No abstract

To determine critically the selenium (Se) requirement for weanling female rats, we used glutathione peroxidase (GSH: H2O2 oxidoreductase, EC 1.11.1.9) (GPX) mRNA and a number of other parameters to assess Se status. Rats were fed a basal torulayeast diet (0.007 micrograms Se/g) supplemented with Se as Na2SeO3 in graded levels from 0 to 0.3 micrograms Se/g diet for 32 d (3 rats/group). Selenium supplementation had no effect on growth, showing that the Se requirement for growth is less than 0.007 micrograms Se/g diet, whereas other parameters showed significant increases with Se supplementation. In rats fed the Se-deficient basal diet, liver Se concentration was 4 +/- 0%, plasma GPX activity was 8 +/- 1%, erythrocyte GPX activity was 40 +/- 3%, liver GPX activity was 2 +/- 1%, and liver GPX mRNA levels were 11-17% of the levels in rats fed 0.1 micrograms Se/g diet. Liver Se concentration and GPX activity in plasma, erythrocytes and liver all reached a plateau breakpoint at or near 0.1 micrograms Se/g diet, indicating that the dietary Se requirement for maximal GPX activity in growing female rats is 0.1 micrograms Se/g diet. Liver GPX mRNA levels reached the plateau breakpoint at 0.05 micrograms Se/g diet, showing that the minimum dietary Se requirement for maximal GPX mRNA levels in female rats is half of the Se requirement for maximal GPX activity. This experiment demonstrates that GPX mRNA can be used to determine the dietary Se requirement; the gap between the dietary Se necessary for maximal GPX mRNA and that for maximal GPX activity may represent an evolutionarily derived biological margin of safety.

Weanling male rats were fed a basal torula yeast diet (0.007 μg Se/g diet) supplemented with graded levels of Se (0 to 0.2 μg Se/g diet as Na 2 SeO 3 ) (three rats/group) to evaluate classical glutathione peroxidase (GPX1, GSH:H 2 O 2 , oxidoreductase, EC 1.11.1.9) mRNA level as an indicator of intracellular Se status. Growth was followed throughout the dietary treatment and a number of Se-dependent parameters including liver GPX1 mRNA levels were determined after 33 days. Growth was not impaired at any level of dietary Se supplementation. In rats fed the Sedeficient basal diet, liver Se concentration was 5 ± 1%, liver GPXI mRNA levels were 10 ± 2%. plasma GPX activity was 2 ± 1%, erythrocyte GPX activity was 37 ± 1%, and liver GPX activity was 0 ± 2% of the levels in rats fed 0.1 μg Se/g diet; these parameters increased sigmoidally with increasing dietary Se, showing a breakpoint near 0.1 μg Se/g diet. Graphical analysis indicated that the increase in liver GPX1 mRNA level with increasing dietary Se, preceded the increase in liver GPX activity. Se supplementation had no effect on polyadenylated mRNA levels or on β-actin mRNA levels, demonstrating that Se regulation of GPX1 mRNA is specific. Se-deficient liver selenoprotein P mRNA levels were 69 ± 2% of the levels in rats fed 0.1 μg Se/g diet. We hypothesize that GPX1 mRNA is a primary target of the Se regulatory mechanism, making GPX1 mRNA level a potentially useful indicator of the status of an important intracellular regulatory pool of Se.

The hierarchy of selenium (Se) requirements for growing rats ranges from <0.01 to 0.1 microg Se/g diet, depending on the choice of Se status parameter. To further evaluate the efficacy of molecular biology markers to determine Se requirements in later periods of the life cycle, which are less amenable to traditional approaches, we studied pregnant and lactating rats. Female weanling rats were fed a Se-deficient diet (<0.01 microg Se/g) or supplemented with graded levels of dietary Se (0-0.3 microg Se/g) for >10 wk, bred, and killed on d 1, 12, and 18 of pregnancy and d 7 and 18 of lactation; Se response curves were determined for 10 parameters including liver glutathione peroxidase (GPX). Growth, and mRNA levels for selenoprotein P, 5'-deiodinase, and GPX4 were not decreased by Se deficiency. GPX4 activity required 0.05 microg Se/g diet for maximum activity, similar to growing rats. Dietary Se requirements for plasma GPX3 activity decreased 33% in pregnancy, but returned during lactation to the requirement of growing rats. The Se requirement for GPX1 activity decreased 25% in pregnancy but not in lactation. GPX1 mRNA required 0.05 microg Se/g diet for maximum levels in both pregnancy and lactation, similar to growing rats. Clearly, Se requirements do not increase during pregnancy and lactation relative to Se requirements in growing rats. Unexpectedly, Se-adequate levels of GPX1 mRNA and activity declined to <40 and 50%, respectively, of nonpregnant Se-adequate levels during pregnancy and lactation, illustrating the need to fully understand biomarkers at all stages of the life cycle.

This qualitative study explores experiences of individuals with chronic pain in their attempt to find meaning in the presence of continual pain. Fifteen participants at Loma Linda University Behavioral Medicine Center were interviewed. Emerging themes from this study show that (1) meaning is initially defined as the ability to engage in productive activities and positive relationships; (2) chronic pain is perceived as the factor that removes meaning from the lives of sufferers; (3) medication is used to cope with pain, leading to addiction; (4) addiction results in greater loss of meaning; and (5) rediscovery of meaning takes place through a more complex understanding of the self that embraces suffering and thus is able to explain the interrelation of pain, emotions, and addiction. A change in self-understanding makes the reintegration of meaning possible.