Antinociceptive and hypothermic effects of trimethyltin

Trimethyltin (TMT) induced a dose-dependent antinociceptive and hypothermic effect in mice. Antinociception was not attenuated by naloxone but was reversed by atropine. TMT, however, was ineffective in displacing (³H)-QNB binding $\text{in vitro}$ and did not affect (³H)-QNB binding or acetylcholinesterase activity after $\text{in vivo}$ administration. The ethyl ester of nipecotic acid, a specific inhibitor of synaptosomal GABA uptake, exerted a similar antinociceptive effect that could be blocked by atropine. The GABA receptor antagonist bicuculline attenuated antinociception induced by TMT and nipecotic acid ethyl ester but not by morphine or oxotremorine. γ-Vinyl GABA, an irreversible inhibitor of GABA metabolism, prolonged TMT but not morphine-induced antinociception. In contrast, neither the dose-response nor the time course of TMT-induced hypothermia were affected by any of the drugs tested. The findings suggest that the GABAergic system may be involved in TMT induced antinociception; however, the mechanism responsible for the hypothermic effect of TMT is not apparent.     

Ultrastructure and X-Ray Microanalysis of Blood Cells of Ascidia malaca

Ultrastructural studies of Ascidia malaca blood reveal particular cell types, which are characterized by a polymorphism in the organization of the electron dense cytoplasmic material. A new pathway of morula cell differentiation is suggested. X-ray microanalysis shows that vanadium is localized in vacuolated, granular and morular cells. Iron, which is accumulated by this species to a lesser degree than vanadium, is found in vacuolated amebocytes and, together with vanadium, in granular cells. Our results are discussed in the light of the relations between selective metal absorption in blood cells and their specialization and differentiation.     

Nuclear inositide signaling: An appraisal of phospholipase C β1 behavior in myelodysplastic and leukemia cells

Location impinges on function of some of the main players of nuclear inositol lipid cycle. Here we have discussed the behavior of PI-PLCβ1 in myelodysplastic and cultured leukemia cells.The presence of a cryptic deletion of PI-PLCβ1 gene in high-risk MDS patients is accompanied by altered expression of its mRNA in that the overall decrease of mRNA is characterized by a dramatic decrease of the splicing variant 1a, which is cytosolic and partially nuclear, whilst the splicing variant 1b is still highly represented. This suggests that altered expression of nuclear PI-PLCβ1 could be involved in a disregulation of the cell cycle and have also important effects on cell apoptotic pathways.Moreover, in cultured leukemia cells (Felc) it has been reported by means of a proteomic approach that the splicing factor SRp20 interacts with nuclear PI-PLCβ1 and its expression is modulated by this signaling molecule.All in all, it appears more and more evident that nuclear signaling elicited by PI-PLCβ1 is a key event in the control of cell cycle progression.     

Apoptosis and cell proliferation in proximal tubular cells exposed to apoptotic bodies. Novel pathophysiological implications in cisplatin-induced renal injury

The therapeutic efficacy of the antineoplastic drug cisplatin is limited by its nephrotoxicity, which affects particularly to proximal tubular cells (PTC). Cisplatin-induced cytotoxicity appears to be multifactorial and involves inflammation, oxidative stress as well as apoptosis. We have recently shown that the cyclo-oxygenase-2 (COX-2)/intracellular prostaglandin E₂ (iPGE₂)/EP receptor pathway mediates the apoptotic effect of cisplatin on human proximal tubular HK-2 cells. Here, we studied the effects on HK-2 cells of apoptotic bodies (ABs) generated after treatment of HK-2 cells with cisplatin. We found that ABs inhibited cell growth, induced apoptosis and increased COX-2 expression and iPGE₂ in ABs-recipient HK-2 cells. Inhibition of the COX-2/iPGE₂/EP receptor pathway in these cells prevented the effects of ABs without interfering with their internalization. Interestingly, 2nd generation ABs (i.e. ABs released by cells undergoing apoptosis upon treatment with ABs) did not trigger apoptosis in naïve HK-2 cells, and stimulated cell proliferation through the COX-2/iPGE₂/EP receptor pathway. These results suggest that ABs, through iPGE₂-dependent mechanisms, might have a relevant role in the natural history of cisplatin-induced acute kidney failure because they contribute first to the propagation of the noxious effects of cisplatin to non-injured PTC and then to the promotion of the proliferative tubular response required for proximal tubule repair. Since iPGE₂ also mediates both cisplatin-induced HK-2 cell apoptosis, intervention in the COX-2/iPGE₂/EP receptor pathway might provide us with new therapeutic avenues in patients with cisplatin-induced acute kidney injury.