The elderly health status and its correlation with ageing biomarkers: the European Project Mark-Age

According to the latest statistics projections formulated by Eurostat, the proportion of elderly EU-27’s population aged over 65 years old is predicted to increase from 17.5 % in 2011 to 29.5 % by 2060. This "population explosion" makes extremely important to identify the different genetic and molecular mechanisms which underpin the morbidity and mortality along with new strategies able to counteract or slow down its progress. In this scenario fits the European Project MARK-AGE whose aim was to identify a robust set of biomarkers of human ageing able to discriminate between chronological and biological ageing and to derive a model for healthy ageing through the analysis of three populations from different European countries, supposed to be characterized by different ageing rate: 1. Subjects representing the “Normal” or “Physiological” aging. 2. Subjects representing the “successful” or “decelerate” aging 3. Subjects representing the “accelerated” aging. The aim of this work was to recruit and characterize volunteers, to perform an accurate analysis of the health status of elderly recruited subjects (60-79 years) verifying any possible dissimilarity in their aging trajectories, to identify a set of robust ageing biomarkers and investigate possible correlations between ageing biomarkers and health status of recruited volunteers. The model proposed by MARK-AGE Project regarding different ageing trajectories has been confirmed and several ageing biomarkers have been identified

Diagnostic proteomic biomarkers to detect kidney diseases

Urinary proteomics is primarily applied to the study of renal and urogenital tract disorders. Here are reported two distinct successful examples of this approach for the discovery of early urinary biomarkers of kidney­ related dysfunctions: diabetic nephropathy (DN), a well ­known complication of diabetes frequently leading to dialysis, and drug­induced nephrotoxicity, a possible condition caused by medication ­overuse headache (MOH). Early detection of kidney disorders based on selective biomarkers could permit to diagnose patients at the initial stage of the disease, where the therapy is still possible to stop or prevent occurrence of advance disease. Urine samples were first concentrated and desalted. Subsequently, they were subjected to two­-dimensional gel electrophoresis (2­DE) coupled to mass spectrometry (MS) for protein identification. Furthermore, some proteins were verified by Western blot and ELISA test. In diabetes-­related study, 11 differentially expressed proteins were detected (8 up­regulated and 3 down­regulated) in type 2 diabetic (T2D) and T2DN patients compared to the healthy control subjects. In MOH study, a total of 21 over­excreted proteins was revealed in urine of non­-steroidal anti­inflammatory drugs (NSAIDs) and mixtures abusers vs controls. Particularly, 4 proteins were positively validated by immunoblotting and ELISA. Urinary proteomics allows non­invasive assessment of renal diseases at an early stage by the identification of characteristic protein pattern

Exploration of candidate serum biomarkers potentially related to the chronic pain condition in Medication-overuse headache

Background Medication Overuse Headache (MOH) is a prevalent and disabling disorder resulting from the overuse of analgesic drugs, triptans or other acute headache medications. In previous proteomic studies, several proteins have been found at high concentrations in the urine of MOH patients and in the serum of rats with neuropathic pain. The aim of this study was to compare the serum levels of lipocalin-type Prostaglandin D2 synthase (L-PGDS), Vitamin D-binding protein (VDBP), apolipoprotein E (APOE) and apolipoprotein A1 (APOA1) in MOH patients and healthy individuals, further exploring their relationship with cutaneous pain thresholds (CPTs) in the territories innervated by the trigeminal nerve. Methods 69 MOH patients and 42 age- and sex-matched healthy volunteers were enrolled in the study. Von Frey-like filaments were applied to the skin territories innervated by the trigeminal nerve, to determine the CPTs. L-PGDS, VDBP, APOE and APOA1 were quantified in the serum by Enzyme-linked Immunosorbent Assay (ELISA). Clinical and laboratory data were collected. Comparisons between MOH patients and healthy individuals were performed using independent t test or χ2 test. To correlate serum proteins with CPTs, Pearson correlation coefficient or Spearman's rank correlation coefficient were used. Results CPTs were lower among MOH patients. L-PGDS, VDBP and APOE had significantly different serum concentrations between groups (p < 0.01), but no correlation was found with CPTs. APOA1 serum concentrations did not differ between patients and healthy individuals. Conclusions L-PGDS, VDBP and APOE had abnormal serum levels in MOH patients, confirming their alteration in some conditions of chronic headache and neuropathic pain. The in-depth study of target proteins represents a promising approach for a better understanding of MOH, as well as the detection of candidate biomarkers for chronic headache or the risks associated with overuse medications

Comparison of Oxford Cognitive Screen and Montreal Cognitive Assessment feasibility in the stroke unit setting. A pilot study

Background: : Cognitive status evaluation is not routine in the acute stroke setting and there is no consensus on which neuropsychological tool is more feasible and informative. The aim of this pilot study was to compare the feasibility and acceptability of two brief cognitive tests, the Montreal Cognitive Assessment (MoCA) and the Oxford Cognitive Screen (OCS), in acute stroke, with a focus on patients' experience, administration time, and the cognitive data obtained. Methods: : Patients with a diagnosis of ischemic or hemorrhagic stroke or of transient ischemic attack admitted to two stroke units were included. The sample consisted of 34 participants (mean age ±SD 71.1 ± 16.1 years, 25 males). Within five days of onset, patients were evaluated by means of the MoCA and OCS by a trained neuropsychologist. Results: Both tests were feasible in the stroke unit setting and had a high level of acceptability by patients. MoCA test was fully completed by 25 patients, OCS by 21 patients. The OCS administration time was longer than that of the MoCA. However, OCS was perceived less demanding than MoCA by patients. Twenty patients completed both the MoCA and the OCS entirely, and only 2 of them did not show any impairment in both tests. Seventeen patients showed at least an impaired domain on the OCS and 15 patients presented with a MoCA global score below cut-off for cognitive impairment. Conclusions: Our preliminary study did not show a superiority of the OCS over the widely used MoCA, and suggests the need for further validation in larger samples of stroke patients, exploring tests accuracy in detecting cognitive post-stroke impairment

