Publications by authors named "Concetta Scazzone"

40 Publications

Preliminary reference intervals of Glycated Albumin in healthy Caucasian pregnant women.

Clin Chim Acta 2021 Aug 12;519:227-230. Epub 2021 May 12.

Institute of Clinical Biochemistry, Clinical Molecular Medicine and Laboratory Medicine, Department of Biomedicine, Neurosciences and Advanced Diagnostics, University of Palermo, Palermo, Italy; Department of Laboratory Medicine, University Hospital "P. Giaccone", Palermo, Italy. Electronic address:

Background And Aims: Glycated albumin (GA) could represent a useful biomarker in pregnant women for diagnosing and monitoring gestational diabetes mellitus (GDM). The establishment of reference intervals (RI) is mandatory before assessing its clinical usefulness. The RIs of GA in healthy pregnant women are not well defined. The aim of the current study was to establish the RI in a cohort consisting of Caucasian pregnant women without overt diabetes mellitus or gestational diabetes mellitus.

Methods: The study included 183 healthy pregnant women. GA was measured on plasma by an enzymatic method (quantILab Glycated Albumin, IL Werfen, Germany). The RI was calculated by the non-parametric and robust methods.

Results: The RI of GA in the whole population was 10.16% (90%CI 9.60-10.70) and 15.44% (90%CI 14.90-16.90). GA levels decreased during pregnancy, with lower levels in the third trimester: 10.11 (90%CI 9.48-10.79) and 15.72 (90%CI 15.15-16.27) in the first trimester, 10.49 (90%CI 10.05-10.96) and 15.49 (90%CI 15.05-15.92) in the second trimester, 9.84 (90%CI 9.50-10.22) and 14.57 (90%CI 14.11-15.01) in the third trimester. Finally, a weak negative correlation was found between GA levels and body mass index.

Conclusion: This is the first study establishing the RIs of GA in Caucasian healthy pregnant women.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.cca.2021.05.009DOI Listing
August 2021

Clinical Utility of Midregional Proadrenomedullin in Patients with COVID-19.

Lab Med 2021 Apr 30. Epub 2021 Apr 30.

Department of Biomedicine, Neurosciences and Advanced Diagnostics, Institute of Clinical Biochemistry, Clinical Molecular Medicine and Laboratory Medicine, University of Palermo, Palermo, Italy.

Objective: The aim of the study was to assess the role of midregional proadrenomedullin (MR-proADM) in patients with COVID-19.

Methods: We included 110 patients hospitalized for COVID-19. Biochemical biomarkers, including MR-proADM, were measured at admission. The association of plasma MR-proADM levels with COVID-19 severity, defined as a requirement for mechanical ventilation or in-hospital mortality, was evaluated.

Results: Patients showed increased levels of MR-proADM. In addition, MR-proADM was higher in patients who died during hospitalization than in patients who survived (median, 2.59 nmol/L; interquartile range, 2.3-2.95 vs median, 0.82 nmol/L; interquartile range, 0.57-1.03; P <.0001). Receiver operating characteristic curve analysis showed good accuracy of MR-proADM for predicting mortality. A MR-proADM value of 1.73 nmol/L was established as the best cutoff value, with 90% sensitivity and 95% specificity (P <.0001).

Conclusion: We found that MR-proADM could represent a prognostic biomarker of COVID-19.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/labmed/lmab032DOI Listing
April 2021

A new tool for sepsis screening in the Emergency Department.

Clin Chem Lab Med 2021 Apr 13. Epub 2021 Apr 13.

Department of Biomedicine, Neurosciences and Advanced Diagnostics, Institute of Clinical Biochemistry, Clinical Molecular Medicine and Laboratory Medicine, University of Palermo, Palermo, Italy.

Objectives: In this study, we developed and evaluated the diagnostic accuracy of the Sepsis Index for early sepsis screening in the Emergency Department (ED).

Methods: Sepsis Index is based on the combination of monocyte distribution width (MDW) and mean monocyte volume (MMV). Sepsis Index≥1 was selected to define sepsis. We tested its diagnostic accuracy in an ED population stratified in four groups: controls, Systemic Inflammatory Response Syndrome (SIRS), infection, and sepsis, according to Sepsis-2 criteria.

Results: Patients with sepsis displayed higher median Sepsis Index value than patients without sepsis. At the receiver operating characterictis (ROC) curve analysis for the prediction of sepsis, the area under the curve (AUC) of MDW and Sepsis Index were similar: 0.966 (95%CI 0.947-0.984), and 0.964 (95%CI 0.942-0.985), respectively. Sepsis Index showed increased specificity than MDW (94.7 vs. 90.6%), without any decrease in sensitivity (92.0%). Additionally, LR+ increased from 9.8 (MDW) to 17.4 (Sepsis Index), without any substantial change in LR- (respectively 0.09 vs. 0.08). Finally, PPV increased from 0.286 (MDW) to 0.420 (Sepsis Index).

Conclusions: Sepsis Index improves the diagnostic accuracy of MDW alone for sepsis screening.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1515/cclm-2021-0208DOI Listing
April 2021

FOXP3 and GATA3 Polymorphisms, Vitamin D3 and Multiple Sclerosis.

Brain Sci 2021 Mar 25;11(4). Epub 2021 Mar 25.

Department of Biomedicine, Neurosciences and Advanced Diagnostics, Institute of Clinical Biochemistry, Clinical Molecular Medicine and Laboratory Medicine, University of Palermo, 90127 Palermo, Italy.

