Papers by Giovanni Lombardi
Muscle traction and bone metabolism are functionally linked and co-regulated by a series of facto... more Muscle traction and bone metabolism are functionally linked and co-regulated by a series of factors. Although a role for steroid hormones was hypothesized, a clear definition of the bone–muscle interconnection still lacks. To investigate this relationship, we studied bone metabolism, muscle activity, and salivary steroid hormones profile in relation with the physical effort across a cycling stage race, a model of effort in absence of load. Nine pro-cyclists were recruited; body weight and power output/energy expenditure were recorded. Diet was kept constant. Saliva was collected at days −1, 4, 8, 12, 14, 19, and 23; blood and urine were collected at days −1, 12, and 23. Salivary steroid hormones [cortisol, dehydroepiandrosterone (DHEA), testosterone, and estradiol], serum lactate dehydrogenase (LDH), aspar-tate aminotransferase (AST) and creatine kinase (CK) activities, plasma sclerostin, and urinary calcium and phosphorous were measured. Cortisol remained constant , testosterone decreased at day 4, and estradiol and DHEA firstly increased and then returned to basal levels. Hormone concentrations were not correlated with plasma volume shifts. LDH, CK, AST, sclerostin, and urinary calcium and phosphorous increased. DHEA and estradiol correlated with the physical effort and the bone-muscular markers. A relationship between muscle activity, in absence of load, and bone resorption emerged under a putative regulation by DHEA and estradiol.
Myokines are likely to be involved in the whole-body metabolic adaptive changes that occur in res... more Myokines are likely to be involved in the whole-body metabolic adaptive changes that occur in response to regular exercise. We aimed to investigate the association of the two myokines (adropin and apelin) with physical performance in professional soccer players. To this purpose, we analyzed the fluctuations of circulating levels of both adropin and apelin in professional soccer players during a season and evaluated the possible association of these myokines with the performance level. Creatine kinase (CK) and lactate dehydrogenase (LDH) activity as well as iron, transferrin and high-sensitivity C-Reactive protein (hsCRP), ferritin, soluble transferrin receptor (sTfR), free testosterone/cortisol ratio (FTCR), total iron binding capacity (TIBC) were also determined. Fifteen male professional soccer players from an Italian Serie A team were included in this study. Regarding the results of the biochemical analyses, the patterns of changes in the biomarkers of fatigue and inflammation, i.e., HsCRP, CK and LDH reflected the effects of the training throughout the season. No significant changes were observed in adropin, while apelin exhibited variations that seem not to be related with performance. In addition, both adropin and apelin did not represent valuable strategy to assist in the performance assessment of professional soccer players.
Osteocalcin (OC) is the main non-collagenous hydroxyapatite-binding protein synthesized by osteob... more Osteocalcin (OC) is the main non-collagenous hydroxyapatite-binding protein synthesized by osteoblasts, odontoblasts, and hypertrophic chondrocytes. It has a regulatory role in mineralization and it is considered a marker of bone cell metabolism. Recent findings evidenced new extra-skeletal roles for OC, depicting it as a real hormone. OC shares many functional features with the common hormones, such as tissue-specific expression, circadian rhythm, and synthesis as a pre-pro-molecule. However, it has some peculiar features making it a unique molecule: OC exists in different forms based on the degree of carboxylation. Indeed, OC has three glutamic acid residues, in position 17, 21, and 24, which are subject to c-carboxylation, through the action of a vitamin K-dependent c-glutamyl carboxytransferase. The degree of carboxylation, and thus the negative charge density, determines the affinity for the calcium ions deposited in the extracellular matrix of the bone. The modulation of the carboxylation could, thus, represent the mechanism by which the body controls the circulating levels, and hence the hormonal function, of OC. There are evidences linking OC, and the bone metabolism, with a series of endocrine (glucose metabolism, energy metabolism, fertility) physiological (muscle activity) and pathological functions (ectopic calcification). Aim of this review is to give a full overview of the physiological roles of OC by collecting the newest experimental findings on this intriguing molecule.
