The histologic evaluation of pulsed carbon dioxide laser resurfacing versus phenol chemical peels in vivo.

BACKGROUND: Carbon dioxide (CO2) lasers and phenol chemical peels have been used extensively for facial skin resurfacing. OBJECTIVE: The purpose of this study is to compare the histologic effects of phenol chemical peels and CO2 laser ablations. METHODS: Local preauricular areas were treated with lasers on one side of the face and a phenol peel on the other. One day after the procedures, the affected areas were biopsied for histologic evaluation. The areas were biopsied again after 3 months. RESULTS: The initial biopsies demonstrated that the CO2 lasers ablate more superficial skin than the peels, but the 3-month biopsy specimens showed that the zone of new collagen formation was thicker as a result of the phenol peels. CONCLUSION: With the parameters used in this study, phenol peels resulted in the formation of a thicker zone of collagen despite the deeper ablation depth of the laser.

Modification of subcutaneous adipose tissue by a methylxanthine formulation: a double-blind controlled study.

BACKGROUND: Excessive subcutaneous adipose tissue is typically treated by physically removing the fat through liposuction, but cost and accessibility have popularized alternative treatments for reducing adipose tissue thickness. OBJECTIVE: The purpose of this study was to test the absolute and relative effectiveness of a liposome-encapsulated caffeine-based cream in modifying subcutaneous adipose tissue. METHODS: Forty-one patients consented and completed the double-blind, single-center, placebo-controlled study. Caliper measurements, tape measurements, and photographs were taken over a 2-month period. RESULTS: Both concentrations of the cream were found to significantly reduce the thickness of the adipose tissue in all areas of the body. In addition, the more concentrated cream was significantly more effective than the less concentrated cream in the areas of the hips and the triceps. CONCLUSION: The caffeine-based liposome-encapsulated cream significantly reduced the thickness of the subcutaneous fat over a 2-month period.

Clinical and histological effects of glycolic acid at different concentrations and pH levels.

BACKGROUND: Much has been said about the effects of glycolic acid with little scientific evidence to substantiate the findings. OBJECTIVE. This study reports on the clinical and histological effects of glycolic acid at pH levels 3.25, 3.80, and 4.40, and at 3.25%, 6.50%, 9.75%, and 13.00% on ichthyotic/xerotic skin. METHODS: Product treatment consisted of a 2-week washout period followed by 3 weeks of product application (BID) with A 1-week regression period. Shave biopsies and clinical evaluations for dryness, moisturization, and transepidermal water loss were made at baseline, 1, 2, and 3 weeks of use, and at the regression period. RESULTS: Clinically, ichthyotic/xerotic skin was normalized with histologic evidence of stratum corneum thinning, viable epidermal thickening, and marked increases in glycosaminoglycan and collagen content. CONCLUSION: All pH levels and concentrations demonstrated significant improvement in the condition of the skin with trends implying that increasing the pH increases efficacy.

Comparison of the effect of various chemical peeling agents in a mini-pig model.

BACKGROUND: With the advent of newer chemical peels, there is now a wide range of peeling agents that can be applied on specific patients. OBJECTIVE: The purpose of this study was to closely examine the more common chemical peeling agents at different concentrations. METHODS: The study methods were carried out by thoroughly cleansing the skin surface with acetone. Different concentrations of the chemical peels were applied on different skin areas (2 x 2 cm each) and left on the skin for 15 minutes: phenol-Bakers, 25%, 50%, 75%, 88%; trichloroacetic acid, 25%, 50%, 75%; glycolic acid, 50%, 70%; and pyruvic acid, 50%, 100%. Serial biopsies were taken from each peeling site at 1, 7, and 21 days post-peel. Biopsies were then evaluated for epidermal changes, inflammation, and collagen deposition. RESULTS: The results show that Bakers phenol peel caused the most inflammation and nonspecific reaction, and in addition, a proportionate amount of new collagen deposition. Plus, increasing concentrations of phenol and TCA caused increasing amount of epidermal sloughing and inflammation after 1 day post-peel. The extent of reaction from the phenol and TCA was directly proportional to the collagen deposition at 21 days. CONCLUSIONS: The glycolic acid and pyruvic acid caused minimal nonspecific reaction. However, the collagen deposition caused by the glycolic acid and pyruvic acid was disproportionately increased suggesting a direct stimulatory effect by the two agents.

