Osteoimmunology in rheumatoid and psoriatic arthritis: potential effects of tofacitinib on bone involvement.

Chronic inflammation, such as that present in rheumatoid arthritis (RA) and psoriatic arthritis (PsA), leads to aberrations in bone remodeling, which is mediated by several signaling pathways, including the Janus kinase-signal transducer and activator of transcription (JAK-STAT) pathway. In this light, pro-inflammatory cytokines are now clearly implicated in these processes as they can perturb normal bone remodeling through their action on osteoclasts and osteoblasts at both intra- and extra-articular skeletal sites. As a selective inhibitor of JAK1 and JAK3, tofacitinib has the potential to play a role in the management of rheumatic diseases such as RA and PsA. Preclinical studies have demonstrated that tofacitinib can inhibit disturbed osteoclastogenesis in RA, which suggests that targeting the JAK-STAT pathway may help limit bone erosion. Evidence from clinical trials with tofacitinib in RA and PsA is encouraging, as tofacitinib treatment has been shown to decrease articular bone erosion. In this review, the authors summarize current knowledge on the relationship between the immune system and the skeleton before examining the involvement of JAK-STAT signaling in bone homeostasis as well as the available preclinical and clinical evidence on the benefits of tofacitinib on prevention of bone involvement in RA and PsA

Extraskeletal effects of vitamin D

In the last years we observed an increasing number of publications about the vitamin D, due to its recognised therapeutic actions and to the widespread hypovitaminosis D. In addition to the well known skeletal benefits, vitamin D can have multiple effects on other tissues.Muscular apparatus: hypovitaminosis D is associated with myopathy, sarcopenia, muscular strength reduction and increased risk of falls. The vitamin D supplementation increases the muscle functionality indexes. Cardiovascular system: low levels of vitamin D are related to increased levels of cardiovascular risk factors, heart failure, stroke, and cardiovascular mortality, while a good vitamin D status is associated with a decreased incidence of cardiovascular diseases. Diabetes and metabolic syndrome: a good vitamin D status is related to a decreased incidence of type 2 diabetes and metabolic syndrome; a vitamin D supplementation in the early childhood reduces (nearly 30%) the risk of having type 1 diabetes. Cancer: vitamin D deficit is associated with breast, colorectal cancer and melanoma relapses. Low and high levels of 25-hydroxy-vitamin D (25(OH)D) are related to a higher neoplastic mortality. Infectious diseases: hypovitaminosis D is associated with higher incidence of upper respiratory tract infections and worse interferon response in chronic hepatitis C. Vitamin D supplementation decreases the risk of having type A influence. Rheumatic diseases: in rheumatoid arthritis low serum levels of vitamin D metabolites are related to a higher disease activity, while a good vitamin D status is associated with a higher probability of remission or response to therapy and a lower degree of disability. Neurologic diseases: associations between vitamin D deficit and risk of multiple sclerosis, depression, cognitive deficits, and Parkinson’s disease have been reported.There is evidence of the extraskeletal effects of vitamin D, but most derive from observational studies: clinical trials are required the better to determine the therapeutic role of vitamin D

Pathogenesis of Bone Erosions in Rheumatoid Arthritis: Not Only Inflammation

It is a matter of fact that the inflammatory pathogenesis does not explain all the skeletal manifestations of Rheumatoid Arthritis (RA), and the development of bone involvement is sometimes unconnected from the clinical scores of inflammation. On the basis of recent studies, we would like to make a point of the new available evidence about the metabolic pathogenic component of bone erosions. We assume that in this process an additional role could be played by metabolic factors, such as the parathyroid hormone (PTH), DKK1 (the inhibitor of the Wnt/β catenin pathway) and cortical bone mineral density. The result is a new pathogenic hypothesis for bone erosion in RA, which supplements the inflammatory one: the reduction of osteoblasts activity and the increase of the osteoclasts one, involved in the pathogenesis of bone erosions and osteoporosis, are not only the consequence of the action of inflammatory cytokines, but also of increased levels of DKK1 and PTH. On the other hand, osteoporosis, in particular at the cortical sites, facilitates the appearance of erosions

Bilateral 5 Hz transcranial alternating current stimulation on fronto-temporal areas modulates resting-state EEG

Rhythmic non-invasive brain stimulations are promising tools to modulate brain activity by entraining neural oscillations in specific cortical networks. The aim of the study was to assess the possibility to influence the neural circuits of the wake-sleep transition in awake subjects via a bilateral transcranial alternating current stimulation at 5 Hz (theta-tACS) on fronto-temporal areas. 25 healthy volunteers participated in two within-subject sessions (theta-tACS and sham), one week apart and in counterbalanced order. We assessed the stimulation effects on cortical EEG activity (28 derivations) and self-reported sleepiness (Karolinska Sleepiness Scale). theta-tACS induced significant increases of the theta activity in temporo-parieto-occipital areas and centro-frontal increases in the alpha activity compared to sham but failed to induce any online effect on sleepiness. Since the total energy delivered in the sham condition was much less than in the active theta-tACS, the current data are unable to isolate the specific effect of entrained theta oscillatory activity per se on sleepiness scores. On this basis, we concluded that theta-tACS modulated theta and alpha EEG activity with a topography consistent with high sleep pressure conditions. However, no causal relation can be traced on the basis of the current results between these rhythms and changes on sleepines

