James Robert Schwartz

Zinc Pyrithione Inhibits Yeast Growth through Copper Influx and Inactivation of Iron-Sulfur Proteins

ABSTRACT Zinc pyrithione (ZPT) is an antimicrobial material with widespread use in antidandruff shampoos and antifouling paints. Despite decades of commercial use, there is little understanding of its antimicrobial mechanism of action. We used a combination of genome-wide approaches (yeast deletion mutants and microarrays) and traditional methods (gene constructs and atomic emission) to characterize the activity of ZPT against a model yeast, Saccharomyces cerevisiae. ZPT acts through an increase in cellular copper levels that leads to loss of activity of iron-sulfur cluster-containing proteins. ZPT was also found to mediate growth inhibition through an increase in copper in the scalp fungus Malassezia globosa. A model is presented in which pyrithione acts as a copper ionophore, enabling copper to enter cells and distribute across intracellular membranes. This is the first report of a metal-ligand complex that inhibits fungal growth by increasing the cellular level of a different metal.

A Comprehensive Pathophysiology of Dandruff and Seborrheic Dermatitis: Towards a More Precise Definition of Scalp Health

Despite an increasing knowledge of dandruff and seborrheic dermatitis (D/SD), the pathophysiological understanding is still incomplete but suggests a role of Malassezia yeasts in triggering inflammatory and hyper-proliferative epidermal responses. The objective of this report is to review published literature from in vivo studies of D/SD populations to provide a more complete description of overall scalp health. New biomolecular capabilities establish a depth of pathophysiological understanding not previously achievable with traditional means of investigation. Biomarkers representing inflammation, hyper-proliferation and barrier function are all perturbed by the D/SD condition and robustly respond to therapeutic resolution. These biomarkers can be sampled noninvasively, enabling their use in routine clinical evaluations as either surrogate endpoints or complementary ones to classical signs/symptoms to broaden the etiological learning.

Epidermal changes associated with symptomatic resolution of dandruff: biomarkers of scalp health

Background  Dandruff is a common scalp condition characterized by flakes, pruritus and sometimes mild erythema. These symptoms reflect underlying histopathologic and biochemical events that must be reversed if treatment is to be effective.

The antifungal mechanism of action of zinc pyrithione.

Background  Zinc pyrithione (ZPT) is the active ingredient most commonly used in many antidandruff treatments. Despite decades of successful use to treat human scalps, little is understood about the antifungal mechanism of action of ZPT.

New insights on dandruff/seborrhoeic dermatitis: the role of the scalp follicular infundibulum in effective treatment strategies

Background  Pathogenesis of dandruff/seborrhoeic dermatitis (D/SD) involves Malassezia yeasts, leading to the most widely accepted treatment strategy of topical application of antifungal agents, usually from rinse‐off shampoos. The scalp spatial distribution of Malassezia must be mirrored by the distribution of the active agent to realize the full benefit of the active material.

Therapeutic efficacy of anti‐dandruff shampoos: A randomized clinical trial comparing products based on potentiated zinc pyrithione and zinc pyrithione/climbazole

Dandruff is a chronic, relapsing scalp condition that negatively impacts the quality of life of sufferers. Regular use of anti‐fungal shampoos represents a proven therapeutic strategy to improve the most common symptoms of flakes and itch. Two recent approaches for enhancing the efficacy of anti‐fungal shampoos are maximizing bio‐availability of the active material or the addition of a second active material. Our aim is to compare the therapeutic efficacy of these two approaches – maximization of bio‐availability of the zinc pyrithione (ZPT) active material or the combination of ZPT with a secondary active material.

Assessing therapeutic effectiveness of scalp treatments for dandruff and seborrheic dermatitis, part 1: a reliable and relevant method based on the adherent scalp flaking score (ASFS)

Background: Dandruff and seborrheic dermatitis (D/SD) are common and troublesome scalp conditions with the primary signs and symptoms being presence of skin flakes, pruritus, a tight feeling, and sometimes erythema. Aim: To demonstrate the reliability and relevance of a clinical model for the assessment of therapeutic efficacy of a treatment using the Adherent Scalp Flaking Score (ASFS) method to quantitate the flaking severity. Methods: Six randomized, double-blind, parallel design studies were conducted in either North America or Asia with subjects suffering from dandruff using the ASFS grading method before and after a 3-week test product treatment period. Results: Treatment with a commercial potentiated 1% zinc pyrithione (ZPT) shampoo resulted in statistically significant (p < 0.0001) improvements in total ASFS compared with the placebo cosmetic shampoo. Results were consistent across all studies, geographies, and product usage protocols (controlled on-site versus home use conditions), and were associated with statistically significant improvements in self-perception of scalp condition. Conclusion: The ASFS-based clinical model was demonstrated to be a reliable and proven methodology to assess the effectiveness of widely used anti-dandruff treatments. The results are consistent with patient self-assessments, establishing this methodology as relevant to patient perception of product benefits.

Treatment of seborrheic dermatitis of the scalp

Background  Seborrheic dermatitis and dandruff are common conditions dominated by flakes and itch symptoms. Beyond these observable conditions, the epidermis is highly perturbed and in an inflammation‐driven hyperproliferative condition.

Attenuation of Surfactant-Induced Interleukin 1α Expression by Zinc Pyrithione

Background: Dandruff is believed to be a fungus-mediated disease which responds to the topical delivery of antifungal agents. Although the primary causative factor is fungus related, distal events include an inflammatory cascade that eventually expresses itself as corneocyte flakes. The most common vehicle for dandruff treatment includes surfactants (i.e. shampoos), which as a chemical group have the potential to promote dermatitis. Objective: To evaluate the effect of antidandruff agents and antimicrobials on the potential contact irritancy of surfactants. Methods: Excretion of interleukin 1α by human skin equivalent cultures was measured after topical application of test materials. Results: Zinc pyrithione specifically reduces surfactant-induced expression of interleukin 1α. Neither its sodium salt nor other antimicrobial/antifungal agents had a similar effect. Conclusion: These data suggest that in addition to its known antifungal activity, zinc pyrithione may provide an additional benefit by reducing the potential irritancy of surfactant vehicles.

The role of oxidative damage in poor scalp health: ramifications to causality and associated hair growth

The oxidative stress element of unhealthy scalp leads to compromised pre‐emergent hair formation and poorly formed hair as it grows. Only cosmetic solutions can minimize the impact of unhealthy hair and to achieve healthy looking and feeling hair, the scalp health must be normalized first. The objectives of this research were to both investigate whether oxidative stress was a relevant aetiological element in scalp dandruff and seborrhoeic dermatitis and whether scalp condition affects the quality of hair that grows from it. Further, this research was designed to determine whether an effective anti‐dandruff shampoo would repair and protect the scalp and pre‐emergent hair from oxidative stress. This study demonstrated that oxidative stress is an aetiological element relevant to the dandruff condition and that a potentiated ZPT shampoo effectively improves scalp condition, including a reduction in oxidative stress. The compromised hair condition associated with dandruff is concomitantly improved when the scalp condition is improved. It appears that there is a direct link between hair quality and scalp health.