No specific characteristics have been identified as predictors of peripheral blood stem cells (PBSC) mobilization in healthy donors. In this study, clinical characteristics and laboratory data for 122 healthy donors who underwent apheresis on day 5 of treatment with recombinant granulocyte colony-stimulating factor (G-CSF) were retrospectively analyzed for correlations with CD34(+) cell mobilization. The variables that were analyzed included age, sex, body weight, basal complete blood count, and maximum white blood count (WBC) before apheresis, G-CSF type, and dosage. Median age and body weight were 42.5 years (range 16-65) and 72.5 kg (range 47-121), respectively. By univariate analysis, male sex (P = 0.007), body weight (< or = 70 vs. >70 kg, P = 0.04), and donor's age (< or = 50 vs. > 50 years; P = 0.015) were correlated with the number of CD34(+) cells mobilized. By multivariate analysis, donor's age and male sex were the only two variables that significantly predicted a high CD34(+) cell level. In conclusion, our data suggest that male sex and younger age are the only factors that significantly affect CD34(+) mobilization in healthy donors.

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Mobilization of CD34+ into peripheral blood is attained by either glycosylated (lenograstim) or non-glycosylated recombinant G-CSF (filgrastim). 101 donors, 57 males, median age 42 years (range 16-63) entered this retrospective study. Group I (55 cases) received filgrastim and group II lenograstim subcutaneously for 5-6 days. The peak number of CD34+ cells/microl blood observed on day 4 and 5 was not significantly different in the two groups. No differences were shown in terms of both circulating CFU-GM at the time of harvesting and CD34+ target of collection. The most frequent side effects were bone pain (18.2% grade I; 36.4% grade II, 7.3% grade III), headache (18.2%), nausea (9.1%), fever (5.5%) and a mild splenomegaly (> 2 cm) (5.5%) in filgrastim group, and bone pain (37.0% grade I, 26.1% grade II, 2.2% grade III), headache (17.4%), nausea (15.2%), fever (4.4%) and a mild splenomegaly (4.3%) in lenograstim group, respectively. CD34+ collection was associated with thrombocytopenia, which was not significantly different between the two groups. No donor in either group developed long-term adverse effects. We conclude that both G-CSFs are comparable in terms of CD34+ cell collection, safety and tolerability.

A longitudinal, prospective, observational, single-center, cohort study on healthy donors (HDs) was designed to identify predictors of CD34 + cells on day 5 with emphasis on the predictive value of the basal CD34 + cell count. As potential predictors of mobilization, age, sex, body weight, height, blood volume as well as white blood cell count, peripheral blood (PB) mononuclear cells, platelet count, hematocrit, and hemoglobin levels were considered. Two different evaluations of CD34 + cell counts were determined for each donor: baseline (before granulocyte colony-stimulating factor [G-CSF] administration) and in PB after G-CSF administration on the morning of the fifth day (day 5). A total of 128 consecutive HDs (66 males) with a median age of 43 years were enrolled. CD34 + levels on day 5 displayed a non-normal distribution, with a median value of 75.5 cells/ μL. To account for the non-normal distribution of the dependent variable, a quantile regression analysis to predict CD34 + on day 5 using the baseline value of CD34 + as the key predictor was performed. On crude analysis, a baseline value of CD34 + ranging from .5 cells/μL to 1 cells/μL predicts a median value of 50 cells/μL on day 5; a value of 2 cells/μL predicts a median value of 70.7 cells/μL; a value of 3 cells/μL to 4 cells/μL predicts a median value of 91.3 cells/μL, and a value ≥ 5 predicts a median value of 112 cells/μL. In conclusion, the baseline PB CD34 + cell count correlates with the effectiveness of allogeneic PB stem cell mobilization and could be useful to plan the collection.