Polycyclic aromatic hydrocarbons in atmospheric depositions around the Venice Lagoon

Studies have revealed the potential risks to which human health and ecosystems are exposed in the Venice Lagoon, due to the atmospheric deposition of persistent pollutants such as trace metals and organic compounds. A total of 77 atmospheric bulk deposition samples were collected monthly from April 2002 to December 2004, from three sites located in the cities of Mestre and Venice, and inside the industrial area of Porto Marghera. Samples were analyzed by HRGC/HRMS for polycyclic aromatic hydrocarbon (PAH) content. Spatial variations of atmospheric fallout were investigated, and source identification was attempted using diagnostic ratios and multivariate statistical analysis. Different conditions were recorded, with three anthropic signatures: i) industrial, mainly affected by local industrial sources and diesel engine emissions, ii) urban, mostly influenced by high traffic density, especially petrol car emissions and iii) lagoonal, characterized by dieselemissions from boat engines and oil burning, with random transport of industrial emissions

Parvovirus B19 Infection and Severe Anemia in Renal Transplant Recipients

Kidney transplant (KT) recipients can develop symptomatic Parvovirus (PV) B19 infections, frequently associated with persistent anemia. The aim of this study was to evaluate the prevalence and clinical significance of PV B19 infection in anemic and non-anemic KT patients. Overall, out of 64 patients monitored for the presence of PV B19 by real-time PCR, 2 (3.12%) had an active PV B19 infection, in absence of other viral coinfections. The 2 cases occurred in nonanemic kidney transplant patients group (2/50, 4%), while none of the anemic transplant patients (0/14) was found to suffer from this infection. Moreover, patients affected by active PV B19 infection showed viral loads not exceeding 1 × 105 genome copies/reaction. In conclusion, in this study, PV B19 infection was not common in renal transplant population and wasn't associated with severe anemia

The brain network organization during sleep onset after deprivation

Objective: Aim of the present study is to investigate the alterations of brain networks derived from EEG analysis in pre- and post-sleep onset conditions after 40 h of sleep deprivation (SD) compared to sleep onset after normal sleep in 39 healthy subjects. Methods: Functional connectivity analysis was made on electroencelographic (EEG) cortical sources of current density and small world (SW) index was evaluated in the EEG frequency bands (delta, theta, alpha, sigma and beta). Results: Comparing pre- vs. post-sleep onset conditions after a night of SD a significant decrease of SW in delta and theta bands in post-sleep onset condition was found together with an increase of SW in sigma band. Comparing pre-sleep onset after sleep SD versus pre-sleep onset after a night of normal sleep a decreased of SW index in beta band in pre-sleep onset in SD compared to pre-sleep onset in normal sleep was evidenced. Conclusions: Brain functional network architecture is influenced by the SD in different ways. Brain networks topology during wake resting state needs to be further explored to reveal SD-related changes in order to prevent possible negative effects of SD on behaviour and brain function during wakefulness. Significance: The SW modulations as revealed by the current study could be used as an index of an altered balance between brain integration and segregation processes after SD

Analysis of drug utilization and health care resource consumption in patients with psoriasis and psoriatic arthritis before and after treatment with biological therapies

To describe the therapeutic pathways of patients with psoriasis (PSO) and psoriatic arthritis (PsA) before and after treatment with biological therapies in a real-world setting and to determine the relative consumption of health care resources

Effects of secukinumab on serum adipocytokines: preliminary data

Psoriatic arthritis (PsA) is a chronic inflammatory disease that affects joints, connective tissues and the axial skeleton. Metabolic syndrome is an independent risk factor for psoriasis (Pso) development and is associated with more severe forms of Pso. Adipocytokines are secreted by white adipose tissue and are thought to link obesity with the development of metabolic and cardiovascular diseases. Secukinumab is a new monoclonal antibody with a different mechanism of action. This antibody selectively binds to and neutralizes interleukin-17 (IL-17) and it has shown efficacy in the treatment of PsA. The aim of this study was to evaluate the possible interferences of secukinumab on different adipocytokines. We enrolled 28 patients with PsA, classified with the CASPAR criteria. Serum samples were stored at baseline and then at the first, the third and the sixth month of therapy. Resistin, chemerin, adiponectin and C-reactive protein (CRP) were dosed. When tested globally, none of the adipokine tested showed any statistically significant variation. However, when the male group was tested, both resistin and chemerin at M6 showed a significant decrease from baseline. CRP did not show any variation at any time point. Our study demonstrated that treatment with secukinumab has little influence on the levels of adipokines tested within the first six months of treatment even though it might exert different influence between males and females from a metabolic perspective. Further studies with greater numbers of patients are needed to determine whether these preliminary results have clinical relevance