Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 21.728
Filtrar
1.
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
2.
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
3.
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
4.
Toxicol Lett ; 314: 27-36, 2019 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-31295538

RESUMO

Some cosmetic ingredients can act as a chemical hapten to induce an immune response; therefore, evaluating the sensitizing potential of cosmetic ingredients is essential. We previously developed a novel in chemico direct peptide reactivity assay involving a spectrophotometric evaluation (Spectro-DPRA) for animal skin sensitization tests (local lymph node assay; LLNA). Based on previous research, we expanded the test materials to confirm the effectiveness of the Spectro-DPRA method for predicting the animal skin sensitization potential, and further determined the feasibility of the method for estimating the human skin sensitization potential. Spectro-DPRA showed 83.1% or 89.1% accuracy compared to a conventional LLNA or prediction based on human data, respectively, with a combination model using both a cysteine peptide and lysine peptide cut-off. To identify the effect of the lipophilicity of a chemical on predicting the skin sensitization potential, we applied our prediction model to chemicals with a Log Pow range of -1 to 4. Overall predictability was increased, and the accuracy compared to the LLNA and human data was 91.5% and 94.9%, respectively, in the combination cut-off prediction model. In conclusion, Spectro-DPRA serves as an easy, rapid, and high-throughput in chemico screening method with high accuracy to predict the human skin sensitization potential of chemicals.


Assuntos
Alternativas aos Testes com Animais/métodos , Ensaios de Triagem em Larga Escala , Oligopeptídeos/química , Testes de Irritação da Pele/métodos , Pele/efeitos dos fármacos , Animais , Cisteína , Estudos de Viabilidade , Humanos , Ensaio Local de Linfonodo , Lisina , Estrutura Molecular , Reprodutibilidade dos Testes , Medição de Risco , Pele/imunologia , Espectrofotometria , Relação Estrutura-Atividade
5.
Medicine (Baltimore) ; 98(27): e16045, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31277098

RESUMO

RATIONALE: Synovitis, acne, pustulosis, hyperostosis, and osteitis (SAPHO) syndrome is a rare auto-inflammatory disease with no standardized treatment. Systemic corticosteroids are only transiently effective, but long-term use would bring complications and would not bring long-term remission. Bone scintigraphy is a first-line method for systematic evaluation of osteoarticular lesions but seems to show an "imprinting" pattern. PATIENT CONCERNS: A 31-year-old female patient presented significant palmoplantar pustulosis and nail lesion as well as typical tracer accumulation feature on bone scintigraphy with normal hypersensitivity C-reactive protein and erythrocyte sedimentation rate, but an elevated serum immunoglobulin E level. DIAGNOSIS: The diagnosis was made by dermatological manifestations and classical sign in bone scintigraphy in accordance with the diagnostic criteria proposed in 1988. INTERVENTIONS: Methylprednisolone was given with a primary dose of 40 mg/day for 1 week followed with a subsequent 20 mg/day oral prednisone for another 1 week and then reduced in a rate of 5 mg/week until the eventual cessation. OUTCOMES: Long-term remarkable remission on clinical manifestations, MRI performance, and quantitative analysis of bone scintigraphy was achieved. LESSONS: Identification of specific subtype of SAPHO patient according to skin and nail manifestations as well as immunoglobulin E level may guide the selection of short-term systemic corticosteroids strategy, leading to remarkable long-term remission. Besides, the lesions on bone scintigraphy can hardly disappear in SAPHO patients, and instead, the quantitative analysis of bone scintigraphy and MRI performances may better reflect the change of disease condition and serve as indicator for treatment efficiency.


Assuntos
Síndrome de Hiperostose Adquirida/tratamento farmacológico , Glucocorticoides/administração & dosagem , Metilprednisolona/administração & dosagem , Prednisona/administração & dosagem , Administração Oral , Adulto , Biomarcadores/sangue , Osso e Ossos/diagnóstico por imagem , Osso e Ossos/patologia , Feminino , Humanos , Imunoglobulina E/sangue , Unhas/efeitos dos fármacos , Cintilografia , Indução de Remissão/métodos , Pele/efeitos dos fármacos
6.
J Photochem Photobiol B ; 197: 111539, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31301638