Background and Aims: Grapevine (Vitis vinifera L.) is one of the earliest domesticated crops, dating back 6000 years ago in the Near East before spreading into Europe. Despite the abundance of historical, archaeological and genetic records, until now secondary domestication events in European regions are not well demonstrated. Here, a genetic characterisation of grape germplasm from Calabria in Southern Italy, a crucial area of the Mediterranean Basin, aims to validate this area as a secondary centre of crop domestication. Methods and Results: True-to-type cultivar classification of 72 accessions was carried out by using microsatellite loci (simple sequence repeat) along with the main Organisation Internationale de la Vigne et du Vin ampelographic descriptors. The classification highlighted a high level of genetic diversity (H e = 0.83) among native cultivars from Calabria. A decay of genetic diversity moving from southern Italy to north-western Mediterranean regions was observed, probably because of repeated founder effects during the grapevine expansion from the Mediterranean Basin to Europe. Single nucleotide polymorphism analysis showed an admixture genetic structure at K = 7, clarifying a complex network of pedigree relationships generated by crosses among cultivars. Parentage analysis underlined a high proportion of parent-offspring relationships (76%) in Mantonico Bianco and Pecorello, hypothesising their key role in the pedigree of many native cultivars from the southern Mediterranean area. Conclusion: Overall, our results appear to indicate a pivotal role of cultivars from Calabria in the grape genetic diversity of southern Italy. Furthermore, genetic analysis of grape wild accessions from Calabria should be of value in a discussion of a secondary centre of grape domestication. Significance of the Study: A large grape collection from Calabria was for the first time characterised through ampelographic and genetic analysis.

We investigated by means of telethermography the contractile response of cutaneous vessels to recombinant erythropoietin (rHuEPO) and the effects of this hormone on the vasodilatation induced by either acetylcholine, which is endothelium-dependent, and nitroprusside, which is endothelium-indepen-dent. Experiments were carried out in 12 healthy volunteers. Graded doses of rHuEPO (25, 50, 500U/min), acetylcholine (7.5 and 15µg/min), sodium nitroprusside (3 and 10 µg/min), and saline solution (sodium chloride 0.9%) were infused in the dorsal pedal artery of the lower limb. rHuEPO reduced the cutaneous temperature in a dose-dependent manner compared to the saline solution, thus suggesting that the hormone causes vasoconstriction. In contrast graded doses of acetylcholine and nitroprusside provoked vasodilatation: in fact both increased the cutaneous temperature compared to controls in a dose-dependent manner. The infusion of vasoconstrictive doses of rHuEPO in association with acetylcholine (15 µg/min) reverted the increase in the cutaneous temperature induced by the endothelium-dependent vasodilator. In contrast rHuEPO administered in combination with nitroprusside failed to block the vasodilatation induced by the endothelium-independent vasodilator. Therefore our data suggest that rHuEPO exerts an indirect vasoconstrictive effect and that acetylcholine-induced vasodilatation, which is endothelium-dependent, is blunted by the vasoconstrictive activity of rHuEPO, thus demonstrating that the hormone may impair the synthesis of endothelial nitric oxide.

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A short-course administration of non-glycosylated granulocyte-colony-stimulating factor (G-CSF) was investigated in 68 healthy donors (HDs) in order to collect > or = 4 x 10(6) CD34+ cells per kilogram of recipient's body weight. G-CSF was given at 10 microg/kg per day administered in two divided doses for 3 days. Leukapheresis was scheduled on day 4, 12 h after the last dose of G-CSF. A median of 35.6 circulating CD34+ cells microL(-1) (range, 3.1-185) was found on the day of leukapheresis. This allowed a median collection of CD34+ cells of 4.2 x 10(6) per kilogram of recipient's weight (range, 1.0-17.4). One single procedure was sufficient to reach the target level of CD34+ cells in 36 (53%) of 68 donors; significant correlations were found between the number of CD34+ cells collected on day 4 and the patient's sex, body-weight and volume of blood processed. A retrospective analysis was made with a historical group of HDs collected on day 5. The day 5 schedule allowed a more consistent achievement of the target cell dose with one leukapheresis (P = 0.005) and resulted in the initial collection of a significantly larger number of CD34+ cells (P = 0.006).