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1.
J Forensic Sci ; 64(5): 1544-1547, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30786026

RESUMO

We present the first report of pneumopericardium observed by autopsy and on postmortem computed tomography (PMCT) images. The subject was a woman who died of self-inflicted stab wounds to the abdomen. The PMCT scan revealed air in the pericardial sac, a "flattened heart" sign, and retroperitoneal hemorrhage. Medicolegal autopsy revealed two abdominal stab wounds near the xiphoid process that had cut the apical pericardium and adjacent diaphragm and liver. Examination of the open thorax confirmed that the pericardial sac was distended with air. The wound extended to the abdominal aorta, causing retroperitoneal hemorrhage. PMCT images showed that the pneumopericardial volume was 133 mL. We believe that cardiac tamponade occurred resulting from the tension pneumopericardium; however, the effects were mitigated by hypovolemia secondary to the retroperitoneal hemorrhage as well as obstructive shock. Therefore, the cause of death appears to have been low-pressure cardiac tamponade.


Assuntos
Traumatismos Abdominais/diagnóstico por imagem , Traumatismos Abdominais/patologia , Pneumopericárdio/diagnóstico por imagem , Pneumopericárdio/patologia , Ferimentos Perfurantes/diagnóstico por imagem , Ferimentos Perfurantes/patologia , Adulto , Aorta Abdominal/lesões , Aorta Abdominal/patologia , Autopsia , Tamponamento Cardíaco/etiologia , Feminino , Medicina Legal , Hemorragia/diagnóstico por imagem , Hemorragia/patologia , Humanos , Suicídio , Tomografia Computadorizada por Raios X
2.
Forensic Sci Int ; 249: 165-72, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25700112

RESUMO

Forensic toxicological drug analyses of human specimens are usually performed immediately after autopsy or on frozen preserved tissues. Occasionally, cases require analysis of drugs from tissues fixed in formalin solution. To improve the estimation of the level of drug in tissues following formalin fixation, we studied drug concentrations in human tissues, liver and kidney, that were collected from a drug-positive autopsy case. Parts of tissues were preserved in formalin solution for 1, 3, 6 and 13 months. Tissues obtained before and after preservation, along with tissue-exposed fixatives, were assayed using gas chromatography-mass spectrometry; all of the samples were assayed for the presence of drugs and changes in the drug concentrations both before and after preservation in formalin. Concentrations of assayed drugs decreased upon fixation in formalin; levels of these drugs did not necessarily show further decreases during subsequent storage in fixative, up to 13 months. Distinct trends in drug levels were found in liver and kidney. In liver, the levels of chlorpromazine, levomepromazine, and promethazine decreased to 23-39% at 1 month after preservation; all 3 of these drugs were detected at all tested time points of preservation. Bromazepam was not detected at 13 months after preservation. Milnacipran was the most unstable after preservation in formalin solution among all of the assayed drugs. In kidney, all assayed drugs exhibited reduced stability during preservation compared to levels in liver. Methamphetamine and methylenedioxymethamphetamine were not detected in any time points of tissues. The proportions of the drugs that remained within the tissues differed between liver and kidney. Also, S-oxide compounds of chlorpromazine and levomepromazine, which were not observed before preservation, were detected in fixed liver tissues and their fixatives at 3, 6 and 13 months of preservation. These results suggest that analyses in formalin-fixed tissues need to include analysis of various organ-tissues and their fixatives at multiple time points for the duration of preservation. These analyses should include detection of chemical degradation/denaturation products, such as S-oxides of chlorpromazine and levomepromazine.


Assuntos
Antipsicóticos/análise , Fixadores , Formaldeído , Rim/química , Fígado/química , Entorpecentes/análise , Preservação de Órgãos/métodos , Adulto , Bromazepam/análise , Clorpromazina/análise , Ciclopropanos/análise , Estabilidade de Medicamentos , Toxicologia Forense , Cromatografia Gasosa-Espectrometria de Massas , Humanos , Masculino , Metanfetamina/análise , Metotrimeprazina/análise , Milnaciprano , N-Metil-3,4-Metilenodioxianfetamina/análise , Prometazina/análise , Fatores de Tempo
3.
Medicine (Baltimore) ; 94(4): e463, 2015 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-25634188

