Search

Psoriasis is a chronic immune-mediated inflammatory disease with predominant skin lesions. External therapy is an important area of treatment for such patients. Non-steroidal anti-inflammatory drugs based on zinc pyrithione do not have side effects inherent in the glucocorticosteroid drug and can be an alternative to them. Evaluation of the effectiveness of drugs is not always convenient in humans. The use of laboratory models allows us to study changes in the clinical, histological and immunohistochemical characteristics of the skin during topical therapy. Goal. On laboratory models of psoriasis, conduct a comparative assessment of the anti-inflammatory effectiveness of Skin-cap in comparison with other drugs. Materials and methods. In the experiment, 50 Balb / c inbred mice were used, randomized to 5 groups. The formation of a model of psoriasis by listening to them, after which I perform euthanasia with a skin biopsy in mice. Group II mice are treated with activated zinc pyrithione cream (Skin-cap), group III - zinc pyrithione cream (Zinocap), group IV betamethasone dipropionate cream (Akriderm) 2 p/d 14 days. Group V was monitored without therapy. The Clinical PASI Index (mPASI) score is given daily. On the 29 day of studies, group II-V mice undergo euthanasia and skin biopsies, which were examined histologically (epidermal thickness, severe inflammatory infiltrate) and immunohistochemical methods (Ki-67, CD3). The differences were considered significant at p0.05. Results. The initial mPASI index value was 7.2 [5.29.3]. The mPASI index in the Skin-cap group was 1.8 [1.13.2], zinc pyrithione 2.9 [2.14.2] and betamethasone dipropionate 1.3 [1.0] 3.1], which is significantly lower than in the group without therapy 5.8 [5.06.8] (p 0.05). A histological examination in mice receiving zinc pyrithione-activated showed a more pronounced decrease in the thickness of the epidermis (2.7 times) than with pyrithione zinc (2 times) and, immunohistochemical analysis showed the most significant decrease in the proliferative activity of the epidermis and the number of T-lymphocytes when using betamethasone and zinc pyrithione activated. Conclusions: it was found that the use of the drug leads to the suppression of the inflammatory process in the skin, comparable in effectiveness with a strong topical glucocorticosteroid. Skin-cap has no atrophogenic effect, which allows us to recommend this drug for the treatment of psoriasis patients with any localization of rashes.

Copper-only superoxide dismutases (SODs) represent a new class of SOD enzymes that are exclusively extracellular and unique to fungi and oomycetes. These SODs are essential for virulence of fungal pathogens in pulmonary and disseminated infections, and we show here an additional role for copper-only SODs in promoting survival of fungal biofilms. The opportunistic fungal pathogen Candida albicans expresses three copper-only SODs, and deletion of one of them, SOD5, eradicated candidal biofilms on venous catheters in a rodent model. Fungal copper-only SODs harbor an irregular active site that, unlike their Cu,Zn-SOD counterparts, contains a copper co-factor unusually open to solvent and lacks zinc for stabilizing copper binding, making fungal copper-only SODs highly vulnerable to metal chelators. We found that unlike mammalian Cu,Zn-SOD1, C. albicans SOD5 indeed rapidly loses its copper to metal chelators such as EDTA, and binding constants for Cu(II) predict that copper-only SOD5 has a much lower affinity for copper than does Cu,Zn-SOD1. We screened compounds with a variety of indications and identified several metal-binding compounds, including the ionophore pyrithione zinc (PZ), that effectively inhibit C. albicans SOD5 but not mammalian Cu,Zn-SOD1. We observed that PZ both acts as an ionophore that promotes uptake of toxic metals and inhibits copper-only SODs. The pros and cons of a vulnerable active site for copper-only SODs and the possible exploitation of this vulnerability in antifungal drug design are discussed.

