Loredana Pratelli

Vitamin D, thyroid hormones and muscle mass influence natural killer (NK) innate immunity in healthy nonagenarians and centenarians

Increasing evidence has demonstrated that the immune system closely interacts with other physiological systems, whose communications are mediated by circulating cytokines and hormones. The aim of our study was to test whether the number and cytolytic activity of NK cells in a group of relatively healthy Italian nonagenarians and centenarians were affected by the modifications of endocrine, metabolic and functional parameters that occur during ageing. Because of the extreme age of the study population, a cross‐sectional analysis was performed. This study revealed that the group of oldest subjects with the highest number of NK cells and the best preserved cytolytic function also presented a preserved metabolism of thyroid hormones and vitamin D and integrity of muscle mass. In fact, the NK cell number and/or cytolytic activity of healthy subjects > 90 years old was positively associated with serum levels of vitamin D, while T3, FT4, i‐PTH hormones and lean body mass were associated only with NK cell number. In conclusion, our results stress the paramount importance of nutritional evaluation in the clinical assessment of elderly people.

Determinants of functional status in healthy Italian nonagenarians and centenarians: A comprehensive functional assessment by the instruments of geriatric practice

OBJECTIVE: To evaluate the physical ability and psychocognitive status of a population more than 90 years of age with regard to sociodemographic, behavioral, and biomedical variables known to affect functional status in old age.

Preparation method and growth factor content of platelet concentrate influence the osteogenic differentiation of bone marrow stromal cells

BACKGROUND AIMS An extensive debate about the clinical benefits of autologous platelet concentrates used as a treatment option for patients with orthopedic injuries is ongoing. The aim of this study was to determine whether different compositions of platelet concentrates may affect the osteogenic differentiation of bone marrow stromal cells (BMSC). METHODS Pure platelet-rich plasma (P-PRP) and leukocyte-PRP (L-PRP) were characterized for platelet and leukocyte content. As an indicative marker of the delivery of growth factors (GFs), the release of basic fibroblast growth factor (bFGF) from platelet gel (PG) was measured at 1, 18, 48 and 72 h and at 7 d. The ability of different PGs to induce proliferation and differentiation of BMSC was evaluated by using bioactivity assays. RESULTS The platelet recovery was significantly higher in L-PRP, either fresh or frozen. PGs derived from L-PRP and P-PRP showed significant differences in terms of bFGF release and biological activity. bFGF release was faster both in fresh and frozen L-PRP preparations. Moreover, L-PRP samples were able to induce a significantly higher proliferation of BMSC compared with P-PRP or PPP samples. Even though all PG preparations allowed the deposition of mineral nodules in BMSC cultures, the mineralization activity correlated significantly with bFGF levels. CONCLUSIONS The biological activity of platelet concentrates differs according to preparation technique, which affects platelet and leukocyte content and GF availability. Because GF levels are not always optimal in subjects with defective bone healing, composition and bioactivity of PRP should be analyzed to test the reliability and potential effectiveness of the regenerative treatment.

Regular moderate intensity physical activity and blood concentrations of endogenous anabolic hormones and thyroid hormones in aging men

BACKGROUND Physical activity has been reported to affect endocrine function in elderly men. OBJECTIVE To establish an association between regular moderate physical activity and endogenous anabolic hormone levels in healthy aging men. PARTICIPANTS Twenty four middle-aged (57.4+/-4.7 years) and 24 elderly (68.3+/-2.6 years) physically active men who in the past 10 years had been regularly bicycling during leisure time were compared with 24 middle-aged (57.9+/-4.0 years) and 24 elderly (67.2+/-1.7 years) sedentary men. Groups did not differ for body composition. MEASUREMENTS Serum dehydroepiandrosterone sulfate (DHEAS), insulin-like growth factor-I (IGF-1), free testosterone (FT), and thyroid hormone levels were assessed. RESULTS In general, elderly men had lower IGF-1 (P<0.001), DHEAS (P=0.013), and triodothyronine levels (P<0.001) than their middle-aged counterparts. Independently of age, however, physically active men had on average higher IGF-1 (P=0.031), DHEAS (P=0.001), and triodothyronine serum levels (P<0.001) than sedentary men. FT and thyroid stimulating hormone (TSH) serum concentrations did not differ across age groups, but physically active men had lower TSH values than sedentary men (P=0.021). CONCLUSIONS Our results suggest that, in aging men, regular moderate physical activity is associated with higher levels of IGF-1 and DHEAS levels and with thyroid function alterations.

Does Platelet-Rich Plasma Freeze-Thawing Influence Growth Factor Release and Their Effects on Chondrocytes and Synoviocytes?

