimed to investigate the clinical significance of microRNA-200b-3p (miR-200b-3p), an upstream inhibitor of high-mobility group box 1 (HMGB1), in acute paraquat poisoning patients for the prediction of MODS and survival. METHODS: This study enrolled 80 patients with MODS induced by paraquat and 94 healthy volunteers. The interaction between miR-200b-3p and HMGB1 was identified by luciferase reporter assay. miR-200b-3p levels were measured by quantitative real-time (QRT) PCR. High-mobility group box 1 levels were measured by enzyme-linked immune sorbent assay (ELISA). Receiver operating characteristic analysis was used to evaluate the diagnostic value of miR-200b-3p in screening MODS patients. The relationship between miR-200b-3p and the 28-day survival of MODS patients was evaluated by Kaplan-Meier curves and log-rank test. Cox regression analysis was used to assess the prognostic value of miR-200b-3p. Correlation between miR-200b-3p and HMGB1 was confirmed by Pearson's correlation analysis. RESULTS: miR-200b-3p directly target HMGB1. miR-200b-3p, decreased in MODS patients, had high diagnostic value to screen MODS patients from healthy controls. Additionally, serum miR-200b-3p was decreased in non-survivors, and patients with low miR-200b-3p level had poor 28-day survival. Serum miR-200b-3p could independently predict the survival prognosis. Moreover, serum HMGB1 level was increased in MODS patients, and was negatively correlated with miR-200b-3p level. CONCLUSION: Decreased miR-200b-3p may function as a biomarker for the diagnosis and survival prognosis of MODS patients, and miR-200b-3p may be involved in the progression of acute paraquat-induced MODS via regulating inflammatory responses by targeting HMGB1.


Assuntos
Proteína HMGB1 , MicroRNAs , Insuficiência de Múltiplos Órgãos , Paraquat , Biomarcadores , Proteína HMGB1/genética , Humanos , Insuficiência de Múltiplos Órgãos/induzido quimicamente , Paraquat/envenenamento , Prognóstico
17.
Environ Res ; 212(Pt A): 113225, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-35390304

RESUMO

BACKGROUND: Perfluoroalkyl substances (PFAS) have been consistently associated with cardio-metabolic traits. Occupational exposures to multiple PFAS with health outcomes have been poorly investigated. The aim of the present study was to examine these associations among former workers involved in PFAS production. METHODS: We considered 232 male ex-employees who had worked in a factory (Trissino, Veneto Region, Italy), which produced PFAS and other chemicals during 1968-2018. Out of twelve serum PFAS, only four (PFOA, PFOS, PFHxS, and PFNA) were quantifiable in at least 50% of samples. Non-fasting serum total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), systolic blood pressure (SBP) and diastolic blood pressure (DBP) were measured. The associations between serum PFAS mixture and considered outcomes were assessed through linear regression mixed models and Weighted Quantile Sum (WQS) regression, adjusting for potential confounders. RESULTS: PFOA was detected at the highest level, with a median concentration (in ng/mL) of 80.8 (min-max: 0.35-13,033), followed by PFOS (median: 8.55, min-max: 0.35-343), PFHxS (median: 6.8, min-max: 0.35-597) and PFNA (median: 0.8, min-max: 0.35-5). We observed that each A quartile increase in the WQS index was positively associated with the levels of TC (ß: 8.41, 95% IC: 0.78-16.0), LDL-C (ß: 8.02, 95% IC: 1-15.0) and SBP (ß: 3.21, 95% IC: 0.82-5.60). No association of serum PFAS concentration on HDL cholesterol and DBP emerged. WQS analyses revealed a major contribution of PFNA and PFHxS for the cholesterol levels, although PFOA reported the highest concentration. PFOA and PFOS emerged as chemicals of concern regarding the association with SBP. CONCLUSIONS: The results showed a clear association between serum PFAS levels and markers of cardiovascular risk and support the importance of clinical surveillance of cardiovascular risk factors in population with a high exposure to PFAS, especially in the occupational setting.


Assuntos
Ácidos Alcanossulfônicos , Fluorcarbonetos , Ácidos Alcanossulfônicos/efeitos adversos , Ácidos Alcanossulfônicos/envenenamento , Biomarcadores , Pressão Sanguínea , LDL-Colesterol , Fluorcarbonetos/efeitos adversos , Fluorcarbonetos/envenenamento , Humanos , Itália , Modelos Lineares , Masculino , Exposição Ocupacional/efeitos adversos
18.
Arch Toxicol ; 96(6): 1751-1766, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-35384471

