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Maria Stella Graziani

Deputy Director
Martina Zaninotto

Associate Editors
Ferruccio Ceriotti
Davide Giavarina
Bruna Lo Sasso
Giampaolo Merlini
Martina Montagnana
Andrea Mosca
Paola Pezzati
Rossella Tomaiuolo
Matteo Vidali

International Advisory Board Khosrow Adeli Canada
Sergio Bernardini Italy
Marcello Ciaccio Italy
Eleftherios Diamandis Canada
Philippe Gillery France
Kjell Grankvist Sweden
Hans Jacobs The Netherlands
Eric Kilpatrick UK
Magdalena Krintus Poland
Giuseppe Lippi Italy
Mario Plebani Italy
Sverre Sandberg Norway
Ana-Maria Simundic Croatia
Tommaso Trenti Italy
Cas Weykamp The Netherlands
Maria Willrich USA
Paul Yip Canada

Biomedia srl
Via L. Temolo 4, 20126 Milano

Responsible Editor
Giuseppe Agosta

Editorial Secretary
Andrea di Bello
Biomedia srl
Via L. Temolo 4, 20126 Milano
Tel. 0245498282


ISSN print: 0393 – 0564
ISSN digital: 0392- 7091

BC: Articoli scritti da L. Agnello

Galectin-3 and Lp(a) plasma concentrations and advanced carotid atherosclerotic plaques: correlation with plaque presence and features
<p>Introduction: atherosclerosis is one of the leading causes of death and morbidity worldwide. It consists in thedevelopment of plaques in the intima media layers of arteries due to lipid accumulation and oxidation, causingmassive inflammation. We aim to better understand the role of Galectin-3 (Gal-3) and Lipoprotein(a) [Lp(a)] aspossible peripheral markers of plaque presence.<br />Methods: Gal-3 and Lp(a) were measured in plasma samples from 99 patients undergoing carotid endarterectomyand 78 healthy controls, by immunometric assays. Plaques were classified histologically, according to the AmericanHeart Association (AHA) guidelines as type Va (fibroatheroma), Vb (mainly calcific) and Vl (complicated lesion).<br />Results: Gal-3 and Lp(a) plasma levels are higher in patients compared to controls [19.8 ng/mL (SD 5.8) vs 14.0ng/mL (3.6)], p&lt;0.0001 and 8.4 mg/dL (IQR 4.0-25.1) vs 4.7 mg/dL (2.4-12.7), p=0.0003, respectively). Analysis ofROC curves confirmed the discriminating power of these markers obtaining an area under the curve of 0.806(p&lt;0.0001) for Gal-3 and 0.657 (p=0.0001) for Lp(a). At multivariate logistic regression, Gal-3 and Lp(a) plasma levelswere associated with plaque presence independently of each other as well as of age, sex, LDL-C levels and previousmyocardial infarction with an odds ratio of 1.22 (95%CI 1.08-1.38, p=0.002) and 1.05 (1.00-1.09, p=0.048)respectively. No differences of Gal-3 and Lp(a) plasma levels were observed among the plaque types.<br />Conclusion: our data showed that Gal-3 and Lp(a) are reliable markers of advanced atherosclerotic plaques. Theabsence of differences among the different lesion types suggests that the increase of Gal-3 and Lp(a) is independentof the specific plaque features.</p>
Biochimica Clinica ; 43(3) 289-295
Contributi Scientifici - Scientific Papers
Un nuovo ruolo del CYP2R1nella sclerosi multipla
A new role of CYP2R1 in multiple sclerosis
<p>Multiple sclerosis (MS) is a neurodegenerative autoimmune disease resulting from a complex interaction of genetic and environmental factors. Among these, vitamin D and genetic variants associated with vitamin D metabolism have gained great attention. The aim of our study was to assess two single nucleotide polymorphisms (SNPs) in CYP2R1 in relation to serum 25-OH-vitamin D3 levels in MS patients and healthy controls. 