Successful treatment of recalcitrant cutaneous sarcoidosis with fumaric acid esters

BACKGROUND: Sarcoidosis is a multisystem disease of unknown origin characterized by the formation of noncaseating granulomas, in particular in the lungs, lymph nodes, eyes, and skin. Systemic treatment for cutaneous sarcoidosis can be used for large disfiguring lesions, generalized involvement, or recalcitrant lesions that did not respond to topical therapy. CASE PRESENTATIONS: We report three patients with recalcitrant cutaneous sarcoidosis who were treated with oral fumaric acid esters (FAE). Three female patients presented with cutaneous sarcoidosis that have proved to be refractory to various therapies, including corticosteroids and chloroquine. We treated the patients with FAE in tablet form using two formulations differing in strength (Fumaderm(® )initial, Fumaderm(®)). Dosage of FAE was performed according to the standard therapy regimen for psoriasis patients. After treatment with FAE (4–12 months), a complete clearance of skin lesions was achieved in the three patients. The side effects observed in this trial correspond to the well-known spectrum of adverse effects of FAE (flush, minor gastrointestinal complaints, lymphopenia). CONCLUSIONS: On the basis of our findings FAE therapy seems to be a safe and effective regimen for patients with recalcitrant cutaneous sarcoidosis. Nevertheless further investigations are necessary to confirm our preliminary results

The role of the p90 ribosomal S6 kinase family in prostate cancer progression and therapy resistance.

Prostate cancer (PCa) is the second most commonly occurring cancer in men, with over a million new cases every year worldwide. Tumor growth and disease progression is mainly dependent on the Androgen Receptor (AR), a ligand dependent transcription factor. Standard PCa therapeutic treatments include androgen-deprivation therapy and AR signaling inhibitors. Despite being successful in controlling the disease in the majority of men, the high frequency of disease progression to aggressive and therapy resistant stages (termed castrate resistant prostate cancer) has led to the search for new therapeutic targets. The p90 ribosomal S6 kinase (RSK1-4) family is a group of highly conserved Ser/Thr kinases that holds promise as a novel target. RSKs are effector kinases that lay downstream of the Ras/Raf/MEK/ERK signaling pathway, and aberrant activation or expression of RSKs has been reported in several malignancies, including PCa. Despite their structural similarities, RSK isoforms have been shown to perform nonredundant functions and target a wide range of substrates involved in regulation of transcription and translation. In this article we review the roles of the RSKs in proliferation and motility, cell cycle control and therapy resistance in PCa, highlighting the possible interplay between RSKs and AR in mediating disease progression. In addition, we summarize the current advances in RSK inhibitor development and discuss their potential clinical benefits

Entwicklung des Wissens über das Reflexionsgesetz: Die Rolle der Vorstellung

In dieser Studie wurde das Wissen über das Reflexionsgesetz und die Entwicklung der Fähigkeit unter-sucht, eine vorgestellte Bewegung eines Objektes mit den Augen zu verfolgen. Grundschulkinder undErwachsene hatten die Aufgabe, die Bahn einer Kugel, die an einer Wand abprallt, aufzuzeichnen oderdie vorgestellte Bahn mit den Augen zu verfolgen. Die Augenbewegung wurde dabei aufgezeichnet.Die Aufgabenschwierigkeit wurde variiert, indem die Kugel entweder an einer oder an zwei Wändenabprallen konnte. Das Wissen über das Reflexionsgesetz sowie die Fähigkeit vorgestellte Bahnen mitden Augen zu verfolgen wurde mit zunehmendem Alter besser. Diese Vorstellungsleistung blieb beiKindern beider Altersgruppen jedoch hinter der Zeichenleistung zurück. Erst Erwachsene konntenunabhängig von der Aufgabenschwierigkeit sowohl die Bewegungsbahn zeichnen als auch mit denAugen verfolgen. Dies zeigt, dass im Laufe der Kindheit der Zugriff auf Repräsentationen über Ob-jektbewegungen immer unabhängiger von Handlungen (wie dem Zeichnen) wird und die Fähigkeit,sich physikalische Objektbewegungen vorzustellen, verfügbar wird

Gaze behavior in analytical and holistic face processing

We conducted two experiments examining children's and adults' gaze behavior when processing faces analytically (focusing on a single feature) or holistically (comparing the overall similarity of the faces). Children 6-8 and 9-10 years of age and adults were instructed to assign schematically drawn faces in Experiment 1 and photos of real faces in Experiment 2 to two categories. The categories were constructed so as to allow either an analytical or holistic categorization of the faces. During all trials, gaze behavior was recorded from stimulus onset until reaction. The location and duration of the fixations used were analyzed. Whereas the holistic processors fixated the whole area of the eyes and nose most and longest independently of age, analytical processors showed a more feature-specific gaze behavior, focusing their fixations upon the particular feature used for subsequent processing. Thus, differences in analytical and holistic face processing can be detected early in gaze behavior-that is, at the visual encoding stage

The vacuum ultraviolet photochemistry of the allyl radical investigated using synchrotron radiation

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