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1.
Front Endocrinol (Lausanne) ; 13: 846137, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35370980

RESUMO

The increasing use of technological devices for the management of diabetes is related to the prolonged exposure of patients' skin to chemical and mechanical agents and, consequently, to the increased risk of developing dermatological complications. Among these, contact dermatitis is the most insidious skin disorder. Despite the magnitude of the issue, no universally accepted recommendations on the management of this common complication are currently available. Our observational study aimed to describe all the solutions adopted by patients and their caregivers to treat and prevent the appearance of contact dermatitis and to describe the clinical impact of this cutaneous complication. Twenty-one pediatric patients (mean age 12.1 ± 3.7 years) with type 1 diabetes were recruited in the study. The most common treatment used to treat acute skin lesions was the application of topical corticosteroids, sometimes associated with topical antibiotics (9.5%). In order to prevent the further appearance of dermatitis, the most frequently adopted measure was the use of hydrocolloid and/or silicone-based adhesives, followed by the application of protective barrier films. One patient reported benefit from the off-label use of fluticasone propionate nasal spray. However, only 52.4% of the study participants achieved a definitive resolution of the skin issue, and 38.1% of patients were forced to discontinue insulin pump therapy and/or continuous glucose monitoring. No differences were observed in glycated hemoglobin values between the period before and after the onset of contact dermatitis. Our study confirms the severity of this dermatological complication that may hinder the spread of new technologies for the management of diabetes. Finally, our findings highlight the importance of establishing close collaboration both with pediatric allergy specialists to prescribe the most suitable treatment and with manufacturing companies to ensure that adhesives of technological devices are free of harmful well-known sensitizers.


Assuntos
Dermatite de Contato , Diabetes Mellitus Tipo 1 , Adolescente , Glicemia , Automonitorização da Glicemia , Criança , Dermatite de Contato/tratamento farmacológico , Dermatite de Contato/etiologia , Diabetes Mellitus Tipo 1/complicações , Diabetes Mellitus Tipo 1/tratamento farmacológico , Humanos , Sistemas de Infusão de Insulina/efeitos adversos
2.
PLoS One ; 17(3): e0265615, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35312729

RESUMO

The medicinal mushroom Ganoderma lucidum is traditionally used for treating multiple diseases, including cancer. This study examined skin cancer preventive activity of a commercial product containing spore and fruiting body in 30:8 ratio (GLSF). Extracts of GLSF and spore component (GLS) were prepared using artificial gastrointestinal juice and examined on JB6 cells. GLSF and GLS dose-dependently inhibited epidermal growth factor-induced JB6 transformation at non-toxic concentrations. SKH-1 mice which were fed with diets containing GLSF (1.25%), GLS (0.99%) or the fruiting body (GLF) (0.26%) were exposed to chronic low-dose ultraviolet (UV) radiation to assess their effects on skin carcinogenesis. GLSF, but not GLS or GLF, reduced skin tumor incidence and multiplicity. In non-tumor skin tissues of mice, GLSF attenuated UV-induced epidermal thickening, expression of Ki-67, COX-2 and NF-κB, while in tumor tissues, GLSF increased expression of CD8 and Granzyme B. To examine the effects of GLSF on UV-induced immunosuppression, mice which were fed with GLSF were evaluated for the contact hypersensitivity (CHS) response to dinitrofluorobenzene (DNFB). GLSF significantly reversed UV-mediated suppression of DNFB-induced CHS by increasing CD8+ and decreasing CD4+ and FoxP3+ T-cells in mouse ears. Therefore, GLSF prevents skin cancer probably via attenuating UV-induced immunosuppression.


