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Biomedical subjects

Tania J Phillips

Publications and source records attributed to Tania J Phillips.

At least 19 recordsLinked to original sources
PubMed2005

Estrogen and skin: the effects of estrogen, menopause, and hormone replacement therapy on the skin.

UNLABELLED: Aging is associated with declining levels of several hormones, including estrogen. Although the effects of estrogen on the skin are still not fully understood, it is known that, in women, declining estrogen levels are associated with a variety of cutaneous changes, many of which can be reversed or improved by estrogen supplementation. Estrogens are C-18 steroids synthesized from cholesterol in the ovary premenopausally and in the peripheral tissue in postmenopausal women. Two estrogen receptors, alpha and beta, have been cloned and found in various tissue types. Studies of postmenopausal women indicate that estrogen deprivation is associated with dryness, atrophy, fine wrinkling, poor healing, and hot flashes. Epidermal thinning, declining dermal collagen content, diminished skin moisture, decreased laxity, and impaired wound healing have been reported in postmenopausal women. This article reviews the effects of declining estrogen levels on the skin and the effects of estrogen supplementation. LEARNING OBJECTIVE: At the conclusion of this learning activity, participants should be familiar with the pathways of estrogen synthesis, sites of estrogen receptors, age-dependent variations in serum estrogen concentration, the changes seen in postmenopausal skin, and the effects of estrogen supplementation.

Aging↗
PubMed2005

Chronic wound fluid suppresses proliferation of dermal fibroblasts through a Ras-mediated signaling pathway.

Wound fluid collected from chronic venous leg ulcers (chronic wound fluid (CWF)) has been shown to inhibit the growth of dermal fibroblasts by interfering with cell-cycle progression from G1 into S phase. Specifically, CWF was shown to downregulate the levels of hyperphosphorylated retinoblastoma tumor-suppressor gene (Rb) and cyclin D1, known to be critical for entering the S phase of the cell cycle. To further elucidate the effects of CWF, a Ras-mediated signaling pathway involving the mitogen-activated protein kinase kinase (MEK), known to modulate the expression of these cell-cycle-regulatory proteins, was examined. Transient transfection of dermal fibroblasts with constitutively active Ras abrogated the growth suppressive effects of CWF on hyperphosphorylated Rb (ppRb) and cyclin D1. In contrast, an MEK inhibitor PD 98059 mimicked the effects of CWF on these cell-cycle-regulatory proteins. Concurrent treatment with PD 98059 and CWF produced additive effects. Taken together, these results suggest that CWF inhibits the growth of dermal fibroblasts at least in part by decreasing the level of active Ras, resulting in decreased levels of ppRb and cyclin D1. Therefore, a Ras-dependent signaling pathway may mediate the growth inhibitory effect of CWF, and reconstitution of Ras activity may overcome this growth inhibitory effect.

Apoptosis↗
PubMed2005

Long-term clinical outcomes following treatment of actinic keratosis with imiquimod 5% cream.

BACKGROUND: The results from four phase III, randomized, vehicle-controlled studies showed that imiquimod 5% cream (imiquimod) was safe and effective in the treatment of actinic keratosis (AK). Patients applied imiquimod or vehicle cream to AK lesions on the face or balding scalp, dosing three times per week or two times per week for 16 weeks. OBJECTIVE: To obtain long-term safety follow-up data and estimate AK recurrence in patients who completely cleared their AK lesions in the treatment area at the 8-week post-treatment visit in the phase III studies. METHODS: One hundred forty-six patients from 30 study centers in the United States were evaluated for clinical evidence of AK, and safety data were collected. RESULTS: After a median follow-up period of 16 months, 24.7% (19 of 77) of the patients administered imiquimod three times per week and 42.6% (23 of 54) of the patients administered imiquimod two times per week had a recurrence of AK (the appearance of at least one AK lesion) in the original treatment area. The median number of AK lesions present was one lesion for both patients receiving imiquimod three times and those receiving imiquimod two times per week compared with a median of six lesions at baseline in the combined three times per week and two times per week phase III studies. There were no long-term safety issues, and the skin quality seen in the imiquimod-treated patients at the end of the phase III studies was maintained. CONCLUSION: One and a half years following treatment, imiquimod continued to provide a long-term clinical benefit in a majority of patients who experienced complete clearance of their AK lesions.

Adjuvants, Immunologic↗
PubMed2005

Wound chronicity and fibroblast senescence--implications for treatment.

