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Critical limb ischemia (CLI), foot ulcers, former amputation, and impaired regeneration are independent risk factors for limb amputation in subjects with diabetes. The present work investigates whether and by which mechanism diabetes negatively impacts on functional properties of muscular pericytes (MPs), which are resident stem cells committed to reparative angiomyogenesis. We obtained muscle biopsy samples from patients with diabetes who were undergoing major limb amputation and control subjects. Diabetic muscles collected at the rim of normal tissue surrounding the plane of dissection showed myofiber degeneration, fat deposition, and reduction of MP vascular coverage. Diabetic MPs (D-MPs) display ultrastructural alterations, a differentiation bias toward adipogenesis at the detriment of myogenesis and an inhibitory activity on angiogenesis. Furthermore, they have an imbalanced redox state, with downregulation of the antioxidant enzymes superoxide dismutase 1 and catalase, and activation of the pro-oxidant protein kinase C isoform -II (PKCII)- dependent p66Shc signaling pathway. A reactive oxygen species scavenger or, even more effectively, clinically approved PKCII inhibitors restore D-MP angiomyogenic activity. Inhibition of the PKCII-dependent p66Shc signaling pathway could represent a novel therapeutic approach for the promotion of muscle repair in individuals with diabetes. This work has been supported by British Heart Foundation grants RJ5905 and RM/13/2/30158 and Italian Ministry of Health grant RF-2011-02346867 to P.M., Cariplo Foundation grant 2013-0887 to G.S., European Research Council grant N322749 DEPTH to G.C., and Uncovering Excellence Grant 2014 MDESMPLAT to C.G. Scopus

A mathematical ARMAX model of daily SO 2 pollution in an urban area (Milan, Italy) during the domestic heating season (from mid-October to the end of March) is described. The real-time predictor derived from this model supplies a forecast of SO 2 pollution one day ahead, by using as inputs actual pollution, mean daily wind speed and temperature and a synoptic meteorological category, defined on the basis of forecast synoptic maps. By means of this predictor, a forecast and alarm system has been implemented in real time on the computer of the local Public Health Office during the 1979/1980 heating season. Forecast pollution values have been published every day by the local papers.

Carboxyl ester lipase (CEL) is an enzyme that hydrolyzes a wide variety of lipid substrates, including ceramides, which are known to show inhibitory regulation of pituitary hormone secretion in experimental models. Because no studies on CEL expression in human pituitary and pituitary adenomas have been reported in the literature, we investigated CEL expression in 10 normal pituitary glands and 86 well-characterized pituitary adenomas [12 FSH/LH cell, 17 α-subunit/null cell, 6 TSH cell, 21 ACTH cell, 11 prolactin (PRL) cell, and 19 GH cell adenomas] using IHC, immunoelectron microscopy, Western blotting, and quantitative RT-PCR. In normal adenohypophysis, CEL was localized in GH, ACTH, and TSH cells. In adenomas, it was mainly found in functioning GH, ACTH, and TSH tumors, whereas its expression was poor in the corresponding silent adenomas and was lacking in FSH/LH cell, null cell, and PRL cell adenomas. Ultrastructurally, CEL was localized in secretory granules close to their membranes. This is the first study demonstrating CEL expression in normal human pituitary glands and in functioning GH, ACTH, and TSH adenomas. Considering that CEL hydrolyzes ceramides, inactivating their inhibitory function on pituitary hormone secretion, our findings suggest a possible role of CEL in the regulation of hormone secretion in both normal and adenomatous pituitary cells. (J Histochem Cytochem 58:881–889, 2010)