Psoriasis is a chronic autoimmune disease mediated by dysregulated immune responses in dendritic cells (DC) and T cells. The stress-response enzyme heme oxygenase-1 (HO-1) has been described as protective in animal models of psoriasis, however, implementation of HO-1-based therapies is hindered by the lack of clinically-suitable HO-1 inducers. The plant-derived polyphenols, carnosol and curcumin, have been identified as candidate HO-1 inducers however there has been little investigation into their effects on human immune cells. We demonstrate that treatment of human DC with these polyphenols limits DC maturation, reduces pro-inflammatory cytokine production, and prevents induction of allospecific T cell responses, in a manner partially dependent on carbon monoxide (CO). We also characterised their effects in ex-vivo psoriasis PBMC and report that curcumin, but not carnosol, strongly reduces T cell proliferation and cytokine poly-functionality, with reduced expression of psoriatic cytokines IFNγ, IL-17, GM-CSF and IL-22. This study therefore supports reports highlighting the therapeutic potential of curcumin in psoriasis by providing insight into its immunological effects on healthy human DC and psoriasis PBMC. We also demonstrate, for the first time, the anti-inflammatory effects of carnosol in human immune cells.
Observational research has identified low serum levels of 25-hydroxyvitamin D (25[OH]D) in many non-skeletal diseases. Whether this is causal or due to underlying illness is unknown. Low serum 25[OH]D levels are also reported in the general population. Observational and experimental studies identify that vitamin D supplementation may be beneficial in reducing all-cause mortality in elderly women, as well as cancer mortality. Our aim was to review the literature to identify the relevance of serum 25[OH]D levels in psoriasis. Forty-five studies were included in our analysis. Most of these studies identified low serum 25[OH]D levels in psoriasis patients. Evidence of causality is lacking. Treatment with phototherapy leads to an increase in serum 25[OH]D. There is little evidence that the increase in 25[OH]D after phototherapy correlates with improved disease severity. Multiple studies report an improvement in psoriasis with vitamin D supplementation. These data are predominantly from small observational or non-randomised interventional studies. Randomised controlled trials to date have had small numbers and short follow-up periods. The optimal dose of supplementation is unknown and dosing is not standardised across different studies. The definition of vitamin D insufficiency varies across studies. Low serum 25[OH]D levels may be associated with comorbidities in psoriasis patients, including metabolic syndrome and cardiovascular risk. Evidence of causation is absent. Until further high-quality evidence is available, the relevance of low serum 25[OH]D levels in psoriasis patients is unknown, as is the benefit of supplementation on disease control. Supplementation in patients with low 25[OH]D is of benefit to those at risk of impaired bone health.
Background:Methadone maintenance treatment in primary care is cost-eff ective and improves outcomes for opiate-dependent patients. A more developed understanding of the evolving needs of this important cohort will facilitate further improvements in their integrated care within the community. Objectives: The aim of this study was to compare the burden of chronic disease, multi-morbidity and intensity of health-service use between methadone-maintained patients (MMPs) and matched controls in primary care. Methods: This is a retrospective matched case-control design. Data on chronic disease and health service use was collected in 13 computerized GP surgeries on 414 patients (207 MMPs and 207 controls). Twelve months of records were examined. MMPs were compared with controls matched by gender, age, socio-economic status (SES) and GP surgery. Results: MMPs suff ered more chronic disease (OR ϭ 9.1, 95% CI: 5.4 -15.1, P Ͻ 0.001) and multi-morbidity (OR ϭ 6.6, 95% CI: 4.3 -10.2, P Ͻ 0.001). They had higher rates of respiratory, psychiatric and infectious disease. MMPs of lower SES had more chronic disease than their peers (OR ϭ 7.2, 95% CI: 2.4 -22.0, P Ͻ 0.001). MMPs attended the doctor more often with medical problems (OR ϭ 15.4, 95% CI: 8.2 -28.7, P Ͻ 0.001), with a frequent requirement to have medical issues addressed during methadone-management visits. Their care generated more telephone calls (OR ϭ 4.4, 95% CI: 2.8 -6.8, P Ͻ 0.001), investigations (OR ϭ 1.8, 95% CI: 1.2 -2.7, P ϭ 0.003), referrals (2.6, 95% CI: 1.7 -4.0, P Ͻ 0.001), emergency department visits (2.1, 95% CI: 1.3 -3.6, P ϭ 0.004), outpatient attendances (2.3, 95% CI: 1.51 -1.43, P Ͻ 0.001) and hospital admissions (3.6, 95% CI: 1.6 -8.1, P ϭ 0.001). Conclusion:Correcting for routine methadone care and drug-related illnesses, MMPs had a higher burden of chronic disease and used both primary and secondary health services more intensively than matched controls.
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