A proportion of chronic wounds fail to heal in response to standard therapy. For venous leg ulcers, a correlation exists between longer duration before treatment initiation and poor healing response to compression therapy. Differences identified between the healing wound microenvironment and that of the non healing chronic wound suggests that many potential mechanisms exist to impair healing. One contributory mechanism may be inhibition of fibroblast proliferation and induction of a stress-induced premature senescence phenotype by the continuing inflammation found in chronic wounds. Senescent fibroblasts exhibit an extracellular matrix degradative phenotype that contributes to wound chronicity. Accumulation of greater than 15% senescent fibroblasts has been described as a threshold beyond which wounds become hard to heal. The ratio of senescent : non senescent cells is therefore critical to determining response to treatment, and adjunctive therapies that modulate this ratio in favour of non senescent cells are likely to enhance therapeutic healing rates. A number of tissue-engineered dermal replacements contain non senescent fibroblasts and can donate cells to the wound environment additional to releasing growth factors and reversing the antiproliferative activity of chronic wound exudate. Recognition of the role of fibroblast senescence in wound chronicity may allow for identification of those wounds that will respond positively to these products.

Cellular Senescence↗
PubMed2005

An update on the safety and efficacy of topical retinoids.

Adapalene, tazarotene, and tretinoin are topical retinoids that are approved by the US Food and Drug Administration (FDA) and have overall favorable safety profiles. These agents are effective in a variety of skin disorders. Local adverse events, seen especially during the early course of treatment, include peeling, erythema, dryness, burning, and itching. The degree of local skin intolerance varies among patients and may relate to the vehicle formulation used. These local effects can be minimized by decreasing exposure to sunlight, avoiding extreme temperatures, and using moisturizers. Use of these agents has been found to be advantageous over current systemic retinoids from a toxicologic perspective. This article reviews the safety, efficacy, and photostability of the available topical retinoids.

Acne Vulgaris↗
PubMed2004

Photodynamic therapy with aminolevulinic acid topical solution and visible blue light in the treatment of multiple actinic keratoses of the face and scalp: investigator-blinded, phase 3, multicenter trials.

OBJECTIVE: To determine the safety and efficacy of photodynamic therapy (PDT) using 20% wt/vol aminolevulinic acid hydrochloride (hereinafter "ALA") and visible blue light for the treatment of multiple actinic keratoses of the face and scalp. DESIGN: Randomized, placebo-controlled, uneven parallel-group study. INTERVENTIONS: Patients (N = 243) were randomized to receive vehicle or ALA followed within 14 to 18 hours by PDT. Follow-up visits occurred 24 hours and 1, 4, 8, and 12 weeks following PDT. Target lesions remaining at week 8 were re-treated. MAIN OUTCOME MEASURE: Clinical response based on lesion clearing by week 8. RESULTS: Most patients in both groups had 4 to 7 lesions. Complete response rates for patients with 75% or more of the treated lesions clearing at weeks 8 and 12 were 77% (128/166) and 89% (133/149), respectively, for the drug group and 18% (10/55) and 13% (7/52), respectively, for the vehicle group (P<.001, Cochran-Mantel-Haenszel general association test). The 95% confidence interval for the difference in response rates at week 8 was 46.9% to 71.0% and at week 12, 65.3% to 86.3%. The week 12 response rate includes 30% of patients who received a second treatment. Most patients experienced erythema and edema at the treated sites, which resolved or improved within 1 to 4 weeks after therapy, and stinging or burning during light treatment, which decreased or resolved by 24 hours after light treatment. CONCLUSION: Findings indicate that topical ALA PDT is an effective and safe treatment for multiple actinic keratoses of the face and scalp.

Administration, Topical↗
PubMed2003

Modulations of nerve growth factor and Bcl-2 in ultraviolet-irradiated human epidermis.

