Identification of a deletion in plakoglobin in arrhythmogenic right ventricular cardiomyopathy with palmoplantar keratoderma and woolly hair (Naxos disease).

Tissue engineering combines cell and molecular biology with materials and mechanical engineering to replace damaged or diseased organs and tissues. Fibrin is a critical blood component responsible for hemostasis, which has been used extensively as a biopolymer scaffold in tissue engineering. In this review we summarize the latest developments in organ and tissue regeneration using fibrin as the scaffold material. Commercially available fibrinogen and thrombin are combined to form a fibrin hydrogel. The incorporation of bioactive peptides and growth factors via a heparin-binding delivery system improves the functionality of fibrin as a scaffold. New technologies such as inkjet printing and magnetically influenced self-assembly can alter the geometry of the fibrin structure into appropriate and predictable forms. Fibrin can be prepared from autologous plasma, and is available as glue or as engineered microbeads. Fibrin alone or in combination with other materials has been used as a biological scaffold for s...

Fibrin: a versatile scaffold for tissue engineering applications.

Psoriasis is a common, chronic, inflammatory, multisystem disease with predominantly skin and joint manifestations affecting approximately 2% of the population. In this second of 5 sections of the guidelines of care for psoriasis, we give an overview of psoriatic arthritis including its cardinal clinical features, pathogenesis, prognosis, classification, assessment tools used to evaluate psoriatic arthritis, and the approach to treatment. Although patients with mild to moderate psoriatic arthritis may be treated with nonsteroidal anti-inflammatory drugs and/or intra-articular steroid injections, the use of disease-modifying antirheumatic drugs, particularly methotrexate, along with the biologic agents, are considered the standard of care in patients with more significant psoriatic arthritis. We will discuss the use of disease-modifying antirheumatic drugs and the biologic therapies in the treatment of patients with moderate to severe psoriatic arthritis.

https://www.jaad.org/article/S0190-9622(09)00012-7/pdf

Guidelines of care for the management of psoriasis and psoriatic arthritis: Section 2. Psoriatic arthritis: Overview and guidelines of care for treatment with an emphasis on the biologics

Research on psoriasis pathogenesis has largely increased knowledge on skin biology in general. In the past 15 years, breakthroughs in the understanding of the pathogenesis of psoriasis have been translated into targeted and highly effective therapies providing fundamental insights into the pathogenesis of chronic inflammatory diseases with a dominant IL-23/Th17 axis. This review discusses the mechanisms involved in the initiation and development of the disease, as well as the therapeutic options that have arisen from the dissection of the inflammatory psoriatic pathways. Our discussion begins by addressing the inflammatory pathways and key cell types initiating and perpetuating psoriatic inflammation. Next, we describe the role of genetics, associated epigenetic mechanisms, and the interaction of the skin flora in the pathophysiology of psoriasis. Finally, we include a comprehensive review of well-established widely available therapies and novel targeted drugs.

Psoriasis Pathogenesis and Treatment.

Of the 131 studies on monotherapy or combination therapy assessed, 56 studies on the different forms of phototherapy fulfilled the criteria for inclusion in the guidelines. Approximately three-quarters of all patients treated with phototherapy attained at least a PASI 75 response after 4 to 6 weeks, and clearance was frequently achieved (levels of evidence 2 and 3). Phototherapy represents a safe and very effective treatment option for moderate to severe forms of psoriasis vulgaris. The onset of clinical effects occurs within 2 weeks. Of the unwanted side effects, UV erythema from overexposure is by far the most common and is observed frequently. With repeated or long-term use, the consequences of high, cumulative UV doses (such as premature aging of the skin) must be taken into consideration. In addition, carcinogenic risk is associated with oral PUVA and is probable for local PUVA and UVB. The practicability of the therapy is limited by spatial, financial, human, and time constraints on the part of the physician, as well as by the amount of time required by the patient. From the perspective of the cost-bearing institution, phototherapy has a good cost-benefit ratio. However, the potentially significant costs for, and time required of, the patient must be considered.

https://www.huidziekten.nl/richtlijnen/european-guideline-psoriasis-2009.pdf

European S3-guidelines on the systemic treatment of psoriasis vulgaris

Background : Psoriasis vulgaris may benefit from treatment with fumaric acid and/or its derivatives; however, because different preparations have been used, results have been contradictory and difficult to interpret. Objective : The purpose of this clinical trial was to evaluate the therapeutic value of fumaric acid derivatives. Methods : A randomized double-blind study was carried out in patients with psoriasis, comparing a well-characterized formulation of fumaric acid derivatives with placebo. Results : The results indicated statistically significant superiority of the fumaric acid derivatives over placebo. Adverse events (flush, gastrointestinal disturbances) were initially relatively frequent, but decreased thereafter. Conclusion : Fumaric acid derivatives were found to be effective and safe in the treatment of psoriasis.

