Leukotrienes B 4 , C 4 and D 4 stimulate DNA synthesis in cultured human epidermal keratinocytes

Leukotrienes in psoriatic skin lesions are potent mediators of inflammation. We have studied the capacity of leukotrienes to stimulate the DNA synthesis of cultured human epidermal keratinocytes. At concentrations ranging from 10 −12 to 10 −8 M, LTB 4 produced a 100% increase of DNA synthesis determined both as the incorporation of [ 3 H] thymidine and as the labelling index. In comparison, LTB 4 had no effect on the DNA synthesis of dermal fibroblast cultures. 5S, 12S-LTB 4 and 5S, 12S-all-trans-LTB 4 did not change the DNA synthesis of keratinocytes, but the effect of LTB 4 was abolished in the presence of 5S, 12S-all- trans HLTB 4 . Being less potent than LTB 4 the peptidoleukotrienes (LTC 4 , LTD 4 ) also stimulated keratinocyte DNA synthesis. The effect of the peptidoleukotrienes, but not of LTB 4 , was antagonized by EPL 55712. These results show that leukotrienes B 4 , C 4 and D 4 exert potent and stereospecific mitogenic effects on cultured human keratinocytes. The presence of these arachidonic acid metabolites in psoriatic skin lesions may be pertinent to both inflammation and aberrant epidermal growth in psoriasis.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/74813/1/j.1365-2133.1985.tb02043.x.pd

Interleukin-8 stimulates the formation of 15-hydroxy-eicosatetraenoic acid by human neutrophils in vitro

Interleukin-8 (IL-8), is a potent activator of polymorphonuclear leukocyte (PMN) functions including chemotaxis, superoxide anion production, and enzyme release and it is also chemotactic for lymphocytes. Additionally, it has recently been shown that IL-8 stimulates the formation of 5-lipoxygenase (LO) products of arachidonic acid (AA) by human PMNs. The purpose of the present study was to determine whether IL-8 also might affect the formation of 15-LO products from AA. Purified PMNs in phosphate buffered saline were preincubated with and without exogenous AA (10 −5 –10 −4 M ) for 10 min. Then IL-8 was added in biologically relevant concentrations ranging from 0.1 to 100 ng/ml and incubation was carried out for 5 min at 37°C. Lipids were then extracted from supernatants, and eicosanoids were determined by quantitative RP-HPLC. Compared with unstimulated cells, IL-8 resulted in a dose dependent increase in both LTB 4 and 15-HETE (up to 125% and 40% at 100 ng/ml, respectively). This increase in eicosanoid formation required the presence of exogenous AA. These results indicate that IL-8 is both a potent stimulator of 5-LO activity and of 15-LO activity. LTB 4 can induce both inflammation and contribute to hyperproliferation in the skin. 15-HETE in contrast has the ability to inhibit the effects induced by LTB 4 . Because IL-8 is able to stimulate both LTB 4 and 15-HETE formation, the effect of IL-8 as a putative regulator of inflammatory processes may be dependent on the relative stimulation of 5-LO and 15-LO.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/45125/1/11_2005_Article_BF01997504.pd

Efficacy and safety of a new combination of calcipotriol and betamethasone dipropionate (once or twice daily) compared to calcipotriol (twice daily) in the treatment of psoriasis vulgaris: a randomized, double-blind, vehicle-controlled clinical trial.