PRP cryopreservation remains a controversial point. Our purpose was to investigate the effect of freezing/thawing on PRP molecule release, and its effects on the metabolism of chondrocytes and synoviocytes. PRP was prepared from 10 volunteers, and a half volume underwent one freezing/thawing cycle. IL-1β, HGF, PDGF AB/BB, TGF-β1, and VEGF were assayed 1 hour and 7 days after activation. Culture media of chondrocytes and synoviocytes were supplemented with fresh or frozen PRP, and, at 7 days, proliferation, gene expression, and secreted proteins levels were evaluated. Results showed that in the freeze-thawed PRP the immediate and delayed molecule releases were similar or slightly lower than those in fresh PRP. TGF-β1 and PDGF AB/BB concentrations were significantly reduced after freezing both at 1 hour and at 7 days, whereas HGF concentration was significantly lower in frozen PRP at 7 days. In fresh PRP IL-1β and HGF concentrations underwent a significant further increase after 7 days. Similar gene expression was found in chondrocytes cultured with both PRPs, whereas in synoviocytes HGF gene expression was higher in frozen PRP. PRP cryopreservation is a safe procedure, which sufficiently preserves PRP quality and its ability to induce proliferation and the production of ECM components in chondrocytes and synoviocytes.

Platelet-Rich Plasma: The Choice of Activation Method Affects the Release of Bioactive Molecules

Platelet-Rich Plasma (PRP) is a low-cost procedure to deliver high concentrations of autologous growth factors (GFs). Platelet activation is a crucial step that might influence the availability of bioactive molecules and therefore tissue healing. Activation of PRP from ten voluntary healthy males was performed by adding 10% of CaCl2, 10% of autologous thrombin, 10% of a mixture of CaCl2 + thrombin, and 10% of collagen type I. Blood derivatives were incubated for 15 and 30 minutes and 1, 2, and 24 hours and samples were evaluated for the release of VEGF, TGF-β1, PDGF-AB, IL-1β, and TNF-α. PRP activated with CaCl2, thrombin, and CaCl2/thrombin formed clots detected from the 15-minute evaluation, whereas in collagen-type-I-activated samples no clot formation was noticed. Collagen type I produced an overall lower GF release. Thrombin, CaCl2/thrombin, and collagen type I activated PRPs showed an immediate release of PDGF and TGF-β 1 that remained stable over time, whereas VEGF showed an increasing trend from 15 minutes up to 24 hours. CaCl2 induced a progressive release of GFs from 15 minutes and increasing up to 24 hours. The method chosen to activate PRP influences both its physical form and the releasate in terms of GF amount and release kinetic.

Serum levels of fibroblast growth factor 2 in children with orthopedic diseases: Potential role in predicting bone healing

Fibroblast growth factor 2 (FGF‐2) plays an important role in the early phases of bone healing. In this study, we measured FGF‐2 serum levels in 88 children undergoing surgical treatment for congenital (n = 49) or acquired (n = 39) orthopedic conditions, which were associated (n = 35) or not (n = 53) with bone lesions, to assess whether serum levels of FGF‐2 varied according to the underlying disease and may predict clinical outcomes. FGF‐2 serum levels were significantly lower in patients who did not heal after surgery (p = 0.008). Diagnostic accuracy was validated statistically, and the ROC curve provided a threshold value useful in discriminating good versus poor outcomes. The relationship between FGF‐2 and bone healing was supported by in vitro experiments. A mineralization assay was performed on bone marrow stromal cells from three patients with congenital pseudarthrosis, who had low serum levels of FGF‐2 and a poor clinical outcome after surgical treatment. Autologous serum alone was not sufficient to induce in vitro mineralization, but it did occur when cells were cultured with different sources of exogenous growth factors (GFs), including recombinant FGF‐2 and homologous serum collected from children with fractures, high FGF‐2 levels, and a good clinical outcome. In conclusion, our findings suggest that osteoinductive GFs are essential for bone repair, and that the amount of circulating FGF‐2 may predict bone healing.

Dehydroepiandrosterone sulphate and dementia

Summary Animal and human studies suggest that the adrenal androgen dehydroepiandrosterone sulphate (DHEAS) may be related to cognitive function. Aim of this study was to explore the relationships between circulating serum levels of DHEAS and cognitive function in a sample of over 90-year-olds. Thirty-four subjects (7 males, 27 females) aged 91–104 years were recruited in long-stay elderly facilities or at home in Bologna. Each subject received a semi-structured interview assessing medical history in order to exclude as much as possible the influence of medical conditions, pharmacological treatments and nutritional status on DHEAS levels. The diagnosis of dementia was made for 18 subjects according to the guidelines of the American Psychiatric Association. No differences were found between DHEAS concentrations of demented and non-demented subjects (sex and age-adjusted ANOVA F = 2.003, p = 0.168). No significant correlations were found between DHEAS and a number or cognitive testing scores, when adjusting for sex and age. In conclusion, our data do not suggest a causal role of DHEAS in senile dementia. The low DHEAS levels observed by some authors in patients with organic brain syndromes could be an artifact deriving from infectious or debilitating conditions.