(summary of doctoral dissertation) It has become increasingly apparent in recent years that there are important differences of many cardiovascular disorders including ventricular tachycardias in men and women. Gender differences have been observed in the epidemiology, pathogenesis and clinical presentation of various ventricular arrhythmias. Physiological menopause occurs as a part of a woman's normal aging process being based on the natural cessation of estradiol and progesterone production by the ovaries. The dramatic fall in circulating estrogens levels at menopause impacts many tissues including cardiovascular system. Because the incidence of coronary heart disease (CHD) rises significantly after menopause, it has been hypothesized that women's CHD advantage before menopause (in comparison to men of the same age) could be due to the protective effects of estrogens. However, controversial results have been reported since early nineties until today. While some studies found reduction in the incidence of CHD and in mortality from cardiovascular diseases some other studies failed to provide any evidence for an independent role of estradiol levels in determining CHD in postmenopausal women and some studies even found positive association of endogenous estradiol with the risk of CHD among women above...

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Orientador: Hernandes Faustino de Carvalho / Dissertação (mestrado) - Universidade Estadual de Campinas, Instituto de Biologia / Made available in DSpace on 2018-08-09T08:33:52Z (GMT). No. of bitstreams: 1 Escobar_EsdrasLauniOliveira_M.pdf: 992060 bytes, checksum: 84890f8de9a24a3d1c8b06e7da089112 (MD5) Previous issue date: 2007 / Resumo: A próstata é uma glândula acessória do trato reprodutor masculino. Muitos são os fatores envolvidos no carcinogênese prostática. Os nutricionais são usualmente associados com a etiopatogenia do câncer de próstata, sendo que os ácidos graxos estão entre os mais importantes. O objetivo deste trabalho foi avaliar o efeito dos ácidos graxos presentes na dieta sobre o crescimento da próstata ventral de ratos, sobre a organização do tecido e sobre a expressão do receptor de andrógeno (AR) e do receptor dos ativadores da proliferação dos peroxissomos ? (PPAR?). Ratos Wistar machos foram utilizados, divididos em 5 grupos que receberam dietas isocalóricas por 10 semanas após o desmame. O grupo I foi tratado com dieta cuja porção lipídica continha óleo de soja. O grupo II recebeu óleo de soja e óleo de linhaça (1:1). O grupo III foi alimentado com óleo de linhaça. O grupo IV teve na dieta óleo de soja e banha de porco (1:1). O grupo V foi tratado com banha de porco. Ao fim do tratamento, as próstatas foram removidas e processadas para imunohistoquímica ou congeladas para análises bioquímicas. Os níveis circulantes de testosterona e do estradiol foram medidos. Os ensaios demonstraram que a banha de porco e o óleo de linhaça causaram efeitos opostos em relação ao crescimento prostático. Enquanto o primeiro promoveu um aumento no peso prostático, o outro causou uma significativa diminuição no órgão. A análise histológica revelou nítida hiperplasia epitelial, que foi confirmada pela análise estereológica, em resposta ao tratamento com dieta contendo apenas banha de porco como componente lipídico. Esta estrutura epitelial está associada a um aumento na taxa de proliferação epitelial, como demonstrado pela quantificação de células em proliferação, com o uso do antígeno Ki67. Experimentos de imunohistoquímica e Western blotting demonstraram um aumento na expressão de AR e PPAR? nos grupos que receberam banha de porco na dieta, enquanto o óleo de linhaça (contido) promoveu uma diminuição nos níveis de ambas as proteínas nucleares. Estes resultados sugerem que o crescimento prostático é influenciado por ácidos graxos presentes na dieta, e que esta influência pode ocorrer através de um aumento da expressão de AR e de PPAR?. Estes dados sugerem que PPAR? pode representar o elo de ligação entre a dieta e a predisposição ao câncer do próstata, sendo que a expressão e a função do AR podem ser alvos de regulação pelo PPAR?. Como os níveis circulantes de testosterona mostraram-se alterados é também possível que as alterações prostáticas sejam secundárias aos efeitos sistêmicos da dieta / Abstract: The prostate is an accessory gland of the male reproductive tract. Many factors are involved in prostate carcinogenesis. Nutritional factors are usually associated with