Background Calcipotriol and betamethasone dipropionate are both widely used, effective treatments for psoriasis. Vitamin D analogues and topical corticosteroids have different mechanisms of action in the treatment of psoriasis. A new vehicle has been developed in order to contain both calcipotriol (50 micro g g-1) and betamethasone dipropionate (0.5 mg g-1) in an ointment form. By using calcipotriol and a corticosteroid together, greater efficacy may be achieved than by using either compound alone. Objectives The present study was conducted in order to compare the clinical efficacy and safety of the combined ointment formulation used once daily with the vehicle ointment used twice daily, calcipotriol ointment used twice daily and the combined formulation used twice daily in psoriasis vulgaris. Methods This was an international, multicentre, prospective, randomized, double-blind, vehicle-controlled, parallel group, 4-week study in patients with psoriasis vulgaris amenable to topical treatment. Patients were randomized to one of four treatment groups: combined formulation once daily, combined formulation twice daily, calcipotriol twice daily or vehicle twice daily. Efficacy and safety were assessed. Results There was no statistically significant difference in the mean percentage change in the Psoriasis Area and Severity Index (PASI) from baseline to end of treatment between the two combined formulation groups, but the difference in PASI reduction was significantly higher in the combined formulation groups (68.6% once daily, 73.8% twice daily) than in both the twice daily calcipotriol group (58.8%) and the vehicle group (26.6%). Safety data showed the frequency of adverse events to be less in the combined formulation groups than in both the calcipotriol group and the vehicle group. The proportion of patients with lesional/perilesional adverse reactions was less in the combined formulation groups and vehicle group than in the calcipotriol group (9.9% combined formulation once daily, 10.6% combined formulation twice daily, 19.8% calcipotriol, 12.5% vehicle). Conclusions No statistically significant nor clinically relevant difference in efficacy was seen between the combined formulation used once daily and twice daily. When compared to vehicle ointment or calcipotriol ointment alone, the combined formulation was shown to be clearly more efficacious

Psoriatic Arthritis and Burden of Disease: Patient Perspectives from the Population-Based Multinational Assessment of Psoriasis and Psoriatic Arthritis (MAPP) Survey

Introduction: Psoriatic arthritis (PsA) is underdiagnosed and has a substantial impact on quality of life, disability, and work productivity. The population-based Multinational Assessment of Psoriasis and Psoriatic Arthritis (MAPP) survey examined the impact of PsA on patients’ activities of daily living and unmet treatment needs. Methods: This large-scale, random digit dialing, telephone survey of patients self-reporting a diagnosis of psoriasis and/or PsA was conducted in North America and Europe. Results: In all, 3426 patients participated in the survey, including 712 (21%) who identified themselves as having PsA. Over half of the patients reported severe PsA involving more than four joints. Eighty-three percent of patients with PsA visited a health-care provider within the past 12 months. Approximately one-quarter saw their primary care provider or dermatologist most often for their disease; 37% responded that their rheumatologist was the health-care provider seen most often for PsA. Patients with PsA reported a substantial impact of disease on physical function. One-third of patients with PsA reported missing work because of their disease and PsA impacted their ability to work full time. Over half of the patients with PsA (58%) reported receiving no treatment or topical therapy only, leaving their joint disease untreated. Factors associated with lack of adherence were perceived lack of efficacy and concerns about long-term safety. Conclusions: The MAPP survey confirms that PsA has a significant impact on physical function and activities of daily living. Undertreatment of PsA suggests a need for improved screening and diagnosis as well as education about treatment options and adherence

The sunburn response in human skin is characterized by sequential eicosanoid profiles that may mediate its early and late phases.

yesSunburn is a commonly occurring acute inflammatory process, with dermal vasodilatation and leukocyte infiltration as central features. Ultraviolet (UV) B-induced hydrolysis of membrane phospholipids releases polyunsaturated fatty acids and their subsequent metabolism by cyclooxygenases (COX) and lipoxygenases (LOX) may produce potent eicosanoid mediators modulating different stages of the inflammation. Our objective was to identify candidate eicosanoids formed during the sunburn reaction in relation to its clinical and histological course. We exposed skin of healthy humans (n=32) to UVB and for 72h examined (i) expression of pro- and anti-inflammatory eicosanoids using LC/ESI-MS/MS and (ii) immunohistochemical expression of COX-2, 12-LOX, 15-LOX and leucocyte markers, while (iii) quantifying clinical erythema. We show that vasodilatory prostaglandins (PG)E2, PGF2¿ and PGE3 accompany the erythema in the first 24-48h, associated with increased COX-2 expression at 24h. Novel, potent leukocyte chemoattractants 11-, 12- and 8-monohydroxy-eicosatetraenoic acid (-HETE) are elevated from 4-72h, in association with peak dermal neutrophil influx at 24h, and increased dermal CD3+ lymphocytes and 12- and 15-LOX expression from 24-72h. Anti-inflammatory metabolite 15-HETE shows later expression, peaking at 72h. Sunburn is characterized by overlapping phases of increases in COX products followed by LOX products that may regulate subsequent events and ultimately its resolution.The Wellcome Trus

