RESUMO
BACKGROUND AND OBJECTIVES: Elevated troponin T (cTnT) values are associated with comorbidities and early mortality, in both cardiovascular and noncardiovascular diseases. The objective of this study is to evaluate the prognostic accuracy of the sole utilization of prehospital point-of-care cardiac troponin T to identify the risk of early in-hospital deterioration, including mortality within 28 days. METHODS: We conducted a prospective, multicentric, controlled, ambulance-based, observational study in adults with acute diseases transferred with high priority by ambulance to emergency departments, between 1 January and 30 September 2020. Patients with hospital diagnosis of acute coronary syndrome were excluded. The discriminative power of the predictive cTnT was assessed through a discrimination model trained using a derivation cohort and evaluated by the area under the curve of the receiver operating characteristic on a validation cohort. RESULTS: A total of 848 patients were included in our study. The median age was 68 years (25th-75th percentiles: 50-81 years), and 385 (45.4%) were women. The mortality rate within 28 days was 12.4% (156 cases). The predictive ability of cTnT to predict mortality presented an area under the curve of 0.903 (95% CI: 0.85-0.954; P < .001). Risk stratification was performed, resulting in three categories with the following optimal cTnT cut-off points: high risk greater than or equal to 100, intermediate risk 40-100 and low risk less than 40 ng/L. In the high-risk group, the mortality rate was 61.7%, and on the contrary, the low-risk group presented a mortality of 2.3%. CONCLUSIONS: The implementation of a routine determination of cTnT on the ambulance in patients transferred with high priority to the emergency department can help to stratify the risk of these patients and to detect unknown early clinical deterioration.
Assuntos
Deterioração Clínica , Serviços Médicos de Emergência , Mortalidade Hospitalar , Troponina T/sangue , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Ambulâncias , Área Sob a Curva , Doenças Cardiovasculares/sangue , Doenças do Sistema Digestório/sangue , Feminino , Humanos , Infecções/sangue , Masculino , Pessoa de Meia-Idade , Mortalidade , Doenças do Sistema Nervoso/sangue , Testes Imediatos , Intoxicação/sangue , Valor Preditivo dos Testes , Prognóstico , Estudos Prospectivos , Curva ROC , Doenças Respiratórias/sangue , Ferimentos e Lesões/sangue , Adulto JovemRESUMO
Transdermal absorption of isopropyl alcohol (IPA) can cause toxicity at high doses, but case reports of this phenomenon are limited. This is a single patient encounter and chart review describing a 33-year-old previously healthy female who presented obtunded, wrapped in IPA soaked round cotton pads with overlying shrink wrap, her family's home remedy for a mild persistent rash. This case highlights several interesting aspects of IPA toxicity, including evidence that toxic doses of IPA are possible through transdermal absorption and creatinine may be falsely elevated due to acetone's interference with the measurement of creatinine on some assays.
Assuntos
2-Propanol/intoxicação , Transtornos da Consciência/induzido quimicamente , Hidratação , Intoxicação/terapia , Solventes/intoxicação , Adulto , Creatinina/sangue , Exantema/terapia , Reações Falso-Positivas , Feminino , Taxa de Filtração Glomerular , Humanos , Intoxicação/sangue , Absorção CutâneaRESUMO
BACKGROUND: Paraquat and diquat are widely used in agricultural production in many countries, which are very toxic to human beings. Paraquat can be detected in some diquat solution sold in the market. The blood concentration of paraquat or diquat is an important indicator for clinical diagnosis of paraquat or diquat poisoning. So, it is very meaningful to develop a method for simultaneous determination of paraquat and diquat in human plasma. OBJECTIVE: To develop and validate a HPLC-DAD method for simultaneous determination of paraquat and diquat in human plasma and to apply it in the acute poisoning patients by these two herbicides. METHODS: Paraquat and diquat were simultaneously determined by HPLC-DAD. The plasma was treated using Waters OASIS® Column and then separated on a Thermo Hypersil GOLD (250 × 4.6 mm, 5 µm) Column with the mobile phase consisted of 75 mmol/L sodium heptane sulfonate (containing 0.1 mol/L phosphoric acid, pH 3.0) and acetonitrile (87:13, v:v) at a flow rate of 1.0 mL/min. The full-wavelength scanning was 200-400 nm, and the detection wavelength of paraquat and diquat was 257nm and 310nm, respectively. 120 and 30 plasma samples from patients with paraquat and diquat poisoning were collected and analyzed by the established method. RESULTS: The standard curve for paraquat and diquat ranged from 0.05 to 20 µg/mL, and the precision of LLOQ for paraquat was 16.49%, which was required to be less than 20%. The precision of other concentrations was less than 14.14%. The recovery of paraquat and diquat was 95.38%-103.97% and 94.79%-98.40%, respectively. The results showed that paraquat and diquat were stable under various storage conditions. 120 plasma samples of paraquat poisoning patients and 30 plasma samples of diquat poisoning patients were determined by the established method. The blood concentration of paraquat ranged from 0.10 to 20.62 µg/mL, with an average of 3.61 µg/mL, while for diquat, the concentration ranged from 0 to 26.59 µg/mL, with an average of 2.00 µg/mL. Among the diquat suspected poisoning samples, 5 samples were detected not only diquat but also paraquat, and 2 samples were detected only paraquat, no diquat. CONCLUSION: The HPLC-DAD method established in this study was high throughput, high sensitivity, simple operation, and wide linear ranges. It can be used for the screening analysis and quantitative detection of paraquat and diquat in acute poisoning patients, which can provide basis for the treatment and prognosis of these two herbicides poisoning patients.