BACKGROUND: Ultraviolet (UV) irradiation to the skin causes apoptosis of keratinocytes. Melanocytes are more resistant to UV-induced apoptosis, due, in part, to high levels of antiapoptotic proteins such as Bcl-2. In vitro studies have shown that nerve growth factor (NGF), a neurotrophic polypeptide, is produced by keratinocytes and exerts a protective role for melanocytes by upregulating Bcl-2. The purpose of this study was to determine NGF and Bcl-2 modulations in UV-irradiated human skin. METHODS: Nine volunteers were irradiated with two minimal erythema doses using solar-simulated UV irradiation. Seventy-two hours post irradiation, skin biopsies were obtained from irradiated and sun-protected skin. The skin specimens were stained with anti-tyrosinase-related protein-1 monoclonal antibody IgG2a (Mel-5), anti-Bcl-2 (monoclonal antibody IgG-kappa), and with anti-NGF (polyclonal antibody IgG). RESULTS: NGF staining was identified within the cytoplasm of epidermal melanocytes, similar to the staining observed for TRP-1 and Bcl-2. While no significant difference in the number of TRP-1- and Bcl-2-positive melanocytes was observed between irradiated and non-irradiated skin within 72 h, the number of NGF-positive melanocytes decreased significantly, 72 h after UV irradiation (p < 0.024). NGF was also identified within keratinocytes, and while non-irradiated skin exhibited cytoplasmic NGF staining throughout the epidermis, NGF staining was reduced in the lower epidermal layers after UV irradiation. CONCLUSIONS: This is the first in vivo study showing NGF to be present in melanocytes, as well as showing modulations of NGF and Bcl-2 in melanocytes, following solar-simulated UV irradiation.

Adult↗
PubMed2003

Evaluation of the role of exogenous estrogen in postoperative progress after laser skin resurfacing.

BACKGROUND: Recent studies indicate that exogenous estrogens may promote wound healing. Many laser skin resurfacing (LSR) patients use hormone replacement therapy (HRT) or oral contraceptive pills (OCPs). OBJECTIVE: To evaluate the effect of exogenous estrogen on LSR postoperative healing. METHODS: This is a retrospective case control study of 44 female patients who underwent combination CO2/Er:YAG full-face LSR. Sixteen postmenopausal patients using oral HRT during procedure and follow-up were compared with 16 controls. Six premenopausal patients on estrogen-containing OCPs during the procedure and follow-up were compared with six controls. Case and control groups were matched by age, skin type, and treatment technique. Premenopausal and postmenopausal groups were compared. The variables evaluated included erythema, swelling, crusting, purpura, pain, pruritus, reepithelialization, complications, and patient assessment of outcome. RESULTS: For premenopausal and postmenopausal women, there were no significant differences in outcome measures of postoperative morbidity between groups receiving and not receiving estrogen. The incidence of complications, time until re-epithelialization, and patient assessment of outcome were similar between groups. CONCLUSION: Our findings suggest that exogenous estrogen in the form of HRT or OCPs does not clinically alter postoperative progress in combination CO2/Er:YAG LSR patients. Premenopausal women heal comparably to postmenopausal women after LSR.

Adult↗
PubMed2002

Effect of sunscreen application on UV-induced thymine dimers.

BACKGROUND: Exposure to UV radiation is a major risk factor for skin cancer, including malignant melanoma. Photocarcinogenesis is caused largely by mutations at sites of incorrectly repaired DNA photoproducts, of which the most common is the thymine dimer. Over the past decade, controversy has arisen over the use of sunscreens to prevent UV-induced skin cancer. OBJECTIVES: To determine if daily application of a broad-spectrum sunscreen with a sun protection factor (SPF) of 15 protects human skin against UV-induced DNA damage as determined by the formation of thymine dimers after repeated exposures to simulated solar light and, if so, to determine whether daily applications are required to achieve this protective effect. METHODS: Over 4 consecutive days, an SPF 15 sunscreen was applied homogeneously to each of 4 buttock sites of 18 women 30 minutes before exposure to 2 minimum erythemal doses of UV radiation. Of these 4 sites, 1 was treated with SPF 15 daily, and the remaining 3 were treated on 3 of the 4 irradiation days, skipping application on day 2, 3, or 4. A fifth site served as the untreated control and was also not irradiated. The number of cells per square millimeter positive for thymine dimer formation was determined using immunohistochemical and image analyses. RESULTS: There was no significant difference in thymine dimer formation between nonirradiated and irradiated skin when application of sunscreen preceded each irradiation. However, when sunscreen application was omitted even once prior to irradiation, a statistically significant increase in thymine dimer formation was apparent. At 48 hours after irradiation of unprotected skin, 50% of epidermal dimers present 24 hours after irradiation had been removed; at 72 hours, more than 75% were gone. CONCLUSIONS: Our study indicates that regular use of a broad-spectrum sunscreen is effective in preventing a major form of UV-induced DNA damage. Irregular and inadequate use of sunscreen during exposure to UV radiation results in thymine dimer formation, which may lead to mutation and subsequent cancer development.

Administration, Topical↗
PubMed2002

Efficacy of 0.1% tazarotene cream for the treatment of photodamage: a 12-month multicenter, randomized trial.