Definition of treatment goals for moderate to severe psoriasis: a European consensus

Patients with moderate to severe psoriasis are undertreated. To solve this persistent problem, the consensus programme was performed to define goals for treatment of plaque psoriasis with systemic therapy and to improve patient care. An expert consensus meeting and a collaborative Delphi procedure were carried out. Nineteen dermatologists from different European countries met for a face-to-face discussion and defined items through a four-round Delphi process. Severity of plaque psoriasis was graded into mild and moderate to severe disease. Mild disease was defined as body surface area (BSA) ≤10 and psoriasis area and severity index (PASI) ≤10 and dermatology life quality index (DLQI) ≤10 and moderate to severe psoriasis as (BSA > 10 or PASI > 10) and DLQI > 10. Special clinical situations may change mild psoriasis to moderate to severe including involvement of visible areas or severe nail involvement. For systemic therapy of plaque psoriasis two treatment phases were defined: (1) induction phase as the treatment period until week 16; however, depending on the type of drug and dose regimen used, this phase may be extended until week 24 and (2) maintenance phase for all drugs was defined as the treatment period after the induction phase. For the definition of treatment goals in plaque psoriasis, the change of PASI from baseline until the time of evaluation (ΔPASI) and the absolute DLQI were used. After induction and during maintenance therapy, treatment can be continued if reduction in PASI is ≥75%. The treatment regimen should be modified if improvement of PASI is <50%. In a situation where the therapeutic response improved ≥50% but <75%, as assessed by PASI, therapy should be modified if the DLQI is >5 but can be continued if the DLQI is ≤5. This programme defines the severity of plaque psoriasis for the first time using a formal consensus of 19 European experts. In addition, treatment goals for moderate to severe disease were established. Implementation of treatment goals in the daily management of psoriasis will improve patient care and mitigate the problem of undertreatment. It is planned to evaluate the implementation of these treatment goals in a subsequent programme involving patients and physicians

German evidence-based guidelines for the treatment of Psoriasis vulgaris (short version)

Psoriasis vulgaris is a common and chronic inflammatory skin disease which has the potential to significantly reduce the quality of life in severely affected patients. The incidence of psoriasis in Western industrialized countries ranges from 1.5 to 2%. Despite the large variety of treatment options available, patient surveys have revealed insufficient satisfaction with the efficacy of available treatments and a high rate of medication non-compliance. To optimize the treatment of psoriasis in Germany, the Deutsche Dermatologische Gesellschaft and the Berufsverband Deutscher Dermatologen (BVDD) have initiated a project to develop evidence-based guidelines for the management of psoriasis. The guidelines focus on induction therapy in cases of mild, moderate, and severe plaque-type psoriasis in adults. The short version of the guidelines reported here consist of a series of therapeutic recommendations that are based on a systematic literature search and subsequent discussion with experts in the field; they have been approved by a team of dermatology experts. In addition to the therapeutic recommendations provided in this short version, the full version of the guidelines includes information on contraindications, adverse events, drug interactions, practicality, and costs as well as detailed information on how best to apply the treatments described (for full version, please see Nast et al., JDDG, Suppl 2:S1–S126, 2006; or http://www.psoriasis-leitlinie.de)

“Es fundamental que la información que se transmita sea confiable”

El flamante Doctor Honoris Causa de la UNLP, Emilio Luque Fadón, de la Universidad Autónoma de Barcelona, fue uno de los conferencistas de CACIC 2017. Durante su estadía por la ciudad de La Plata, el español habló acerca de las nuevas tecnologías, su tolerancia a los fallos y el consumo energético.Facultad de Informátic