Assuntos
Cromatografia Líquida de Alta Pressão/métodos , Diquat/sangue , Paraquat/sangue , Intoxicação/sangue , Calibragem , Cromatografia Líquida de Alta Pressão/instrumentação , Diquat/intoxicação , Herbicidas/sangue , Herbicidas/intoxicação , Humanos , Limite de Detecção , Paraquat/intoxicação , Reprodutibilidade dos TestesRESUMO
BACKGROUND: Emergency medical services (EMS) routinely face complex scenarios where decisions should be taken with limited clinical information. The development of fast, reliable and easy to perform warning biomarkers could help in such decision-making processes. The present study aims at characterizing the validity of point-of-care lactate (pLA) during prehospital tasks for predicting in-hospital mortality within two days after the EMS assistance. MATERIALS AND METHODS: Prospective, multicentric, ambulance-based and controlled observational study without intervention, including six advanced life support and five hospitals. The pLA levels were recorded during EMS assistance of adult patients. The validity of pLA to determine the in-hospital mortality was assessed by the area under the curve (AUC) of the receiver operating curve (ROC). RESULTS: A total of 2997 patients were considered in the study, with a median of 69 years (IQR 54-81) and 41.4% of women. The median pLA value was 2.7 mmol/L (1.9-3.8) in survivors and 5.7 mmol/L (4.4-7.6) in nonsurvivors. The global discrimination level of pLA reached an AUC of 0.867, being 1.9 mmol/L and 4 mmol/L the cut-off point for low and high mortality. The discrimination value of pLA was not affected by sex, age or pathology. CONCLUSIONS: Our results highlight the clinical importance of prehospital pLA to determine the in-hospital risk of mortality. The incorporation of pLA into the EMS protocols could improve the early identification of risky patients, leading to a better care of such patients.
Assuntos
Serviços Médicos de Emergência , Mortalidade Hospitalar , Ácido Láctico/sangue , Testes Imediatos , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Ambulâncias , Área Sob a Curva , Doenças Cardiovasculares/sangue , Doenças Cardiovasculares/mortalidade , Feminino , Hospitalização , Humanos , Infecções/sangue , Infecções/mortalidade , Unidades de Terapia Intensiva , Masculino , Pessoa de Meia-Idade , Doenças do Sistema Nervoso/sangue , Doenças do Sistema Nervoso/mortalidade , Intoxicação/sangue , Intoxicação/mortalidade , Estudos Prospectivos , Curva ROC , Reprodutibilidade dos Testes , Respiração Artificial , Doenças Respiratórias/sangue , Doenças Respiratórias/mortalidade , Ferimentos e Lesões/sangue , Ferimentos e Lesões/mortalidade , Adulto JovemRESUMO
BACKGROUND: Methanol is widely used in industry; however, methanol poisoning is not common. In this regard, a number of outbreaks have been recently reported due to inappropriate processing of alcoholic beverages. Shiraz, a city located in the southern part of Iran, faced one of such outbreaks in 2020 during COVID-19 pandemic. There is no sufficient literature on the electrocardiographic findings in methanol toxicity. This study aimed to address this gap in the literature. METHOD: A total of 356 cases with methanol toxicity referred to Shiraz University of Medical Science Tertiary Hospitals (Faghihi and Namazi) in March and April, 2020. The clinical findings of blindness and impaired level of consciousness, lab data such as arterial blood gas, electrolytes, and creatinine, and the most common findings from ECGs were collected. RESULTS: The most common ECG findings were J point elevation (68.8%), presence of U wave (59.2%), QTc prolongation (53.2% in males and 28.6% in females), and fragmented QRS (33.7%). An outstanding finding in this study was the presence of myocardial infarction in 5.3% of the cases. This finding, to the best of our knowledge, has only been reported in a few case reports. Brugada pattern (8.1%) and Osborn wave (3.7%) were the other interesting findings. In multivariate analysis, when confounding factors were adjusted, myocardial infarction, atrioventricular conduction disturbances, sinus tachycardia, and the prolonged QTC > 500 msecond were four independent factors correlated with methanol toxicity severity measured with arterial blood PH on arterial blood gas measurements, with odds ratios of 12.82, 4.46, 2.32 and 3.15 (P < 0.05 for all), respectively. CONCLUSION: Electrocardiographic variations during methanol intoxication are remarkable and well-correlated with poisoning severity. Myocardial infarction was an egregious and yet a common concerning finding in this sample, which need to be ruled out in methanol toxicity.