RESUMO

The guidelines on the indications for gastric lavage were published in 1997, and a less-aggressive initial approach has been used for poisoned patients. Clinical studies have shown that the outcomes of retrieval of residual toxic substances in the stomach are variable and that no beneficial effect is obtained. However, the presence of residual toxic substances in the stomach before gastric lavage has not been estimated. The objective of this study was to evaluate the residual stomach contents on admission of patients with oral drug overdoses using upper gastrointestinal endoscopy. A 2-year prospective study of 167 patients with oral drug overdoses was performed. Endoscopy was performed on admission to observe the gastric body, fornix, and pyloric antrum. Patients were classified into 3 groups according to the digestive phase (tablet/food phase, soluble/fluid phase, and reticular/empty phase). The groups were compared with respect to time elapsed since ingestion, and numbers and variety of orally overdosed drugs. The numbers of patients in each phase were as follows: tablet/food phase, 73; soluble/fluid phase, 50; and reticular/empty phase, 44. The tablet/food and soluble/fluid phase groups contained the greatest numbers of patients who presented within 1 to 2 hours since ingestion. In the tablet/food group, only 12 of 73 patients (16%) presented within 1 hour since ingestion, and 3 patients presented >12 hours since ingestion. In the soluble/fluid phase group, only 9 of 50 patients (18%) presented within 1 hour since ingestion, and 2 patients presented >12 hours since ingestion. The reticular/empty phase group contained the greatest number of patients presenting within 2 to 4 hours since ingestion, and 3 patients presented within 1 hour since ingestion. The residual stomach contents before lavage were variable in all of the groups. The residual gastric content before the performance of gastric lavage is variable in overdosed patients on admission. This may influence the efficiency of gastric lavage with respect to retrieval of residual toxic substances in the stomach. This study may contribute to the development of a strategy for treating patients who have orally overdosed on drugs in the future.


Assuntos
Digestão , Overdose de Drogas , Endoscopia Gastrointestinal , Conteúdo Gastrointestinal , Administração Oral , Adolescente , Adulto , Idoso , Feminino , Esvaziamento Gástrico , Lavagem Gástrica , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Adulto Jovem
4.
Biochim Biophys Acta ; 1842(5): 691-700, 2014 May.
Artigo em Inglês | MEDLINE | ID: mdl-24491919

RESUMO

The underlying mechanisms of cardiotoxicity of 3,4-methylenedioxymethylamphetamine (MDMA, "ecstasy") abuse are unclear. Autophagy exerts either adaptive or maladaptive effects on cardiac function in various pathological settings, but nothing is known on the role of autophagy in the MDMA cardiotoxicity. Here, we investigated the mechanism through which autophagy may be involved in MDMA-induced cardiac contractile dysfunction. Rats were injected intraperitoneally with MDMA (20mg/kg) or saline. Left ventricular (LV) echocardiography and LV pressure measurement demonstrated reduction of LV systolic contractility 24h after MDMA administration. Western blot analysis showed a time-dependent increase in the levels of microtubule-associated protein light chain 3-II (LC3-II) and cathepsin-D after MDMA administration. Electron microscopy showed the presence of autophagic vacuoles in cardiomyocytes. MDMA upregulated phosphorylation of adenosine monophosphate-activated protein kinase (AMPK) at Thr172, mammalian target of rapamycin (mTOR) at Thr2446, Raptor at Ser792, and Unc51-like kinase (ULK1) at Ser555, suggesting activation of autophagy through the AMPK-mTOR pathway. The effects of autophagic inhibitors 3-methyladenine (3-MA) and chloroquine (CQ) on LC3-II levels indicated that MDMA enhanced autophagosome formation, but attenuated autophagosome clearance. MDMA also induced release of cathepsins into cytosol, and western blotting and electron microscopy showed cardiac troponin I (cTnI) degradation and myofibril damage, respectively. 3-MA, CQ, and a lysosomal inhibitor, E64c, inhibited cTnI proteolysis and improved contractile dysfunction after MDMA administration. In conclusion, MDMA causes lysosome destabilization following activation of the autophagy-lysosomal pathway, through which released lysosomal proteases damage myofibrils and induce LV systolic dysfunction in rat heart.


