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1.
Chemosphere ; 240: 124746, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31568946

RESUMO

The skin is one of the main organs exposed to airborne particulate matter (PM), which may contain various pollutants linked to a wide range of adverse health endpoints. In the present work, we analyzed the proinflammatory and oxidative effects of some PM components leading to inflammatory responses, cell proliferation or cell death. We investigated four redox-active chemicals, such as Cu (II) metal and quinones generated from polycyclic aromatic hydrocarbons (PAHs), i.e., 9,10 phenanthrenequinone and isomers 1,2 and 1,4 naphthoquinone. We performed in vitro biological tests on human keratinocyte (HaCaT) cells and also acellular assays based on the oxidation of dithiothreitol and ascorbic acid, antioxidants to assess the oxidative potential (OP). We found that treated keratinocytes showed increased activation of the redox-sensitive transcription factor NFκB and increased transcript levels of the NFκB-dependent gene IL8. Moreover, the treatment with Cu(II) and quinones increased the activities and the expression of genes involved in the redox response, SOD1 and GPX, suggesting that PM components induced cellular damage due to redox imbalances. Finally, we found alteration of the mitochondrial ultrastructure and increased apoptosis after 24 h of treatment. The results presented suggest that all of the analyzed pollutant components are able to modulate similar signal transduction pathways, resulting in activation of inflammatory processes in the skin, followed by oxidative damage. Altogether these observations indicate that exposure of skin to air pollutants modifies the redox equilibrium of keratinocytes, which could explain the increased skin damage observed in populations that live in high-pollution cities.


Assuntos
Poluentes Atmosféricos/toxicidade , Queratinócitos/efeitos dos fármacos , Estresse Oxidativo/fisiologia , Material Particulado/toxicidade , Poluentes Atmosféricos/análise , Antioxidantes/metabolismo , Humanos , Metais/análise , Mitocôndrias/metabolismo , Oxirredução , Estresse Oxidativo/efeitos dos fármacos , Material Particulado/análise , Hidrocarbonetos Policíclicos Aromáticos/análise , Quinonas/metabolismo , Transdução de Sinais/efeitos dos fármacos , Pele/efeitos dos fármacos
2.
Toxicol Lett ; 317: 68-81, 2019 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-31580885

RESUMO

Skin sensitization, frequently leading to allergic contact dermatitis (ACD), is authenticated to be a significant endpoint in the field of drug discovery and cosmetics. The initiation of ACD, also known as the skin sensitization mechanism, has been documented as an adverse outcome pathway (AOP), which can be studied experimentally and computationally. In this study, we collected 154 haptens and applied systems toxicology methods to develop a reaction-substructure-compound- target-pathway network system. For the collected haptens, their key substructures were identified and associated with their protein binding reactions. The targets of haptens, including the known targets collected from four databases and the potential targets predicted via our balanced substructure-drug-target network-based inference (bSDTNBI) method, were matched to skin proteins to obtain skin targets. The dermatitis-related pathways were enriched and were subject to literature verification. The network system we developed can be applied to predict the reactions, targets and pathways of new haptens, which contributed to evaluating chemical safety and optimizing chemical structures. The study of skin sensitization mechanism is helpful for understanding the skin immunity and resisting ACD.


Assuntos
Dermatite Alérgica de Contato/etiologia , Haptenos/toxicidade , Pele/efeitos dos fármacos , Biologia de Sistemas , Toxicologia/métodos , Animais , Dermatite Alérgica de Contato/imunologia , Dermatite Alérgica de Contato/metabolismo , Haptenos/química , Humanos , Estrutura Molecular , Ligação Proteica , Mapas de Interação de Proteínas , Medição de Risco , Transdução de Sinais/efeitos dos fármacos , Pele/imunologia , Pele/metabolismo , Relação Estrutura-Atividade
3.
Toxicol Lett ; 317: 45-52, 2019 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-31557510

RESUMO

This study involved an attempt to establish a new photosafety screening system for dermally-applied chemicals consisting of a reactive oxygen species (ROS) assay and an in vitro skin permeation test. The ROS assay was undertaken to evaluate photoreactivity of six test compounds, acridine (ACD), furosemide (FSM), hexachlorophene (HCP), 8-methoxypsoralen (MOP), norfloxacin (NFX), and promethazine (PMZ), and the in vitro skin permeation test was conducted to obtain steady-state concentration (Css) values of test compounds in removed rat skin. All test compounds were photoreactive based on ROS generation under simulated sunlight exposure. In particular, ROS generation from ACD was high compared with other test compounds, and photoreactivity of ACD was deduced to be potent. The Css values of ACD, HCP, MOP, and PMZ were over 50 µg/mL, and skin exposure to FSM and NFX was found to be extremely low. Upon these findings, ACD was judged to be highly phototoxic. The rank for phototoxic risk of test compounds based on photoreactivity and in vitro skin exposure was mostly in agreement with outcomes on their in vivo phototoxicity in rats. The proposed strategy, an alternative to animal testing, would be efficacious for photosafety evaluation of drug candidates in early stages of pharmaceutical development.