Muscular damage, consequent to strenuous activities, could exceed the recovery potential of muscl... more Muscular damage, consequent to strenuous activities, could exceed the recovery potential of muscles and determine renal failure. Whole body cryostimulation is a cold-based therapy used to improve recovery or overcome fatigue symptoms. This study aimed to evaluate the effects of repeated sessions of cryostimulation on muscle damage, renal function, and their relationship. Serum samples, from 27 elite rugby players, under training, before and after 2 sessions/day of cryotherapy over 7 days, were tested for markers of muscular (creatine kinase, lactate dehydrogenase, and aspartate aminotransferase) and renal (creatinine, cystatin C) functions. eGFR was calculated with two formulas based on either serum creatinine concentration (MDRD) or serum creatinine and cystatin C concentrations (creatinine/cystatin C CKD EPI). Pre-and posttreatment differences were determined by Wilcoxon's test; correlations were evaluated with Spearman's test. Cryostimulation helped muscular recovery (increased lactate dehydrogenase activity (í µí± < 0.001) and the stabile creatine kinase and aspartate aminotransferase activities). Creatinine was unaffected while cystatin C was increased (í µí± = 0.013). Creatinine-based eGFR was not affected by cryostimulation, while creatinine/cystatin C-based eGFR showed a slight decrease (í µí± = 0.015). eGFR and muscular biomarkers were not correlated, suggesting a real recovery effect of cryotherapy. Cystatin C seemed more sensible than creatinine in evaluating the kidney function.
Background. Intense training can lead to a pathophysiological change in serum concentration of a ... more Background. Intense training can lead to a pathophysiological change in serum concentration of a variety of biomarkers. Traditional biomarkers of cardiac injury are very useful in monitoring CVD patients, but in healthy subjects or athletes they cannot be informative enough about the cardiovascular risk, because in these cases their serum levels do not increase over the pathological limit. Therefore novel cardiovascular biomarkers are required in order to allow a better monitoring of sport performance, prediction of overtraining and diagnosis of sport-related cardiac injuries. Growth differentiation factor-15 (GDF-15) is emerging as a powerful cardiovascular injury risk indicator. In this study we investigate the effect of intense physical training of on the circulating levels of GDF-15 in rugby professional players. Methods. Serum GDF-15, Erythropoietin, IL-6, the cardiovascular parameter ST-2, NT-proBNP and routine hematological parameters were measured in a group of 30 rugby players before and after a session of intense training. Results. While ST-2, IL-6 and hsCRP displayed no signifi cant changes after intense training, NT-proBNP and GDF-15 showed a signifi cant increase, even without reaching the pathological level. Discussion. The measure of GDF-15 in professional rugby players could be a useful tool to monitoring their cardiovascular status during training and competition session in order to prevent the onset of collateral cardiovascular adverse event due to the intense training and, in the case of cardiac injury, it could possibly allow a very early diagnosis at the beginning of the pathogenic process.
Despite a wide number of studies performed on the general population, little is known about the V... more Despite a wide number of studies performed on the general population, little is known about the Vitamin D status of athletes. A particular influence of many factors, including skin pigmentation, early-or late-day training, indoor training, geographic location and extensive sunscreen use, has been observed in this specific population. The need of supplementation with Vitamin D in athletes is not defined or, when supplementation is needed, even the optimal amount of Vitamin D to be used is not specified. The periodic measurement of Vitamin D is the only procedure capable to define athletes' status. Although various methods for the measurement of Vitamin D are routinely used, they often give discordant and poorly reproducible results; thus, it is necessary to standardize the various methods, in order to have comparable results. In conclusion, current available data indicate both that little is known about the Vitamin D status of athletes and that is still unclear if supplementation could be desirable. Finally, it must be pointed out that all the papers about Vitamin D status should indicate in detail the method used for really allowing a correct interpretation of data.