Assuntos
Agaricales , Dermatite de Contato , Reishi , Neoplasias Cutâneas , Animais , Carcinogênese , Dinitrofluorbenzeno , Camundongos , Pele/patologia , Neoplasias Cutâneas/etiologia , Neoplasias Cutâneas/patologia , Neoplasias Cutâneas/prevenção & controle , Raios Ultravioleta/efeitos adversos
3.
J Vis Exp ; (181)2022 03 10.
Artigo em Inglês | MEDLINE | ID: mdl-35343948

RESUMO

Parallel to traditional Th1/Th2/Th17/Treg lineages, granulocyte-macrophage colony-stimulating factor-producing T helper (Th-GM) cells have been identified as a distinct subset of T helper cells (GM-CSF+ IFN-γ- IL-17A- IL-22- effector CD4+ T cells) in human and mice. Contact hypersensitivity (CHS) is considered an excellent animal model for allergic contact dermatitis (ACD) in human, manifesting an intact T cell-mediated immune response. To provide a standardized and comprehensive assay to analyze the Th-GM cell subset in the T cell-dependent immune response in vivo, a murine CHS model was induced by sensitization/challenge with a reactive, low-molecular-weight, organic hapten, 2,4-dinitrofluorobenzene (DNFB). The Th-GM subset in effector CD4+ T cells generated upon immunization with the hapten was analyzed by flow cytometry. We found that Th-GM was mainly expanded in lesions and draining lymph nodes in the DNFB-induced CHS mouse model. This method can be applied to further study the biology of Th-GM cells and pharmacological research of therapeutic strategies centered on GM-CSF in various conditions, such as ACD.


Assuntos
Dermatite de Contato , Fator Estimulador de Colônias de Granulócitos e Macrófagos , Animais , Haptenos , Camundongos , Linfócitos T Reguladores , Células Th17
4.
Poult Sci ; 101(4): 101768, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35245808

RESUMO

In this study, the mobility, incidence, and severity of contact dermatitis and litter moisture content were assessed in 14 strains of broiler chickens differing in growth rate. The strains encompassed 2 conventional (CONV; ADG0-48 > 60 g/d) and 12 slower growing (SG) strains categorized as FAST (ADG0-62 = 53-55 g/d), MOD (ADG0-62 = 50-51 g/d), and SLOW (ADG0-62 < 50 g/d), with 4 strains in each category. A total of 7,216 mixed-sex birds were equally allocated into 164 pens (44 birds/pen; 30 kg/m2) in a randomized incomplete block design, with each strain represented in 8 to 12 pens over 2-3 trials. From each pen, 4 to 6 birds were tested in the latency-to-lie (LTL) and group obstacle tests 1 wk prior to the birds reaching 2 target weights (TWs) of approximately 2.1 kg (TW1: 34 d for CONV and 48 d for SG strains) and 3.2 kg (TW2: 48 d for CONV and 62 d for SG strains). The incidence of footpad dermatitis (FPD) and hock burns (HB) were evaluated a day prior to each TW. Litter moisture content was determined biweekly from d 14 to d 56. At TW1, CONV and SLOW had longer LTL than FAST birds. At TW2, CONV, MOD, and FAST birds had similar LTL. At both TWs, CONV birds were lighter than FAST birds in the group obstacle test, yet their number of obstacle crossings was similar. At TW1, CONV birds had greater incidence of FPD than FAST and MOD, while at TW2, CONV birds had greater incidence than the other categories. The incidence of HB in CONV and MOD was greater than SLOW birds at TW1, while at TW2, the incidence of HB was greater in CONV and FAST birds vs. MOD and SLOW birds. Litter moisture content was high in all categories from d 28 onward. Our results indicate that both BW and growth rate influence leg strength and walking ability, whereas the overall high litter moisture content and to a lesser extent growth rate influenced the incidence of contact dermatitis.


Assuntos
Dermatite de Contato , Doenças das Aves Domésticas , Animais , Galinhas , Dermatite de Contato/epidemiologia , Dermatite de Contato/etiologia , Dermatite de Contato/veterinária , Dieta/veterinária , Incidência , Doenças das Aves Domésticas/epidemiologia , Doenças das Aves Domésticas/etiologia , Caminhada
5.
J Immunol ; 208(6): 1424-1433, 2022 03 15.
Artigo em Inglês | MEDLINE | ID: mdl-35197329