Assuntos
Acridinas/toxicidade , Dermatite Fototóxica/etiologia , Pele/efeitos dos fármacos , Acridinas/administração & dosagem , Acridinas/farmacocinética , Acridinas/efeitos da radiação , Administração Cutânea , Alternativas aos Testes com Animais , Animais , Dermatite Fototóxica/metabolismo , Técnicas In Vitro , Masculino , Permeabilidade , Ratos Sprague-Dawley , Espécies Reativas de Oxigênio/metabolismo , Medição de Risco , Pele/metabolismo , Absorção Cutânea , Raios Ultravioleta
4.
J Drugs Dermatol ; 18(9): 918-923, 2019 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-31524348

RESUMO

Background: Facial chemical peels are highly sought after by patients with photodamage, acne, and melasma. An advanced, physician-strength superficial peel, containing 3% retinol with other firming and volumizing ingredients was developed to exfoliate, improve the appearance of fine lines and wrinkles, and plump and firm skin, while promoting a bright, even complexion. Objective: A clinical study was conducted to evaluate the tolerability, safety, and efficacy of the 3% retinol peel with a supportive homecare regimen across a range of peel candidates, females aged 18-65 years, with photodamage, acne, hyperpigmentation or melasma, and skin of color, over a series of 2-4 peels. Method: The 3% retinol peel formulation was administered under physician direction in 6-week intervals. Subjects with photodamaged skin, acne, hyperpigmentation/melasma, or skin of color (Fitzpatrick skin types IV-VI) received 2-4 peels along with a supportive homecare regimen. Dermatologist grading, self-assessment, and digital photography documented tolerability and efficacy parameters. Results: 24 subjects participated in the study with a total of 78 peels administered (Photodamage group, n=14 [with an Acne subgroup, n=5]; Melasma group, n=5; Skin of Color, n=5). The 3% retinol peel along with the homecare regimen was well tolerated under physician direction in all skin types and conditions assessed. Obvious peeling was noticeable in many subjects 3 days post-peel and resolved by day 7. In the photodamaged group, dermatologist clinical grading of fine lines, wrinkles, pore size, laxity, mottled pigmentation, lack of clarity/radiance, and overall photodamage was significantly improved (P<0.05). Benefits were observed in all groups and supported by self-assessment. Digital photography demonstrated tolerability in the days immediately post-peel, along with benefits to photodamage. Conclusion: The 3% retinol superficial peel was well tolerated and an efficacious cosmetic treatment under physician supervision in subjects of all skin types to firm skin, improve fine lines and wrinkles, and promote a bright, even complexion. J Drugs Dermatol. 2019;18(9):918-923.


Assuntos
Acne Vulgar/tratamento farmacológico , Abrasão Química/métodos , Melanose/tratamento farmacológico , Envelhecimento da Pele/efeitos dos fármacos , Vitamina A/administração & dosagem , Administração Cutânea , Adolescente , Adulto , Idoso , Abrasão Química/efeitos adversos , Relação Dose-Resposta a Droga , Feminino , Humanos , Pessoa de Meia-Idade , Medidas de Resultados Relatados pelo Paciente , Autoadministração , Pele/efeitos dos fármacos , Pigmentação da Pele/efeitos dos fármacos , Resultado do Tratamento , Vitamina A/efeitos adversos , Adulto Jovem
5.
J Drugs Dermatol ; 18(9): 929-935, 2019 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-31524350

RESUMO

Injectable poly-L-lactic acid (PLLA) is a biodegradable synthetic polymer that stimulates collagen production, leading to gradual volume restoration. The treatment of sagging skin in body areas is still a big challenge, as there are few aesthetic procedures aiming to improve it. This article provides recommendations on the use of PLLA in the treatment of skin laxity in off-face areas, as the neck, décolletage, arms, abdomen, buttocks, and thighs, including the patient selection, product preparation, and injection techniques. The use of PLLA is a promising method for the treatment of skin laxity in corporal areas, improving body contour and appearance. Further investigation is needed to better understand the efficacy and durability of PLLA in non-facial indications and to provide the best evidence for optimal patient outcomes. J Drugs Dermatol. 2019;18(9):929-935.


Assuntos
Celulose/administração & dosagem , Técnicas Cosméticas/normas , Elasticidade/efeitos dos fármacos , Ácido Láctico/administração & dosagem , Manitol/administração & dosagem , Envelhecimento da Pele/efeitos dos fármacos , Fatores Etários , Celulose/efeitos adversos , Técnicas Cosméticas/efeitos adversos , Estética , Feminino , Humanos , Injeções Subcutâneas/efeitos adversos , Ácido Láctico/efeitos adversos , Manitol/efeitos adversos , Pessoa de Meia-Idade , Seleção de Pacientes , Guias de Prática Clínica como Assunto , Rejuvenescimento , Pele/efeitos dos fármacos , Pele/metabolismo
6.
J Drugs Dermatol ; 18(9): 940-942, 2019 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-31524352

RESUMO

Prurigo nodularis (PN) is a disease in which chronic scratching and picking of the skin due to intense pruritis results in papulonodules, notably in areas that are accessible to the patient. The pathophysiology is hypothesized to be mediated by a Th2 helper cell response, similar to that seen in atopic dermatitis, therefore, treatment of PN with dupilumab would be expected to elicit a therapeutic response. We demonstrated that treatment of PN with dupilumab significantly decreased pruritis and the size and number of new lesions after 2 months of treatment. J Drugs Dermatol. 2019;18(9):940-942.