Background: Regulatory T cells (Tregs) alterations have been implicated in the pathogenesis of Multiple Sclerosis (MS). Recently, a crucial role of the X-Linked Forkhead Box P3 (FoxP3) for the development and the stability of Tregs has emerged, and FOXP3 gene polymorphisms have been associated with the susceptibility to autoimmune diseases. The expression of Foxp3 in Tregs is regulated by the transcription factor GATA binding-protein 3 (GATA3) and vitamin D. The aim of this retrospective case-control study was to investigate the potential association between FOXP3 and GATA3 genetic variants, Vitamin D, and MS risk.

Methods: We analyzed two polymorphisms in the FOXP3 gene (rs3761547 and rs3761548) and a polymorphism in the GATA3 gene (rs3824662) in 106 MS patients and 113 healthy controls. Serum 25(OH)D3 was also measured in all participants.

Results: No statistically significant genotypic and allelic differences were found in the distribution of FOXP3 rs3761547 and rs3761548, or GATA3 rs3824662 in the MS patients, compared with controls. Patients that were homozygous for rs3761547 had lower 25(OH)D3 levels.

Conclusions: Our findings did not show any association among FOXP3 and GATA3 SNPs, vitamin D, and MS susceptibility.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/brainsci11040415DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8066599PMC
March 2021

The Role of Vitamin D as a Biomarker in Alzheimer's Disease.

Brain Sci 2021 Mar 6;11(3). Epub 2021 Mar 6.

Institute of Clinical Biochemistry, Clinical Molecular Medicine and Laboratory Medicine, Department of Biomedicine, Neurosciences and Advanced Diagnostics, University of Palermo, 90127 Palermo, Italy.

Vitamin D and cognition is a popular association, which led to a remarkable body of literature data in the past 50 years. The brain can synthesize, catabolize, and receive Vitamin D, which has been proved to regulate many cellular processes in neurons and microglia. Vitamin D helps synaptic plasticity and neurotransmission in dopaminergic neural circuits and exerts anti-inflammatory and neuroprotective activities within the brain by reducing the synthesis of pro-inflammatory cytokines and the oxidative stress load. Further, Vitamin D action in the brain has been related to the clearance of amyloid plaques, which represent a feature of Alzheimer Disease (AD), by the immune cell. Based on these considerations, many studies have investigated the role of circulating Vitamin D levels in patients affected by a cognitive decline to assess Vitamin D's eventual role as a biomarker or a risk factor in AD. An association between low Vitamin D levels and the onset and progression of AD has been reported, and some interventional studies to evaluate the role of Vitamin D in preventing AD onset have been performed. However, many pitfalls affected the studies available, including substantial discrepancies in the methods used and the lack of standardized data. Despite many studies, it remains unclear whether Vitamin D can have a role in cognitive decline and AD. This narrative review aims to answer two key questions: whether Vitamin D can be used as a reliable tool for diagnosing, predicting prognosis and response to treatment in AD patients, and whether it is a modifiable risk factor for preventing AD onset.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/brainsci11030334DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8000099PMC
March 2021

COVID-19 and Alzheimer's Disease.

Brain Sci 2021 Feb 27;11(3). Epub 2021 Feb 27.

Clinical Molecular Medicine and Laboratory Medicine, Department of Biomedicine, Neurosciences and Advanced Diagnostics, Institute of Clinical Biochemistry, University of Palermo, 90127 Palermo, Italy.

The Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is a neurotropic virus with a high neuroinvasive potential. Indeed, more than one-third of patients develop neurological symptoms, including confusion, headache, and hypogeusia/ageusia. However, long-term neurological consequences have received little interest compared to respiratory, cardiovascular, and renal manifestations. Several mechanisms have been proposed to explain the potential SARS-CoV-2 neurological injury that could lead to the development of neurodegenerative diseases, including Alzheimer's Disease (AD). A mutualistic relationship between AD and COVID-19 seems to exist. On the one hand, COVID-19 patients seem to be more prone to developing AD. On the other hand, AD patients could be more susceptible to severe COVID-19. In this review, we sought to provide an overview on the relationship between AD and COVID-19, focusing on the potential role of biomarkers, which could represent precious tool for early identification of COVID-19 patients at high risk of developing AD.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/brainsci11030305DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7997244PMC
February 2021

Validation of monocyte distribution width decisional cutoff for sepsis detection in the acute setting.

Int J Lab Hematol 2021 Feb 26. Epub 2021 Feb 26.

Institute of Clinical Biochemistry, Clinical Molecular Medicine and Laboratory Medicine, Department of Biomedicine, Neurosciences and Advanced Diagnostics, University of Palermo, Palermo, Italy.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/ijlh.13496DOI Listing
February 2021

Vitamin D increases the production of IL-10 by regulatory T cells in patients with systemic sclerosis.

Clin Exp Rheumatol 2020 Nov-Dec;38(6):1276. Epub 2020 Dec 3.

Dipartimento Biomedico di Medicina Interna e Specialistica, Sezione di Reumatologia, University of Palermo, Italy.

View Article and Find Full Text PDF

Download full-text PDF

Source
December 2020

Vitamin D and Genetic Susceptibility to Multiple Sclerosis.

Biochem Genet 2021 Feb 7;59(1):1-30. Epub 2020 Nov 7.

Department of Biomedicine, Neurosciences and Advanced Diagnostics, Institute of Clinical Biochemistry, Clinical Molecular Medicine and Laboratory Medicine, University of Palermo, Via del Vespro, 129, CAP 90127, Palermo, Sicily, Italy.