RESUMO

Treatment of burn injury is clinically challenging one, therefore several steps and noteworthy approaches have been taken to improve wound mechanisms. Citrus pectin plays a stabilizing agent to synthesis of ZnO nanoparticles (ZnO NPs). The present study is focused on ZnO loaded collagen/chitosan nanofibrous were synthesized by electrospinning method using ZnO NPs. The chemical structure, phase purity and morphological observation were investigated under spectroscopic and mircoscopic techniques and demonstrated their suitable properties as a wound healing material. In addition, that prepared nanoparticles loaded biopolymeric fibrous nanomaterial showed suitable antibacterial activity against S. aureus and E. coli bacterial pathogens and also in vitro studies was confirmed the enhanced proliferation, cell viability and biocompatibility. In vitro evaluations have been exhibited acceptable cell proliferation is observed throughout the ZnO loaded Coll/CS nanofibrous within 3 days, which was comparable to the control material. In vivo wound healing ability was monitored on the rat wound experimental model. From the in vivo observations, revealed that the loaded of ZnO NPs with Coll/CS nanofibrous can effectively quicken wound healing mechanism, expressed in the initial stage healing process. These results suggest that ZnO loaded collagen/chitosan nanofibrous is a potential candidate for wound healing applications with enhanced biological properties.


Assuntos
Queimaduras/patologia , Quitosana/química , Colágeno/química , Nanopartículas Metálicas/química , Nanofibras/química , Animais , Antibacterianos/química , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Bacteriemia/prevenção & controle , Queimaduras/veterinária , Linhagem Celular , Proliferação de Células/efeitos dos fármacos , Escherichia coli/efeitos dos fármacos , Fibroblastos/citologia , Fibroblastos/efeitos dos fármacos , Fibroblastos/metabolismo , Humanos , Nanofibras/uso terapêutico , Nanofibras/toxicidade , Ratos , Pele/efeitos dos fármacos , Pele/patologia , Staphylococcus aureus/efeitos dos fármacos , Cicatrização/efeitos dos fármacos , Óxido de Zinco/química
7.
Cancer Invest ; 37(6): 253-264, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31303065

RESUMO

We fully investigate the skin toxicities of epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) in cancer patients. The studies about randomized controlled trials in cancer treatment with EGFR-TKIs were retrieved and the systematic evaluation was conducted. The results suggest that EGFR-TKIs significantly increase the risk of skin toxicities including all-grade rash, pruritus, dry skin, and high-grade rash, pruritus. However, the risk of high-grade dry skin did not increase. Rash was the most common toxicity. Physicians should be aware of skin toxicities and should monitor cancer patients when receiving EGFR-TKIs.


Assuntos
Receptores ErbB/antagonistas & inibidores , Neoplasias/tratamento farmacológico , Inibidores de Proteínas Quinases/efeitos adversos , Inibidores de Proteínas Quinases/uso terapêutico , Pele/efeitos dos fármacos , Exantema/induzido quimicamente , Humanos , Ensaios Clínicos Controlados Aleatórios como Assunto
8.
J Photochem Photobiol B ; 197: 111556, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31326842