Assuntos
Anticorpos Monoclonais/administração & dosagem , Prurigo/tratamento farmacológico , Prurido/tratamento farmacológico , Adulto , Anticorpos Monoclonais Humanizados , Feminino , Humanos , Injeções Subcutâneas , Prurigo/diagnóstico , Prurigo/patologia , Prurido/diagnóstico , Prurido/patologia , Pele/efeitos dos fármacos , Pele/patologia , Resultado do Tratamento
7.
J Drugs Dermatol ; 18(9): 943-945, 2019 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-31524993

RESUMO

Raynaud's phenomenon is an exaggerated physiological response of blood vessels in the distal extremities to emotional stress and cold. It can be idiopathic or secondary to a connective tissue disorder, such as scleroderma or systemic lupus erythematosus. Treatment for Raynaud's phenomenon consists primarily of lifestyle modifications; if unsuccessful, pharmacotherapy with dihydropyridine calcium channel blockers can be added. Botulinum toxin (BTX-A) is a neurotoxic protein produced by Clostridium botulinum spores. While most widely known for its cosmetic use, BTX-A has many therapeutic utilities due to its ability to inhibit multiple neurotransmitters. In this report, we present a patient with Raynaud's phenomenon refractory to standard therapies whose symptoms resolved after treatment with BTX-A. Follow-up with the patient after one and five years showed no relapse or recurrence of symptoms. J Drugs Dermatol. 2019;18(9):943-945.


Assuntos
Toxinas Botulínicas Tipo A/administração & dosagem , Neurotoxinas/administração & dosagem , Doença de Raynaud/tratamento farmacológico , Pele/patologia , Resistência a Medicamentos , Feminino , Dedos , Humanos , Injeções Subcutâneas , Necrose/tratamento farmacológico , Necrose/etiologia , Doença de Raynaud/complicações , Pele/efeitos dos fármacos , Fatores de Tempo , Resultado do Tratamento , Adulto Jovem
8.
Anticancer Res ; 39(9): 5179-5184, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31519631

RESUMO

BACKGROUND/AIM: The pesticide dimethoate (O-dimethyl-S- Nmethylcarbamoylmethyl phosphorodithioate) is able to induce severe acute toxicity in living organisms. The aim of this study was to evaluate the effects of ultraviolet radiation, alone or combined with exposure to dimethoate, on the rat skin. MATERIALS AND METHODS: A total of 38 Wistar female rats (Rattus norvegicus albinus), were distributed into four groups: A (n=9) control group, B (n=10) exposed to ultraviolet-B radiation (UV-B), C (n=10) exposed to UV-B followed by application of dimethoate (UV-B+AGRO) and group D (n=9) exposed to dimethoate (AGRO). Histological examination of the tissues, as well as immunohistochemistry for cleaved caspase 3, Ki-67 and COX-2 expression were performed to all groups. RESULTS: Animals submitted to UV-B exhibited hyperkeratosis with moderate cell atypia. Regarding exposure to UV-B+AGRO, the animals presented hyperkeratosis and atrophy, whereas in animals exposed to AGRO, only atrophy was noticed. The immunohistochemical results on skin revealed that UVB, AGRO and UVB+AGRO decreased cleaved caspase 3 and Ki-67 expression when compared to the control group (p<0.05). COX-2 expression decreased to UVB or AGRO groups compared to controls (p<0.05). CONCLUSION: UV-B or AGRO exposure is able to induce histopathological changes and altered expression of cleaved caspase-3 and Ki-67 in rat skin, thus being categorized as a risk condition for skin carcinogenesis.


Assuntos
Dimetoato/farmacologia , Pele/efeitos dos fármacos , Pele/efeitos da radiação , Raios Ultravioleta , Animais , Apoptose/efeitos dos fármacos , Apoptose/efeitos da radiação , Biomarcadores , Proliferação de Células/efeitos dos fármacos , Proliferação de Células/efeitos da radiação , Feminino , Imuno-Histoquímica , Ratos , Ratos Wistar , Pele/metabolismo
9.
Adv Gerontol ; 32(3): 331-337, 2019.
Artigo em Russo | MEDLINE | ID: mdl-31512418

RESUMO

Aging of extracellular proteins colloidal systems is one of major synchronizing mechanism in mammal`s «biological clock¼. We hypothesized that induced controllable modification of connective tissue composition could reverse aging. In murine experimental models collagenase was used for selective destruction of old collagen. Oxygen consumption, urine hydroxyproline excretion, density and distribution of mature and old collagen and elastine fibers in dermal biopsies were determined. Collagenase injections significantly increased hydroxyproline excretion. We observed reduced density of mature and old collagen fibers and increased oxygen consumption in dermal biopsies after course of collagenase injections. Collagenase treatment intensified the destruction of mature and old collagen matrix and enhanced synthesis of new collagen and elastine fibers. Furthermore oxygen consumption increased. Our findings can be considered as indicator of collagenase systemic anti-aging (rejuvenation) activity.