OBJECTIVE: To determine the efficacy and safety of 0.1% tazarotene cream for the treatment of photodamage. DESIGN: A 24-week multicenter, double-blind, randomized, vehicle-controlled intervention study followed by a 28-week open-label extension. SETTING: Ambulatory patients in private and institutional practice. PATIENTS: Of 563 patients with facial photodamage, 91% and 86% completed the double-blind and open-label phases, respectively. In the double-blind phase, 20 of 283 tazarotene-treated patients and 1 of 280 vehicle-treated patients discontinued treatment owing to adverse events. INTERVENTION: Once-daily application of 0.1% tazarotene cream or nonmedicated vehicle cream to the face for 24 weeks. Then, all continuing patients received treatment with 0.1% tazarotene cream for another 28 weeks. MAIN OUTCOME MEASURES: Primarily, fine wrinkling and mottled hyperpigmentation. Also, lentigines, elastosis, pore size, irregular depigmentation, tactile roughness, coarse wrinkling, telangiectasia, actinic keratoses, overall integrated assessment of photodamage, global response to treatment, patients' overall assessment of photodamage, and plasma levels of tazarotenic acid. RESULTS: Compared with the vehicle, at week 24 tazarotene resulted in a significantly greater incidence of patients achieving treatment success (>or=50% global improvement) and at least a 1-grade improvement in fine wrinkling, mottled hyperpigmentation, lentigines, elastosis, pore size, irregular depigmentation, tactile roughness, coarse wrinkling, and the overall integrated assessment of photodamage (P<.01). Additional clinical improvement occurred with continued tazarotene treatment and had not plateaued by week 52. Plasma tazarotenic acid concentrations did not exceed 0.71 ng/mL. CONCLUSIONS: Once-daily applications of 0.1% tazarotene cream significantly reduced multiple signs of photodamage. Plasma levels of tazarotenic acid remained below those of endogenous retinoids.

Administration, Topical↗
PubMed2002

The longevity of a bilayered skin substitute after application to venous ulcers.

BACKGROUND: A bilayered skin substitute composed of allogeneic keratinocytes and fibroblasts in a collagen gel has been approved by the US Food and Drug Administration for the treatment of venous and diabetic ulcers. Its mechanism of action has not been fully determined. OBJECTIVE: To determine the longevity of allogeneic fibroblasts and keratinocytes in a bilayered skin substitute in patients with venous leg ulcers. METHODS: Ten patients with venous leg ulcers were treated with a bilayered skin substitute on day 0, days 3 to 5, and weeks 1 through 3. Biopsy specimens of the grafted wound were taken. We used polymerase chain reaction analysis to determine whether allogeneic DNA was present in the biopsy specimens. RESULTS: We detected allogeneic DNA in 2 of 8 specimens at 1 month after initial grafting. Neither of the 2 patients showed persistence of allogeneic DNA at 2 months after initial grafting. CONCLUSIONS: Allogeneic cells from a bilayered skin substitute do not appear to survive permanently after grafting for treatment of venous leg ulcers. Other mechanisms of action might include cytokine release, structural support, or provision of a moist wound environment.

Collagen↗
PubMed2002

Factors that influence healing in chronic venous ulcers treated with cryopreserved human epidermal cultures.

BACKGROUND: Cryopreserved epidermal cultures (CEC) offer an "off the shelf" treatment for chronic wounds. These cultures are derived from neonatal foreskin and grow rapidly in vitro to form epidermal sheets. They do not require a biopsy from the patient, an advantage compared to autografts. They seem to act as a biological dressing, stimulating epithelialization from the wound edges and adnexae, probably through growth factor release. OBJECTIVE: To summarize our recent experience with the use of CEC in chronic venous leg ulcers and to determine the factors that influence healing in chronic venous ulcers treated with CEC. PATIENTS AND METHODS: A single arm, open label study including a total of 11 patients with documented venous ulcers was performed. The study involved the application of cryopreserved epidermal cultures every other week to nonhealing leg ulcers for a total of 12 weeks or until complete healing of the ulcer. RESULTS: A total of 11 patients with one or more leg ulcers were treated. The average age was similar in healed and unhealed groups. Seven patients completely healed after an average of 4.14 CEC applications. Four patients did not heal after a total of 12 CEC applications. CONCLUSION: Predictors for failure to heal after CEC application in our patients were long wound duration, wound size, presence of lipodermatosclerosis, and history of failed prior split-thickness skin grafts.

Adult↗