Sheldon R. Pinnell

Topical vitamin C protects porcine skin from ultraviolet radiation‐induced damage

Summary Ultraviolet radiation damage to the skin is due, in part, to the generation of reactive oxygen species. Vitamin C (l‐ascorbic acid) functions as a biological co‐factor and antioxidant due to its reducing properties. Topical application of vitamin C has been shown to elevate significantly cutaneous levels of this vitamin in pigs, and this correlates with protection of the skin from UVB damage as measured by erythema and sunburn cell formation. This protection is biological and due to the reducing properties of the molecule. Further, we provide evidence that the vitamin C levels of the skin can be severely depleted after UV irradiation, which would lower this organs innate protective mechanism as well as leaving it at risk of impaired healing after photoinduced damage. In addition, vitamin C protects porcine skin from UVA‐mediated phototoxic reactions (PUVA) and therefore shows promise as a broad‐spectrum photoprotectant.

Evidence supporting zinc as an important antioxidant for skin

Antioxidants play a critical role in keeping skin healthy. The antioxidant benefits of vitamin C and E are well known, but the importance of the trace mineral, zinc, has been overlooked. This article reviews the evidence supporting zincs antioxidant role in protecting against free radical‐induced oxidative damage. Zinc protects against UV radiation, enhances wound healing, contributes to immune and neuropsychiatric functions, and decreases the relative risk of cancer and cardiovascular disease. All body tissues contain zinc; in skin, it is five to six times more concentrated in the epidermis than the dermis. Zinc is required for the normal growth, development and function of mammals. It is an essential element of more than 200 metalloenzymes, including the antioxidant enzyme, superoxide dismutase, and affects their conformity, stability, and activity. Zinc also is important for the proper functioning of the immune system, and for glandular, reproductive and cell health.

Topical minoxidil in early male pattern baldness

One-hundred twenty-six healthy men with early male pattern baldness completed a 12-month double-blind, controlled trial of 2% and 3% topical minoxidil. Subjects were initially randomly assigned to use placebo or 2% or 3% topical minoxidil. After 4 months of study, the placebo group was crossed over to 3% topical minoxidil. Both objective measurement of hair growth by counting of vellus, terminal, and total hairs in a vertex target balding area and subjective assessment by subject and investigator were done. Treatment of subjects with topical minoxidil for 4 months resulted in a statistically significant increase in terminal hair growth in comparison with placebo therapy. In addition, subjects initially treated with placebo, when crossed over to topical minoxidil, showed a significant increase in the number of terminal hairs. No subject had a net hair loss in the target area during the study. These results indicate that topical minoxidil can increase terminal hair growth in early male pattern baldness.

Urinary excretion of hydroxylysine and its glycosides as an index of collagen degradation.

Urimary excretion of hydroxyprolin (Hyp) is one index of total collagen degradation, from all sources. Since some of the Hyp released from collagen may be further metabolized before it is excreted, other markers are necessary to measure collagen breakdown. Excretion of the glycosides of hydroxylysine (Hyl), glucosyl galactosyl hydroxylysine (Hy1[Gl)cGa1]), and galactosyl hydroxylysine (Hyl[Ga)]), more accurately reflects collagen metabolism since these products occur in specificratios in different tissue collagens and are themselves metabolized only to a minor degree. The ratios of total Hy1/Hyp and Hyl(GlcGal)/Hyl(Ga1) were measured in the urine of norma. subjects and of patients with Pagets disease of bone, hyperphosphatasia, and extensive thermal burns. In patients with extensive thermal burns the pattern of urinary Hy1 and its glycosides was consistent with degradation of collagen in dermis and fascia. When bone collagen degradation was dominant, the pattern of urinary metabolites reflected that source. Pagetic bone collagen has an amino acid composition similar to normal bone and Hy1(G1cGa1/Hyl(G1) of 0.396-0.743,vs. normal of 0.474+/-0.088. In untreated patients with severe Pagets disease of bone or hyperphosphatasia (urinary Hyp greater than 2.0 micronmol/mg creatinine) urinary Hyl/Hyp averaged 0.052+/-0.042 (0.042+/-0.009 in normal bone) and Hy1(G1cGa1)/Hy1(Ga1) 0.601+/-0.017 (0.47+/-0.009 in normal bone). When bone resorption was decreased sufficiently with calcitonin or disodium etidronate in these patients, both the urinary ratios of Hy1/Hyp and Hy1(G1cGa1)/Hyl(Gal) rose. In normal subjects treated with calcitonin and excreting relatively little Hyp, the ratio of Hy1/H)P approached 0.7 and Hy1(G1ycGa1)/Hy1(Ga1) approached 3.5. There increased ratios reveal the existence of a source of collagen breakdown other than skin or bone. The first subcompoent of complement, Clq, which has collagen-like sequences, relatively high amounts of Hy1, and most of the glycosylated Hy1 as Hy1(G1cGa1), could be the source of these metabolites.