Assuntos
Envelhecimento , Colágeno , Envelhecimento/efeitos dos fármacos , Animais , Colágeno/metabolismo , Colagenases/farmacologia , Hidroxiprolina/metabolismo , Camundongos , Modelos Animais , Consumo de Oxigênio/efeitos dos fármacos , Pele/efeitos dos fármacos
10.
Eur J Pharm Biopharm ; 144: 154-164, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31542438

RESUMO

Curcumin, a multi-targeting pharmacologically active compound, is a promising molecule for the treatment of skin inflammation and infection in chronic wounds. However, its hydrophobic nature remains to be a challenge in development of its pharmaceutical products, including dermatopharmaceuticals. Here we propose deformable liposomes (DLs) as a mean to overcome the curcumin limitations in skin treatment. We explored the properties and biological effects of curcumin containing DLs (curcumin-DLs) with varying surface charge by preparing the neutral (NDLs), cationic (CDLs) and anionic (ADLs) nanocarriers. The vesicles of mean diameter 200-300 nm incorporated high curcumin load mirroring the type of employed surfactant. Curcumin-CDLs provided the most sustained ex vivo penetration of curcumin through the full thickness human skin. Although the curcumin-CDLs were the most potent regarding the in vitro anti-inflammatory activity, all curcumin-DLs were superior to curcumin in solution (control). No cytotoxicity in human skin fibroblasts was detected. All DLs significantly inhibited bacterial Staphylococcus aureus and Streptococcus pyogenes growth in vitro. The curcumin-CDLs were found superior to other DLs. The incorporation of curcumin in DLs enabled both its sustained skin penetration and enhancement of its biological properties. Cationic nanocarriers enhanced the activities of curcumin to the greatest extent.


Assuntos
Curcumina/administração & dosagem , Curcumina/química , Lipossomos/química , Pele/efeitos dos fármacos , Infecções Cutâneas Estafilocócicas/tratamento farmacológico , Administração Cutânea , Cátions/química , Sobrevivência Celular/efeitos dos fármacos , Portadores de Fármacos/química , Fibroblastos/efeitos dos fármacos , Humanos , Interações Hidrofóbicas e Hidrofílicas , Nanopartículas/química , Tamanho da Partícula , Pele/microbiologia , Absorção Cutânea/efeitos dos fármacos , Infecções Estafilocócicas/tratamento farmacológico , Infecções Estafilocócicas/microbiologia , Infecções Cutâneas Estafilocócicas/microbiologia , Staphylococcus aureus/efeitos dos fármacos , Infecções Estreptocócicas/tratamento farmacológico , Infecções Estreptocócicas/microbiologia , Streptococcus pyogenes/efeitos dos fármacos , Tensoativos/química
11.
Acta Cir Bras ; 34(7): e201900701, 2019 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-31531536

RESUMO

PURPOSE: To compare the use of new cyanoacrylate surgical adhesive associated with macroporous tapes in cutaneous synthesis. METHODS: Male Wistar rats with a longitudinal incision of 4cm were used on the back, divided into four groups: GI used octyl-cyanoacrylate (Dermabond®), GII used N-2-butylcyanoacrylate, GIII used octyl-cyanoacrylate and macroporous tape and GIV used N-2-butyl cyanoacrylate and macroporous tape. On the fourteenth day, the rats were submitted to euthanasia, were divided in two parts, and a layer of skin subcutaneous tissue through an area of operative healing was removed. One part was submitted to the study of rupture strength with the use of tensiometer, and in the other part histological examination was performed. RESULTS: No force test was similar between groups I and II, being different from groups III and IV (P <0.001), which were identical to each other (P> 0.05). The units were compared among the studied groups, and they were different with the use of macroporous tapes (P> 0.05). CONCLUSIONS: The purpose of macroporous tapes is associated with CA adhesives in cutaneous tissues that provide more resistant scars. The use of a combination of macroporous tapes leads to complete re-epithelialization, without provoking foreign body reaction, has hemostatic properties and does not cause an absorptive reaction.


Assuntos
Embucrilato/farmacologia , Pele/efeitos dos fármacos , Deiscência da Ferida Operatória/prevenção & controle , Adesivos Teciduais/farmacologia , Cicatrização/fisiologia , Animais , Masculino , Ratos , Ratos Wistar , Técnicas de Sutura
12.
Toxicol Lett ; 314: 172-180, 2019 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-31404593