Glycolic acid modulation of collagen production in human skin fibroblast cultures in vitro.

BACKGROUND: Glycolic acid has been used extensively for the treatment of photoaging and wrinkles. Suggestions have been made that glycolic acid may have specific dermal effects, although biochemical studies are limited. OBJECTIVE: This study's purpose was to examine the effect of glycolic acid on the radioactively labeled collagen production in human skin fibroblasts in culture. METHODS: Normal dermal fibroblasts were grown to semi-confluence and incubated in the presence of glycolic acid for 24 hours. Radioactive proline was added to the cultures. Using a specific amino acid assay, the amount of radioactive hydroxyproline was measured and was used as an accurate index of collagen production. RESULTS: Results show that glycolic acid caused an elevated collage production in the fibroblasts. CONCLUSION: These results demonstrate a specific stimulatory effect by the glycolic acid and could explain some of the positive benefits from the clinical use of glycolic acid.

Clinical improvement of photoaged skin with 50% glycolic acid. A double-blind vehicle-controlled study.

BACKGROUND: Although there is increasing interest in the use of glycolic acid in the treatment of photoaged skin, to our knowledge, no controlled study has been done to assess the efficacy or the mode of this agent. OBJECTIVE: The purpose of this study was to determine whether 50% glycolic acid can improve photoaged skin and to study the histological basis for this improvement. METHODS: Forty-one volunteers were recruited into this double-blind vehicle-controlled study. Glycolic acid (50%) or vehicle was applied topically for 5 minutes to one side of the face, forearms, and hands, once weekly for 4 weeks. Punch biopsies were taken at pretherapy and at 5 weeks for histologic study. RESULTS: Significant improvement noted included decrease in rough texture and fine wrinkling, fewer solar keratoses, and a slight lightening of solar lentigines. Histology showed thinning of the stratum corneum, granular layer enhancement, and epidermal thickening. Some specimens showed an increase in collagen thickness in the dermis. CONCLUSION: The results of this study demonstrate that the application of 50% glycolic acid peels improves mild photoaging of the skin.

Management of acute wounds.

Acute wounds are defined as a disruption in the integrity of the skin, including the epidermis and dermis. Healing is the reparative process by the skin to protect itself and to generate new cutaneous structures. Medical and surgical intervention in wounds can greatly affect the resultant scar and the time of healing.

Spectrin cagliari. an Ala-->Gly substitution in helix 1 of beta spectrin repeat 17 that severely disrupts the structure and self-association of the erythrocyte spectrin heterodimer.

The spectrin tetramer, the principal structural element of the red cell membrane skeleton, is formed by stable head-to-head self-association of two spectrin heterodimers. The self-association site appears to be formed by interactions between helices 1 and 2 of beta spectrin repeat 17 of one dimer with helix 3 of alpha spectrin repeat 1 of the other dimer to form two combined alpha-beta triple-helical segments. The head of the heterodimer appears to involve similar intradimer interactions. We describe the first example of an amino acid substitution in helix 1 of this combined alpha-beta triple-helical segment, which, although relatively minor, profoundly impairs tetramer formation. Strikingly, low angle rotary shadowing electron microscopy of isolated spectrin dimers reveals that this mutation also severely disrupts the head of the heterodimer causing it to be open. Following linkage studies which were most consistent with a beta spectrin gene mutation, a nucleotide change was identified in codon 2018, resulting in an Ala-->Gly substitution in the first helical domain of beta spectrin repeat 17. Because glycine is a strong helix breaker, this change is predicted to disrupt the conformation of this helical domain. Our results indicate that this helical domain must play direct roles in the alpha-beta interdimer interactions that form the self-association site of the tetramer and in the alpha-beta intradimer interactions at the head of the heterodimer.

Glycolic acid peels for the treatment of wrinkles and photoaging.

