Protease activity, localization and inhibition in the human hair follicle.

OBJECTIVE: In humans, the process of hair shedding, referred to as exogen, is believed to occur independently of the other hair cycle phases. Although the actual mechanisms involved in hair shedding are not fully known, it has been hypothesized that the processes leading to the final step of hair shedding may be driven by proteases and/or protease inhibitor activity. In this study, we investigated the presence of proteases and protease activity in naturally shed human hairs and assessed enzyme inhibition activity of test materials. METHODS: We measured enzyme activity using a fluorescence-based assay and protein localization by indirect immunohistochemistry (IHC). We also developed an ex vivo skin model for measuring the force required to pull hair fibres from skin. RESULTS: Our data demonstrate the presence of protease activity in the tissue material surrounding club roots. We also demonstrated the localization of specific serine protease protein expression in human hair follicle by IHC. These data provide evidence demonstrating the presence of proteases around the hair club roots, which may play a role during exogen. We further tested the hypothesis that a novel protease inhibitor system (combination of Trichogen) and climbazole) could inhibit protease activity in hair fibre club root extracts collected from a range of ethnic groups (U.K., Brazil, China, first-generation Mexicans in the U.S.A., Thailand and Turkey) in both males and females. Furthermore, we demonstrated that this combination is capable of increasing the force required to remove hair in an ex vivo skin model system. CONCLUSION: These studies indicate the presence of proteolytic activity in the tissue surrounding the human hair club root and show that it is possible to inhibit this activity with a combination of Trichogen and climbazole. This technology may have potential to reduce excessive hair shedding.

Investigation of the mechanism of action of nonablative pulsed-dye laser therapy in photorejuvenation and inflammatory acne vulgaris.

BACKGROUND: Nonablative lasers are widely used for treatment of wrinkles, atrophic scars and acne. These lasers stimulate dermal remodelling and collagen production, but the early molecular stimulus for this is unknown. The mechanism of nonablative lasers in inflammatory acne is variously suggested to be damage either to sebaceous glands or to Propionibacterium acnes. Their effects on cytokine production are unknown. OBJECTIVES: To assess the in vivo effects of a short pulse duration nonablative pulsed-dye laser (NA-PDL) previously used for photorejuvenation and treatment of acne, on cytokine production, P. acnes colonization density and sebum excretion rate (SER). METHODS: We examined the effect of NA-PDL (NliteV; Chromogenex Light Technologies, Llanelli, U.K.) on P. acnes colonization before and after laser therapy using a scrub-wash technique and culture at 0 and 24 h (n = 15), on SER using absorptive tape at 0, 2, 4, 8 and 12 weeks (n = 19) and on cytokine mRNA using reverse transcription-polymerase chain reaction from skin biopsies at 0, 3 and 24 h (n = 8). Results NA-PDL had no effect on P. acnes or SER. Transforming growth factor (TGF)-beta1 mRNA increased fivefold after 24 h and 15-fold in two subjects (P = 0.012). CONCLUSIONS: TGF-beta is known to be a potent stimulus for neocollagenesis and a pivotal immunosuppressive cytokine which promotes inflammation resolution. Its upregulation by NA-PDL provides a possible unifying molecular mechanism linking stimulation of dermal remodelling in photorejuvenation with inhibition of inflammation in acne. Damage to P. acnes or sebaceous glands cannot explain the effect of this device in acne.

Safety and side effects of the acne drug, oral isotretinoin.

Isotretinoin is a very effective medication for the treatment of severe recalcitrant acne. However, its use is associated with many side effects, some of which can be very serious. The most important issue is its teratogenicity, which has resulted in new pregnancy prevention policies and programmes implemented by the manufacturer. Recently, the association of isotretinoin with depression has been recognised and new guidelines have been adopted for this possible side effect. The most common adverse events, observed during treatment, are mucocutaneous and ophthalmological. In addition, laboratory abnormalities and effects in the nervous, musculoskeletal, gastrointestinal, pulmonary and other systems have been described.

Pulsed-dye laser treatment for inflammatory acne vulgaris: randomised controlled trial.

BACKGROUND: Low-fluence (low irradiation energy density) pulsed-dye lasers (PDLs) have been used for atrophic acne scarring, and anecdotal experience suggests that long-term improvements in inflammatory acne can be seen after one PDL treatment. Our aim was to compare the efficacy and tolerability of such PDL treatment with sham treatment in patients with facial inflammatory acne in a double-blind, randomised controlled trial. METHODS: We recruited 41 adults with mild-to-moderate facial inflammatory acne. We randomly assigned patients to PDL (n=31) or sham treatment (n=10). Treatment was given at baseline and patients were seen after 2, 4, 8, and 12 weeks. Assessors and participants were unaware of treatment allocations. Primary outcome measures were acne severity after 12 weeks and adverse events at any time. Secondary measures were change in lesion counts after 12 weeks and change in acne severity with time. Analysis was by intention-to-treat. FINDINGS: After 12 weeks, acne severity (measured by Leeds revised grading system) was reduced from 3.8 (SD 1.5) to 1.9 (1.5) in the PDL group and 3.6 (1.8) to 3.5 (1.9) in the sham group (p=0.007). Treatment was well tolerated. Total lesion counts fell by 53% (IQR 19 to 64) in PDL patients and 9% (-16 to 38) in controls (p=0.023), and inflammatory lesion counts reduced by 49% (30 to 75) in PDL patients and 10% (-8 to 49) in controls (p=0.024). The most rapid improvements were seen in the first 4 weeks after treatment. INTERPRETATION: PDL therapy improves inflammatory facial acne 12 weeks after one treatment with no serious adverse effects.