Publications by authors named "Caterina Maria Gambino"

32 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.
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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.
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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.
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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.
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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.
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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.
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http://dx.doi.org/10.3390/brainsci11030305DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7997244PMC
February 2021

Prognostic Role of CSF β-amyloid 1-42/1-40 Ratio in Patients Affected by Amyotrophic Lateral Sclerosis.

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

Unit of Neurology, Department of Biomedicine, Neurosciences and Advanced Diagnostics, University of Palermo, 90129, Palermo, Italy.

The involvement of β-amyloid (Aβ) in the pathogenesis of amyotrophic lateral sclerosis (ALS) has been widely discussed and its role in the disease is still a matter of debate. Aβ accumulates in the cortex and the anterior horn neurons of ALS patients and seems to affect their survival. To clarify the role of cerebrospinal fluid (CSF) Aβ 1-42 and Aβ 42/40 ratios as a potential prognostic biomarker for ALS, we performed a retrospective observational study on a cohort of ALS patients who underwent a lumbar puncture at the time of the diagnosis. CSF Aβ 1-40 and Aβ 1-42 ratios were detected by chemiluminescence immunoassay and their values were correlated with clinical features. We found a significant correlation of the Aβ 42/40 ratio with age at onset and Mini Mental State Examination (MMSE) scores. No significant correlation of Aβ 1-42 or Aβ 42/40 ratios to the rate of progression of the disease were found. Furthermore, when we stratified patients according to Aβ 1-42 concentration and the Aβ 42/40 ratio, we found that patients with a lower Aβ 42/40 ratio showed a shorter survival. Our results support the hypothesis that Aβ 1-42 could be involved in some pathogenic mechanism of ALS and we suggest the Aβ 42/40 ratio as a potential prognostic biomarker.
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http://dx.doi.org/10.3390/brainsci11030302DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7997395PMC
February 2021

Tau protein as a diagnostic and prognostic biomarker in amyotrophic lateral sclerosis.

Eur J Neurol 2021 Jun 19;28(6):1868-1875. Epub 2021 Mar 19.

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

Background And Purpose: To test the hypothesis that total tau (tTau), tau phosphorylated at threonine 181 (pTau) and pTau/tTau ratio in the cerebrospinal fluid (CSF) are diagnostic and prognostic biomarkers of amyotrophic lateral sclerosis (ALS), we performed a retrospective observational study in a large cohort of ALS patients and controls.

Methods: We enrolled 196 ALS patients and 91 controls, who included patients with ALS-mimicking diseases and those with non-neurodegenerative diseases. All patients underwent lumbar puncture for CSF analysis at the time of the diagnostic evaluation or to first referral. We measured tTau and pTau levels in the CSF by chemiluminescence enzyme immunoassay.

Results: Patients with ALS showed significantly higher levels of CSF tTau and a lower pTau/tTau ratio than controls (tTau: 245 vs. 146 pg/ml; p < 0.001; pTau/tTau ratio: 0.12 vs. 0.18; p < 0.001, respectively). No differences in pTau levels were detected. Receiver-operating characteristic curve analysis showed a good diagnostic accuracy of tTau and pTau/tTau ratio (tTau: area under the curve [AUC] 0.685, 95% confidence interval [CI] 0.616-0.754, p = 0.039; pTau/tTau ratio: AUC 0.777, 95% CI 0.707-0.848, p < 0.001). Among ALS patients, increased tTau levels were associated with advanced age of onset, increased revised amyotrophic lateral sclerosis functional rating scale (ALSFRS-R) score (ΔFS) rate of progression, and spinal onset. Multivariate analysis showed that in ALS patients, this biomarker was an independent negative predictor of overall survival.

Conclusions: Our findings suggest that tTau and pTau/tTau ratio can be diagnostic biomarkers of ALS. In addition, CSF tTau level at diagnosis might play a relevant prognostic role in the disease.
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http://dx.doi.org/10.1111/ene.14789DOI Listing
June 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.

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

Monocyte distribution width as a biomarker of sepsis in the intensive care unit: A pilot study.

Ann Clin Biochem 2021 01 16;58(1):70-73. Epub 2020 Nov 16.