Activation of zinc pyrithione gives it complementary pharmacodynamic properties — antimicrobial and antifungal effects, which determine its effectiveness in psoriasis and atopic dermatitis. The use of Skin-cap in these diseases is accompanied by the activation of apoptosis of cells of the lower layers of the epidermis and cells-effectors of allergic inflammation. The level of neutrophils and lymphocytes in the skin also decreases. The results of randomized controlled studies indicate a high efficacy of this drug in atopic dermatitis and psoriasis. Due to a wide range of pharmacological activity and clinical experience, Skin-cap is recognized as a safe non-steroid drug for external therapy. This allows recommending it for use in dermatology, pediatrics and allergology., Активирование цинка пиритиона придает ему взаимодополняющие фармакодинамические свойства — противо­мик­робное и противогрибковое действие, которые обусловливают его эффективность при псориазе и атопическом дерматите. Применение «Скин-капа» при этих заболеваниях сопровождается активацией апоптоза клеток нижних слоев эпидермиса и клеток — эффекторов аллергического воспаления, а также снижается уровень нейтрофилов и лимфоцитов в коже. Результаты проведенных рандомизированных контролируемых исследований свидетельствуют о высокой эффективности этого препарата при атопическом дерматите и псориазе. Благодаря широкому спектру фармакологической активности и клиническому опыту «Скин-кап» признан безопасным нестероидным препаратом для наружной терапии. Это позволяет рекомендовать его к применению в дерматологии, педиатрии и аллергологии., Активація цинку піритіону надає йому взаємодоповнюючих фармакодинамічних властивостей — протимікробна і протигрибкова дія зумовлює його ефективність при псоріазі та атопічному дерматиті. Застосування препарату «Скін-кап» при цих захворюваннях супроводжується стимулюванням апоптозу клітин нижніх шарів епідермісу і клітин — ефекторів алергійного запалення, а також зниженням рівня нейтрофілів і лімфоцитів у шкірі. Результати рандомізованих контрольованих досліджень свідчать про високу ефективність цього препарату при атопічному дерматиті і псоріазі. Завдяки широкому спектру фармакологічної активності та клінічному досвіду застосування «Скін-кап» визнано безпечним нестероїдним засобом для зовнішньої терапії. Це дає підстави рекомендувати його до використання в дерматології, педіатрії і алергології.

The article deals with the clinical aspects of inflammatory manifestations of dermatoses at an early age. It presents the results of the use of a non-steroidal anti-inflammatory drug based on activated pyrithione zinc

Oral squamous cell carcinoma (OSCC) patients diagnosed in late stages have limited chemotherapeutic options, underscoring the great need for development of new anticancer agents for more effective disease management. We aimed to identify novel anticancer agents for OSCC using quantitative high throughput assays for screening six chemical libraries consisting of 5170 small molecule inhibitors. In depth characterization resulted in identification of pyrithione zinc (PYZ) as the most effective cytotoxic agent inhibiting cell proliferation and inducing apoptosis in OSCC cells in vitro. Further, treatment with PYZ reduced colony forming, migration and invasion potential of oral cancer cells in a dose‐dependent manner. PYZ treatment also led to altered expression of several key components of the major signaling pathways including PI3K/AKT/mTOR and WNT/β‐catenin in OSCC cells. In addition, treatment with PYZ also reduced expression of 14‐3‐3ζ, 14‐3‐3σ, cyclin D1, c‐Myc and pyruvate kinase M2 (PKM2), proteins identified in our earlier studies to be involved in development and progression of OSCCs. Importantly, PYZ treatment significantly reduced tumor xenograft volume in immunocompromised NOD/SCID/Crl mice without causing apparent toxicity to normal tissues. Taken together, we demonstrate in vitro and in vivo efficacy of PYZ in OSCC. In conclusion, we identified PYZ in HTS assays and demonstrated in vitro and in vivo pre‐clinical efficacy of PYZ as a novel anticancer therapeutic candidate in OSCC.

Dandruff is a chronic scalp disorder characterized by scaling and itching. A successful anti-dandruff shampoo not only has to provide superior anti-dandruff relief to ensure patient compliance. It also needs to offer excellent cosmetic and hair conditioning benefits at the same time. In this study, the efficacy of a shampoo containing 0.5% piroctone olamine and 0.45% climbazole (shampoo 1) was compared with a widely available commercial shampoo containing 1% zinc pyrithione (shampoo 2). In vitro studies investigating the anti-mycotic efficacy of a combination of 0.5% piroctone olamine and 0.45% climbazole as well as 1% zinc pyrithione were performed. To study substantivity, pig skin punches were used as a model system and a test of wet combability was performed to characterize combing ease. In vivo home-in-use studies were carried out to determine the efficacy of both shampoos to improve scalp condition and reduce itching in subjects suffering from moderate to severe dandruff. Results demonstrated a comparable anti-fungal effectiveness for 0.5% piroctone olamine plus 0.45% climbazole and 1% zinc pyrithione, respectively. Shampoo 1 showed a significantly higher anti-mycotics substantivity compared to shampoo 2. After treatment with shampoo 1, the wet combing force was significantly reduced compared with shampoo 2, suggesting a better combability following the use of shampoo 1. In an in vivo split head design study, shampoo 1 was shown to be equally effective in reducing the amount of dandruff on the scalp compared with shampoo 2. The approval rate of volunteers regarding the question 'The use of this shampoo decreases the itching of my scalp?' after a 4-week treatment with shampoo 1 equaled 90%. Overall, the shampoo formulation with 0.5% piroctone olamine and 0.45% climbazole effectively reduces the amount of dandruff and, at the same time, provides hair conditioning advantages.