Assuntos
Autofagia/efeitos dos fármacos , Lisossomos/efeitos dos fármacos , Contração Miocárdica/efeitos dos fármacos , N-Metil-3,4-Metilenodioxianfetamina/toxicidade , Regulação para Cima/efeitos dos fármacos , Adenilato Quinase/metabolismo , Animais , Western Blotting , Cromatografia Líquida , Masculino , Microscopia Eletrônica , Ratos , Ratos Sprague-Dawley , Transdução de Sinais/efeitos dos fármacos , Serina-Treonina Quinases TOR/metabolismo , Espectrometria de Massas em Tandem
5.
Chudoku Kenkyu ; 27(4): 327-32, 2014 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-25771667

RESUMO

BACKGROUND: Benzalkonium chloride (BZK) is widely used as a germicide in hospitals and other places. Although several cases of accidental oral intake of BZK have been reported, there have been few reported cases of BZK toxicity due to intravenous injection. CASE REPORT: A male nurse in his 40 s injected 15 mL of 10% BZK (Osvan S) directly into his left antebrachial vein while at home, as a suicide attempt. The patient was admitted to our hospital 1 hour later. Acute respiratory distress syndrome (ARDS) was diagnosed by blood gas analysis, chest X-ray, and CT scan. Due to extracorporeal blood purification therapy, including hemoperfusion and plasma exchange, serum BZK became undetectable. However, the ARDS was not improved. Extracorporeal blood purification therapy consisting of continuous hemodiafiltration (CHDF) was continued to treat the ARDS. After performing CHDF for the next 36 hours, improvement of both the PaO2/FiO2 ratio and chest X-ray findings was noted. Tracheal extubation was performed on day 9 and no further complications occurred after this period, he was discharged on day 21. CONCLUSION: Extracorporeal blood purification therapy is probably effective for treatment of BZK intoxication by intravenous injection.


Assuntos
Compostos de Benzalcônio/administração & dosagem , Compostos de Benzalcônio/intoxicação , Síndrome do Desconforto Respiratório/induzido quimicamente , Síndrome do Desconforto Respiratório/terapia , Desintoxicação por Sorção/métodos , Tentativa de Suicídio , Hemodiafiltração , Humanos , Injeções Intravenosas , Masculino , Pessoa de Meia-Idade , Troca Plasmática , Resultado do Tratamento
6.
J Nippon Med Sch ; 80(5): 350-61, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-24189353

RESUMO

Aconitine, well-known for its high cardiotoxicity, causes severe arrhythmias, such as ventricular tachycardia and ventricular fibrillation, by opening membrane sodium channels. Tetrodotoxin, a membrane sodium-channel blocker, is thought to antagonize aconitine activity. Tetrodotoxin is a potent blocker of the skeletal muscle sodium-channel isoform Na(v)1.4 (IC50 10 nM), but micromolar concentrations of tetrodotoxin are required to inhibit the primary cardiac isoform Na(v)1.5. This suggests that substantial concentrations of tetrodotoxin are required to alleviate the cardiac toxicity caused by aconitine. To elucidate the interaction between aconitine and tetrodotoxin in the cardiovascular and respiratory systems, mixtures of aconitine and tetrodotoxin were simultaneously administered to mice, and the effects on electrocardiograms, breathing rates, and arterial oxygen saturation were examined. Compared with mice treated with aconitine alone, some mice treated with aconitine-tetrodotoxin mixtures showed lower mortality rates and delayed appearance of arrhythmia. The decreased breathing rates and arterial oxygen saturation observed in mice receiving aconitine alone were alleviated in mice that survived after receiving the aconitine-tetrodotoxin mixture; this result suggests that tetrodotoxin is antagonistic to aconitine. When the tetrodotoxin dose is greater than the dose that can block tetrodotoxin-sensitive sodium channels, which are excessively activated by aconitine, tetrodotoxin toxicity becomes prominent, and the mortality rate increases because of the respiratory effects of tetrodotoxin. In terms of cardiotoxicity, mice receiving the aconitine-tetrodotoxin mixture showed minor and shorter periods of change on electrocardiography. This finding can be explained by the recent discovery of tetrodotoxin-sensitive sodium-channel cardiac isoforms (Na(v)1.1, 1.2, 1.3, 1.4 and 1.6).


Assuntos
Aconitina , Antiarrítmicos/farmacologia , Arritmias Cardíacas/prevenção & controle , Bloqueadores dos Canais de Sódio/farmacologia , Tetrodotoxina/farmacologia , Animais , Arritmias Cardíacas/sangue , Arritmias Cardíacas/induzido quimicamente , Arritmias Cardíacas/metabolismo , Arritmias Cardíacas/fisiopatologia , Biomarcadores/sangue , Modelos Animais de Doenças , Eletrocardiografia , Frequência Cardíaca/efeitos dos fármacos , Masculino , Camundongos , Camundongos Endogâmicos ICR , Miocárdio/metabolismo , Oxigênio/sangue , Taxa Respiratória/efeitos dos fármacos , Fatores de Tempo , Canais de Sódio Disparados por Voltagem/efeitos dos fármacos , Canais de Sódio Disparados por Voltagem/metabolismo
7.
Anal Bioanal Chem ; 405(30): 9879-88, 2013 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-24173661

