RESUMEN
AIM: To investigate the changes of bile acid metabolism in healthy adults after taking acetaminophen. METHODS: Ten healthy subjects were enrolled and the serum samples of subjects before and after multiple administration of acetaminophen were collected. They were divided into pre-dose group (PD), fifth-dose gro-up (FD) and eighth-dose group (ED). A high performance liquid chromatography-tandem mass spectrometric method (HPLC-MS/MS) was used to quantify 15 target-edbile acid metabolites in human plasma, combined with principal component analysis (PCA), orthogonal partial least squares discriminant analysis (OPLS-DA)to investigate the changes of bile acid metabolism profile in healthy adults after taking acetaminophen. And the biochemical indicators of each group were detected. RESULTS: There was a change in the bile acid spectrum of human serum after taking acetaminophen. Compared with group PD, the taurochenodeoxycholicacid (TCDCA), glycocholicacid (GCA), glycochenodeoxycholic acid (GCDCA) and tauroursodeoxycholic acid (TUDCA) levels were significantly increased (P<0.05). There was no obvious changes in biochemical indicators. GCA and GCDCA were the most sen-sitive indicators of bile acid. CONCLUSION: GCA and GCDCA can be used as potential biomarkers of early liver injury caused by acetaminophen.
RESUMEN
Objective:To explore the effect of adhesion molecule nectin-1 expression on epileptic seizure and mossy fiber sprouting.Methods:(1) Adult male SD rats were randomly divided into control group ( n=6), empty vector group ( n=6) and lentivirus interfered group ( n=24), and rats in the lentivirus interfered group were further divided into 4 subgroups ( n=6) according to the time points of lentivirus injection (3, 7, 14 and 30 d after injection). The protein expression of nectin-1 in the hippocampus of rats was detected by Western blotting. (2) Another 12 male SD rats were randomly selected and divided into lentivirus epilepsy group ( n=6) and empty vector epilepsy group ( n=6). Lentivirus and empty lentivirus vector were injected into the hippocampus of the above two groups respectively, and then, pilocarpine epilepsy models were kindled; the behavior changes of these rats were recorded, and changes of mossy fiber sprouting in the hippocampus were observed by Timm staining. Results:(1) There were significant differences in hippocampal nectin-1 protein expressions in each group ( F=76.120, P=0.000); the nectin-1 expression in the 7, 14, and 30 d subgroups was significantly decreased as compared with that in the control group and empty vector group ( P<0.05). (2) The results of behavior changes showed that the times required for the lentivirus epilepsy group to be kindled successfully ([34.33±2.38] min) were significantly longer than those for the empty vector epilepsy group ([24.50±2.06] min, t=7.650, P=0.000). In terms of seizure level, the seizure level of rats in the lentivirus epilepsy group was significantly lower at each time point within one h modeling than that of rats in the empty vector epilepsy group ( P<0.05). After kindling, the time of spontaneous seizure appeared in the lentivirus epilepsy group was significantly longer than that in the empty vector epilepsy group, and the frequencies of spontaneous seizure in the lentivirus epilepsy group were significantly decreased as compared with those in the empty vector epilepsy group ( P<0.05). Timm staining scores in the lentivirus epilepsy group (3.500±0.224) were significantly lower than those in the empty vector epilepsy group (4.667±0.211, t=9.289, P=0.000). Conclusion:Inhibition of nectin-1 expression in hippocampal area of epileptic rats can delay the occurrence of epilepsy and reduce the frequencies of spontaneous seizures of epileptic rats, whose mechanism may be related to the reduction of nectin-1 in the formation of mossy fiber sprouting in abnormal neural circuits of hippocampal area.
RESUMEN
Objective The pathogenesis of intractable epilepsy was explored by examining the expression of the P-gp , GST-Pi as well as MDR1 in peripheral blood of the patients with intractable epilepsy. The potential of the above mentioned three genes as the biomarkers for treatment of intractable epilepsy was investigated. Methods Thirty-one sub?jects with refractory epilepsy, 33 subjects under good circumstances by antiepileptic drugs, and 37 healthy subjects were included in the present study. fluorescence quantitative polymerase chain reaction and flow cytometry were used to detect mRNA levels of MDR1 and GST-Pi and P-gp of MDR1 in the peripheral blood of the patients, respectively. Results The expression levels of MDR1 and GST-Pi were significantly higher in the AEDs intractable group(1.36±0.14,0.585±0.257) than in the treatment group(0.82±0.15,0.309±0.217, P<0.05)The expression levels of MDR1 and GST-Pi were signifi?cantly higher in the AEDs treatment group than in the normal group(0.27±0.07,0.134±0.223,P<0.05). The expression levels of P-gp were significantly higher in the AEDs of the intractable group(0.104±0.084)than in the treatment group (0.063 ± 0.030, P<0.05). The GST-Pi gene expression levels were significantly higher in three(0.535 ± 0.256)or two (0.425±0.254)kinds of antiepileptic drugs combination therapy than in single drug treatment(0.267±0.265, P<0.05). Leucocyte P-gp levels were significantly higher in combination therapy of three kinds of antiepileptic drugs(0.141 ± 0.096)than in combination therapy of two kinds of antiepileptic drugs(0.071±0.020)or in monotherapy(0.050±0.020, P<0.05). Conclusion MDR1 and GST-Pi gene expression levels of peripheral blood can be used as the reference in?dex for treatment of intractable epilepsy and the resistant index of combination treatment for intractable epilepsy.
RESUMEN
Objective To establish an LC-MS/MS method for the detection of landiolol concentration in human blood.Methods After pretreatment with neostigmine and a deproteinization procedure, landiolol and the internal standard venlafaxine were eluted isocratically using a mobile phase consisting of acetonitrile and 10 mmoL·L-1 ammonium acetate with 0. 1% formic acid in a ratio of 3664 ( V/V ) . Separation of the respective compounds was achieved on a Waters XTerra? RP18 column (150 mmí4. 6 mm,5 μm). Quantitative analysis of landiolol was conducted by a triple-quadrupole mass spectrometer with positive-electrospray ionization source,monitored under a multiple reaction monitoring ( MRM) mode. The extracted ions monitored following MRM transitions were m/z 510. 5→423. 1 for landiolol and m/z 278. 2→215. 1 for the internal standard venlafaxine. ResultsThe calibration curve of landiolol in human blood showed good linear relationship in the range of 1. 010-2 020 μg·L-1 . The lower limit of quantitation was 1. 010 μg · L-1 . The RSD of within-day and between-day precision was less than 6. 5% and 4. 8%, respectively. The recovery rate was 92. 6%-100. 9%. Conclusion The method is proven to be simple,rapid and reliable,and can be applied to study the pharmacokinetics of landiolol hydrochloride in healthy Chinese volunteers.