Erythropoietin (Epo) is a hydrophobic sialoglycoproteic hormone produced by the kidney and responsible for the proliferation, maturation, and differentiation of the precursors of the erythroid cell line. Human recombinant erythropoietin (rHuEpo) is used to treat different types of anemia, not only in uremic patients but also in newborns with anemia of prematurity, in patients with cancer-related anemia or myeloproliferative disease, thalassemias, bone marrow transplants, or those with chronic infectious diseases. The pleiotropic functions of Epo are well known. It has been shown that this hormone can modulate the inflammatory and immune response, has direct hemodynamic and vasoactive effects, could be considered a proangiogenic factor because of its interaction with vascular endothelial growth factor, and its ability to stimulate mitosis and motility of endothelial cells. The multifunctional role of Epo has further been confirmed by the discovery in the central nervous system of a specific Epo/Epo receptor (EpoR) system. Both Epo and EpoR are expressed by astrocytes and neurons and Epo is present in the cerebrospinal fluid (CSF). Therefore, novel functions of Epo, tissue-specific regulation, and the mechanisms of action have been investigated. In this review we have tried to summarize the current data on the role of Epo on brain function. We discuss the different sites of cerebral expression and mechanisms of regulation of Epo and its receptor and its role in the development and maturation of the brain. Second, we discuss the neurotrophic and neuroprotective function of Epo in different conditions of neuronal damage, such as hypoxia, cerebral ischemia, and subarachnoid hemorrhage, and the consequent possibility that rHuEpo therapy could soon be used in clinical practice to limit neuronal damage induced by these diseases.

HDF and HDF(k) have significantly different effects on QT(c). ECG data demonstrate that the risk of arrhythmia could be lower, with a variable removal of potassium during haemodialysis. With HDF but not HDF(k), hyperpolarization of the cell membrane is detected, and this could have a destabilizing effect on different types of cardiac cell, giving rise to retrograde circuits.

In order to ascertain whether erythropoietin plays a role in early and late repair processes following ischaemic skin flap injury, a dorsal, caudally based skin flap was created in rats. The rats were successively divided into four groups. Group 1 was not treated. The other groups were treated with a subcutaneous administration of 0.9% NaCl saline solution (group 2), a subcutaneous administration of vehicle (group 3) or a subcutaneous administration of 300 IU/kg/day of recombinant human erythropoietin (group 4). We evaluated the possible relationships between neutrophil accumulation, myeloperoxidase activity and content in flap tissue, flap survival, flap temperature (using telethermography) and flap revascularization (using videocapillaroscopy). Necrosis in the flap was significantly less extensive in group 4 than in groups 1, 2 and 3. A significant increase in neutrophil infiltration occurred between the 1st and 24th hour in these groups, but this was not observed in group 4. These findings were confirmed by biochemical data of myeloperoxidase activity and malonyldialdehyde content. Between the 1st and 7th days, we recorded an increase of about 20% in flap temperature in groups 1, 2 and 3, whereas no significant variation was observed in group 4. On the 7th day, videocapillaroscopic findings showed an increase in the mean vascularization index in group 4. Our findings suggest that recombinant human erythropoietin administration can improve the wound healing process, in both early and late stages of injury, by reducing inflammatory response, increasing the density of capillaries in ischaemic flaps and allowing earlier repair of a damaged area.

It is now widely known that erythropoietin (Epo) does not only affect the haematopoietic system, but it can be considered a multifunctional trophic factor with an effect on the general homoeostasis of the entire organism. The recent discovery of a specific Epo/Epo-receptor system in the central nervous system (CNS) and cerebrospinal fluid, independently of the haematopoietic system, has further paved the way for new studies aimed at investigating the different sites of cerebral expression of Epo and its receptor, the regulation of their expression and, finally, the effects that this hormone has on the development and maturation of the brain. A further aim has been to investigate how it influences CNS homoeostasis and neurotransmission in adult brain. Attention has also been focused on the neurotrophic and neuroprotective function of Epo in different conditions of neuronal damage, such as hypoxia, cerebral ischaemia and subarachnoid haemorrhage, and therefore on the possibility that human recombinant Epo therapy could soon be used in clinical practice, also to limit neuronal damage induced by these diseases.

Thanks to the administration of hypocholesterolemic drugs, important advances have been made in the treatment of patients with progressive renal disease. In vitro and in vivo findings demonstrate that statins, the inhibitors of HMG-CoA reductase, can provide protection against kidney diseases characterized by inflammation and/or enhanced proliferation of epithelial cells occurring in rapidly progressive glomerulonephritis, or by increased proliferation of mesangial cells occurring in IgA nephropathy. Many of the beneficial effects obtained occur independent of reduced cholesterol levels because statins can directly inhibit the proliferation of different cell types (e.g., mesangial, renal tubular, and vascular smooth muscle cells), and can also modulate the inflammatory response, thus inhibiting macrophage recruitment and activation, as well as fibrosis. The mechanisms underlying the action of statins are not yet well understood, although recent data in the literature indicate that they can directly affect the proliferation/apoptosis balance, the down-regulation of inflammatory chemokines, and the cytogenic messages mediated by the GTPases Ras superfamily. Therefore, as well as reducing serum lipids, statins and other lipid-lowering agents may directly influence intracellular signaling pathways involved in the prenylation of low molecular weight proteins that play a crucial role in cell signal transduction and cell activation. Statins appear to have important potential in the treatment of progressive renal disease, although further studies are required to confirm this in humans.