RESUMO

Facile green synthesis of copper nanoparticles from different biological procedures has been indicated, but among all, biosynthesis of copper nanoparticles from medicinal plants is considered as the most suitable method. The use of medicinal plant material increases the therapeutical effects of copper nanoparticles. The aim of this study was green synthesis of copper nanoparticles from aqueous extract of Falcaria vulgaris leaf (CuNPs) and assessment of their cytotoxicity, antioxidant, antifungal, antibacterial, and cutaneous wound healing properties. These nanoparticles were characterized by X-ray diffraction (XRD), fourier-transform infrared spectroscopy (FT-IR), ultraviolet-visible spectroscopy (UV), transmission electron microscopy (TEM), and field emission scanning electron microscopy (FE-SEM) analysis. The synthesized CuNPs had great cell viability dose-dependently (Investigating the effect of the CuNPs on human umbilical vein endothelial cell (HUVEC) line) and indicated this method was nontoxic. Also, 2,2-diphenyl-1-picrylhydrazyl (DPPH) test was done to assess the antioxidant activities, which indicated similar antioxidant potentials for CuNPs and butylated hydroxytoluene. In part of cutaneous wound healing property of CuNPs, after creating the cutaneous wound, the rats were randomly divided into six groups: treatment with 0.2% CuNPs ointment, treatment with 0.2% CuSO4 ointment, treatment with 0.2% F. vulgaris ointment, treatment with 3% tetracycline ointment, treatment with Eucerin basal ointment, and untreated control. These groups were treated for 10 days. Treatment with CuNPs ointment remarkably increased (p ≤ .01) the wound contracture, vessel, hexosamine, hydroxyl proline, hexuronic acid, fibrocyte, and fibrocytes/fibroblast rate and substantially reduced (p ≤ .01) the wound area, total cells, neutrophil, and lymphocyte compared to other groups. In antibacterial and antifungal parts of this research, the concentration of CuNPs with minimum dilution and no turbidity was considered minimum inhibitory concentration (MIC). To determine minimum fungicidal concentration (MFC) and minimum bactericidal concentration (MBC), 60 µL MIC and three preceding chambers were cultured on Sabouraud Dextrose Agar and Muller Hinton Agar, respectively. The minimum concentration with no fungal and bacterial growth were considered MFC and MBC, respectively. CuNPs inhibited the growth of all fungi at 2-4 mg/mL concentrations and removed them at 4-8 mg/mL concentrations (p ≤ .01). In case of antibacterial effects of CuNPs, they inhibited the growth of all bacteria at 2-8 mg/mL concentrations and removed them at 4-16 mg/mL concentrations (p ≤ .01). The results of XRD, FT-IR, UV, TEM, and FE-SEM confirm that the aqueous extract of F. vulgaris leaf can be used to yield copper nanoparticles with notable amount of antioxidant, antifungal, antibacterial, and cutaneous wound healing potentials without any cytotoxicity. Further clinical trials are necessary for confirmation these therapeutical effects of CuNPs in human.


Assuntos
Apiaceae/química , Cobre/química , Nanopartículas Metálicas/química , Extratos Vegetais/química , Animais , Antibacterianos/síntese química , Antibacterianos/química , Antibacterianos/farmacologia , Antifúngicos/síntese química , Antifúngicos/química , Antifúngicos/farmacologia , Antioxidantes/química , Apiaceae/metabolismo , Candida/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Bactérias Gram-Negativas/efeitos dos fármacos , Bactérias Gram-Positivas/efeitos dos fármacos , Química Verde , Células Endoteliais da Veia Umbilical Humana , Humanos , Masculino , Nanopartículas Metálicas/toxicidade , Testes de Sensibilidade Microbiana , Folhas de Planta/química , Folhas de Planta/metabolismo , Ratos , Pele/efeitos dos fármacos , Pele/patologia , Cicatrização/efeitos dos fármacos
9.
J Photochem Photobiol B ; 197: 111545, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31326847

RESUMO

Proper waste utilization in order to promote value added product is a promising scientific practice in recent era. Inspiring from the recurring trend, we propose a single step oxidative pyrolysis derived fluorescent carbon dots (C-dots) from Allium sativum peel, which is a natural, nontoxic, and waste raw material. Because of its excellent optical properties, and photostability this C-dots have been used in versatile area of applications. Due to its immediate water dispersing character, C-dots reinforced Poly(acrylic acid) (PAA) films revealed improvement in uniaxial stretching behavior and can be used as transparent sunlight conversion film. The nanocomposite film has been tested against rigorous simulated sunlight which proved almost identical sunlight conversion behavior with no photo-bleachable character which is definitely added an extra quality of transparent polymer films. Moreover, the C-dots dispersion has been used as in vitro biomarker for living cells owing to its ease in solubility, biocompatibility, non-cytotoxicity and bright fluorescence even in subcutaneous environment. For this case, adipose derived mesenchymal stem cells (ADMSCs) have been chosen and injected to rabbit ear skin to perform two-photon imaging experiment. The present work opens a new avenue towards the large-scale synthesis of bio-waste based fluorescent C-dots, paving the way for their versatile applications.