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

Background: Monocyte distribution width has been recently proposed as a sepsis biomarker in the emergency department. The aim of this study was to assess the role of monocyte distribution width as a diagnostic biomarker of sepsis in the intensive care unit.

Methods: In this prospective observational study, we included all consecutive patients admitted to the intensive care unit of the University Hospital "P. Giaccone" of Palermo. Patients were classified into three groups according to Sepsis-3 criteria: (1) patients without sepsis; (2) patients developing sepsis during their hospital stay; (3) patients admitted with sepsis. Monocyte distribution width was measured at admission (groups 1, 2, 3) and daily until the developing of sepsis (group 2) or the end of hospitalization (group 1).

Results: Monocyte distribution width was significantly higher in group 3 than group 1 and group 2 (30.9 [25.6-36.0] vs. 20.3 [18.3-23.6] and 21.4 [19.4-25.2]). Among patients belonging to group 2, monocyte distribution width values, measured at the day when sepsis was clinically diagnosed, were significantly higher than those found at admission: 29.4 (26.7-36.0) vs. 21.4 (19.4-25.2),  = 0.001.

Conclusion: Monocyte distribution width could represent a reliable biomarker of sepsis in the intensive care unit.
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http://dx.doi.org/10.1177/0004563220970447DOI Listing
January 2021

Comparison of a rapid immunochromatographic test with a chemiluminescence immunoassay for detection of anti-SARS-CoV-2 IgM and IgG.

Biochem Med (Zagreb) 2020 Oct;30(3):030901

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

Introduction: The 2019 Coronavirus disease (COVID-19) has been characterized as a pandemic, representing a serious global public health emergency. Serological tests have been proposed as reliable tools for detecting Coronavirus SARS-CoV-2 antibodies in infected patients, especially for surveillance or epidemiological purposes. The aim of this study is to evaluate the agreement between the IgM/IgG rapid assays, based on lateral flow immunochromatographic assay, and the fully automated 2019-nCoV IgM and IgG, based on chemiluminescence immunoassay.

Materials And Methods: SARS-CoV-2 antibodies were measured with the BIOSYNEX COVID-19 BSS IgM/IgG test (BIOSYNEX, Illkirch-Graffenstaden, France) and the MAGLUMI CLIA (IgM and IgG) (SNIBE - Shenzhen New Industries Biomedical Engineering, Shenzhen, China) in 70 serum samples from patients with PCR-confirmed diagnosis. The strength of the agreement of the two methods was calculated by using the Cohen Kappa index.

Results: The results showed a good grade of concordance between the two immunoassays with a Cohen's kappa coefficient of 0.71 (95%CI: 0.54-0.87) for IgG SARS-CoV-2 antibodies and 0.70 (95%CI: 0.53-0.87) for IgM SARS-CoV-2 antibodies. In addition, the rapid assays BIOSYNEX COVID-19 BSS for detecting SARS-CoV-2 antibodies showed a positive likelihood ratio (LR) of 10.63 (95%CI: 2.79-40.57) for IgG and a LR of 6.79 (95%CI: 2.93-15.69) for IgM.

Conclusion: Our results suggest that the immunochromatographic rapid IgM/IgG test and the chemiluminescence IgM and IgG immunoassay have a good degree of concordance, suggesting that both could be considered as useful tools for epidemiologic surveillance.
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http://dx.doi.org/10.11613/BM.2020.030901DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7528641PMC
October 2020

Autoimmunity Features in Patients With Non-Celiac Wheat Sensitivity.

Am J Gastroenterol 2021 May;116(5):1015-1023

Unit of Internal Medicine, "V. Cervello" Hospital, Ospedali Riuniti "Villa Sofia-Cervello," Department of Health Promotion Sciences, Maternal and Infant Care, Internal Medicine and Medical Specialties (PROMISE), University of Palermo, Palermo, Italy.

Introduction: Nonceliac wheat sensitivity (NCWS) is characterized by intestinal and extraintestinal manifestations consequent to wheat ingestion in subjects without celiac disease and wheat allergy. Few studies investigated the relationship between NCWS and autoimmunity. The aim of this study is to evaluate the frequency of autoimmune diseases (ADs) and autoantibodies in patients with NCWS.