Assuntos
Bloqueio Atrioventricular/induzido quimicamente , Cegueira/induzido quimicamente , Transtornos da Consciência/induzido quimicamente , Síndrome do QT Longo/induzido quimicamente , Metanol/intoxicação , Infarto do Miocárdio/induzido quimicamente , Solventes/intoxicação , Taquicardia Sinusal/induzido quimicamente , Adolescente , Adulto , Idoso , Bebidas Alcoólicas , Bloqueio Atrioventricular/sangue , Bloqueio Atrioventricular/fisiopatologia , Betacoronavirus , Cegueira/sangue , Cegueira/fisiopatologia , Gasometria , Síndrome de Brugada/sangue , Síndrome de Brugada/induzido quimicamente , Síndrome de Brugada/fisiopatologia , COVID-19 , Transtornos da Consciência/sangue , Transtornos da Consciência/fisiopatologia , Infecções por Coronavirus , Eletrocardiografia , Feminino , Contaminação de Alimentos , Humanos , Concentração de Íons de Hidrogênio , Irã (Geográfico) , Síndrome do QT Longo/sangue , Síndrome do QT Longo/fisiopatologia , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Infarto do Miocárdio/sangue , Infarto do Miocárdio/fisiopatologia , Pandemias , Pneumonia Viral , Intoxicação/sangue , Intoxicação/fisiopatologia , SARS-CoV-2 , Fatores Sexuais , Taquicardia Sinusal/sangue , Taquicardia Sinusal/fisiopatologia , Adulto JovemRESUMO
BACKGROUND: Examination of serum lactate level and its changes, as an indicator of tissue oxygenation, as well as level of creatine kinase (CK) inhibitors, as a factor of mortality which partially expresses heart, brain, and muscle damage, may be considered as tools to determine prognosis in critically ill patients. We aimed to evaluate these two factors as potential prognostic factors in critically poisoned patients admitted to our toxicology ICU. METHOD: This is a cross-sectional descriptive-analytic study that was performed on poisoned patients referred to emergency department of Loghman Hakim Hospital. One-hundred critically poisoned patients who had been admitted to ICU were conveniently chosen using a random number table and included into the study after obtaining consent forms from their next of kin. Their serum lactate and CK levels were checked on admission. These levels were compared subsequently between survivors and non-survivors to seek for their potential prognostic role. RESULTS: In a total of 100 patients enrolled, 61 were male. Serum level of lactate (with a cut off of 26 mg/dL) and serum CK with a cutoff point of 169 U/L could have prognosticated death with sensitivity and specificity of 78 and 77% (for lactate) and 74 and 62% (for serum CK), respectively. CONCLUSIONS: In poisoned patients, serum lactate and CK can be used as possible prognostic factors because they rapidly increase in the serum and are easily detectable.
Assuntos
Creatina Quinase/sangue , Ácido Láctico/sangue , Intoxicação/sangue , Adulto , Biomarcadores/sangue , Estudos Transversais , Serviço Hospitalar de Emergência , Feminino , Humanos , Irã (Geográfico) , Masculino , Intoxicação/mortalidade , Prognóstico , Sensibilidade e Especificidade , Taxa de SobrevidaRESUMO
We present the forensic analyses of plasma samples of human victims exposed to sulfur mustard (SM) in a crisis region in the Middle East in 2015. A few hours after exposure, poisoned persons showed typical signs and symptoms of percutaneous SM exposure including erythema and later on blisters and hardly healing skin wounds. Blood samples were collected 15 days after poisoning to be analyzed for the presence of long-lived protein-adduct biomarkers to verify SM poisoning. We applied a novel bioanalytical toolbox targeting four human serum albumin-derived biomarkers that were made accessible after plasma proteolysis. These adducts contained the SM-specific hydroxyethylthioethyl moiety either bound to the thiol group of a cysteine residue (C34*) or to the side-chain carboxylic group of a glutamic acid residue (E230*). Peptide biomarkers were produced from plasma of the victims using proteinase K (C34*PF), pronase (C34*P) and pepsin (AE230*VSKL and LQQC34*PFEDHVKL) for enzymatic protein cleavage. Separation and detection were carried out by selective micro-liquid chromatography-electrospray ionization high-resolution tandem mass spectrometry (µLC-ESI MS/HR MS). In addition to this site-specific adduct detection, a general approach after alkaline hydrolysis of the plasma protein fraction was applied. Liberated thiodiglycol (TDG) was derivatized with heptafluorobutyric anhydride and detected by gas chromatography-electron ionization mass spectrometry (GC-EI MS). The different bioanalytical methods yielded congruent results confirming SM poisoning for all patients who showed clinical signs and symptoms. This is the first time that real cases of SM poisoning were confirmed and presented by such a broad compilation of protein-derived biomarkers.