RESUMO

NF-erythroid 2-related factor 2 (Nrf2) is a major transcription factor to protect cells against reactive oxygen species (ROS) and reactive toxicants. Meanwhile, Nrf2 can inhibit contact dermatitis through redox-dependent and -independent pathways. However, the underlying mechanisms of how Nrf2 mediates irritant contact dermatitis (ICD) are still unclear. In this article, we elucidated the role of Nrf2 in 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced acute ICD. Our study demonstrated that the ear thickness, redness, swelling, and neutrophil infiltration were significantly increased, accompanied by increased expression of inflammatory cytokines (IL-1α, IL-1ß, IL-6, etc.) and decreased expression of antioxidant genes (HO-1 and NQO1) in Nrf2 knockout mice. Moreover, ERK phosphorylation was elevated in mouse embryonic fibroblasts (MEFs) from Nrf2 knockout mouse. Inhibition of ERK significantly alleviated TPA-induced cutaneous inflammation and ROS accumulation in MEFs derived from mouse. Conversely, ROS scavenging inhibited the ERK activation and TPA-induced inflammation in MEFs. Taken together, the findings illustrate the key role of the Nrf2/ROS/ERK signaling pathway in TPA-induced acute ICD.


Assuntos
Dermatite de Contato , Fator 2 Relacionado a NF-E2 , Animais , Fibroblastos/metabolismo , Fator de Transcrição de Proteínas de Ligação GA/metabolismo , Heme Oxigenase-1/metabolismo , Inflamação , Irritantes , Camundongos , Camundongos Knockout , Fator 2 Relacionado a NF-E2/genética , Fator 2 Relacionado a NF-E2/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Transdução de Sinais , Acetato de Tetradecanoilforbol
6.
Molecules ; 27(4)2022 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-35209219

RESUMO

Nickel-induced contact dermatitis is a severe allergic reaction to objects or environments that contain nickel. Many nanomaterials have been developed to reduce skin allergies by capturing nickel, but few agents are effective and safe. In this work, mesoporous silica nanoparticles (MSN) were synthesized and decorated with hexa-histidine peptides (denoted as MSN-His6), making it a strong nickel chelator. Subsequently, a dietary polyphenol, chlorogenic acid, was loaded into the mesopores of MSN (denoted as MSN-His6@CGA), realizing the potential of its anti-inflammatory properties. In vitro and in vivo experiments revealed that the synthesized MSN-His6@CGA nanoparticles exhibited more stable and stronger chelation, better biocompatibility, and ideal allergy-relieving ability, whether for environmental metal contamination or for allergic contact dermatitis caused by prolonged nickel exposure. Thus, the application of mesoporous silica-based nanoparticles may represent an ideal approach to alleviate skin allergies by capturing nickel, which would benefit people who suffer from metal-induced contact dermatitis.


Assuntos
Ácido Clorogênico/química , Dermatite de Contato/etiologia , Dermatite de Contato/terapia , Histidina/química , Nanopartículas/química , Níquel/efeitos adversos , Dióxido de Silício/química , Adsorção , Antialérgicos/administração & dosagem , Antialérgicos/química , Anti-Inflamatórios/administração & dosagem , Anti-Inflamatórios/química , Sobrevivência Celular/efeitos dos fármacos , Quelantes , Fenômenos Químicos , Técnicas de Química Sintética , Ácido Clorogênico/administração & dosagem , Humanos , Estrutura Molecular , Níquel/química , Porosidade
7.
Pediatr Dermatol ; 39(2): 320-321, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-35014095

RESUMO

Contact dermatitis usually presents as erythematous macules, papules, and vesicles. Sometimes, unusual clinical presentations of contact dermatitis are reported, including pustular, lymphomatoid, lichenoid, and pigmented variants. We describe the first patient with bullous irritant contact dermatitis caused by perfume, mimicking impetigo lesions. We report this case to raise awareness concerning the possibility of serious cutaneous reactions, such as bullous impetigo-like irritant contact dermatitis due to perfumes which are ubiquitous, especially after direct contact with the solution. Perfume ingredients, such as fragrance, solvents, and preservatives all may cause or contribute to irritant contact dermatitis.


