Genome-wide expression profiling of the response to terbinafine in Candida albicans using a cDNA microarray analysis / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Candida albicans is the most frequently seen opportunistic human fungal pathogen. Terbinafine is an allylamine antifungal agent that has been proven to have high clinical efficacy in the therapy of fungal infections, the mechanism of action of terbinafine involves the specific inhibition of fungal squalene epoxidase, resulting in ergosterol deficiency and accumulation of intracellular squalene. We used cDNA microarray analysis technology to monitor global expression profile changes of Candida albicans genes in response to terbinafine treatment, and we anticipated a panoramic view of the responses of Candida albicans cells to the representatives of allylamine antifungal agents at the molecular level in an effort to identify drug class-specific and mechanism-independent changes in gene expression.</p><p><b>METHODS</b>Candida albicans strain ATCC 90028 was exposed to either medium alone or terbinafine at a concentration equivalent to the 1/2 minimal inhibitory concentrations (MICs, 4 mg/L) for 90 minutes. RNA was isolated and gene expression profiles were compared to identify the changes in the gene expression profile using a cDNA microarray analysis. Differential expression of 10 select genes detected by cDNA microarray analysis was confirmed by semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR).</p><p><b>RESULTS</b>A total of 222 genes were found to be responsive to terbinafine, including 121 up-regulated genes and 101 down-regulated genes. These included genes encoding membrane transport proteins belonging to the members of the ATP-binding cassette (ABC) or major facilitator superfamily (MFS; CDR1, AGP2, GAP6, PHO84, HOL3, FCY23, VCX1), genes involved in stress response and detoxification (CDR1, AGP2, HOL3), and gene involved in the ergosterol biosynthesis pathway (ERG12). The results of semi-quantitative RT-PCR were consistent with that of the cDNA microarray analysis.</p><p><b>CONCLUSIONS</b>The up-regulation of the gene encoding the multidrug resistance efflux pump CDR1 may contribute to the terbinafine resistance in Candida albicans. However, the precise roles of other affected genes remain unclear, further studies of these genes and their respective products that play roles in the context of antifungal resistance are warranted.</p>

Study on the relationship between genesis and development of cervical cancer and the infection of human papillomavirus type 16/18, human herpesvirus II and cytomegalovirus / 中华流行病学杂志

<p><b>OBJECTIVE</b>To investigate the correlation between genesis and the development of cervical cancer and infection of human papillomavirus (HPV) type 16/18, human herpesvirus II (HSV- II) and cytomegalovirus(CMV).</p><p><b>METHODS</b>Different viruses were determined by polymerase chain reaction in 156 specimens of uterine including cervix 43 cervical cancer specimens,47 cervical intraepithelial neoplasia (CIN) specimens, 56 cervicitis specimens and 10 normal cervix specimens.</p><p><b>RESULTS</b>(1) Positive rates on different viruses: the positive rates of HSV- II, HPV16/18 and CMV were declining in the cervical cancer specimens, CIN specimens or CIN III specimens and CIN I - II specimens, with significant differences. (2)Positive rate and grading, staging and histogenesis of cervical cancer on different viruses as well as positive rates of HPV16/18 in II staging cervical cancer specimens were significantly higher than that in I staging cervical cancer specimens while positive rates of HPV16/18 and HSV- II in high differentiation of cervical cancer specimens were significantly higher than those with medium differentiation from cervical cancer specimens. Positive rates of CMV did not seem to correlate with positive rate of HSV- II and CMV was not correlated to grading, staging or histogenesis of cervical cancer. (3)Copies of infected virus, HSV-II and HPV16/18 showing cervical cancer>CIN> cervicitis while with CMV:cervical cancer>CIN. (4) There were mixed infections of different viruses as HPV16/18 + HSV- II > HPV16/18 + CMV seen in the study.</p><p><b>CONCLUSION</b>HPV 16/18, HSV- II and CMV infection were closely related to the genesis of cervical cancer and quantity of viruses which might have played an important role in carcinogenesis of cervical lesions.</p>

Investigation on the antibiotic resistance and risky factors of nosocomial infections caused by Stenotrophomonas maltophilia / 中华烧伤杂志

<p><b>OBJECTIVE</b>To investigate the antibiotic resistance and risky factors of nosocomial infections caused by Stenotrophomonas maltophilia, so as to help elucidate the difference of drug resistance between metallic beta-lactamase (MBL) producing and non-MBL producing strains.</p><p><b>METHODS</b>Standard agar dilution method of NCCLS was employed in the isolation of 36 strains of Stenotrophomonas maltophilia from patients with nosocomial infection with respect to their in vitro antibiotic resistance to 18 kinds of antibiotics. MBL strains were identified by MBL-E test method.</p><p><b>RESULTS</b>Stenotrophomonas maltophilia in our hospital was mainly identified in the lower respiratory tract (88.9%), in which 88.2% (30/34) of the patients had serious original diseases, 50% of whom had received Imipenem/cilastatin sodium treatment. Thirty-six strains of Stenotrophomonas maltophilia were susceptible to new types of fluoquinolone antibiotics, i.e. Sparfloxacin, levofloxacin, gatifloxacin and doxycycline, with inhibitory rate ranging 97.2%, 94.4%, 91.7% to 83.3%, respectively. They could also be inhibited by SMZ/TMP and Ticarcillin/Lavulanic acid with inhibitory rate of 63.9% and 58.3%, respectively. There were 16 strains out of 36 of MBL bacteria with complete resistance to Imipenem/cilastatin sodium, but with higher susceptibility to aztreonam than those non-MBL producing strains.</p><p><b>CONCLUSION</b>The nosocomial infection in our hospital caused by Stenotrophomonas maltophilia seemed to be related with severe primary disease and the use of Imipenem/cilastatin sodium. The newly developed fluoroquinolones possessed powerful antibacterial potency on Stenotrophomonas maltophilia found in nosocomial infection.</p>