The Tumor Necrosis Factor-α-blocking Agent Infliximab Inhibits Interleukin 1ß (IL-1ß) and IL-6 Gene Expression in Human Osteoblastic Cells

Objective.Tumor necrosis factor-α (TNF-α) is a proinflammatory cytokine involved in the pathogenesis of several rheumatic diseases, including rheumatoid arthritis (RA), associated with systemic bone loss and subchondral bone erosions. TNF-α-blocking agents such as infliximab have been successful in treatment of disease-modifying antirheumatic drug-resistant rheumatic diseases. Infliximab therapy in RA also had beneficial effects on local bone destruction and bone mineral density. We assessed effects of infliximab treatment on the bone tissue compartment and cytokine profile expression in vitro.Methods.Osteoblast-like cells were exposed for 24 h to sera of RA patients collected at baseline and after 1 month (T1) and 3 years (T2) of infliximab treatment. Total RNA was extracted, and expression of interleukin 1ß (IL-1ß), IL-6, and osteoprotegerin (OPG) was measured by RT-PCR.Results.IL-1ß gene expression was significantly reduced by the T1 serum, and the same decrease was elicited by the T2 serum. IL-6 downregulation was evident with the T2 serum. OPG was unaffected.Conclusion.The finding of downregulation of inflammatory cytokines was interesting, particularly IL-6, which plays a crucial role in arthritis-related bone loss due to its involvement in osteoclast recruitment and activation. These results may represent a biological explanation and a link for the clinical observation of the beneficial effects of anti-TNF-α agents on the progression of rheumatic diseases at the bone level

Metabolic Syndrome and All-Cause and Cardiovascular Mortality in an Italian Elderly Population: The Progetto Veneto Anziani (Pro.V.A.) Study

OBJECTIVE—The purpose of this study was to explore the association of metabolic syndrome and each of its components with all-cause and cardiovascular mortality in a general Italian elderly population

Poor Physical Performance Predicts Future Onset of Depression in Elderly People: Pro.V.A. Longitudinal Study

Background: Reduced physical performance is predictive of deleterious outcomes in older adults. Data considering objective physical performance and incident depression is sparse. Objective: We investigated whether objective physical performance can predict incident depression among non-depressed older adults during a 4-year study. Design: longitudinal. Methods: From 3,099 older individuals initially enrolled in the Progetto Veneto Anziani study, 970 participants without depression at baseline were included (mean age 72.5 years, 54.6% females). Physical performance measures included the Short Physical Performance Battery (SPPB), 4m gait speed, five times sit-to-stand test, leg extension and flexion, handgrip strength, and 6-Minute Walking Test (6MWT), categorized in gender-specific tertiles. Depression was classified based on the Geriatric Depression Scale (GDS) and a diagnosis from a geriatric psychiatrist. Area under the curve (AUC) and logistic regression analyses were conducted. Results: At baseline, participants developing depression during follow-up (n = 207) scored significantly worse across all physical performance measures than those who did not develop depression. The AUC and predictive power for each physical performance test was similar for all the tests assessed. In logistic regression analysis, after adjusting for 14 potential confounders, worse physical performance across all tests increased the risk of depression. The lowest tertile of the SPPB were at notable odds of developing depression (OR = 1.79; 95%CI: 1.18-2.71). The association between poor physical performance and depression was typically stronger in women than in men, except for 4m gait speed. Limitations: no gold standard used for depression diagnosis; oxidative stress and inflammatory markers were not included; high rate of missing data at follow-up. Conclusion: Low physical performance appears to be an independent predictor of depression over a 4.4-year follow-up in our sample of elderly people

European Project on Osteoarthritis (EPOSA): methodological challenges in harmonization of existing data from five European population-based cohorts on aging

BackgroundThe European Project on OSteoArthritis (EPOSA), here presented for the first time, is a collaborative study involving five European cohort studies on aging. This project focuses on the personal and societal burden and its determinants of osteoarthritis (OA). The aim of the current report is to describe the purpose of the project, the post harmonization of the cross-national data and methodological challenges related to the harmonization process MethodsThe study includes data from cohort studies in five European countries (Germany, Italy, the Netherlands, Spain and the United Kingdom) on older community-dwelling persons aged ? 59 years. The study design and main characteristics of the five cohort studies are described. Post harmonization algorithms are developed by finding a "common denominator" to merge the datasets and weights are calculated to adjust for differences in age and sex distribution across the datasets. ResultsA harmonized database was developed, consisting of merged data from all participating countries. In total, 10107 persons are included in the harmonized dataset with a mean age of 72.8 years (SD 6.1). The female/male ratio is 53.3/46.7%. Some variables were difficult to harmonize due to differences in wording and categories, differences in classifications and absence of data in some countries. The post harmonization algorithms are described in detail in harmonization guidelines attached to this paper. ConclusionsThere was little evidence of agreement on the use of several core data collection instruments, in particular on the measurement of OA. The heterogeneity of OA definitions hampers comparing prevalence rates of OA, but other research questions can be investigated using high quality harmonized data. By publishing the harmonization guidelines, insight is given into (the interpretation of) all post harmonized data of the EPOSA study. <br/

