Avaliar a biocompatibilidade do fio lifting biológico - fio serrilhado de poliuretana de óleo de mamona - e sua eficácia no rejuvenescimento facial. Na primeira etapa deste trabalho implantamos os fios no dorso de camundongos, que foram sacrificados com 03, 07, 15 e 30 dias com posterior análise histológica por microscopia óptica. Na segunda fase implantamos os fios na face de pacientes com flacidez dérmica e analisamos, fotograficamente e através de uma modelagem numérico-computacional o resultado (rejuvenescimento), com intervalos entre 07 e 60 dias. As análises histológicas demonstraram uma rápida integração do fio ao tecido celular subcutâneo com formação abundante de colágeno e as fotografias dos pacientes revelaram uma maior firmeza da derme e um rejuvenescimento facial, comprovados pela análise computacional. Suas características químicas e físicas e os resultados iniciais nos permitem acreditar que o fio lifting biológico - fio serrilhado de poliuretana do óleo de mamona - apresenta elevada biocompatibilidade com uma rápida integração ao tecido subcutâneo sendo uma excelente opção no rejuvenescimento facial. / Evaluate the biological lifting thread - castor oil polyurethane serrulate thread - bio-compatibility and it´s eficacy on facial rejuvenation. At first we implanted the threads in subcutaneous tissues on mice backs that were sacrificed after 03, 07, 15 and 30 days, followed by histological analysis of material by using optical microscopy. Later, implants were carried out in patients with facial dermal flaccidity, and comparisons were made through photographs between 7 and 60 days, than we made a numerical-computational modelling comparision of this photographs. Histological analysis showed a quick thread integration with the celular subcutaneous tissue by a large amount of colagen syntesis and the patients photographs showed facial rejuvenation with improvement of the skin flaccidity comproved by numerical modelling. It`s chemical and physical characteristics and the initial results allow us belive that the biological lifting thread - castor oil polyurethane serrulate thread - has good bio-compatibility and fast integration with the celular subcutaneous tissue being an excellent option for the facial rejuvenation.

Ainda que resulte na sobrevida do paciente, o tratamento atual de queimaduras profundas e extensas é imperfeito. A contratura cicatricial e o aspecto rendilhado persistentes na área enxertada produzem resultados estéticos e funcionais pobres. A principal dificuldade no adequado restabelecimento do tegumento destes pacientes é o déficit de derme, decorrente da reposição das perdas com enxertos relativamente finos. Neste trabalho são relatados quatro casos, decorrentes da familiaridade obtida em nossa prática clínica com o emprego de pele preservada em glicerol, nos quais foi utilizada a enxertia combinada, isto é, derme alógena residual sobreposta por enxertos de espessura parcial autógenos, como forma de reposição de matriz dérmica. Os tegumentos resultantes da enxertia combinada mostraram-se estáveis e duráveis, dentro do período de seguimento dos casos apresentados. / Although it results in the patient\'s survival, the current treatment of deep and extensive burns is imperfect. Scar contracture and the persistent lacy aspect in the grafted area produce aesthetic and functional poor results. The main difficulty in the appropriate re-establishment of the tegument of these patients is the deficit of dermis, due to the replacement of the skin losses with relatively thin grafts. In this work, decurrent of the familiarity obtained in our clinical practice with glycerol preserved cadaver skin, four cases are reported, which the combined grafting was used, that is, residual allogeneous dermis put upon by split thickness autogenous grafts, as form of replacement of dermal matrix. The resulting teguments of the combined grafting were shown stable and durable, inside the follow-up period of the presented cases.