Assuntos
Allium/química , Nitrogênio/química , Fotodegradação/efeitos da radiação , Pontos Quânticos/química , Enxofre/química , Luz Solar , Resinas Acrílicas/química , Tecido Adiposo/citologia , Allium/metabolismo , Animais , Materiais Biocompatíveis/química , Carbono/química , Sobrevivência Celular/efeitos dos fármacos , Frutas/química , Frutas/metabolismo , Química Verde , Masculino , Células-Tronco Mesenquimais/citologia , Células-Tronco Mesenquimais/efeitos dos fármacos , Células-Tronco Mesenquimais/metabolismo , Microscopia de Fluorescência , Pontos Quânticos/toxicidade , Coelhos , Pele/efeitos dos fármacos , Pele/patologia , Solubilidade
10.
J Photochem Photobiol B ; 197: 111538, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31247385

RESUMO

The effects of topically administered snake (Deinagkistrodon acutus) oil and its main fatty acid components on skin photodamage were explored. Epidermal thickness, mice body weight, antioxidant enzymes (superoxide dismutase, glutathione peroxidase, catalase), inflammatory cytokines (tumor necrosis factor alpha and interleukin-6), skin histology, collagen content, and metalloproteinase-1 indicators were analyzed. The results show that topical application of both snake oil and its main fatty acids recovered ultraviolet B (UVB) irradiation induced antioxidant enzymes depletion, prevented metalloproteinase-1. Snake oil and its main fatty acids suppressed dermal infiltration of inflammatory cells and reduced inflammatory cytokines levels. Notably, there was no significant difference in the antioxidant activity but a significant difference in the anti-inflammatory activity between fatty acids and snake oil under the same dose. Finally, snake oil and its main fatty acids inhibited UVB-induced histological damage such as epidermal thickening, collagen fiber and elastic fiber destruction. Our study demonstrated for the first time in KM mice that snake oil exhibited prominent photoprotection activity by protecting the activity of antioxidant enzymes and inhibiting inflammatory factors, as well as reducing the generation of MMP-1. What's more, the main fatty acids in snake oil play an important role in preventing photo-damage especially in protecting antioxidant enzyme activity.


Assuntos
Anti-Inflamatórios/farmacologia , Ácidos Graxos/farmacologia , Óleos Voláteis/química , Pele/efeitos dos fármacos , Serpentes/metabolismo , Raios Ultravioleta , Animais , Anti-Inflamatórios/química , Antioxidantes/metabolismo , Catalase/metabolismo , Citocinas/metabolismo , Epiderme/fisiologia , Ácidos Graxos/química , Feminino , Cromatografia Gasosa-Espectrometria de Massas , Glutationa Peroxidase/metabolismo , Hidroxiprolina/análise , Interleucina-6/genética , Interleucina-6/metabolismo , Metaloproteinase 1 da Matriz/metabolismo , Camundongos , Pele/metabolismo , Pele/patologia , Pele/efeitos da radiação , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/metabolismo
11.
Pharm Res ; 36(8): 122, 2019 Jun 19.
Artigo em Inglês | MEDLINE | ID: mdl-31218556

RESUMO

PURPOSE: A non-propellant based foam (NPF) system was developed incorporating the antibiotics, pectin capped green nano-silver and sulfadiazine (SD) for the topical treatment of burn wounds as a convenient alternative to the existing therapies. METHODS: NPF were prepared using various surfactants and oils forming a nanoemulsion. Anti-microbial studies by resazurin microtitre assay, ex vivo diffusion, in vivo skin permeation and deposition studies, and acute irritation studies were carried out. NPF was applied onto secondary thermal wounds manifested on mice models followed by macroscopic and histological examinations. RESULTS: NPF had an average globule size of <75 nm. The viscosity was ~10 cP indicating the feasibility of expulsion from the container upon actuation. With no skin irritation, the foams showed a higher skin deposition of SD. A high contraction and an evident regeneration of the skin tissue upon treatment with NPF indicated a good recovery from the thermal injury was apparent from the histology studies. CONCLUSION: NPF represents an alternative topical formulation that can be employed as a safe and effective treatment modality for superficial second degree (partial thickness) burn wounds. With a minimal requirement of mechanical force, the no-touch application of NPF makes it suitable for sensitive and irritant skin surfaces.


