beyond rheumatology a new challenge devoted to the advancement of knowledge in all rheumatology related fields

Not availabl

nutritional aspects of bone health not only a matter of vitamin d

In every stage of life an adequate intake of several micro- and macro-nutrients can favorably affect bone health. In pre-adult life an adequate consumption of such nutrients is essential to build peak bone mass. Later in life, a correct nutrition has a role in maintaining skeletal mass and blunt menopause- and age-related bone loss. The main involved nutrients are calcium, phosphate, vitamin D and proteins. Recent data also stress the relevance of flavonoids and other micro-nutrients. The skeletal availability of single nutritional factors also relies to their reciprocal proportion in diet composition. An adequate nutrition plays a relevant role in the maintenance of bone health throughout life, but should not be regarded as a treatment for osteoporosis

Kidney involvement in systemic sclerosis.

Kidney involvement in systemic sclerosis (SSc) is primarily manifested by scleroderma renal crisis (SRC). More than 30 years ago, it was the main cause of death in these patients. The use of AC inhibitors has modified the prognosis and nowadays SRC has become a much more easily treatable complication of SSc. Furthermore, although there are still many patients who do not survive to this complication, the early diagnosis and prompt therapy of SRC can have an excellent outcome. Renal abnormalities independent of SRC are possible but are attributed to different pathogenetic mechanisms. Further understanding of pathogenesis of SRC may lead to additional improvement in the therapy of this serious complication

Ocular involvement in Behçet's Disease: relevance of new diagnostic tools

n/

catastrophic antiphospholipid syndrome a narrative review

The catastrophic antiphospholipid syndrome (CAPS) is a lifethreatening disorder characterized by the rapid development of multiple organs/systems thrombosis, in patients with persistently detectable antiphospholipid antibodies. The vascular occlusions predominantly affect small vessels, leading to a disseminated thrombotic microangiopathic syndrome. Most CAPS episodes are related to the presence of a precipitating factor, such as infections and malignant diseases, usually ending up in multiple organ failure. Clinical manifestations may vary according to the extent of the thrombosis, predominantly affecting kidneys, lungs, brain, heart, and skin. Treatment is based on the administration of anticoagulants, corticosteroids, plasma exchange and/or intravenous immunoglobulins. Cyclophosphamide is recommended in CAPS associated with systemic lupus erythematosus. Additionally, rituximab and eculizumab have been used in refractory cases. Overall mortality is still 36.9%, despite recent progress in the therapeutic approach

Multifaceted enrichment analysis of RNA-RNA crosstalk reveals cooperating micro-societies in human colorectal cancer

Alterations in the balance of mRNA and microRNA (miRNA) expression profiles contribute to the onset and development of colorectal cancer. The regulatory functions of individual miRNA-gene pairs are widely acknowledged, but group effects are largely unexplored. We performed an integrative analysis of mRNA–miRNA and miRNA–miRNA interactions using high-throughput mRNA and miRNA expression profiles obtained from matched specimens of human colorectal cancer tissue and adjacent non- tumorous mucosa. This investigation resulted in a hypernetwork-based model, whose functional back- bone was fulfilled by tight micro-societies of miR- NAs. These proved to modulate several genes that are known to control a set of significantly enriched cancer-enhancer and cancer-protection biological processes, and that an array of upstream regulatory analyses demonstrated to be dependent on miR-145, a cell cycle and MAPK signalling cascade master regulator. In conclusion, we reveal miRNA-gene clusters and gene families with close functional relationships and highlight the role of miR-145 as potent upstream regulator of a complex RNA–RNA crosstalk, which mechanistically modulates several signalling path- ways and regulatory circuits that when deranged are relevant to the changes occurring in colorectal carcinogenesis

Aging related changes of circadian rhythmicity of cytotoxic lymphocyte subpopulations

<p>Abstract</p> <p>Background</p> <p>Immunosenescence is a process that affects all cell compartments of the immune system and the contribution of the immune system to healthy aging and longevity is still an open question. Lymphocyte subpopulations present different patterns of circadian variation and in the elderly alteration of circadian rhythmicity has been evidenced. The aim of our study was to analyze the dynamics of variation of specific cytotoxic lymphocyte subsets in old aged subjects.</p> <p>Methods</p> <p>Lymphocyte subpopulation analyses were performed and cortisol serum levels were measured on blood samples collected every four hours for 24 hours from fifteen healthy male young-middle aged subjects (age range 36-55 years) and fifteen healthy male old aged subjects (age range 67-79 years).</p> <p>Results</p> <p>In healthy young-middle aged subjects CD20 were higher and at 06:00 h CD8+ dim correlated positively with CD16+ and positively with γδTCR+ cells, CD16 correlated positively with γδTCR+ cells At 18:00 h CD8+ dim correlated positively with CD16+ and positively with γδTCR+ cells, CD16+ correlated positively with γδTCR+ cells and a clear circadian rhythm was validated for the time-qualified changes of CD3+, CD4+, CD20+, CD25+ and HLA-DR+ cells with acrophase during the night and for the time-qualified changes of CD8+, CD8+ bright, CD8+ dim, CD16+ and γδTCR+ cells with acrophase during the day. In old aged subjects CD25, DR+ T cells and cortisol serum levels were higher, but there was no statistically significant correlation among lymphocyte subpopulations and a clear circadian rhythm was evidenced for time-qualified changes of CD3+ and CD25+ cells with acrophase during the night and for the time-qualified changes of CD8+ cells and cortisol with acrophase during the day.</p> <p>Conclusion</p> <p>Our study has evidenced aging-related changes of correlation and circadian rhythmicity of variation of cytotoxic lymphocyte subpopulations that might play a role in the alteration of immune system function in the elderly.</p

