The Effects of Steady Freddy, a Lidocaine-Based Pump Spray for the Treatment of Premature Ejaculation (PE).

Premature ejaculation (PE) is reported to be the most common sexual dysfunction in men and is defined as the inability to control or delay ejaculation. Steady Freddy is a lidocaine-based ejaculation-delaying spray. This article examines the effects of Steady Freddy on the sexual experience of men that have self-reported to suffer from PE. Under the conditions of a randomized single-blind placebo-controlled clinical trial, 150 participants received either placebo or treatment for the duration of 12 weeks and completed an internet-based questionnaire for the quality of their sexual experience. Prior to product usage, participant average latency time was <1 min, 70% claimed to be very sexually dissatisfied, and 67% claimed to be very dissatisfied with ejaculation control. Upon product usage, sexual experience was significantly improved (p<.01). Participant average latency time increased to >2 min, 80% claimed to be sexually satisfied, and 70% claimed to be satisfied with ejaculation control. These effects were not present in the placebo group throughout the trial. These findings provide evidence for the effectiveness of Steady Freddy in significantly improving the quality of sexual experience and suggest that Steady Freddy can assist with PE.

PTEN as a target in melanoma.

PTEN is a well-known tumour suppressor protein that is frequently found to be mutated, inactivated or deleted in a wide range of different cancers. Its tumour suppressive properties result predominantly from its inhibitory effects on the PI3K-AKT signalling pathway. In melanoma, numerous different PTEN mutations have been identified in both melanoma cell lines and melanoma tissue. A number of different molecules can act on PTEN to either promote its suppression of melanoma, while other molecules may antagonise PTEN to inhibit its mechanism of action against melanoma. This review will discuss how the interactions of PTEN with other molecules may have a positive or negative impact on melanoma pathogenesis, giving rise to the potential for PTEN-targeted therapies against melanoma.

PTEN: A novel target for vitamin D in melanoma.

Melanoma is the most dangerous form of skin cancer, with poor prognosis in advanced stages. Vitamin D, also produced by ultraviolet radiation, is known for its anti-proliferative properties in some cancers including melanoma. While vitamin D deficiency has been associated with advanced melanoma stage and higher levels of vitamin D have been associated with better outcomes, the role for vitamin D in melanoma remains unclear. Vitamin D synthesis is initiated upon UVB exposure of skin cells and results in formation of the active metabolite 1,25-dihydroxyvitamin D3 (1,25D). We have previously demonstrated that 1,25D plays a role in protection against ultraviolet radiation-induced DNA damage, immune suppression, and skin carcinogenesis. In this study 1,25D significantly reduced cell viability and increased caspase levels in human melanoma cell lines. This effect was not present in cells that lacked both phosphatase and tensin homolog deleted on chromosome 10 (PTEN), a well-known tumour suppressor, and the vitamin D receptor (VDR). PTEN is frequently lost or mutated in melanoma. Incubation of selected melanoma cell lines with 1,25D resulted in significant increases in PTEN levels and downregulation of the AKT pathway and its downstream effectors. This suggests that 1,25D may act to reduce melanoma cell viability by targeting PTEN.

Skin protective and regenerative effects of RM191A, a novel superoxide dismutase mimetic.

Superoxide dismutase (SOD) is known to be protective against oxidative stress-mediated skin dysfunction. Here we explore the potential therapeutic activities of RM191A, a novel SOD mimetic, on skin. RM191A is a water-soluble dimeric copper (Cu2+-Cu3+)-centred polyglycine coordination complex. It displays 10-fold higher superoxide quenching activity compared to SOD as well as significant antioxidant, anti-inflammatory and immunomodulatory activities through beneficial modulation of several significant inflammatory cytokines in vitro and in vivo. We tested the therapeutic potential of RM191A in a topical gel using a human skin explant model and observed that it significantly inhibits UV-induced DNA damage in the epidermis and dermis, including cyclobutane pyrimidine dimers (CPD), 8-oxo-guanine (8-oxoG) and 8-nitroguanine (8NGO). RM191A topical gel is found to be non-toxic, non-teratogenic and readily distributed in the body of mice. Moreover, it significantly accelerates excisional wound healing, reduces 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced inflammation and attenuates age-associated oxidative stress in skin, demonstrating both skin regenerative and geroprotective properties of RM191A.