Assuntos
Antibacterianos/farmacologia , Queimaduras/tratamento farmacológico , Nanopartículas Metálicas/química , Prata/química , Sulfadiazina/farmacologia , Cicatrização/efeitos dos fármacos , Administração Tópica , Animais , Antibacterianos/administração & dosagem , Queimaduras/patologia , Queimaduras/fisiopatologia , Composição de Medicamentos/métodos , Quimioterapia Combinada , Emulsões , Escherichia coli/efeitos dos fármacos , Química Verde , Humanos , Masculino , Camundongos , Óleos/química , Tamanho da Partícula , Permeabilidade , Pele/efeitos dos fármacos , Pele/patologia , Pele/fisiopatologia , Staphylococcus aureus/efeitos dos fármacos , Sulfadiazina/administração & dosagem , Tensoativos/química
12.
Nat Commun ; 10(1): 2730, 2019 06 21.
Artigo em Inglês | MEDLINE | ID: mdl-31227691

RESUMO

Recently our groups discovered lugdunin, a new cyclic peptide antibiotic that inhibits Staphylococcus aureus epithelial colonization in humans and rodents. In this work, we analyzed its immuno-modulatory and antimicrobial potential as a single agent or in combination with other microbiota- or host-derived factors. We show that pretreatment of primary human keratinocytes or mouse skin with lugdunin in combination with microbiota-derived factors results in a significant reduction of S. aureus colonization. Moreover, lugdunin increases expression and release of LL-37 and CXCL8/MIP-2 in human keratinocytes and mouse skin, and results in the recruitment of monocytes and neutrophils in vivo, both by a TLR/MyD88-dependent mechanism. Interestingly, S. aureus elimination by lugdunin is additionally achieved by synergistic antimicrobial activity with LL-37 and dermcidin-derived peptides. In summary, our results indicate that lugdunin provides multi-level protection against S. aureus and may thus become a promising treatment option for S. aureus skin infections in the future.


Assuntos
Antibacterianos/farmacologia , Imunidade Inata/efeitos dos fármacos , Peptídeos Cíclicos/farmacologia , Infecções Estafilocócicas/tratamento farmacológico , Staphylococcus aureus/efeitos dos fármacos , Tiazolidinas/farmacologia , Animais , Antibacterianos/uso terapêutico , Peptídeos Catiônicos Antimicrobianos/imunologia , Células Cultivadas , Modelos Animais de Doenças , Feminino , Humanos , Queratinócitos/efeitos dos fármacos , Queratinócitos/imunologia , Queratinócitos/microbiologia , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Microbiota/efeitos dos fármacos , Microbiota/imunologia , Peptídeos/imunologia , Peptídeos Cíclicos/uso terapêutico , Cultura Primária de Células , Pele/efeitos dos fármacos , Pele/imunologia , Pele/microbiologia , Infecções Estafilocócicas/imunologia , Infecções Estafilocócicas/microbiologia , Tiazolidinas/uso terapêutico
13.
J Immunoassay Immunochem ; 40(4): 439-447, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31204576

RESUMO

The beneficial effects promoted from the use of biomolecular substances into the formulations of personal care products are considered useful ingredients in cosmetic and therapeutic applications. Innovations in cosmetics are based on new bioactive formulations such as vitamins, oils, peptides, and protein hydrolysates. In skin care, the monomeric amino acids such as serine, threonine, alanine are common ingredients in cosmetics as they function as natural moisturizing factors which act as water-binding molecules. Amino acids and their salts e.g., arginine, glycine, etc. are also used as hair- and skin-conditioning agents in cosmetic formulations. The peptides are composed of short chain of amino acids and are used in cosmetics due to their numerous pathophysiological properties including anti-aging. There is growing interest in bioactive peptides in products for stimulating collagen and elastin synthesis in skin and improve surface healing. The main benefit of using proteins in cosmeceuticals is to improve the hydration of skin. Proteins increase the dehydration in the skin which helps to reduce wrinkles and improves the functions of the skin barrier. This review article describes the peptides, proteins that are most frequently used in cosmeceuticals and their potential benefits and practical use in cosmetic science and skincare.


