Correlations of SELENOF and SELENOP genotypes with serum selenium levels and prostate cancer.

BACKGROUND: Selenium status is inversely associated with the incidence of prostate cancer. However, supplementation trials have not indicated a benefit of selenium supplementation in reducing cancer risk. Polymorphisms in the gene encoding selenoprotein 15 (SELENOF) are associated with cancer incidence/mortality and present disproportionately in African Americans. Relationships among the genotype of selenoproteins implicated in increased cancer risk, selenium status, and race with prostate cancer were investigated. METHODS: Tissue microarrays were used to assess SELENOF levels and cellular location in prostatic tissue. Sera and DNA from participants of the Chicago-based Adiposity Study Cohort were used to quantify selenium levels and genotype frequencies of the genes for SELENOF and the selenium-carrier protein selenoprotein P (SELENOP). Logistic regression models for dichotomous patient outcomes and regression models for continuous outcome were employed to identify both clinical, genetic, and biochemical characteristics that are associated with these outcomes. RESULTS: SELENOF is dramatically reduced in prostate cancer and lower in tumors derived from African American men as compared to tumors obtained from Caucasians. Differing frequency of SELENOF polymorphisms and lower selenium levels were observed in African Americans as compared to Caucasians. SELENOF genotypes were associated with higher histological tumor grade. A polymorphism in SELENOP was associated with recurrence and higher serum PSA. CONCLUSIONS: These results indicate an interaction between selenium status and selenoprotein genotypes that may contribute to the disparity in prostate cancer incidence and outcome experienced by African Americans.

Analgesic effect of perineural magnesium sulphate for sciatic nerve block for diabetic toe amputation: A randomized trial.

BACKGROUND AND OBJECTIVES: High concentrations of local anesthetics may be neurotoxic for diabetic patients. Additive perineural administration of magnesium was reported to decrease the consumption of local anesthetics for nerve block. It was hypothesized that MgSO4 added to dilute ropivacaine was equianalgesic to more concentrated ropivacaine for toe amputations in diabetic patients. METHODS: Seventy diabetic patients were allocated into 3 groups: 1) perineural 200 mg MgSO4 added to 0.25% ropivacaine, 2) 0.25% ropivacaine alone, and 3) 0.375% ropivacaine alone. All patients underwent popliteal sciatic nerve block that was guided by ultrasonography using the respective regimens. Time of onset, duration of motor and sensory block were recorded. Spontaneous and evoked pain score, worst pain score, additional analgesic consumption, satisfaction score and initial time of analgesic requirement of each patient were documented up to 48 hours postoperatively. RESULTS: In comparison with 0.25% ropivacaine alone, magnesium supplement prolonged the duration of sensory block (p = 0.001), as well as better evoked pain score at 6 hour postoperatively (p = 0.001). In comparison with evoked pain score (1.6/10) in group of 0.375% ropivacaine, magnesium plus 0.25% ropivacaine presented a little higher score (2.5/10) at 6 hour postoperatively (p = 0.001), while lower worst pain score (p = 0.001) and less postoperative total analgesic consumption (p = 0.002). CONCLUSIONS: The regimen of adding 200mg MgSO4 to 0.25% ropivacaine for sciatic nerve block yields equal analgesic effect in comparison with 0.375% ropivacaine. These findings have suggested that supplemental MgSO4 could not improve analgesic quality except reducing the total amount of local anesthetics requirement in diabetic toe amputations with sciatic nerve blocks.

A Critical Role for Cysteine 57 in the Biological Functions of Selenium Binding Protein-1.

The concentration of selenium-binding protein1 (SBP1) is often lower in tumors than in the corresponding tissue and lower levels have been associated with poor clinical outcomes. SBP1 binds tightly selenium although what role selenium plays in its biological functions remains unknown. Previous studies indicated that cysteine 57 is the most likely candidate amino acid for selenium binding. In order to investigate the role of cysteine 57 in SBP1, this amino acid was altered to a glycine and the mutated protein was expressed in human cancer cells. The SBP1 half-life, as well as the cellular response to selenite cytotoxicity, was altered by this change. The ectopic expression of SBP1(GLY) also caused mitochondrial damage in HCT116 cells. Taken together, these results indicated that cysteine 57 is a critical determinant of SBP1 function and may play a significant role in mitochondrial function.

Molecular cross-talk between members of distinct families of selenium containing proteins.

Dietary intake of selenium has been associated with reduced risk of several cancer types, and this is likely due to its role as a specific constituent of selenium containing proteins. One of these, selenium-binding protein 1 (SBP1), is a protein of unknown function that has been shown to be reduced in tumors of diverse tissue types as compared to the corresponding normal tissue. More importantly, SBP1 has also been reported to be a predictor of clinical outcome. Levels of SBP1 are inversely associated with the levels of another protein representative of a different class of selenoproteins, glutathione peroxidase1 (GPx-1). GPx-1 is an anti-oxidant, selenocysteine containing enzyme implicated in several diseases, including cancer, due to the association of specific alleles with disease risk. The relationship between SBP1 and GPx-1 represents a unique example of a molecular interaction between selenium containing proteins with a likely significant impact on human health and disease.