Assuntos
Substâncias para a Guerra Química/intoxicação , Toxicologia Forense/métodos , Gás de Mostarda/intoxicação , Albumina Sérica Humana/química , Biomarcadores/sangue , Substâncias para a Guerra Química/química , Humanos , Gás de Mostarda/química , Intoxicação/sangue , Ligação Proteica , Proteólise , Espectrometria de Massas por Ionização por Electrospray , Espectrometria de Massas em TandemRESUMO
BACKGROUND: The herbicide paraquat (1, 1'-dimethyl-4, 4'-bipyridylium dichloride; PQ) is a poison well-known to cause delayed mortality due to acute kidney injuries (AKI). This study examines the changes in serum amino acids (AAs) metabolite profiles as surrogate markers of renal cell metabolism and function after paraquat poisoning. METHODS: To identify the metabolic profiling of free serum AAs and its metabolites, serum from 40 paraquat-poisoned patients with or without AKI is collected. LC-MS/GC-MS is performed to analyze AA molecules. A Cox proportional hazard model was used to assess for incidence of AKI. Receiver operating characteristic (ROC) curve is applied to evaluate AKI occurrence and prognosis. RESULTS: A total of 102 serum AAs and its metabolites were identified. Compared with non-AKI patients, 37 varied significantly in AKI patients. The univariate Cox proportional hazard model analysis revealed that the estimated PQ amount, plasma PQ concentration, urine PQ concentration, APACHE, SOFA scores and 16 amino acids correlated with the incidence of AKI. Further analyses revealed that 3-methylglutarylcarnitine, 1-methylimidazoleacetate, and urea showed higher cumulative hazard ratios for the occurrence of AKI during follow-up (P < 0.05). The area under the curve (AUC) of 3-methylglutarylcarnitine, 1-methylimidazoleacetate and urea were 0.917, 0.857, 0.872, respectively. CONCLUSION: 3-methylglutarylcarnitine, 1-methylimidazoleacetate and urea were associated with AKI in patients with paraquat intoxication.
Assuntos
Injúria Renal Aguda/sangue , Aminoácidos/sangue , Carnitina/análogos & derivados , Glutaratos/sangue , Herbicidas/intoxicação , Imidazóis/sangue , Paraquat/intoxicação , Ureia/sangue , Injúria Renal Aguda/induzido quimicamente , Adulto , Área Sob a Curva , Biomarcadores/sangue , Carnitina/sangue , Estudos de Casos e Controles , Feminino , Herbicidas/sangue , Herbicidas/urina , Humanos , Masculino , Metaboloma , Pessoa de Meia-Idade , Paraquat/sangue , Paraquat/urina , Intoxicação/sangue , Intoxicação/urina , Modelos de Riscos Proporcionais , Curva ROC , Adulto JovemRESUMO
BACKGROUND: Iron intoxication can occur accidentally in children or intentionally by adolescents as a suicide attempt. They usually present with various symptoms including vomiting and diarrhea. Clinical studies in this field has been reported different doses of ingested elemental iron that caused serious toxicity, but none of these studies determined the minimum cut-off of ingested iron that triggered the risk of severe toxicity. The aim of this study was therefore to investigate the demographic features of iron intoxication in Turkish children and to determine the lowest cut-off of ingested elemental iron triggering serious intoxication and the need for prompt management. METHODS: This retrospective study investigated 83 Turkish patients with accidental and intentional iron poisoning. RESULTS: Of the 83 cases of acute iron intoxication, accidental iron consumption was more common than intentional use. Fifty-three patients ingested a median toxic dose of elemental iron of 40.0 mg/kg (IQR, 33.5 mg/kg). The median serum iron concentration in the first 6 h of ingestion was 150 µg/dL (IQR, 282 µg/dL). Twenty patients were given deferoxamine, whereas 63 patients were given supportive treatment. CONCLUSION: The cut-off of ingested elemental iron that triggered serious toxicity and the need for deferoxamine in children <18 years of age was 28 mg/kg.