Assuntos
Cosmecêuticos/química , Cosmecêuticos/farmacologia , Peptídeos/análise , Proteínas/análise , Rejuvenescimento/fisiologia , Higiene da Pele/métodos , Pele/efeitos dos fármacos , Animais , Cosmecêuticos/uso terapêutico , Técnicas Cosméticas , Humanos , Peptídeos/farmacologia , Peptídeos/uso terapêutico , Proteínas/farmacologia , Proteínas/uso terapêutico , Pele/imunologia , Pele/patologia
14.
AAPS PharmSciTech ; 20(5): 212, 2019 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-31165303

RESUMO

Psoriasis is an autoimmune disorder disease with pink-colored plaques and excessive proliferation which is hard to be cured completely. The study focuses on the anti-psoriatic efficacy of O/O paclitaxel ointment which can promote the assembly of microtubules and lead to death of overproliferation cells of the psoriasis epidermal. A high-speed shearing method was adopted in preparing the ointment, in which propylene carbonate was used as the internal oil phase to solve paclitaxel completely. It was characterized by the appearance, particle size, rheological behavior, and in vitro release. The amount of paclitaxel retained in normal skin and psoriatic skin was 1.00 ± 0.50 versus 1.53 ± 0.48 µg/g for 0.03% PTX ointment, 1.30 ± 0.39 versus 2.77 ± 0.49 µg/g for 0.1% PTX ointment, and 2.22 ± 0.92 versus 6.65 ± 0.87 µg/g for 0.3% PTX ointment, respectively, which implied that paclitaxel could better retain in inflamed skin than in normal skin; also the amount of drug retained in the skin was proportional to drug content. Paclitaxel ointment displayed good topical tolerance after repeated application on normal mice skin. The therapeutic efficacy of paclitaxel ointment was evaluated with an imiquimod-induced psoriatic model. A significant improvement has been shown both in the phenotypic and histopathological features of psoriatic skin treated with the ointment. There was also a significant reduction in the epidermal thickness compared to the imiquimod group. The findings confirm that the O/O PTX ointment without any surfactant appears to be a promising approach for the treatment of psoriasis.


Assuntos
Paclitaxel/uso terapêutico , Psoríase/tratamento farmacológico , Administração Tópica , Animais , Humanos , Imiquimode/efeitos adversos , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Pomadas , Paclitaxel/administração & dosagem , Tamanho da Partícula , Psoríase/induzido quimicamente , Pele/efeitos dos fármacos , Tensoativos
15.
Int J Nanomedicine ; 14: 2485-2495, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31040670

RESUMO

Background: Triamcinolone acetonide (TAA) is an effective and the most commonly used corticosteroid hormone for the treatment of hypertrophic scars (HSs). However, the clinically used dosage has poor tissue permeability and injection safety. By contrast, lipid nanoparticles (LNPs) have the advantage of high affinity for the skin. Materials and methods: This article describes the preparation of TAA-LNPs using poly(lactic-co-glycolic acid) as a carrier material, which have good biocompatibility and biodegradability. Based on a systematic investigation of its physicochemical properties, a rabbit ear HSs model was established to evaluate the percutaneous permeability of TAA-LNPs in scar tissue in vitro as well as to assess its curative effect and skin irritation. Results: The results showed that the TAA-LNPs formed uniform and round particles under fluoroscopy and had a complex structure in which a nanoparticle core was surrounded by multiple vesicles. The particles were 232.2±8.2 nm in size, and the complimentary potential was -42.16 mV. The encapsulation efficiency was 85.24%, which is greater than that of other common liposomes and nanoparticles. A test of in vitro scar tissue permeability showed that penetration into scar tissue was twofold and 40-fold higher for TAA-LNPs than for common liposome and commercial suspensions, respectively. The concentration of the absorbed drug effectively inhibited fibroblast proliferation, achieved a therapeutic effect in HSs, and did not stimulate intact or damaged skin. Conclusion: The preparation of TAA into LNPs for transdermal administration can enhance transdermal permeation performance and the safety of this drug, which is beneficial for the treatment of HSs.


Assuntos
Lipídeos/química , Nanopartículas/química , Triancinolona Acetonida/administração & dosagem , Triancinolona Acetonida/farmacologia , Administração Cutânea , Animais , Cicatriz/patologia , Orelha/patologia , Fluorescência , Lipossomos , Masculino , Nanopartículas/ultraestrutura , Tamanho da Partícula , Permeabilidade , Coelhos , Rodaminas/metabolismo , Pele/efeitos dos fármacos , Absorção Cutânea/efeitos dos fármacos , Testes de Irritação da Pele
16.
BMC Neurol ; 19(1): 88, 2019 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-31053120

