Alterations of Dermal Connective Tissue Collagen in Diabetes: Molecular Basis of Aged-Appearing Skin.

Alterations of the collagen, the major structural protein in skin, contribute significantly to human skin connective tissue aging. As aged-appearing skin is more common in diabetes, here we investigated the molecular basis of aged-appearing skin in diabetes. Among all known human matrix metalloproteinases (MMPs), diabetic skin shows elevated levels of MMP-1 and MMP-2.

Expression of catalytically active matrix metalloproteinase-1 in dermal fibroblasts induces collagen fragmentation and functional alterations that resemble aged human skin.

Increased expression of matrix metalloproteinase-1 (MMP-1) and reduced production of type I collagen by dermal fibroblasts are prominent features of aged human skin. We have proposed that MMP-1-mediated collagen fibril fragmentation is a key driver of age-related decline of skin function. To investigate this hypothesis, we constructed, characterized, and expressed constitutively active MMP-1 mutant (MMP-1 V94G) in adult human skin in organ culture and fibroblasts in three-dimensional collagen lattice cultures.

Molecular analysis of aggressive microdermabrasion in photoaged skin.

Objective: To investigate dermal remodeling effects of crystal-free microdermabrasion on photodamaged skin.

Design: Biochemical analyses of human skin biopsy specimens following microdermabrasion treatment in vivo.

Setting: Academic referral center.

Topical fluorouracil for actinic keratoses and photoaging: a clinical and molecular analysis.

Objective: To examine clinical and molecular changes after topical fluorouracil treatment of photodamaged human facial skin for actinic keratoses.

Design: Nonrandomized, open-label 2-week treatment with fluorouracil cream, 5%, followed by clinical and molecular evaluation.

Setting: Academic referral center.

Molecular effects of photodynamic therapy for photoaging.

Objective: To quantitatively examine the epidermal and dermal cellular and molecular changes that occur after photodynamic therapy of photodamaged human skin.

Design: Serial in vivo biochemical and immunohistochemical analyses after photodynamic therapy using topical 5-aminolevulinic acid (5-ALA) and pulsed-dye laser treatment.

Setting: Academic referral center, Department of Dermatology, University of Michigan, Ann Arbor.

Effect of increased pigmentation on the antifibrotic response of human skin to UV-A1 phototherapy.

Objective: To investigate the efficacy, potential limitations, and biological mechanisms of UV-A1 phototherapy for skin sclerosis due to collagen deposition disorders.

Design: Before-and-after trial of UV-A1 irradiation of sclerotic skin; in vivo biochemical analyses after UV-A1 irradiation of normal skin.

Setting: Academic referral center.

The effects of laser-mediated hair removal on immunohistochemical staining properties of hair follicles.

Background: The mechanisms involved in laser-mediated hair removal remain unclear. One means of reducing hair growth is alteration of follicular stem cells.

Objective: We sought to examine the effects of laser hair removal on the immunohistochemical staining properties of human hair follicles, including the putative stem cells of the bulge region.

Microdermabrasion with and without aluminum oxide crystal abrasion: a comparative molecular analysis of dermal remodeling.

Background: Microdermabrasion is a popular method of superficial skin resurfacing with effects on dermal remodeling.

Objective: The purpose of this study was to evaluate the relative importance of the two components of microdermabrasion, negative pressure and abrasion, in stimulating expression of key genes involved in dermal remodeling.

Methods: Ten subjects were treated with a microdermabrasion machine using focal crystal abrasion and negative pressure or negative pressure alone for 3 seconds.

Dermal matrix remodeling after nonablative laser therapy.

Objective: Nonablative laser therapy is widely practiced for cutaneous rejuvenation. We sought to quantify dermal molecular changes after exposure of photodamaged skin to nonablative laser energy.

Methods: Nonablative laser therapy of forearm skin using either a 585-nm wavelength pulsed dye laser or a 1320-nm wavelength neodymium:yttrium-aluminum-garnet laser was performed.

Long-term efficacy and safety of tretinoin emollient cream 0.05% in the treatment of photodamaged facial skin: a two-year, randomized, placebo-controlled trial.

Background: Long-term (>1 year) placebo-controlled studies of tretinoin in the treatment of photodamaged skin have not been conducted. Recently, we conducted a 2-year placebo-controlled study of tretinoin emollient cream 0.05%, including histopathologic assessment of safety and analysis of markers of collagen deposition.

Inflammation and extracellular matrix degradation mediated by activated transcription factors nuclear factor-kappaB and activator protein-1 in inflammatory acne lesions in vivo.

Acne is the most common skin disease, causing significant psychosocial problems for those afflicted. Currently available agents for acne treatment, such as oral antibiotics and isotretinoin (Accutane), have limited use. Thus, development of novel agents to treat this disease is needed.

Microdermabrasion: a molecular analysis following a single treatment.

Background: Microdermabrasion is a popular method of superficial skin resurfacing. It is unclear if dermal remodeling actually occurs.

Objective: To rigorously investigate the molecular alterations observed following a single microdermabrasion treatment.

Tretinoin treatment before carbon-dioxide laser resurfacing: a clinical and biochemical analysis.

Background: Tretinoin is often prescribed before laser resurfacing in an attempt to enhance results.

Objective: We sought to assess the clinical and biochemical effects of preoperative tretinoin use before laser resurfacing.

Methods: Patients were randomized to apply tretinoin to one forearm and placebo to the other for 3 weeks.

Connective tissue remodeling induced by carbon dioxide laser resurfacing of photodamaged human skin.

Objective: To quantitatively examine the dynamics of molecular alterations involved in dermal remodeling after carbon dioxide (CO(2)) laser resurfacing of photodamaged human skin.

Design: Serial in vivo biochemical analyses after laser therapy.

Setting: Academic referral center, Department of Dermatology, University of Michigan, Ann Arbor.

Effect of carbon dioxide laser resurfacing on epidermal p53 immunostaining in photodamaged skin.

Objective: To quantitatively examine changes in p53 tumor suppressor gene immunostaining after carbon dioxide (CO(2)) laser resurfacing of photodamaged skin to assess the potential value of this treatment in reducing the risk of progression to cutaneous carcinoma.

Design: Serial in vivo immunohistochemical analyses after laser therapy.

Setting: Academic referral center, Department of Dermatology, University of Michigan, Ann Arbor.

Treatment of acne vulgaris with a pulsed dye laser: a randomized controlled trial.

Context: The high prevalence of acne vulgaris and its significant morbidity underscore the need for convenient, low-risk, and efficacious therapy. Treatment with various lasers has been reported to improve acne.

Objective: To evaluate the clinical efficacy of pulsed dye laser therapy in the treatment of acne.