the etiopathogenesis of the prostate cancer and fatty acids are among the most important ones. The objective of this work was to evaluate the effect of dietary fatty acid on the rat ventral prostate growth, tissue organization, and expression of androgen receptor (AR) and peroxisome proliferation-activator receptor ? (PPAR?). Male Wistar rats were used and divided in 5 groups that received isocaloric diets for 10 weeks after weaning. Group I was treated with soybean oil. Group II received soybean oil and linseed oil (1:1). Group III was fed on linseed oil. Group IV had soybean oil and rendered pork fat (1:1). Group V was treated with rendered pork fat. At the end of treatment, the prostates were removed and processed for immunohistochemistry or frozen for biochemical analyses. Circulating levels of testosterone and estradiol were measured. Experiments demonstrated that lard and linseed oil caused opposite effects on prostatic growth. While the former promoted an increase in prostatic weight, the latter resulted in a significantly lighter organ. Epithelial hyperplasia was observed by histological inspection and confirmed by stereology as the major tissue response to the rendered pork fat diet. This aspect was associated with higher proliferative rates as demonstrated by counting proliferating cell expressing the KI-67 antigen. Immunohistochemistry and Western blotting demonstrated increased expression of AR and PPAR? in groups receiving lard as the source of fatty acids, while linseed oil promotes a decrease on the protein levels of both nuclear receptors. These results suggest that prostate growth is influenced by dietary fatty acids and that this influence might occur via enhanced expression of PPAR? and AR. One suggests that PPAR? might represent the link between diet and predisposition to prostate cancer and that AR expression and function could be targeted by PPAR? activation. Since the levels of circulating testosterone were altered it is also possible that prostatic changes are secondary to systemic effects of the diet / Mestrado / Histologia / Mestre em Biologia Celular e Estrutural

Orientador: Maricilda Palandi de Mello / Dissertação (mestrado) - Universidade Estadual de Campinas, Instituto de Biologia / Made available in DSpace on 2018-08-15T17:10:17Z (GMT). No. of bitstreams: 1 Petroli_ReginaldoJose_M.pdf: 2303670 bytes, checksum: 1836c8a6df94a76ee177d830781dc293 (MD5) Previous issue date: 2010 / Resumo: Considera-se que insensibilidade androgênica seja a causa mais freqüente dos distúrbios da diferenciação do sexo em pacientes com cariótipo 46,XY. Trata-se de uma anomalia recessiva ligada ao cromossomo X, que pode se manifestar de forma branda, parcial ou completa, com um amplo espectro de variação fenotípica. O gene do receptor de andrógenos (AR) está localizado no cromossomo X, na região Xq11-12, sendo organizado em oito exons separados por introns de até 26 kb. Sua região codificante apresenta aproximadamente 2.757 pares de bases traduzindo uma proteína de 919 aminoácidos, cujo peso molecular é de aproximadamente 110 kDa. A proteína AR apresenta três domínios funcionais: domínio de regulação transcricional (amino-terminal), domínio de ligação ao DNA que contém dois dedos de zinco (zinc finger) e domínio de ligação ao esteróide (carboxi-terminal). O domínio amino-terminal possui repetições dos aminoácidos glutamina e glicina cujos números podem variar dentro da população normal. O domínio de ligação ao esteróide (carboxi-terminal), apresenta o maior número de mutações, cerca de 55% das descritas neste gene. Entre o domínio de ligação ao DNA e o domínio de ligação ao esteróide encontra-se a região hinge que contém um sinal responsável pela localização nuclear necessária para a translocação do complexo andrógeno/receptor do citoplasma para o núcleo da célula. Pacientes com cariótipo 46,XY e diagnóstico de insensibilidade androgênica geralmente apresentam fenótipo feminino ou ambigüidade genital, porém a produção de testosterona é normal. Nestes pacientes a investigação de mutações no gene do receptor de andrógeno é indicada para a identificação da alteração molecular relacionada à doença. Desta maneira, o presente estudo teve como objetivo a caracterização das alterações moleculares do gene AR, através da análise de seus oito exons e junções exons-introns por reação da cadeia da polimerase (PCR) seguida de sequenciamento dos fragmentos amplificados. Das 47 famílias que compõem a casuística deste trabalho, 