Reticulocytes are young red blood cells which develop from erythroblasts and circulate in the blo... more Reticulocytes are young red blood cells which develop from erythroblasts and circulate in the bloodstream for about 1-4 days before maturing into erythrocytes. With the introduction of reticulocyte count in equations and statistical models for detecting suspected blood doping, its application to sports medicine has attracted growing interest in reticulocyte behavior during training and competition seasons in athletes and experimental blood doping treatment in healthy volunteers. An update on recent publications is therefore needed to improve the interpretation of reticulocyte analysis and its variability in sportsmen.
Calcium and phosphate are essential for cell functions, and their serum concentrations result fro... more Calcium and phosphate are essential for cell functions, and their serum concentrations result from the balance between intestinal absorption, bony storage, and urinary excretion. Fibroblast growth factor 23 (FGF23), expressed by osteocytes and osteoblasts, acts in the kidney, leading to hypophosphatemia and low 1,25-dihydroxycholecalciferol synthesis, but suppresses par-athyroid function. The aim of this study was to explore the effects of a high-energy demanding cycling race on this bone–kidney–parathyroid axis. We studied nine cyclists during the 2011 Giro d'Italia stage race. Pre-analytical and analytical phases followed academic and anti-doping recommendations. Serum parathyroid hormone (PTH), 25(OH)D, total calcium, inorganic phosphorus , and plasma FGF23 were measured on days-1, 12, and 22 and corrected for changes in plasma volume. Dietary calcium and phosphorus, anthropometric parameters (height, weight, and body mass index) and indexes of metabolic effort (net energy expenditure, power output) were recorded. Dietary calcium and phosphorus intakes were kept at the same levels throughout the race. Twenty-five (OH)D, PTH, and calcium concentrations remained stable. FGF23 increased 50% with a positive correlation with the indexes of metabolic effort and, consequently, phosphorous decreased, although only in the first half. The strong metabolic effort acts on the bone–kidney– parathyroid system, and the rise in FGF23 plasma concentration might be aimed at maintaining calcium and phosphorus homeostasis.
Cold-based therapies are commonly applied to alleviate pain symptoms secondary to inflammatory di... more Cold-based therapies are commonly applied to alleviate pain symptoms secondary to inflammatory diseases, but also to treat injuries or overuse, as done in sports rehabilitation. Whole body cryotherapy, a relatively new form of cold therapy, consists of short whole-body exposure to extremely cold air (2110uC to 2140uC). Cryostimulation is gaining wider acceptance as an effective part of physical therapy to accelerate muscle recovery in rugby players. The aim of this study was to evaluate the effect of repeated cryostimulation sessions on the hematological profile and martial status markers in professional rugby players. Twenty-seven professional rugby players received 2 daily cryostimulation treatments for 7 consecutive days. Blood samples were collected before and after administration of the cryotherapic protocol and hematological profiles were obtained. No changes in the leukocyte count or composition were seen. There was a decrease in the values for erythrocytes, hematocrit, hemoglobin and mean corpuscular hemoglobin content, and an increase in mean corpuscular volume and red cell distribution width. Platelet count and mean volume remained unchanged. Serum transferrin and ferritin decreased, while soluble transferrin receptor increased. Serum iron and transferrin saturation were unchanged, as was reticulocyte count, whereas the immature reticulocyte fraction decreased substantially. In conclusion, in this sample of professional rugby players, cryostimulation modified the hematological profile, with a reduction in erythrocyte count and hemoglobinization paralleled by a change in martial status markers.