Multiple sclerosis (MS) is an autoimmune disease affecting the central nervous system (CNS), resulting from the interaction among genetic, epigenetic, and environmental factors. Vitamin D is a secosteroid, and its circulating levels are influenced by environment and genetics. In the last decades, research data on the association between MS and vitamin D status led to hypothesize a possible role for hypovitaminosis D as a risk factor for MS. Some gene variants encoding proteins involved in vitamin D metabolism, transport, and function, which are responsible for vitamin D status alterations, have been related to MS susceptibility. This review explores the current literature on the influence of vitamin D-related genes in MS susceptibility, reporting all single-nucleotide polymorphisms (SNPs) investigated to date in 12 vitamin D pathway genes. Among all, the gene codifying vitamin D receptor (VDR) is the most studied. The association between VDR SNPs and MS risk has been reported by many Authors, with a few studies producing opposite results. Other vitamin D-related genes (including DHCR7/NADSYN1, CYP2R1, CYP27A1, CYP3A4, CYP27B1, CYP24A1, Megalin-DAB2-Cubilin, FGF-23, and Klotho) have been less investigated and achieved more conflicting evidence. Taken together, findings from the studies reviewed cannot clarify whether and to what extent vitamin D-related gene variants can influence MS risk.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s10528-020-10010-1DOI Listing
February 2021

Monocyte distribution width (MDW) as a screening tool for sepsis in the Emergency Department.

Clin Chem Lab Med 2020 10;58(11):1951-1957

Institute of Clinical Biochemistry, Clinical Molecular Medicine and Laboratory Medicine, Department of Biomedicine, Neurosciences and Advanced Diagnostics, University of Palermo, Palermo, Italy.

Objectives The diagnosis of sepsis in the Emergency Department (ED) is challenging and a reliable biomarker is needed. The current study aimed to evaluate the diagnostic accuracy of monocyte distribution width (MDW) for the early identification of sepsis in the ED. Methods We performed a large observational study including consecutive adult patients (≥18 years of age) presenting to the ED between September and November 2019, with an order for complete blood count (CBC) evaluation. A total of 2,215 patients were enrolled and classified based on Sepsis-2 criteria as the control group (1,855), infection group (172), Systemic Inflammatory Response Syndrome (SIRS) group (100), and sepsis group (88). Results MDW levels were higher in patients with sepsis than in all other groups (p<0.001). ROC curve analysis showed an optimal diagnostic accuracy of MDW for sepsis prediction at a cut-off point of 23.5, with an AUC of 0.964, sensitivity and specificity of 0.920 and 0.929, respectively. Conclusions Our findings encourage further investigation to validate the use of MDW as a screening tool for the early identification of patients at risk of sepsis in the ED.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1515/cclm-2020-0417DOI Listing
October 2020

Klotho and vitamin D in multiple sclerosis: an Italian study.

Arch Med Sci 2020 2;16(4):842-847. Epub 2019 Aug 2.

Department of Biomedicine, Neuroscience, and Advanced Diagnostics, Institute of Clinical Biochemistry, Clinical Molecular Medicine, and Laboratory Medicine, University of Palermo, Palermo, Italy.

Introduction: Low vitamin D levels have been recognised as an important risk factor for autoimmune diseases, including multiple sclerosis (MS). MS is a multifactorial disease, the pathogenesis of which contributes both to genetic and environmental factors. Polymorphisms in genes codifying molecules involved in vitamin D homeostasis have been associated with hypovitaminosis D. However, the influence of polymorphisms of Klotho, which codify a protein with a pivotal role in vitamin D metabolism, have never been investigated. The aim of this study was to evaluate the association among genetic variants of Klotho, namely rs1207568 and rs9536314, serum 25(OH)D levels, and multiple sclerosis (both risk and disease progression).

Material And Methods: 107 patients with MS and 133 healthy controls were enrolled in this study. Serum 25(OH)D levels and genotyping of Klotho SNPs were evaluated in all participants by high-performance liquid chromatography and real-time polymerase chain reaction, respectively.

Results: Allelic and genotypic frequencies did not differ between patients and controls. Concerning rs1207568, we found a trend toward lower serum 25(OH)D levels in MS patients with A allele (mutant), both in heterozygosis (AG) and in homozygosis (AA), in comparison to MS patients with G allele in homozygosis (GG) (AG + AA 20.5 ±6.3 µg/l; GG 22.5 ±7.5 µg/l, = 0.07).

Conclusions: Our findings did not identify a role of Klotho in the genetic susceptibility to MS.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.5114/aoms.2019.86969DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7286339PMC
August 2019

Clinical Use of κ Free Light Chains Index as a Screening Test for Multiple Sclerosis.

Lab Med 2020 Jul;51(4):402-407

Department of Biomedicine, Neurosciences and Advanced Diagnostics, Institute of Clinical Biochemistry, Clinical Molecular Medicine and Laboratory Medicine, University of Palermo, Italy.

Objective: To assess the usefulness of the κ free light chain index (κFLCi) as a screening test to identify patients with suspected MS.

Methods: The study included 56 patients with a request to test for oligoclonal bands (OCBs). OCBs were detected by isoelectric focusing, followed by immunofixation. Cerebrospinal fluid (CSF) and serum κFLC were measured by a turbidimetric assay. Also, the κFLC index (κFLCi) was calculated.

Results: CSF κFLC levels and κFLCi were significantly higher in patients with multiple sclerosis (MS) than in patients with other neurological diseases (NDs; P < .001 and P < .001, respectively). At the cutoff value of 2.9, the κFLCi detected MS with sensitivity of 97% and specificity of 65%. Overall, 92% patients with κFLCi of 2.9 or greater and who had tested positive for OCBs were diagnosed as having MS.

Conclusion: Our findings support the use of κFLCi as a screening test when MS is suspected, followed by OCB detection as a confirmatory test for the diagnosis of MS.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/labmed/lmz073DOI Listing
July 2020

Vitamin D increases the production of IL-10 by regulatory T cells in patients with systemic sclerosis.

