Mildly oxidised LDL induces more macrophage death than moderately oxidised LDL:roles of peroxidation, lipoprotein-associated phospholipase A2 and PPARgamma

AbstractDeath of macrophages and smooth muscle cells (SMC) can lead to progression of atherosclerosis. Mildly oxidised low-density lipoprotein (mildly-oxLDL) induced more overall death and apoptosis than moderately oxidised LDL, in human monocyte-macrophages (HMM). Mildly-oxLDL also induced more overall death in human SMC than did moderately-oxLDL. Mildly-oxLDL contained more hydroperoxides, but less oxysterol, malondialdehyde and negative charge than moderately-oxLDL. Specific inhibition of lipoprotein-associated phospholipase A2 (by SB222657) diminished death induction in HMM by both oxLDL types. Peroxisome proliferator-activated receptor γ (PPARγ) antagonist (GW9662) and agonist (ciglitazone) experiments suggested that non-hydrolysed, oxidised phospholipids in oxLDL activate PPARγ as a cellular defence mechanism. These results may be relevant to LDL oxidation within atherosclerotic plaques and may suggest strategies for combating atherosclerosis progression

Targeting and quality of nursing home care. A five-nation study

The objective of this study was to demonstrate that appropriate targeting and quality monitoring of institutional care of the elderly is possible using person-based information on residents of nursing homes. This cross-sectional study used Minimum Data Set (MDS) assessments of nursing home residents in 6 US states, Copenhagen, Reykjavik, and selected locations in Italy and Japan. The outcome measures were life expectancy at age 65, population over 65, percentage over 65's in nursing homes, and clinical characteristics of nursing home residents from a multinational database of RAI/MDS assessments. We found that Japan has the highest life expectancy, and the second lowest expenditure on health care. The United States has the highest expenditure on health care and intermediate life expectancy. Italy has the highest proportion of population over 65 and the lowest proportion of over 65's in nursing homes. Iceland, a relatively young country, has the highest proportion of over 65's in nursing homes. Residents in Italy and the United States had the most severe physical, cognitive and clinical characteristics, those in Iceland the least. There was wide variation in markers of quality of care, with no country either uniformly good or bad across multiple measures. In conclusion, headline statistics comparing nations' percentage of Gross Domestic Product (GDP) spent on health care, age structure of the population, percentage of over 65's in nursing homes and clinical characteristics bear no consistent relationship. Local policy and practice also affect quality of care. Standardized assessment enables comparisons at local, national and international levels making possible further research on targeting and the appropriate use of institutional care, thus permitting a range of efficiency measures to be developed to inform policy. (C) 1999, Editrice Kurtis

Molecular characterization of macbecin as an Hsp90 inhibitor

Macbecin compares favorably to geldanamycin as an Hsp90 inhibitor, being more soluble, stable, more potently inhibiting ATPase activity (IC50 = 2 mu M) and binding with higher affinity (K-d = 0.24 mu M). Structural studies reveal significant differences in their Hsp90 binding characteristics, and macbecin-induced tumor cell growth inhibition is accompanied by characteristic degradation of Hsp90 client proteins. Macbecin significantly reduced tumor growth rates (minimum TIC: 32%) in a DU145 murine xenograft. Macbecin thus represents an attractive lead for further optimization