O objetivo desse estudo foi comparar duas técnicas cirúrgicas para recobrimento radicular e avaliar qual delas ofereceu o melhor resultado estético e menor morbidade. Foram selecionados 20 participantes adultos, não fumantes, que apresentaram retrações gengivais múltiplas bilaterais, classe I ou II de Miller, localizadas em caninos, primeiros e segundos pré-molares. As duas técnicas utilizaram a MDA como enxerto. Porém, em um quadrante foi realizado um retalho parcial com incisões relaxantes unidas através de uma incisão intrasucular, a MDA foi posicionada a 1 mm apical a junção amelocementária (JAC) e o retalho posicionado a 1 mm coronal a JAC. No quadrante oposto foi realizada uma técnica minimamente invasiva de envelope supra periosteal que não utiliza incisões relaxantes, preserva as papilas, além de evitar eventuais cicatrizes. Os parâmetros clínicos (profundidade clínica de sondagem, nível clínico de inserção, índice de sangramento a sondagem, altura e largura da retração gengival e altura e espessura de gengiva queratinizada) foram avaliados 2 semanas após a terapia periodontal básica e após 6 meses aos procedimentos cirúrgicos. No exame inicial todos os parâmetros foram similares, tanto para grupo teste como para grupo controle. Não houve diferença estatisticamente significante favorecendo nenhuma das técnicas, porém o grupo controle teve números sutilmente melhores do que o grupo teste. Apesar de ambos procedimentos cirúrgicos terem proporcionado melhora significativa em todos os parâmetros analisados, com exceção da PCS, a técnica controle obteve melhores resultados, porém sem diferenças estatisticamente significantes. / Aim: The aim of this study is to compare two surgical techniques using acelular dermal matrix (ADM)for the treatment of gingival recessions. Material and Methods: Twenty patients with bilteral class I and II multiple gingival recession were selected for a Split mouth study design. At one side a modified extended coronally advanced flap (MECAF) was used. At the contralateral a supra periosteal flap (TUN) was performed. Both sides were associated with ADM, so that the technique was the only variable. The clinical parameter evaluated were: probing pocket depth (PD), relative clinical attachment level (RCAL), gingival index (GI), gingival recession height (GR), width of keratinized tissue (KT), keratinized tissu thickness (TKT), and gingival recession area (GRA). Post-operative pain was evaluated with a visual analog scale (VAS) weekly on the first month post operative. Clinical examination was performed at baseline and 6 months post operative. Results: At baseline, no differences at any of the parameters examined could be detected between groups. Both groups were effective to reduce GR, but no difference was detected between them (ΔGR: MECAF= 2.28 &plusmn 1.01; TUN= 1.93 &plusmn 1.36mm). The % of root coverage was numerically superior favoring (MECAF = 61.24 &plusmn 23.42%; TUN= 56.07 &plusmn 22.02%), without significant differences between groups. PD Did not changed significantly after treatment and a clincial attachment gain associated with reduction of gingival recession was noted. Post operative pain was more frequent on MECAF, but no significant difference between groups could be noticed. Conclusions: Both treatments were effective on reducing gingival recession and might be valuable for the treatment of multiple gingival recessions. No significant differences could be shown despite a numerical advantage favored MECAF.