Assuntos
Ingestão de Alimentos , Ferro/administração & dosagem , Ferro/intoxicação , Intoxicação/diagnóstico , Oligoelementos/administração & dosagem , Oligoelementos/intoxicação , Adolescente , Criança , Desferroxamina/uso terapêutico , Feminino , Humanos , Ferro/sangue , Masculino , Intoxicação/sangue , Intoxicação/tratamento farmacológico , Estudos Retrospectivos , Sensibilidade e Especificidade , Sideróforos/uso terapêutico , Oligoelementos/sangue , TurquiaRESUMO
The purpose of the work is the development of mathematical models in the forensic diagnosis of poisonings by the main groups of toxicologically important substances, on the basis of biochemical characteristics of blood. The most informative forensic and biochemical indicators of cadaveric blood used to detect lethal poisoning are the urea content, total protein content, and the ratio of urea to creatinine. Mathematical models of poisoning can be used to diagnose poisoning with narcotic drugs, psychotropic substances and substitutes of ethyl alcohol.
Assuntos
Etanol/sangue , Medicina Legal/métodos , Entorpecentes/sangue , Intoxicação/diagnóstico , Psicotrópicos/sangue , Cadáver , Etanol/intoxicação , Humanos , Modelos Teóricos , Entorpecentes/intoxicação , Intoxicação/sangue , Psicotrópicos/intoxicaçãoRESUMO
Coupled plasma filtration adsorption (CPFA) is a detoxification system that combines a plasma adsorption circuit with a continuous renal replacement therapy. The circuit consists of a plasma filter, a resin/adsorbent cartridge and a haemofilter. It differs from many other types of extracorporeal therapies in that the upper part of the circuit can be considered a "closed loop". In this manner, the plasma separated by the plasma filter passes through an adsorbent cartridge containing a resin with high affinity to many cytokines, mediators and toxins/poisons. After passing through the cartridge, the purified plasma is returned to the patient. The second part of the circuit, the haemofilter, can then be used to remove small toxins that are not adsorbed by the resin or to modulate the patient hematic volume. Although more complex, the use of a plasma-separation step prior to the passage through the resin cartridge offers advantages over adsorption by haemoperfusion. The plasma passes through the resin cartridge with a lower velocity than the blood flow, and this allows better contact time for the toxins with the resin, and more thorough penetration into the resin pores. The adsorption of many toxins is highly dependent on a factor expressed as linear velocity. In addition, the plasma does not contain cells or a very limited number of platelets, allowing less potential activation upon contact with the resin. Although the technique was originally developed for the treatment of sepsis and septic shock, there are many additional applications where there can be an advantage of having access to larger molecular weight toxins (compared to haemofiltration) and avoiding the loss of important physiologic substances such as albumin. Some of these new applications, in patients with or without acute kidney injury, include liver failure, rhabdomyolysis, severe autoimmune exacerbations and poisonings. In this article, we discuss some of the basic principles involved in sorbent technology, and how these may contribute to treatment efficacy, review the actual experiences with CPFA and finally discuss the results of recent human studies and their implications. Video Journal Club "Cappuccino with Claudio Ronco" at http://www.karger.com/?doi=490234.
Assuntos
Plasma , Diálise Renal/instrumentação , Diálise Renal/métodos , Injúria Renal Aguda/sangue , Injúria Renal Aguda/terapia , Velocidade do Fluxo Sanguíneo , Humanos , Falência Hepática Aguda/sangue , Falência Hepática Aguda/terapia , Intoxicação/sangue , Intoxicação/terapia , Porosidade , Rabdomiólise/sangue , Rabdomiólise/terapia , Choque Séptico/sangue , Choque Séptico/terapiaRESUMO
This paper reports the case of collective acute phosphide (PH3) intoxication among the crew aboard a merchant ship. All the intoxicated individuals were hospitalized 3 months after the accident. The aim of examinations was to identify late health effects of the accident. Laboratory tests and consultations were performed during their stay in the hospital. There were 5 cases of toxic liver damage. other 5 patients were diagnosed with posttraumatic stress disorder and adjustment disorders. The results of the study suggest that in cases of acute phosphide intoxication, the assessment of patients' psychological functioning should be an indispensable part of diagnostic procedure. Med Pr 2018;69(3):337-344.