RESUMO

Vesicants cause a multitude of cutaneous reactions like erythema, blisters and ulcerations. After exposure to sulfur mustard (SM) and related compounds, patients present dermal symptoms typically known for chemicals categorized as skin sensitizer (e.g. hypersensitivity and flare-up phenomena). However, although some case reports led to the assumption that SM and other alkylating compounds represent sensitizers, a comprehensive investigation of SM-triggered immunological responses has not been conducted so far. Based on a well-structured system of in chemico and in vitro test methods, the Organization for Economic Co-operation and Development (OECD) established procedures to categorize agents on their skin sensitizing abilities. In this study, the skin sensitizing potential of SM and three related alkylating agents (AAs) was assessed following the OECD test guidelines. Besides SM, investigated AAs were chlorambucil (CHL), nitrogen mustard (HN3) and 2-chloroethyl ethyl sulfide (CEES). The methods are described in detail in the EURL ECVAM DataBase service on ALternative Methods to animal experimentation (DB-ALM). In accordance to OECD recommendations, skin sensitization is a pathophysiological process starting with a molecular initiating step and ending with the in vivo outcome of an allergic contact dermatitis. This concept is called adverse outcome pathway (AOP). An AOP links an adverse outcome to various key events which can be assayed by established in chemico and in vitro test methods. Positive outcome in two out of three key events indicates that the chemical can be categorized as a skin sensitizer. In this study, key event 1 "haptenation" (covalent modification of epidermal proteins), key event 2 "activation of epidermal keratinocytes" and key event 3 "activation of dendritic cells" were investigated. Covalent modification of epidermal proteins measured by using the DPRA-assay provided distinct positive results for all tested substances. Same outcome was seen in the KeratinoSens assay, investigating the activation of epidermal keratinocytes. The h-CLAT assay performed to determine the activation of dendritic cells provided positive results for SM and CEES but not for CHL and HN3. Altogether, following OECD requirements, our results suggest the classification of all investigated substances as skin sensitizers. Finally, a tentative AOP for SM-induced skin sensitization is suggested.


Assuntos
Substâncias para a Guerra Química/toxicidade , Irritantes/toxicidade , Gás de Mostarda/toxicidade , Testes de Irritação da Pele/normas , Pele/efeitos dos fármacos , Biomarcadores/metabolismo , Substâncias para a Guerra Química/classificação , Clorambucila/classificação , Clorambucila/toxicidade , Guias como Assunto , Humanos , Irritantes/classificação , Queratinócitos/efeitos dos fármacos , Queratinócitos/imunologia , Queratinócitos/metabolismo , Células de Langerhans/efeitos dos fármacos , Células de Langerhans/imunologia , Células de Langerhans/metabolismo , Mecloretamina/classificação , Mecloretamina/toxicidade , Gás de Mostarda/análogos & derivados , Gás de Mostarda/classificação , Medição de Risco , Pele/imunologia , Pele/metabolismo
13.
J Dermatol ; 46(10): 898-901, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31373046

RESUMO

Kaposiform hemangioendothelioma (KHE) and tufted angioma (TA) are rare infiltrative vascular tumors. Currently, no standard treatment regimens exist for KHE/TA. The purpose of our study was to evaluate the efficacy and safety of topical application of tacrolimus for superficial KHE/TA. We examined six patients with superficial KHE/TA. All patients were treated with tacrolimus 0.1% ointment twice daily for at least 12 months. The response rate was 100%, including three nearly complete remissions. Only one patient experienced local pruritus during treatment. The data constituted an intriguing rationale for clinical trials of topical tacrolimus in the treatment of superficial KHE/TA.


Assuntos
Hemangioendotelioma/tratamento farmacológico , Hemangioma/tratamento farmacológico , Síndrome de Kasabach-Merritt/tratamento farmacológico , Sarcoma de Kaposi/tratamento farmacológico , Neoplasias Cutâneas/tratamento farmacológico , Tacrolimo/administração & dosagem , Administração Cutânea , Biópsia , Pré-Escolar , Feminino , Hemangioendotelioma/diagnóstico por imagem , Hemangioendotelioma/patologia , Hemangioma/diagnóstico por imagem , Hemangioma/patologia , Humanos , Lactente , Síndrome de Kasabach-Merritt/diagnóstico por imagem , Síndrome de Kasabach-Merritt/patologia , Masculino , Uso Off-Label , Pomadas , Fotografação , Prurido/induzido quimicamente , Sarcoma de Kaposi/diagnóstico por imagem , Sarcoma de Kaposi/patologia , Pele/diagnóstico por imagem , Pele/efeitos dos fármacos , Pele/patologia , Neoplasias Cutâneas/diagnóstico por imagem , Neoplasias Cutâneas/patologia , Tacrolimo/efeitos adversos , Resultado do Tratamento
14.
J Photochem Photobiol B ; 198: 111565, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31374350

RESUMO

The incidence of skin cancers has increased worldwide, requiring more prevention of this type of cancer. The use of sunscreen and the control of the time of exposure to sunlight are the recognized forms of prevention. However, new substances have been researched in order to develop formulations with more efficient protective activity. Citral is a natural compound with lemon scent that is used in food and cosmetic industries. The present work evaluated the chemoprotective effect of citral during UVB-induced skin carcinogenesis. Male hairless mice HRS/J, 8-12 weeks old, were exposed to UVB irradiation for 24 weeks, with a cumulative radiation dose of 13.875 J/cm2. Citral (0.1, 0.5 and 1%) was applied to the skin at a dosage of 0.1 g/animal, 5 min after UVB exposure. At the end of the experiment, the number of lesion/animal, and size of lesions were measured. The histological sections of the skin were evaluated for the presence and intensity of actinic keratosis and squamous cell carcinoma. TUNEL assay was performed for apoptosis evaluation. Skin samples were used for the measurement of oxidative stress parameters (total radical-trapping antioxidant parameter of skin, glutathione, catalase activity and malondialdehyde), and cytokines levels (IL-1ß, IL-4, IL-10, IL-23, TNF-α, and IFNγ). Citral 1% completely inhibited UVB-induced skin carcinogenesis by reducing levels of oxidative stress and pro-inflammatory cytokines, increasing apoptotic rate in the skin.


