Antiglucocorticoid RU38486 reduces net protein catabolism in experimental acute renal failure

BACKGROUND: In acute renal failure, a pronounced net protein catabolism occurs that has long been associated with corticoid action. By competitively blocking the glucocorticoid receptor with the potent antiglucocorticoid RU 38486, the present study addressed the question to what extent does corticoid action specific to uremia cause the observed muscle degradation, and does inhibition of glucocorticoid action reduce the protein wasting? METHODS: RU 38486 was administered in a dose of 50 mg/kg/24 h for 48 h after operation to fasted bilaterally nephrectomized (BNX) male adult Wistar rats and sham operated (SHAM) controls. Protein turnover was evaluated by high performance liquid chromatography (HPLC) of amino acid efflux in sera from isolated perfused hindquarters of animals treated with RU 38486 versus untreated controls. RESULTS: Administration of RU 38486 reduces the total amino acid efflux (TAAE) by 18.6% in SHAM and 15.6% in BNX and efflux of the indicator of net protein turnover, phenylalanine (Phe) by 33.3% in SHAM and 13% in BNX animals as compared to the equally operated, but untreated animals. However, the significantly higher protein degradation observed in BNX (0.6 ± 0.2 nmol/min/g muscle) versus SHAM (0.2 ± 0.1 nmol/min/g muscle) rats, as demonstrated by the marker of myofribrillar proteolytic rate, 3-Methylhistidine (3 MH) remains unaffected by administration of RU 38486 (0.5 ± 0.1 v. 0.2 ± 0.1 nmol/min/g muscle in BNX v. SHAM). CONCLUSION: RU 38486 does not act on changes of muscular protein turnover specific to uremia but reduces the effect of stress- stimulated elevated corticosterone secretion arising from surgery and fasting. A potentially beneficial effect against stress- induced catabolism in severe illness can be postulated that merits further study

Fragments and Reflexes of Kingship Theory in Ælfric\u27s Comments on Royal Authority

For some time now, scholars have mined the homiletic writings of Ælfric of Eynsham in order to gain insight into late Anglo-Saxon notions of royal authority. While Ælfric generally preferred to talk about kingship in moral terms, discussing what constitutes a good or bad king, some passages have been interpreted as reflecting the homilist\u27s own views about royal legitimacy. The utility of these passages as providing honest glimpses into Ælfric\u27s theory of kingship have since been called into question based on the nature of the homilist\u27s sources and our understanding of Anglo-Saxon political practices. On occasion, the relevant passages have also been read against each other as expressing potentially conflicting notions regarding royal authority. While acknowledging the difficulty of consulting passages that were originally applied in moral or theological contexts, this paper reassesses the usefulness of Ælfric\u27s comments on kingship in reconstructing the homilist\u27s views on royal authority and demonstrates that he likely viewed elective kingship, theocratic authority and hereditary birthright as complementary notions consonant with late tenth-century and early eleventh-century political ideologies

Educator and Participant Perceptions and Cost Analysis of Stage-tailored Educational Telephone Calls

Objective: To identify strengths and weaknesses of nutrition education via telephone calls as part of a larger stage-of-change tailored intervention with mailed materials. Design: Evaluative feedback was elicited from educators who placed the calls and respondents who received the calls. Setting: An internet and telephone survey of 10 states in the midwestern United States. Participants: 21 educators in 10 states reached via the internet and 50 young adults reached via telephone. Variables Measured and Analysis: Rankings of intervention components, ratings of key aspects of educational calls, and cost data (as provided by a lead researcher in each state) were summarized via descriptive statistics. Results, Conclusions, and Implications: Educational calls used 6 to 17 minutes of preparation time, required 8 to 15 minutes of contact time, and had a mean estimated cost of $5.82 per call. Low-income young adults favored print materials over educational calls. However, the calls were reported to have positive effects on motivating participants to set goals. Educators who use educational telephone calls to reach young adults, a highly mobile target audience, may require a robust and flexible contact plan. © 2008 SOCIETY FOR NUTRITION EDUCATION

Context-dependent regulation of immunoglobulin mutagenesis by p53.

p53 plays a major role in genome maintenance. In addition to multiple p53 functions in the control of DNA repair, a regulation of DNA damage bypass via translesion synthesis has been implied in vitro. Somatic hypermutation of immunoglobulin genes for affinity maturation of antibody responses is based on aberrant translesion polymerase action and must be subject to stringent control to prevent genetic alterations and lymphomagenesis. When studying the role of p53 in somatic hypermutation in vivo, we found altered translesion polymerase-mediated A:T mutagenesis in mice lacking p53 in all organs, but notably not in mice with B cell-specific p53 inactivation, implying that p53 functions in non-B cells may alter mutagenesis in B cells. During class switch recombination, when p53 prevents formation of chromosomal translocations, we in addition detected a B cell-intrinsic role for p53 in altering G:C and A:T mutagenesis. Thus, p53 regulates translesion polymerase activity and shows differential activity during somatic hypermutation versus class switch recombination in vivo. Finally, p53 inhibition leads to increased somatic hypermutation in human B lymphoma cells. We conclude that loss of p53 function may promote genetic instability via multiple routes during antibody diversification in vivo