Assuntos
Dermatite Alérgica de Contato , Dermatite de Contato , Dermatite Irritante , Impetigo , Perfumes , Lesões dos Tecidos Moles , Dermatite Alérgica de Contato/etiologia , Dermatite de Contato/etiologia , Dermatite Irritante/diagnóstico , Dermatite Irritante/tratamento farmacológico , Dermatite Irritante/etiologia , Humanos , Impetigo/diagnóstico , Impetigo/tratamento farmacológico , Irritantes
9.
J Immunol ; 208(3): 633-641, 2022 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-35031579

RESUMO

Calcitonin gene-related peptide (CGRP) can bias the outcome of Ag presentation to responsive T cells in vitro away from Th1-type immunity and toward the Th2 and Th17 poles through actions on endothelial cells (ECs). To test the in vivo significance of this observation, we engineered a mouse lacking functional CGRP receptors on ECs (EC receptor activity modifying protein 1 [RAMP1] knockout mice). On percutaneous immunization to 1-fluoro-2,4-dinitrobenzene, stimulated CD4+ T cells from draining lymph nodes showed significantly reduced IL-17A expression with significantly increased IFN-γ, IL-4, and IL-22 expression at the protein and mRNA levels compared with control mice. Retinoic acid receptor-related orphan receptor γ t mRNA was significantly reduced, while mRNAs for T-box expressed in T cells and GATA binding protein 3 were significantly increased. In addition, EC RAMP1 knockout mice had significantly reduced contact hypersensitivity responses, and systemic administration of a CGRP receptor antagonist similarly inhibited contact hypersensitivity in wild-type mice. These observations provide compelling evidence that CGRP is a key regulator of cutaneous immunity through effects on ECs and suggest a novel pathway for potential therapeutic manipulation.


Assuntos
Peptídeo Relacionado com Gene de Calcitonina/genética , Dermatite de Contato/imunologia , Células Endoteliais/imunologia , Proteína 1 Modificadora da Atividade de Receptores/genética , Pele/imunologia , Animais , Apresentação do Antígeno/imunologia , Peptídeo Relacionado com Gene de Calcitonina/metabolismo , Dinitrofluorbenzeno/imunologia , Fator de Transcrição GATA3/metabolismo , Interferon gama/biossíntese , Interleucina-17/biossíntese , Interleucina-4/biossíntese , Interleucinas/biossíntese , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Membro 1 do Grupo F da Subfamília 1 de Receptores Nucleares/genética , Células Th1/imunologia , Células Th17/imunologia , Células Th2/imunologia
12.
Int J Mol Sci ; 23(1)2022 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-35008942

RESUMO

Atopic dermatitis (AD) is a chronic inflammatory skin disease associated with excessive inflammation and defective skin barrier function. Activated protein C (APC) is a natural anticoagulant with anti-inflammatory and barrier protective functions. However, the effect of APC on AD and its engagement with protease activated receptor (PAR)1 and PAR2 are unknown. Methods: Contact hypersensitivity (CHS), a model for human AD, was induced in PAR1 knockout (KO), PAR2KO and matched wild type (WT) mice using 2,4-dinitrofluorobenzene (DNFB). Recombinant human APC was administered into these mice as preventative or therapeutic treatment. The effect of APC and PAR1KO or PARKO on CHS was assessed via measurement of ear thickness, skin histologic changes, inflammatory cytokine levels, Th cell phenotypes and keratinocyte function. Results: Compared to WT, PAR2KO but not PAR1KO mice displayed less severe CHS when assessed by ear thickness; PAR1KO CHS skin had less mast cells, lower levels of IFN-γ, IL-4, IL-17 and IL-22, and higher levels of IL-1ß, IL-6 and TGF-ß1, whereas PAR2KO CHS skin only contained lower levels of IL-22 and IgE. Both PAR1KO and PAR2KO spleen cells had less Th1/Th17/Th22/Treg cells. In normal skin, PAR1 was present at the stratum granulosum and spinosum, whereas PAR2 at the upper layers of the epidermis. In CHS, however, the expression of PAR1 and PAR2 were increased and spread to the whole epidermis. In vitro, compared to WT cells, PAR1KO keratinocytes grew much slower, had a lower survival rate and higher para permeability, while PAR2KO cells grew faster, were resistant to apoptosis and para permeability. APC inhibited CHS as a therapeutic but not as a preventative treatment only in WT and PAR1KO mice. APC therapy reduced skin inflammation, suppressed epidermal PAR2 expression, promoted keratinocyte growth, survival, and barrier function in both WT and PAR1KO cells, but not in PAR2KO cells. Conclusions: APC therapy can mitigate CHS. Although APC acts through both PAR1 and PAR2 to regulate Th and mast cells, suppression of clinical disease in mice is achieved mainly via inhibition of PAR2 alone. Thus, APC may confer broad therapeutic benefits as a disease-modifying treatment for AD.