Assuntos
Carcinoma de Células Escamosas/patologia , Monoterpenos/farmacologia , Neoplasias Cutâneas/patologia , Pele/efeitos dos fármacos , Raios Ultravioleta , Animais , Antioxidantes/metabolismo , Carcinoma de Células Escamosas/prevenção & controle , Catalase/metabolismo , Citocinas/metabolismo , Glutationa/metabolismo , Ceratose/patologia , Masculino , Malondialdeído/metabolismo , Camundongos , Camundongos Pelados , Monoterpenos/uso terapêutico , Estresse Oxidativo/efeitos dos fármacos , Estresse Oxidativo/efeitos da radiação , Pele/metabolismo , Pele/efeitos da radiação , Neoplasias Cutâneas/prevenção & controle
15.
Life Sci ; 233: 116714, 2019 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-31376370

RESUMO

Increased levels of particulate matter (PM) air pollutants in East Asia have resulted in detrimental health impacts increasing morbidity and mortality. Epidemiological studies suggest a possible relation between the cutaneous exposure of PM and increased oxidative stress and inflammation which lead to skin lesions. The present study utilizes an integrated cell culture model of keratinocytes and fibroblasts to mimic viable skin layers and investigate the possible effects of PM exposure after penetration through corneocytes. The skin perfection is upheld by homeostatic functionality of epidermal cells and the integrity of connective tissues. Exposure to xenobiotics could alter the skin cell homeostasis aggravating premature skin aging. Stimulation of HaCaT keratinocytes by PM collected from Beijing, China (CPM) increased the intracellular ROS levels triggering a cascade of events aggravating inflammatory responses and connective tissue degradation. In HDF fibroblasts, treatment with preconditioned keratinocyte culture media augmented inflammatory responses, cellular differentiation, and connective tissue degradation. Above events were marked by the increased intracellular ROS, inflammatory mediators, pro-inflammatory cytokines, matrix metalloproteinases (MMP)-1 and -2 levels, collagenase, and elastase activity. Fucosterol treatment of keratinocytes dose-dependently attenuated the detrimental effects both in keratinocytes and fibroblasts restoring the conditions near to physiological levels. Further evaluations could be advanced on developing fucosterol, in forms such as rejuvenating cosmeceuticals which could attenuate detrimental responses of CPM exposure.


Assuntos
Fibroblastos/efeitos dos fármacos , Inflamação/tratamento farmacológico , Queratinócitos/efeitos dos fármacos , Material Particulado/efeitos adversos , Dermatopatias/tratamento farmacológico , Pele/efeitos dos fármacos , Estigmasterol/análogos & derivados , Poluentes Atmosféricos/efeitos adversos , Células Cultivadas , Técnicas de Cocultura , Citocinas/metabolismo , Fibroblastos/metabolismo , Fibroblastos/patologia , Humanos , Inflamação/etiologia , Inflamação/metabolismo , Inflamação/patologia , Queratinócitos/metabolismo , Queratinócitos/patologia , NF-kappa B/metabolismo , Estresse Oxidativo , Espécies Reativas de Oxigênio/metabolismo , Pele/patologia , Dermatopatias/etiologia , Dermatopatias/metabolismo , Dermatopatias/patologia , Estigmasterol/farmacologia
16.
J Drugs Dermatol ; 18(8): 828-830, 2019 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-31424716

RESUMO

A 56-year-old Caucasian male with a history of chronic plaque psoriasis, primary sclerosing cholangitis status-post liver transplant on tacrolimus, and ulcerative colitis on infliximab developed a progressive erythematous eruption with associated fatigue, anorexia, myalgias, and arthralgias. On two separate occasions, his skin biopsy demonstrated a lichenoid interface dermatitis (LID). Despite multiple courses of oral prednisone, topical steroids, and a short course of hydroxychloroquine, his symptoms continued to relapse and remit. When a temporal association between increasing his infliximab dose and the global progression of his disease was identified, he was ultimately diagnosed with a TNF-α inhibitor-induced psoriasis flare. Despite the patient's long-standing history of psoriasis, a plausible psoriasis rebound reaction after systemic steroids was not strongly considered in light of his histopathology. Though lichenoid interface dermatitis is a commonly reported histologic finding in patients on TNF-α inhibitors, it has scarcely been reported in patients with psoriasiform eruptions clinically.


