Massimiliano Marco Corsi Romanelli

Matrix metalloproteinases as biomarkers of disease: updates and new insights.

Abstract Matrix metalloproteinases (MMPs) play a pivotal role in remodeling the extracellular matrix (ECM) and are therefore of interest for new diagnostic tools for the clinical management of diseases involving ECM disruption. This setting ranges from the classical areas of MMP studies, such as vascular disease, cancer progression or bone disorders, to new emerging fields of application, such as neurodegenerative disease or sepsis. Increasing the knowledge about the role of MMPs in the pathogenesis of diseases where a clear diagnostic panel is still lacking could provide new insight and improve the identification and the clinical treatment of these human diseases. This review focuses on the latest descriptions of the clinical use of MMP as biomarkers in the diagnosis, prognosis and monitoring of different diseases, such as diabetes, cardiovascular diseases, cancer and metastasis, neurodegenerative disorders and sepsis.

Vitamin D and Erectile Dysfunction

INTRODUCTION Endothelial dysfunction has been demonstrated to play an important role in pathogenesis of erectile dysfunction (ED) and vitamin D deficiency is deemed to promote endothelial dysfunctions. AIM To evaluate the status of serum vitamin D in a group of patients with ED. METHODS Diagnosis and severity of ED was based on the IIEF-5 and its aetiology was classified as arteriogenic (A-ED), borderline (BL-ED), and non-arteriogenic (NA-ED) with penile-echo-color-Doppler in basal condition and after intracaversous injection of prostaglandin E1. Serum vitamin D and intact PTH concentrations were measured. MAIN OUTCOME MEASURES Vitamin D levels of men with A-ED were compared with those of male with BL-ED and NA-ED. RESULTS Fifty patients were classified as A-ED, 28 as ED-BL and 65 as NA-ED, for a total of 143 cases. Mean vitamin D level was 21.3 ng/mL; vitamin D deficiency (<20 ng/mL) was present in 45.9% and only 20.2% had optimal vitamin D levels. Patients with severe/complete-ED had vitamin D level significantly lower (P = 0.02) than those with mild-ED. Vitamin level was negatively correlated with PTH and the correlation was more marked in subjects with vitamin D deficiency. Vitamin D deficiency in A-ED was significantly lower (P = 0.01) than in NA-ED patients. Penile-echo-color-Doppler revealed that A-ED (PSV ≤ 25 cm/second) was more frequent in those with vitamin D deficiency as compared with those with vitamin >20 ng/dL (45% vs. 24%; P < 0.05) and in the same population median PSV values were lower (26 vs. 38; P < 0.001) in vitamin D subjects. CONCLUSION Our study shows that a significant proportion of ED patients have a vitamin D deficiency and that this condition is more frequent in patients with the arteriogenic etiology. Low levels of vitamin D might increase the ED risk by promoting endothelial dysfunction. Men with ED should be analyzed for vitamin D levels and particularly to A-ED patients with a low level a vitamin D supplementation is suggested.

Interleukin-15 and Soluble Interleukin-15 Receptor α in Coronary Artery Disease Patients: Association with Epicardial Fat and Indices of Adipose Tissue Distribution

Interleukin-15 (IL-15) is a pro-inflammatory cytokine which signals via a specific alpha receptor subunit (IL-15Rα). Increased IL-15 level has been observed in cardiovascular patients and IL-15 immunoreactivity has been detected at vulnerable atherosclerotic plaques. Due to the association between adipose tissue distribution, inflammation and coronary artery disease (CAD), we quantified IL-15 and IL-15Rα in CAD patients with different adiposity and adipose tissue distribution and we evaluated whether epicardial adipose tissue (EAT), a visceral fat depot surrounding and infiltrating myocardium, may be a source of both molecules. IL-15 and IL-15Rα proteins were quantified by enzyme-linked immunosorbent assays. Gene expression of IL-15 and IL-15Rα in EAT depots was evaluated by one colour microarray platform. EAT thickness was measured by echocardiography. Plasmatic IL-15 and IL-15Rα levels were higher in CAD than non-CAD patients. After classification according to adipose tissue distribution, IL-15 was higher in CAD patients with increased abdominal adiposity. Increased level of IL-15Rα was observed both in CAD and non-CAD patients with increased abdominal fat. EAT was a source of IL-15 and IL-15Rα and their expression was higher in CAD patients with increased EAT thickness. In conclusion, our data suggest that circulating levels of IL-15 and IL-15Rα seem to reflect visceral distribution of adipose tissue and that EAT may be a potential source of both IL-15 and IL-15Rα. Future studies on the relationship between IL-15, visceral fat and characteristics of atherosclerotic plaques could help to better understand the complex biology of this cytokine.

Glycated albumin: from biochemistry and laboratory medicine to clinical practice

This review summarizes current knowledge about glycated albumin. We review the changes induced by glycation on the properties of albumin, the pathological implications of high glycated albumin levels, glycated albumin quantification methods, and the use of glycated albumin as a complementary biomarker for diabetes mellitus diagnosis and monitoring and for dealing with long-term complications. The advantages and limits of this biomarker in different clinical settings are also discussed.

Toll-Like Receptor 2 in Serum: a Potential Diagnostic Marker of Prosthetic Joint Infection?

