OBJECTIVETo evaluate the effect of dibutyl phthalate (DBP) and di-(2-ethylhexyl) phthalate (DEHP) on urine superoxide dismutase (SOD) activity and malondialdehyde (MDA) content in rats.

METHODSAccording to 2×2 factorial analysis, 60 adult male SD rats were randomized into 10 groups (n=6), including a control group (fed with sesame oil), 3 DBP groups (fed with DBP at the doses of 30, 100 and 300 mg/kg), 3 DEHP groups (with DEHP at 50, 150, and 450 mg/kg), and 3 DBP+DEHP groups (with 30 mg/kg DBP+50 mg/kg DEHP, 100 mg/kg DBP+150 mg/kg DEHP, and 300 mg/kg DBP +450 mg/kg DEHP). The agents were administered in a single dose through gavage in a volume of 2 ml. After the treatments, the 24, 48, 72, and 96 h urine samples were collected to determine the SOD activity and MDA content.

RESULTSDBP and DEHP, either alone or in combination, significantly decreased SOD activity and increased MDA content in the urine collected at 24 h but not at the other time points. Such changes were gradually reversed with time.

CONCLUSIONDBP or DEHP treatment alone can result in significant oxidative damage in the kidney of rats, and the toxic effect of the combined exposure is even more obvious.

Animals ; Dibutyl Phthalate ; toxicity ; Diethylhexyl Phthalate ; toxicity ; Environmental Pollutants ; toxicity ; Kidney ; drug effects ; physiopathology ; Male ; Malondialdehyde ; urine ; Oxidative Stress ; drug effects ; Rats ; Rats, Sprague-Dawley ; Superoxide Dismutase ; metabolism ; urine

OBJECTIVETo assess the association of genetic polymorphisms of CYP2C19*2,*3,*17 with the recurrence risk of ischemic stroke during clopidogrel prevention in ethnic Han Chinese from Fujian Province.

METHODSClinical data of 985 patients with acute ischemic stroke was collected. After 1 year postdischarge follow-up evaluations, only 114 patients with persistence of clopidogrel were enrolled. CYP2C19 genetic polymorphisms were detected by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP)and direct sequencing ,then we analysis the correlation between polymorphisms and the recurrence of stroke.

RESULTSAmong the 114 patients, 23 had a second onset whilst receiving clopidogrel treatment. During the antiplatelet therapy with clopidogrel, carriers of CYP2C19 poor metabolizer (CYP2C19*2/*2 or *2/*3) had a higher rate of recurrent stroke compared with extensive metabolizers (CYP2C19*1/*1) (OR=4.71, 95%CI: 1.18-18.80, P<0.05). Carriers of CYP2C19 *2 mutant allele had increased recurrence compared with those carrying none loss-of-function allele (OR=2.31, 95%CI: 1.20-4.46, P<0.05). The rate of recurrent stroke in those carrying homozygous mutant *2 allele (CYP2C19*2/*2) was 6.14 times greater than the rate of wild-type homozygotes (CYP2C19*1/*1) (95%CI: 1.54-24.54, P<0.05). Patients with previous stroke history had increased risk of recurrence (OR= 4.146, 95%CI: 1.259-13.655, P<0.05). However, CYP2C19*17 was not detected in the group.

CONCLUSIONFor ethnic Han Chinese patients receiving clopidogrel treatment, carriers of poor metabolizer or homozygous mutant *2 allele (CYP2C19*2/*2) have a higher risk of recurrent stroke. The CYP2C19 *2 allele is an independent risk factor for recurrent stroke. Those with previous history of stroke are more prone to the recurrence.

Aged ; Alleles ; Asian Continental Ancestry Group ; genetics ; Brain Ischemia ; complications ; ethnology ; China ; Cytochrome P-450 CYP2C19 ; genetics ; Female ; Gene Frequency ; Genetic Predisposition to Disease ; ethnology ; genetics ; Genotype ; Humans ; Linkage Disequilibrium ; Logistic Models ; Male ; Middle Aged ; Platelet Aggregation Inhibitors ; therapeutic use ; Polymerase Chain Reaction ; Polymorphism, Restriction Fragment Length ; Polymorphism, Single Nucleotide ; Recurrence ; Risk Factors ; Sequence Analysis, DNA ; Stroke ; ethnology ; etiology ; genetics ; prevention & control ; Ticlopidine ; analogs & derivatives ; therapeutic use ; Time Factors