Assuntos
Dermatite de Contato/metabolismo , Proteína C/metabolismo , Receptor PAR-2/genética , Pele/metabolismo , Animais , Dermatite de Contato/patologia , Dinitrofluorbenzeno/toxicidade , Feminino , Regulação da Expressão Gênica , Humanos , Inflamação , Camundongos , Camundongos Knockout , Receptor PAR-1/genética , Receptor PAR-2/metabolismo , Pele/patologia
13.
Molecules ; 27(2)2022 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-35056807

RESUMO

Cannabigerol (CBG) is a minor non-psychoactive cannabinoid present in Cannabis sativa L. (C. sativa) at low levels (<1% per dry weight) that serves as the direct precursor to both cannabidiol (CBD) and tetrahydrocannabinol (THC). Consequently, efforts to extract and purify CBG from C. sativa is both challenging and expensive. However, utilizing a novel yeast fermentation technology platform, minor cannabinoids such as CBG can be produced in a more sustainable, cost-effective, and timely process as compared to plant-based production. While CBD has been studied extensively, demonstrating several beneficial skin properties, there are a paucity of studies characterizing the activity of CBG in human skin. Therefore, our aim was to characterize and compare the in vitro activity profile of non-psychoactive CBG and CBD in skin and be the first group to test CBG clinically on human skin. Gene microarray analysis conducted using 3D human skin equivalents demonstrates that CBG regulates more genes than CBD, including several key skin targets. Human dermal fibroblasts (HDFs) and normal human epidermal keratinocytes (NHEKs) were exposed in culture to pro-inflammatory inducers to trigger cytokine production and oxidative stress. Results demonstrate that CBG and CBD reduce reactive oxygen species levels in HDFs better than vitamin C. Moreover, CBG inhibits pro-inflammatory cytokine (Interleukin-1ß, -6, -8, tumor necrosis factor α) release from several inflammatory inducers, such as ultraviolet A (UVA), ultraviolet B (UVB), chemical, C. acnes, and in several instances does so more potently than CBD. A 20-subject vehicle-controlled clinical study was performed with 0.1% CBG serum and placebo applied topically for 2 weeks after sodium lauryl sulfate (SLS)-induced irritation. CBG serum showed statistically significant improvement above placebo for transepidermal water loss (TEWL) and reduction in the appearance of redness. Altogether, CBG's broad range of in vitro and clinical skin health-promoting activities demonstrates its strong potential as a safe, effective ingredient for topical use and suggests there are areas where it may be more effective than CBD.


Assuntos
Anti-Inflamatórios/farmacologia , Canabinoides/biossíntese , Canabinoides/farmacologia , Fármacos Dermatológicos/farmacologia , Saccharomyces cerevisiae/genética , Anti-Inflamatórios/uso terapêutico , Antioxidantes/farmacologia , Antioxidantes/uso terapêutico , Canabidiol/farmacologia , Canabinoides/uso terapêutico , Células Cultivadas , Dermatite de Contato/tratamento farmacológico , Dermatite de Contato/etiologia , Fármacos Dermatológicos/uso terapêutico , Feminino , Regulação da Expressão Gênica/efeitos dos fármacos , Voluntários Saudáveis , Humanos , Inflamação/etiologia , Inflamação/prevenção & controle , Masculino , Modelos Biológicos , Propionibacteriaceae , Pele/efeitos dos fármacos , Envelhecimento da Pele/efeitos dos fármacos , Testes de Irritação da Pele , Dodecilsulfato de Sódio/toxicidade , Acetato de Tetradecanoilforbol/efeitos adversos , Análise Serial de Tecidos , Raios Ultravioleta/efeitos adversos
14.
J Nat Med ; 76(1): 144-151, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-34510369