Fibromyalgia is a chronic widespread pain disorder in which, the neurogenic origin of the pain, f... more Fibromyalgia is a chronic widespread pain disorder in which, the neurogenic origin of the pain, featured by allodynia and hyperalgesia, results from an imbalance in the levels of neurotransmitters and consequently of the peripheral pro-and anti-inflammatory mediators. Whole body cryotherapy is a peculiar physical therapy known to relieve pain and inflam-matory symptoms characteristics of rheumatic diseases, through the regulation of the cytokine expression. The aim of this study was to qualitatively evaluate the effects of cryotherapy on the clinical output of fibromyalgic patients. A total of 100 fibromyalgic patients (age range 17–70 years) were observed; 50 subjects were addressed to cryotherapy, while the second group (n=50) did not underwent to the cryotherapic treatment. All subjects kept the prescribed pharmacological therapy during the study (analgesic and antioxidants). The referred health status pre-and post-observation was evaluated with the following scales: Visual Analogue Scale, Short Form-36, Global Health Status and Fatigue Severity Scale. Fibromyalgic patients treated with cryotherapy reported a more pronounced improvement of the quality of life, in comparison with the non-cryo treated fibromyalgic subjects, as indicated by the scores of the qualitative indexes and sub-indexes, that are widely recognized tools to assess the overall health status and the effect of the treatments. We speculate that this improvement is due to the known direct effect of cryotherapy on the balance between pro-and anti-inflammatory mediators having a recognized role in the modulation of pain.
Background: Osteopontin is a glycoprotein widely expressed in many tissues and in different physi... more Background: Osteopontin is a glycoprotein widely expressed in many tissues and in different physiological conditions. Osteopontin concentrations are usually measured through immunological methods; however, little is known about the pre-analytical management of the sample. We evaluated the effects of different times and temperatures storage conditions on serum and plasma concentrations of osteopontin. Methods: Serum and plasma aliquots were frozen at – 80 ° C, following storage at 4 ° C or room temperature for 0, 2, 4, 8, 12, 24 and 48 h. Osteopontin concentrations were determined by enzymoimmunometric assay. Serum samples obtained from tubes with or without gel separator were compared to verify the effect of gel. Western blotting analysis was performed to characterize the antibody. Results: Osteopontin concentrations were stable over time in all conditions in both serum and plasma. Plasma showed 3.8 – 4.8-fold higher concentrations than serum. Comparable levels were found between serum tubes with or without gel separator and always lower than those in plasma, demonstrating no effect of gel in serum tubes. Western blotting analysis showed various osteopontin bands, indicating that the antibody recognizes the entire panel of different osteopontin forms. Conclusions: We demonstrated the stability across 48 h of osteopontin in serum and plasma at either room temperature or 4 ° C, when the evaluation is carried out by an immune-based method. The minimal variations observed over time were always lower than the calculated intra-and inter-assay coeffi cients of variation. Plasma specimens should be preferred when osteopontin concentration are assayed by immu-nological methods.
Background: Haematological assessment is crucial for evaluating athletes healthy status. Professi... more Background: Haematological assessment is crucial for evaluating athletes healthy status. Professional athletes experience physiological modifi cations during competitions and over a season: the risk of sports anaemia is high. Few descriptions of haematological parameters behaviour during a 3-weeks cycling stage race have been published. Methods: We studied nine professional cyclists engaged in the 2011 Giro d ' Italia stage race. Pre-analytical and analytical phases tightly followed academic and anti-doping authorities ' recommendations. Haematological and iron metabolism parameters were measured days −1 (pre-race), 12 and 22 during the race. Results: Haemoglobin, red blood cells and haematocrit decreased during the race with a stabilisation in the second half, but fi nal values were lower than baseline. Reticulocytes did not modify, whilst the immature reticulocyte fraction increased. No differences were found in red blood cells volume and corpuscular haemoglobin content, neither in iron metabolism markers. The acute phase proteins, haptoglobin and C-reactive protein, both increased over the race, while haemoglobin and haptoglobin were inversely related. Conclusions: These data are important for improving the knowledge of physiological modifi cations in haematological and iron metabolism parameters of professional athletes during highly demanding competitions. This is the fi rst report, in the ambit of a stage race, in which the pre-analytical phase standardisation has been applied.
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Papers by Giovanni Lombardi