RESUMO

The phenomenon "matrix-induced chromatographic response enhancement" (matrix effect) causes quantitative errors in gas chromatography (GC) analyses. This effect varies according to the analyte nature, matrix type and concentration, and GC-system parameters. By focusing on the physicochemical properties of analytes, a predictive model was developed for the matrix effect using quantitative structure-property relationships. Experimental values of the matrix effect were determined for 58 compounds in a serum extract obtained from solid-phase extraction as the matrix. Eight molecular descriptors were selected, and the matrix-effect model was developed by multiple linear regression. The developed model predicted values for the matrix effect without any further experimental measurements. It also indicated that the molecular polarity (particularly H-bond donors) and volume of the analyte increase the matrix effect, while hydrophobicity and increasing number of nonpolar carbon atoms in the analyte decrease the matrix effect. The model was applied to the analysis of barbiturates. The predicted values indicated that N-methylation decreases the matrix effect, and the relative predicted values were effective for the selection of an internal standard. The obtained insight into the matrix effect and the prediction data will be helpful for developing quantitative analysis strategies.


Assuntos
Cromatografia Líquida de Alta Pressão/métodos , Cromatografia Gasosa-Espectrometria de Massas/métodos , Preparações Farmacêuticas/sangue , Relação Quantitativa Estrutura-Atividade , Colesterol/química , Humanos , Interações Hidrofóbicas e Hidrofílicas , Extração em Fase Sólida
8.
J Forensic Leg Med ; 20(8): 962-4, 2013 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-24237799

RESUMO

The authors present a fatal case of poisoning with Tolfenpyrad (TFP), a pesticide first approved in Japan in 2002. A man in his fifties was found dead in the supine position at his son's home and the small towel with a smell of naphthalene was found nearby. Forensic autopsy was unremarkable, except for a very small amount of light pink fluid in the stomach, with naphthalene odour. The toxicological analyses revealed the presence of TFP and its major metabolite PTCA (4-[4-[(4-chloro-3-ethyl-1-methylpyrazol-5-yl)carbonylaminomethyl]phenoxy]benzoic acid), together with naphthalene and methyl naphthalenes in the post-mortem sample, with liquid chromatography-mass spectrometry (LC-MS) and gas chromatography-mass spectrometry (GC-MS) respectively. The plasma concentrations of each substance were quantified as 1.97 µg/ml (TFP), 2.88 µg/ml (PTCA), 1.70 µg/ml (naphthalene), 0.67 µg/ml (1-methyl naphthalene) and 1.44 µg/ml (2-methyl naphthalene). According to these results together with autopsy findings, the cause of his death was determined to be acute Tolfenpyrad poisoning. This is the first case report of fatal poisoning attributable to an intake of TFP product.


Assuntos
Inseticidas/intoxicação , Pirazóis/intoxicação , Cromatografia Gasosa , Cromatografia Líquida , Evolução Fatal , Toxicologia Forense , Conteúdo Gastrointestinal/química , Humanos , Inseticidas/análise , Inseticidas/química , Japão , Masculino , Espectrometria de Massas , Pessoa de Meia-Idade , Estrutura Molecular , Naftalenos/análise , Pirazóis/análise , Pirazóis/química
9.
Int J Emerg Med ; 6(1): 39, 2013 Oct 22.
Artigo em Inglês | MEDLINE | ID: mdl-24148152

RESUMO

BACKGROUND: In Japan, ultrathin transnasal esophagogastroduodenoscopy (EGD) with a 4.9-mm diameter endoscope (Olympus XP260) is routinely used to examine the upper gastrointestinal tract. This procedure does not require sedation and does not affect vital signs. Gastric lavage is not empirically employed in the management of all poisoning patients. It is considered only for potentially life-threatening overdoses when the procedure can be performed within 1 h of ingestion of the poison. However, there are no absolute indications for gastric lavage. EGD may increase the indications, efficiency and safety of gastric lavage in poisoning patients. FINDINGS: A 35-year-old female was admitted to our emergency department 2 h after ingesting multiple drugs, including a critical dose of the tricyclic antidepressant (TCA) amitriptyline, at which time she was confused and had a Glasgow Coma Scale score of 8 (E1V2M5). Endotracheal intubation was performed. To confirm the type of TCA and in order to determine whether gastric lavage was required, we decided to perform EGD. Endoscopy demonstrated adherence of residual drugs to the stomach wall, in a soluble form and not as a mass. Hence, gastric lavage was performed via the EGD to avoid passage of these drugs into the small bowel. The patient was extubated on day 2, without the development of complications such as aspiration pneumonia, and was discharged on day 5. CONCLUSION: EGD may be useful in poisoning patients for determining the amount of residual drug in the stomach, also allowing direct observation of the effectiveness of gastric lavage.

