Diante da hipótese de que micropartículas poliméricas podem atravessar a barreira epidérmica através da rota transfolicular, e baseado na evidência de que a iontoforese é um método que consegue direcionar a liberação de fármacos para os folículos pilosos, este trabalho teve como objetivo estudar in vitro a permeação cutânea do minoxidil sulfato (MXS), fármaco utilizado no tratamento da alopecia androgênica, tanto em sua forma microencapsulada como não encapsulada utilizando ou não a iontoforese, na tentativa de aumentar, controlar e direcionar a sua liberação tópica para o folículo piloso. O MXS foi primeiramente incorporado em um gel hidrofílico contendo 2,0% (m/m) do ativo e sua permeação e retenção cutânea in vitro verificada com e sem a presença de corrente elétrica durante 6 h, utilizando células de difusão e pele de orelha de porco. A quantidade de MXS retida no EC da pele foi determinada e diferenciada daquela retida nos folículos pilosos utilizando-se a técnica denominada tape stripping diferencial. Foi observado que o fluxo passivo de fármaco através da pele aumentou 150 vezes com aplicação de iontoforese anódica e que o aumento do pH da formulação de 3,5 para 5,5 restringiu 3 vezes essa permeação iontoforética e aumentou a retenção do MXS no EC e folículos pilosos. Estes resultados mostram que a iontoforese do MXS nestas condições é capaz de promover a liberação folicular do fármaco de maneira bastante significativa. Uma série de micropartículas de quitosana contendo MXS foi obtida por spray drying modificando quantidades e proporções de polímero e fármaco. O sistema selecionado para estudo foi obtido a partir de 1,50 g de polímero e 0,75 g de MXS, e apresentou alta eficiência de encapsulação (~82%), diâmetro médio igual a 3,05 µm, morfologia esférica e sem porosidades, e potencial zeta igual a + 5,87 mV. Quando incorporadas a uma formulação hidroalcoólica, essas micropartículas sofreram intumescimento, aumentando 1,5 vezes o seu diâmetro médio, mas não tiveram sua morfologia esférica alterada. Experimentos de liberação in vitro mostraram que as micropartículas obtidas foram capazes de sustentar 3,5 vezes a liberação do MXS. As micropartículas ainda restringiram a permeação passiva do fármaco, reduzindo 2 vezes seu fluxo de permeação e aumentando em 5 vezes a retenção de fármaco na região folicular, apesar das partículas em si não penetrarem a pele após administração passiva. Assim, este sistema foi capaz de promover uma liberação mais sustentada do fármaco, o que deve reduzir o número de aplicações do produto pelo paciente ao longo do dia, e garantiu a entrada de grandes quantidades do fármaco nos folículos pilosos, seu alvo de ação. A iontoforese dessas micropartículas, apesar de também não fazê-las penetrar a pele, conseguiu direcioná-las mais rapidamente para as aberturas foliculares, como mostrou os estudos de microscopia confocal de varredura a laser das micropartículas marcadas. Adicionalmente, a iontoforese aumentou 6 vezes a quantidade de MXS retida nos folículos já nas primeiras 3 h de aplicação, garantindo assim que grandes quantidades do fármaco atingissem seu local de ação mais rapidamente que quando as partículas foram aplicadas passivamente sobre a pele. / Given the hypothesis that polymeric microparticles can penetrate the skin barrier along the transfollicular route, and based on the evidence that iontophoresis is a method that can direct the delivery of drugs to the hair follicles, this work aimed to study the in vitro skin permeation of minoxidil sulfate (MXS), a drug used to treat androgenic alopecia, both in its micro-encapsulated and non-encapsulated form, using or not iontophoresis, in an attempt to increase, control and direct its topical delivery to the hair follicle. The MXS was first incorporated in a hydrophilic gel containing 2.0% (w/w) MXS and its skin permeation and retention was in vitro observed with and without the presence of electric current for 6 h, using diffusion cells and skin of porcine\'s ears. The amount of MXS retained in EC was determined and differentiated from that retained in the hair follicles using the technique called differential tape stripping. It was observed that the passive flux of drug through the skin was increased 150-fold with the application of anodal iontophoresis and, by increasing the pH of the formulation from 3.5 to 5.5, iontophoretic permeation of MXS was 3-fold restricted, whereas it increased its retention in stratum corneum and hair follicles. These results show that iontophoresis