Apolipoprotein D expression in human brain reactive astrocytes.

Astrocytosis is a hallmark of damage that frequently occurs during aging in human brain. Astrocytes proliferate in elderly subjects, becoming hypertrophic and highly immunoreactive for glial fibrillary acidic protein (GFAP). These cells are one type that actively responds in the repair and reorganization of damage to the neural parenchyma and are a source of several peptides and growth factors. One of these biomolecules is apolipoprotein D (apo D), a member of the lipocalin family implicated in the transport of small hydrophobic molecules. Although the role of apo D is unknown, increments in brain apo D expression have been observed in association with aging and with some types of neuropathology. We have found an overexpression of apo D mRNA in reactive astrocytes by in situ hybridization in combination with immunohistochemistry for apo D in normal aged human brains. The number of double-labeled cells varied according to the cerebral area and the gliosis grade. The possible significance of this increased synthesis of apo D in reactive astrocytes is discussed in relation to the role of apo D in aging and in glial function.     

The critical role of alpha‐folate receptor in the resistance of melanoma to methotrexate

Although methotrexate (MTX) is an effective drug for several types of cancer, it is not active against melanoma. Experiments following methotrexate treatment indicated a reduced accumulation of the drug in the cytosolic compartment in melanoma cells, suggesting that the mechanisms that control the transport and retention of this drug could be altered in melanoma. For this reason, we analyzed the presence and function of folate receptor‐α (FRα) in melanoma cells. In this study, we have identified the presence of FRα in normal and pathological melanocytes and demonstrated that MTX is preferentially transported through this receptor in melanoma cells. FRα‐induced endocytic transport of MTX, together with drug melanosomal sequestration and cellular exportation, ensures reduced accumulation of this cytotoxic compound in intracellular compartments. The critical role of FRα in this mechanism of resistance and the therapeutic consequences of these findings are also discussed.     

Glycoproteins from Bufo arenarum vitelline envelope with fertility-impairing effect on homologous spermatozoa

When spermatozoa from Bufo arenarum are incubated with molecules extracted from the vitelline envelopes of homologous oocytes, they lose their fertilizing capacity. Those molecules are glycoproteins, and the elimination of mannoside residues from them results in activity loss, while digestion of the proteic moiety did not alter their biological effect. Sepharose-concanavalin A columns were used to purify the glycoproteins, since the active fraction binds to the column. The fertility-impairing effect observed does not seem to be mediated by an acrosome reaction-inducing effect.     

A synthetic analog of prostaglandin E2 is able to induce in vivo theta antigen on spleen cells of adult thymectomized mice

The effect of prostaglandins on the in vivo induction of theta antigen in splenic spontaneous rosette-forming cells derived from adult thymectomized mice was studied. A long-acting synthetic analog of prostaglandin E₂, di-M-PGE₂, mimicked the effects of thymic hormone and was active when mice were treated with as little as 0.1 μg ip. In addition, indomethacin, a potent inhibitor of prostaglandin biosynthesis, was able to reverse the inductive effects of exogenous thymic hormone and inhibit the expression of theta antigen in normal mice, presumably by interfering with the effect of endogenous thymic factors. Finally, indomethacin also partially suppressed the stimulatory effects of exogenously administered di-M-PGE₂, suggesting that this agent is effective, at least in part, because it stimulates endogenous prostaglandin biosynthesis. Possible mechanisms of action for the effects of prostaglandins are presented.