RESUMO

Orengedokuto (OGT) is a Kampo prescription that has been used for the treatment of inflammation, hypertension, gastrointestinal disorders, and liver and cerebrovascular diseases. It is also used for the treatment of skin diseases such as urticaria and atopic dermatitis. We previously studied its anti-allergic effects of OGT on the murine model of 2,4,6-trinitrochlorobenzene (TNCB)-induced contact hypersensitivity (CHS) and demonstrated that it significantly suppresses ear swelling in a dose-dependent manner. However, the mechanism underlying this activity remained unknown. Here, we sought to identify the mechanism involved. Using a murine model of TNCB-induced CHS, together with adoptive cell transfer experiments, we found that the anti-allergic effects of OGT may be due to the inhibition of effector T cell activation and not the induction and/or activation of regulatory T cells. Flow cytometry analysis revealed that oral administration of OGT suppressed the increase in CD8+CD44highCD62L+ cell number in draining lymph nodes (dLNs) of mice sensitized with 5% TNCB. Additionally, ex vivo experiments confirmed the suppressive effect of OGT on the activation of effector T cells, as interferon-γ (IFN-γ) production by cultured lymphocytes obtained from 5% TNCB-sensitized mice and stimulated with anti-CD3ε and anti-CD28 monoclonal antibodies was reduced by OGT administration. In conclusion, our finding suggests that OGT exerts anti-allergic effects by regulating the activation of effector T cells involved in inflammatory skin diseases such as atopic dermatitis.


Assuntos
Antialérgicos , Dermatite de Contato , Animais , Dermatite de Contato/tratamento farmacológico , Modelos Animais de Doenças , Camundongos , Camundongos Endogâmicos C57BL , Linfócitos T
15.
Chem Biol Interact ; 351: 109751, 2022 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-34826398

RESUMO

p-phenylenediamine (PPD) is a common component of hair dye known to induce immediate allergy, even acute dermatitis and contact dermatitis. MAS-related G protein coupled receptor-X2 (MRGPRX2) in mast cells (MCs) mediates small molecular substances-induced pseudo-allergic reactions. However, the role of MRGPRX2 in PPD-induced immediate contact allergy needs further exploration. The aim of this study was to investigate whether PPD activates MCs via MRGPRX2 and induces immediate allergies that contribute to contact dermatitis. Wild-type (WT) and kitw-sh/w-sh mice (MUT) were treated with PPD to observe local inflammation and MC degranulation in vivo. The release of inflammatory mediators was measured in vitro. Histamine 1 receptor (H1R)-/- mice were used to analyze itch type. PPD caused immediate contact allergy in WT mice, induced scratching, and local inflammatory reactions, while exhibiting minimal effects on MUT mice. PPD did not induce histamine release, but induced significant tryptase release in vivo and in vitro. PPD activated MRGPRX2 to induce MC degranulation in vitro. PPD caused immediate contact allergy in WT mice, induced scratching and local inflammatory reactions, while exhibited minimal effect on MUT mice. PPD did not induce histamine release, while induced significant tryptase release in vivo and in vitro. PPD induced immediate contact allergy by MCs activation via MRGPRX2 and lead to tryptase release. The scratching times showed no significant difference in WT mice or H1R-/- mice, which indicated PPD caused non-histaminergic itch. The results showed that PPD activated MCs via MRGPRX2 and induced immediate contact allergy, leading to the release of tryptase without monoamine release, which might induce non-histaminergic itch.


Assuntos
Dermatite de Contato/etiologia , Hipersensibilidade Imediata/etiologia , Fenilenodiaminas/farmacologia , Receptores Acoplados a Proteínas G/metabolismo , Animais , Linhagem Celular , Dermatite de Contato/metabolismo , Dermatite de Contato/patologia , Técnicas de Silenciamento de Genes , Hipersensibilidade Imediata/metabolismo , Hipersensibilidade Imediata/patologia , Inflamação/induzido quimicamente , Inflamação/metabolismo , Inflamação/patologia , Masculino , Mastócitos/efeitos dos fármacos , Mastócitos/metabolismo , Camundongos Endogâmicos C57BL , Prurido/induzido quimicamente , Prurido/enzimologia , Prurido/metabolismo , Receptores Acoplados a Proteínas G/genética , Pele/efeitos dos fármacos , Pele/metabolismo , Pele/patologia , Triptases/metabolismo
16.
Regul Toxicol Pharmacol ; 128: 105088, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-34838871