BACKGROUND: Glycolic acid is an alpha hydroxyacid that is useful as a chemical peeling agent. OBJECTIVE: To discuss the techniques using glycolic acid to remove actinic keratoses, fine wrinkles, lentigines, melasma, and seborrheic keratoses. METHOD: Applied in a carefully timed manner, the depth of penetration can be titrated by the timed duration of application of acid on the skin. Chemical peels are left on the skin for 3 to 7 minutes for most patients. For ideal results, the chemical peel can be repeated 3 to 4 times. RESULT: Glycolic acid can easily be used to peel skin of all skin types with minimal risk. CONCLUSION: We have found glycolic acid can be an ideal adjunct to other cosmetic modalities such as soft tissue augmentation.

Systemic isotretinoin: effects on dermal wound healing in a rabbit ear model in vivo.

Clinical observations have suggested that wound healing may be altered in patients treated with systemic isotretinoin. In this study, we examined the effects of systemic isotretinoin on dermal wound healing and connective tissue metabolism in a rabbit ear model. Forty 6-mm punch-biopsy wounds were created in the ears of two control rabbits as well as two experimental animals fed isotretinoin, 4 mg/kg per day. Clinical inspection and histologic examination revealed no difference between the control and isotretinoin-treated rabbits in terms of the time required for complete wound healing or the appearance of the final scar. The tissue removed from the wound site at days 0, 7, 14, and 21 after wounding was subjected to analysis of a collagen production and collagen gene expression. Collagen production, determined by the synthesis of [3H]hydroxyproline after incubation of tissue slices with [3H]proline in vitro or by the measurement of the steady-state levels of types I and III procollagen mRNAs, was not significantly different between the two groups. The results indicate that systemic administration of isotretinoin does not affect collagen synthesis in the rabbit ear model of wound healing.

Selectively enhanced procollagen gene expression in sclerosing (morphea-like) basal cell carcinoma as reflected by elevated pro alpha 1(I) and pro alpha 1(III) procollagen messenger RNA steady-state levels.

Sclerosing or morphea-like variant of basal cell carcinoma (BCC) is characterized by an extensive connective tissue stroma, and histopathology has suggested that the extracellular matrix is largely composed of collagen. In addition, fibronectin deposition has been proposed to modulate tumor growth in BCC. In this study, we examined the expression of genes coding for type I, III, and IV procollagens, as well as for fibronectin, in tissue from 10 patients with sclerosing BCC. For comparison, tissues from 5 patients with nodular BCC and 4 controls were examined. Total RNA was isolated by CsCl density gradient centrifugation, and messenger RNA (mRNA) steady-state levels were determined by slot-blot hybridizations with human sequence specific complementary DNAs (cDNAs). The abundance of type I procollagen mRNA in sclerosing BCC tissue was increased to 233.6 +/- 36.7% of the controls (mean +/- SEM). The corresponding value for type III procollagen mRNA in sclerosing BCC was 281.8 +/- 54.8% of the controls. Consequently, the steady-state ratio of type I/III procollagen mRNAs in sclerosing BCCs (5.0 +/- 1.2; mean +/- SD) was within the control range. Thus, there is a coordinate increase in type I and type III procollagen mRNA levels in sclerosing BCC. In contrast, the values for type I and type III procollagen mRNAs in nodular BCC were not different from the controls. In addition, type IV procollagen and fibronectin mRNA levels were not different from the controls either in sclerosing or nodular BCCs, attesting to the selectivity of the increase in type I and III procollagen mRNA levels in sclerosing BCC. These observations may relate to the excessive deposition of the extracellular matrix stroma surrounding the tumor cells in sclerosing BCC.

Lipoid proteinosis: ultrastructural and biochemical studies.