Clin Exp Rheumatol 2019 Jul-Aug;37 Suppl 119(4):76-81. Epub 2019 Oct 3.

Dipartimento Biomedico di Medicina Interna e Specialistica, Sezione di Reumatologia, University of Palermo, Italy.

Objectives: Vitamin D status influences the risk to develop autoimmune diseases affecting the percentage and/or functions of regulatory T cells (Tregs). Since low levels of 25 (OH) D have been decreased in patients with systemic sclerosis (SSc), we aimed to study the effect of Vitamin D3 (cholecalciferol) supplementation on Tregs frequencies and functions.

Methods: Peripheral blood and sera samples were obtained from 45 SSc patients and controls (HC). A number of eighteen SSc patients had consumed Cholecalciferol (orally) at the dose of 25.000 UI/month for 6 months at the time of enrollment. 25(OH)D serum levels were measured and VDR polymorphisms, were genotyped by polymerase chain reaction (PCR). Tregs isolated from peripheral blood mononuclear cells were in vitro expanded and a suppression assay was performed. Flow cytometry analysis was then carried out. Finally, IL-10 production was assayed by ELISA.

Results: Low serum levels of 25(OH)D were detected in SSc patients. The percentage of Tregs in SSc patients was similar to controls, but, among SSc patients, it was higher in those patients taking cholecalciferol. Tregs capability to suppress T cell proliferation was impaired in SSc patients and not restored after in vitro pre-treatment with the active form of Vitamin D (1,25(OH)2D3); but at the same time the production of IL-10 was increased in treated samples obtained from patients. The lack of response of Tregs from SSc patients to 1,25(OH)2D3 treatment in vitro was not due to altered Vitamin D/VDR signalling.

Conclusions: Altogether, our results indicate that the increased production of IL-10 by 1,25(OH)2D3 -treated Tregs could provide a "suppressive" cytokine milieu able to modulate immune response but it is not sufficient to restore the immune suppressive functions of Tregs.
View Article and Find Full Text PDF

Download full-text PDF

Source
October 2019

Standardized measurement of circulating vitamin D [25(OH)D] and its putative role as a serum biomarker in Alzheimer's disease and Parkinson's disease.

Clin Chim Acta 2019 Oct 19;497:82-87. Epub 2019 Jul 19.

Department of Biomedicine, Neuroscience and Advanced Diagnostics, Institute of Clinical Biochemistry, Clinical Molecular Medicine and Laboratory Medicine, University of Palermo, Via del Vespro 129, 90141 Palermo, Italy; Department of Laboratory Medicine, University-Hospital, Via del Vespro 129, 90141 Palermo, Italy. Electronic address:

The current review provides an overview on the development of 25(OH)D measurement standardization tools over the last three decades and clarifies whether there is a role as a serum biomarker for vitamin D in neurological diseases. In the past, a lack of internationally recognized 25(OH)D reference measurement procedures and reference standard materials led to unstandardized serum total 25(OH)D results among research and clinical care laboratories. The vitamin D Standardization Program (VDSP) has been introduced in 2010 to address this problem, however, vitamin D External Quality Assessment Scheme (DEQAS) reports still show substantial sample- to- sample variability. Further, immunoassays, which are mainly used in clinical care laboratories, display analytical issues, including matrix-effects interferences, which cannot be overcome by the standardization process. Hence, liquid chromatography-tandem mass spectrometry (LC/MS-MS) methods should be used to measure 25(OH)D. Low vitamin D serum levels have been found in patients affected by Alzheimer's disease and Parkinson's disease, suggesting a role for vitamin D as a serum biomarker in these diseases. However, few studies reported 25(OH)D standardized results, thus, no clear evidence on the potential role of 25(OH)D serum levels in these diseases exists.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.cca.2019.07.022DOI Listing
October 2019

Non-Skeletal Activities of Vitamin D: From Physiology to Brain Pathology.

Medicina (Kaunas) 2019 Jul 5;55(7). Epub 2019 Jul 5.

Institute of Clinical Biochemistry, Clinical Molecular Medicine and Laboratory Medicine, Department of Biomedicine, Neuroscience and Advanced Diagnostics, University of Palermo, 90127 Palermo, Italy.

Vitamin D is a secosteroid hormone regulating the expression of almost 900 genes, and it is involved in the regulation of calcium and phosphate metabolism, immune response, and brain development. Low blood vitamin D levels have been reported in patients affected by various diseases. Despite a large amount of literature data, there is uncertainty surrounding the role of vitamin D as a serum biomarker in Alzheimer's disease (AD) and Parkinson's disease (PD). Indeed, the lack of internationally recognized 25(OH)D reference measurement procedures and standard materials in the past led to unstandardized serum total 25(OH)D results among research and clinical care laboratories. Thus, most of the literature studies reported unstandardized data, which are of little use and make it difficult to draw conclusions of the role of vitamin D in AD and PD. This review summarizes the extra-skeletal actions of vitamin D, focusing its role in immunomodulation and brain function, and reports the issue of lacking standardized literature data concerning the usefulness of vitamin D as a biomarker in AD and PD.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/medicina55070341DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6680897PMC
July 2019

Establishing the 99 percentile for high sensitivity cardiac troponin I in healthy blood donors from Southern Italy.

Biochem Med (Zagreb) 2019 Jun;29(2):020901

Institute of Clinical Biochemistry, Clinical Molecular Medicine and Laboratory Medicine, Department of Biomedicine, Neurosciences and Advanced Diagnostics, University of Palermo, Palermo, Italy.

Introduction: The knowledge of high sensitivity cardiac troponin I (hsTnI) distribution in a reference population is mandatory for its introduction in clinical practice. The aim of this study was to define the Upper Reference Limit (URL) of hsTnI measured by Single Molecule Counting technology (SMC) in an accurately selected reference population.