Antipsoriatic effect of fumaric acid derivatives. Results of a multicenter double-blind study in 100 patients.

Cultured autologous keratinocytes in fibrin glue suspension, exclusively and combined with STS-allograft (preliminary clinical and histological report of a new technique).

Background: Recent results suggest decreased interferon gamma (IFN-γ) but high interleukin 4 (IL-4) production in patients with atopic dermatitis (AD). Because the relative activities of IL-4 and IFN-γ seem to regulate the amplitude of the IgE response we suggested a role for IFN-γ in the treatment of AD. Objective: The purpose of this study was to assess the efficacy of systemic IFN-γ treatment in patients with severe AD. Methods: Patients with severe AD ( n = 14) were treated with recombinant IFN-γ for 6 weeks. During the study only basic local therapy with steroid-free hydrophilic or emollient ointments was allowed. Results: Eight patients (57%) showed marked clinical improvement during systemic IFN-γ therapy, Four of these patients showed continuous improvement 3 months after treatment was discontinued. Mean total and antigen-specific serum IgE concentrations were not statistically different during and after treatment, whereas mean spontaneous IgE production in vitro was significantly lower after 6 weeks of IFN-γ therapy. Conclusion: Our results suggest that IFN-γ treatment may represent a novel therapeutic approach in patients with severe AD.

https://www.jaad.org/article/0190-9622(93)70152-J/pdf

Systemic interferon gamma treatment in severe atopic dermatitis

In vitro interferon-gamma (IFNγ) and neopterin generation by peripheral blood mononuclear cells (PBMC) from 15 patients with severe atopic dermatitis (AD) and 10 healthy controls was investigated. A s

Immunoglobulin E and immunoglobulin G subclass distribution in vivo and relationship to in vitro generation of interferon-gamma and neopterin in patients with severe atopic dermatitis.

Topically applied acetylsalicylic acid (ASA), salicylic acid (SA) and indomethacin were tested in an experimental pain model that provides direct nociceptor excitation through cutaneous tissue acidosis. In 30 volunteers, sustained burning pain was produced in the palmar forearm through a continuous intradermal pressure infusion of a phosphate-buffered isotonic solution (pH 5.2). In 5 different, double-blind, randomized cross-over studies with 6 volunteers each, the flow rate of the syringe pump was individually adjusted to result in constant pain ratings of around 20% (50% in study 4) on a visual analog scale (VAS). The painful skin area was then covered with either placebo or the drugs which had been dissolved in diethylether. In the first study on 6 volunteers, ASA (60 mg/ml) or lactose (placebo) in diethylether (10 ml) was applied, using both arms at 3-day intervals. Both treatments resulted in sudden and profound pain relief due to the cooling effect of the evaporating ether. With lactose, however, the mean pain rating was restored close to the baseline within 6-8 min while, with ASA, it remained significantly depressed for the rest of the observation period (another 20 min). This deep analgesia was not accompanied by a loss of tactile sensation. The further studies served to show that indomethacin (4.5 mg/ml) and SA (60 mg/ml) were equally effective as ASA (each 92-96% pain reduction) and that the antinociceptive effects were due to local but not systemic actions, since ASA and SA dis not reach measurable plasma levels up to 3 h after topical applications. With a higher flow rate of acid buffer producing more intense pain (VAS 50%). ASA and SA were still able to significantly reduce the ratings by 90% or 84%, respectively. On the other hand, by increasing the flow rate by a factor of 2 on average, during the period of fully developed drug effect it was possible to overcome the pain suppression, which suggests a competitive mechanism of (acetyl-) salicylic antinociception.

Hans W. Kreysel

Papers

Antipsoriatic effect of fumaric acid derivatives. Results of a multicenter double-blind study in 100 patients.

Cultured autologous keratinocytes in fibrin glue suspension, exclusively and combined with STS-allograft (preliminary clinical and histological report of a new technique).

Systemic interferon gamma treatment in severe atopic dermatitis

Immunoglobulin E and immunoglobulin G subclass distribution in vivo and relationship to in vitro generation of interferon-gamma and neopterin in patients with severe atopic dermatitis.

Topical acetylsalicylic, salicylic acid and indomethacin suppress pain from experimental tissue acidosis in human skin