Cleaved forms of soluble urokinase receptor (c-suPAR) have been detected in body fluids from patients affected by various tumors. We recently reported increased c-suPAR levels in sera of healthy donors during granulocyte colony-stimulating factor (G-CSF)-induced mobilization of CD34 + hematopoietic stem cells (HSC). In vitro, c-suPAR or its derived chemotactic peptide (uPAR [84][85][86][87][88][89][90][91][92][93][94][95] ) stimulated migration of human CD34 + HSCs and inactivated CXCR4, the chemokine receptor primarily responsible for HSC retention in bone marrow. These results suggested that c-suPAR could potentially contribute to regulate HSC trafficking from and to bone marrow. Therefore, we investigated uPAR 84-95 effects on mobilization of mouse CD34 + hematopoietic stem/progenitor cells (HSC/HPC). We first showed that uPAR 84-95 stimulated in vitro dose-dependent migration of mouse CD34 + M1 leukemia cells and inactivated murine CXCR4. uPAR [84][85][86][87][88][89][90][91][92][93][94][95] capability to induce mouse HSC/ HPC release from bone marrow and migration into the circulation was then investigated in vivo. uPAR 84-95 i.p. administration induced rapid leukocytosis, which was associated with an increase in peripheral blood CD34 + HSCs/HPCs. In vitro colony assays confirmed that uPAR 84-95 mobilized hematopoietic progenitors, showing an absolute increase in circulating colony-forming cells. uPAR [84][85][86][87][88][89][90][91][92][93][94][95] mobilizing activity was comparable to that of G-CSF; however, neither synergistic nor additive effect was observed in combining the two molecules. These findings show for the first time in vivo biological effects of c-suPAR. Its capability to mobilize HSCs suggests potential clinical applications in HSC transplantation. (Cancer Res 2006; 66(22): 10885-90)
Skin, lymph node (popliteal), and bone marrow samples were collected from 50 red foxes (Vulpes vulpes) from May 2004 to May 2005 in southern Italy. Samples were tested for Leishmania infantum by polymerase chain reaction (PCR). The parasite was detected by PCR from 20 of 50 (40%) fox carcasses. All 20 positive cases were PCR-positive from lymph node and bone marrow samples, whereas 17 of 20 positive cases were PCR-positive from skin samples. Infection status was not related to age or sex. This is the first report of leishmaniasis in red foxes in Italy based on PCR results, and these results reinforce the assumption that this wild canid can serve as a reservoir for Leishmania.
The present study describes the effects of losartan and the angiotensin-converting enzyme inhibitor enalapril on blood pressure, echocardiographically calculated left ventricular mass, renal function evaluated by glomerular filtration rate and quality of life. The renin-angiotensin-aldosterone system is of importance for cardiovascular growth. There is substantial experimental documentation in animals that the angiotensin II antagonist, losartan, decreases the cardiac hypertrophy response caused by elevated arterial pressure as well as intravascular volume overload. However, data in humans is scarce. This is a 3-year, randomised, doubleblind study with parallel group design in 50 patients with essential hypertension. The results show that both drugs reduced blood pressure equally effectively, and also left ventricular mass (P Ͻ 0.001). After 3 years of treatment glomerular filtration rate significantly increased with losartan (P Ͻ 0.005). Serum uric acid fell modestly although significantly, dose-dependent in los-
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