Association between genetic polymorphisms of cytochrome P450 2C19 and the risk of cerebral ischemic stroke in Chinese

BACKGROUND: Cytochrome P450 (CYP) 2C19 is a very important drug metabolizing enzyme. Although the single nucleotide polymorphisms (SNPs) of CYP2C19 G681A and G636A have been suggested that they may increase the incidence of cardiovascular events, the relationship between SNPs in CYP2C19 and cerebral ischemic stroke (CIS) are unclear. The aim of this study was to investigate the correlation between the distribution of G681A and G636A polymorphisms in CYP2C19 gene and the risk of CIS in Chinese. METHODS: The peripheral blood DNA was extracted from 299 patients with CIS and 295 healthy controls. The genotyping was conducted using the polymerase chain reaction-restriction fragment length polymorphism. The sampled sequencing was applied to verify the correctness of genotyping results. Both the genotype and allele distributions were compared in patients with CIS and healthy controls. RESULTS: The frequencies of CYP2C19 681AA (11.7% vs. 2.7%; P = 0.000), 636AA (4.0% vs. 0.7%; P = 0.007), 636AG (7.0% vs. 2.2%; P = 0.038) genotype, CYP2C19 681A (30.9% vs. 20.8%; P = 0.000) and 636A (13.0% vs. 5.8%; P = 0.000) allele in the CIS group are significantly higher than those in the controls. The frequencies of CYP2C19 681AA (16.7% vs. 8.6%; P = 0.036), CYP2C19 636AA (7.0% vs. 2.2%; P = 0.038) genotype, CYP2C19 681A (36.4% vs. 27.6%; P = 0.023) and CYP2C19 636A (17.5% vs.10.3%; P = 0.010) allele in the recurrent stroke group are significantly higher than those in the first onset group. Multivariate logistic regression analysis of risk factors for cerebral ischemic stroke and recurrent stroke respectively suggests that the CYP2C19 681AA genotype may be an independent risk factor for CIS (OR = 6.179, 95% CI: 2.285 ~ 16.708; P = 0.000) and recurrent stroke (OR = 2.305, 95% CI: 1.121 ~ 4.743; P = 0.023). CONCLUSIONS: The AA genotype and A allele of CYP2C19 G681A may be related to the occurrence and recurrence of cerebral ischemic stroke

Antimicrobial susceptibility of hospital acquired Stenotrophomonas maltophilia isolate biofilms

Aims: We sought to characterize the antibiotic susceptibility of strains of Stenotrophomonas maltophilia isolated from clinical samples, and the role of Stenotrophomonas maltophilia biofilm in antibiotic resistance. Methods: Fifty-one clinical Stenotrophomonas maltophilia isolates were obtained from patients with nosocomial infection in the surgical wards and ICUs of six general hospitals in Tianjin, China. In vitro models of Stenotrophomonas maltophilia biofilms were established and confirmed by scanning electron microscopy and fluorescence microscopy with silver staining. The minimal inhibitory concentrations and biofilm inhibitory concentrations of commonly used antibiotics were determined. Results: 47 of 51 strains were resistant to three or more antibiotics. 42 of 51 strains formed Stenotrophomonas maltophilia biofilms in vitro. Stenotrophomonas maltophilia biofilm formation greatly reduced sensitivity to most tested antibiotics, but not to levofloxacin. However, in the presence of erythromycin scanning electron microscopy revealed that levofloxacin inhibited Stenotrophomonas maltophilia biofilm formation. Factorial ANOVA revealed that erythromycin enhanced susceptibility to levofloxacin, cefoperazone/sulbactam, and piperacillin (p < 0.05), and an ΔE model revealed that levofloxacin and erythromycin acted synergistically in biofilms, suggesting specific use of combined macrolide therapy may represent an effective treatment for Stenotrophomonas maltophilia infection. Conclusions: Antibiotics could act synergistically to combat the protection conferred to clinical isolates of Stenotrophomonas maltophilia by biofilms. Macrolide antibiotics may be effective where used in combination. Keywords: Stenotrophomonas maltophilia, Biofilm, Antibiotic resistance, Nosocomia

The relationship between the average optical density (AOD) scores of MACC1 immunohistochemical (IHC) staining obtained in Image Pro Plus anaysis and the staining intensity scores determined by visual assessment.

<p>(A), Patients with RPC were manually divided into three groups according to their visual assessment scores in IHC stained tissue sections (negative, low MACC1 expression group, and high MACC1 expression group, respectively). The AOD value of MACC1 obtained from Image Pro Plus analysis was evidently increased in the low MACC1 expression group compared to the negative group, and was further elevated in the high MACC1 expression group (<i>p</i><0.001). AOD =  the integrated optical density (IOD)/Area of positive MACC1 staining in each IHC staining image; B, Spearman correlation coefficient analysis measuring the strength of the linear relationship between MACC1 AOD Image Pro Plus scores and visual assessment scores. A statistically significant positive linear relationship was observed between these two sets of scores in RPC (<i>r</i> = 0.669, <i>p</i><0.001).</p

Multivariate Cox regression analysis of several prognostic factors (TNM stage, nuclear grade, and MACC1 protein expression levels) with respect to five-year overall survival (OS) and disease-free survival (DFS) of patients with renal pelvis carcinoma (RPC).

<p>‘CI’ refers to confidence interval; ‘HR’ refers to hazard ratio.</p

Representative illustrations of immunohistochemical (IHC) staining of MACC1 in the normal renal pelvis (A & A′, B & B′) and in renal pelvis carcinoma (RPC) tissue samples (C–E & C′–E′).

<p>(A) negtive control staining; (B) MACC1 positive staining; (C–E) representative images of negtive, low, high MACC1 expression in RPC tissues, respectively. (A′–E′) a higher magnification of the selected area in (A–E), respectively. Magnification: ×100 in (A–E); ×200 in (A′–E′).</p

The average optical density (AOD) of immunohistochemical (IHC) staining strength of MACC1 was measured quantitatively by Image Pro Plus in renal pelvis carcinoma (RPC) tissue specimens, adjacent non-tumorous renal pelvis epithelial tissue (ANRPET) and normal renal pelvis epithelial tissue (NRPET) specimens.

<p>Since there was no substantial difference between ANRPETs and NRPETs (<i>p</i>>0.05), these two groups were combined as a single group, ‘normal epithelium (NE)’.</p><p>*ANRPETs VS NRPETs.</p>#<p>RPC VS NE.</p

The correlation between immunohistochemical scores of MACC1 protein expression (indicated as the values of the average optical density (AOD) measured by Image Pro Plus in renal pelvis carcinoma tissue sections) and prognostic factors (gender, age, TNM stage, and nuclear grade).

<p>The correlation between immunohistochemical scores of MACC1 protein expression (indicated as the values of the average optical density (AOD) measured by Image Pro Plus in renal pelvis carcinoma tissue sections) and prognostic factors (gender, age, TNM stage, and nuclear grade).</p