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Peroxisome proliferator-activated receptor-alpha (PPAR-α) and its exogenous activators (fibrates) promote autophagy. However, whether the deleterious effects of PPAR-α deficiency on doxorubicin (DOX)-induced podocytopathy are associated with reduced autophagy remains to be clarified. We investigated the mechanisms of PPAR-α in DOX-induced podocytopathy and tubular injury in PPAR-α knockout (PAKO) mice and in a murine podocyte cell line. DOX-treated PAKO mice showed higher serum levels of triglycerides and non-esterified fatty acids and more severe podocytopathy than DOX-treated wild-type mice, as evidenced by higher urinary levels of proteins and podocalyxin at 3 days to 2 weeks and higher blood urea nitrogen and serum creatinine levels at 4 weeks. Additionally, there was an increased accumulation of p62, a negative autophagy marker, in the glomerular and tubular regions in DOX-treated PAKO mice at Day 9. Moreover, DOX-treated PAKO mice showed more severe glomerulosclerosis and tubular damage and lower podocalyxin expression in the kidneys than DOX-treated control mice at 4 weeks. Furthermore, DOX treatment increased p-p53, an apoptosis marker, and cleaved the caspase-3 levels and induced apoptosis, which was ameliorated by fenofibrate, a PPAR-α activator. Fenofibrate further enhanced AMPK activation and autophagy under fed and fasting conditions. Conclusively, PPAR-α deficiency enhances DOX-induced podocytopathy, glomerulosclerosis, and tubular injury, possibly by reducing autophagic activity in mouse kidneys. [ABSTRACT FROM AUTHOR]

Measles epidemic occurred in southern part of Fukushima Prefecture from April 2002 to July 2003. Public Iwase hospital in Sukagawa City was the central hospital in the measles epidemic area and 382 patients with measles were admitted to the hospital during the epidemic. Based on clinical records, age distribution, vaccination history, familiar infection and complications were retrospectively investigated. Moreover, the vaccination rates and their calculating methods in the area were compared and the problems on immunization against measles were discussed. As the result, we found that 1) measles epidemic centered on unvaccinated infants, 2) measles was still serious disease with many complications and sometimes fatal, 3) measles was highly infectious and there was no way for prevention except vaccination, 4) the actual condition of measles vaccination was not reflected exactly by the current calculating methods used for the local health reports by the Ministry of Health Labour and Welfare. For the prevention of measles epidemic, it is necessary to know the exact numbers of patients infected with measles and patients deceased due to measles, to calculate precise vaccination rate, and to form the consensus among parents, physicians and administrators to control measles epidemic by the vaccination.