Background. The antibacterial activity of pyrithione zinc against S. aureus in therapy of atopic dermatitis was studied. Methods. Pyrithione zinc cream (0,2%) was used topically during 21 days in 1 to 13-years old patients with slight atopic dermatitis two times daily, and with lichenoid atopic dermatitis once a day. Pyrithione zinc aerosol (0,2%) was used in patients with eczematization or oedema two times daily. Results and conclusion. The clinical efficacy of pyrithione zinc was observed. S. aureus density on the patient's skin as well as the expression of coccal virulence factors were decreased.

Zinc pyrithione (ZnPT) is widely applied in conjunction with copper (Cu) in antifouling paints as a substitute for tributyltin. The combined effects of ZnPT and Cu on marine organisms, however, have not been fully investigated. This study examined the toxicities of ZnPT alone and in combination with Cu to the diatom Thalassiosira pseudonana, polychaete larvae Hydroides elegans and amphipod Elasmopus rapax. Importantly, ZnPT and Cu resulted in a strong synergistic effect with isobologram interaction parameter lambda>1 for all test species. The combined toxicity of ZnPT and Cu was successfully modelled using the non-parametric response surface and its contour. Such synergistic effects may be partly due to the formation of copper pyrithione. It is, therefore, inadequate to assess the ecological risk of ZnPT to marine organisms solely based on the toxicity data generated from the biocide alone. To better protect precious marine resources, it is advocated to develop appropriate water quality criteria for ZnPT with the consideration of its compelling synergistic effects with Cu at environmentally realistic concentrations.

The photochemical behavior of the antifouling agent zinc pyrithione (ZnPT) was studied in aqueous media of different composition under simulated solar irradiation using a xenon light source. The influence of important constituents of natural water (dissolved organic matter and nitrate) was also examined using a multivariate kinetic model. It was found that photodegradation proceeds via a pseudo first-order reaction. Kinetic experiments were monitored by LC-MS and photolytic half-lives ranging between 9.2 and 15.1 min have been observed. The increasing concentration of dissolved organic matter (DOM) accelerates the photolysis reaction, while the effect of nitrate ions was also positive since it increased the degradation rate, but to a lesser extent. Irradiation of the aqueous ZnPT solutions gave rise to several transformation products that were isolated by means of solid-phase extraction using poly(styrene-divinylbenzene) extraction disks. These byproducts were identified using liquid chromatography-atmospheric pressure chemical ionisation mass spectrometry. Besides 2-pyridinesulfonic-acid, other degradation products formed included pyridine-N-oxide, 2-mercaptopyridine, 2,2'-dithiobis(pyridine-N-oxide), 2,2-dipyridyl disulfide and the pyridine/pyrithione mixed disulfide, 2,2'-dithiobispyridine mono-N-oxide (PPMD).

Dandruff is a chronic condition of the scalp requiring vigilant treatment to ameliorate the symptoms of scaling and itching. Frequent shampooing is key to controlling these symptoms while contributing to the cosmetic appearance of the hair. The success of the treatment depends not only on the ability of the shampoo to control the dandruff but also on patient compliance engendered by the cosmetic attributes of the shampoo. This double-blind cross-over study enrolled 40 women with mild to moderate dandruff. Following a 1-wk washout with an unmedicated basic cleansing shampoo, all subjects used each of the two study shampoos for 1 wk. Subjects preferred the 1% pyrithione zinc conditioning shampoo over the 2% ketoconazole shampoo by 75% in terms of overall performance. The dermatologist investigator confirmed the subject preference by noting that hair-combing ease, hair smoothness, and hair frizz/flyaway were statistically significantly better in subjects who used the 1% pyrithione zinc conditioning shampoo for 1 wk. This study suggests that hair condition is an important consideration in the treatment of dandruff due to compliance.