Methods: Ninety-one patients (13 men and 78 women; mean age of 40.9 years) with NCWS, recruited in a single center, were included. Seventy-six healthy blood donors (HBD) and 55 patients with a diagnosis of irritable bowel syndrome (IBS) unrelated to NCWS served as controls. Autoantibodies levels were measured. Human leukocyte antigen haplotypes were determined, and duodenal histology performed in all patients carrying the DQ2/DQ8 haplotypes. Participants completed a questionnaire, and their medical records were reviewed to identify those with ADs.

Results: Twenty-three patients with NCWS (25.3%) presented with ADs; autoimmune thyroiditis (16 patients, 17.6%) was the most frequent. The frequency of ADs was higher in patients with NCWS than in HBD (P = 0.002) and in patients with IBS (P = 0.05). In the NCWS group, antinuclear antibodies tested positive in 71.4% vs HBD 19.7%, and vs patients with IBS 21.8% (P < 0.0001 for both). The frequency of extractable nuclear antigen antibody (ENA) positivity was significantly higher in patients with NCWS (21.9%) than in HBD (0%) and patients with IBS (3.6%) (P = 0.0001 and P = 0.004, respectively). Among the patients with NCWS, 9.9% tested positive for antithyroglobulin, 16.5% for antithyroid peroxidase, and 14.3% for antiparietal cell antibodies; frequencies were not statistically different from controls. The presence of ADs was related to older age at NCWS diagnosis, female sex, duodenal lymphocytosis, and eosinophil infiltration.

Discussion: One in 4 patients with NCWS suffered from AD, and serum antinuclear antibodies were positive in a very high percentage of cases. These data led us to consider NCWS to be associated to ADs.
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http://dx.doi.org/10.14309/ajg.0000000000000919DOI Listing
May 2021

Neurogranin as a Novel Biomarker in Alzheimer's Disease.

Lab Med 2021 Mar;52(2):188-196

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

Background: In this study, we investigated the possible role of 2 novel biomarkers of synaptic damage, namely, neurogranin and α-synuclein, in Alzheimer disease (AD).

Methods: The study was performed in a cohort consisting of patients with AD and those without AD, including individuals with other neurological diseases. Cerebrospinal fluid (CSF) neurogranin and α-synuclein levels were measured by sensitive enzyme-linked immunosorbent assays (ELISAs).

Results: We found significantly increased levels of CSF neurogranin and α-synuclein in patients with AD than those without AD. Neurogranin was correlated with total tau (tTau) and phosphorylated tau (pTau), as well as with cognitive decline, in patients with AD. Receiver operating characteristic (ROC) curve analysis showed good diagnostic accuracy of neurogranin for AD at a cutoff point of 306 pg per mL with an area under the curve (AUC) of 0.872 and sensitivity and specificity of 84.2% and 78%, respectively.

Conclusions: Our findings support the use of CSF neurogranin as a biomarker of synapsis damage in patients with AD.
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http://dx.doi.org/10.1093/labmed/lmaa062DOI Listing
March 2021

Reference interval of monocyte distribution width (MDW) in healthy blood donors.

Clin Chim Acta 2020 Nov 22;510:272-277. Epub 2020 Jul 22.

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: The aim of the study was to accurately establish the reference interval (RI) of monocyte distribution width (MDW) in healthy blood donors by the direct method using different statistical approaches.

Methods: MDW was measured in 486 subjects. RI of MDW was calculated by the non-parametric method, the robust method and, the Harrell-Davis bootstrap method and using different tests to identify potential outliers (Dixon-Reed and Tukey).

Results: Lower and upper reference limits of the RI calculated by the non-parametric method were, 16.22 (90%CI 15.78-16.47) - 23.15 (90%CI 22.80-24.10) (without outlier removal), and 16.44 (90%CI 16.21-16.67) - 22.99 (90%CI 22.33-23.22) (after outlier removal). The RIs based on the robust method were, respectively, 16.29-22.98 (without) and 16.50-22.67 (with outlier removal). Finally, the RIs calculated by the Harrell-Davis bootstrap method, without or after outlier removal, were 16.19-23.24 and 16.43-22.93. Thus, the RIs obtained by the three calculation methods were very similar. Additionally, no RI partition was done since no significant gender or age association was found.