RESUMO

The whole or ground seeds of the food ingredient Nigella sativa L., known in Western culture as "black cumin" or "black caraway", has a three-millennial history of use in Middle- and Far-Eastern cultures as a food ingredient. The seed and its extracts have also been increasingly reported as a successful therapeutic agent with efficacy often attributed to the presence of the powerful antioxidant, thymoquinone. However, quantitative analysis of the seed (especially the volatile fraction) yields widely variable results, which may be due to one or a combination of different crop origins or possible varietal differences, contamination/adulteration, method of extraction, stage of maturation of the extracted seed and other factors. Nonetheless, despite the reported wide variability in bioactive constituents, many publications cite quantifiable outcomes in in vitro and in vivo toxicity testing and in clinical trials. There are a few reports describing allergic reactions in humans when N. sativa extracts are applied to the skin. Notwithstanding the foregoing, N. sativa seeds, used as a food ingredient at historical levels of consumption and as traditionally practiced are safe and Generally Recognized As Safe.


Assuntos
Ingredientes de Alimentos/toxicidade , Nigella sativa/toxicidade , Animais , Dermatite de Contato/etiologia , Relação Dose-Resposta a Droga , Humanos , Camundongos , Nigella sativa/química , Nigella sativa/classificação , Nigella sativa/crescimento & desenvolvimento , Óleos Voláteis/administração & dosagem , Extratos Vegetais/farmacologia , Plantas Medicinais/química , Plantas Medicinais/classificação , Plantas Medicinais/toxicidade , Ratos , Sementes , Especiarias , Estados Unidos , United States Food and Drug Administration/normas
17.
Biochem Biophys Res Commun ; 586: 100-106, 2022 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-34837833

RESUMO

Lipopolysaccharide (LPS) is the principal component of the outer membrane of gram-negative bacteria. The prior oral administration of LPS attenuates inflammatory responses, such as intestinal injury and atopic dermatitis, in mouse models; however, the underlying mechanism remains unclear. Here, we examined the effect of topical LPS application on allergic contact dermatitis and its mechanism of action using a murine contact hypersensitivity (CHS) model. Prolonged LPS application to the skin significantly suppressed 2,4-dinitrofluorobenzene (DNFB)-induced CHS. LPS application to the skin also reduced the phagocytosis of fluorescein isothiocyanate (FITC)-dextran by Langerhans and dendritic cells. Cutaneous cell migration into the skin-draining lymph nodes (LNs) induced by FITC painting was reduced by LPS application. During the CHS response, DNFB application induced T-cell proliferation and inflammatory cytokine production in skin-draining LNs, whereas prolonged LPS application inhibited DNFB-induced T-cell growth and interferon gamma production, indicating suppression of DNFB-induced sensitization. These results suggest that prolonged LPS application suppressed DNFB-induced sensitization and subsequently CHS response. Our findings imply that topical application of LPS may prevent allergic dermatitis such as CHS.


Assuntos
Dermatite de Contato/tratamento farmacológico , Fatores Imunológicos/farmacologia , Lipopolissacarídeos/farmacologia , Linfócitos/efeitos dos fármacos , Pele/efeitos dos fármacos , Administração Cutânea , Animais , Linhagem Celular , Movimento Celular/efeitos dos fármacos , Células Dendríticas/citologia , Células Dendríticas/efeitos dos fármacos , Células Dendríticas/imunologia , Dermatite de Contato/etiologia , Dermatite de Contato/imunologia , Dermatite de Contato/patologia , Dextranos/metabolismo , Dinitrofluorbenzeno/administração & dosagem , Orelha , Fluoresceína-5-Isotiocianato/análogos & derivados , Fluoresceína-5-Isotiocianato/metabolismo , Queratinócitos/citologia , Queratinócitos/efeitos dos fármacos , Queratinócitos/imunologia , Células de Langerhans/citologia , Células de Langerhans/efeitos dos fármacos , Células de Langerhans/imunologia , Linfonodos/citologia , Linfonodos/efeitos dos fármacos , Linfonodos/imunologia , Ativação Linfocitária/efeitos dos fármacos , Linfócitos/citologia , Linfócitos/imunologia , Camundongos , Camundongos Endogâmicos C57BL , Fagocitose/efeitos dos fármacos , Cultura Primária de Células , Pele/imunologia , Pele/patologia
18.
Photodermatol Photoimmunol Photomed ; 38(2): 99-103, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-34328236

