POLYPEPTIDE growth factors (GFs) 1 play a fundamental role during embryogenesis and regeneration (e.g., wound healing) by stimulating proliferation and differentiation of certain cell populations. Some GFs can be responsible also for malignant transformation and tumor growth (e.g., FGF-4: hst1 oncogene). GF receptors (GFRs) are generally known as plasma membrane proteins which "send" signals to the nucleus principally via the MAPK and the JAK-STAT pathways (Karin and Hunter, 1995). However, in the past few years data were accumulating to suggest that, surprisingly, nuclear targeting and action of GFs and GF receptors could occur as well. This alternative or complementary signaling pathway appears to be involved in the induction of cell proliferation. In addition, nuclear GF-GFR complexes may participate in the activation of cell line-specific genes as well. Since by far the largest body of data has been published in relation to FGF-1 and -2 (aFGF and bFGF), we have focused here on the nuclear role of these GFs.

Background: Psychosocial stress and depression have been recognized as major risk factors of coronary artery disease (CAD). Although monocytes are known to be key players in atherosclerosis, monocyte-based associations with psychoneuroendocrino-immuno-inflammatory (PNI) markers have not been widely investigated in stable CAD. Objective: We examined associations between the monocyte-to-lymphocyte ratio (MLR) and key PNI markers in stable CAD. Methods: We studied 23 patients with stable CAD who completed the Beck Depression Inventory (BDI) and Rahe's Brief Stress and Coping Inventory. A white blood cell differential was performed, and levels of cortisol, chromogranin A (CgA), LL-37, interleukin-6 (IL-6) and C-reactive protein (CRP) were assayed in plasma. Results: Monocyte fraction, MLR and plasma CgA levels exceeded reference values, the social support score was low, and 7 patients had elevated BDI scores. In the multivariate-adjusted analysis, a higher MLR was associated with greater depressive symptom severity (r = 0.624, p < 0.01) as well as with higher concentrations of CgA (r = 0.660, p < 0.01), LL-37 (r = 0.643, p < 0.01), IL-6 (r = 0.532, p < 0.05) and CRP (r = 0.470, p < 0.05). BDI scores associated with CgA concentration (r = 0.618, p < 0.01) and CgA level correlated negatively with the social support score (r = -0.511, p < 0.05). Conclusions: Our findings suggest that, in patients with stable CAD, elevated MLR may be associated with depressive symptoms, with increased neuroendocrine-sympathetic activity (marked by CgA) and inflammatory markers that are pertinent to atherosclerosis initiation and progression. The increased neuroendocrine-sympathetic activity correlated with low social support and depressive symptom severity. The MLR might serve as an easy-to-obtain and inexpensive proxy measure of an activated PNI network in stable CAD.

When compared with gelatin or dextran solutions, hydroxyethyl starch provided a therapeutic advantage in this setting by exerting an inhibitory effect on the ischemia-reperfusion-induced local and systemic leukocyte reactions and the postischemic periosteal microvascular dysfunction.

We examined local and systemic antiinflammatory consequences of ischemic preconditioning (IPC) in a rat model of limb ischemia-reperfusion (I-R) by characterizing the leukocyte-endothelial interactions in the periosteum and the expression of adhesion molecules playing a role in leukocyte-mediated inflammatory processes. IPC induction (2 cycles of 10 min of complete limb ischemia and 10 min of reperfusion) was followed by 60 min of ischemia/180 min of reperfusion or sham-operation. Data were compared with those on animals subjected to I-R and sham-operation. Neutrophil leukocyte-endothelial cell interactions (intravital videomicroscopy), intravascular neutrophil activation (CD11b expression changes by flow cytometry), and soluble and tissue intercellular adhesion molecule-1 (ICAM-1; ELISA and immunohistochemistry, respectively) expressions were assessed. I-R induced enhanced leukocyte rolling and adherence in the periosteal postcapillary venules after 120 and 180 min of reperfusion. This was associated with a significantly enhanced CD11b expression (by $80% and 72%, respectively) and moderately increased soluble and periosteal ICAM-1 expressions. IPC prevented the I-R-induced increases in leukocyte adherence and CD11b expression without influencing the soluble and tissue ICAM-1 levels. The results show that limb IPC exerts not only local, but distant antiinflammatory effects through significant modulation of neutrophil recruitment. ß