Assuntos
Compostos de Alumínio/intoxicação , Pesqueiros , Doenças Profissionais/induzido quimicamente , Exposição Ocupacional/efeitos adversos , Fosfinas/intoxicação , Navios , Adulto , Humanos , Masculino , Intoxicação/sangueRESUMO
The duration of hemodialysis (HD) sessions for the treatment of acute ethylene glycol poisoning is dependent on concentration, the operational parameters used during HD, and the presence and severity of metabolic acidosis. Ethylene glycol assays are not readily available, potentially leading to undue extension or premature termination of HD. We report a prediction model for the duration of high-efficiency HD sessions based retrospectively on a cohort study of 26 cases of acute ethylene glycol poisoning in 24 individuals treated by alcohol dehydrogenase competitive inhibitors, cofactors and HD. Two patients required HD for more than 14 days, and two died. In 19 cases, the mean ethylene glycol elimination half-life during high-efficiency HD was 165 minutes (95% confidence interval of 151-180 minutes). In a training set of 12 patients with acute ethylene glycol poisoning, using the 90th percentile half-life (195 minutes) and a target ethylene glycol concentration of 2 mmol/l (12.4 mg/dl) allowed all cases to reach a safe ethylene glycol under 3 mmol/l (18.6 mg/dl). The prediction model was then validated in a set of seven acute ethylene glycol poisonings. Thus, the HD session time in hours can be estimated using 4.7 x (Ln [the initial ethylene glycol concentration (mmol/l)/2]), provided that metabolic acidosis is corrected.
Assuntos
Etilenoglicol/intoxicação , Modelos Teóricos , Diálise Renal/estatística & dados numéricos , Adulto , Etilenoglicol/sangue , Feminino , Meia-Vida , Humanos , Masculino , Pessoa de Meia-Idade , Nomogramas , Intoxicação/sangue , Intoxicação/terapia , Estudos RetrospectivosRESUMO
We have identified, by quantitative real-time PCR, hundreds of miRNAs that are dramatically elevated in the plasma or serum of acetaminophen (APAP) overdose patients. Most of these circulating microRNAs decrease toward normal levels during treatment with N-acetyl cysteine (NAC). We identified a set of 11 miRNAs whose profiles and dynamics in the circulation during NAC treatment can discriminate APAP hepatotoxicity from ischemic hepatitis. The elevation of certain miRNAs can precede the dramatic rise in the standard biomarker, alanine aminotransferase (ALT), and these miRNAs also respond more rapidly than ALT to successful treatment. Our results suggest that miRNAs can serve as sensitive diagnostic and prognostic clinical tools for severe liver injury and could be useful for monitoring drug-induced liver injury during drug discovery.
Assuntos
Acetaminofen/intoxicação , Acetilcisteína/uso terapêutico , Hepatite/sangue , Isquemia/sangue , MicroRNAs/sangue , Alanina Transaminase/sangue , Hepatite/complicações , Humanos , Intoxicação/sangue , Intoxicação/tratamento farmacológico , Reação em Cadeia da Polimerase em Tempo RealRESUMO
MicroRNAs (miRNAs) have been shown to be critical mediators of many cellular and developmental processes and have been implicated in different human diseases. Since the observation of extracellular miRNAs present in various biofluids, much attention and excitement have been garnered toward understanding the functional roles of these circulating extracellular miRNAs and establishing their potential use as noninvasive diagnostic biomarkers. Here, we will review the current state of miRNA biomarkers for many human diseases, including their emerging use in toxicological applications, and discuss the current challenges in the field, with an emphasis on technical issues that often hinder discovery-based miRNA biomarker studies.
Assuntos
MicroRNAs/sangue , Toxicologia/métodos , Animais , Biomarcadores/sangue , Biomarcadores Tumorais/sangue , Doenças Cardiovasculares/sangue , Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/metabolismo , Diabetes Mellitus/sangue , Diabetes Mellitus/diagnóstico , Diabetes Mellitus/metabolismo , Detecção Precoce de Câncer/tendências , Diagnóstico Precoce , Humanos , MicroRNAs/metabolismo , Neoplasias/sangue , Neoplasias/induzido quimicamente , Neoplasias/diagnóstico , Neoplasias/metabolismo , Intoxicação/sangue , Intoxicação/diagnóstico , Intoxicação/metabolismo , Toxicologia/tendênciasRESUMO
This study is aimed at evaluating the association between occupational exposure to organophosphate (OP) and carbamate (CB) pesticides and semen quality as well as levels of reproductive and thyroid hormones of pesticide sprayers in Malihabad, Lucknow, Uttar Pradesh, India. Thirty-five healthy men (unexposed group) and 64 male pesticide sprayers (exposed group) were recruited for clinical evaluation of fertility status. Fresh semen samples were evaluated for sperm quality and analyzed for DNA fragmentation index (DFI) by flow cytometry. Pesticide exposure was assessed by measuring erythrocyte acetylcholinesterase and plasma butyrylcholinesterase (BuChE) with a Test-mate ChE field kit. Serum levels of total testosterone (Tt), prolactin (PRL), follicle-stimulating hormone (FSH), luteinizing hormone (LH), thyroid-stimulating hormone (TSH), and free thyroxine (FT4) were analyzed using enzyme immunoassay kits. Evidence of pesticide exposure was found in 88.5% of sprayers and significant increments were observed in sperm DFI with significant decrease in some semen parameters. DFI was negatively correlated with BuChE, sperm concentration, morphology, and vitality in these pesticide sprayers. The levels of Tt, PRL, FT4, and TSH appeared to be normal; however, there was a tendency for increased LH and FSH levels in exposed workers. The results confirm the potential impact of chronic occupational exposure to OP and CB pesticides on male reproductive function, which may cause damage to sperm chromatin, decrease semen quality, and produce alterations in reproductive hormones, leading to adverse reproductive health outcomes.
