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%.

Tolerance to coxibs in patients with intolerance to non-steroidal anti-inflammatory drugs (NSAIDs): a systematic structured review of the literature.

Adverse events triggered by non-steroidal anti-inflammatory drugs (NSAIDs) are among the most common drug-related intolerance reactions in medicine; they are possibly related to inhibition of cyclooxygenase-1. Coxibs, preferentially inhibiting cyclooxygenase-2, may therefore represent safe alternatives in patients with NSAID intolerance. We reviewed the literature in a systematic and structured manner to identify and evaluate studies on the tolerance of coxibs in patients with NSAID intolerance.

Diminished thrombus formation and alleviation of myocardial infarction and reperfusion injury through antibody- or small-molecule-mediated inhibition of selectin-dependent platelet functions.

Background And Objectives: P-selectin ctin has been implicated in important platelet functions. However, neither its role in thrombus formation and cardiovascular disorders nor its suitability as a therapeutic target structure is entirely clear.

Design And Methods: Platelet aggregation was assessed in complementary in vitro settings by measurements of static aggregation, standardized aggregometry and dynamic flow chamber assays.

Psoriasis: a possible risk factor for development of coronary artery calcification.

Background: Psoriasis is a chronic inflammatory skin disorder affecting about 2% of white-skinned individuals. Epidemiological data on the prevalence and degree of coronary artery calcification (CAC) as an indicator for cardiovascular diseases in patients with psoriasis are contradictory.

Objectives: To study the prevalence and degree of CAC as an indicator for cardiovascular diseases in 32 patients with psoriasis matched for age, sex and risk factors to an equally sized control population.

Management of cutaneous type IV hypersensitivity reactions induced by heparin.

Localized hypersensitivity reactions to subcutaneous heparin injections have been described since 1952. Yet, the incidence of these reactions, which are distinct from skin lesions associated with heparin-induced thrombocytopenia type II (HIT II), remains uncertain. However, in the last 10 years an increasing number of patients have been reported, leading to the assumption that cutaneous hypersensitivity reactions towards heparin are underreported.

Structural requirements of heparin and related molecules to exert a multitude of anti-inflammatory activities.

Chronic inflammatory diseases are common and still remain a therapeutic challenge for both efficacy and safety reasons. Hence, novel therapeutics addressing these issues would for example improve treatment of severe diseases such as psoriasis, rheumatoid arthritis, inflammatory bowel disease and multiple sclerosis. Inappropriate leukocyte homing to the affected compartments is a common feature of these diseases.

Recommendations for the use of etanercept in psoriasis: a European dermatology expert group consensus.

Background: Psoriasis is a chronic, inflammatory skin disorder that has a significant impact on quality of life and, particularly in moderate to severe cases, adversely affects the patient's overall health and well-being. Biological treatments, such as etanercept, are being widely adopted across Europe for treatment of moderate to severe psoriasis due to favourable safety and efficacy profiles. The increase in usage, combined with a growing body of clinical evidence, has identified a need to clarify the best use of etanercept within its current treatment label.

Leukocyte adhesion: a suitable target for anti-inflammatory drugs.

Inflammatory responses in all tissue compartments require the emigration of leukocytes from the microvasculature through endothelial cells into the respective microenvironment. Adhesion to endothelial cells is the most crucial step in order to facilitate selective and effective capture of leukocytes. The sequence of adhesions events, e.

Diminished lymphocyte adhesion and alleviation of allergic responses by small-molecule- or antibody-mediated inhibition of L-selectin functions.

Selectins are attractive targets for specific anti-inflammatory therapies. Using human lymphocytes as well as an L-selectin-transfected pre-B-cell line in dynamic flow chamber experiments, we could demonstrate that the small-molecule compound efomycine M blocks L-selectin-mediated lymphocyte rolling on sialylated Lewis(X), an action that was confirmed by plasmon resonance spectroscopy. Recruitment of naive lymphocytes to peripheral lymph nodes depends on L-selectin-mediated adhesion to high endothelial venules.

Eukaryotic expression of the broad-spectrum chemokine receptor antagonist vMIP-II and its effects on T-cell function in vitro and in vivo.

Pro-inflammatory chemokines and their receptors exhibit elementary functions in cell migration and in Th1-driven inflammatory conditions. One therapeutic strategy to prevent accumulation of pro-inflammatory immune cells is the use of specific chemokine receptor antagonists. An interesting and promising candidate in this context is the viral antagonist MIP-II (vMIP-II) that acts on a broad spectrum of chemokine receptors.

The influence of various structural parameters of semisynthetic sulfated polysaccharides on the P-selectin inhibitory capacity.

Selectin-mediated leukocyte rolling along the endothelium is of key importance for maintaining the cellular immune response. The anti-inflammatory activities of heparin have partly been related to inhibition of P-selectin binding. Heparin, however, suffers from its heterogeneous variable structure, the animal origin and multiple in vivo effects.

Biologic therapies for psoriasis. A systematic review.

Alefacept, efalizumab, etanercept, and infliximab are currently approved for the treatment of adults with moderate to severe plaque psoriasis, and phase 3 trials for adalimumab are ongoing. The high level of evidence from large randomized, double-blind, placebo-controlled clinical studies for each of these biologics allows high-grade recommendations and helps define uncertainties, one of which is longterm safety. For tumor necrosis factor-a blocking agents, safety profiles are available from clinical experience in other indications.

Structure-function relation of efomycines, a family of small-molecule inhibitors of selectin functions.

Selectin-mediated leukocyte adhesion to endothelia, the crucial first step initiating the pathogenic cascade of inflammation, is an attractive target for specific therapies. The small-molecule macrolide, efomycine M, inhibits selectin-mediated leukocyte adhesion in vitro and in vivo, and effectively alleviates inflammatory disorders in vivo. To define the molecular basis of the therapeutically relevant antiadhesive properties of efomycines, several new species of this family were purified and/or synthesized.

Molecular weight determines the frequency of delayed type hypersensitivity reactions to heparin and synthetic oligosaccharides.

Eczematous lesions, resulting from type IV sensitizations are well-known and relatively frequent cutaneous adverse effects of s.c. heparin therapy.

Chronic venous insufficiency - a potential trigger for localized scleroderma.

Localized scleroderma is a cutaneous disease that is characterized by an initial inflammatory response, followed by sclerosis of the skin. The cause of localized scleroderma has not yet been determined. Seifarth et al.

Safety and efficacy of alefacept in elderly patients and other special populations.

Background: The safety of biologic agents for psoriasis treatment is of particular importance in patient groups at higher risk for adverse events. We assessed the safety and efficacy of alefacept in elderly, obese, and diabetic patients with moderate to severe chronic plaque psoriasis by integrating data from phase 2 and 3 clinical studies and their extensions.

Observations: Ninety-nine elderly, 652 obese, and 122 diabetic patients received at least 1 course of alefacept.

Junctional adhesion molecules (JAM)-B and -C contribute to leukocyte extravasation to the skin and mediate cutaneous inflammation.

Leukocyte extravasation is a finely tuned process, in which transmigration is the final step. Transmigration depends on molecules located at borders of endothelial cells; e.g.