of MXS in these conditions can promote the follicular delivery of the drug quite significantly. A series of chitosan microparticles containing MXS was obtained by spray drying, modifying quantities and proportions of polymer and drug. The system selected for study was obtained from 1.50 g of polymer and 0.75 g of MXS, and showed high encapsulation efficiency (~ 82%), mean diameter of 3.05 µm, spherical morphology without porosities, and zeta potential equal to + 5.87 mV. When incorporated into a hydro ethanolic formulation, these microparticles suffered swelling, increasing 1.5 times its diameter, but their spherical morphology was not modified. Permeation experiments showed in vitro that the microparticles obtained were able to sustain 3.5 times the release of MXS. The microparticles also restricted the passive permeation of the drug, reducing 2-fold its permeation flux and increasing by 5-fold the retention of drug in the follicular region, although the microparticles themselves did not penetrate the skin after passive administration. Thus, this system was able to promote a more sustained release of the drug, which must reduce the number of product applications by the patient throughout the day, and ensured the entry of large amounts of drug in hair follicles, their target. Iontophoresis of microparticles, although not making them penetrate the skin either, was able to direct them quickly to the follicular openings, as shown by laser confocal scanning microscopy studies of the labeled microparticles. In addition, iontophoresis increased 6-fold the amount of MXS retained in the follicles within the first 3 h of application, thereby ensuring that large quantities of the drug achieved its site of action more quickly than when the particles were applied passively to the skin.

Orientador: Helio Amante Miot / Resumo: Introdução: Minoxidil tópico é o único medicamento com aprovação pelo FDA (Food and Drug Administration) para tratamento da alopecia de padrão feminino (APF). Muitas pacientes interrompem o tratamento prematuramente devido a falta de eficácia, intolerância ou por alteração na textura dos fios de cabelo. Minoxidil oral mostrou-se efetivo para tratamento da APF em estudo não controlado. Objetivo: Comparar eficácia, segurança e tolerabilidade do minoxidil 1 mg oral uma vez ao dia versus minoxidil 5% solução tópica uma vez ao dia no tratamento da APF. Métodos: Estudo prospectivo, randomizado, paralelo, comparativo, avaliador cego com duração de 24 semanas conduzido em um único centro de janeiro de 2017 a março de 2018 incluindo 52 mulheres (18-65 anos) com APF. Participantes foram randomizadas para receber minoxidil oral 1 mg ao dia ou minoxidil 5% tópico uma vez ao dia. O desfecho primário foi a variação na densidade de fios na área alvo. Desfechos secundários: variação na densidade de fios terminais na área alvo, escore na avaliação fotográfica panorâmica por avaliadores cegos, variação no escore da escala de queda, variação no escore do Women's Androgenetic Alopecia Quality of Life Questionnaire (WAA-QoL). Resultados: Participantes de ambos os grupos apresentaram melhora na densidade de fios na área alvo (p<0,01), porém, sem diferença entre os grupos (p=0,09): oral 12% (IC95%: 8,0 – 16,1%) e tópico 7,2% (IC95%: 1,5 - 12,9%). Houve melhora na densidade de fios terminais: oral 6... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: Introduction: Topical minoxidil is the only FDA (Food and Drug Administration) approved drug for female pattern hair loss (FPHL). Many patients discontinue treatment prematurely due to lack of efficacy, intolerance or altered hair texture. Oral minoxidil was effective for FPHL in uncontrolled studies. Objectives: To compare the efficacy, safety and tolerability of once-daily treatment with 1 mg oral minoxidil versus once-daily 5% minoxidil solution applied topically for FPHL. Methods: A 24-week, prospective, randomized, open-label, parallel, two-arm comparative, evaluator-blinded study conducted in a single center from January 2017 through March 2018 including 52 women (18-65 years old) with FPHL. Participants were randomly assigned to receive once daily minoxidil 1 mg orally or once a day minoxidil 5% solution applied topically. The primary endpoint was change from baseline in hair density from a target area at week 24. Secondary endpoints were change in terminal hair density, global photographic assessment by three group-blinded evaluators, hair shedding score, and the Women's Androgenetic Alopecia Quality of Life Questionnaire (WAA-QoL). Results: Participants of both groups had improvement of hair density in the target area (p<0.01), without difference between the groups (p=0.09): oral 12% (CI95%: 8.0- 16.1%) and topical 7,2% (CI95%: 1.5-12.9%). There was improvement on terminal hair density: oral 6% (IC95%: 2.9 – 8.6%) and topical 2,7% (IC95%: -1.4 – 6.8%), with no differ... (Complete abstract click electronic access below) / Doutor