Assuntos
Doenças dos Trabalhadores Agrícolas/induzido quimicamente , Carbamatos/toxicidade , Cromatina/efeitos dos fármacos , Organofosfatos/toxicidade , Praguicidas/toxicidade , Intoxicação/fisiopatologia , Espermatozoides/efeitos dos fármacos , Adolescente , Adulto , Doenças dos Trabalhadores Agrícolas/sangue , Doenças dos Trabalhadores Agrícolas/patologia , Doenças dos Trabalhadores Agrícolas/fisiopatologia , Biomarcadores/sangue , Butirilcolinesterase/sangue , Cromatina/patologia , Estudos Transversais , Fragmentação do DNA , Frutas/crescimento & desenvolvimento , Humanos , Índia , Infertilidade Masculina/etiologia , Masculino , Mangifera/crescimento & desenvolvimento , Pessoa de Meia-Idade , Mutagênicos/toxicidade , Exposição Ocupacional/efeitos adversos , Intoxicação por Organofosfatos/sangue , Intoxicação por Organofosfatos/patologia , Intoxicação por Organofosfatos/fisiopatologia , Intoxicação/sangue , Intoxicação/patologia , Autorrelato , Análise do Sêmen , Espermatozoides/patologia , Adulto JovemRESUMO
The aim of this work was to study whether the increase in antioxidant defenses associated with orchiectomy may account for the reduced susceptibility to aluminum (Al) in male kidney and also to examine whether the reduced antioxidant defenses are associated with androgen levels in orchiectomized (ORX) rats treated with testosterone propionate (TP). Rats were divided into nine groups, namely, intact males (without treatment, treated with sodium lactate, and treated with Al), sham males, ORX males (without treatment, treated with sodium lactate, treated with TP, treated with Al, and treated with TP and Al). Al groups were chronically treated with aluminum lactate for 12 weeks (0.575 mg Al/100 g of body weight, intraperitoneally, three times per week). We reported that ORX rats treated with Al had significantly less lipid peroxidation and an increased level of reduced glutathione (GSH) and GSH/oxidized glutathione ratio in the kidney when compared with intact and TP-treated ORX rats. The activity of superoxide dismutase, catalase, and glutathione peroxidase in ORX rats was much greater than in intact or TP-administered ORX rats. Castration reduced the glomerular alterations caused by Al as well as the number of necrotic tubular cells and nuclear abnormalities. However, we observed a slight alteration in brush border, dilation of proximal tubules, mononuclear infiltrates, and interstitial fibrosis. Castrated males treated with TP showed that this intervention cancels the protective effect of the ORX. This finding suggests that androgens contribute to the development of renal alterations and proteinuria in rats treated with Al. Our results showed that ORX rats are protected against the induction of oxidative stress by Al, but the morphological damage to the kidney tissue induced by the cation was only reduced. Male intact rats treated with Al had more severe glomerulosclerosis, tubular damage, and proteinuria than ORX rats.