RESUMO

BACKGROUND: Photodermatoses are sun-related inflammatory skin diseases. They usually require phototesting in diagnosis. However, fewer and fewer medical centers in France are equipped with photobiological equipment. OBJECTIVES: The main purpose was to evaluate the relevance of phototesting in photodermatosis diagnosis. The second goal was to study the proportions of the different kinds of photodermatosis found in this particular study. METHODS: This study was descriptive, retrospective, and mono-centric. It was based on 100 consecutive patients, who have been phototested in a French University Hospital from 2014 to 2018. Phototesting included determination of the minimal erythematous dose (MED), UVA and UVB phototests, and photopatch testing. RESULTS: The use of phototesting led to 60% of photodermatosis diagnosis and formally eliminated the latter in 13% of the cases. The diagnosis remained undetermined in 27% of the cases. Nineteen cases of polymorphous light eruption (PLE), 14 cases of photocontact dermatitis (PCD), 10 cases of solar urticaria, 8 cases of photo-aggravated atopic eczema, 5 cases of chronic actinic dermatitis, and 2 cases of systemic photosensitization were diagnosed. The allergens involved in PCD were topical non-steroidal anti-inflammatory drug (NSAID) in 9 cases, sunscreens in 3 cases, and fragrance in 2 cases. The average amount of time between the first symptoms and actual phototesting was about 7,5 years. CONCLUSION: This study confirms phototesting is truly useful. PLE was the most common form of photodermatosis, followed by PCD and solar urticaria. As photodermatosis could imply severe diseases sometimes requiring hospitalization, it is critical to maintain this expertise.


Assuntos
Dermatite de Contato , Transtornos de Fotossensibilidade , Urticária , Humanos , Transtornos de Fotossensibilidade/diagnóstico , Estudos Retrospectivos , Protetores Solares , Urticária/diagnóstico , Urticária/etiologia
19.
J Invest Dermatol ; 142(1): 145-154.e8, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34310947

RESUMO

PD-1 is an immunoregulatory receptor that can bind PD-L1 or PD-L2 expressed on stimulated antigen-presenting cells. In this study, isolated antigen-presenting cells (macrophages and dendritic cells) were cultured with IFN-γ, IL-4, or IL-17A, and the expression of PD-L1 and PD-L2 was compared by flow cytometry. Strong upregulation of PD-L1 expression was observed on IFN-γ stimulation of both antigen-presenting cells as well as in response to IL-17A stimulation of macrophages compared with the expression in unstimulated controls. In contrast, only stimulation with IL-4 could upregulate PD-L2 expression on both antigen-presenting cells. Therefore, experiments were performed in murine models, including DNFB-induced contact hypersensitivity, calcipotriol-induced atopic dermatitis-like skin inflammation, and imiquimod-induced psoriasis-like dermatitis models, to trigger IFN-γ‒mediated T helper type (Th)1-, IL-4‒mediated Th2-, and IL-17A‒mediated Th17-type responses, respectively. In both Th1- and Th17-type immunity models, changes in ear thickness were more severe in Pd-l1‒deficient mice than in wild-type or Pd-l2‒deficient mice. In the Th2-type immunity model, changes in thickness in Pd-l2‒deficient mice were more severe than that in wild-type or Pd-l1‒deficient mice. Collectively, PD-L1 has predominant roles in Th1 and Th17 type immunity, whereas PD-L2 is involved in Th2-type immunity.


Assuntos
Antígeno B7-H1/metabolismo , Células Dendríticas/imunologia , Dermatite Atópica/imunologia , Dermatite de Contato/imunologia , Inflamação/imunologia , Macrófagos/imunologia , Proteína 2 Ligante de Morte Celular Programada 1/metabolismo , Psoríase/imunologia , Pele/patologia , Células Th1/imunologia , Células Th17/imunologia , Células Th2/imunologia , Animais , Apresentação do Antígeno , Antígeno B7-H1/genética , Calcitriol/análogos & derivados , Células Cultivadas , Citocinas/metabolismo , Dinitrofluorbenzeno , Modelos Animais de Doenças , Humanos , Imiquimode , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Proteína 2 Ligante de Morte Celular Programada 1/genética , Pele/imunologia
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