Alcohol-based products for skin antisepsis have a long history of safety and efficacy in the United States and abroad. However, alcohol alone lacks the required antimicrobial persistence to provide for the sustained periods of skin antisepsis desired in the clinical environment. Therefore, alcohol-based products must have a preservative agent such as iodine/iodophor compounds, chlorhexidine gluconate, or zinc pyrithione, to extend its antimicrobial effects. Iodine, iodophors, and chlorhexidine gluconate are well-characterized antimicrobials and preservatives. The thrust of our effort was to examine the characteristics of the lesser-known zinc pyrithione and to evaluate its utility as a preservative in the formulation of alcohol-based products for skin antisepsis. This work includes a literature review of current zinc pyrithione applications in drugs and cosmetics, a safety and toxicity evaluation, consideration of the proposed mechanisms of antimicrobial action, in vitro and in vivo efficacy data, and a discussion of the mechanisms that confer the desired antimicrobial persistence. In addition, alcohol-based, zinc pyrithione-preserved, commercially available products of skin antisepsis are compared with other commercially available antimicrobials used for skin antisepsis and with additional alcohol-based products with different preservatives. The authors' conclusion is that zinc pyrithione is not only a safe and effective antimicrobial but that its use in certain alcohol-based formulations results in antimicrobial efficacy exceeding that of iodine and chlorhexidine gluconate.

Zinc pyrithione (ZPT) is an antibacterial and antifungal reagent that is often utilized for the antidandruff activity in hair-care shampoos with a composition level up to 1% in the formulation. It has some adverse effects to human and animal if consumed orally. A disposable type of cobalt phthalocyanide modified screen-printed carbon electrode (CoPc/SPE) in couple with flow injection analysis (FIA) was developed for easy and selective analysis of ZPT in commercial hair-care products. Under the optimized FIA conditions, the CoPc/SPE yielded a linear calibration plot in the window of 6-576muM with sensitivity and detection limit of 1.65nAmuM(-1) and 0.9muM (i.e. 1.42pg in 5mul sample loop), respectively, in 0.1M KOH solution at an applied potential of 0.3V versus Ag/AgCl. Since the approach is simple, easy, selective, and inexpensive, it offers a potential application of daily ZPT analysis in hair-care products.

Superoxide dismutases (SODs) are metalloenzymes that disproportionate superoxide produced by aerobic metabolism as well as the oxidative bursts present at the host-pathogen interface. Bimetallic eukaryotic Cu/Zn SOD molecules are potent antioxidants found in most intracellular compartments and in extracellular locations. Our lab has recently discovered a new class of extracellular copper-only SODs found only in the fungal kingdom that are structurally distinct from bimetallic Cu/Zn SODs while still retaining equivalent catalytic efficiency. This novel class of copper only SODs are unique in that they lack zinc-binding residues and an electrostatic loop, creating an open active site that is accessible to solvent. Importantly these copper only SODs have been shown to be virulence factors in fungal pathogens such as Candida albicans and Histoplasma capsulatum. The uniquely accessible active site of these copper only SODs and their role in pathogenesis make them good candidates for selective drug design. We screened for compounds that selectively inhibit copper-only C. albicans SOD5 over mammalian Cu/Zn SOD1. We found that pyrithione zinc (PZ), a well-known antifungal in dandruff shampoo, has highly selective and potent activity against C. albicans copper only SOD5. The metal complex of pyrithione (Zn or Cu) appears to be more effective against SOD5 than pyrithione alone, suggesting the di-pyrithione structure selectively targets the open active site of fungal Cu-only SODs. Metal-pyrithione complexes are promising candiates for new anti-fungals that target the curious family of fungal Cu-only SODs.

Gas chromatography-mass spectrometry (GC-MS) with a temperature-programmable pyrolyzer was used for the analysis of waterborne paints. Evolved gas analysis (EGA) profiles of the waterborne paints were obtained by this temperature-programmed pyrolysis directly coupled with MS via a deactivated metal capillary tube. The EGA profile suggested the optimal thermal desorption conditions for solvents and additives and the subsequent optimal pyrolysis temperature for the remaining polymeric material. Polymers were identified from pyrograms with the assistance of a new polymer library. The solvents were identified from the electron ionization mass spectra with the corresponding chemical ionization mass spectra. The additive was identified as zinc pyrithione by comparison with authentic standard. Zinc pyrithione cannot be analyzed by GC-MS as it is. However, the thermal decomposition products of zinc pyrithione could be detected. The information on the decomposition temperature and products was useful for the identification of the original compound.