Conclusions: Our results support the use of a unique RI of MDW, independently of sex and age.
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http://dx.doi.org/10.1016/j.cca.2020.07.036DOI Listing
November 2020

Pro-inflammatory status is not a limit for longevity: case report of a Sicilian centenarian.

Aging Clin Exp Res 2021 May 23;33(5):1403-1407. Epub 2020 Jun 23.

Laboratory of Immunopathology and Immunosenescence, Department of Biomedicine, Neuroscience and Advanced Diagnostics, University of Palermo, Corso Tuköry, 211, 90134, Palermo, Italy.

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http://dx.doi.org/10.1007/s40520-020-01628-7DOI Listing
May 2021

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

The Phenotypic Characterization of the Cammalleri Sisters, an Example of Exceptional Longevity.

Rejuvenation Res 2020 Dec 11;23(6):476-484. Epub 2020 May 11.

Laboratory of Immunopathology and Immunosenescence, Department of Biomedicine, Neuroscience and Advanced Diagnostics, University of Palermo, Palermo, Italy.

This article shows demographic, clinical, anamnestic, cognitive, and functional data as well as biochemical, genetic, and epigenetic parameters of two exceptional siblings: Diega (supercentenarian) and Filippa (semisupercentenarian) Cammalleri. The purpose of this study is to provide new insights into the extreme phenotypes represented by semisupercentenarians and supercentenarians. Different studies have been published on supercentenarians, but to the best of our knowledge, this is the only concerning two sisters and the most detailed from a phenotypic point of view. Our findings agree with the suggestion that supercentenarians have an increasing relative resistance to age-related diseases, approximating the limits of the functional human reserve to address successfully the acute causes of death. More interestingly, our data agree with, and extend, the suggestion that inflammation and oxidative stress predict centenarian mortality.
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http://dx.doi.org/10.1089/rej.2019.2299DOI Listing
December 2020

Immunosenescence and Its Hallmarks: How to Oppose Aging Strategically? A Review of Potential Options for Therapeutic Intervention.

Front Immunol 2019 25;10:2247. Epub 2019 Sep 25.

Laboratory of Immunopathology and Immunosenescence, Department of Biomedicine, Neuroscience and Advanced Diagnostics, University of Palermo, Palermo, Italy.

Aging is accompanied by remodeling of the immune system. With time, this leads to a decline in immune efficacy, resulting in increased vulnerability to infectious diseases, diminished responses to vaccination, and a susceptibility to age-related inflammatory diseases. An age-associated immune alteration, extensively reported in previous studies, is the reduction in the number of peripheral blood naïve cells, with a relative increase in the frequency of memory cells. These two alterations, together with inflamm-aging, are considered the hallmarks of immunosenescence. Because aging is a plastic process, it is influenced by both nutritional and pharmacological interventions. Therefore, the role of nutrition and of immunomodulation in immunosenescence is discussed, due to the multifactorial influence on these hallmarks. The close connection between nutrition, intake of bioactive nutrients and supplements, immune function, and inflammation demonstrate the key role of dietary strategies as regulators of immune response and inflammatory status, hence as possible modulators of the rate of immunosenescence. In addition, potential options for therapeutic intervention are clarified. In particular, the use of interleukin-7 as growth factor for naïve T cells, the function of checkpoint inhibitors in improving T cell responses during aging and, the potential of drugs that inhibit mitogen-activated protein kinases and their interaction with nutrient signaling pathways are discussed. Finally, it is suggested that the inclusion of appropriate combinations of toll-like receptor agonists may enhance the efficacy of vaccination in older adults.
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http://dx.doi.org/10.3389/fimmu.2019.02247DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6773825PMC
October 2020

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.
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http://dx.doi.org/10.1016/j.cca.2019.07.022DOI Listing
October 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.
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http://dx.doi.org/10.11613/BM.2019.020901DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6559611PMC
June 2019

Vitamin D and the nervous system.

Neurol Res 2019 Sep 30;41(9):827-835. Epub 2019 May 30.