10.
J Nippon Med Sch ; 80(4): 307-11, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23995574

RESUMO

Nicotine, which is found in tobacco, is one of the most toxic of all known poisons. A 31-year-old woman was brought to our emergency department 2 hours after ingesting a usually fatal dose of a tobacco extract. Although gastric lavage was once commonly used to treat poisoning cases of this type, lavage can lead to such complications as aspiration, hypoxia, oropharyngeal and gastric trauma, and electrolyte disturbances. Recent guidelines have suggested less-aggressive gastric-emptying procedures as initial treatments. Currently, there are no absolute indications for gastric lavage use. The present patient had a history of depressive episodes and had attempted suicide by ingesting an extract derived from 20 cigarettes mixed with alcohol. There was no evidence of vomiting or seizures occurring before arrival of the ambulance. Physical examination revealed no signs of sweating, although the patient appeared to be confused, which is often seen with nicotine intoxication. She admitted using 2 kinds of cigarette, each of which typically contain 11.2 mg of nicotine. The patient's nicotine level was suspected to be higher than 40 to 60 mg, which is normally fatal. To determine whether gastric lavage was indicated in this case, we performed ultrathin transnasal esophagogastroduodenoscopy, which neither requires sedation nor compromises the airways. Although 2 hours had passed since ingestion, the tobacco extract and food were directly visualized within the stomach. Subsequently, gastric lavage was performed with 2,000 mL of water administered through a nasogastric tube. Ultrathin esophagogastroduodenoscopy made it possible to directly observe the gastric lavage and to ensure the stomach contents had been completely removed. No changes were noted in the vital signs, and no obstruction of the airways was observed. The patient recovered quickly and was discharged the following day. Ultrathin esophagogastroduodenoscopy helped determine the diagnosis and ensure that gastric lavage had been performed without complications.


Assuntos
Endoscopia do Sistema Digestório , Lavagem Gástrica/métodos , Nicotiana/intoxicação , Nicotina/intoxicação , Extratos Vegetais/intoxicação , Adulto , Feminino , Humanos , Intoxicação/diagnóstico , Intoxicação/terapia , Tentativa de Suicídio , Fatores de Tempo , Resultado do Tratamento
11.
Forensic Sci Int ; 227(1-3): 95-9, 2013 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-23290298

RESUMO

A sensitive method for the simultaneous determination of quazepam and two of its metabolites, 2-oxoquazepam and 3-hydroxy-2-oxoquazepam, in human urine was developed using gas chromatography-mass spectrometry (GC/MS) with an Rtx-5MS capillary column. The quazepam and its metabolites were extracted from human urine using a simple solid-phase extraction Oasis(®) HLB cartridge column, and the 3-hydroxy-2-oxoquazepam was derivatised using BSTFA/1%TMCS and pyridine at 60 °C for 30 min. The mass spectrometric detection of the analytes was performed in the full scan mode, m/z 60-480, and selected ion monitoring (SIM) mode, m/z 386, for quazepam; m/z 342, for 2-oxoquazepam; m/z 429, for 3-hydroxy-2-oxoquazepam-TMS; and m/z 284, for alprazolam-d5 (internal standard), by electron ionization. The calibration curves of quazepam and its metabolites in urine showed good linearity in the concentration range of 2.5-500 ng/0.2 ml of urine. The average recoveries of quazepam and its metabolites from 0.2 ml of urine containing 500 ng and 50 ng of each drug were 71-83% and 88-90%, respectively. The limits of detection of quazepam, 2-oxoquazepam and 3-hydroxy-2-quazepam in urine by the selected ion monitoring mode were 0.096-0.37 ng/ml. This method would be applicable to other forensic biological materials containing low concentrations of quazepam and its metabolites.