O crescente aumento da resistência microbiana aos antibióticos disponíveis impulsiona a busca por novas substâncias, com características superiores às correntemente usadas. Neste sentido, este trabalho propôs investigar as propriedades terapêuticas do xilitol visando a sua aplicação no controle da dermatite atópica, patologia que acomete a pele e que é agravada pela presença da bactéria Staphylococcus aureus. No presente estudo foram executados ensaios in vitro de atividade antimicrobiana do xilitol e verificado se este composto atua na aderência bacteriana, sobre a bactéria Staphylococcus aureus ATCC 25923. Foi avaliada a ação do xilitol produzido tanto pela via química quanto pela biotecnológica, sendo este último obtido a partir de fermentação do hidrolisado hemicelulósico da palha de trigo, nas concentrações de 1, 5 e 10 % (p/ v). A seguir, foram executados testes de toxicidade dérmica aguda com doses repetidas com xilitol nas concentrações de 5 e 10 % (p/ p), nas formas farmacêuticas de creme e de gel, em coelhos albinos da raça Nova Zelândia e testes de fototoxicidade, na concentração de 10 % (p/ p), nas formas farmacêuticas de creme e de gel, utilizando cobaias albinas da raça Durkin-Hartley. Em relação aos ensaios in vitro, observou-se que o xilitol, nas concentrações testadas, não impediu o crescimento bacteriano, mas inibiu a aderência da bactéria a uma superfície de prova, evidenciando ser este o provável mecanismo de ação desta substância sobre as bactérias. Em testes toxicológicos realizados, todas as formulações contendo xilitol foram classificadas como não irritantes quando foram avaliadas quanto à toxicidade dérmica aguda com doses repetidas. Entretanto, nos testes da fototoxicidade, as formulações testadas apresentaram certa fototoxicidade, sugerindo ser a formulação a base de creme mais fototóxica do que aquela a base de gel. Estes resultados evidenciam a aplicabilidade do xilitol no controle da dermatite atópica, como princípio ativo de formulações seguras, observando que a aplicação deve ser realizada com o uso de protetor solar. Este estudo buscou contribuir de maneira expressiva na elucidação do mecanismo de ação do xilitol e verificar os cuidados que devem ser considerados quando realizada sua aplicação pela via dérmica. / Since the microorganisms\' resistance to antibiotics increases, it is imperative to look for different substances that can combat these pathogens growth, with greater advantages. The propose of this work was to study therapeutic properties of xylitol in order to control atopic dermatitis, a dermal disease characterized by the presence of Staphylococcus aureus bacterium. Xylitol is a substance that can be obtained by chemical and biotechnological means, being the latter a relevant alternative that produces high-value compounds obtained by fermentation of lignocelullosic hydrolysates. In the present study in vitro assays were performed in order to check if wxylitol (obtained by chemical and biotechnological means) has antimicrobial activity at 1, 5 and 10 % (w/ v) concentrations. Other assays were also performed to verify if xylitol properties, at the same concentrations, hinder the adherence of Staphylococcus aureus ATCC 25923 bacterium. Xylitol was produced by biotechnological means using wheat straw hemicellulosic hydrolysate. Afterwards, in vivo assays were performed to investigate if xylitol is safe for skin application. Acute dermal toxicity tests with repeated doses were done with New Zealand rabbits using concentrations of 5 and 10 % (w/ w) xylitol, in either cream or gel. Phototoxicity assays were also performed with Durkin-Hartley guinea pigs, using only 10 % (w/ w) xylitol, in cream and gel forms. It was observed that xylitol does not have antimicrobial properties on S. aureus at all tested concentrations, but this compound has the capability of inhibiting this bacterium adherence on a surface, at all tested concentrations. In relation to toxicity assays, formulations contaning xylitol are nonirritative. However, xylitol has phototoxicity properties, mainly when cream is the base. Xylitol is an adequate alternative to be applied for atopic dermatitis control, and its application on the skin should be done with sunscreen. This study aimed to clarify xylitol action mechanism and to check the cares that should be taken when xylitol is applied on skin.