Time related variations in stem cell harvesting of umbilical cord blood

Umbilical cord blood (UCB) contains hematopoietic stem cells and multipotent mesenchymal cells useful for treatment in malignant/nonmalignant hematologic-immunologic diseases and regenerative medicine. Transplantation outcome is correlated with cord blood volume (CBV), number of total nucleated cells (TNC), CD34+ progenitor cells and colony forming units in UCB donations. Several studies have addressed the role of maternal/neonatal factors associated with the hematopoietic reconstruction potential of UCB, including: gestational age, maternal parity, newborn sex and birth weight, placental weight, labor duration and mode of delivery. Few data exist regarding as to how time influences UCB collection and banking patterns. We retrospectively analyzed 17.936 cord blood donations collected from 1999 to 2011 from Tuscany and Apulia Cord Blood Banks. Results from generalized multivariable linear mixed models showed that CBV, TNC and CD34+ cell were associated with known obstetric and neonatal parameters and showed rhythmic patterns in different time domains and frequency ranges. The present findings confirm that volume, total nucleated cells and stem cells of the UCB donations are hallmarked by rhythmic patterns in different time domains and frequency ranges and suggest that temporal rhythms in addition to known obstetric and neonatal parameters influence CBV, TNC and CD34+ cell content in UBC units

Chronobiologic study of the GH-IGF1 axis and the ageing immune system

One of the many systems that weakens as we age is our immune system and there is a reduction in the GH-IGF1 axis activity with increasing age. In this study we evaluated the immune system and the GH-IGF1 axis function in healthy ageing. CD3, CD4, CD20, CD25, HLA-DR and GH showed acrophase during the night, whereas CD8, CD16 and TCRγδ expressing cells showed acrophase during the day. MESOR of CD3 was higher in the old aged subjects, MESOR of CD20 and CD20 values at 14:00h and at 02:00h were higher in the young middle aged subjects, MESOR of CD25 and CD25 values at 10:00 were higher in the elderly subjects, MESOR of HLA-DR was higher in the young middle aged subjects, whereas MESOR of DR+T cells and HLA-DR at 02:00h were higher in the elderly subjects, MESOR of TCRγδ bearing cells was higher in the elderly subjects, GH value at 18:00h was also higher in the elderly subjects, and MESOR of IGF1 was higher in the young middle aged subjects. There was a statistically significant difference for the acrophases of CD25, HLA-DR and IGF1. There were different and opposing correlations among lymphocyte subpopulations and GH-IGF1 axis hormones in young and middle aged subjects in comparison with old aged subjects. Linear regression evidenced a statistically significant positive trend between age and the 24h mean of CD3 and CD25 and a statistically significant negative trend between age and the 24h mean of CD20 and GH. In conclusion, ageing is associated with an altered GH and IGF1 secretion, with decreased peripheral B cell compartment, increased peripheral T cell compartment and alterations of circadian rhythmicity

Altered time structure of neuro-endocrine-immune system function in lung cancer patients

<p>Abstract</p> <p>Background</p> <p>The onset and the development of neoplastic disease may be influenced by many physiological, biological and immunological factors. The nervous, endocrine and immune system might act as an integrated unit to mantain body defense against this pathological process and reciprocal influences have been evidenced among hypothalamus, pituitary, thyroid, adrenal, pineal gland and immune system. In this study we evaluated differences among healthy subjects and subjects suffering from lung cancer in the 24-hour secretory profile of melatonin, cortisol, TRH, TSH, FT4, GH, IGF-1 and IL-2 and circadian variations of lymphocyte subpopulations. </p> <p>Methods</p> <p>In ten healthy male volunteers (age range 45-66) and ten male patients with untreated non small cell lung cancer (age range 46-65) we measured melatonin, cortisol, TRH, TSH, FT4, GH, IGF-1 and IL-2 serum levels and percentages of lymphocyte subpopulations on blood samples collected every four hours for 24 hours. One-way ANOVA between the timepoints for each variable and each group was performed to look for a time-effect, the presence of circadian rhythmicity was evaluated, MESOR, amplitude and acrophase values, mean diurnal levels and mean nocturnal levels were compared.</p> <p>Results</p> <p>A clear circadian rhythm was validated in the control group for hormone serum level and for lymphocyte subsets variation. Melatonin, TRH, TSH, GH, CD3, CD4, HLA-DR, CD20 and CD25 expressing cells presented circadian rhythmicity with acrophase during the night. Cortisol, CD8, CD8^bright, CD8^dim, CD16, TcRδ1 and δTcS1 presented circadian rhythmicity with acrophase in the morning/at noon. FT4, IGF-1 and IL-2 variation did not show circadian rhythmicity. In lung cancer patients cortisol, TRH, TSH and GH serum level and all the lymphocyte subsubsets variation (except for CD4) showed loss of circadian rhythmicity. MESOR of cortisol, TRH, GH, IL-2 and CD16 was increased, whereas MESOR of TSH, IGF-1, CD8, CD8^bright, TcRδ1 and δTcS1 was decreased in cancer patients. The melatonin/cortisol mean nocturnal level ratio was decreased in cancer patients.</p> <p>Conclusion</p> <p>The altered secretion and loss of circadian rhythmicity of many studied factors observed in the subjects suffering from neoplastic disease may be expression of gradual alteration of the integrated function of the neuro-immune-endocrine system</p