NQO1 is an antioxidant enzyme, important in the detoxification of environmental carcinogens. A single nucleotide polymorphism (C3 T) at position 609 of the NQO1 cDNA has been associated with susceptibility to tumours induced by chemical carcinogens. In our case-control study, we determined the prevalence of the C609T NQO1 polymorphism by PCR-RFLP analysis in Caucasian patients with oesophageal adenocarcinoma (OAC; n,)16؍ cardiac adenocarcinoma (CAC; n)021؍ or gastric adenocarcinoma (GAC; n)302؍ vs. a control group that consisted of 252 healthy blood donors. Additionally, NQO1 mRNA expression and NQO1 protein expression were determined by RT-PCR and immunohistochemistry in a subset of cases. The NQO1 C609T genotype distribution was significantly different among controls (C/C, 73.4%; C/T, 25.0%; T/T, 1.6%) as compared to OAC patients (C/C, 49.2%; C/T, 47.5%; T/T, 3.3%; p,)4000.0؍ CAC patients (C/C, 55.8%; C/T, 40.0%; T/T, 4.2%; p)5000.0؍ and with GAC patients (C/C, 65.5%; C/T; 30.6%, T/T; 3.9%; p.)7730.0؍ The 609T allele overall frequency was 0.141 in controls, 0.270 in OAC patients, 0.241 in CAC patients and 0.192 in GAC patients. Individuals carrying 1 or 2 609T alleles had a 2.85-fold higher risk (95% CI: 1.61-5.07; p)3000.0؍ for the development of OAC and a 2.18-fold higher risk (95% CI: 1.38 -3.44; p)7000.0؍ for the development of CAC than wild-type gene homozygotes. Immunohistochemical analysis showed NQO1 protein expression in 133 carcinomas, whereas 17 carcinomas were negative. Negativity for NQO1 protein expression correlated strongly with the NQO1 genotype being present in 3.9% of cases with C/C, 13.9% of cases with C/T and 62.5% of cases with T/T genotype (p<0.001). In contrast, NQO1 mRNA expression was detectable irrespective of underlying genotype. In conclusion, determination of the NQO1 genotype may gain importance as a stratification marker in future prevention trials for adenocarcinoma of upper gastrointestinal tract.
OBJECTIVE. To explore the efficacy of low- and high-stretch compression bandaging for edema management in the stroke-affected upper limb. METHOD. A single-case, ABA-design study was conducted with 8 participants alternately allocated to receive low- or high-stretch bandaging. Edema was measured with circumferential tape at four specified points from the hand to the mid-forearm. All measurements were represented graphically for visual analysis, and celeration lines were calculated to indicate the degree of slope in each phase. RESULTS. Visual analysis indicated fluctuating edema volume in the first baseline phase, decreasing edema volume in the intervention phase, and increasing edema volume in the second baseline phase. The results did not clearly distinguish between the two bandaging groups. CONCLUSION. Compression bandaging may have benefits in the management of edema after stroke. Further research is required to identify factors contributing to the long-term maintenance of reductions gained after compression bandaging.
Flavoenzymes mediate
a multitude of chemical reactions and are
catalytically active both in different oxidation states and in covalent
adducts with reagents. The transfer of such reactivity to the organic
laboratory using simplified molecular flavins is highly desirable,
and such applications in (photo)oxidation reactions are already established.
However, molecular flavins have not been used for the reduction of
organic substrates yet, although this activity is known and well-studied
for DNA photolyase enzymes. We report a catalytic method using reduced
molecular flavins as photoreductants and γ-terpinene as a sacrificial
reductant. Additionally, we present our design for air-stable, reduced
flavin catalysts, which is based on a conformational bias strategy
and circumvents the otherwise rapid reduction of O2 from
air. Using our catalytic strategy, we were able to replace superstoichiometric
amounts of the rare-earth reductant SmI2 in a 5-exo-trig cyclization of substituted barbituric acid derivatives.
Such flavin-catalyzed reductions are anticipated to be beneficial
for other transformations as well and their straightforward synthesis
indicates future use in stereo- as well as site-selective transformations.
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