RESUMO

BACKGROUND: Cholinesterase inhibitors remain the first line therapy for people with mild to moderate Alzheimer's disease (AD). Response is modest and difficult to predict from pre-treatment characteristics. We hypothesise that skin vascular response to iontophoresis of acetylcholine, which is partly determined by the level of cholinesterase activity, may be a pre-treatment measure that could predict response to therapy. METHODS: Twenty-four people with probable AD underwent iontophoresis of acetylcholine to the volar surface of the forearm skin prior to treatment with a cholinesterase inhibitor. The peak skin vascular response and the resolution to baseline levels were measured using laser Doppler perfusion imaging. Response to treatment was assessed after 6 months using criteria from the National Institute for Health and Care Excellence (NICE) and iontophoresis with acetylcholine was repeated. Blindness between clinical and laboratory assessments was maintained. RESULTS: Fourteen out of twenty-four people responded to treatment using NICE criteria. By comparison to non-responders, responders to treatment had a faster resolution to baseline from acetylcholine-induced vasodilation prior to treatment, which slowed with treatment. In this pilot study there was a high level of accuracy in the classification of response using this variable. No baseline cognitive or functional measures discriminated end-point responders from non-responders. CONCLUSION: Cholinesterase inhibitors are well tolerated but the number of people with adverse effects would be reduced if it was possible to predict response. The role of vasodilator response to acetylcholine and recovery as a potential biomarker for efficacy of treatment should now be evaluated and may possibly be of relevance in stratifying samples for interventional studies in AD and other forms of dementia. We feel that a more definitive study is now justified.


Assuntos
Acetilcolina/farmacologia , Doença de Alzheimer/classificação , Doença de Alzheimer/tratamento farmacológico , Inibidores da Colinesterase/uso terapêutico , Pele/efeitos dos fármacos , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Iontoforese , Masculino , Projetos Piloto , Vasodilatadores/farmacologia
17.
Drugs Aging ; 36(5): 411-417, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-31037642

RESUMO

Increased aging of the general population is a well-known fact with serious effects on health systems worldwide. Skin aging involves various immunological and structural changes that increase the risk of numerous skin diseases such as contact dermatitis. Contact dermatitis is characterized by an inflammation of the skin caused by an interaction between the skin and external agents and is divided into irritant and allergic contact dermatitis. Irritant contact dermatitis occurs on skin areas directly exposed to irritant substances, which results in a stream of pro-inflammatory cytokines mediating the skin injury. Asteatotic and perineal irritant contact dermatitis are the most important subtypes of irritant contact dermatitis in the elderly. Allergic contact dermatitis is a T cell-mediated inflammatory reaction and requires a prior sensitization. The most common allergens responsible for allergic contact dermatitis in the elderly are fragrance mix, nickel, and balsam of Peru. Elderly patients with stasis dermatitis, chronic wounds, and chronic venous insufficiency have an increased prevalence of sensitization due to the frequent exposure to topical treatments. In this review, the most common types of contact dermatitis in the elderly are enumerated in order to assist dermatologists and other physicians to identify contact dermatitis in this distinct group of the population.


Assuntos
Envelhecimento/efeitos dos fármacos , Alérgenos/toxicidade , Dermatite Alérgica de Contato/etiologia , Dermatite Irritante/etiologia , Pele/efeitos dos fármacos , Idoso , Envelhecimento/efeitos da radiação , Dermatite Alérgica de Contato/imunologia , Dermatite Alérgica de Contato/terapia , Dermatite Irritante/imunologia , Dermatite Irritante/terapia , Gerenciamento Clínico , Feminino , Humanos , Masculino , Prevalência , Fatores de Risco , Pele/efeitos da radiação
18.
Int J Mol Sci ; 20(9)2019 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-31067675

RESUMO

BACKGROUND: We have characterized a new reconstructed full-thickness skin model, T-Skin™, compared to normal human skin (NHS) and evaluated its use in testing anti-aging compounds. METHODS: The structure and layer-specific markers were compared with NHS using histological and immunohistological staining. In anti-aging experiments, T-SkinTM was exposed to retinol (10 µM) or vitamin C (200 µM) for 5 days, followed by immunohistological staining evaluation. RESULTS: T-Skin™ exhibits a well stratified, differentiated and self-renewing epidermis with a dermal compartment of functional fibroblasts. Epidermal (cytokeratin 10, transglutaminase 1), dermo-epidermal junction (DEJ) (laminin 5, collagen-IV, collagen VII) and dermally-located (fibrillin 1, procollagen I) biomarkers were similar to those in NHS. Treatment of T-Skin™ with retinol decreased the expression of differentiation markers, cytokeratin 10 and transglutaminase 1 and increased the proliferation marker, Ki67, in epidermis basal-layer cells. Vitamin C increased the expression of DEJ components, collagen IV and VII and dermal procollagen 1. CONCLUSIONS: T-Skin™ exhibits structural and biomarker location characteristics similar to NHS. Responses of T-Skin™ to retinol and vitamin C treatment were consistent with those of their known anti-aging effects. T-Skin™ is a promising model to investigate responses of epidermal, DEJ and dermal regions to new skin anti-ageing compounds.