Materials And Methods: In the study 1140 blood donors were included and selected on the basis of medical history and biomarkers. High sensitivity cardiac troponin I was measured by SMC technology (Clarity, Singulex, Alamed, USA). The 99th percentile was calculated by the non-parametric method according to the Clinical and Laboratory Standard Institute - CLSI C28-A3.

Results: The median age was 41 years (IQR: 28 - 50) and 69% were males. The overall 99th percentile was 5 ng/L (90% CI: 4.2 - 5.6). When considering sex-related differences, we found slight differences between the 99th percentile in males and females. Moreover, the 99th percentile trended with age, especially in females.

Conclusions: We defined the 99th percentile of hs-cTnI measured by SMC technology in a highly selected healthy population, with only minor differences between males and females. Our findings provide the basic criteria for the reliable interpretation of hsTnI concentrations measured by the SMC technology in clinical settings.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.11613/BM.2019.020901DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6559611PMC
June 2019

Reference interval by the indirect approach of serum thyrotropin (TSH) in a Mediterranean adult population and the association with age and gender.

Clin Chem Lab Med 2019 Sep;57(10):1587-1594

Institute of Clinical Biochemistry, Clinical Molecular Medicine and Laboratory Medicine, Department of Biomedicine, Neurosciences and Advanced Diagnostics, University of Palermo, Palermo, Italy.

Background The serum concentration of thyrotropin (TSH) represents a first-line test in diagnostic algorithms. The estimation of TSH reference intervals (RIs) is still a matter of debate due to the high prevalence of subclinical disease making difficult the definition of truly healthy subjects. The aim of this study was to estimate TSH RIs in healthy subjects and to evaluate the effect of age and gender on TSH concentration. Methods Forty-four thousand one hundred and fifty-six TSH data were collected between July 2012 and April 2018 at the Department of Laboratory Medicine, University-Hospital, Palermo. Common and sex-specific RIs were estimated by Arzideh's indirect method after exclusion of individuals younger than 15 years, subjects with repeated TSH tests and with abnormal free thyroxine (fT4), free triiodothyronine (fT3) or anti-thyroid-peroxidase antibodies. The combined effect of age and gender on TSH values was evaluated. Results RIs estimated in the selected individuals (n = 22602) were, respectively, 0.18-3.54 mIU/L (general), 0.19-3.23 mIU/L (men) and 0.18-3.94 mIU/L (women). Women showed significantly higher median TSH than men (1.46 vs. 1.39 mIU/L; p < 0.0001). Both in men and in women, median TSH decreased along with age; however, although up to 60 years in both men and women showed similar values, afterwards women showed constantly higher TSH than men. Accordingly, statistical analysis showed a significant interaction between gender and age (p = 0.001), suggesting that the effect of age on TSH is different between genders. Conclusions Our findings suggest that the indirect method, with appropriate cleaning of data, could be useful to define TSH RIs.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1515/cclm-2018-0957DOI Listing
September 2019

Proton-irradiated breast cells: molecular points of view.

J Radiat Res 2019 Jul;60(4):451-465

Istituto di Bioimmagini e Fisiologia Molecolare-Consiglio Nazionale delle Ricerche (IBFM-CNR), Cefalù (PA), Italy.

Breast cancer (BC) is the most common cancer in women, highly heterogeneous at both the clinical and molecular level. Radiation therapy (RT) represents an efficient modality to treat localized tumor in BC care, although the choice of a unique treatment plan for all BC patients, including RT, may not be the best option. Technological advances in RT are evolving with the use of charged particle beams (i.e. protons) which, due to a more localized delivery of the radiation dose, reduce the dose administered to the heart compared with conventional RT. However, few data regarding proton-induced molecular changes are currently available. The aim of this study was to investigate and describe the production of immunological molecules and gene expression profiles induced by proton irradiation. We performed Luminex assay and cDNA microarray analyses to study the biological processes activated following irradiation with proton beams, both in the non-tumorigenic MCF10A cell line and in two tumorigenic BC cell lines, MCF7 and MDA-MB-231. The immunological signatures were dose dependent in MCF10A and MCF7 cell lines, whereas MDA-MB-231 cells show a strong pro-inflammatory profile regardless of the dose delivered. Clonogenic assay revealed different surviving fractions according to the breast cell lines analyzed. We found the involvement of genes related to cell response to proton irradiation and reported specific cell line- and dose-dependent gene signatures, able to drive cell fate after radiation exposure. Our data could represent a useful tool to better understand the molecular mechanisms elicited by proton irradiation and to predict treatment outcome.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1093/jrr/rrz032DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6640903PMC
July 2019

Fructose-1,6-Bisphosphate Protects Hippocampal Rat Slices from NMDA Excitotoxicity.

Int J Mol Sci 2019 May 7;20(9). Epub 2019 May 7.

Neurotrauma and Ophthalmology Research Group, School of Clinical and Experimental Medicine, College of Medical and Dental Sciences, University of Birmingham, Edgbaston, Birmingham B15 2TT, UK.