Assuntos
Benzodiazepinas/urina , Hipnóticos e Sedativos/urina , Benzodiazepinonas/urina , Toxicologia Forense , Cromatografia Gasosa-Espectrometria de Massas/métodos , Humanos , Masculino , Extração em Fase Sólida , Detecção do Abuso de Substâncias/instrumentação , Triazolam/análogos & derivados , Triazolam/urina
12.
Forensic Sci Int ; 227(1-3): 45-7, 2013 Apr 10.
Artigo em Inglês | MEDLINE | ID: mdl-23116635

RESUMO

There are few reports from Japan on the analysis of fluids in survivors of body-packer syndrome. We analyzed the concentrations of stimulants in the serum, plasma and urine collected from three patients suspected of being body packers at immigration that were referred to hospitals between 2010 and 2011. The drugs were extracted with solid-phase columns and analyzed by gas chromatography-mass spectrometry (GC-MS). In all cases, wrapped, cylindrical packets of foreign bodies were detected in the intestinal tract on plain X-ray (X-P) and computed tomography (CT), and they were eventually removed surgically. In case 1, the patient presented with convulsions and tachycardia at admission to the hospital and one of the packets was found to have ruptured. In case 2, although the subject appeared to have an intestinal obstruction caused by the packets on the third day, he exhibited no symptoms on arrival and the packets did not appear to have ruptured. In case 3, the patient exhibited restlessness on the first day and one of the removed packets had ruptured. In all cases, methamphetamine (MA) and amphetamine (AP) were detected in serum, plasma and urine. In this study, we report the variation in MA and AP concentrations in survivors of body-packer syndrome. The serum and plasma concentrations of MA were high in subjects that exhibited symptoms of MA intoxication. MA and AP were also detected in the case in which the patient exhibited no symptoms of intoxication and the packets had not ruptured. These results suggest either that the stimulants may have seeped through the wrap of the packets, or that the subject had been abusing the drugs.


Assuntos
Anfetamina/sangue , Anfetamina/urina , Crime , Corpos Estranhos/diagnóstico por imagem , Metanfetamina/sangue , Metanfetamina/urina , Adulto , Estimulantes do Sistema Nervoso Central/sangue , Estimulantes do Sistema Nervoso Central/urina , Corpos Estranhos/cirurgia , Toxicologia Forense , Cromatografia Gasosa-Espectrometria de Massas , Trato Gastrointestinal/diagnóstico por imagem , Trato Gastrointestinal/cirurgia , Humanos , Drogas Ilícitas/sangue , Drogas Ilícitas/urina , Obstrução Intestinal/etiologia , Japão , Limite de Detecção , Masculino , Agitação Psicomotora/etiologia , Radiografia , Convulsões/induzido quimicamente , Taquicardia/induzido quimicamente
13.
J Anal Toxicol ; 36(7): 529-37, 2012 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-22802573

RESUMO

Tolfenpyrad (TFP) is a pesticide that was first approved in 2002 in Japan under the trade name of Hachi-hachi. Analyses of TFP and its major metabolite, 4-[4-[(4-chloro-3-ethyl-1-methylpyrazol-5-yl)carbonylaminomethyl]phenoxy]benzoic acid (PTCA), in plasma obtained from a cadaver suspected to have died of TFP poisoning, were conducted by liquid chromatography-mass spectrometry. The existence of TFP and PTCA was confirmed by scan mode and quantitative analysis was performed by selected ion monitoring mode. Calibration curves showed good linearity over the range of 0.1-4 and 0.25-4 µg/mL, and concentrations were estimated to be 1.97 ± 0.02 and 2.88 ± 0.04 µg/mL for TFP and PTCA, respectively. The plasma extract was further examined to find other metabolites using quadrupole time-of-flight MS, and the results revealed three more metabolites, which were suggested to be hydroxy-TFP, dehydro-TFP and hydroxy-PTCA. Plausible metabolic pathways of TFP in humans are: (i) oxidation of the methyl group on the benzene ring, and (ii) hydroxylation followed by dehydration at the ethyl group on the pyrazole ring.


