Metabolic viability based high throughput assays like MTT and MTS are widely used in assessing the cell viability. However, alteration in both mitochondrial content and metabolism can influence the metabolic viability of cells and radiation is a potential mitochondrial biogenesis inducer. Therefore, we tested if MTT assay is a true measure of radiation induced cell death in widely used cell lines. Radiation induced cellular growth inhibition was performed by enumerating cell numbers and metabolic viability using MTT assay at 24 and 48 hours (hrs) after exposure. The extent of radiation induced reduction in cell number was found to be larger than the decrease in MTT reduction in all the cell lines tested. We demonstrated that radiation induces PGC-1α and TFAM to stimulate mitochondrial biogenesis leading to increased levels of SDH-A and enhanced metabolic viability. Radiation induced disturbance in calcium (Ca2+) homeostasis also plays a crucial role by making the mitochondria hyperactive. These findings suggest that radiation induces mitochondrial biogenesis and hyperactivation leading to increased metabolic viability and MTT reduction. Therefore, conclusions drawn on radiation induced growth inhibition based on metabolic viability assays are likely to be erroneous as it may not correlate with growth inhibition and/or loss of clonogenic survival.
These results do not support the concern that antioxidants might protect cancer cells from the free radical damage induced by chemotherapy. Larger trials are needed to demonstrate whether high-dose multiple antioxidants in conjunction with chemotherapy increase the response rates and/or survival time in advanced lung cancer.
There have been few studies examining the outcome of schizophrenia in later life. Using five conceptual models, we test two hypotheses with respect to range of outcomes among older schizophrenia outpatients and how they compare to their age peers in the community. We operationalized five outcome measures from the following conceptual models: Remission, adapting criteria of Andreasen et al. (The American Journal of Psychiatry, 162:441-449, 2005); Recovery, adapting the criteria by Liberman et al. (International Review of Psychiatry, 14:256-272, 2002); Community Integration using the model of Wong and Solomon (Mental Health Services Research, 4:13-28, 2002); Subjective and Objective Successful Aging using the model of Rowe and Kahn (Science, 237:143-149, 1987). The schizophrenia (S) group consisted of 198 community-dwelling persons aged 55 and over who developed schizophrenia before age 45 and a community comparison (CC) group (N = 113). Remission and recovery criteria were met by 49 and 17% of the S group, respectively. There were significant differences between the S and CC groups in the distribution of community integration and successful aging scales: 41% of the CC group met at least 10 of 12 criteria versus 23% of the S group on the Community Integration Scale; 19% of the CC group met all six criteria vs. 2% of the S group on the Objective Successful Aging Scale; 27% of the CC group vs. 13% of the S group met all six criteria on the Subjective Successful Aging Scale. Correlations among the five outcome measures ranged from r = .19 to .48 (median value: r = .26 or 7% shared variance). There is wide variability in outcome in later life depending on which measure is used. Rather than one universal indicator, each measure offers a different perspective that can provide useful guidelines for researchers, clinicians, and policy makers.
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