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2.
Sci Rep ; 12(1): 21940, 2022 12 19.
Artigo em Inglês | MEDLINE | ID: mdl-36535986

RESUMO

2-Methyl-4-chlorophenoxyacetic acid (MCPA) is a widely used chlorophenoxy herbicide. MCPA poisoning causes mitochondrial dysfunction, which can lead to kidney injury and death. The objective of this study is to describe the epidemiology, case fatality and extent of renal injury in a large cohort of MCPA self-poisonings. The study consists of two parts: (1) A report of epidemiological data and clinical outcomes in MCPA poisoned patients in Sri Lanka between 2002 and 2019; (2) Evaluation of acute kidney injury (AKI) using renal biomarkers in a subset from this cohort. Serum creatinine (sCr) and biomarkers were measured soon after hospitalization (2 [IQR 1-3] h) and at different time intervals. We measured serum biomarkers: sCr, cystatin C (sCysC), creatine kinase (CK), and urinary biomarkers: creatinine, kidney injury molecule-1 (KIM-1), clusterin, albumin, beta-2-microglobulin (ß2M), cystatin C, neutrophil gelatinase-associated lipocalin (NGAL), osteopontin (OPN), trefoil factor 3 (TFF3) and cytochrome C (CytoC). Kidney Disease Improving Global Outcomes (KDIGO) criteria was used to define acute kidney injury (AKI). There were 1653 patients; 65% were male. The median time from ingestion to examination was 3:54 (IQR 2:19-6:57) h. The overall case-fatality rate was 5.3%. Patients who died were older (42 [IQR 33.5-54] vs 27 [IQR 20-37] for survivors). The median estimated amount of MCPA ingested by patients who died was also greater (88 [IQR 34-200] vs. 30 [IQR 15-63] ml in survivors). Moderate to severe AKI (AKI2/3) was uncommon (6/59 patients in the biomarker study had KDIGO stage 2 or 3). Most patients in AKI2/3 group with increased sCr were older (median age 35 years [IQR 27-41]) compared to No AKI (23 years (19-29) years) or AKI1 (26 years (21-40) years) group who had no or mild increase in sCr. These patients had no pre-existing kidney diseases. In these patients, serum creatinine (maximum medium concentration; 1.12 [IQR 0.93-1.67] mg/dl) and CK (maximum medium concentration; 284 [IQR 94-428] U/l) were increased but sCysC (maximum medium concentration; 0.79 [IQR 0.68-0.81] mg/l) remained in the normal range within 72 h. All urinary biomarkers performed poorly in diagnosing AKI (area under the receiver operating characteristic curve < 0.68). The higher numbers of men with MCPA poisoning likely reflects greater occupational access to pesticides. Fatal outcome and higher ingested dose were more common in the elderly. Significant AKI with tubular injury biomarkers was uncommon. Most people with raised sCr were older and appeared to have no pre-existing kidney disease.


Assuntos
Ácido 2-Metil-4-clorofenoxiacético , Injúria Renal Aguda , Adulto , Feminino , Humanos , Masculino , Ácido 2-Metil-4-clorofenoxiacético/envenenamento , Injúria Renal Aguda/etiologia , Biomarcadores , Creatinina , Cistatina C , Rim , Lipocalina-2 , Estudos Prospectivos
3.
PLoS One ; 17(12): e0279694, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36584001

RESUMO

A perfluorocarbon (PFC) investigated for treatment of traumatic brain injury (TBI) delivers oxygen to support brain function, but causes transient thrombocytopenia. TBI can cause acute inflammation with resulting thrombocytopenia; an interaction between the PFC effects and TBI inflammation might exacerbate thrombocytopenia. Therefore, PFC effects on platelet (PLT) function and hemostasis in a lipopolysaccharide (LPS) model of inflammation in the baboon were studied. Animals were randomized to receive saline ±LPS, and ± one of two doses of PFC. PLT count, transmission electron microscopy, and microparticle populations were quantified at baseline (BL) and at 2, 24, 48, 72, and 96 hours; hemostatic parameters for aggregometry and for blood clotting were measured at baseline (BL) and days 3 and 4. Injection of vehicle and LPS caused thrombocytopenia within hours; PFCs caused delayed thrombocytopenia beginning 48 hours post-infusion. LPS+PFC produced a more prolonged PLT decline and decreased clot strength. LPS+PFC increased ADP-stimulated aggregation, but PFC alone did not. Microparticle abundance was greatest in the LPS+PFC groups. LPS+PFC caused diffuse microvascular hemorrhage and death in 2 of 5 baboons in the low dose LPS-PFC group and 2 of 2 in the high dose LPS-PFC group. Necropsy and histology suggested death was caused by shock associated with hemorrhage in multiple organs. Abnormal morphology of platelets and red blood cells were notable for PFC inclusions. In summary, PFC infusion caused clinically significant thrombocytopenia and exacerbated LPS-induced platelet activation. The interaction between these effects resulted in decreased hemostatic capacity, diffuse bleeding, shock and death.