25-OH-vitamin D3 serum concentrations and genotyping of CYP2R1-SNPs gene were analysed both in MS patients and in healthy controls. In particular, rs10741657 and rs10766197 of CYP2R1 gene were assessed by real-time allelic discrimination Taq-Man assay (Applied Biosystems, Forster City, USA); 25-OH-vitamin D3 serum concentration was measured by a high-performance liquid chromatography (HPLC) method. Statistical analysis was performed by a SPSS software (version 13.0). The analysis of the obtained results showed lower 25-OH-vitamin D3 concentrations in MS patients than in controls. When comparing genotype distribution and allele frequencies of the two selected SNPs between cases and controls, significant differences were observed only for CYP2R1 rs10766197. Minor allele of CYP2R1 rs10766197 (A) was significantly represented in MS patients, demonstrating an association of allele A to MS. Analysis of the CYP2R1 rs10766197 distribution in MS patients showed that patients carrying the genotype AA had a trend of lower levels of 25-OH-vitamin D3 in comparison to those with genotype GG or GA, although not statistically significant. Moreover, after stratifying MS patients according to gender, we found that the minor allele A of rs10766197 in homozygosis was associated with disease progression, assessed by Expanded Disability Status Scale and Multiple Sclerosis Severity Score scores, only in men. Our study demonstrates a role of CYP2R1 in both risk and progression of MS, with sex-related differences</p>
Biochimica Clinica ; 42(4) 294-299
Contributi Scientifici - Scientific Paper
Glycated albumin is correlated to insulin resistance and β-cell secretory function in subjects at risk of developing diabetes
<p>Insulin resistance and &beta;-cell secretory function represent two main issues in the pathogenesis of type 2 diabetes mellitus (T2DM). Conflicting results have been obtained about the association between glycated albumin (GA) and body mass index (BMI), insulin resistance and &beta;-cell function in diabetic patients. Actually, the relationship (if any) between GA and the markers of glucose homeostasis and insulin resistance in subjects at risk of developing diabetes, has not been completely elucidated yet. Two hundred and one patients undergoing to oral glucose tolerance test (OGTT) were enrolled in the study. Routine laboratory tests, including fasting insulin, were performed at enrollment. GA was measured on plasma-EDTA by quantILab<sup>&reg;</sup> Glycated Albumin (Instrumentation Laboratory, A Werfen Company) on ILab Taurus analyzer. According to the plasma glucose concentration measured after 2 hours of glucose intake (2h- PG), 13 subjects (6.4%) were classified as impaired glucose tolerance (IGT). GA weakly correlated with fasting plasma glucose (FPG) (r=0.21; P=0.002), with HbA1c (r=0.16; P=0.024) but not with 2h-PG (P=0.7). GA, but not HbA1c, was negatively correlated to HOmeostasis Model Assessment for &beta; cell fuction (HOMA-&beta;) (r<sup>2</sup>=0.23; P&lt;0.001), to HOMA for insulin resistence (HOMA-IR) (r<sup>2</sup>=0.15; P&lt;0.0001) and to BMI (r<sup>2</sup>=0.05; P=0.001). In a stepwise multivariate regression analysis including HbA1c, HOMA-&beta;, plasma albumin, BMI, eGFR, age, FPG, and HOMA-IR as predictors of GA, only HbA1c (&beta;-coefficient: 0.04; P=0.038) and HOMA-&beta; (&beta;-coefficient: -0.01; P&lt;0.0001) were able to predict GA levels (r<sup>2</sup>=0.26; P&lt;0.001 for the model). Our results demonstrated that GA was associated to HOMA-&beta; and, to a lesser extent, to HOMA-IR and BMI. The increase of GA values can be explained by the reduction of &beta;-cell secretory function in subjects with no significant increase of FPG and 2h-PG.</p>
Biochimica Clinica ; 42(3) 234-239
Contributi Scientifici - Scientific papers
Incremento acuto di troponina I in assenza di malattia coronarica ostruttiva: un caso di sindrome di Takotsubo
Acute troponin I increase in absence of obstructive coronary disease: a case of Takotsubo syndrome
C. Bellia  |  B. Lo Sasso  |  L. Agnello  |  G. Bivona  |  G. Novo  |  M. Ciaccio  | 
