These results indicate that either local exogenous S1P administration or endogenous S1P overproduction promotes post-ischaemic angiogenesis and blood flow recovery. These observations suggest potential therapeutic usefulness of S1P for tissue ischaemia.

No abstract

Therapeutic angiogenesis is a promising strategy for treating ischemia. The lysophospholipid mediator sphingosine-1-phosphate (S1P) acts on vascular endothelial cells to stimulate migration and tube formation, and plays the critical role in developmental angiogenesis. We developed poly(lactic-co-glycolic-acid) (PLGA)-based S1P-containing microparticles (PLGA-S1P), which are biodegradable and continuously release S1P, and studied the effects of PLGA-S1P on neovascularization in murine ischemic hindlimbs. Intramuscular injections of PLGA-S1P stimulated blood flow in C57BL/6 mice dose-dependently, with repeated administrations at a 3-day interval, rather than a single bolus or 6-day interval, over 28 days conferring the optimal stimulating effect. In Balb/c mice that exhibit limb necrosis and dysfunction due to retarded blood flow recovery, injections of PLGA-S1P stimulated blood flow with alleviation of limb necrosis and dysfunction. PLGA-S1P alone did not induce edema in ischemic limbs, and rather blocked vascular endothelial growth factor-induced edema. PLGA-S1P not only increased the microvessel densities in ischemic muscle, but promoted coverage of vessels with smooth muscle cells and pericytes, thus stabilizing vessels.PLGA-S1P stimulated Akt and ERK with increased phosphorylation of endothelial nitric oxide synthase in ischemic muscle. The effects of the nitric oxide synthase inhibitor, Nω-nitro-L-arginine methylester, showed that PLGA-S1P-induced blood flow stimulation was partially dependent on nitric oxide. Injections of PLGA-S1P also increased the expression of 3 angiogenic factors and the recruitment of CD45-, CD11b-and Gr-1-positive myeloid cells, which are implicated in post-ischemic angiogenesis, into ischemic muscle. These results indicate that PLGA-based, sustained local delivery of S1P is a potentially useful therapeutic modality for stimulating post-ischemic angiogenesis.

Metastasis of one tumor to another tumor within the same individual is considered rare. Lung cancer metastatic to renal cell carcinoma represents the most common combination of such tumor-to-tumor metastases.We present the autopsy case of a 97-year-old woman with metastatic adenocarcinoma of the lung to renal cell carcinoma.

Significantly Stokes-shifted fluorescence induced by the UV photoexcitation of 2,2′-bipyridin-3-ol in 3-methylpentane exhibits a dramatic temperature dependence such that dual fluorescence spectra (λ max ) 560 and 585 nm) at room temperature are replaced by a single fluorescence spectrum (λ max ) 560 nm) below 200 K. The respective emitting species responsible for the short-and long-wavelength bands may be ascribed to the excited-state primary phototautomer (S 1 ′) and its rotamer (S 1 ′′), which is generated by the rotational isomerization of S 1 ′ with an activation barrier.