A reappraisal of the role of the various opioid receptor subtypes in cell-mediated immunity.

Opioid peptides have been shown by several studies to modulate various parameters of the immune response, but scant experimental findings exist on the role played by specific opioid receptor subtypes in the control of immune mechanisms. This study focuses on the in vitro influences of [Trp4,Asn7]dermorphin, a mu-selective agonist, [D-Ala2]deltorphin I, a delta-selective agonist and U50,488, a kappa-selective agonist, on the proliferative response of splenocytes to concanavalin A (Con A). [Trp4,Asn7]dermorphin at low concentrations (10(-11P) and 10(-12) M) enhanced the proliferative response to Con A, whereas higher concentrations (10(-6) to 10(-7) M) inhibited it. Both effects were antagonized by naloxone. [D-Ala2]deltorphin I at very low concentrations (10(-12) to 10(-13) M) also produced a significant increase in the proliferative response of splenocytes to Con A. This effect was significantly antagonized by natrindole, a specific delta-receptor antagonist. Finally U50,488 at concentrations ranging from 10(-8) to 10(-9) M inhibited the proliferative response to Con A. The effects of U50,488 were mediated by the stimulation of the kappa-opioid receptors, since a preincubation of splenocytes with the selective antagonist norbinaltorphimine significantly reduced or abolished the U50,488-induced suppression of the mitotic response. In conclusion, our results clearly indicate that the different opioid receptor subtypes play a different role in the control of immune mechanisms and suggest that immunoenhancing effects of opioid peptides are very likely due to the stimulation of mu- and delta-receptors, whereas the immunosuppressive effects are mediated through the stimulation of kappa-opioid receptors

PARAQUAT TOXICITY AND OXIDATIVE DAMAGE. REDUCTION BY MELATONIN.

I.P. 2001: 3.3

Potent protective effect of melatonin on in vivo paraquat-induced oxidative damage in rats

The in vivo effect of melatonin on paraquat-induced oxidative damage in rat lung and liver was studied using two parameters: the concentration of malonaldehyde and 4-hydroxyalkenals as indices of lipid peroxidation; changes in total and oxidized glutathione. Melatonin (10 mg/kg) or an equal volume of saline were administered intraperitoneally (ip) to rats 30 min prior to an ip injection of paraquat (20mg/kg or 70 mg/kg). After paraquat treatment, the animals received melatonin or saline ip injections every six hours for 24 hours. Rats were killed 24 hours after paraquat injection. In lung, both the low and high dose of paraquat, when administered with saline, augmented lipid peroxidation (100% and 18%) respectively) above levels found in control animals. Treatment with melatonin completely reversed this effect. In liver, paraquat (70 mg/kg) increased lipid peroxidation by 40% over the levels of control animals. The increase was completely abolished by treatment with melatonin. Paraquat at 20 mg/kg did not induce any significant change in liver lipid peroxidation. Paraquat treatment resulted in a significant decrease of total glutathione concentration and increased oxidized glutathione in both lung and liver. These effects were abolished by treatment with melatonin. The results suggest that melatonin confers marked protection against paraquat-induced oxidative toxicity in both the lung and liver

Psychometric evaluation of an Italian custom 4-item short form of the PROMIS anxiety item bank in immune-mediated inflammatory diseases: an item response theory analysis