Effects of fructose 1,6-bisphosphate (F-1,6-P2) towards -methyl-d-aspartate NMDA excitotoxicity were evaluated in rat organotypic hippocampal brain slice cultures (OHSC) challenged for 3 h with 30 μM NMDA, followed by incubations (24, 48, and 72 h) without (controls) and with F-1,6-P2 (0.5, 1 or 1.5 mM). At each time, cell necrosis was determined by measuring LDH in the medium. Energy metabolism was evaluated by measuring ATP, GTP, ADP, AMP, and ATP catabolites (nucleosides and oxypurines) in deproteinized OHSC extracts. Gene expressions of phosphofructokinase, aldolase, and glyceraldehyde-3-phosphate dehydrogenase were also measured. F-1,6-P2 dose-dependently decreased NMDA excitotoxicity, abolishing cell necrosis at the highest concentration tested (1.5 mM). Additionally, F-1,6-P2 attenuated cell energy imbalance caused by NMDA, ameliorating the mitochondrial phosphorylating capacity (increase in ATP/ADP ratio) Metabolism normalization occurred when using 1.5 mM F-1,6-P2. Remarkable increase in expressions of phosphofructokinase, aldolase and glyceraldehyde-3-phosphate dehydrogenase (up to 25 times over the values of controls) was also observed. Since this phenomenon was recorded even in OHSC treated with F-1,6-P2 with no prior challenge with NMDA, it is highly conceivable that F-1,6-P2 can enter into intact cerebral cells producing significant benefits on energy metabolism. These effects are possibly mediated by changes occurring at the gene level, thus opening new perspectives for F-1,6-P2 application as a useful adjuvant to rescue mitochondrial metabolism of cerebral cells under stressing conditions.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3390/ijms20092239DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6540300PMC
May 2019

Vitamin D in malaria: more hypotheses than clues.

Heliyon 2019 Feb 6;5(2):e01183. Epub 2019 Feb 6.

Section of Clinical Biochemistry and Clinical Molecular Medicine, Department of Biomedicine, Neuroscience and Advanced Diagnostics, University of Palermo, Italy.

Vitamin D is a secosteroid hormone regulating calcium and phosphate metabolism, immune response and brain development. Low blood 25(OH)D levels have been reported in patients affected by infectious diseases caused by parasites, including malaria. Despite the high effectiveness of antimalarials, malaria is burdened with high morbidity and mortality, and the search for additional therapies is rapidly growing. Furthermore, available preventive measures have proved to be barely effective so far. Finding new prevention and therapy tools is a matter of urgency. Studies on animal models and humans have hypothesized some mechanisms by which the hormone can influence malaria pathogenesis, and the role of Vitamin D supplementation in preventing and treating this disease has been suggested. Few studies on the association between Vitamin D and malaria are available and disagreeing results have been reported. Studies in humans reporting an association between low 25(OH)D circulating levels and Malaria have a small sample size and observational study-set. Randomized controlled trials are needed in order to understand if Vitamin D administration might play a role in preventing and treating malaria.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.heliyon.2019.e01183DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6370580PMC
February 2019

CYP27A1, CYP24A1, and RXR-α Polymorphisms, Vitamin D, and Multiple Sclerosis: a Pilot Study.

J Mol Neurosci 2018 Sep 7;66(1):77-84. Epub 2018 Aug 7.

Department of Biopathology and Medical Biotechnologies, Section of Clinical Biochemistry and Clinical Molecular Medicine, University of Palermo, Via del Vespro, 129, 90127, Palermo, Italy.

Multiple sclerosis (MS) is a neurodegenerative autoimmune disease resulting from a complex interaction of genetic and environmental factors. Hypovitaminosis D seems to contribute to MS susceptibility as both an environmental and a genetic risk factor. The aim of our study was to investigate the association of SNPs in CYP27A1, CYP24A1, and RXR- α genes, vitamin D status, and MS risk. We performed a nested case-control study on patients with multiple sclerosis and healthy controls. Serum 25(OH)D levels and genotyping of CYP27A1, CYP24A1, and RXR-α -SNPs were investigated both in MS patients and in healthy controls. Serum 25(OH)D levels were measured by a high-performance liquid chromatography (HPLC). Molecular analysis was performed by real-time PCR. The distribution of genotypic and allelic frequencies was not significantly different between patients and controls, except for rs2248137 CYP24A1. In particular, CC genotype (C minor allele) showed a higher frequency in MS patients in comparison to healthy controls. Moreover, we observed significantly lower serum 25(OH)D3 levels in MS patients with CC genotype in comparison to MS patients with GG and GC genotype. The findings of our study suggest a role of rs2248137 CYP24A1 in multiple sclerosis risk.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s12031-018-1152-9DOI Listing
September 2018

Establishing the upper reference limit of Galectin-3 in healthy blood donors.

Biochem Med (Zagreb) 2017 Oct;27(3):030709

Section of Clinical Biochemistry and Clinical Molecular Medicine, Department of Biopathology and Medical Biotechnologies, University of Palermo, Italy.

Introduction: Galectin-3 (Gal-3) is an independent predictor of poor outcomes and mortality in patients with heart failure (HF). Thus, it has been proposed as a reliable prognostic biomarker for HF. The definition of reference intervals is mandatory for interpreting the findings of experimental studies and encouraging the routine use of biomarkers in clinical practice. To date, no study assessed the reference intervals of Gal-3 and identified the biological variables that affect its concentration in a well-defined healthy population. The aim of this study was to determine the upper reference limit (URL) of Gal-3 in a highly reliable population of healthy subjects.

Materials And Methods: We recruited 714 blood donors. After measuring surrogate biomarkers to identify underlying diseases, 8 subjects were excluded. A final population of 706 individuals (385 men (54.5%); median age 39 (18-65) years) was included. The URL was calculated using the non-parametric percentile approach.

Results: The 97.5th percentile URL of plasma Gal-3 in our study population (90% CI) was 26.1 (23.3-31.5) ng/mL. After stratifying subjects according to age, the URL of Gal-3 was found to be considerably higher in older (> 45 years) than in younger subjects (31.5 (26.2-51.4) vs 21.8 (21-26.1) ng/mL, respectively). No sex-related differences were found in Gal-3 plasma concentration.

