Methylated derivatives of myricetin enhance life span in Caenorhabditis elegans dependent on the transcription factor DAF-16.

Only certain flavonoids have been shown to enhance life span. This was pointed out for e.g. myricetin in the nematode Caenorhabditis elegans. However, the structural requirements responsible for this effect are not known. We used methylated derivatives of myricetin (laricitrin, syringetin, myricetintrimethylether) to investigate if free OH moieties in the B-ring are necessary for the life span extending effect. In analogy to myricetin, all derivatives increased the life span, decreased oxidative stress (DCF) and decreased the accumulation of lipofuscin. In contrast to myricetin, the methylated compounds strongly enhanced the resistance against thermal stress. Furthermore, treatment with the derivatives induced a much stronger nuclear localization of the DAF-16 transcription factor (FoxO homologue). Additionally, no antioxidant effects and only minor effects on life span prolongation and stress resistance were detectable for the methylated compounds in a DAF-16 deficient nematode strain. Comparable to the dietary flavonoid myricetin, the methylated myricetin derivatives laricitrin, syringetin and myricetintrimethylether strongly enhance the life span of C. elegans. Therefore, OH groups of ring B are not necessary for this effect. Only the methylated compounds increase the stress resistance of the nematode which was dependent on DAF-16. These findings suggest that methylation of myricetin increases the biofunctionality.

Impact of a guideline-based disease management team on outcomes of hospitalized patients with congestive heart failure.

BACKGROUND: Congestive heart failure is the most common reason for hospitalization in the United States, and guidelines to improve the quality of care for patients with congestive heart failure have been developed. However, adherence is typically low. We hypothesized that a guideline-based care management team would result in greater quality and efficiency of care than guidelines alone. METHODS: A faculty cardiologist and nurse care manager at an academic medical center reviewed each patient's data and made guideline-based recommendations. Hospital length of stay, total costs, and use of recommended guidelines were compared between 173 patients before team implementation but with available guidelines, 283 care-managed patients, and 126 concurrent non-care-managed patients. RESULTS: Care-managed patients achieved higher rates of use of angiotensin-converting enzyme inhibitor than baseline or non-care-managed patients (95%, 60%, and 75%, respectively; P<.001), as well as increased adherence to guidelines for daily weight monitoring and assessment of left ventricular function. Hospital length of stay was lower (median, 3, 4, and 5 days, respectively; P<.001) as were costs of hospitalization (median, $2934, $3209, and $4830, respectively; P<.01). These differences persisted after adjustment for severity of illness. CONCLUSIONS: When compared with dissemination of guidelines alone, an active care management approach was associated with significant improvements in quality and efficiency of care for hospitalized patients with congestive heart failure.

Reflex control in heart failure: a primer for physicians.

Heart failure, cause notwithstanding, is characterized by adaptive (but harmful) increases in sympathetic activity and hormone levels, as well as by abnormal cardiovascular reflexes. Such reflex derangements may contribute to neurohumoral excitation. Consequently, normalization of the reflexes may be an important determinant of the effectiveness of therapy.