14 apresentaram mutações no gene, sendo uma relacionada ao fenótipo brando da insensibilidade androgênica (p.P694S), sete relacionadas ao fenótipo parcial da insensibilidade androgênica (p.Q58L, p.A596T, p.S597R, p.M742V, p.Q798E, p.L830F e p.A896V) e seis relacionadas ao fenótipo completo da insensibilidade androgênica (p.R774H, p.P766S, p.C806F, p.R832Term, p.R855H e p.V866M). Uma paciente apresentou duas alterações, ambas no exon 6 deste gene. Quatro mutações estão sendo descritas pela primeira vez neste trabalho em pacientes com insensibilidade androgênica / Abstract: The androgen insensitivity syndrome (AIS) is considered the most frequent disorders of sex differentiation in patients with 46,XY karyotype. It is a recessive X linked disorder, which manifests as mild, partial or complete forms, with a broad spectrum of phenotypic variation. The androgen receptor gene (AR) is located on the X chromosome within Xq11-12 region. It is organized in eight exons separated by introns up to 26 kb in length. Its coding region comprises approximately 2,757 base pairs translating a protein of 919 amino acids, whose molecular weight is approximately 110 kDa. The AR protein has three functional domains: the transcriptional regulatory domain, the DNA binding domain which contains two zinc fingers and the steroid binding domain in the carboxy-terminal region. The amino-terminal domain presents repeats of glutamine and glycine whose numbers of residues vary within the normal population. The steroid-binding domain presents the highest number of mutations, around 55% of the mutations described in this gene are located in this region. Between the DNA-binding domain and the steroid-binding domain there is a hinge region that contains a signal responsible for nuclear localization required for translocation of the complex androgen/receptor from the cytoplasm to the cell nucleus. Patients with 46,XY karyotype and androgen insensitivity diagnosis usually have female or ambiguous genitalia, but normal testosterone production. In these patients the investigation of androgen receptor gene mutations is indicated to identify the molecular changes related with AIS. Therefore, the aim of this study was to characterize molecular alterations in the AR gene, by analysis of the eight exons and introns-exons junctions by polymerase chain reaction (PCR) followed by sequencing the amplified fragments. Fourteen out of 46 families comprised in this study had mutations identified. One mutation corresponded to the mild phenotype of androgen insensitivity (p.P694S), seven were related to the partial androgen insensitivity phenotype (p.Q58L, p.A596T, P. S597R, p.M742V, p.Q798E, p.L830F and p.A896V), and six were associated to the complete androgen insensitivity phenotype (p.R774H, p.P766S, p.C806F, p.R832Term, p.R855H and p.V866M). One patient presented two mutations, both located in exon 6 of the gene. Four mutations were described for the first time in this research in patients with androgen insensitivity / Mestrado / Genetica Animal e Evolução / Mestre em Genética e Biologia Molecular

Orientadores: Cássio Luís Zanettini Riccetto, Benedicto de Campos Vidal / Dissertação (mestrado) - Universidade Estadual de Campinas, Faculade de Ciências Médicas / Made available in DSpace on 2018-08-21T00:28:08Z (GMT). No. of bitstreams: 1 Feitosa_IsabelCristinaAlbuquerque_M.pdf: 2111462 bytes, checksum: 4056f4a3329834819c83f886cc2bfe79 (MD5) Previous issue date: 2012 / Resumo: Introdução: A incontinência urinária é um problema de saúde muito prevalente, afetando entre 10% a 50% das mulheres em algum momento de sua vida, causando morbidade social e redução na qualidade de vida. Nas mulheres entre 40-59 anos a incontinência urinária de esforço é mais frequente e naquelas acima de 60 anos a urge-incontinência é mais prevalente. A mudança de padrão de incontinência com o aumento da idade pode sugerir que o envelhecimento em geral e as alterações fisiológicas decorrentes deste processo possam contribuir com a sua patogênese. Há vários anos foi demonstrado que os tecidos originados do seio urogenital são sensíveis aos hormônios sexuais, principalmente o estrógeno. Recentemente, tem surgido importante interesse no uso da suplementação de andrógenos nas mulheres. Embora existam significativos interesses nas aplicações clínicas dos andrógenos em mulheres, não se sabe exatamente como se dá a atuação destes hormônios no assoalho pélvico e trato urinário inferior. Objetivo: Analisar o