Summary, The effect of ketone bodies on ihe growth, in culture, of transformed lymphoblasts (Raji cells) was investigated. Cell growth was inhibited and this efTect was reversible, non-toxic, and proportional to the concentmtion of D-j^-hydroxybutyrate up to 20mM. The total glucose utilisation and the total lactate production were reduced in proportion to the inhibition of cell proliferaiion. D-^-hydroxybutyrate was not metabolised by the eells. Other glycolytic inhibitors and chemical analogues of f5-^-hydroxybutyrate either did not inhibit or proved to be too toxic for cell growth. D-/?-hydroxybutyrate also inhibited the growth of rabbit kidney (RK13), HeLa, mouse melanoma (BIft), fibroblast and trypsin-dispersed human ihyroid and beef tcstis cells. Moreover, in vivo dietary-induced ketosis redticed the number of B16 melanoma deposits in the lungs of C57BL/6 mice by two-thirds. The sinnificunce of these results in the clinical management of cancer cachexia is discussed.
Figure 6 shows a A T vs. urea concentration response curve for the sample loop system. The sensitivity, a(An/aC,. is 5 X "C M-'; this is of the order of magnitude expected for a diffusionally limited device ( 4 ) and is about two orders of magnitude less sensitive than devices that carry the reaction to completion (7-14).In conclusion, this study demonstrates the ability to make relatively high resolution AT measurements with an open-flow channel configuration and under conditions compatible with immobilized enzyme use. This configuration has allowed us to address several significant effects on A T measurements:(a) the common mode rejection ratio to temperature (CMRRT) of a thermistor pair, which partially decouples variations in temperature of the incoming stream from A T measurements;(b) the CMRRT coupling between flow variations and A T caused by the thermistors' dissipation constants; (c) the motion or nucleation of bubbles near the thermistors; and (d) the thermal cross-talk that can occur between closely spaced thermistors.These findings suggest that future TEP devices, employed as immersible probes in a well-stirred solution, will need to address several problems. First, since temperature variations with time will occur for turbulent flow, better CMRRT values are needed. Second, since turbulent flow also imposes a spatial, fluctuating temperature gradient, closely spaced thermistors appear to be desirable. Therefore, higher average velocities and smaller excitation powers are required to reduce thermal cross-talk. However, reduced excitation power renders other sources of noise significant (17). Low-duty cycle, pulsed excitation may help, since the average power could be significantly reduced.In short, while experiments that directly address these issues in turbulent flow are desirable, the present study suggests that a limit for AT measurements in T E P s that are immersed in a well-stirred flow may not have been reached. Further, this work is also relevant to column devices; given their intrinsically higher sensitivity of about 10 "C M-I, if comparable AT measurements can be made in more open columns with quiet, laminar flow and degassing where necessary and permissible, then significantly improved detection limits (below lo4 M) should be obtained. LITERATURE CITED(1) Rich, S.; Ianniello, R. M.; Jespersen, N. D.A rapid, one-step procedure is described for the determination of oxalate. Oxalate oxidase, immobilized in a continuous-flow system, converts oxalate to hydrogen peroxide which is detected by a color reaction with 4-aminophenazone. The assay Is Sensitive to oxalate concentrations as low as 5 1M and is hlghty reproducible. A range of inorganic ions, alcohols, mons and polycarboxylic acids, sugars, and nltrogenous substances do not interfere with the assay. Although ascorbate and NADH did not affect the enzyme reaction, they did reduce the color formation with 4-aminophenazone. The immobilized enzyme system can, however, be readily adapted to more specific detection systems.
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