Assuntos
Erupção por Droga/diagnóstico , Infliximab/efeitos adversos , Erupções Liquenoides/diagnóstico , Psoríase/tratamento farmacológico , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Biópsia , Diagnóstico Diferencial , Erupção por Droga/etiologia , Erupção por Droga/patologia , Humanos , Erupções Liquenoides/patologia , Masculino , Pessoa de Meia-Idade , Psoríase/diagnóstico , Pele/efeitos dos fármacos , Pele/patologia , Exacerbação dos Sintomas
17.
Int J Nanomedicine ; 14: 5849-5863, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31440050

RESUMO

Background: Topical application of tacrolimus (FK506) was effective in treating atopic dermatitis (AD); however, the therapeutic efficiency is hampered by its poor penetration into the skin and local side effects of transient irritation symptoms with a burning sensation, a feeling of warmth or heat. Menthol and camphor have been widely used in topical compound formulations for adjunctive pharmacotherapy for antipruritics and analgesics owing to their cool nature, and both present skin penetration enhancing effects. Moreover, they can form a liquid eutectic oil to solubilize hydrophobic drugs. Purpose: Taking advantages of menthol/camphor eutectic (MCE), this work aims to integrate FK506 into MCE to construct a microemulsion system, i.e., FK506 MCE ME, which simultaneously enhances the percutaneous delivery and treatment efficacy, while reduces the side effects of FK506. Methods: The formulation of FK506 MCE ME was optimized and characterized. Different formulations containing FK506 were topically administered to treat 1-chloro-2, 4-dinitrobenzene (DNCB)-induced murine AD. Results: MCE solubilized FK506. FK506 in MCE ME penetrated skin in vitro more than in the commercial ointment, and MCE predominantly exerted the enhancing effects in MCE ME. FK506 MCE ME or FK506 MCE ME gel had greater effects on clinical symptoms, histological analysis, and IgE than did commercial FK506. The anti-pruritic and down-regulation of substance P effects of MCE ME vehicle mitigated the side effects of FK506 application. Conclusion: MCE ME presented the excellent properties of simultaneously enhancing the percutaneous delivery and treatment efficacy, while reducing the side effects of FK506 for AD. Therefore, MCE ME is a promising nanoscale system for FK506 to effectively treating AD with low irritation and high medication adherence. Chemical compounds studied in this article: Tacrolimus (PubChem CID: 445643); menthol (PubChem CID: 1254); camphor (PubChem CID: 2537).


Assuntos
Dermatite Atópica/tratamento farmacológico , Emulsões/química , Óleos/química , Tacrolimo/efeitos adversos , Tacrolimo/uso terapêutico , Administração Cutânea , Animais , Cânfora/química , Morte Celular/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Dermatite Atópica/induzido quimicamente , Regulação para Baixo/efeitos dos fármacos , Orelha/patologia , Humanos , Imunoglobulina E/sangue , Imunossupressores/administração & dosagem , Masculino , Mentol/química , Camundongos , Camundongos Endogâmicos BALB C , Ratos Sprague-Dawley , Pele/efeitos dos fármacos , Pele/patologia , Absorção Cutânea/efeitos dos fármacos , Baço/efeitos dos fármacos , Substância P/metabolismo , Tacrolimo/administração & dosagem , Tacrolimo/farmacologia , Resultado do Tratamento , Perda Insensível de Água/efeitos dos fármacos
18.
Int J Nanomedicine ; 14: 6135-6150, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31447556

RESUMO

Background: Nanostructured lipid carriers (NLCs) are emerging as attractive drug carriers in transdermal drug delivery. The surface modification of NLCs with cell-penetrating peptides (CPPs) can enhance the skin permeation of drugs. Purpose: The objective of the current study was to evaluate the ability of the cell-penetrating peptide (CPP) polyarginine to translocate NLCs loaded with lornoxicam (LN) into the skin layers and to evaluate its anti-inflammatory effect. Methods: The NLCs were prepared using an emulsion evaporation and low temperature solidification technique using glyceryl monostearates, triglycerides, DOGS-NTA-Ni lipids and surfactants, and then six histidine-tagged polyarginine containing 11 arginine (R11) peptides was modified on the surface of NLCs. Results: The developed NLCs formulated with LN and R11 (LN-NLC-R11) were incorporated into 2% HPMC gels. NLCs were prepared with a particle size of (121.81±3.61)-(145.72±4.78) nm, and the zeta potential decreased from (-30.30±2.07) to (-14.66±0.74) mV after the modification of R11 peptides. The encapsulation efficiency and drug loading were (74.61±1.13) % and (7.92±0.33) %, respectively, regardless of the surface modification. Cellular uptake assays using HaCaT cells suggested that the NLC modified with R11 (0.02%, w/w) significantly enhanced the cell internalization of nanoparticles relative to unmodified NLCs (P<0.05 or P<0.01). An in vitro skin permeation study showed better permeation-enhancing ability of R11 (0.02%, w/w) than that of other content (0.01% or 0.04%). In carrageenan-induced rat paw edema models, LN-NLC-R11 gels inhibited rat paw edema and the production of inflammatory cytokines compared with LN-NLC gels and LN gels (P<0.01). Conclusion: In our investigation, it was strongly demonstrated that the surface modification of NLC with R11 enhanced the translocation of LN across the skin, thereby alleviating inflammation.