<p>A 66-year-old woman was admitted to the Emergency Department of Policlinico P. Giaccone, in Palermo, for nonradiating chest pain that occurred after an emotional stress. Her medical history included a positive family history for cardiovascular disease, arterial hypertension, gastro-esophageal reflux disease, and anxiety-depressive syndrome. Upon admission, the electrocardiogram showed diffuse ST-T abnormalities with an elevation of the ST segment; Troponin I was 3790 ng/L, creatine phosphokinase was 374 U/L, which became normal within 48 hours. No evidence of significant coronary artery stenosis was detected on the angiography. The echocardiogram showed apical akinesia and hyperkinesia of the basal segments of left ventricle, with moderately impaired ventricular function (Left Ventricular Ejection Fraction, LVEF=43%). Cardiac magnetic resonance imaging ruled out myocarditis and confirmed the diagnosis of Takotsubo cardiomyopathy. Supportive therapy with Angiotensin Converting Enzyme inhibitors, spironolactone and acetylsalicylic acid was initiated. After 30 days, the echocardiogram showed a complete recovery of left ventricular function. Takotsubo syndrome was diagnosed based on instrumental, clinical and biochemical findings.</p>
Biochimica Clinica ; 41(3) e19-e21
Casi clinici - Case report
Polimorfismo I/D del gene per l’enzima di conversione dell’angiotensina (ACE): gene della longevità o fattore di rischio nella patologia ipertensiva?
Polymorphism of the angiotensin converting enzyme gene: longevity gene or risk factor in hypertensive disease?
<p>In recent decades, the increase in life expectancy stimulated the study of aging processes and the search for&nbsp;candidate genes involved in longevity. The angiotensin converting enzyme (ACE), present in all endothelial cells, plays&nbsp;an essential role in maintaining the homeostasis of blood flow by regulating the production of the vasoconstrictor&nbsp;angiotensin II and inactivating the bradykinin. Some studies reported a possible association between the polymorphism&nbsp;I/D of ACE gene and either hypertension and longevity. The present study was aimed to confirm these data. We studied&nbsp;two large cohorts of nonagenarians and centenarians. One was from Sardinia (200 subjects, 88 males, mean age: 96&nbsp;years) and their data were compared to a group of 222 subjects (106 males, mean age: 44 years) from the general&nbsp;population of the same geographic area. The latter group of longeve subjects (161 subjects, 71 males, mean age: 97&nbsp;years) was from Southern Italy. Furthermore, we studied 146 hypertensive patients (98 males, mean age: 51 years) and&nbsp;172 normotensive subjects (86 males, mean age: 33 years) from Southern Italy. The ACE I/D polymorphism was typed&nbsp;by polymerase chain reaction; the amplified 490 bp (allele I) and 190 bp (allele D) were visualized on 2% agarose gel.&nbsp;Hypertensive subjects had a significantly different distribution of ACE genotypes as compared to normotensive ones&nbsp;(P=0.001) and a higher frequency of the D/D genotype. Long-lived subjects from Sardinia showed a significantly different&nbsp;distribution of ACE genotypes as compared to subjects from the general population of the same geographic area (P&nbsp;&lt;0.001), to long-lived subjects from Southern Italy (P &lt;0.001), to hypertensive patients (P=0.011) and to normotensive&nbsp;subjects from Southern Italy (P &lt;0.001). Surprisingly, they had the highest frequency of the D/D genotype among the&nbsp;compared groups. Our study indicates that: i) centenarians of different ethnic origin have a different genetic background,&nbsp;ii) there is a possible association between longevity and allelic variants of ACE, even if only in specific ethnic groups (i.e.,&nbsp;Sardinian) and iii) ACE polymorphisms are a predisposing factor to hypertension.</p>
Biochimica Clinica ; 37(6) 461-464
Contributi scientifici - Scientific papers