Objetivo: Estudar os efeitos do emprego de dois materiais consideravelmente diferentes quanto à origem e custo na correção intra-uterina da meningomielocele criada experimentalmente em feto de ovino. Métodos: Em 36 fetos de ovinos foi criado um defeito aberto de tubo neural, com 75 de dias de gestação. Os casos foram divididos em três grupos: o controle onde o defeito não foi corrigido, grupo corrigido A onde o material utilizado para cobrir a medula exposta foi a matriz dérmica humana acelular (MDHA) e o grupo corrigido B onde o material foi a celulose biossintética (CB). Após a correção realizada com 100 dias, os fetos eram mantidos intra-útero até o termo da gestação. Os sacrifícios foram realizados com 140 dias e a coluna fetal era submetida à análise macro e microscópica onde foi observada a aderência dos materiais à pele, medula ou tecido nervoso remanescente. Resultados: Na fase inicial (piloto), 11 fetos foram operados e 4 sobreviveram (37%). Na segunda fase (estudo) 25 fetos foram operados e 17 sobreviveram (68%). No grupo de estudo, 6 fetos não foram submetidos à correção (grupo controle), 11 casos foram corrigidos e ocorreu 1 perda fetal. Do total de 10 casos, 4 constituíram o grupo A e 6, o grupo B. À macroscopia observou-se deslizamento da pele e tecidos subjacentes sobre a CB em todos os casos onde ela foi empregada e isto não ocorreu em nenhum dos casos onde a MDHA foi utilizada. Para comparar a aderência, foram considerados 4 casos do grupo A e 4 do grupo B. A aderência, caracterizada pela migração de células do hospedeiro e proliferação de vasos para dentro da MDHA, foi observada em 100% dos casos do grupo A e em nenhum caso no grupo B (p < 0,05). No grupo B observou-se formação de uma camada de fibroblastos ao redor do material, protegendo a medula, caracterizando a formação de uma \"neoduramater\". Conclusão: A utilização da película de celulose biossintética parece ser mais adequada como substituto de dura-máter para cobertura e proteção do tecido nervoso que a matriz dérmica humana acelular. Ela parece promissora na correção intra-uterina da meningomielocele, evitando a aderência do tecido nervoso aos planos superficiais (\"medula presa\") minimizando os efeitos deletérios do ambiente intra-uterino sobre a medula espinhal. / Purpose: The aim of this study was to compare the effectiveness of two dura-mater substitutes, namely human acellular dermal matrix (HADM) and biosynthetic cellulose (BC), in repairing, in utero, surgically-induced meningomyelocele (MMC) in fetal sheep. Methods: A neural tube defect was created at 74-77 days gestation in 36 fetal sheep. They were divided into 3 groups, the control group that did not receive pre-natal corrective surgery, and the other two groups that received corrective surgery using HADM (Group A) or BC (Group B). Both materials were used as a dura-mater substitutes between the neural tissue and the sutured skin. Correction was performed at gestation day 100 and the fetuses were maintained in utero until term. Sheep were sacrificed on gestation day 140. The fetal spine was submitted to macro and microscopic analysis. At microscopy, adherence of the material to the skin and neural tissue was analyzed. Results: In the initial phase (pilot), experimentally-induced MMC was performed on 11 fetuses and 4 survived (37%). In the second phase (study), 25 fetuses received surgery and 17 survived (68%). In the study group, 6 fetuses did not undergo repair (control group), 11 cases were submitted to corrective surgery (experimental group) and one fetal loss occurred. Of the surviving cases in the experimental group, 4 constituted Group A and 6 in Group B. Macroscopically, skin and underlying tissues where easily displaced from the BC in all cases it was used; in contrast, HADM adhered to these tissues. To compare the adherence, 4 cases from Group A and 4 in Group B were studied. We observed adherence, host cell migration and vessel proliferation into the HADM all sections from Group A and this aspect was not present in any cases in Group B (p < 0.05). In Group B, we also observed that a new fibroblast layer formed around the BC thus protecting the medulla and constituting a \"neoduramater\". Conclusion: The use of BC seems to be more adequate as a dura-mater substitute to cover the damaged neural tissue than HADM. It seems promising for use in the in utero correction of MMC because to does not adhere to neural tissue of superficial and deep layers (\"tethered spinal cord\"). Thus, BC minimizes the mechanical and chemical intrauterine damage to the spinal medulla.