Vitamin D and Physical Performance in Elderly Subjects: The Pro.V.A Study

Background The role of Vitamin D in musculoskeletal functionality among elderly people is still controversial. We investigated the association between serum 25-hydroxyvitamin D (25OHD) levels and physical performance in older adults. Methods 2694 community-dwelling elderly women and men from the Progetto Veneto Anziani (Pro.V.A.) were included. Physical performances were assessed by: tandem test, 5 timed chair stands (TCS), gait speed, 6-minute walking (6 mW) distance, handgrip strength, and quadriceps strength. For each test, separate general linear models and loess plots were obtained in both genders, in relation to serum 25OHD concentrations, controlling for several potential confounders. Results Linear associations with 25OHD levels were observed for TCS, gait speed, 6 mW test and handgrip strength, but not for tandem test and quadriceps strength. After adjusting for potential confounders, linear associations with 25OHD levels were still evident for the 6 mW distance in both genders (p = .0002 in women; <.0001 in men), for TCS in women (p = .004) and for gait speed (p = .0006) and handgrip strength (p = .03) in men. In loess analyses, performance in TCS in women, in gait speed and handgrip strength in men and in 6 mW in both genders, improved with increasing levels of 25OHD, with most of the improvements occurring for 25OHD levels from 20 to 100 nmol/L. Conclusion lower 25OHD levels are associated with a worse coordination and weaker strength (TCS) in women, a slower walking time and a lower upper limb strength in men, and a weaker aerobic capacity (6 mW) in both genders. For optimal physical performances, 25OHD concentrations of 100 nmol/L appear to be more advantageous in elderly men and women, and Vitamin D supplementation should be encouraged to maintain their 25OHD levels as high as this threshold

Edentulism and prosthetic rehabilitation in older men and women. Does gender matter? Results from the longitudinal Pro.V.A. Study

This data set is part of the Pro.V.A. Study database. The Pro.V.A. Study is an observational cohort study of an Italian population aged ≥65 yrs living in Northeastern Italy, focused on the effects of cardiovascular and osteoarticular diseases on disability. The study population included 3099 subjects at baseline /started in 1995), 2196 at follow up 1 and 1641 at follow up 2 (5 and 7 yrs later, respectively)

Polyunsaturated fatty acids and renal fibrosis:pathophysiologic link and potential clinical implications

The role of polyunsaturated fatty acids in renal fibrosis. Several studies suggest a close relationship between polyunsaturated fatty acids (PUFA) and renal inflammation and fibrosis, which are crucial stages in chronic kidney disease (CKD). Beneficial effects of n-3 PUFA on the course of experimental and human nephropathies have been reported. PUFA can ameliorate chronic, progressive renal injury beyond the simple reduction of serum lipid levels. These pleiotropic effects of PUFA are due to their properties of interfering with the synthesis of a variety of inflammatory factors and events, through effects related both to the modulation of the balance of n-6 and n-3-derived eicosanoids and to direct action on the cellular production of the major cytokine mediators of inflammation and on endothelium function. The mechanisms by which PUFA can favorably interfere with some stages in renal fibrosis processes, such as mesangial cell activation and proliferation and extracellular matrix protein synthesis, include the regulation of some pro-inflammatory cytokine production, renin and nitric oxide (NO) systems and peroxisome proliferator-activated receptor gene expression. An optimal n-6/n-3 PUFA ratio dietary intake could offer new therapeutic strategies aimed at interrupting the irreversible process of renal fibrosis and ameliorating chronic renal injury. However, further experimental, epidemiological and clinical investigations are needed to confirm the role of PUFA in the renal fibrosis pathway and the natural history of chronic nephropathies

Misdiagnosis and Mistreatment of a Rare Case of Intracranial Oncogenic Osteomalacia with an Altered Amino Acid Profile