A topical antioxidant solution containing vitamins C and E stabilized by ferulic acid provides protection for human skin against damage caused by ultraviolet irradiation

BACKGROUND Skin cancer and photoaging changes result from ultraviolet (UV)-induced oxidative stress. Topical antioxidants may protect skin from these effects. OBJECTIVE We sought to determine whether a stable topical formulation of 15% L-ascorbic acid, 1% alpha-tocopherol, and 0.5% ferulic acid (CEFer) could protect human skin in vivo from substantial amounts of solar-simulated UV radiation. METHODS CEFer and its vehicle were applied to separate patches of normal-appearing human skin for 4 days. Each patch was irradiated with solar-simulated UV, 2 to 10 minimal erythema doses, at 2-minimal erythema dose intervals. One day later, skin was evaluated for erythema and sunburn cells, and immunohistochemically for thymine dimers and p53. UV-induced cytokine formation, including interleukin (IL)-1alpha, IL-6, IL-8, and IL-10, and tumor necrosis factor-alpha, were evaluated by real-time polymerase chain reaction. RESULTS CEFer provided significant and meaningful photoprotection for skin by all methods of evaluation. LIMITATIONS The number of patients evaluated was relatively small. CONCLUSION CEFer provided substantial UV photoprotection for skin. It is particularly effective for reducing thymine dimer mutations known to be associated with skin cancer. Its mechanism of action is different from sunscreens and would be expected to supplement the sun protection provided by sunscreens.

Microfine Zinc Oxide is a Superior Sunscreen Ingredient to Microfine Titanium Dioxide

Background. Microfine zinc oxide and microfine titanium dioxide are particulate sunscreen ingredients that absorb broad‐spectrum ultraviolet (UV) irradiation. Objective. We compare microfine zinc oxide and microfine titanium dioxide for their abilities to attenuate UVA radiation and their relative whiteness in cosmetic formulations. Methods. UVA attenuation was measured by diffuse reflectance spectroscopy on normal human skin in vivo. Whiteness was determined by reflectance density of dried coatings on a black background of the two particulates at varying concentrations. Results. Microfine zinc oxide demonstrates superior protection compared to microfine titanium dioxide in the UV spectrum between 340 and 380 nm. Microfine zinc oxide is less white than titanium dioxide at all concentrations. Conclusion. Microfine zinc oxide is superior to microfine titanium dioxide as a sunscreen ingredient. It is more protective against long‐wave UVA and is less white at a given concentration.

Ehlers-Danlos syndrome type VI: Clinical manifestations of collagen lysyl hydroxylase deficiency

We reviewed the clinical findings in 10 patients with lysyl hydroxylase deficiency (Ehlers-Danlos syndrome type VI) and report here the range of clinical severity in these patients. The distinctive feature common to all patients was muscle hypotonia with joint laxity in the newborn period, and moderate to severe kyphoscoliosis either was present or developed in almost all patients. Most patients also had some degree of skin abnormality observed in other types of Ehlers-Danlos syndrome: bruisability, abnormal scarring, and soft, distensible skin. These patients also are at risk for potentially catastrophic arterial rupture.

