Search

Numerous people die of paraquat (PQ) poisoning because they were not diagnosed and treated promptly at an early stage. Till now, determination of PQ levels in blood or urine is still the only way to confirm the PQ poisoning. In order to develop a new diagnostic method, the potential of machine learning technique was explored in this study. A newly developed classification technique, extreme learning machine (ELM), was taken to discriminate the PQ-poisoned patients from the healthy controls. 15 PQ-poisoned patients recruited from The First Affiliated Hospital of Wenzhou Medical University who had a history of direct contact with PQand 16 healthy volunteers were involved in the study. The ELM method is examined based on the metabolites of blood samples determined by gas chromatography coupled with mass spectrometry in terms of classification accuracy, sensitivity, specificity and AUC (area under the receiver operating characteristic (ROC) curve) criterion, respectively. Additionally, the feature selection was also investigated to further boost the performance of ELM and the most influential feature was detected. The experimental results demonstrate that the proposed approach can be regarded as a success with the excellent classification accuracy, AUC, sensitivity and specificity of 91.64%, 0.9156%, 91.33% and 91.78%, respectively. Promisingly, the proposed method might serve as a new candidate of powerful tools for diagnosis of PQ-poisoned patients with excellent performance. [ABSTRACT FROM AUTHOR]

Hydrogen sulfide (H2S) is the second leading cause of toxin related death (after carbon monoxide) in theworkplace. H2S is absorbed by the upper respiratory tractmucosa, and it causes histotoxic hypoxemia and respiratory depression. Cocktail method was used to evaluate the influences of acute H2S poisoning on the activities of cytochrome P450 isoforms CYP2B6, CYP2D6, CYP3A4, CYP1A2, CYP2C19, and CYP2C9, which were reflected by the changes of pharmacokinetic parameters of six specific probe drugs, bupropion, metoprolol, midazolam, phenacetin, omeprazole, and tolbutamide, respectively. The experimental rats were randomly divided into two groups, control group and acute H2S poisoning group (inhaling 300 ppm for 2 h). The mixture of six probes was given to rats by oral administration and the blood samples were obtained at a series of time points through the caudal vein. The concentrations of probe drugs in rat plasma were measured by LC-MS. The results for acute H2S poisoning and control groups were as follows: there was a statistically significant difference in the AUC and Cmax for bupropion, metoprolol, phenacetin, and tolbutamide, while there was no statistical pharmacokinetic difference for midazolam and omeprazole. Acute H2S poisoning could inhibit the activity of CYP2B6, CYP2D6, CYP1A2, and CYP2C9 in rats. [ABSTRACT FROM AUTHOR]

MGCD0103, an isotype-selective histone deacetylase inhibitor (HDACi), has been clinically evaluated for the treatment of hematologic malignancies and advanced solid tumors, alone and in combination with standard-of-care agents. In order to investigate the effects of MGCD0103 on the metabolic capacity of cytochrome P450 (CYP) enzymes, a cocktail method was employed to evaluate the activities of human CYP2B1, CYP1A2, CYP2C11, CYP2D6, CYP3A4, and CYP2C9. The rats were randomly divided into MGCD0103 group (Low, Medium, and High) and control group. The MGCD0103 group rats were given 20, 40, and 80?mg/kg (Low, Medium, and High) MGCD0103 by continuous intragastric administration for 7 days. Six probe drugs, bupropion, phenacetin, tolbutamide, metoprolol, testosterone, and omeprazole, were given to rats through intragastric administration, and the plasma concentrations were determined by UPLC-MS/MS. Statistical pharmacokinetics difference for tolbutamide in rats were observed by comparing MGCD0103 group with control group. Continuous 7-day intragastric administration of MGCD0103 slightly induces the activities of CYP2C11 of rats. [ABSTRACT FROM AUTHOR]