Conclusions: We established the URL of Gal-3 in a highly selected healthy population. Our findings indicate that age is an important determinant of Gal-3 plasma concentration, so that multiple diagnostic cut-offs should be preferably used according to the different age classes.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.11613/BM.2017.030709DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5696745PMC
October 2017

Association of CYP2R1 rs10766197 with MS risk and disease progression.

J Neurosci Res 2018 02 23;96(2):297-304. Epub 2017 Aug 23.

Section of Clinical Biochemistry and Clinical Molecular Medicine, Department of Biopathology and Medical Biotechnologies, University of Palermo, Via del Vespro 129, 90127, Italy.

Background: 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 gain great attention. The aim of our study was to assess five SNPs in NADSYN1 and CYP2R1 genes in relation to serum 25-OH-vitamin D3 levels in MS patients and controls.

Methods: 25-OH-vitamin D3 levels and genotyping of CYP2R1- and NADSYN1-SNPs were investigated both in MS patients and in healthy controls.

Results: The analysis revealed lower 25-OH-vitamin D3 concentrations in MS patients than in controls and an association of rs10766197 CYP2R1 SNP with MS risk. After stratifying MS patients according to gender, we found that the minor allele A of rs10766197 had a higher frequency in men in comparison to women affected by MS. Additionally, the presence of allele A in men was associated with disease progression, assessed by EDSS and MSSS scores.

Conclusion: The findings of our study open new perspectives for a role of CYP2R1 in both risk and progression of MS, with sex-related differences.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/jnr.24133DOI Listing
February 2018

Heart-type fatty acid binding protein is a sensitive biomarker for early AMI detection in troponin negative patients: a pilot study.

Scand J Clin Lab Invest 2017 Oct 26;77(6):428-432. Epub 2017 Jun 26.

a Sezione Biochimica Clinica e Medicina Molecolare, Dipartimento di Biopatologia e Biotecnologie Mediche , Università degli studi di Palermo , Palermo , Italy.

Background: Early detecting AMI in individuals presenting to the ED with chest pain continues to be a challenge. cTn is the gold standard for AMI diagnosis but early presenters (<1 hours from symptom onset) maybe cTn negative on admission. We analysed the diagnostic value of h-FABP and hs-TnI in patients presenting to ED with chest pain and no cTnI elevations.

Methods: 28 AMI and 28 no-AMI individuals both presented to ED within one hour from pain onset were included. Blood donors were analysed for h-FABP cut-off identification. Among AMI patients, 55% were positive for h-FABP and 34.6% were positive for hs-TnI (p = .015), thus 21% were positive only for h-FABP. The diagnostic accuracy was assessed by ROC curve. h-FABP showed a higher sensitivity but lower specificity than hs-TnI.

Conclusions: In our study, the frequency of h-FABP positivity among AMI patients was higher than that of hs-TnI, which would have missed six of them; however, hs-TnI AUC was superior to that of h-FABP. These preliminary findings might confirm that h-FABP may be a good candidate for AMI rule-in/rule-out within the ED context.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/00365513.2017.1335880DOI Listing
October 2017

Galectin-3 in acute coronary syndrome.

Clin Biochem 2017 Sep 26;50(13-14):797-803. Epub 2017 Apr 26.

Sezione Biochimica Clinica e Medicina Molecolare Clinica, Dipartimento di Biopatologia e Biotecnologie Mediche, Università degli Studi di Palermo, Italy; UOC Medicina di Laboratorio - CoreLab, AOUP "P. Giaccone", Palermo, Italy. Electronic address:

Acute coronary syndrome (ACS) is a very common cause of hospitalizations worldwide each year. In the past decades biomarkers have become an indispensable tool for diagnosis, risk stratification and prognosis of cardiovascular disease, including ACS. Despite Troponin is considered the gold standard in diagnosis of ACS, several molecules have been investigated to identify predictive biomarkers of prognosis. Among these, Gal-3 has emerged as a promising prognostic marker. It has a pivotal role in inflammation and fibrosis. Both experimental and clinical studies have shown Gal-3 is an independent predictor of all-cause mortality, cardiovascular death and occurrence of HF following ACS. This article reviews the literature data regarding the role of Galectin-3 in ACS setting.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.clinbiochem.2017.04.018DOI Listing
September 2017

Short-term Changes in Gal 3 Circulating Levels After Acute Myocardial Infarction.

Arch Med Res 2016 10;47(7):521-525

Dipartimento di Biopatologia e Biotecnologie Mediche, Sezione di Biochimica Clinica e Medicina Molecolare Clinica, Università degli Studi di Palermo, Italy; UOC Medicina di Laboratorio-CoreLab, AOUP P. Giaccone, Palermo, Italy. Electronic address:

Background And Aims: Galectin 3 (Gal 3) is a β-galactoside-binding lectin known to play a part in inflammation, adverse remodeling and fibrosis. Gal 3 seems to be linked to atherogenesis and Coronary Artery Disease (CAD), but less is known about the relationship between Gal 3 and acute myocardial infarction (AMI). The aim of the present study is to assess circulating levels of Gal 3 after AMI and to evaluate short-term changes of the biomarker within 5 days from the acute event.

Methods: Two hundred fifteen confirmed AMI patients (125 STEMI, M/F = 2.8; mean age: 65.4 ± 13.8 years) were enrolled in the present study; two blood samples were collected from each patient: first, within 1 h from admission to the Emergency Area (T1) and then upon discharge (T2).

Results: Kinetics of Gal 3 during AMI show that the marker boosts during the acute event (T1) and then decreases from baseline, being significantly lower at T2 (18 [14.2-25] vs. 16.8 [12.7-23.4]; p = 0.006). Gal 3 levels were correlated to hsTnI and eGFR on admission (r = 0.2; p <0.001 and r = -0.25; p <0.001, respectively). Linear regression analysis confirms an association between Gal 3 and ejection fraction (r = 0.037; p = 0.005).

