Jerry L. McCullough

Prevention and Treatment of Skin Aging

Abstract:  Skin aging is a complex biological process that is a consequence of both intrinsic or genetically programmed aging that occurs with time, and extrinsic aging caused by environmental factors. The dramatic increase in the aging population and the psychosocial impact of skin aging has created a demand for effective interventions. The advances that have been made in the past 25 years in our understanding of the clinical, biochemical, and molecular changes associated with aging have led to the development of many different approaches to reduce, postpone, and in some cases, repair the untoward effects of intrinsic programmed aging and extrinsic environmental injury.

Selective photosensitizer distribution in vulvar condyloma acuminatum after topical application of 5-aminolevulinic acid

OBJECTIVE Our purpose was to determine the feasibility of selective photosensitization of vulvar condylomas by use of tropical application of 5-aminolevulinic acid. STUDY DESIGN In vivo fluorescence was assessed and biopsy specimens of condylomas were taken for fluorescence microscopy in 24 patients at different times after application of 2.5% 5-aminolevulinic acid ointment or 20% 5-aminolevulinic acid cream. RESULTS Both in vivo fluorescence imaging and fluorescence microscopy showed selective fluorescence of condylomas of the labia minora and vestibule only within short time intervals, because fluorescence of poorly keratinized normal epithelium was induced by both 5-aminolevulinic acid formulations. In non-hair-bearing skin, lesional fluorescence remained highly selective. Fluorescence microscopy showed that 90 minutes after drug application peak selectivity in epithelial lesional fluorescence was significantly higher with 2.5% 5-aminolevulinic acid ointment (4.5 +/- 0.9) than it was with 20% cream (2.1 +/- 0.2). CONCLUSION Selective fluorescence of vulvar condyloma acuminatum can be induced by nonselective topical 5-aminolevulinic acid application. Studies evaluating selective photodynamic destruction of condylomas are justified.

NEW APPROACHES TO CHEMOTHERAPY WITH FOLATE ANTAGONISTS: USE OF LEUCOVORIN “RESCUE” AND ENZYMIC FOLATE DEPLETION*

This paper will be concerned with two new concepts in folate antagonist chemotherapy that our group at Yale has been working on, both in the clinic and in the laboratory, namely the use of leucovorin ( N5-formyltetrahydrofolate, folinic acid, citrovorum factor) “rescue” to improve the therapeutic index of amethopterin (Methotrexate) (MTX), and the use of an enzyme, carboxypeptidase G,, to cause folate depletion.

Ablation of human nail by pulsed lasers

The hard and resistant structure of the nail plate forms a natural barrier that limits the penetration of topical drugs. To overcome this barrier, the use of pulsed laser systems has been suggested. The purpose of this study was to evaluate the effect of four laser systems on nail plate ablation rates, ablation efficiencies, and subsequent craters morphology.

Topical kinetin 0.1% lotion for improving the signs and symptoms of rosacea

Many patients with rosacea are unable to tolerate extended treatment periods with topical agents because of the unusually high skin sensitivity that often accompanies rosacea. Kinetin (N6‐furfuryladenine) is a plant cytokinin that reportedly helps restore skin barrier function and may be useful to ameliorate the signs and symptoms of rosacea. The purpose of this open‐label study was to determine the tolerance and efficacy of twice‐daily application of kinetin 0.1% lotion for improving the signs and symptoms of mild to moderate facial rosacea. Subjects applied kinetin 0.1% lotion twice daily to the face, with daily use of a sunscreen of sun protection factor 30. Subjects were evaluated at baseline and at 4‐week intervals for 12 weeks to assess efficacy and tolerance. Results of this study suggest that kinetin 0.1% lotion is a well‐tolerated moisturizing lotion option for subjects with mild to moderate inflammatory rosacea.

Inhibition of growth of leukemia cells by enzymic folate depletion.

A new bacterial enzyme, designated as carboxypeptidase G1, inhibited growth of the L5178Y and L1210 murine leukemias, as well as the Walker carcinoma and the human lymphoblastoid line (RPMI 4265), propogated in vitro. This enzyme hydrolyzes the glutamate moiety from both oxidized and reduced folate forms, and thus it may prove to be of value in creating rapid folate depletion in vivo.

Topical cyclosporine: effects on allergic contact dermatitis in guinea pigs.

Cyclosporine (CSA) is an effective immunosuppressive agent and is used in tissue transplantation. The present investigation was undertaken to determine the effect of topical delivery of CSA on allergic contact dermatitis in guinea pigs, Topical 15% CSA in an azone (l‐dadecychlohepatan‐2–one)containing vehicle blocked local elicitation in previously dintrochlorobenezene(DNCB) sensitized animals that received a single topical application just prior to elicitation. Elicitation was not blocked at a distant site, indicating a local effect of topical CSA. In contrast, topical CSA when applied twice daialy for a total of 5 applications during sensitization only, did not block subsequent elicitation. These experiments suggest that cyclosporine tna be beneficial in the therapy of human contact dermatitis, as well as other T cell mediated dermatoses.

PHOTOSENSITIZERS IN DERMATOLOGY

Abstract Systemic injection of hematoporphyrin derivative (HpD) in combination with visible light (red or blue‐green) delivered by laser was used to treat a patient with psoriasis. The psoriatic lesions responded vigorously to laser treatments, forming eschars by 1 week post irradiation. In contrast, only minimal erythema was observed in the noninvolved, clinically normal appearing skin. Two approaches for localized HpD administration were investigated in the guinea‐pig and minipig models as a means of achieving local photodynamic effects. Intracutaneous injection of HpD produced localized cutaneous photosensitization with either UVA or red light. Azone increased percutaneous penetration of HpD in human skin in vitro. Topical application of HpD and irradiation with UVA produced localized cutaneous photosensitivity and inhibition of epidermal DNA synthesis.

DISCUSSION PAPER: KINETIC INVESTIGATION OF THE REACTION MECHANISM OF DIHYDROFOLATE REDUCTASE FROM L1210 CELLS*

Dihydrofolate reductase, a low molecular weight enzyme obtainable in high purity and yield from the L1210 murine lymphoma, is a suitable enzyme for the kinetic study of a two-substrate pyridine nucleotide-dependent reaction. Although several kinetic properties of this enzyme have been previously investigated, the reaction mechanism is as yet undefined. An understanding of this mechanism would be of considerable importance in characterizing those species of the enzyme with which pharmacologically important inhibitors react. In this study the reaction mechanism of dihydrofolate reductase has been studied by (1) initial velocity measurements in the forward direction; (2) product inhibition; and ( 3 ) inhibition by the folate analogue, triamterene.

Medical students educate teens about skin cancer: what have we learned?

Skin cancer is a serious societal problem, and public awareness outreach, including to youth, is crucial. Medical students have joined forces to educate adolescents about skin cancer with significant impacts; even one 50-min interactive outreach session led to sustained changes in knowledge and behavior in a cohort of 1,200 adolescents surveyed. Medical students can act as a tremendous asset to health awareness public outreach efforts: enthusiastic volunteerism keeps education cost-effective, results in exponential spread of information, reinforces knowledge and communication skills of future physicians, and can result in tangible, life-saving benefits such as early detection of melanoma.