Polymorphism of inflammatory genes and arsenic methylation capacity are associated with urothelial carcinoma.

Chronic exposure to arsenic can generate reactive oxidative species, which can induce certain proinflammatory cytokines such as tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6) and interleukin-8 (IL-8). TNF-α, IL-6 and IL-8 have been shown to be involved in the development and progression of various cancers, including bladder cancer. This study aimed to investigate the joint effect of the polymorphism of TNF-α -308 G/A, IL-6 -174 G/C, IL-8 -251 T/A and urinary arsenic profiles on urothelial carcinoma (UC) risk. This study evaluated 300 pathologically-confirmed cases of UC and 594 cancer-free controls. Urinary arsenic species were detected using high-performance liquid chromatography-linked hydride generator and atomic absorption spectrometry. The polymorphism of TNF-α -308 G/A, IL-6 -174 G/C and IL-8 -251 T/A was determined using polymerase chain reaction-restriction fragment length polymorphism. The joint effects on UC risk were estimated by odds ratios and 95% confidence intervals using unconditional logistic regression. We found that the TNF-α -308 A/A and IL-8 -251 T/T polymorphisms were significantly associated with UC. Moreover, significant dose-response joint effect of TNF-α -308 A/A or IL-8 -251 T/T genotypes and arsenic methylation indices were seen to affect UC risk. The present results also showed a significant increase in UC risk in subjects with the IL-8 -251 T/T genotype for each SD increase in urinary total arsenic and MMA%. In contrast, a significant decrease in UC risk was found in subjects who carried the IL-8 -251 T/T genotype for each SD increase in DMA%.

Environmental tobacco smoke and arsenic methylation capacity are associated with urothelial carcinoma.

BACKGROUND/PURPOSE: Cigarette smoking, exposure to secondhand smoke, and arsenic exposure are well known risk factors for developing urothelial carcinoma (UC). We investigated the combined effects of cigarette smoking, exposure to secondhand smoke, and the presence of urinary total arsenic on the risk of developing UC. METHODS: We conducted a hospital-based, case-control study involving 261 UC patients and 672 cancer-free control individuals between September 2002 and May 2009. RESULTS: Individuals who had smoked <100 cigarettes in their lifetime (never smokers) and had a high urinary total arsenic level (≥15.40 µg/g creatinine), and those who had smoked >100 cigarettes in their lifetime (ever smokers) and had a high urinary total arsenic level, had increased risks of developing UC (3.20-fold and 6.45-fold greater), respectively, compared to individuals who were never smokers and had a low urinary total arsenic level. Individuals who had high urinary total arsenic levels and had been exposed to secondhand smoke, and individuals with high urinary arsenic levels who had not been exposed to secondhand smoke, had increased chances (2.71-fold and 5.00-fold greater, respectively) of developing UC, compared to individuals who were not exposed to secondhand smoke and had low urinary total arsenic levels. Ever smokers who had been exposed to secondhand smoke and had a high urinary total arsenic level had the greatest increased risk for developing UC (10.82-fold greater). CONCLUSION: Individuals in a Taiwanese population who smoked cigarettes, were exposed to secondhand smoke, and a high urinary total arsenic level, had a significant risk for developing UC.

Risk factors for acquiring extended-spectrum ß-lactamase-producing Enterobacteriaceae in geriatric patients with multiple comorbidities in respiratory care wards.

AIM: Extended-spectrum ß-lactamase (ESBL)-producing Enterobacteriaceae is associated with a high mortality rate and increased medical care costs. Elderly patients might receive mechanical ventilation with respiratory treatment for the long term in respiratory care wards (RCW). This retrospective case-control study sought to determine the risk factors for geriatric patients who acquire a urinary tract infection with ESBL-producing Escherichia coli or Klebsiella pneumoniae in this type of hospital. METHODS: Two RCW participated in this study from September 2006 to March 2007. Patients suspected of having a UTI were enrolled in this study. Urine samples were collected for culture. The medical records and demographic data of patients, including days of hospitalization, comorbidities and duration of invasive instruments, were recorded. UTI was diagnosed by physicians. ESBL-producing isolates were detected using the phenotypic confirmatory tests according to the Clinical and Laboratory Standard Institute standards. RESULTS: There were 109 patients having 240 sets of clinical data and laboratory specimens. The prevalence of ESBL-producing isolates of E. coli. and K. pneumoniae were 39.5% and 69.7%, respectively. Patients with multiple underlying comorbidities (OR=2.88, P<0.05) or receiving more than two antimicrobial agents (OR=3.71, P<0.05) were at an increased risk for acquiring the ESBL-producing microorganisms after adjustment for sex, age and days of hospitalization. CONCLUSIONS: Geriatric patients with recent exposure to two or more antibiotics and two or more numbers of comorbidities were at risk for ESBL-producing organism infection. Our results suggest that infection control procedures in RCW should be concerned with reducing antimicrobial prescriptions and patient comorbidities.

Characterization and large-scale production of recombinant Streptoverticillium platensis transglutaminase.

Recombinant Streptomyces platensis transglutaminase (MtgA) produced by the Streptomyces lividans transformant 25-2 was purified by ammonium sulfate fractionation, followed by CM-Sepharose CL-6B fast flow, and blue-Sepharose fast flow chromatography. The purification factor was approximately 33.2-fold, and the yield was 65%. The molecular weight of the purified recombinant MtgA was 40.0 KDa as estimated by SDS-PAGE. The optimal pH and the temperature for the enzyme activity were 6.0 and 55 degrees C, respectively, and the enzyme was stable at pH 5.0-6.0 and at temperature 45-55 degrees C. Enzyme activity was not affected by Ca(2+), Li(+), Mn(2+), Na(+), Fe(3+), K(+), Mg(2+), Al(3+), Ba(2+), Co(2+), EDTA, or IAA but was inhibited by Fe(2+), Pb(2+), Zn(2+), Cu(2+), Hg(2+), PCMB, NEM, and PMSF. Optimization of the fermentation medium resulted in a twofold increase of recombinant MtgA activity in both flasks (5.78 U/ml) and 5-l fermenters (5.39 U/ml). Large-scale productions of the recombinant MtgA in a 30-l air-lift fermenter and a 250-l stirred-tank fermenter were fulfilled with maximal activities of 5.36 and 2.54 U/ml, respectively.