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

: to summarise the activities that Vitamin D (VD) carries out in the brain and to clarify the potential role of VD in neurological diseases. : a literature research has been performed in Pubmed using the following keywords: 'Vitamin D', 'nervous system', 'brain'. : the studies reviewed show that VD contributes to cerebral activity in both embryonic and adult brain, helping the connectivity of neural circuits responsible for locomotor, emotional and reward-dependent behavior. Low VD serum levels have been found in patients affected by Alzheimer Disease, Parkinson Disease, Multiple Sclerosis, Autism Spectrum Disorders, Sleep Disorders and Schizophrenia. : findings are controversial and should be interpreted with caution, since most of the studies performed have observational study set and few interventional studies are available, producing conflicting results. Overall, it can be stated that the potential role of Vitamin D in neurological diseases is mostly unclear and further randomised controlled trials are needed to understand better whether Vitamin D supplementation treatment can be useful in brain disorders.
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http://dx.doi.org/10.1080/01616412.2019.1622872DOI Listing
September 2019

Genotypic and Phenotypic Aspects of Longevity: Results from a Sicilian Survey and Implication for the Prevention and Treatment of Age-related Diseases.

Curr Pharm Des 2019 ;25(3):228-235

Section of General Pathology, Department of Biomedicine, Neurosciences and Advanced Technologies, University of Palermo, Corso Tukory 211, Palermo 90134, Italy.

Background: It is well known that long living individuals are a model of successful ageing and that the identification of both genetic variants and environmental factors that predispose to a long and healthy life is of tremendous interest for translational medicine.

Methods: We present the preliminary findings obtained from an ongoing study on longevity conducted on a sample of Sicilian long-lived individuals.

Results: We review the characteristics of longevity in Sicily, taking into account lifestyle, environment, genetics, hematochemical values, body composition and immunophenotype. In addition, we discuss the possible implications of our data for the prevention and/or treatment of age-related diseases.

Conclusion: As widely discussed in this review, the explanation of the role of genetics and lifestyle in longevity can provide important information on how to develop drugs and/or behaviours that can slow down or delay ageing. Thus, it will be possible to understand, through a "positive biology" approach, how to prevent and/or reduce elderly frailty and disability.
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http://dx.doi.org/10.2174/1381612825666190313115233DOI Listing
February 2020

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

Role of Immunogenetics in the Outcome of HCMV Infection: Implications for Ageing.

Int J Mol Sci 2019 Feb 5;20(3). Epub 2019 Feb 5.

Department of Microbiology and Immunology, Medical University of South Carolina, 171 Ashley Ave, Charleston, SC 29425, USA.

The outcome of host-virus interactions is determined by a number of factors, some related to the virus, others to the host, such as environmental factors and genetic factors. Therefore, different individuals vary in their relative susceptibility to infections. Human cytomegalovirus (HCMV) is an important pathogen from a clinical point of view, as it causes significant morbidity and mortality in immunosuppressed or immunosenescent individuals, such as the transplanted patients and the elderly, respectively. It is, therefore, important to understand the mechanisms of virus infection control. In this review, we discuss recent advances in the immunobiology of HCMV-host interactions, with particular emphasis on the immunogenetic aspects (human leukocyte antigens, HLA; killer cell immunoglobulin-like receptors, KIRs; immunoglobulin genetic markers, GM allotypes) to elucidate the mechanisms underlying the complex host-virus interaction that determine various outcomes of HCMV infection. The results, which show the role of humoral and cellular immunity in the control of infection by HCMV, would be valuable in directing efforts to reduce HCMV spurred health complications in the transplanted patients and in the elderly, including immunosenescence. In addition, concerning GM allotypes, it is intriguing that, in a Southern Italian population, alleles associated with the risk of developing HCMV symptomatic infection are negatively associated with longevity.
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http://dx.doi.org/10.3390/ijms20030685DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6386818PMC
February 2019

Association of immunoglobulin GM allotypes with longevity in long-living individuals from Southern Italy.

Immun Ageing 2018 6;15:26. Epub 2018 Nov 6.

4Department of Microbiology and Immunology, Medical University of South Carolina, Charleston, SC 29425 USA.

Background: The aim of this study was to analyse the role of GM allotypes, i.e. the hereditary antigenic determinants expressed on immunoglobulin polypeptide chains, in the attainment of longevity. The role played by immunoglobulin allotypes in the control of immune responses is well known as well as the role of an efficient immune response in longevity achievement. So, it is conceivable that particular GM allotypes may contribute to the generation of an efficient immune response that supports successful ageing, hence longevity.