ABSTRACT Prosthetic joint infection (PJI) is a severe complication of arthroplasty and is still lacking diagnostic gold standards. PJI patients display high Toll-like receptor 2 (TLR2) serum levels, correlating with canonical inflammatory markers (C-reactive protein [CRP], interleukin 6 [IL-6], tumor necrosis factor alpha [TNF-α], and IL-1). Therefore, TLR2 serum levels could be considered a new potential diagnostic tool in the early detection of PJI.

Irisin: A Potential Link between Physical Exercise and Metabolism—An Observational Study in Differently Trained Subjects, from Elite Athletes to Sedentary People

We compared irisin levels among groups of differently trained healthy individuals to explore the role of irisin as a physiological linker between exercise and metabolic health. Irisin and biochemical parameters of glucose and lipid metabolism were assessed in 70 healthy volunteers stratified for sport performance level into four groups: (1) 20 elite athletes of national level, (2) 20 subelite athletes of local level, (3) 20 recreational athletes, and (4) 10 sedentary subjects. All biochemical parameters were within the ranges of normality. Fasting glucose, HOMA-IR, and total cholesterol levels were inversely related to the degree of physical activity. HbA1c was higher in elite athletes compared to all the other groups (p < 0.01). A U-shaped relation between free fatty acids and the degree of physical activity was observed. All groups showed similar plasma irisin levels. After correction for the degree of insulin resistance (irisin/HOMA-IR), elite athletes showed higher levels compared to sedentary and recreational subjects (p < 0.01 and p < 0.05, resp.). In addition, the number of metabolic parameters correlated with irisin increased at increasing the training status. Our study suggests a correlation between sport performance, insulin sensitivity, and irisin levels. Irisin may be one potential mediator of the beneficial effects of exercise on metabolic profile.

Bone remodelling biomarkers after whole body cryotherapy (WBC) in elite rugby players

Whole body cryotherapy (WBC) consists of a brief exposure to extreme cold air (-110°C) in a controlled chamber and it is applied in sports medicine to improve recovery from musculoskeletal trauma. The aim of this study is to better define the beneficial effect of WCB on the musculoskeletal system of athletes, in particular on bone remodelling. Remodelling osteoimmunological biomarkers OPG, RANKL and RANK were measured after WBC treatment in 10 male rugby players randomly selected from the Italian National team. OPG levels were increased significantly, supporting the view that WBC induces an osteogenic effect. Further studies evaluating the effect of WBC on bone metabolism are desirable.

Soluble urokinase-type plasminogen activator receptor (suPAR) as new biomarker of the prosthetic joint infection: Correlation with inflammatory cytokines

Post-operative prosthetic joint infection (PJI) is the most common cause of failure of total joint arthroplasty, requiring revision surgery, but a gold standard for the diagnosis and the treatment of PIJ is still lacking. PJI is mainly due to Gram-positive bacteria, in particular, Staphylococcus Aureus, and more rarely by Gram-negative bacteria such as Pseudomonas. This study aimed to examine the diagnostic value of SuPAR in post-operative PJI, in order to explore the possible application of this new biomarker in the early diagnosis of PJI. The level of SuPAR has been measured in PJI patients and healthy controls, correlated with canonical inflammatory markers, such as C-reactive protein, IL-6, IL-1 and TNFα and the chemokine CCL2. Serum suPAR displayed a strongly significative increase in PJI patients compared to not infected controls, and a significative positive correlation with C-reactive protein, IL-6, IL-1 and TNFα and the chemokine CCL2. Also serum CCL2 showed statistically significative increase in PJI patients, and it displayed a strong positive correlation with serum suPAR. This study provides a clear indication of the diagnostic potential of suPAR, in association to routine inflammatory parameters such as CRP, in the diagnosis of PJI.

Procoagulatory State in Inflammatory Bowel Diseases Is Promoted by Impaired Intestinal Barrier Function

Inflammatory and immune mediated disorders are risk factors for arterial and venous thromboembolism. Inflammatory bowel diseases (IBD) confer an even greater risk of thromboembolic events than other inflammatory conditions. It has been shown that IBD patients display defective intestinal barrier functions. Thus, pathogen-associated molecular patterns (PAMPs) coming from the intestinal bacterial burden might reach systemic circulation and activate innate immunity receptors on endothelial cells and platelets, promoting a procoagulative state. Aim of the study was to test this hypothesis, correlating the presence of circulating PAMPs with the activation of innate immune system and the activation of the coagulatory cascade in IBD patients. Specifically, we studied lipopolysaccharide (LPS), Toll-like receptor (TLR) 2, TLR4, and markers of activated coagulation (i.e., D-Dimer and prothrombin fragment F1+2) in the serum and plasma of IBD patients. We found that LPS levels are increased in IBD and correlate with TLR4 concentrations; although a mild correlation between LPS and CRP levels was detected, clinical disease activity does not appear to influence circulating LPS. Instead, serum LPS correlates with both D-Dimer and F1+2 measurements. Taken together, our data support the role of an impairment of intestinal barrier in triggering the activation of the coagulatory cascade in IBD.

Acute exercise in elite rugby players increases the circulating level of the cardiovascular biomarker GDF-15

Abstract 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 significant changes after intense training, NT-proBNP and GDF-15 showed a significant 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.