Estudo qualitativo, desenvolvido no Hospital Regional do Câncer de Passos, que teve como objetivo compreender o significado da alopecia para mulheres com câncer de mama, em tratamento quimioterápico, utilizando como referencial teórico o Interacionismo Simbólico e, como metodológico, a Teoria Fundamentada em Dados. O projeto de pesquisa foi encaminhado ao CEP da UNIFAL-MG, sendo aprovado conforme parecer nº 478.376. Foi realizada entrevista com treze mulheres, que tinham diagnóstico de câncer de mama e estavam em tratamento quimioterápico adjuvante que apresentasse como evento adverso a alopecia. A questão norteadora da entrevista foi: “Como tem sido para você a queda do cabelo e dos pelos do corpo durante o tratamento?”. Através desta pergunta, obtivemos os dados que, após a análise, permitiram a criação de dois diagramas: 1- Reconhecendo o novo corpo: refere-se às consequências do tratamento quimioterápico e às estratégias de enfrentamento da mulher perante a alopecia. 2- Descobrindo Redes de Apoio para enfrentar a alopecia: refere-se às instituições de apoio que fortalecem a mulher para o enfrentamento da doença e das consequências do tratamento quimioterápico, como a alopecia. A categoria central foi denominada como “A alopecia da mulher no câncer de mama: entendendo nas estratégias de enfrentamento da doença”. Essa categoria permitiu que afirmássemos que a alopecia e considerada o pior momento do tratamento e que a queda dos cabelos e da sobrancelha tem efeito depressivo nas mulheres, pois elas além de estar fisicamente debilitadas, têm que refazer a construção do seu self, além de estar sofrendo a pressão da sociedade que as vê com doentes. As interações humanas estiveram presentes no desenrolar de cada fase da vivência da alopecia e no enfrentamento da situação, sendo que o modo como a mulher enfrenta a alopecia possui analogia com as relações humanas e com o que é culturalmente imposto pela sociedade. Os dados permitiram verificar que o significado dado à perda do cabelo e de pelos é individual e chamou a atenção que os profissionais de saúde devem estar atentos a orientar as mulheres nesse momento em que a alopecia está ocorrendo, pois esse evento tras implicações para a na vida das mesmas. / This is a qualitative study, developed in the Cancer Regional Hospital of Passos, aimed at understand the meaning of alopecia for women with breast cancer under chemotherapy, using Symbolic Interactionism as theory reference and Data Based Theory as methodological reference. The research project was sent to CEP of UNIFAL-MG, approved by number 478.376. There were interviews with thirteen women who had breast cancer diagnosis and were under adjuvant chemotherapy treatment, showing alopecia as an adverse event. The guided question for the interview was: “How is it for you losing hair and body hair during this treatment?” Through this question, we obtained data that after its analysis, it was possible to create two diagrams: 1- Recognizing the new body: about the consequences of chemotherapy treatment and women´s coping strategies against alopecia. 2- Discovering Support Networks for alopecia coping: about support institutions helping women with the disease and the consequences of chemotherapy with alopecia. The main category was called as “Alopecia in women´s breast cancer: understanding the coping strategies for the disease”. This category stated that alopecia is considered the worst moment of treatment and hair losing and eyebrows losing having a depressive effect in women, because besides being physically weaken, they have to rebuild their self, in addition to being suffering society pressure seeing them as sick women. Human interactions were present in all phases of alopecia and coping situations, and how women face alopecia has an analogy between human relationships and what is culturally imposed by the society. Data helped to verify the hair and hair body losing meaning as individual and it was observed that the health professionals should be alert to guide women when alopecia occurs, because this event brings implications in their lives.