Assuntos
Fluorcarbonetos , Inflamação , Animais , Modelos Animais de Doenças , Eritrócitos/efeitos dos fármacos , Eritrócitos/patologia , Fluorcarbonetos/envenenamento , Hemorragia/induzido quimicamente , Hemostáticos , Inflamação/tratamento farmacológico , Lipopolissacarídeos , Trombocitopenia/induzido quimicamente
4.
Zhonghua Wei Zhong Bing Ji Jiu Yi Xue ; 34(12): 1320-1324, 2022 Dec.
Artigo em Chinês | MEDLINE | ID: mdl-36567591

RESUMO

OBJECTIVE: To investigate the effect of continuous hemoperfusion (HP) on the levels of soluble CD14 isoform (sCD14-st) and neutrophil gelatinase-associated lipocalin (NGAL) on patients with diquat (DQ) poisoning and its significance. METHODS: A total of 86 patients with acute DQ poisoning admitted to the department of emergency medicine, Harrison International Peace Hospital Affiliated to Hebei Medical University from May 2018 to August 2021 were enrolled and divided into the intermittent HP group (40 cases) and the continuous HP group (46 cases) according to the random number table method. All patients received basic treatment and continuous veno-venous hemofiltration (CVVH) within 24 hours after admission. On this basis, the intermittent HP group received HP treatment within 2 hours, lasting 2 hours each time for every 8 hours, 3 times in all; the continuous HP group received continued HP treatment until there was no DQ component in urine samples. Serum NGAL levels were detected in all patients before treatment and at 3 hours, 12 hours, 24 hours, 2 days, 3 days, 5 days, and 7 days after treatment. At the same time, serum sCD14-st, blood lactate (Lac), arterial partial pressure of oxygen (PaO2), serum creatinine (SCr), MB isoenzyme of creatine kinase (CK-MB) and interleukin-18 (IL-18) levels were detected before treatment and at 24 hours, 3 days, and 7 days after treatment. Kaplan-Meier survival curve was drawn to analyze the 28-day survival of patients. RESULTS: Before treatment, there was no significant difference in serum NGAL, sCD14-st, Lac, PaO2, SCr, CK-MB and IL-18 levels between the two groups. With the prolongation of treatment, the serum levels of NGAL, sCD14-st, Lac, SCr, CK-MB and IL-18 in the intermittent HP group increased at first and then decreased. Serum levels of NGAL, sCD14-st, CK-MB and IL-18 reached their peaks at 24 hours after treatment, and the Lac and SCr levels reached their peaks at 3 days after treatment. In addition, the levels of the above indexes at each time point in the continuous HP group were all significantly lower than those in the intermittent HP group [after 24 hours of treatment: NGAL (µg/L) was 345.90±30.75 vs. 404.24±38.79, sCD14-st (ng/L) was 1 941.88±298.02 vs. 2 656.35±347.93, CK-MB (U/L) was 30.67±9.11 vs. 43.28±8.06, IL-18 (ng/L) was 139.49±16.29 vs. 177.98±27.85; 3 days of treatment: Lac (mmol/L) was 2.98±0.26 vs. 3.72±0.49, SCr (µmol/L) was 125.01±24.24 vs. 156.74±28.88; all P < 0.05]. However, there was no significant difference in PaO2 levels between the two groups at each time point after treatment. The Kaplan-Meier survival curve showed that the 28-day mortality of patients in the continuous HP group was significantly lower than that in the intermittent HP group [26.09% (12/46) vs. 52.50% (21/40); Log-Rank test: χ 2 = 7.288, P = 0.007]. CONCLUSIONS: Continuous HP could effectively reduce serum sCD14-st, NGAL levels and 28-day mortality in patients with DQ poisoning, with good curative effect.


Assuntos
Diquat , Hemoperfusão , Lipocalina-2 , Receptores de Lipopolissacarídeos , Intoxicação , Humanos , Diquat/envenenamento , Hemoperfusão/métodos , Interleucina-18/sangue , Lipocalina-2/sangue , Receptores de Lipopolissacarídeos/sangue , Intoxicação/sangue , Intoxicação/mortalidade , Intoxicação/terapia , Terapia de Substituição Renal Contínua/métodos
5.
J Forensic Leg Med ; 92: 102450, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36399917

RESUMO

Pesticides play a pivotal role in modern agricultural practices and effective domestic pest control. Despite their advantages, pesticides pose a great danger to humans and animals due to their toxicity. Pesticides, particularly carbamates, are extensively used all over the world in crop protection and domestic pest control, however, also causing morbidity and mortality on a larger scale, which is of great significance in both clinical and criminal justice management.Carbamates are derived from a carbamic acid (NH2COOH) that are commonly used as insecticides. Ethienocarb, Sevin, Carbaryl, Fenoxycarb, Furadan, Carbofuran, Aldicarb, and 2-(1-Methylpropyl) phenyl N-methylcarbamate are examples of insecticides that include the carbamate functional group. By reversibly inactivating the enzyme acetylcholinesterase, these insecticides can induce cholinesterase inhibition poisoning.Chromatographic methods, notably gas and liquid chromatography have traditionally been employed to analyse carbamate pesticides and their metabolites in various matrices. These approaches are employed due to their ability to separate the chemicals contained in a sample; as well as identify and quantify these compounds utilizing advanced detection systems. Aside from these GC and LC conventional methods, other detection and/or hyphenated techniques such as single-quadrupole, ion-trap, triple-quadrupole, or tandem mass spectrometry, have been used in carbamate analysis to provide quick results with excellent sensitivity, precision, and accuracy.The objective of this review is to describe various analytical techniques used to detect and determine carbamate pesticides in various matrices which include urine, blood, and tissues that are commonly encountered in emergency hospital laboratories and forensic science laboratories.


Assuntos
Carbamatos , Inseticidas , Praguicidas , Animais , Humanos , Acetilcolinesterase , Carbamatos/envenenamento , Carbaril/envenenamento , Carbofurano/envenenamento , Toxicologia Forense , Inseticidas/envenenamento , Praguicidas/envenenamento
6.
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
7.
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
10.
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
11.
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
12.
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
14.
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
15.
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
17.
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
18.
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
19.
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
20.
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
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