Background There has recently been growing interest in the roles of inflammation in contributing to the development of anxiety in people with immune-mediated inflammatory diseases (IMID). Patient-reported outcome measures can facilitate the assessment of physical and psychological functioning. The National Institutes of Health (NIH)’s Patient-Reported Outcomes Measurement Information System (PROMIS®) is a set of Patient-Reported Outcomes (PROs) that cover physical appearance, mental health, and social health. The PROMIS has been built through an Item Response Theory approach (IRT), a model-based measurement in which trait level estimates depend on both persons’ responses and on the properties of the items that were administered. The aim of this study is to test the psychometric properties of an Italian custom four-item Short Form of the PROMIS Anxiety item bank in a cohort of outpatients with IMIDs. Methods We selected four items from the Italian standard Short Form Anxiety 8a and administered them to consecutive outpatients affected by Inflammatory Bowel disease (n = 246), rheumatological (n = 100) and dermatological (n = 43) diseases, and healthy volunteers (n = 280). Data was analyzed through an Item Response Theory (IRT) analysis in order to evaluate the psychometric properties of the Italian adaptation of the PROMIS anxiety short form. Results Taken together, Confirmatory Factor Analysis and Exploratory Factor analysis suggest that the unidimensionality assumption of the instrument holds. The instrument has excellent reliability from a Classical Theory of Test (CTT) standpoint (Cronbach’s α = 0.93, McDonald’s ω = 0.92). The 2PL Graded Response Model (GRM) model provided showed a better goodness of fit as compared to the 1PL GRM model, and local independence assumption appears to be met overall. We did not find signs of differential item functioning (DIF) for age and gender, but evidence for uniform (but not non-uniform) DIF was found in three out of four items for the patient vs. control group. Analysis of the test reliability curve suggested that the instrument is most reliable for higher levels of the latent trait of anxiety. The groups of patients exhibited higher levels of anxiety as compared to the control group (ps < 0.001, Bonferroni-corrected). The groups of patients were not different between themselves (p = 1, Bonferroni-corrected). T-scores based on estimated latent trait and raw scores were highly correlated (Pearson’s r = 0.98) and led to similar results. Discussion The Italian custom four-item short form from the PROMIS anxiety form 8a shows acceptable psychometric properties both from a CTT and an IRT standpoint. The Test Reliability Curve shows that this instrument is mostly informative for people with higher levels of anxiety, making it particularly suitable for clinical populations such as IMID patients

Bv8/prokineticin 2 is involved in Aβ-induced neurotoxicity

Bv8/Prokineticin 2 (PROK2) is a bioactive peptide initially discovered as a regulator of gastrointestinal motility. Among multiple biological roles demonstrated for PROK2, it was recently established that PROK2 is an insult-inducible endangering mediator for cerebral damage. Aim of the present study was to evaluate the PROK2 and its receptors' potential involvement in amyloid beta (Aβ) neurotoxicity, a hallmark of Alzheimer's disease (AD) and various forms of traumatic brain injury (TBI). Analyzing primary cortical cultures (CNs) and cortex and hippocampus from Aβ treated rats, we found that PROK2 and its receptors PKR1 and PKR2 mRNA are up-regulated by Aβ, suggesting their potential involvement in AD. Hence we evaluated if impairing the prokineticin system activation might have protective effect against neuronal death induced by Aβ. We found that a PKR antagonist concentration-dependently protects CNs against Aβ(1-42)-induced neurotoxicity, by reducing the Aβ-induced PROK2 neuronal up-regulation. Moreover, the antagonist completely rescued LTP impairment in hippocampal slices from 6 month-old Tg2576 AD mice without affecting basal synaptic transmission and paired pulse-facilitation paradigms. These results indicate that PROK2 plays a role in cerebral amyloidosis and that PROK2 antagonists may represent a new approach for ameliorating the defining pathology of AD

Joint American Academy of Dermatology-National Psoriasis Foundation guidelines of care for the management and treatment of psoriasis with phototherapy

Psoriasis is a chronic inflammatory disease involving multiple organ systems and affecting approximately 3.2% of the world\u27s population. In this section of the guidelines of care for psoriasis, we will focus the discussion on ultraviolet (UV) light-based therapies, which include narrowband and broadband UVB, UVA in conjunction with photosensitizing agents, targeted UVB treatments such as with an excimer laser, and several other modalities and variations of these core phototherapies, including newer applications of pulsed dye lasers, intense pulse light, and light-emitting electrodes. We will provide an in-depth, evidence-based discussion of efficacy and safety for each treatment modality and provide recommendations and guidance for the use of these therapies alone or in conjunction with other topical and/or systemic psoriasis treatments