Made available in DSpace on 2013-08-07T19:05:33Z (GMT). No. of bitstreams: 1 000385561-Texto+Completo-0.pdf: 1030216 bytes, checksum: e224065ca6fb4a1d5a9468a932755962 (MD5) Previous issue date: 2006 / Introduction and Objectives Follicular Units are commonly used in baldness surgery, and they have became a global procedure for both male and female patients. The micrografts yield varies between 70 to 85% and even we handle carefully to harvest and prepare it from the donor area and doing the implantation procedure under strict protocol, we need to consider to apoptosis and necrosis the main subjects that can interfere in this procedure. In order to improve hair density and stimulate follicular unit growth, an experimental study has been designed using platelet rich plasma with their growth factors obtained from the patient’s autologous blood. According to scientific papers published in this area, mainly in the areas as traumatology, odontology, maxilo-facial and plastic surgery we intended to bring a new contribution to the follicular units baldness surgery. Material and Methods The amount of twenty three patients was selected with male pattern baldness in between 22 to 55 years old and delineated a paired scientific protocol within subjects design. Experimental and control baldness areas of 2. 5 cm x 2. 5 cm have been compared and defined that at the right side of the patient they should be implanted follicular units imbibed with platelet rich plasma and its growth factors and at the left side the follicular units considered controls. By the end of seven months when all the follicular units were grown it was done the counting of it. The data was summarized using mean and standard deviation. To compare the two procedures involved we used the paired Student t-test, since data showed a Gaussian distribution. Analyses were performed using SPSS version 12. 0. Significance level was set to alpha 0. 05.Results There was a statistically significant difference observed in the yield of follicular units when comparing the two groups (P < 0. 001). The experimental group with the platelet rich plasma with the growth factors showed a density of 18. 9 FU/ per cm2 while the control group showed 16. 7 FU/ per cm2 represented a 13. 6% increase in the capillary density. Some patients have experienced less then 5% while others, considered exceptionals, showed 31% and 52% increase of follicular units yields. These varyabilities should be observed with caution and new researches should be established regarding age, smoking, exercises and food diet. Conclusion According the obtained results a considerable effect of 13. 6% was observed in the right side where has been used follicular units embibed with platelet rich plasma with growth factors. It has been an efficiency and a better yield resulting in more follicles and in more hair density that brought a positive result for the male pattern baldness surgery with platelet rich plasma and their growth factors. / Introdução e Objetivos: A cirurgia com a utilização dos microimplantes capilares (MICs) tem sido adotada amplamente no tratamento da calvície masculina e feminina. A integração destes microenxertos pode variar entre 70% a 85% e, embora todos os cuidados sejam tomados desde sua obtenção na área doadora até sua preparação e implantação na área calva, é necessário levar em conta a apoptose e a necrose como fatores que interferem neste processo. Considerando esta perda como relevante na cirurgia da calvície, estabeleceu-se um trabalho experimental utilizando o plasma rico em plaquetas (PRP) e seus fatores de crescimento, obtido do próprio sangue do paciente, no intuito de estimular a integração e o crescimento dos MICs. A exemplo de outros trabalhos publicados com PRP e seus fatores plaquetários, sobretudo nas áreas da traumatologia, odontologia, maxilofacial e na cirurgia plástica, acreditou-se neste protocolo cirúrgico como uma nova contribuição para a cirurgia da calvície com a utilização dos MICs. Material e Métodos: Foram selecionados 23 pacientes masculinos portadores de calvície do tipo padrão, na faixa etária de 22 a 55 anos, para um trabalho experimental de controle interno, emparelhado, em que cada paciente serviu como seu próprio controle. Delinearam-se duas áreas calvas de 2,5 cm x 2,5 cm em que, à direita do paciente, se implantaram os MICs embebidos em PRP com seus fatores de crescimento e, à esquerda, os MICS considerados controles. Ao final de 7 meses de pós-operatório realizou-se a contagem definitiva dos microimplantes desenvolvidos. Os dados quantitativos foram descritos com média e desvio padrão. A comparação do lado controle com o lado experimental foi realizada por teste t de Student para amostras emparelhadas. Foi também estimado o efeito do método experimental sobre o controle através da diferença média entre o número de MICs dos dois lados seguido de seu intervalo de confiança de 95%. Os dados foram processados e analisados com o auxílio do programa SPSS versão 12. 0.Resultados: Na comparação da contagem de MICs entre o lado experimental tratado com PRP e seus FCs e o lado controle, foi observada uma diferença estatisticamente significativa (P < 0,001). O lado esquerdo, considerado controle, teve um crescimento médio de 16,7 MICs/cm2 enquanto o lado direito, onde se utilizou o PRP, teve um crescimento de 18,9 MICs/cm2. Isto representou uma diferença de 13,6% a maior na densidade capilar. Alguns pacientes tiveram diferenças menores do que 5% e outros foram considerados casos excepcionais, com 31% e 52% de aumento na densidade capilar. Esta variabilidade deve ser considerada com cautela e novos estudos deverão ser estabelecidos observando-se também idade, fumo, exercícios físicos e dieta alimentar. Conclusão: De acordo com os resultados obtidos, houve um rendimento considerável superior de 13,6% no lado direito onde se utilizaram os MICs embebidos no PRP e seus FCPs. Houve eficácia e integração melhores, resultando num maior número de folículos e numa maior densidade capilar, o que trouxe um resultado positivo na cirurgia da calvície masculina do tipo padrão com o uso do PRP e seus FCPs.