Conclusions: Gal 3 is reasonably supposed to be a part of those mechanisms leading to formation, destabilization and rupture of plaque; however, the usefulness of Gal 3 as a biomarker in CAD/AMI is far from being elucidated.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.arcmed.2016.12.009DOI Listing
October 2016

Association between hypovitaminosis D and systemic sclerosis: True or fake?

Clin Chim Acta 2016 Jul 3;458:115-9. Epub 2016 May 3.

Sezione Biochimica Clinica e Medicina Molecolare Clinica, Dipartimento di Biopatologia e Biotecnologie Mediche, Università degli Studi di Palermo, Italy; UOC Medicina di Laboratorio - CoreLab, AOUP "P. Giaccone", Palermo, Italy. Electronic address:

Background: Vitamin D insufficiency/deficiency is considered a major factor triggering and enhancing several autoimmune disorders; hypovitaminosis D has been reported to be common in Systemic Sclerosis (SSc). Previous studies assessing vitamin D insufficiency/deficiency in SSc have been reviewed, and the relation with pathogenesis and clinical features has been examined.

Content: Eligibility criteria were: reporting measurement of Vitamin D serum levels in all participants and evaluating adult onset-SSc individuals as patients group.

Results: The association between clinical features and low hormone levels is controversial. Manifold data have shown vitamin D insufficiency/deficiency to have a potential role in the pathogenesis of disease, providing inconclusive findings.

Summary: Promoting the onset of SSc depends on the interaction between genetics, environment and infections. It remains a sound question whether Vitamin D insufficiency/deficiency is an environment-linked immunological heckler, making infectious agents taking root.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.cca.2016.04.026DOI Listing
July 2016

Corrigendum to "Procalcitonin and community-acquired pneumonia (CAP) in children" [Clin Chim Acta. 451(Pt B) (2015 Dec 7) 215-8].

Clin Chim Acta 2016 Jul 20;458:165. Epub 2016 Apr 20.

Sezione Biochimica Clinica e Medicina Molecolare, Dipartimento di Biopatologia e Biotecnologie Mediche, Università degli studi di Palermo, Italy; UOC Medicina di Laboratorio-CoreLab, AOUP Policlinico P. Giaccone, Palermo, Italy.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.cca.2016.04.006DOI Listing
July 2016

Fetuin-A is Associated to Serum Calcium and AHSG T256S Genotype but Not to Coronary Artery Calcification.

Biochem Genet 2016 Jun 29;54(3):222-231. Epub 2016 Jan 29.

Sezione Biochimica Clinica e Medicina Molecolare Clinica, Dipartimento di Biopatologia e Biotecnologie Mediche, Università degli Studi di Palermo, Palermo, Italy.

Vascular calcification has been recently associated to an increased cardiovascular risk and mortality. In few studies, Fetuin-A showed an association to coronary artery calcification (CAC), although the physiopathological mechanism underlying this association has not been fully established yet. Seventy-four patients with one or more cardiovascular risk factor and asymptomatic for coronary vasculopathy were included in the study. CAC was evaluated by Agatston score. Serum Fetuin-A levels were determined by ELISA. Molecular analysis of AHSG T256S gene variant (rs4918) was performed by PCR-RFLP. Serum Fetuin-A was correlated to serum calcium (r = 0,321; P = 0,018), but not to serum phosphorous. Multivariate linear regression analysis confirmed this association and showed that calcium and AHSG genotype were independent predictors of Fetuin-A (P = 0.037, P = 0.014, respectively). In particular, subjects carrying the SS genotype had lower levels of Fetuin-A and calcium (P = 0.037 and P = 0.038, respectively). When we compare subjects with CAC 0-10 with subjects with CAC > 10, we found that only age and male gender (P < 0.001, P = 0.035, respectively), but not Fetuin-A, were associated to CAC. Fetuin-A is not associated to CAC in subjects with low cardiovascular risk profile and asymptomatic for coronary vasculopathy, suggesting that in this setting Fetuin-A, although correlated to serum levels of calcium, could be not involved in mineral deposition on coronary vessels.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s10528-016-9714-4DOI Listing
June 2016

Procalcitonin and community-acquired pneumonia (CAP) in children.

Clin Chim Acta 2015 Dec 3;451(Pt B):215-8. Epub 2015 Oct 3.

Sezione Biochimica Clinica e Medicina Molecolare, Dipartimento di Biopatologia e Biotecnologie Mediche, Università degli studi di Palermo, Italy; UOC Medicina di Laboratorio-CoreLab, AOUP Policlinico P. Giaccone, Palermo, Italy. Electronic address:

The role of procalcitonin (PCT) as a biomarker for sepsis in adults is well documented, while its role in infections affecting neonatal children remains controversial. Among these infections, Community-Acquired pneumonia (CAP) has been studied extensively, because it's the second cause of death in children in developing countries, and one of the most frequent causes of hospitalization in industrialized countries. The PubMed database and the Cochrane Library were used to search for the following keywords: CAP, procalcitonin, and children. Thirteen articles were studied to determine the role of PCT in CAP management, specifically its usefulness for distinguishing pneumococcal infections from viral and unknown infections, for predicting severity and the correct antibiotic treatment. This paper focuses on the studies performed to identify the best inflammatory biomarker for CAP management. Although there is an increase in studies confirming the usefulness of PCT in CAP management in children, further studies are needed to have better understanding of its role for pediatric CAP management.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.cca.2015.09.031DOI Listing
December 2015