Assuntos
Portadores de Fármacos/química , Sistemas de Liberação de Medicamentos , Edema/tratamento farmacológico , Lipídeos/química , Nanoestruturas/química , Peptídeos/farmacologia , Piroxicam/análogos & derivados , Administração Cutânea , Animais , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Carragenina , Morte Celular/efeitos dos fármacos , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Peptídeos Penetradores de Células/farmacologia , Edema/induzido quimicamente , Edema/metabolismo , Emulsões/química , Endocitose/efeitos dos fármacos , Géis/química , Humanos , Camundongos Endogâmicos BALB C , Nanopartículas/química , Nanopartículas/ultraestrutura , Oligopeptídeos/farmacologia , Oligopeptídeos/uso terapêutico , Piroxicam/administração & dosagem , Piroxicam/farmacologia , Piroxicam/uso terapêutico , Coelhos , Ratos Sprague-Dawley , Pele/efeitos dos fármacos , Absorção Cutânea/efeitos dos fármacos , Testes de Irritação da Pele
19.
Am J Vet Res ; 80(9): 862-867, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31449448

RESUMO

OBJECTIVE: To evaluate erythema and number of CFUs on the skin of dogs with hair clipped by use of 2 sizes of clipper blades. ANIMALS: 67 client-owned dogs receiving an epidural. PROCEDURES: Hair was clipped with a No. 10 blade (approx hair length, 1.5 mm) on one half and a No. 40 blade (approx hair length, 0.25 mm) on the other half of each epidural site. Skin was surgically scrubbed with 2% chlorhexidine gluconate and 70% isopropyl alcohol. Samples were obtained immediately after clipping, after skin was scrubbed, and again 24 hours after clipping. Number of CFUs for both sides of the clipped areas, types of microorganisms, and growth on MacConkey agar were evaluated every 24 hours for 72 hours. Colonies were evaluated for bacterial morphology and Gram stain characteristics. Sites were evaluated 24 hours after clipping for evidence of erythema. RESULTS: 24 hours after hair was clipped, there was a significantly higher incidence of erythema and higher number of Micrococcaceae bacteria for the side clipped with the No. 40 blade than the side clipped with the No. 10 blade. Number of CFUs did not differ significantly between size of clipper blades. CONCLUSIONS AND CLINICAL RELEVANCE: Clipping hair with a No. 40 blade resulted in a significant increase in the incidence of erythema and higher number of Micrococcaceae bacteria, compared with results for clipping with a No. 10 blade. These results supported use of a No. 10 clipper blade to prevent erythema and reduce variation in the skin microbiome.


Assuntos
Bactérias/isolamento & purificação , Cães/microbiologia , Asseio Animal , Cabelo/microbiologia , Pele/microbiologia , Animais , Clorexidina/análogos & derivados , Doenças do Cão/etiologia , Doenças do Cão/microbiologia , Eritema/etiologia , Eritema/microbiologia , Eritema/veterinária , Feminino , Masculino , Pele/efeitos dos fármacos , Células-Tronco
20.
J Dermatol ; 46(9): 752-758, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31342560

RESUMO

The 52-week results from the CLEAR (NCT02074982) study showed high and superior efficacy of secukinumab versus ustekinumab in clearing skin and improving patient-reported outcomes, with comparable safety profile in subjects with moderate to severe psoriasis. Here, we analyzed the efficacy and safety of secukinumab in Asian subjects from the CLEAR study. In this double-blind, phase IIIb study, eligible subjects with moderate to severe plaque psoriasis were randomized (1:1) to receive s.c. injection of secukinumab 300 mg or ustekinumab as per label. Of 62 subjects included in Asian subanalyses, 23 were randomized to secukinumab and 39 to ustekinumab. A significantly higher proportion of subjects achieved 90% or more improvement in Psoriasis Area and Severity Index (PASI 90) with secukinumab versus ustekinumab at week 16 (78.3% vs 35.9%, P = 0.0010) and at week 52 (60.9% vs 33.3%, P = 0.0196). Similarly, a higher proportion of subjects achieved PASI 100 with secukinumab versus ustekinumab at week 16 (43.5% vs 10.3%, P = 0.0029) and at week 52 (30.4% vs 12.8%, P = 0.0704). The median time to achieve 50% improvement in baseline PASI was 2.8 weeks in the secukinumab group versus 6.3 weeks in the ustekinumab group. The safety profile of secukinumab was in line with the known profile and no deaths occurred. Overall, 95.7% and 84.6% of subjects remained on secukinumab and ustekinumab, respectively. Similar to the core study, secukinumab showed sustained and superior efficacy with faster response versus ustekinumab, and no new or unexpected safety concerns were identified, in Asian subjects with moderate to severe plaque psoriasis.


Assuntos
Anticorpos Monoclonais/administração & dosagem , Fármacos Dermatológicos/administração & dosagem , Psoríase/tratamento farmacológico , Ustekinumab/administração & dosagem , Adulto , Idoso , Anticorpos Monoclonais/efeitos adversos , Anticorpos Monoclonais Humanizados , Grupo com Ancestrais do Continente Asiático , Fármacos Dermatológicos/efeitos adversos , Método Duplo-Cego , Feminino , Humanos , Injeções Subcutâneas , Masculino , Pessoa de Meia-Idade , Psoríase/diagnóstico , Psoríase/patologia , Índice de Gravidade de Doença , Pele/efeitos dos fármacos , Pele/patologia , Fatores de Tempo , Ustekinumab/efeitos adversos
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