no / Alopecia areata is an immunologically mediated disease characterized by extreme variability not only in the time of initial onset of hair loss but in the duration, extent and pattern of hair loss during any given episode of active loss. These variables, as well as the unpredictable nature of spontaneous regrowth and lack of a uniform response to various therapies, has made clinical trials in alopecia areata difficult to plan and implement. In fact, there are currently no drugs FDA-approved specifically for the indication of alopecia areata. To help facilitate well-controlled clinical trials for alopecia areata, this National Alopecia Areata Foundation (NAAF) sponsored subgroup of investigators/clinicians experienced in clinical trials and/or in the clinical care of patients with alopecia areata has outlined some general principles and potential endpoints for clinical studies in alopecia areata. These guidelines build on the Alopecia Areata Investigational Assessment Guidelines published in 1991 which established baseline clinical staging and background information important to gather on any alopecia areata patient involved in clinical research.

No / BACKGROUND: Androgenetic alopecia, or male pattern baldness, is a common, progressive disorder where large, terminal scalp hairs are gradually replaced by smaller hairs in precise patterns until only tiny vellus hairs remain. This balding can cause a marked reduction in the quality of life. Although these changes are driven by androgens, most molecular mechanisms are unknown, limiting available treatments. The mesenchyme-derived dermal papilla at the base of the mainly epithelial hair follicle controls the type of hair produced and is probably the site through which androgens act on follicle cells by altering the regulatory paracrine factors produced by dermal papilla cells. During changes in hair size the relationship between the hair and dermal papilla size remains constant, with alterations in both dermal papilla volume and cell number. This suggests that alterations within the dermal papilla itself play a key role in altering hair size in response to androgens. Cultured dermal papilla cells offer a useful model system to investigate this as they promote new hair growth in vivo, retain characteristics in vitro which reflect their parent follicle's response to androgens in vivo and secrete mitogenic factors for dermal papilla cells and keratinocytes. OBJECTIVES: To investigate whether cultured dermal papilla cells from balding follicles secrete altered amounts/types of mitogenic factors for dermal papilla cells than those from larger, normal follicles. We also aimed to determine whether rodent cells would recognize mitogenic signals from human cells in vitro and whether factors produced by balding dermal papilla cells could alter the start of a new mouse hair cycle in vivo. METHODS: Dermal papilla cells were cultured from normal, balding and almost clinically normal areas of balding scalps and their ability to produce mitogenic factors compared using both human and rat whisker dermal papilla cells as in vitro targets and mouse hair growth in vivo. RESULTS: Normal scalp cells produced soluble factors which stimulated the growth of both human scalp and rat whisker dermal papilla cells in vitro, demonstrating dose-responsive mitogenic capability across species. Although balding cells stimulated some growth, this was much reduced and they also secreted inhibitory factor(s). Balding cell media also delayed new hair growth when injected into mice. CONCLUSIONS: Human balding dermal papilla cells secrete inhibitory factors which affect the growth of both human and rodent dermal papilla cells and factors which delay the onset of anagen in mice in vivo. These inhibitory factor(s) probably cause the formation of smaller dermal papillae and smaller hairs in male pattern baldness. Identification of such factor(s) could lead to novel therapeutic approaches.