Methods: In order to show if GM allotypes play a role in the achievement of longevity, we typed the DNA of 95 Long-living individuals (LLIs) and 96 young control individuals (YCs) from South Italy for GM3/17 and GM23+/- alleles.

Results: To demonstrate the role of GM allotypes in the attainment of longevity we compared genotype and allele frequencies of GM allotypes between LLIs and YCs. A global chi-square test (3 × 2) shows that the distribution of genotypes at the GM 3/17 locus is highly significantly different in LLIs from that observed in YCs ( < 0.0001). The 2 × 2 chi-square test shows that the carriers of the GM3 allele contribute to this highly significant difference. Accordingly, GM3 allele is significantly overrepresented in LLIs. No significant differences were instead observed regarding GM23 allele.

Conclusion: These preliminary results show that GM3 allotype is significantly overrepresented in LLIs. To best of our knowledge, this is the first study performed to assess the role of GM allotypes in longevity. So, it should be necessary to verify the data in a larger sample of individuals to confirm GM role in the attainment of longevity.
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http://dx.doi.org/10.1186/s12979-018-0134-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6219083PMC
November 2018

Translation of Basic Research into Clinics: Killer Immunoglobulin-like Receptors Genes in Autoimmune and Infectious Diseases.

Curr Pharm Des 2018 ;24(26):3113-3122

University of Bari Aldo Moro, Department of Emergency and Organ Trasplants, Piazza G. Cesare 11, 70124, Bari, Italy.

Killer immunoglobulin-like receptors (KIRs) regulate the activation of natural killer cells through their interaction with human leucocyte antigens (HLA). KIRs and HLA loci are highly polymorphic, and some of their combinations have been found to protect against viral infections or to predispose to autoimmune disorders. In particular, some activating KIRs profiles may be detrimental in autoimmune pathogenesis, and specific KIRs may be particularly aggressive in the clearance of different microorganisms, protecting individuals in the control of a given pathogen. So, considering that in the pathogenesis of many autoimmune disorders and infections innate immunity plays a key role, the recent development for KIRs characterization, diseases monitoring, and treatment becomes obvious. Here, we reviewed a growing body of evidence supporting the influence of KIRs variants and their interaction with ligands in the development of the main human autoimmune and viral diseases, highlighting the main applications in clinical practice.
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http://dx.doi.org/10.2174/1381612824666180911123249DOI Listing
October 2019

Sicilian centenarian offspring are more resistant to immune ageing.

Aging Clin Exp Res 2019 Jan 28;31(1):125-133. Epub 2018 Mar 28.

Department of Pathobiology and Medical Biotechnologies, University of Palermo, Palermo, Italy.

Background: Immunosenescence constitutes a major indirect cause of morbidity and mortality in the elderly. Previous analysis of immune signatures in a cohort of centenarian offspring showed an intermediate immunophenotype between age-matched and younger controls.

Aims: To confirm and extend the previous studies performing further phenotypical analysis in centenarian offspring and controls.

Methods: Analysis of Treg cells, γδ T cells, mucosal-associated invariant T cells, and senescent immune T cells was performed in centenarian offspring and controls.

Results: We report significant differences between elderly and centenarian offspring in most of the studied subsets, showing that centenarian offspring subsets present an intermediate phenotyping between elderly and younger people.

Conclusion: The whole present data confirm and extend the previous results showing that centenarian offspring retain more youthful immunological parameters and that the exhaustion of the immune system is less evident than in elderly without centenarian parents, though further investigations are warranted.
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http://dx.doi.org/10.1007/s40520-018-0936-7DOI Listing
January 2019

HLA-C1 ligands are associated with increased susceptibility to systemic lupus erythematosus.

Hum Immunol 2018 Mar 2;79(3):172-177. Epub 2018 Feb 2.

Department of Pathobiology and Medical Biotechnologies (Di.Bi.Med.), University of Palermo, Palermo, Italy.