Validation of potential candidate biomarkers of drug-induced nephrotoxicity and allodynia in medication-overuse headache

Medication-overuse headache (MOH) is a chronic disorder that results from the overuse of analgesics drugs, triptans or other acute headache compounds. Although the exact mechanisms underlying MOH remain still unknown, several studies suggest that it may be associated with development of "central sensitization", which may cause cutaneous allodynia (CA). Furthermore, the epidemiology of drug-induced disorders suggests that medication overuse could lead to nephrotoxicity. The aim of this work was to confirm and validate the results obtained from previous proteomics studies, in which we analyzed the urinary proteome of MOH patients in comparison with healthy non-abusers individuals

The omics in migraine

The term omics consist of three main areas of molecular biology, such as genomics, proteomics and metabolomics. The omics synergism recognise migraine as an ideal study model, due to its multifactorial nature. In this review, the plainly research data featuring in this complex network are reported and analyzed, as single or multiple factor in pathophysiology of migraine. The future of migraine biomolecular research shall be focused on networking among these different and hierarchical disciplines. We have to look for its Ariadne's tread, in order to see the whole painting of migraine molecular biology

The Pandemic in the Trentino Asylum Reception System: Subjectivities Lost Within the "Health of the Facility"

This contribution results from research conducted during the first months of the COVID-19 pandemic. It explores how the restrictions imposed for safety reasons impacted the everyday routines of a group of asylum seekers and beneficiaries of protection hosted in the asylum reception system in the city of Trento, Italy. Drawing on the interviews, the authors enlighten how the "health of the facility" sometimes came at the expense of the health of the individual, reducing their sociability outside the reception facilities and, therefore, their opportunities to develop their paths toward independence

Acute treatment with relaxin protects the kidney against ischaemia/reperfusion injury.

Although recent preclinical and clinical studies have demonstrated that recombinant human relaxin (rhRLX) may have important therapeutic potential in acute heart failure and chronic kidney diseases, the effects of acute rhRLX administration against renal ischaemia/reperfusion (I/R) injury have never been investigated. Using a rat model of 1-hr bilateral renal artery occlusion followed by 6-hr reperfusion, we investigated the effects of rhRLX (5 μg/Kg i.v.) given both at the beginning and after 3 hrs of reperfusion. Acute rhRLX administration attenuated the functional renal injury (increase in serum urea and creatinine), glomerular dysfunction (decrease in creatinine clearance) and tubular dysfunction (increase in urinary excretion of N-acetyl-β-glucosaminidase) evoked by renal I/R. These beneficial effects were accompanied by a significant reduction in local lipid peroxidation, free radical-induced DNA damage and increase in the expression/activity of the endogenous antioxidant enzymes MnSOD and CuZnSOD superoxide dismutases (SOD). Furthermore, rhRLX administration attenuated the increase in leucocyte activation, as suggested by inhibition of myeloperoxidase activity, intercellular-adhesion-molecule-1 expression, interleukin (IL)-1β, IL-18 and tumour necrosis factor-α production as well as increase in IL-10 production. Interestingly, the reduced oxidative stress status and neutrophil activation here reported were associated with rhRLX-induced activation of endothelial nitric oxide synthase and up-regulation of inducible nitric oxide synthase, possibly secondary to activation of Akt and the extracellular signal-regulated protein kinase (ERK) 1/2, respectively. Thus, we report herein that rhRLX protects the kidney against I/R injury by a mechanism that involves changes in nitric oxide signalling pathway

Proteomic research of proteins involved in pain expression in an animal model of chronic pain

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Discovery by a proteomic approach of possible early biomarkers of drug-induced nephrotoxicity in medication-overuse headache

BACKGROUND: Medication-overuse headache (MOH) is a chronic headache condition that results from the overuse of analgesics drugs, triptans, or other antimigraine compounds. The epidemiology of drug-induced disorders suggests that medication overuse could lead to nephrotoxicity, particularly in chronic patients. The aim of this work was to confirm and extend the results obtained from a previous study, in which we analyzed the urinary proteome of 3 MOH patients groups: non-steroidal anti-inflammatory drugs (NSAIDs), triptans and mixtures abusers, in comparison with non-abusers individuals (controls). METHODS: In the present work we employed specialized proteomic techniques, namely two-dimensional gel electrophoresis (2-DE) coupled with mass spectrometry (MS), and the innovative Surface-Enhanced Laser Desorption/Ionization Time-of-Flight mass spectrometry (SELDI-TOF-MS), to discover characteristic proteomic profiles associated with MOH condition. RESULTS: By 2-DE and MS analysis we identified 21 over-excreted proteins in MOH patients, particularly in NSAIDs abusers, and the majority of these proteins were involved in a variety of renal impairments, as resulted from a literature search. Urine protein profiles generated by SELDI-TOF-MS analysis showed different spectra among groups. Moreover, significantly higher number of total protein spots and protein peaks were detected in NSAIDs and mixtures abusers. CONCLUSIONS: These findings confirm the presence of alterations in proteins excretion in MOH patients. Analysis of urinary proteins by powerful proteomic technologies could lead to the discovery of early candidate biomarkers, that might allow to identify MOH patients prone to develop potential drug overuse-induced nephrotoxicity