Assuntos
Praguicidas/sangue , Praguicidas/intoxicação , Pirazóis/sangue , Pirazóis/intoxicação , Benzeno/química , Calibragem , Cromatografia Líquida/métodos , Humanos , Masculino , Pessoa de Meia-Idade , Naftalenos/sangue , Praguicidas/química , Pirazóis/química , Espectrometria de Massas em Tandem/métodos
15.
J Chromatogr B Analyt Technol Biomed Life Sci ; 877(25): 2652-7, 2009 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-19501029

RESUMO

Benzodiazepines and their pharmacologically related drugs, zolpidem and zopiclone are widely prescribed as safe drugs, but these drugs are also abused in cases of crime, suicide and drug-facilitated sexual assault. We developed a rapid and quantitative screening method for 43 benzodiazepines, their metabolites, zolpidem and zopiclone in human plasma by liquid chromatography/mass spectrometry with a small particle column. All drugs were successfully separated within 12 min using combined scan and selected ion recording (SIR) mode. The calibration curves of most drugs were linear in the concentration range 0.5-250 ng/mL with correlation coefficients exceeding 0.99. Within-day precisions (RSD, %) of this method were 1.8-15.6% (10 ng/mL) and 0.6-10.1% (100 ng/mL) and between-day precisions (RSD, %) were 1.6-16.9% (10 ng/mL) and 0.6-16.7% (100 ng/mL). The average recoveries were 70.1% (10 ng/mL) and 87.1% (100 ng/mL). The limit of detection ranged from 0.2 to 8.0 ng/mL in 37 drugs and was below 0.2 ng/mL in 6 drugs. The established method is sensitive and rapid, thus it should be useful in forensic and clinical toxicological analyses.


Assuntos
Compostos Azabicíclicos/sangue , Benzodiazepinas/química , Cromatografia Líquida/métodos , Espectrometria de Massas/métodos , Piperazinas/sangue , Piridinas/sangue , Compostos Azabicíclicos/metabolismo , Benzodiazepinas/sangue , Benzodiazepinas/metabolismo , Cromatografia Líquida/instrumentação , Humanos , Espectrometria de Massas/instrumentação , Piperazinas/metabolismo , Piridinas/metabolismo , Zolpidem
16.
Leg Med (Tokyo) ; 11 Suppl 1: S423-5, 2009 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-19362868

RESUMO

Time-of-flight mass spectrometry coupled with liquid chromatography (TOF-MS) has been developed for screening and determination of benzodiazepines with an exact mass database. Benzodiazepines display similar chemical structures and molecular weights, and thus show similar mass spectra and protonated molecule ions. Discrimination of mass spectrometry at low resolving power using single liquid chromatography mass spectrometry (LC-MS) is commonly difficult. TOF-MS analysis was performed using a 1100 TOF (Agilent Technologies) equipped with a Zorbax C18 Extend column. Purine and fluorine compound solution was always introduced into the ion source, and real-time mass adjusting was performed. Specimens were prepared utilizing the liquid-liquid extraction procedure with 1-chlorobutane. Benzodiazepines are widely used in medical practice in Japan, and data acquired from TOF-MS measurements of 41 benzodiazepines, including active metabolites, were used to create an exact mass database. This database comprised molecular formulae, calculated exact masses and retention times. Calibrations were also included in a database. Precision for the 41 drugs was considered sufficient for quantitative analysis. In analysis of samples from patient who had taken > or =2 benzodiazepines, selectivity was improved using the TOF-MS exact mass database. TOF-MS is effective for forensic toxicology in discriminating between benzodiazepines with similar structure and metabolites.


Assuntos
Benzodiazepinas/análise , Bases de Dados Factuais , Espectrometria de Massas/métodos , Adulto , Cromatografia Líquida , Toxicologia Forense , Conteúdo Gastrointestinal/química , Humanos , Masculino , Detecção do Abuso de Substâncias/métodos
17.
Leg Med (Tokyo) ; 11 Suppl 1: S573-5, 2009 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-19269227

RESUMO

An unconscious 20-year-old female was admitted to hospital with a heart rate of 164, a blood pressure of 132/90 mmHg, and hypokalemia. "Triage" urine screening tests were negative on arrival and 12 h later. The next day, her SGOT and SGPT levels rose remarkably; however, on the third day, the patient regained consciousness. Two Japanese OTC drugs and an American herbal dietary supplement ("7th heaven") were found in her room. The supplement and the patient's samples were analyzed using GC/MS. Ephedrine (2.32 mg/g) and caffeine (17.96 mg/g) were detected in the supplement and in the patient's serum (0.627 mg/L, 383 mg/L, respectively), as well as acetaminophen, bromvalerylurea, and etenzamide, which are constituents of the OTC drugs. The serum ephedrine concentration was above the therapeutic level but did not reach the fatal level. The acetaminophen concentration was sufficient to cause liver damage. Although a prescription is necessary to obtain products containing ephedrine in Japan, this patient had no prescription. Thus, how the patient obtained the drug and the amount ingested were unclear. Information about acquisition of drugs via the Internet or magazine advertisements is constantly changing and unreliable. Thus, it is indispensable to analyze unfamiliar supplements found with patients.