Yes / Humans are social animals that communicate disproportionately via potent genetic signals imbued in the skin and hair, including racial, ethnic, health, gender, and age status. For the vast majority of us, age-related hair pigment loss becomes the inescapable signal of our disappearing youth. The hair follicle (HF) pigmentary unit is a wonderful tissue for studying mechanisms generally regulating aging, often before this becomes evident elsewhere in the body. Given that follicular melanocytes (unlike those in the epidermis) are regulated by the hair growth cycle, this cycle is likely to impact the process of aging in the HF pigmentary unit. The formal identification of melanocyte stem cells in the mouse skin has spurred a flurry of reports on the potential involvement of melanocyte stem cell depletion in hair graying (i.e., canities). Caution is recommended, however, against simple extrapolation of murine data to humans. Regardless, hair graying in both species is likely to involve an age-related imbalance in the tissue's oxidative stress handling that will impact not only melanogenesis but also melanocyte stem cell and melanocyte homeostasis and survival. There is some emerging evidence that the HF pigmentary unit may have regenerative potential, even after it has begun to produce white hair fibers. It may therefore be feasible to develop strategies to modulate some aging-associated changes to maintain melanin production for longer.

Yes / Male sex hormones-androgens-regulate male physique development. Without androgen signaling, genetic males appear female. During puberty, increasing androgens harness the hair follicle's unique regenerative ability to replace many tiny vellus hairs with larger, darker terminal hairs (e.g., beard). Follicle response is epigenetically varied: some remain unaffected (e.g., eyelashes) or are inhibited, causing balding. How sex steroid hormones alter such developmental processes is unclear, despite high incidences of hormone-driven cancer, hirsutism, and alopecia. Unfortunately, existing development models are not androgen sensitive. Here, we use hair follicles to establish an androgen-responsive human organ culture model. We show that women's intermediate facial follicles respond to men's higher androgen levels by synthesizing more hair over several days, unlike donor-matched, androgen-insensitive, terminal follicles. We demonstrate that androgen receptors-androgen-activated gene transcription regulators-are required and are present in vivo within these follicles. This is the first human organ that involves multiple cell types that responds appropriately to hormones in prolonged culture, in a way which mirrors its natural behavior. Thus, intermediate hair follicles offer a hormone-switchable human model with exceptional, unique availability of genetically identical, but epigenetically hormone-insensitive, terminal follicles. This should enable advances in understanding sex steroid hormone signaling, gene regulation, and developmental and regenerative systems and facilitate better therapies for hormone-dependent disorders.

No / It is known that hair growth disorders and hair loss can cause personal distress and affect well‐being. Whilst clinical conditions remain a target for medical research, current research on hair follicle biology and hair growth control mechanisms also provides opportunities for a range of non‐medical and cosmetic interventions that have a modulating effect on the scalp and follicle function. Furthermore, an improvement of the hair fibre characteristics (cuticle structure, cortex size and integrity) could add to the overall positive visual effect of the hair array. Since phytochemicals are a popular choice because of their traditional appeal, this review provides a critical evaluation of the available evidence of their activity for hair benefit, excluding data obtained from animal tests, and offers recommendations on improving study validity and the robustness of data collection in pre‐clinical and clinical studies.

This study explores processes of identity construction among women who have skin conditions and body modifications. Analyzing seven semi-structured qualitative interviews, the author examines how individuals affected by skin conditions employ body modification practices to organize their identities and promote feelings of agency across both personal and social domains. Engaging a Bakhtinian dialogic lens, the author argues that body modification may operate as a de-stigmatization strategy that supports individuals with skin conditions in cultivating a sense of self-determination and bodily sovereignty. Shaped by grounded theory, this study’s findings trace relationships between body modification and the development of agentic identities among women with skin conditions. Confronted by medical, physical, and social disenfranchisement, women affected by skin conditions may implement body modification practices to navigate treatment, incorporate their conditions, and negotiate their relationships. The author additionally suggests implications for the application of body modification practices as somatic therapeutic modalities.