Recently, the role of killer cell immunoglobulin-like receptor (KIR) in autoimmune diseases has received increasing attention. The present study was undertaken to determine the association of KIR genes and the human leukocytes antigen (HLA) ligands with Systemic Lupus Erythematosus (SLE) and accompanying oxidative stress. Presence or absence of 17 KIR and 5 HLA loci was performed using the polymerase chain reaction-sequence specific primer (PCR-SSP) method by case-control study. A total of 45 SLE patients, and 60 healthy controls, all of Sicilian descent, were enrolled. Plasma values of the anti-oxidant molecule Taurine were determined in all subjects by capillary electrophoresis UV detection. The carrier frequency of the KIR2DS2 gene was significantly increased in SLE patients compared to healthy controls (73.3 versus 45.0%; OR = 3.36; 95% CI = 1.46-7.74; p = .005) suggesting a role of KIR2DS2 gene in the susceptibility to disease. We also observed a strong positive association between the presence of HLA-C1 ligands group and the disease (82.2% in SLE patients versus 41.7% in controls; OR = 6.47, 95% CI = 2.58-16.26; p < .0001). Stepwise logistic regression analysis supported the effect of the HLA-C1 ligands in SLE patients (OR = 7.06, 95% CI = 0.07-2.19; p = .002), while the KIR genes were no longer significant. Interestingly, we found that SLE patients HLA-C1 positive showed significantly decreased plasma levels of antioxidant activity marker Taurine (69.38 ± 28.49 μmol/L) compared to SLE patients HLA-C1 negative (108.37 ± 86.09 μmol/L) (p = .03). In conclusion, HLA-C1 ligands group was significantly associated with an increased risk of SLE as well as an increased oxidative stress status overall in SLE patients.
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http://dx.doi.org/10.1016/j.humimm.2018.01.005DOI Listing
March 2018

Targeting Aging with Functional Food: Pasta with Opuntia Single-Arm Pilot Study.

Rejuvenation Res 2018 Jun 10;21(3):249-256. Epub 2017 Oct 10.

1 Department of Pathobiology and Medical Biotechnologies, University of Palermo , Palermo, Italy .

Interventions to extend life span represent the new perspective in aging investigation. Healthy dietary habits are important modifiable factors that can favor a healthy aging phenotype. Many studies have demonstrated benefits for metabolic syndrome and type 2 diabetes mellitus resulting from the traditional Mediterranean foods. Opuntia Ficus Indica (OFI), widespread in the Mediterranean basin, belongs to the Cactaceae family. It is known for its antioxidant and anti-inflammatory properties. Moreover, products containing extracts from OFI fruits or cladodes have been used to control obesity and other metabolic parameters, such as glycemia and lipid profile. The aim of this study was to analyze the antioxidant and anti-inflammatory effect of pasta with 3% of OFI cladode extracts added to show its beneficial effect in human health. We performed a single arm longitudinal intervention study in 42 healthy volunteers, administrating 500 g/week of this functional pasta for 30 days. Our pasta had antioxidant and anti-inflammatory properties with putative effect on the aging process and related metabolic diseases. We also demonstrated a hypoglycemic effect. The results are preliminary, but it is possible to speculate that our pasta could be considered an effective food for the prevention of age-related metabolic disorders.
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http://dx.doi.org/10.1089/rej.2017.1992DOI Listing
June 2018

Nutrient sensing pathways as therapeutic targets for healthy ageing.

Expert Opin Ther Targets 2017 Apr 17;21(4):371-380. Epub 2017 Feb 17.

a Department of Pathobiology and Medical Biotechnologies , University of Palermo , Palermo , Italy.

Introduction: In the present paper, the authors have discussed anti-aging strategies which aim to slow the aging process and to delay the onset of age-related diseases, focusing on nutrient sensing pathways (NSPs) as therapeutic targets. Indeed, several studies have already demonstrated that both in animal models and humans, dietary interventions might have a positive impact on the aging process through the modulation of these pathways. Areas covered: Achieving healthy aging is the main challenge of the twenty-first century because lifespan is increasing, but not in tandem with good health. The authors have illustrated different approaches that can act on NSPs, modulating the rate of the aging process. Expert opinion: Humanity's lasting dream is to reverse or, at least, postpone aging. In recent years, increasing attention has been devoted to anti-aging therapies. The subject is very popular among the general public, whose imagination runs wild with all the possible tools to delay aging and to gain immortality. Some approaches discussed in the present review should be able to substantially slow down the aging process, extending our productive, youthful lives, without frailty.
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http://dx.doi.org/10.1080/14728222.2017.1294684DOI Listing
April 2017