Assuntos
Estimulantes do Sistema Nervoso Central/análise , Suplementos Nutricionais/efeitos adversos , Efedrina/análise , Medicamentos sem Prescrição/química , Acetaminofen/sangue , Adulto , Analgésicos não Narcóticos/sangue , Cafeína/análise , Feminino , Toxicologia Forense , Cromatografia Gasosa-Espectrometria de Massas , Frequência Cardíaca/efeitos dos fármacos , Humanos , Hipopotassemia/induzido quimicamente
18.
Leg Med (Tokyo) ; 11(3): 132-5, 2009 May.
Artigo em Inglês | MEDLINE | ID: mdl-19121599

RESUMO

An accidental case of aconite intoxication occurred after a patient took a therapeutic dose of Kampo herbal medicine containing Aconiti tuber, Uzu but had used the wrong decoction procedure. The poisoning was likely caused by an increased level of Aconitum alkaloids in the decoction; the patient developed aconite intoxication due to incomplete decoction. Aconitum alkaloid levels in the leftover solution which the patient had drunk and in the decoction extracted from 3g Uzu were determined. It was found that decoction makes the medicine safer to drink. Older individuals, especially those with dementia, have a higher risk of aconite poisoning because they sometimes do not boil the medicine appropriately.


Assuntos
Aconitum/intoxicação , Alcaloides/intoxicação , Medicina Tradicional Chinesa/efeitos adversos , Intoxicação por Plantas/diagnóstico , Acidentes , Aconitum/química , Alcaloides/química , Feminino , Humanos , Pessoa de Meia-Idade , Estrutura Molecular , Intoxicação por Plantas/etiologia , Raízes de Plantas
19.
J Pharm Biomed Anal ; 44(1): 1-7, 2007 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-17379468

RESUMO

Miniaturized needle extraction device has been developed as a versatile sample preparation device designed for the rapid and simple analysis of smoking-related compounds in smokers' hair samples and environmental tobacco smoke. Packed with polymeric particle, the resulting particle-packed needle was employed as a miniaturized sample preparation device for the analysis of typical volatile organic compounds in tobacco smoke. Introducing a bundle of polymer-coated filaments as the extraction medium, the needle was further applied as a novel sample preparation device containing simultaneous derivatization/extraction process of volatile aldehydes. Formaldehyde (FA) and acetaldehyde (AA) in smoker's breath during the smoking were successfully derivatized with two derivatization reagents in the polymer-coated fiber-packed needle device followed by the separation and determination in gas chromatography (GC). Smokers' hair samples were also packed into the needle, allowing the direct extraction of nicotine from the hair sample in a conventional GC injector. Optimizing the main experimental parameters for each technique, successful determination of several smoking-related compounds with these needle extraction methods has been demonstrated.


Assuntos
Exposição Ambiental , Cabelo/química , Miniaturização , Agulhas , Fumar , Poluição por Fumaça de Tabaco/análise , Acetaldeído/análise , Testes Respiratórios , Cromatografia Gasosa , Desenho de Equipamento , Formaldeído/análise , Humanos , Miniaturização/instrumentação , Miniaturização/métodos , Nicotina/análise , Compostos Orgânicos/análise , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Volatilização
20.
J Anal Toxicol ; 29(6): 539-543, 2005.
Artigo em Inglês | MEDLINE | ID: mdl-16297284

RESUMO

We evaluated the diagnostic performance of Triage for benzodiazepines in 74 urine specimens from outpatients given therapeutic doses of benzodiazepines and compared the results of EMIT assays. Results obtained in all urine samples were confirmed using liquid chromatography-mass spectrometry (LC-MS). Overall agreement between results of Triage and EMIT assays was 73%. All of the Triage-positive samples were also positive by EMIT assays. Results of Triage and EMIT assays were different for 20 samples obtained from patients given thienodiazepines (etizolam, brotizolam, and clotiazepam) and nitrobenzodiazepines (nitrazepam, flunitrazepam, and clonazepam). LC-MS confirmed parent drugs in urine specimens, consistent with the prescriptions of drugs. The low agreement between Triage and EMIT results in this study might be due to low sensitivity of Triage for thienodiazepines. Thienodiazines are frequently prescribed benzodiazepines, and Triage panel is the most frequently used screening kit in Japan. It should be noted that negative results obtained by a Triage test might not mean the absence of thienodiazepines.

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