Assuntos
Ácido Ascórbico/farmacologia , Envelhecimento da Pele , Pele/efeitos dos fármacos , Vitamina A/farmacologia , Vitaminas/farmacologia , Moléculas de Adesão Celular/metabolismo , Diferenciação Celular , Proliferação de Células , Células Cultivadas , Colágeno/metabolismo , Fibrilina-1/metabolismo , Fibroblastos/citologia , Fibroblastos/efeitos dos fármacos , Humanos , Queratina-10/metabolismo , Queratinócitos/efeitos dos fármacos , Pele/citologia
19.
Eur J Pharm Sci ; 135: 22-31, 2019 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-31078643

RESUMO

Radiation induced fibrosis is a common side-effect after radiotherapy. Pentoxifylline is reported to reverse radiation injuries when used in conjunction with D-α-tocopherol. However, pentoxifylline has a short half-life, limited oral bioavailability, and induces several systemic adverse effects. The objective of this study was to investigate the feasibility of using Er:YAG fractional laser ablation to enable simultaneous cutaneous delivery of pentoxifylline and D- α -tocopherol succinate from poly(lactide-co-glycolide) microparticles prepared using the freeze-fracture technique. In vitro release experiments demonstrated the different release profiles of the two molecules, which were influenced by their very different lipophilicities and aqueous solubilities. Experiments were then performed to investigate the effect of laser fluence on pore depth and so determine the pore volume available to host the topically applied microparticles. Application of the pentoxifylline and D-α-tocopherol succinate containing microparticles, prepared with RESOMER® RG 502H, to laser porated skin for 48 h, resulted in simultaneous delivery of pentoxifylline (69.63 ±â€¯6.41 µg/cm2; delivery efficiency 46.4%) and D-α-tocopherol succinate (33.25 ±â€¯8.91 µg/cm2; delivery efficiency 22.2%). After deposition into the micropores, the poly(lactide-co-glycolide) microparticles containing pentoxifylline and D-α-tocopherol succinate could serve as an intraepidermal depot to enable sustained drug delivery after micropore closure and thereby reduce the need for repeated microporation.


Assuntos
Lasers de Estado Sólido , Pentoxifilina/administração & dosagem , Lesões Experimentais por Radiação/tratamento farmacológico , Protetores contra Radiação/administração & dosagem , alfa-Tocoferol/administração & dosagem , Administração Cutânea , Animais , Portadores de Fármacos , Liberação Controlada de Fármacos , Quimioterapia Combinada , Fibrose , Técnicas In Vitro , Microesferas , Poliglactina 910/química , Porosidade , Pele/efeitos dos fármacos , Pele/efeitos da radiação , Suínos
20.
SAR QSAR Environ Res ; 30(6): 447-455, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31124730

RESUMO

The Index of Ideality of Correlation (IIC) is a new criterion of the predictive potential for quantitative structure-property/activity relationships. The value of the IIC is a mathematical function sensitive to the value of the correlation coefficient and dispersion (expressed via mean absolute error). The IIC has been applied to develop QSAR models for skin sensitization achieving good predictive potential. The 'ideal correlation' is based on elementary fragments of simplified molecular input-line entry system (SMILES) and on the taking into account of the total numbers of nitrogen, oxygen, sulphur and phosphorus in the molecule.


Assuntos
Dermatite Alérgica de Contato/etiologia , Relação Quantitativa Estrutura-Atividade , Pele/efeitos dos fármacos , Cosméticos/química , Cosméticos/toxicidade , Humanos , Modelos Moleculares , Método de Monte Carlo , Compostos Orgânicos/química , Compostos Orgânicos/toxicidade , Pele/patologia , Software
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA