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1.
Medicine (Baltimore) ; 99(39): e22417, 2020 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-32991475

RESUMO

It has become evident that positron emission tomography/computed tomography (PET-CT) using 2-deoxy-2-[F-18]fluoro-D-glucose (FDG) (FDG PET-CT) can detect anti-tumor immune response induced by various immunotherapies. To evaluate whether FDG PET-CT could detect anti-cancer immune response caused by cancer vaccine therapy, we performed a retrospective analysis of FDG PET-CT imaging of patients who were treated with Wilms Tumor 1 (WT1) vaccine therapy in Osaka University during July 2008 and June 2018. Increased FDG uptakes were detected in WT1-vaccinated skin and their draining lymph nodes during the repeated vaccination. While the FDG uptakes seemed to decrease with time after the cessation of WT1 peptide vaccinations, persistence of FDG uptakes for years in WT1-vaccinated skin were also observed in 2 cases who showed good clinical course. Moreover, the FDG uptakes of patients treated with the combination vaccine of WT1 specific cytotoxic T cell (CTL) and helper peptides were significantly stronger than of those treated with the WT1 CTL peptide alone. Since it is evident that the combination vaccine can induce a more robust anti-tumor immunity than can CTL peptide vaccine alone, the FDG uptakes in WT1-vaccinated skin might reflect the degree of immune response. These results suggest that PET-CT might be a good tool for prediction of anti-tumor immune response induced by WT1 vaccine therapy. Larger scale prospective studies therefore seem to be warranted.


Assuntos
Vacinas Anticâncer , Fluordesoxiglucose F18/metabolismo , Tomografia Computadorizada com Tomografia por Emissão de Pósitrons , Pele/diagnóstico por imagem , Proteínas WT1/imunologia , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Pele/imunologia , Pele/metabolismo
2.
Hautarzt ; 71(10): 741-751, 2020 Oct.
Artigo em Alemão | MEDLINE | ID: mdl-32880662

RESUMO

Melanocortins are peptides that share a common central pharmacophor. Melanin pigmentation of interfollicular epidermis and hair via MC1R remains the key physiologic function of the naturally occurring melanocortin peptides in skin. Moreover, the melanocortins are crucially involved in the ultraviolet light-induced tanning response. Under pathophysiologic conditions, melanocortin peptides induce cutaneous hyperpigmentation, likewise via the MC1R axis, e.g. in patients with Addison's disease, ectopic precursor pro-opiomelanocortin (POMC) syndrome and in those with abnormally elevated melanocortin blood levels. Translational research on α­MSH (melanocyte-stimulating hormones) and their antagonists has further revealed a variety of other biological activities beyond pigmentation. They include cytoprotection, antioxidative effects, regulation of collagen metabolism and fibrosis, sebum production, and cutaneous wound healing. These findings have also promoted the development of novel therapies in clinical dermatology including the exploitation of afamelanotide. In 2015, this agent became the first in-class synthetic α­MSH analogue to be approved in dermatology for the treatment of erythropoetic protoporphyria. In addition to afamelanotide, setmelanotide has recently emerged as a highly selective MC4R agonist useful for the treatment of distinct forms of genetically determined obesity, e.g., POMC deficiency. Future perspectives in dermatology reside in treatment of other difficult-to-treat skin diseases with α­MSH analogues, either with topical or systemic formulations. Moreover, synthetic melanocortin peptide derivatives lacking the central pharmacophor but with maintained anti-inflammatory effects could become a promising strategy for the design of new therapies in dermatology.


Assuntos
Dermatologia/tendências , Melanocortinas/química , Peptídeos/química , Pesquisa Médica Translacional , Humanos , Inflamação/metabolismo , Melanocortinas/farmacologia , Peptídeos/farmacologia , Pró-Opiomelanocortina , Pele/metabolismo , alfa-MSH
3.
Adv Exp Med Biol ; 1268: 285-306, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32918224

RESUMO

Cutaneous malignancies including melanomas and keratinocyte carcinomas (KC) are the most common types of cancer, occurring at a rate of over one million per year in the United States. KC, which include both basal cell carcinomas and squamous cell carcinomas, are substantially more common than melanomas and form the subject of this chapter. Ultraviolet radiation (UVR), both UVB and UVA, as occurs with sunlight exposure is generally regarded as causal for these malignancies, but UVB is also required for vitamin D synthesis in the skin. Keratinocytes are the major cell in the epidermis. These cells not only produce vitamin D but contain the enzymatic machinery to metabolize vitamin D to its active metabolite, 1,25(OH)2D, and express the receptor for this metabolite, the vitamin D receptor (VDR). This allows the cell to respond to the 1,25(OH)2D that it produces. Based on our own data and that reported in the literature, we conclude that vitamin D signaling in the skin suppresses UVR-induced epidermal tumor formation. In this chapter we focus on four mechanisms by which vitamin D signaling suppresses tumor formation. They are inhibition of proliferation/stimulation of differentiation with discussion of the roles of hedgehog, Wnt/ß-catenin, and hyaluronan/CD44 pathways in mediating vitamin D regulation of proliferation/differentiation, regulation of the balance between oncogenic and tumor suppressor long noncoding RNAs, immune regulation, and promotion of DNA damage repair (DDR).


Assuntos
Receptores de Calcitriol/metabolismo , Pele/metabolismo , Proteínas Supressoras de Tumor/metabolismo , Humanos , Queratinócitos/metabolismo , Pele/citologia , Neoplasias Cutâneas/metabolismo , Raios Ultravioleta/efeitos adversos , Vitamina D/metabolismo
4.
Adv Exp Med Biol ; 1268: 257-283, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32918223

RESUMO

Nonmelanoma skin cancers including basal and squamous cell carcinomas (SCC and BCC) represent a significant clinical problem due to their relatively high incidence, imposing an economic burden to healthcare systems around the world. It is accepted that ultraviolet radiation (UVR: λ = 290-400 nm) plays a crucial role in the initiation and promotion of BCC and SCC with UVB (λ = 290-320 nm) having a central role in this process. On the other hand, UVB is required for vitamin D3 (D3) production in the skin, which supplies >90% of the body's requirement for this prohormone. Prolonged exposure to UVB can also generate tachysterol and lumisterol. Vitamin D3 itself and its canonical (1,25(OH)2D3) and noncanonical (CYP11A1-intitated) D3 hydroxyderivatives show photoprotective functions in the skin. These include regulation of keratinocyte proliferation and differentiation, induction of anti-oxidative responses, inhibition of DNA damage and induction of DNA repair mechanisms, and anti-inflammatory activities. Studies in animals have demonstrated that D3 hydroxyderivatives can attenuate UVB or chemically induced epidermal cancerogenesis and inhibit growth of SCC and BCC. Genomic and non-genomic mechanisms of action have been suggested. In addition, vitamin D3 itself inhibits hedgehog signaling pathways which have been implicated in many cancers. Silencing of the vitamin D receptor leads to increased propensity to develop UVB or chemically induced epidermal cancers. Other targets for vitamin D compounds include 1,25D3-MARRS, retinoic orphan receptors α and γ, aryl hydrocarbon receptor, and Wnt signaling. Most recently, photoprotective effects of lumisterol hydroxyderivatives have been identified. Clinical trials demonstrated a beneficial role of vitamin D compounds in the treatment of actinic keratosis. In summary, recent advances in vitamin D biology and pharmacology open new exciting opportunities in chemoprevention and treatment of skin cancers.


Assuntos
Neoplasias Cutâneas/etiologia , Neoplasias Cutâneas/prevenção & controle , Vitamina D/química , Animais , Progressão da Doença , Humanos , Receptores de Calcitriol/metabolismo , Pele/efeitos dos fármacos , Pele/metabolismo , Pele/efeitos da radiação , Neoplasias Cutâneas/metabolismo , Neoplasias Cutâneas/patologia , Raios Ultravioleta/efeitos adversos , Vitamina D/metabolismo , Vitamina D/farmacologia , Vitaminas/química , Vitaminas/metabolismo , Vitaminas/farmacologia
5.
Adv Exp Med Biol ; 1268: 381-385, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32918229

RESUMO

BACKGROUND: The rule of thumb "Fill up a handful of sunscreen and spread it all over your body" has been used in several sun safety campaigns. The intention was to increase the applied sunscreen to obtain a quantity of 2 mg/cm2 to all accessible skin. The present study is the first to investigate how this advice works in practice, evaluated by quantity of sunscreen applied and amount of covered skin. METHODS: Seventeen volunteers wearing swimwear were asked to "Fill up a handful and spread it all over your body." Before and after sunscreen application, the volunteers were photographed in black light. As sunscreen absorbs black light, the darkness of the skin increases with increasing amounts of applied sunscreen, making it possible to identify skin left without coverage. The sunscreen container was weighed before and after to quantify the amount of sunscreen applied. RESULTS: A median of 21% of the accessible skin was left completely without coverage. The 79% covered area was covered with a median of 1.12 mg/cm2, not the expected 2 mg/cm2. CONCLUSION: In practice, the advice "Fill up a handful of sunscreen and spread it all over your body" led to a better but still modest protection, compared to the intended effect.


Assuntos
Pele/metabolismo , Protetores Solares/administração & dosagem , Protetores Solares/análise , Administração Cutânea , Cor , Humanos , Protetores Solares/farmacocinética
6.
Adv Exp Med Biol ; 1268: 387-405, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32918230

RESUMO

Exposure to sunlight is a major source of vitamin D for most people. Yet public health advice has focused overwhelmingly on avoiding exposure of unprotected skin because of the risks of erythema and skin cancer. Given that there are also health risks associated with low vitamin D status, we explore the possibilities of achieving a range of targets associated with vitamin D and the accompanying erythema risk. We have calculated the exposure required to gain a number of proposed oral-equivalent doses of vitamin D, as functions of latitude, season, skin type and skin area exposed, together with the associated risk of erythema, expressed in minimum erythema doses. The model results show that a recommended daily intake of 400 IU is readily achievable through casual sun exposure in the midday lunch hour, with no risk of erythema, for all latitudes some of the year, and for all the year at some (low) latitudes. We also show that such daily, sub-erythemal doses at lunchtime during the summer months is sufficient to avoid winter-time vitamin D deficiency for the UK all-weather climate, provided that lower arms and legs are exposed in the warmer months. At the higher proposed vitamin D dose of 1000 IU, lunchtime sun exposure is still a viable route to the vitamin but requires the commitment to expose greater areas of skin and is effective for a shorter period of the year. The highest vitamin D requirement considered was 4000 IU per day. For much of the globe and much of the year, this is not achievable in a lunchtime hour and where it is possible large areas of skin must be exposed to prevent erythema. When the only variable considered was skin type, latitudinal and seasonal limits on adequate vitamin D production were more restrictive for skin type 5 than skin type 2.


Assuntos
Eritema/etiologia , Pele/metabolismo , Pele/efeitos da radiação , Raios Ultravioleta/efeitos adversos , Vitamina D/biossíntese , Humanos , Medição de Risco , Pele/patologia , Deficiência de Vitamina D/prevenção & controle
7.
Pharm Res ; 37(10): 195, 2020 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-32944793

RESUMO

PURPOSE: Design imiquimod-loaded chitosan nanocapsules for transdermal delivery and evaluate the depth of imiquimod transdermal absorption as well as the kinetics of this absorption using Raman Microscopy, an innovative strategy to evaluate transdermal absorption. This nanovehicle included Compritol 888ATO®, a novel excipient for formulating nanosystems whose administration through the skin has not been studied until now. METHODS: Nanocapsules were made by solvent displacement method and their physicochemical properties was measured by DLS and laser-Doppler. For transdermal experiments, newborn pig skin was used. The Raman spectra were obtained using a laser excitation source at 532 nm and a 20/50X oil immersion objective. RESULTS: The designed nanocapsules, presented nanometric size (180 nm), a polydispersity index <0.2 and a zeta potential +17. The controlled release effect of Compritol was observed, with the finding that half of the drug was released at 24 h in comparison with control (p < 0.05). It was verified through Raman microscopy that imiquimod transdermal penetration is dynamic, the nanocapsules take around 50 min to penetrate the stratum corneum and 24 h after transdermal administration, the drug was in the inner layers of the skin. CONCLUSIONS: This study demonstrated the utility of Raman Microscopy to evaluate the drugs transdermal penetration of in the different layers of the skin. Graphical Abstract New imiquimod nanocapsules: evaluation of their skin absorption by Raman Microscopy and effect of the compritol 888ATO® in the imiquimod release profile.


Assuntos
Quitosana/farmacocinética , Sistemas de Liberação de Medicamentos/métodos , Ácidos Graxos/farmacocinética , Imiquimode/farmacocinética , Nanocápsulas/administração & dosagem , Pele/metabolismo , Administração Cutânea , Animais , Quitosana/administração & dosagem , Quitosana/química , Ácidos Graxos/administração & dosagem , Ácidos Graxos/química , Imiquimode/administração & dosagem , Imiquimode/química , Nanocápsulas/química , Microscopia Óptica não Linear/métodos , Absorção Cutânea , Suínos
8.
Adv Exp Med Biol ; 1265: 187-199, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32761577

RESUMO

Amino acids are the building blocks of all proteins, including the most abundant fibrous proteins in the skin, as keratins, collagen and elastin. Sagging and wrinkled skin are features of chronic sun-damaged and aged uncared skin, and they are mainly associated with the deterioration of collagen and elastic fibers. The maintenance of skin structures by self-repair processes is essential to skin health. Thus, amino acids significantly impact the appearance of the skin. Amino acids are important nutrients required for (a) wound healing promotion and repair of the damaged skin; (b) acid-base balance and water retention in cellular layers, such as stratum corneum; (c) protection against sunlight damage; (d) maintenance of an appropriate skin microbiome. This review highlights the contribution of all proteinogenic amino acids and some related metabolites to the skin structures as constituents of the main cutaneous proteins or as signaling molecules for the regulation and determination of skin physiology.


Assuntos
Aminoácidos/metabolismo , Pele/metabolismo , Colágeno , Elastina , Humanos , Queratinas , Pele/citologia , Pele/microbiologia , Envelhecimento da Pele
9.
Artigo em Inglês | MEDLINE | ID: mdl-32748726

RESUMO

The transferability of phthalic acid esters (PAEs) and other plasticizers, from model polyvinyl chloride (PVC) sheets to the skin of 11 subjects was assessed by measuring the amount of substance transferred using PVC sheets containing PAEs and alternative plasticizers of different types and contents. For all subjects, the transferred amount, from sheets containing 28 wt% PAE or from mixed sheets containing 14 wt% each of di (2-ethylhexyl) phthalate (DEHP) and other PAE, was greater than that from sheets containing 15 wt% each of PAE or alternative plasticizer only. A comparison of the transferability of five types of PAE showed that transfer tended to occur more readily as the n-octanol-water partition coefficient increased, suggesting that PAE hydrophobicity affected its transferability. The transferability of the alternative plasticizers di(2-ethylhexyl) terephthalate and 1,2-cyclohexane dicarboxylic acid diisononyl ester showed a similar trend; however, the transferred amount tended to be higher from model PVC sheets containing 28 wt% PAE or mixed with DEHP. The transferability of PAEs and alternative plasticizers was higher for certain subjects, suggesting individual differences in the transferability of chemicals to the subject's skin surface and is the presence of a group of people comparatively more susceptible to such transfer.


Assuntos
Dietilexilftalato/farmacocinética , Modelos Biológicos , Plastificantes/farmacocinética , Cloreto de Polivinila/química , Absorção Cutânea/efeitos dos fármacos , Pele/efeitos dos fármacos , Adulto , Dietilexilftalato/análise , Feminino , Voluntários Saudáveis , Humanos , Masculino , Pessoa de Meia-Idade , Plastificantes/análise , Pele/metabolismo
10.
Nat Commun ; 11(1): 4222, 2020 08 24.
Artigo em Inglês | MEDLINE | ID: mdl-32839436

RESUMO

Our understanding of Na+ homeostasis has recently been reshaped by the notion of skin as a depot for Na+ accumulation in multiple cardiovascular diseases and risk factors. The proposed water-independent nature of tissue Na+ could induce local pathogenic changes, but lacks firm demonstration. Here, we show that tissue Na+ excess upon high Na+ intake is a systemic, rather than skin-specific, phenomenon reflecting architectural changes, i.e. a shift in the extracellular-to-intracellular compartments, due to a reduction of the intracellular or accumulation of water-paralleled Na+ in the extracellular space. We also demonstrate that this accumulation is unlikely to justify the observed development of experimental hypertension if it were water-independent. Finally, we show that this isotonic skin Na+ excess, reflecting subclinical oedema, occurs in hypertensive patients and in association with aging. The implications of our findings, questioning previous assumptions but also reinforcing the importance of tissue Na+ excess, are both mechanistic and clinical.


Assuntos
Edema/metabolismo , Homeostase/fisiologia , Sódio/metabolismo , Equilíbrio Hidroeletrolítico/fisiologia , Envelhecimento/metabolismo , Animais , Edema/diagnóstico , Feminino , Humanos , Hipertensão/diagnóstico , Hipertensão/metabolismo , Hipertensão/fisiopatologia , Fígado/metabolismo , Pulmão/metabolismo , Masculino , Miocárdio/metabolismo , Especificidade de Órgãos , Concentração Osmolar , Potássio/metabolismo , Ratos Endogâmicos WKY , Pele/metabolismo , Fatores de Transcrição/metabolismo
11.
Nat Commun ; 11(1): 4092, 2020 08 14.
Artigo em Inglês | MEDLINE | ID: mdl-32796837

RESUMO

Single nucleotide polymorphisms (SNPs) in the gene encoding kinesin family member 3A, KIF3A, have been associated with atopic dermatitis (AD), a chronic inflammatory skin disorder. We find that KIF3A SNP rs11740584 and rs2299007 risk alleles create cytosine-phosphate-guanine sites, which are highly methylated and result in lower KIF3A expression, and this methylation is associated with increased transepidermal water loss (TEWL) in risk allele carriers. Kif3aK14∆/∆ mice have increased TEWL, disrupted junctional proteins, and increased susceptibility to develop AD. Thus, KIF3A is required for skin barrier homeostasis whereby decreased KIF3A skin expression causes disrupted skin barrier function and promotes development of AD.


Assuntos
Dermatite Atópica/metabolismo , Cinesina/metabolismo , Pele/metabolismo , Adolescente , Adulto , Alelos , Animais , Criança , Dermatite Atópica/genética , Dermatite Atópica/patologia , Feminino , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Cinesina/genética , Masculino , Metilação , Camundongos , Reação em Cadeia da Polimerase em Tempo Real , Pele/patologia , Adulto Jovem
12.
PLoS One ; 15(8): e0237705, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32833973

RESUMO

Polychlorinated biphenyls (PCBs) are environmental pollutants and endocrine disruptors, harmfully affecting reproductive, endocrine, neurological and immunological systems. This broad influence has implications for processes such as wound healing, which is modulated by the immunological response of the body. Conversely, while PCBs can be linked to diminished wound healing, outside of PCB pollution systems, exercise has been shown to accelerate wound healing. However, the potential for moderate intensity exercise to modulate or offset the harmful effects of a toxin like PCB are yet unknown. A key aim of the present study was to examine how PCB exposure at different doses (0, 100, 500, 1000 ppm i.p.) altered wound healing in exercised versus non-exercised subgroups of mice. We examined PCB effects on immune function in more depth by analyzing the concentrations of cytokines, interleukin-1ß (IL-1ß), tumor necrosis factor-α (TNF-α), Interleukin-6 (IL-6) and granulocyte macrophage colony stimulating factor (GM-CSF) in these wounds inflicted by punch biopsy. Mice were euthanized at Day 3 or Day 5 after PCB injection (n = 3-6) and skin excised from the wound area was homogenized and analyzed for cytokine content. Results revealed that wound healing was not signficantly impacted by either PCB exposure or exercise, but there were patterns of delays in healing that depended on PCB dose. Changes in cytokines were also observed and depended on PCB dose and exercise experience. For example, IL-1ß concentrations in Day 5 mice without PCB administration were 33% less in exercised mice than mice not exercised. However, IL-1ß concentrations in Day 3 mice administered 100 ppm were 130% greater in exercised mice than not exercisedmice. Changes in the other measured cytokines varied with mainly depressions at lesser PCB doses and elevations at higher doses. Exercise had diverse effects on cytokine levels, but increased cytokine levels in the two greater doses. Explanations for these diverse effects include the use of young animals with more rapid wound healing rates less affected by toxin exposure, as well as PCB-mediated compensatory effects at specific doses which could actually enhance immune function. Future work should examine these interactions in more detail across a developmental time span. Understanding how manipulating the effects of exposure to environemntal contaminants using behavioral modification could be very useful in certain high risk populations or exposed individuals.


Assuntos
Disruptores Endócrinos/toxicidade , Poluentes Ambientais/toxicidade , Condicionamento Físico Animal/fisiologia , Bifenilos Policlorados/toxicidade , Cicatrização/imunologia , Animais , Citocinas/imunologia , Citocinas/metabolismo , Modelos Animais de Doenças , Feminino , Humanos , Camundongos , Pele/imunologia , Pele/lesões , Pele/metabolismo , Cicatrização/efeitos dos fármacos
13.
PLoS One ; 15(8): e0238076, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32857768

RESUMO

Epidermal lineages and injury induced regeneration are controlled by transcriptional programs coordinating cellular signaling and epigenetic regulators, but the mechanism remains unclear. Previous studies showed that conditional deletion of the transcriptional coactivator Mediator 1 (Med1) changes epidermal lineages and accelerates wound re-epithelialization. Here, we studied a molecular mechanism by which Med1 facilitates these processes, in particular, by focusing on TGFß signaling through genome wide transcriptome analysis. The expression of the TGF ligands (Tgfß1/ß2) and their downstream target genes is decreased in both normal and wounded Med1 null skin. Med1 silencing in cultured keratinocytes likewise reduces the expression of the ligands (TGFß1/ß2) and diminishes activity of TGFß signaling as shown by decreased p-Smad2/3. Silencing Med1 increases keratinocyte proliferation and migration in vitro. Epigenetic studies using chromatin immuno-precipitation and next generation DNA sequencing reveals that Med1 regulates transcription of TGFß components by forming large clusters of enhancers called super-enhancers at the regulatory regions of the TGFß ligand and SMAD3 genes. These results demonstrate that Med1 is required for the maintenance of the TGFß signaling pathway. Finally, we show that pharmacological inhibition of TGFß signaling enhances epidermal lineages and accelerates wound re-epithelialization in skin similar to that seen in the Med1 null mice, providing new insights into epidermal regeneration.


Assuntos
Subunidade 1 do Complexo Mediador/genética , Regeneração/fisiologia , Transdução de Sinais , Fator de Crescimento Transformador beta1/metabolismo , Fator de Crescimento Transformador beta2/metabolismo , Animais , Linhagem da Célula , Movimento Celular , Proliferação de Células , Regulação para Baixo , Epiderme/fisiologia , Queratinócitos/citologia , Queratinócitos/metabolismo , Subunidade 1 do Complexo Mediador/antagonistas & inibidores , Subunidade 1 do Complexo Mediador/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Interferência de RNA , RNA Interferente Pequeno/metabolismo , Pele/metabolismo , Pele/patologia , Proteína Smad3/genética , Proteína Smad3/metabolismo , Fator de Crescimento Transformador beta1/genética , Fator de Crescimento Transformador beta2/genética , Regulação para Cima
14.
PLoS One ; 15(8): e0235898, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32833999

RESUMO

Myo/Nog cells were discovered in the chick embryo epiblast. Their expression of MyoD reflects a commitment to the skeletal muscle lineage and capacity to differentiate into myofibroblasts. Release of Noggin by Myo/Nog cells is essential for normal morphogenesis. Myo/Nog cells rapidly respond to wounding in the skin and eyes. In this report, we present evidence suggesting that Myo/Nog cells phagocytose tattoo ink in tissue sections of human skin and engulf cell corpses in cultures of anterior human lens tissue and magnetic beads injected into the anterior chamber of mice in vivo. Myo/Nog cells are distinct from macrophages in the skin and eyes indicated by the absence of labeling with an antibody to ionized calcium binding adaptor molecule 1. In addition to their primary roles as regulators of BMP signaling and progenitors of myofibroblasts, Myo/Nog cells behave as nonprofessional phagocytes defined as cells whose primary functions are unrelated to phagocytosis but are capable of engulfment.


Assuntos
Miofibroblastos/citologia , Fagócitos/citologia , Células-Tronco/citologia , Animais , Proteínas de Transporte/metabolismo , Diferenciação Celular , Células Cultivadas , Embrião de Galinha , Feminino , Humanos , Cristalino/citologia , Cristalino/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Proteína MyoD/metabolismo , Miofibroblastos/metabolismo , Fagócitos/metabolismo , Fagocitose , Coelhos , Pele/citologia , Pele/metabolismo , Células-Tronco/metabolismo
15.
Hautarzt ; 71(10): 786-790, 2020 Oct.
Artigo em Alemão | MEDLINE | ID: mdl-32852599

RESUMO

Topical hormonal treatment allows anti-aging of the skin when used during and after the menopause without an increase in the blood level of hormones. Natural hormones are only prescribed by medical doctors. In controlled clinical studies versus placebo and application for months, an increase in skin quality parameters, reduction of dryness, increase of glycosaminoglycanes, increase in elastic fibers und increase of collagen precursers and collagen fibers on the mRNA and protein level could be shown, the latter proven by biopsies. Skin with dramatic sun-damage does not respond to this treatment option. Patients with melasma or seborrhoe should not be treated with hormonal topical preparations. Compared to the natural hormones, phytotherapeutics do not bind to hormone receptors in relevant levels. Growth hormones should not be used in anti-aging treatment due to a potential carcinogenic effect.


Assuntos
Terapia de Reposição de Estrogênios/efeitos adversos , Menopausa/fisiologia , Envelhecimento da Pele/efeitos dos fármacos , Pele/efeitos dos fármacos , Administração Tópica , Envelhecimento , Feminino , Humanos , Pele/anatomia & histologia , Pele/metabolismo
16.
Sheng Wu Gong Cheng Xue Bao ; 36(7): 1323-1333, 2020 Jul 25.
Artigo em Chinês | MEDLINE | ID: mdl-32748590

RESUMO

The aim of this study was to investigate the expression of MHCⅠ gene in different tissues of Rana dybowskii under the stress of Aeromonas hydrophila (Ah), and to provide evidence for revealing the anti-infective immune response mechanism of amphibians. The experimental animal model of Aeromonas hydrophila infection was first constructed, and the pathological changes were observed by HE staining. The MHCⅠ gene α1+α2 peptide binding region of Rana dybowskii was cloned by RT-PCR and analyzed by bioinformatics. Real-time PCR was used to detect the transcription level of MHCⅠ in different tissues under Ah stress. After Ah infection, the skin, liver and muscle tissues showed signs of cell structure disappearance and texture disorder. The MHCⅠ gene α1+α2 peptide binding region fragment was 494 bp, encoding 164 amino acids, and homology with amphibians. Above 77%, the homology with mammals was as low as 14.96%, indicating that the α1+α2 region of MHC gene was less conserved among different species. The results of real-time PCR show that the liver, spleen and kidney of the experimental group were under Ah stress. The transcript levels of MHCⅠ gene in skin and muscle tissues were higher than those in the control group at 72 h, but the time to peak of each tissue was different (P<0.01), indicating that the response time of MHCⅠ gene in different tissues was different under Ah stress. This study provides a reference for further exploring the immune function of MHC molecules in anti-infection.


Assuntos
Aeromonas hydrophila , Regulação da Expressão Gênica , Infecções por Bactérias Gram-Negativas , Ranidae , Animais , Perfilação da Expressão Gênica , Regulação da Expressão Gênica/imunologia , Infecções por Bactérias Gram-Negativas/imunologia , Fígado/metabolismo , Ranidae/genética , Ranidae/imunologia , Ranidae/microbiologia , Pele/metabolismo
17.
PLoS One ; 15(8): e0237100, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32760159

RESUMO

PURPOSE: Cobalt exposure is known to cause adverse effects on health. A major use of cobalt is in the manufacture of hard metal. Exposure can lead to asthma, hard metal lung disease, contact allergy and increased risk of cancer. Cobalt is mainly absorbed from the pulmonary tract, however penetration through skin may occur. The relationships between exposure to inhalable cobalt in air and on skin and the uptake in blood and urine will be investigated, as well as the association between dermal symptoms and dermal exposure. METHODS: Cobalt exposure in 71 workers in hard metal production facilities was measured as inhalable cobalt in the breathing zone and cobalt found on skin with acid wash. Uptake of cobalt was determined with concentrations in blood and urine. Correlations between exposure and uptake were analysed. RESULTS: Inhalable cobalt in air and cobalt in blood and urine showed rank correlations with coefficients 0.40 and 0.25. Cobalt on skin and uptake in blood and urine presented correlation coefficients of 0.36 and 0.17. Multiple linear regression of cobalt in air and on skin with cobalt in blood showed regression coefficients with cobalt in blood (ß = 203 p < 0.0010, and ß = 0.010, p = 0.0040) and with cobalt in urine (ß = 5779, p = 0.0010, and ß = 0.10, p = 0.60). CONCLUSIONS: Our data presents statistically significant correlations between exposure to cobalt in air with uptake of cobalt in blood and urine. Cobalt on skin was statistically significant with cobalt in blood but not with urine.


Assuntos
Cobalto/sangue , Intoxicação por Metais Pesados/epidemiologia , Exposição por Inalação/estatística & dados numéricos , Metalurgia/estatística & dados numéricos , Exposição Ocupacional/estatística & dados numéricos , Adulto , Poluentes Ocupacionais do Ar/sangue , Poluentes Ocupacionais do Ar/urina , Cobalto/urina , Feminino , Intoxicação por Metais Pesados/sangue , Intoxicação por Metais Pesados/urina , Humanos , Masculino , Pessoa de Meia-Idade , Pele/metabolismo , Suécia
18.
J Nippon Med Sch ; 87(3): 110-117, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32655090

RESUMO

BACKGROUND: Cutaneous wound healing is a complex, dynamic physiological process. Traditional methods of promoting wound healing are not always effective. Consequently, alternative modalities, such as photodynamic therapy (PDT), are needed. We examined the effectiveness and underlying mechanisms of PDT in a murine model of acute wound healing. METHODS: Two excisional wounds were produced, one on each side of the midline, in C57bL/6J mice. Methyl 5-aminolevulinate hydrochloride (MAL) was applied to the right-side wound. After 1 to 3 hours of incubation, the wound was irradiated with red light. The left-side wound was not treated with MAL or red light. On Day 14, the wounds were excised and subjected to histological and immunohistochemical analysis. RESULTS: During the first week, no difference was seen between the two sides. However, at week 2, PDT-treated wounds exhibited delayed re-epithelialization. On Day 14, hematoxylin and eosin (HE) staining showed a continuous epithelial lining in untreated wounds. In contrast, PDT-treated wounds partially lacked epithelium in the wound bed. Masson's Trichrome (MTC) staining showed a thicker dermis and more collagen fibers and inflammatory cells in PDT-treated wounds than in untreated wounds. Immunohistochemical analyses showed significantly fewer CD31+ blood vessels and greater collagen III density in PDT-treated wounds than in untreated wounds. However, treated and untreated wounds did not differ in collagen I density. CONCLUSIONS: PDT delayed acute wound healing in a murine model of secondary intention wound healing.


Assuntos
Fotoquimioterapia/efeitos adversos , Fenômenos Fisiológicos da Pele , Cicatrização/efeitos da radiação , Animais , Colágeno/metabolismo , Camundongos Endogâmicos C57BL , Modelos Animais , Molécula-1 de Adesão Celular Endotelial a Plaquetas/metabolismo , Pele/metabolismo , Fatores de Tempo , Cicatrização/fisiologia , Infecção dos Ferimentos
19.
AAPS PharmSciTech ; 21(5): 185, 2020 Jul 06.
Artigo em Inglês | MEDLINE | ID: mdl-32632542

RESUMO

The present study aimed to develop, characterize and evaluate the amphotericin B-loaded nanostructured lipid carriers (AmB-NLCs) for topical treatment of cutaneous leishmaniasis (CL) and vulvovaginal candidiasis (VVC). AmB-NLCs were characterized for particle size, zeta potential, encapsulation efficiency and surface morphology. Prepared NLCs were also characterized for in vitro drug release, ex vivo skin permeation and deposition before evaluating their in vitro and in vivo efficacy. Cytotoxicity of NLCs was assessed on MRC-5 cells, whereas skin irritation potential was evaluated in vivo using rats. Significant accumulation of drug in to the skin supported the topical application potential of drug-loaded NLCs. Encapsulation of AmB in NLCs resulted in enhanced in vitro potency against promastigotes and intracellular amastigotes of L. major JISH 118 (IC50 ± SEM = 0.02 ± 0.1 µM for both) compared with free drug (IC50 ± SEM = 0.15 ± 0.2 & 0.14 ± 0.0, respectively). Similar improved potency of AmB-NLCs was also observed for other Leishmania and fungal strains compared with drug solution. Topical application of AmB-NLCs on L. major-infected BALB/c mice caused a significant reduction in parasite burden per mg of lesion (65 × 108 ± 13) compared with the control group (> 167.8 × 108 ± 11). Topical AmB-NLCs gel demonstrated superior efficacy in the vaginal C. albicans rat model for VVC as compared with plain AmB gel. Moreover, results of in vitro cytotoxicity assay and in vivo skin irritation test confirmed AmB-NLCs to be non-toxic and safe for topical use. In conclusion, NLCs may have promising potential as carrier for topical treatment of various conditions of skin and mucosa.


Assuntos
Anfotericina B/administração & dosagem , Candidíase Vulvovaginal/tratamento farmacológico , Leishmaniose Cutânea/tratamento farmacológico , Nanoestruturas/administração & dosagem , Administração Tópica , Animais , Candidíase Vulvovaginal/metabolismo , Portadores de Fármacos/administração & dosagem , Sistemas de Liberação de Medicamentos/métodos , Liberação Controlada de Fármacos , Feminino , Géis/metabolismo , Humanos , Lipídeos/administração & dosagem , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Modelos Animais , Tamanho da Partícula , Ratos , Pele/metabolismo , Absorção Cutânea
20.
AAPS PharmSciTech ; 21(5): 180, 2020 Jun 29.
Artigo em Inglês | MEDLINE | ID: mdl-32601758

RESUMO

Rheumatoid arthritis, a chronic disorder, limits the use of chemical penetration enhancers for a prolonged period of time. Moreover, systemic routes of administration of the first-line drug, methotrexate, have shown undesirable systemic as well as local side effects. The objective of this research was to overcome the limitations associated with treatment of rheumatoid arthritis by utilizing three physical transdermal penetration enhancement techniques namely cold-laser, electroporation, and sonophoresis to deliver methotrexate. Methotrexate patch was prepared using solvent casting method and the ex-vivo release of methotrexate in combination with three physical penetration enhancers (sonophoresis, electroporation, and cold laser) were studied. The best technique was employed in pre-clinical testing in arthritic and control groups of male Wistar rats excluding remaining two techniques. The comparative ex-vivo studies showed that the penetration enhancement of methotrexate is maximum by sonophoresis followed by electroporation and cold laser (sonophoresis > electroporation > cold laser). In pharmacodynamic studies, the reduction in diameter of injected and non-injected paw on day 5 and day 21 for group 4 (ultrasound pre-treated group) was higher as compared to group 3 (group receiving only methotrexate patch). The motility score and the reduction in pain were significantly improved for group 4 than group 3 on both day 5 and day 21 (P Ë‚ 0.05) which confirmed the faster recovery of animals of group 4 due to penetration enhancement of methotrexate patch by ultrasound treatment. From the results, it can be concluded that sonophoresis along with methotrexate patch has shown a significant effect in the treatment of rheumatoid arthritis.


Assuntos
Antirreumáticos/administração & dosagem , Artrite Reumatoide/tratamento farmacológico , Metotrexato/administração & dosagem , Adesivo Transdérmico , Terapia por Ultrassom , Administração Cutânea , Animais , Masculino , Ratos , Ratos Wistar , Pele/metabolismo , Absorção Cutânea
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