efeito da suplementação de metiltestosterona sobre as propriedades anisotrópicas das fibras musculares e colágenas periuretrais de ratas. Métodos: Foi realizado um estudo experimental com 30 ratas que foram divididas em dois grupos: 15 ratas submetidas a suplementação de metiltestosterona por 60 dias e 15 ratas controles. Posteriormente foi removida a bexiga, uretra e região perineal em bloco. A região periuretral foi analisada através de microscopia de polarização, com quantificação da birrefringência das fibras musculares e colágenas. Resultados: A densidade média de brilho da musculatura, no grupo controle foi de 65,3070. No grupo com suplementação de testosterona foi 84,7624, portanto com diferença estatisticamente significativa (p =0,006). Quanto às medidas da birrefringência do colágeno periuretral nos grupos controle e com suplementação de testosterona, foram obtidas com mediana de 95,9436 no controle e a mediana foi de 100,8646 no grupo com testosterona, com diferença estatisticamente significativa entre os dois grupos avaliados, com p = 0,005. Conclusão: O uso de testosterona promoveu um aumento nos valores de birrefringência das fibras colágenas e musculares periuretrais de ratas submetidas a suplementação de metiltestosterona quando comparadas com o grupo controle / Abstract: Introduction: Urinary incontinence is a prevalent health problem, affecting between 10% and 50% of women at some point in their lives, causing social morbidity and reduced quality of life. Among women between 40-59 years of age, stress urinary incontinence is more frequent and in those above 60 years of age urge incontinence is more prevalent. The changing pattern of incontinence with increasing age may suggest that the aging process and the physiological changes resulting from this process may play a role in its pathogenesis. It has been shown for the last years that the tissues derived from urogenital sinus are sensitive to estrogen. Recently, there has been significant interest in the use of androgen supplementation in women. Although there is significant interest in clinical applications of androgens in women, it is not known exactly how occurs the action of these hormones in the pelvic floor and lower urinary tract. Objective: To analyze the effect of methyltestosterone supplementation on the anisotropic properties of the periurethral collagen and muscle fibers of rats. Methods: We conducted an experimental study with 30 female rats that were divided into 2 groups: 15 rats subjected to supplementation of methyltestosterone for 60 days and 15 control rats. Bladder, urethra, and perineum were removed en block after sacrifice. The periurethral region was analyzed by polarized light microscopy with quantification of the birefringence of muscle and collagen fibers. Results: The mean density of brightness of the muscles in the control group was 65.3070. In the group with testosterone supplementation was 84.7624, so the difference was statistically significant (p = 0.006). The measurements of birefringence of periurethral collagen fibers in control and testosterone groups were obtained with a median of 95.9436 in control and 100.8646 in the testosterone group, with statistically significant difference between them, with p = 0.005. Conclusion: The use of testosterone promoted an increase in the values of birefringence of periurethral collagen fibers and muscle tissue of rats submitted to methyltestosterone supplementation when compared with the control group / Mestrado / Fisiopatologia Cirúrgica / Mestre em Ciências

The purpose was to examine the effect of chronic alcohol abuse on the androgen receptor content (AR) in skeletal muscle, and to determine if this effect was influenced by resistance training. Thirty-four male rats (456 ± 1 g; mean ± SE) were divided into 4 groups: Sham exercise-Ethanol, Sham exercise-Normal diet, Exercise-Ethanol, and Exercise-Normal diet. Both Exercise groups underwent a 6-week "squat" resistance training protocol and both Ethanol groups received an alcohol-rich diet throughout the 6-week period. Western blot analysis showed no effect of alcohol or resistance training on the AR of the extensor digitorum longus. For the rectus femoris, alcohol caused a decline in the AR (p=0.01). This reduction was not attenuated by resistance training. The AR of the soleus was not affected by chronic alcohol abuse alone; however, the resistance training induced increase in the AR was prevented by chronic alcohol abuse (p=0.03).