Background. Oncogenic osteomalacia (OO), also known as tumor-induced osteomalacia (TIO), is a rare paraneoplastic syndrome caused by mesechymal tumors secreting fibroblast growth factor 23 (FGF23). Common in middle age, these tumors are often disclosed by progressive generalized bone pain and muscle weakness, along with an altered biochemical profile. Despite its characteristic presentation, the disease is often underrecognized with delayed onset of surgical or pharmacological intervention that can have serious repercussions on the patients&rsquo; health and quality of life. Case presentation. We describe the case of a 65-year-old Caucasian man presenting TIO with intracranial and spinal localizations and Fanconi-like aminoaciduria. The condition was misdiagnosed and mistreated for three years, leading to loss of self-sufficiency and depression. Following proper identification, the spinal mass was excised with complete remission of the functional symptoms. As it was not possible to remove the intracranial lesion, the patient was treated conservatively with calcitriol and phosphorous supplements that granted good metabolic control up to the time of a recent follow-up visit (at 5 years). Conclusions. The finding of an altered amino acid profile, not usually reported in these cases, should prompt clinicians to a wider usage of these molecules as suitable candidates for metabolic diseases. In addition to providing central information, they are easy to obtain and inexpensive to analyze. Such determination could help to speed up the diagnostic process, as a long-lasting history of misdiagnosis and mistreatments can lead primarily to clinical worsening, but also to the use of expensive, useless medications with side effects that contribute to poor patient health

Pazienti affetti da malattie croniche, situazioni critiche e strategie di reazione: uno studio qualitativo tra i pazienti affetti da quattro tipi di malattie croniche, seguiti in centri del nord-est d’Italia

Living with a chronic condition represents a strenuous experience that often could be lived as a sequence of waiting and crisis times. Therapeutic path incidents could represent however a catalysts and revelatory time, useful to patients to discover their own resources. A qualitative study according to the phenomenological hermeneutic perspective was conducted to understand the kind of skills expressed by the patients during a difficult episode, and the characteristics that identify patients who can overcome them better. From September 2019 to August 2020 twenty-three patients followed-up in four Hospital Units of Northeastern of Italy were enrolled. All the patients described an episode linked whit their pathological condition; they mentioned mainly supportive, reactive, or behavioral strategies and an acceptance attitude. The sample characteristics may explain the recurring acceptance attitude; however, the younger individuals, those with a higher level of education and those who faced precedent negative life experiences seem to better overcome challenging events. It can’t be taken for granted that patients possess all the skills necessary to overcome the frequent challenging episodes they have to face; for this reason, healthcare professionals should assess their learning and reactive attitude in order to tailor for them therapeutic education paths.Vivere con una malattia cronica rappresenta un’esperienza stressante che spesso può essere vissuta come un alternarsi di momenti di crisi e di attesa di nuove crisi. Gli incidenti critici presenti nel percorso terapeutico possono comunque rappresentare un momento catalizzatore e rivelatore, utile ai pazienti per scoprire le proprie risorse. È stato condotto uno studio qualitativo secondo la prospettiva della fenomenologia ermeneutica con l’obiettivo di comprendere il tipo di abilità espresse dai pazienti durante un episodio sfidante e le caratteristiche che identificano i pazienti capaci di superarlo meglio. Da settembre 2019 ad agosto 2020 sono stati arruolati nello studio ventitré pazienti seguiti in quattro Unità Ospedaliere del Nordest d’Italia. Tutti i pazienti hanno descritto un episodio legato alla loro condizione patologica; hanno menzionato principalmente strategie di ricerca di supporto, di tipo reattivo o comportamentale e un generale atteggiamento di accettazione. Le caratteristiche del campione possono spiegare il ricorrente atteggiamento di accettazione; tuttavia, gli individui più giovani, quelli con un livello di istruzione più elevato e coloro che hanno affrontato precedenti esperienze di vita negative sembrano superare meglio degli altri alcuni eventi difficili. Non è scontato che i pazienti possiedano tutte le competenze necessarie per superare i frequenti episodi sfidanti che devono affrontare; per questo motivo, gli operatori sanitari dovrebbero preventivamente valutare le loro capacità di apprendimento e le loro strategie di coping al fine di personalizzare i percorsi di educazione terapeutica

Effects of unsaturated free fatty acids on adhesion and on gene expression of extracellular matrix macromolecules in human osteoblast-like cultures

To investigate the possible role for unsaturated free fatty acids in osteoblast adhesion, the effects of two polyunsaturated fatty acids (PUFAs), arachidonic (AA) and eicosapentaenoic (EPA) acids, and of one monounsaturated fatty acid, oleic acid (OA), on adhesion to the substrate and on gene expression of three extracellular matrix macromolecules were investigated in an in vitro model system--cultured osteoblast-like human cells. AA, but neither EPA nor OA, diminished bone cell adhesion, whereas both EPA and OA, but not AA, increased gene expression of type I collagen and fibronectin via a transforming growth factor-beta-independent mechanism. These results extend previous evidence for unsaturated fatty acids in bone cell metabolism