D-penicillamine, a potent melanogenesis inhibitor, lacks any depigmenting effect on black guinea pig skin: the first randomized, evaluator-blinded, vehicle-controlled, in vivo study.

D-penicillamine is a melanogenesis inhibitor. This in vivo study on ten black guinea pigs using a 5% D-penicillamine ointment showed its lack of any skin-lightening effect. The potential reasons for this ineffectiveness are discussed in the paper, which could be very helpful for researchers exploring new skin-lightening agents.

Decrease of insulin growth factor-1 as a novel mechanism for anti-androgen effect of isotretinoin and its reported association with depression in some cases.

Isotretinoin and its desirable effects have received tremendous attention in recent years by scientists. This article reviews the evidence that decrease of insulin growth factor-1 is implicated as a novel mechanism of anti androgenic effect and its reported association with depression in some cases.

Homocysteine may accelerate skin aging: a new chapter in the biology of skin senescence?

Skin aging has received tremendous attention in recent years by both scientists and the lay public. This article reviews the evidence that homocysteine, an intermediary sulfhydryl-containing amino acid implicated in atherosclerosis, can accelerate skin aging and the aging of internal organs (universal aging).

Therapeutic ladder for pemphigus vulgaris: emphasis on achieving complete remission.

BACKGROUND: Pemphigus vulgaris (PV) is a blistering autoimmune bullous disease that is usually fatal without proper treatment. There are no clear treatment guidelines for PV at this time. PURPOSE: We suggest a standard treatment regimen for patients with PV based on the success of our treatment. METHODS: A retrospective chart review of 18 patients with PV was conducted to assess response to a similar approach using mycophenolate mofetil (MMF) and prednisone. Diagnosis was confirmed through routine histology, direct immunofluorescence, and indirect immunofluorescence, and patients were followed up for a total average of 35.2 months. RESULTS: We achieved complete disease control in 89% of patients using our treatment algorithm. Fourteen of 18 patients achieved complete disease control on therapy with prednisone and MMF. Three of the 4 patients who did not achieve control on MMF and prednisone went on to receive rituximab therapy, and two of those patients achieved disease control on rituximab. The average length of time from initiating therapy to 75% clearance of lesions was 4.5 months. Three of 18 patients were able to discontinue therapy after an average of 3 years and have remained in complete remission for more than 1 year. LIMITATIONS: This was a retrospective chart review with a small patient sample size. CONCLUSIONS: The combination therapy of MMF and prednisone is an effective treatment regimen to achieve rapid and complete control of PV. For those patients who fail treatment with MMF and prednisone, rituximab is an efficacious alternative therapy.

Proteinase-activated receptor-2 expression in basal and squamous cell carcinomas compared with normal skin.

Proteinase-activated receptor-2 (PAR-2) is a transmembrane G-protein expressed in many normal tissues and overexpressed in several cancer cell lines. It contributes to metastasis, promotes epidermal growth factor receptor proliferation, angiogenesis and tumor progression in many carcinomas. The purpose of this study was to investigate the expression of PAR-2 in basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) in comparison with that of normal skin. Immunohistochemical (IHC) expression of PAR-2 was examined using paraffin-embedded sections from 30 BCCs, 30 SCCs and also 30 normal sun-exposed skin specimens. PAR-2 was expressed in all specimens of SCC and normal skin. In marked contrast, all BCC specimens had negative IHC staining. Given the important role of PAR-2 in angiogenesis and metastasis, our finding can explain the far less aggressive behavior of BCC as compared with SCC.

Steroid sulfatase inhibitors as novel additions to the antipsoriatic armamentarium.

Psoriasis is a clinical conundrum that affects an estimated 1-3% of the world's population. The psoriatic disease process, characterized by a type 1 cytokine pattern, is supposed to be maintained by a continuing immune response in a "peripheral lymphoid tissue" that forms in lesional skin and is composed of T cells, dendritic cells, and vessels arranged like a T-dependent zone in lymph nodes. Dehydroepiandrosterone (DHEA), produced from dehydroepiandrosterone sulfate (DHEAS) through the enzymatic activity of DHEA-sulfatase, plays a pivotal role in the development of the type 1 immune response generated in peripheral lymphoid organs. Taken together, it could be reasoned that DHEA-sulfatase inhibitors may have utility in the treatment of psoriasis. Furthermore, the addition of DHEA-sulfatase inhibitors to calcipotriol, which encourages type 2 immune response, may provide an additive or synergistic inhibition of the type 1 immune response underlying psoriasis. It has been shown that topical application of cholesterol sulfate in the hairless mouse causes epidermal hyperkeratosis, which can be prevented by co-application of topical cholesterol. Therefore, as the inhibition of conversion of cholesterol sulfate to cholesterol can induce epidermal hyperkeratosis and may thus abbreviate the benefit obtained by inhibition of DHEAS to DHEA conversion, topical sulfatase inhibitors should preferably be co-applied with topical cholesterol, though it is also possible that the beneficial immunological effects of steroid sulfatase inhibitors outweigh their possible hyperkeratosis stimulation. Alternatively, the production of specific DHEA-sulfatase inhibitors can resolve the above concern. DHEA-sulfatase inhibitors may prove invaluable in the treatment of psoriasis.