Orientador: Sebastião Roberto Taboga / Tese (doutorado) - Universidade Estadual de Campinas, Instituto de Biologia / Made available in DSpace on 2018-08-07T21:06:44Z (GMT). No. of bitstreams: 1 Santos_FernandaCristinaAlcantarados_D.pdf: 8013059 bytes, checksum: 981f820c48d983ff59f0fae9c64ba43d (MD5) Previous issue date: 2006 / Resumo: A próstata feminina é uma glândula funcionalmente ativa encontrada em diversas espécies de mamíferos, incluindo humanos e roedores. Em fêmeas adultas de gerbilos, a próstata apresenta localização parauretral, exibindo íntimo contato com a parede da uretra mediana e distal. Esta glândula é homóloga a próstata ventral de roedores machos, sendo formada por um conjunto de glândulas e ductos inseridos em um estroma fibromuscular. Em machos, a fisiologia prostática é regulada por hormônios esteróides, principalmente andrógenos e estrógenos. Em fêmeas, os fatores que influenciam a atividade prostática são pouco conhecidos, embora existam indícios de que alterações hormonais decorrentes da senescência estejam associadas à instalação de lesões prostáticas. Assim, o objetivo deste trabalho foi avaliar os fatores que promovem a regulação hormonal da próstata feminina do gerbilo (Meriones unguiculatus) em condições de hiperandrogenismo e de supressão da atividade estrogênica. Os resultados obtidos com as análises estruturais, ultra-estruturais, sorológicas e imunocitoquímicas permitiram concluir que a próstata feminina do gerbilo é sensível à ação de andrógenos e de agentes anti-estrogênicos. O estímulo androgênico provocou crescimento anormal da próstata, aumento da atividade secretória, além de causar displasia prostática e síndrome de ovário policístico. O tratamento com letrozol resultou em aumento dos níveis séricos de testosterona, hiperplasia glandular, incremento da atividade secretória e crescimento displásico, simulando os efeitos causados por andrógenos exógenos. Os efeitos causados pelo tamoxifeno indicam que este agente endócrino atuou como agonista estrogênico na próstata, causando hipertrofia glandular, diminuição da atividade secretória e desenvolvimento de lesões prostáticas, tais como prostatites e adenocarcinoma. Deste modo, pode-se concluir que a utilização de drogas hormonalmente ativas resulta em uma série de efeitos complexos que comprometem a fisiologia de órgãos hormônio-dependentes, como a próstata feminina e os ovários. O desequilíbrio hormonal provocado pela administração destas drogas causa profundas alterações na morfologia prostática, de maneira muito similar ao que ocorre durante o desenvolvimento de lesões espontâneas em mulheres no período pós-menopausa. Assim, essas terapias devem ser utilizadas com cautela, visto que longos períodos de tratamento podem resultar em lesões malignas da próstata feminina / Abstract: The female prostate is a functionally active gland found in several species of mammals, including humans and rodents. In adult female gerbils, the prostate presents a paraurethral location, showing close contact with the wall of urethra in its median and distal portions. This gland is homologue to the ventral prostate of male rodents and it is formed by a cluster of glands and ducts inserted into a fibermuscular stroma. In males, the prostatic physiology is regulated by steroid hormones, mainly androgen and estrogen. In females, the factors that influence the prostatic activity are unclear, although there are evidences that the hormonal alterations caused by aging are associated with the installation of prostatic lesions. Thus, the objective of this work is to evaluate the factors that promote the hormonal regulation of the gerbil (Meriones unguiculatus) female prostate in hyperandrogenic conditions and estrogenic activity suppression. The results obtained with the structural, ultrastructural, serologic and immunocytochemical analyses showed that the gerbil female prostate is responsive to androgenic and the anti-estrogenic action. The androgenic stimulus has caused an abnormal prostatic growth, increase in secretory activity, and has also caused prostatic dysplasia and polycystic ovary syndrome. The letrozole treatment has stimulated an increase in testosterone serum levels, glandular hyperplasia, increment of the secretory activity and dysplasic growth, simulating the effects provoked by exogenous androgens. The effects caused by tamoxifen indicate that this endocrine agent has acted as an estrogenic agonist on the prostate, causing glandular hypertrophy, decrease in secretory activity and prostatic lesions. Hence, it is possible to conclude that the use of hormonally active drugs results in a series of complex effects that endanger the physiology of hormone-dependent organs, like female prostate and ovaries. The hormonal unbalance caused by the administration of such drugs results in alterations in prostatic morphology similar to what occurs during the development of spontaneous lesions in post-menopausal women. Thus, the utilization of such therapies must occur in a careful manner because a long-term treatment can cause malignant lesions in female prostate / Doutorado / Biologia Celular / Doutor em Biologia Celular e Estrutural

