[Dermatology].
We are going over therapeutic acquisitions in a club-journal including relevant publications in different fields: mecanism of action, therapeutic perspectives in a near future, and side effects.
Depression↗
Biomedical subjects
S Kuenzli
Publications and source records attributed to S Kuenzli.
Treatment of plaque psoriasis by sequential therapy with two 'biologics': the 'hit and run' approach, a report of two cases.
Explore the source record for details and available documents.
Adult↗
[Dermatology].
This year, we are going over therapeutic acquisitions in a club-journal format with a special focus on biologicals for psoriasis. Other sections include relevant publications in different fields: mecanism of action, therapeutic perspectives in a near future, and side effects.
Humans↗
Cutaneous adverse events of biological therapy for psoriasis: review of the literature.
The use of biological agents is expanding worldwide as a new treatment alternative for chronic inflammatory diseases including more recently skin diseases, especially psoriasis. Although frequently observed, the knowledge about acute and chronic dermatological adverse events is limited, and potential pathogenic mechanisms still have to be identified. Exact diagnosis is required considering that dermatological adverse events raise a decisional challenge about potential treatment discontinuation. The object of this publication is to present an overview of the dermatological adverse events of these new treatment alternatives.
Adalimumab↗
Peroxisome proliferator-activated receptors in cutaneous biology.
Peroxisome proliferator-activated receptors (PPARs) are ligand-activated transcription factors that regulate the expression of target genes involved in many cellular functions including cell proliferation, differentiation and immune/inflammation response. The PPAR subfamily consists of three isotypes: PPAR alpha, PPAR beta/delta and PPAR gamma, which have all been identified in keratinocytes. PPAR beta/delta is the predominant subtype in human keratinocytes, whereas PPAR alpha and PPAR gamma are expressed at much lower levels and increase significantly upon keratinocyte differentiation. PPAR beta/delta is not linked to differentiation, but is significantly upregulated upon various conditions that result in keratinocyte proliferation, and during skin wound healing. In vitro and in vivo evidence suggests that PPARs appear to play an important role in skin barrier permeability, inhibiting epidermal cell growth, promoting epidermal terminal differentiation and regulating skin inflammatory response by diverse mechanisms. These proprieties are pointing in the direction of PPARs being key regulators of skin conditions characterized by hyperproliferation, inflammatory infiltrates and aberrant differentiation such as psoriasis, but may also have clinical implications in inflammatory skin disease (e.g. atopic dermatitis), proliferative skin disease, wound healing, acne and protease inhibitor associated lipodystrophia.
Animals↗
Successful treatment of Schnitzler's syndrome with interferon alfa-2b.
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Female↗
Peroxisomal bifunctional enzyme binds and activates the activation function-1 region of the peroxisome proliferator-activated receptor alpha.
The transcriptional activity of peroxisome proliferator-activated receptors (PPARs), and of nuclear hormone receptors in general, is subject to modulation by cofactors. However, most currently known co-activating proteins interact in a ligand-dependent manner with the C-terminal ligand-regulated activation function (AF)-2 domain of nuclear receptors. Since PPARalpha exhibits a strong constitutive transactivating function contained within an N-terminal AF-1 region, it can be speculated that a different set of cofactors might interact with this region of PPARs. An affinity purification approach was used to identify the peroxisomal enoyl-CoA hydratase/3-hydroxyacyl-CoA dehydrogenase (bifunctional enzyme, BFE) as a protein which strongly and specifically interacted with the N-terminal 92 amino acids of PPARalpha. Protein-protein interaction assays with the cloned BFE confirmed this interaction, which could be mapped to amino acids 307-514 of the BFE and the N-terminal 70 amino acids of PPARalpha. Moreover, transient transfection experiments in hepatoma cells revealed a 2.2-fold increase in the basal and ligand-stimulated transcriptional activity of PPARalpha in the presence of BFE. This stimulatory effect is preferentially observed for the PPARalpha isoform and it is significantly stronger (4.8-fold) in non-hepatic cells, which presumably express lower levels of endogenous BFE. Hence, the BFE represents the first known cofactor capable of activating the AF-1 domain of PPAR without requiring additional regions of this receptor. These data are compatible with a model whereby the PPAR-regulated BFE is able to modulate its own expression through an enhancement of the activity of PPARalpha, representing a novel peroxisomal-nuclear feed-forward regulatory loop.
3-Hydroxyacyl CoA Dehydrogenases↗
Retinoids for the treatment of psoriasis: outlook for the future.
Despite the demonstrated clinical success of retinoid therapy in psoriasis, its mechanism of action has not been fully elucidated, and investigators are confronted with two paradoxes. Firstly, the binding of retinoids to nuclear retinoic acid receptors (RARs) does not match their therapeutic efficacy. Secondly, formation of retinoic acid is probably increased in the psoriatic lesions. Answering these questions should result in: (i) the better use of acitretin, an oral synthetic retinoid, and tazarotene, the first compound for topical use; (ii) the development of new retinoids with specific pharmacological profile such as subtype-selective retinoids including molecules with an 'antiretinoid' activity and dissociating antiproliferative retinoids; and (iii) the better characterization of non-genomic effects of retinoids.
Animals↗