Activation of Sirtuin (silent mating type information regulation 2 homolog) 1, or SIRT1, is an unexplored therapeutic approach for treatment of inflammatory diseases. We randomized 40 patients with ...moderate-to-severe psoriasis (4:1) to three escalating doses of SRT2104, a selective activator of SIRT1, or placebo. Across all SRT2104 groups, 35% of patients (p<0.0001) achieved good to excellent histological improvement based on skin biopsies taken at baseline and day 84 but was not consistently in agreement with PASI. Improvement in histology was associated with modulation of IL-17 and TNF-α signaling pathways and keratinocyte differentiation target genes. 27 subjects (69%) across all treatment groups, including placebo, experienced at least one treatment emergent adverse event. The majority of AEs were either mild or moderate. Most common were headache (8%), dizziness (8%), upper respiratory tract infection (8%), and psoriatic arthropathy (8%). Average drug exposure increased in a dose-dependent manner for escalating doses of SRT2104 and had high intra-subject variability in exposure (AUC %CV: 51–89%). Given the interesting signals of clinical activity, impact on gene expression and the generally favorable safety profile seen in this study, further investigation of SIRT1 activators for the treatment of psoriasis is warranted.
Clinicaltrials.gov NCT01154101.
Annular and acral/facial dyskeratotic paraneoplastic disorders are inflammatory dermatoses that occur in association with distant cancers but are not precursors, extensions, or metastases of them. ...There are four classical entities under this rubric: two gyrate entities, erythema annulare centrifugum and erythema gyratum repens, and two acral/facial dyskeratotic entities, acrokeratosis paraneoplastic (Bazex syndrome) and tripe palms. Each of these entities may also occur in association with another etiopathogenesis and may present either as a classical entity or as a barely recognizable disease. We discuss these entities, their associated causes, and their differential diagnoses in turn.
Activation of Sirtuin (silent mating type information regulation 2 homolog) 1, or SIRT1, is an unexplored therapeutic approach for treatment of inflammatory diseases. We randomized 40 patients with ...moderate-to-severe psoriasis (4:1) to three escalating doses of SRT2104, a selective activator of SIRT1, or placebo. Across all SRT2104 groups, 35% of patients (p<0.0001) achieved good to excellent histological improvement based on skin biopsies taken at baseline and day 84 but was not consistently in agreement with PASI. Improvement in histology was associated with modulation of IL-17 and TNF-alpha signaling pathways and keratinocyte differentiation target genes. 27 subjects (69%) across all treatment groups, including placebo, experienced at least one treatment emergent adverse event. The majority of AEs were either mild or moderate. Most common were headache (8%), dizziness (8%), upper respiratory tract infection (8%), and psoriatic arthropathy (8%). Average drug exposure increased in a dose-dependent manner for escalating doses of SRT2104 and had high intra-subject variability in exposure (AUC %CV: 51-89%). Given the interesting signals of clinical activity, impact on gene expression and the generally favorable safety profile seen in this study, further investigation of SIRT1 activators for the treatment of psoriasis is warranted. Trial Registration Clinicaltrials.gov NCT01154101
Alterations in the cutaneous vascular system are prominent in psoriasis and may play an important role in the pathogenesis of this disorder. We evaluated the effects of topically applied capsaicin ...(trans-8-methyl-N-vanillyl-6-nonenamide), a known inhibitor of cutaneous vasodilatation, on moderate and severe psoriasis. Under a double-blind paradigm, forty-four patients with symmetrically distributed psoriatic lesions applied topical capsaicin to one side of their body and identical-appearing vehicle to the other side for 6 weeks. After 3 and 6 weeks of treatment, we performed ratings on changes in scaling and erythema, as well as overall improvement of the psoriasis. Over the course of the study, significantly greater overall improvement was observed on sides treated with capsaicin compared to sides treated with vehicle. Similarly, significantly greater reductions in scaling and erythema accompanied capsaicin application. Burning, stinging, itching, and redness of the skin were noted by nearly half of the patients on initial applications of study medication but diminished or vanished upon continued application. These results suggest that topical application of capsaicin may be a useful new approach in the treatment of psoriasis.
Pyogenic Granuloma Parish, Lawrence C
Pediatrics for Parents,
12/2004, Letnik:
20, Številka:
12
Trade Publication Article
Parish presents a question and answer advisory on Pyogenic Granuloma, small lesions, which usually occurs on the fingers, toes, lips, chest, or back. He asserts that these lesions develop quickly, ...usually within a few weeks of the injury, and, in some cases, bleed easily. Some are like bumps on the skin while others are more like a polyp with a narrow stalk and if irritated, they may crust over like a healing cut. Treatment is easy--removing the pyogenic granuloma by snipping it off or Cryosurgery, using liquid nitrogen to freeze the lesion.
Tinea versicolor Parish, Lawrence C
Pediatrics for Parents,
03/2004, Letnik:
21, Številka:
3
Newsletter, Trade Publication Article
A question and answer advisory on tinea versicolor is presented. Tinea versicolor is a superficial fungal infection caused by Malassezia furfur, a yeast that represents the fungal form of two yeasts.
Keratosis pilaris Parish, Lawrence C
Pediatrics for Parents,
02/2004, Letnik:
21, Številka:
2
Newsletter, Trade Publication Article
A question and answer advisory on goose bumps or keratosis pilaris is presented. Keratosis pilaris, small hard spines that are similar to hard black heads, is common in adolescents and adults. It has ...no known cause and can be treated using a prescribed lotion containing salicylic acid, lactic acid or urea.
Dyshidrosis Parish, Lawrence C
Pediatrics for Parents,
01/2004, Letnik:
21, Številka:
1
Newsletter, Trade Publication Article
A question and answer advisory on dyshidrosis is presented. Dyshidrosis, also called pompholyx or dyshidrotic dermatitis is an abnormality of the sweat glands of the palms and soles. There is a ...malfunctioning of these sweat glands that leads to the formation of water blisters (vesicles) on the palms and soles.
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