Assuntos
Alumínio/toxicidade , Poluentes Ambientais/toxicidade , Intoxicação por Metais Pesados , Rim/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Intoxicação/fisiopatologia , Testículo/metabolismo , Testosterona/metabolismo , Alumínio/administração & dosagem , Animais , Resistência a Medicamentos , Poluentes Ambientais/administração & dosagem , Glutationa/metabolismo , Terapia de Reposição Hormonal/efeitos adversos , Injeções Intraperitoneais , Rim/metabolismo , Rim/patologia , Rim/fisiopatologia , Peroxidação de Lipídeos/efeitos dos fármacos , Masculino , Metais Pesados/sangue , Metais Pesados/metabolismo , Orquiectomia/efeitos adversos , Oxirredução , Oxirredutases/metabolismo , Intoxicação/sangue , Intoxicação/metabolismo , Intoxicação/patologia , Distribuição Aleatória , Ratos Wistar , Insuficiência Renal/etiologia , Insuficiência Renal/prevenção & controle , Testículo/efeitos dos fármacos , Testículo/fisiopatologia , Testosterona/efeitos adversos , Testosterona/sangue , Testosterona/uso terapêuticoRESUMO
There is a great diversity of the acute drugs overdose cases in clinical toxicology. Clinical situation is complicated by the coexistence of factors predisposing to the development of adverse drug reactions (chronic use of drugs, polypharmacy, alcohol or drugs dependence, nutritional disorders) and by the presence of chronic organ damage, especially the liver and the kidney. The aim of this study was to evaluate whether there are sensitive plasma markers belonging to the antioxidant system in patients exposed to various xenobiotics. We measured the activity of antioxidant parameters: catalase (CAT), glutathione peroxidase (GPX3), glutathione (GSH), sulfhydryl groups (-SH), carbonyl groups (=CO) and free radicals (2,2-diphenyl-1-picrylhydrazyl, DPPH, assay) in serum of 49 patients with acute intoxication caused by carbamazepine (CBZ, n = 9), mixed drug intoxication (MDI) (n = 9), alcohol withdrawal syndrome (AWS, n = 9), acetaminophen (APAP, n = 7), tricyclic antidepressants (TCAs) (n = 5), valproic acids (VA, n = 4), narcotics (N, n = 3), and three others (benzodiazepines, BZD, n = 2; barbiturates, n = 1). The results were compared with the parameters of not intoxicated patients (n = 39). All patients had lower catalase activity in comparison to the control group (41.9 ± 16.5 vs. 196.0 ± 82.2 U/mg protein, p = 0.000), while the increase of GSH level was particularly apparent only in patients with AWS (391.3 ± 257.9 µmol/mg protein) compared to the control group (171.4 ± 88.4 µmol/mg protein, p = 0.034) and to patients intoxicated with carbamazepine (152.8 ± 102.5 µmol/mg protein, p = 0.027). Some differences, but without statistical significance, were also observed in GPX3 activity between different groups of poisoned patients.
Assuntos
Antioxidantes/metabolismo , Intoxicação/sangue , Xenobióticos/intoxicação , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , Estudos de Casos e Controles , Catalase/sangue , Feminino , Glutationa/sangue , Glutationa Peroxidase/sangue , Humanos , Masculino , Pessoa de Meia-Idade , Intoxicação/diagnóstico , Carbonilação Proteica/efeitos dos fármacos , Xenobióticos/sangue , Adulto JovemRESUMO
Spreading e-cigarettes popularity comes from relief, the products are safe. They don't contain carcinogenic substances, that are present in tobacco smoke. But nicotine present in e-liquid is a very toxic alkaloid, highly addictive. A case of acute, oral intoxication with e-liquid was described. A patient, 42-years old woman, e-cigarettes addicted, health thus far, by accident drunk a swig of e-liquid containing nicotine at concentration 6 mg/ml. At admission to Toxicology Department she was conscious, with symptoms: dizziness, flushed cheeks, dry skin, dry conjunctivas, medium-wide pupils, nervous twitch, tachycardia, elevated blood pressure. Concentration of cotinine nicotine metabolite, in serum and urine were respectively 2077 and 10236 ng/ml. Applied treatment was: infusive liquids, intravenous alkalization, administration of electrolytes and propranolol. Gradually improvement was reached and on the third day of hospitalization, after psychiatric consultation she was deinstitutionalized in good medical condition to continue treatment in Neurology Clinic. E-fluid intoxications are rare, poisoning course depends on nicotine dose, way of absorption, patient's health state and age.
Assuntos
Sistemas Eletrônicos de Liberação de Nicotina , Nicotina/intoxicação , Intoxicação/terapia , Administração Intravenosa , Adulto , Cotinina/sangue , Cotinina/urina , Eletrólitos/administração & dosagem , Eletrólitos/uso terapêutico , Feminino , Humanos , Intoxicação/sangue , Intoxicação/tratamento farmacológico , Intoxicação/urina , Propranolol/administração & dosagem , Propranolol/uso terapêuticoRESUMO
The objective of the present work was to study peculiarities of detection of 4-nitro-3-(trifluoromethyl)-aniline in the biological material with the use of TLC, GC-MS, and electron spectrophotometry. We have proposed the rationale for the application of acetone as an insulating agent for the extraction of 4-nitro-3-(trifluoromethyl)-aniline from the cadaveric hepatic tissue and biological fluids. It was shown that this compound is possible to separate from endogenous biomaterials on the silicagel L column (40/100 mcm). The results of the quantitative evaluation of different amounts of 4-nitro-3-(trifluoromethyl)-aniline in the cadaveric hepatic tissue, blood, plasma, and urine are presented. The proposed method makes it possible to determine a minimum of 0.12 mg of 4-nitro-3-(trifluoromethyl)-aniline in 100 g of the biological material (cadaveric hepatic tissue), 0.09 mg in 100 g of blood, 0.06 mg and 0.05 mg in 100 u of plasma and urine respectively.