Clobetasol propionate, an anti-inflammatory glucocorticosteroid, was detected in an over-the-counter topical drug product with no indication on the label of this compound as an ingredient. The product was formulated as a topical spray, a cream, or a shampoo and labeled to contain zinc pyrithione as the active ingredient. The finding of clobetasol propionate in the pharmaceutical products was shown by comparison to an authenticated standard of clobetasol propionate by retention time on normal-phase and reversed-phase HPLC, UV spectroscopy, LC–MS and LC–MS–MS. A simple method was developed and validated for the assay of clobetasol propionate by isocratic reversed-phase HPLC. Several lots contained clobetasol propionate at therapeutic levels of 0.02–0.06%. Zinc pyrithione formulations from two other manufacturers were free of clobetasol propionate.

Most active antidandruff shampoos exhibit a strong activity against the yeast Malassezia ovalis. The present study was undertaken to compare the prolonged antifungal effect of three proprietary shampoos containing either 2% ketoconazole, 1.5% zinc pyrithione or 2.5% selenium sulphide. Superficial squames were harvested from the scalp in the days following a 6-week antifungal shampoo treatment. Counts of yeasts highlighted by a fluorochrome were made using computerized image analysis. Data show the increased duration of yeast reduction for the ketoconazole shampoo over the two other formulations. The lingering effect of ketoconazole is explained by the combination of its antifungal and pharmacokinetic properties.

Scalp skin is physiologically very similar to non-palmoplantar skin of the rest of the body, except for the very high concentration of sebaceous glands (Giacometti, 1965). The scalp environment, however, is much different in being covered by a thick fabric of hair. There are about 250 hair fibers per cm, which results, for a typical individual, in a hair surface area of 50,000 cm relative to the scalp surface area of 600 cm. Together, these parameters indicate the relative inaccessibility of the scalp surface to targeted delivery of actives; relatively low delivery efficiency in this protected environment is an inherent challenge to achieving therapeutic benefits. This is especially true of the most patientfriendly format—shampoos—since a rinsing step is involved and the product cannot interfere with achieving desired hair cosmetic benefits (compliance decreases dramatically if hair cosmetics are poor). This places a large demand on actives with high activity since delivery efficiency will be inherently low as well as development of product pharmacologies that maximize the benefit of the actives employed. This situation will be exemplified for the most common scalp care therapeutic products, those designed to treat dandruff and seborrheic dermatitis (D/SD) utilizing anti-fungal actives to reduce Malassezia content on the scalp. The most common anti-fungal materials used in D/SD scalp therapies include those based on rational chemical design principles (ketoconazole, climbazole, pyrithione zinc (PTZ), piroctone olamine and ciclopirox olamine) as well as materials originating from indeterminate histories (selenium sulfide, sulfur, coal tar, and salicylic acid). Because of the aforementioned demands on activity due to challenging delivery, only those materials with high intrinsic anti-fungal activity should be considered as the basis for therapeutic products. Based on measurement of minimal inhibitory concentrations (MIC) against Malassezia, the most potent materials from this group are pyrithione zinc, selenium sulfide, climbazole, and ketoconazole (VanGerven and Odds, 1995; Schmid and Ruhl-Horster, 1996). For a formulated therapeutic product to be effective, a potent active is a necessary but insufficient condition to achieve activity. The way the active is delivered to the scalp from the product formula, i.e., the product pharmacology, is at least as strong a determinant of in-use activity as the intrinsic active potency. For example, a comparison of clinical flake-reduction efficacy of a variety 1% PTZ-based D/ SD shampoo products demonstrates a wide range of magnitude of therapeutic benefits. Much of this variation is likely due to the varying efficiency of delivery of PTZ, a particulate active, to the scalp surface. Particulate PTZ delivery will be affected by the physical size and shape of the particle (as well as other formulation parameters, which will not be covered further here). Particles which are flat cover the scalp surface more efficiently than those that are not. The particle size is also critical as smaller particles provide better surface coverage but are more difficult to retain on the scalp after rinsing. These two opposing factors result in an optimum size to maximize active delivery. Shampoo product formulations utilizing PTZ particles optimized for delivery outperform those utilizing standard forms of the active (Fig 1). This exemplifies one variable, beyond active potency, that must be considered in selecting a therapeutic treatment. Another important pharmacological variable that must be considered is the role of the ‘‘non-functional’’ excipients in