Lactate metabolism during exercise in patients with mitochondrial myopathy

Patients with mitochondrial DNA mutations often have elevated plasma lactate at rest and during exercise, but it is unknown whether the high lactate levels are caused by a high production, an impaired oxidation or a combination. We studied lactate kinetics in 10 patients with mtDNA mutations and 10 matched healthy control subjects at rest and during cycle exercise with a combination of femoral arterio-venous differences of lactate, and lactate tracer dilution methodology. During exercise, lactate concentration and production rates were several-fold higher in patients, but despite mitochondrial dysfunction, lactate was oxidized in muscle to the same extent as in healthy control subjects. This surprisingly high ability to burn lactate in working muscle with defective mitochondria, probably relates to the variability of oxidative capacity among muscle fibers. The data suggests that lactate is not solely an indicator of impaired oxidative capacity, but an important fuel for oxidative metabolism, even in muscle with severely impaired mitochondrial function.     

Measuring social participation: reliability of the LIFE-H in older adults with disabilities

Purpose: Much more attention should be paid to instruments documenting social participation as this area is increasingly considered a pivotal outcome of a successful rehabilitation. The purpose of this study was to document the reliability of a participation measure, the Assessment of Life Habits (LIFE-H), in older adults with functional limitations.

Methods: Eighty-four individuals with physical disabilities living in three different environments were assessed twice with the LIFE-H, an instrument that documents the quality of social participation by assessing a person's performance in daily activities and social roles (life habits).

Results: The intraclass correlation coefficients (ICC) computed for intrarater reliability exceeded 0.75 for seven out of the 10 life habits categories. For interrater reliability, the total score and daily activities subscore are highly reliable (ICC ??0.89), and the social roles subscore is moderately reliable (ICC?=?0.64). ‘Personal care’ is the category with the highest ICC, and for five other categories ICCs are moderate to high (<?0.60).

Conclusion: LIFE-H is a valuable addition to instruments that mostly emphasize the concepts of function or functional independence. It is particularly meaningful to evaluate the participation of older adults in significant social role domains such as recreation and community life. It may be considered among the instruments having the best fit with the ICF definition of participation (the person's involvement in a life situation) and a majority of its related domains.     

TGF-B3 Dependent Modification of Radiosensitivity in Reporter Cells Exposed to Serum From Whole-Body Low Dose-Rate Irradiated Mice

Prior findings in vitro of a TGF-β3 dependent mechanism induced by low dose-rate irradiation and resulting in increased radioresistance and removal of low dose hyper-radiosensitivity (HRS) was tested in an in vivo model. DBA/2 mice were given whole-body irradiation for 1 h at low dose-rates (LDR) of 0.3 or 0.03 Gy/h. Serum was harvested and added to RPMI (4% mouse serum and 6% bovine serum).This medium was transferred to reporter cells (T-47D breast cancer cells or T98G glioblastoma cells). The response to subsequent challenge irradiation of the reporter cells was measured by the colony assay. While serum from unirradiated control mice had no effect on the radiosensitivity in the reporter cells, serum from mice given 0.3 Gy/h or 0.03 Gy/h for 1 h removed HRS and also increased survival in response to doses up to 5 Gy. The effect lasted for at least 15 months after irradiation. TGF-β3 neutralizer added to the medium containing mouse serum inhibited the effect. Serum from mice given irradiation of 0.3 Gy/h for 1 h and subsequently treated with iNOS inhibitor 1400W did not affect radiosensitivity in reporter cells; neither did serum from the unirradiated progeny of mice given 1h LDR whole-body irradiation.