Lipoid proteinosis, a rare autosomal recessive disease, is histologically characterized by deposition of hyalinlike material in the dermis. In this study the pathologic processes of lipoid proteinosis were evaluated by ultrastructural and biochemical analysis of skin and cultured fibroblasts from a patient with classic features of the disease. Transmission electron microscopy revealed the presence of hyalinlike material with a granular appearance interspersed between collagen fibers. Immediately surrounding the blood vessel walls, there was reduplication of basal laminae in an "onionskin" arrangement. The fibroblastic cells in the affected dermis contained peculiar cytoplasmic inclusions. Biochemical studies with the cultured fibroblasts showed that the total synthesis of extracellular matrix components, as detected by the synthesis of radioactive hydroxyproline or the incorporation of 35SO4(2-) and [3H]glucosamine into macromolecules, was not altered in lipoid proteinosis. However, the relative expression of type I and type III procollagen genes, as detected by molecular hybridizations with pro-alpha 1(I) and pro-alpha 1(III) procollagen complementary deoxyribonucleic acid probes, was markedly altered in cultured fibroblasts. Specifically, the type I procollagen messenger ribonucleic acid (mRNA) levels were significantly reduced, resulting in a decreased type I/III procollagen mRNA ratio. Furthermore, the replicative capacity of lipoid proteinosis fibroblasts, as detected by the incorporation of radioactive thymidine, was reduced. Thus the skin fibroblasts from lipoid proteinosis demonstrate ultrastructural changes, as well as alterations in their phenotypic characteristics, and these changes may have relevance to the pathologic processes of this systemic disease affecting the skin and other organs.

PUVA therapy for psoriasis: comparison of oral and bath-water delivery of 8-methoxypsoralen.

A direct clinical comparison has been made of the efficacy of oral 8-methoxypsoralen with bath-water delivery of 8-methoxypsoralen during psoralen ultraviolet A (PUVA) phototherapy for a group of forty patients with stable plaque-type psoriasis vulgaris. The 8-methoxypsoralen concentration was 3.7 mg/liter in the bath water. The efficacy of these treatments was assessed by their ability to improve or clear the psoriasis. The skin of eight of the twenty patients with oral psoralen cleared, and another eight showed good improvement. Of the twenty patients who received 8-methoxypsoralen in bath water, eight patients had clearing of the skin, whereas nine patients had good improvement during the initial 8-week treatment period. Administration of 8-methoxypsoralen in bath water required much lower ultraviolet A irradiance to achieve maximum improvement. There were no systemic side effects in the patients treated by bath-water delivery; however, some patients did develop phototoxic erythema. Minimal phototoxic doses were also studied in patients and in volunteers using both routes of psoralen delivery. The minimal phototoxic dose threshold after psoralen bath delivery gradually declined over five treatments from 5.3 +/- 0.6 joules/cm2 to 2.8 +/- 0.3 joules/cm2, suggesting an accumulation of psoralen in the skin with this method of drug delivery. Bath-water delivery of 8-methoxypsoralen was therefore found to be as effective as oral administration of 8-methoxypsoralen and yet required smaller amounts of ultraviolet A radiation and yielded fewer side effects. It would thus seem to be confirmed as a useful alternative means of 8-methoxypsoralen administration in PUVA therapy.

Phenytoin modulates connective tissue metabolism and cell proliferation in human skin fibroblast cultures.

Phenytoin has been proposed for the treatment of certain dermatologic conditions involving connective tissue abnormalities. To understand the biochemical basis of connective tissue changes, we incubated human skin fibroblasts in culture with varying concentrations of phenytoin. The results indicated that fibroblast proliferation, detected by tritiated thymidine incorporation into cells, was slightly stimulated when short incubation periods and low concentrations of phenytoin were employed. However, with longer incubation times and higher phenytoin concentrations, a significant reduction in fibroblast proliferation was observed. Further studies demonstrated that incubation of cells with phenytoin did not affect the production of procollagen, measured as synthesis of radioactive hydroxyproline in the cultures. However, assay of prolyl hydroxylase, an enzyme participating in the post-translational synthesis of hydroxyproline during collagen biosynthesis, was significantly reduced in the fibroblast cultures. The activity of collagenase, an enzyme participating in degradation of collagen, was markedly decreased in cultures treated with phenytoin. Thus, phenytoin may modulate collagen metabolism primarily by affecting the degradation of collagen. The results support previous suggestions that phenytoin may be useful for treatment of patients with increased levels of collagenase, such as in recessive dystrophic epidermolysis bullosa.