Regulation of collagen synthesis by ascorbic acid. Ascorbic acid increases type I procollagen mRNA

Abstract Ascorbic acid specifically stimulates collagen production in cultured human skin fibroblasts, an effect that appears to be independent of its cofactor role in prolyl and lysyl hydroxylation. In order to investigate the level of regulation of ascorbic acid on collagen synthesis, we have translated mRNA in a cell-free system derived from rabbit reticulocytes. Total RNA was prepared from normal human skin fibroblasts and similar fibroblasts which had been exposed to 100 uM ascorbic acid for four days. Ascorbic acid treatment resulted in a twofold stimulation of procollagen mRNA whereas non-collagenous mRNA was unchanged. These results reveal that ascorbic acid has a preferential stimulating effect on type I procollagen mRNA.

A double-blind, randomized, prospective trial to evaluate topical vitamin C solution for the prevention of radiation dermatitis

Abstract Purpose: The object of this study was to ascertain the value of topical ascorbic acid in the prevention of radiation dermatitis. Methods and Materials: Patients with primary or metastatic brain tumors were eligible. Patients applied a topical solution, twice per day prior to and throughout the course of radiotherapy, to the left and right sides of the head. The radiotherapist and the patient were blinded as to the contents of the solutions. The bottle for one side of the head contained topical ascorbic acid solution. The bottle for the other side of the head contained only vehicle. During and after the course of treatment the radiotherapist scored the skin reaction on both the left and right sides of the irradiated head using a skin reaction scale. The data were analyzed with a matched pair analysis. Since each patient received both treatments (ascorbic acid and control solutions) the statistical analysis concentrated on the paired difference in scores based on the probability of a “preference” for the treatment or control. Results: Eighty-four patients entered the study. Sixty-five were suitable for analysis. In 10 patients there was a preference for ascorbic acid solution (15%), in 20 patients there was a preference for placebo (31%), and there was a preference for neither in 35 patients (54%). Ascorbic acid solution could be considered to have an effect if the percentage of preferences favoring ascorbic acid over placebo, among those subjects with a preference, significantly exceeded the 50% expected by chance. The observed percentage of preferences for ascorbic acid was only 33% (10 of 30 with a preference; p = .10, two-sided sign test). Patient age, race, sex, and total dose of irradiation had no detectable influence on the comparative skin toxicity scores. Conclusion: There is no discernible benefit to ascorbic acid lotion, in the manner in which we used it in this trial, for the prevention of radiation dermatitis.

Induction of Collagen Synthesis by Ascorbic Acid: A Possible Mechanism

L-Ascorbic acid stimulates procollagen synthesis in cultured human skin fibroblasts without appreciably altering noncollagen protein synthesis. The effect is unrelated to intracellular degradation of newly synthesized procollagen. Levels of mRNA for pro alpha 1(I), pro alpha 2(I), and pro alpha 1(III), measured by hybridization with the corresponding cDNA probes, are elevated in the presence of ascorbic acid, whereas the level of mRNA for fibronectin is unchanged. Levels of functional mRNA for procollagen, measured in a cell-free translation assay, are specifically increased in the presence of ascorbic acid. Thus, ascorbic acid appears to control the expression of three different procollagen genes, each of which is located on a separate chromosome. It is proposed that intracellularly accumulated procollagen in ascorbate deficiency may lead to a translational repression of procollagen synthesis. Ascorbic acid may relieve this block by promoting hydroxyproline formation and, consequently, secretion of procollagen from the cell. The increased level of procollagen mRNA under the influence of ascorbic acid may be secondary to increased synthesis of procollagen polypeptides; the control point may be gene transcription or mRNA degradation.