The balance between the costs and benefits of conspicuous signals ensures that the expression of those signals is related to the quality of the bearer. Plastic signals could enable males to maximize conspicuous traits to impress mates and competitors, but reduce the expression of those traits to minimize signaling costs, potentially compromising the information conveyed by the signals. I investigated the effect of signal enhancement on the information coded by the biphasic electric signal pulse of the gymnotiform fish Brachyhypopomus gauderio. Increases in population density drive males to enhance the amplitude of their signals. I found that signal amplitude enhancement improves the information about the signaler’s size. Furthermore, I found that the elongation of the signal’s second phase conveys information about androgen levels in both sexes, gonad size in males and estrogen levels in females. Androgens link the duration of the signal’s second phase to other androgen-mediated traits making the signal an honest indicator of reproductive state and aggressive motivation. Signal amplitude enhancement facilitates the assessment of the signaler’s resource holding potential, important for male-male interactions, while signal duration provides information about aggressive motivation to same-sex competitors and reproductive state to the opposite sex. Moreover, I found that female signals also change in accordance to the social environment. Females also increase the amplitude of their signal when population density increases and elongate the duration of their signal’s second phase when the sex ratio becomes female-biased. Indicating that some degree of sexual selection operates in females. I studied whether male B. gauderio use signal plasticity to reduce the cost of reproductive signaling when energy is limited. Surprisingly, I found that food limitation promotes the investment in reproduction manifested as signal enhancement and elevated androgen levels. The short lifespan and single breeding season of B. gauderio diminishes the advantage of energy savings and gives priority to sustaining reproduction. I conclude that the electric signal of B. gauderio provides reliable information about the signaler, the quality of this information is reinforced rather than degraded with signal enhancement.

No description available.

No / The nervous system communicates with peripheral tissues through nerve fibres and the systemic release of hypothalamic and pituitary neurohormones. Communication between the nervous system and the largest human organ, skin, has traditionally received little attention. In particular, the neuro-regulation of sebaceous glands (SGs), a major skin appendage, is rarely considered. Yet, it is clear that the SG is under stringent pituitary control, and forms a fascinating, clinically relevant peripheral target organ in which to study the neuroendocrine and neural regulation of epithelia. Sebum, the major secretory product of the SG, is composed of a complex mixture of lipids resulting from the holocrine secretion of specialised epithelial cells (sebocytes). It is indicative of a role of the neuroendocrine system in SG function that excess circulating levels of growth hormone, thyroxine or prolactin result in increased sebum production (seborrhoea). Conversely, growth hormone deficiency, hypothyroidism, and adrenal insufficiency result in reduced sebum production and dry skin. Furthermore, the androgen sensitivity of SGs appears to be under neuroendocrine control, as hypophysectomy (removal of the pituitary) renders SGs largely insensitive to stimulation by testosterone, which is crucial for maintaining SG homeostasis. However, several neurohormones, such as adrenocorticotropic hormone and α-melanocyte-stimulating hormone, can stimulate sebum production independently of either the testes or the adrenal glands, further underscoring the importance of neuroendocrine control in SG biology. Moreover, sebocytes synthesise several neurohormones and express their receptors, suggestive of the presence of neuro-autocrine mechanisms of sebocyte modulation. Aside from the neuroendocrine system, it is conceivable that secretion of neuropeptides and neurotransmitters from cutaneous nerve endings may also act on sebocytes or their progenitors, given that the skin is richly innervated. However, to date, the neural controls of SG development and function remain poorly investigated and incompletely understood. Botulinum toxin-mediated or facial paresis-associated reduction of human sebum secretion suggests that cutaneous nerve-derived substances modulate lipid and inflammatory cytokine synthesis by sebocytes, possibly implicating the nervous system in acne pathogenesis. Additionally, evidence suggests that cutaneous denervation in mice alters the expression of key regulators of SG homeostasis. In this review, we examine the current evidence regarding neuroendocrine and neurobiological regulation of human SG function in physiology and pathology. We further call attention to this line of research as an instructive model for probing and therapeutically manipulating the mechanistic links between the nervous system and mammalian skin. / Agency for Science, Technology and Research. Grant Numbers: A*STAR Research Attachment Programme (ARAP), IAF‐PP H17/01/a0/004, IAF‐PP H17/01/a0/008; NIHR Manchester Biomedical Research Centre, Inflammatory Hair Disease Programme; University of Manchester; University of Miami