RESUMO

Approximately 70-90% of mushroom poisoning deaths are caused by α-amanitin-induced liver injury resulting from RNA polymerase II (RNAP II) inhibition. Liver regeneration ability may contribute greatly to individual survival after α-amanitin poisoning. However, it is unclear what cellular pathways are activated to stimulate regeneration. We conducted dose-effect and time-effect studies in mice that were intraperitoneally injected with 0.33-0.66 mg/kg α-amanitin to establish a poisoning model. The liver/body weight ratio, serological indices, and pathology were evaluated to characterize the liver injury. In the time-effect study, the liver transcriptome was analyzed to explore the mRNA changes resulting from RNAP II inhibition and the underlying pathways associated with recovery. Based on the two animal studies, we established a poisoning model with three sequential liver states: early injury, regulation, and recovery. The mRNA changes reflected by the differentially expressed genes (DEGs) in the transcriptome could be used to illustrate the inhibition of RNAP II by α-amanitin. DEGs at four key time points were well matched with the three liver states, including 8-h downregulated genes in the early injury state, 16-h and 72-h upregulated genes in the regulation state, and 96-h upregulated/downregulated genes in the recovery state. By clustering analysis, the mTOR signaling pathway was screened out as the most promising potential pathway promoting recovery. The results of our investigations of the pathways and events downstream of the mTOR pathway indicated that the activation of mTOR probably contributes crucially to liver regeneration, which could be a promising basis for drug development.


Assuntos
Agaricales , Alfa-Amanitina , Fígado , Intoxicação Alimentar por Cogumelos , Transcriptoma , Alfa-Amanitina/envenenamento , Animais , Perfilação da Expressão Gênica , Fígado/efeitos dos fármacos , Fígado/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos ICR , Intoxicação Alimentar por Cogumelos/metabolismo , RNA Polimerase II/genética , RNA Polimerase II/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Serina-Treonina Quinases TOR/metabolismo
19.
Emerg Med Australas ; 34(4): 639-641, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-35475321

RESUMO

Although sodium bicarbonate can be a life-saving antidote for patients with overdoses resulting in sodium channel blockade, there has been a concerning rise in cases referred to the Poisons Information Centre where inappropriately large doses of bicarbonate have been used resulting in iatrogenic harm. We present a series of three clinical cases where excessive bicarbonate was used to treat poisonings and discuss our approach to managing cardiotoxicity secondary to sodium channel blockade. Serial blood gas analysis should be performed when using bicarbonate to ensure pH targets are met and severe alkalaemia, hypernatraemia and hypokalaemia are avoided. We encourage clinicians to contact the Poisons Information Centre (13 11 26) or their local clinical toxicologist when managing patients with life-threatening sodium channel blockade.


Assuntos
Bicarbonatos , Overdose de Drogas , Bloqueadores dos Canais de Sódio , Bicarbonatos/envenenamento , Overdose de Drogas/tratamento farmacológico , Humanos , Bloqueadores dos Canais de Sódio/toxicidade
20.
Toxicol Mech Methods ; 32(9): 678-685, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-35392760

RESUMO

OBJECTIVE: In this study, differentially expressed genes (DEGs) and signaling pathways involved in diquat (DQ) and paraquat (PQ) poisoning were identified via bioinformatics analysis, in order to inform the development of novel clinical treatments. METHODS: Raw data from GSE153959 were downloaded from the Gene Expression Omnibus database. DEGs of the DQ vs. control (CON) and PQ vs. CON comparison groups were identified using R, and DEGs shared by the two groups were identified using TBtools. Subsequently, the shared DEGs were searched in the Gene Ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) databases, using the Database for Annotation, Visualization, and Integrated Discovery. A protein-protein interaction (PPI) network was constructed, and hub genes were identified using the cytoHubba plug-in in Cytoscape software. Finally, circos and contrast plots showing the DEGs shared between mouse and human chromosomes were constructed using TBtools. RESULTS: Thirty-one DEGs shared by the DQ and PQ groups were identified. Enriched biological process terms included positive regulation of cell proliferation and translation. Enriched cellular component terms included extracellular region, intracellular membrane-bounded organelle and mitochondrion. Enriched molecular function terms included transcription factor activity and sequence-specific double-stranded DNA binding. Enriched KEGG pathways included the interleukin-17 signaling pathway, tumor necrosis factor signaling pathway, and human T-cell leukemia virus 1 infection. The top 10 hub genes in the PPI network were prostaglandin-endoperoxide synthase 2 (Ptgs2), chemokine (C-X-C motif) ligand 2 (Cxcl2), colony-stimulating factor 2 (granulocyte-macrophage) (Csf2), matrix metallopeptidase 13 (Mmp13), amphiregulin (Areg), plasminogen activator, urokinase receptor (Plaur), fos-like antigen 1 (Fosl1), epiregulin (Ereg), activating transcription factor 3 (Atf3), and transferrin receptor (Tfrc). Cxcl2, Csf2, and Atf3 played important roles in the mitogen-activated protein kinase (MAPK) signaling pathway. CONCLUSIONS: These pathways and DEGs may serve as targets for gene therapy.


Assuntos
Biologia Computacional , Diquat , Paraquat , Fator 3 Ativador da Transcrição , Anfirregulina , Animais , Quimiocina CXCL2 , Fatores Estimuladores de Colônias , Ciclo-Oxigenase 2 , Diquat/envenenamento , Epirregulina , Perfilação da Expressão Gênica , Humanos , Interleucina-17 , Metaloproteinase 13 da Matriz , Camundongos , Proteínas Quinases Ativadas por Mitógeno , Paraquat/envenenamento , Receptores da Transferrina , Receptores de Ativador de Plasminogênio Tipo Uroquinase , Fatores de Necrose Tumoral
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