Objetivo: O objetivo deste estudo clínico, controlado, randomizado, foi comparar duas técnicas cirúrgicas para recobrimento radicular com enxerto de matriz dérmica acelular (EMDA) para avaliar qual procedimento proporcionaria maior recobrimento radicular e quantidade de tecido queratinizado. Materiais e Métodos: Foram selecionados 15 pacientes com retrações gengivais bilaterais Classe I ou II de Miller. Os 15 pares de retrações foram designados e tratados aleatoriamente no grupo teste, e as retrações contralaterais no grupo controle. O EMDA foi utilizado em ambos os grupos. No grupo controle o enxerto e o retalho foram posicionados no nível da junção amelocementária (JAC), e no grupo teste o enxerto foi estabilizado 1 mm apical a JAC e o retalho 1 mm coronal a JAC. Os parâmetros clínicos avaliados foram profundidade de sondagem (PS), nível clínico de inserção relativo (NCIR), altura da retração gengival (RG), e a altura (GQ) e espessura da gengiva queratinizada (EGQ). A área da retração gengival (ARG), um novo parâmetro, foi medida em fotografias padronizadas através da utilização de um aparelho apropriado e um programa de computador. As medidas foram tomadas antes das cirurgias e após 6 meses das mesmas. Resultados: No exame inicial todos os parâmetros foram similares para ambos grupos. Houve diferença estatisticamente significante favorecendo a técnica proposta para todos os parâmetros com exceção da quantidade de tecido queratinizado após 6 meses. Conclusão: A técnica teste proposta se mostrou mais adequada para procedimentos de recobrimento radicular com EMDA, e o novo parâmetro avaliado parece ser apropriado para análises de recobrimento radicular. (Protocolo de registro Clinicaltrials.gov: NCT01175720) / Aim: The aim of this randomized, controlled, clinical study was to compare two surgical techniques for root coverage with the acellular dermal matrix graft (ADMG) to evaluate which procedure could provide better root coverage and greater amounts of keratinized tissue. Materials and Methods: Fifteen patients with bilateral Miller Class I or II gingival recessions were selected. Fifteen pairs of recessions were treated and assigned randomly to the test group, and the contralateral recessions were assigned to the control group. The ADMG was used in both groups. In the control group the graft and flap were positioned at the level of the cemento-enamel junction (CEJ), and in the test group the graft was positioned 1mm apical to the CEJ and the flap 1mm coronal to the CEJ. The clinical parameters evaluated were probing depth (PD), relative clinical attachment level (RCAL), gingival recession height (GR) and the width (KT) and thickness of keratinized tissue (TKT).The gingival recession area (GRA), a new parameter, was measured in standardized photographs through a special device and software. The measurements were taken before the surgeries and after 6 months. Results: At baseline, all parameters were similar for both groups. There were statistically significant differences favouring the proposed technique for all parameters except for the amount of keratinized tissue at 6 months. Conclusions: The proposed test technique is more suitable for root coverage procedures with ADMG, and the new parameter evaluated appears valuable for root coverage analysis.(Clinicaltrials.gov Identifier: NCT01175720).

Objetivo: Estudar os efeitos do emprego de dois materiais consideravelmente diferentes quanto à origem e custo na correção intra-uterina da meningomielocele criada experimentalmente em feto de ovino. Métodos: Em 36 fetos de ovinos foi criado um defeito aberto de tubo neural, com 75 de dias de gestação. Os casos foram divididos em três grupos: o controle onde o defeito não foi corrigido, grupo corrigido A onde o material utilizado para cobrir a medula exposta foi a matriz dérmica humana acelular (MDHA) e o grupo corrigido B onde o material foi a celulose biossintética (CB). Após a correção realizada com 100 dias, os fetos eram mantidos intra-útero até o termo da gestação. Os sacrifícios foram realizados com 140 dias e a coluna fetal era submetida à análise macro e microscópica onde foi observada a aderência dos materiais à pele, medula ou tecido nervoso remanescente. Resultados: Na fase inicial (piloto), 11 fetos foram operados e 4 sobreviveram (37%). Na segunda fase (estudo) 25 fetos foram operados e 17 sobreviveram (68%). No grupo de estudo, 6 fetos não foram submetidos à correção (grupo controle), 11 casos foram corrigidos e ocorreu 1 perda fetal. Do total de 10 casos, 4 constituíram o grupo A e 6, o grupo B. À macroscopia observou-se deslizamento da pele e tecidos subjacentes sobre a CB em todos os casos onde ela foi empregada e isto não ocorreu em nenhum dos casos onde a MDHA foi utilizada. Para comparar a aderência, foram considerados 4 casos do grupo A e 4 do grupo B. A aderência, caracterizada pela migração de células do hospedeiro e proliferação de vasos para dentro da MDHA, foi observada em 100% dos casos do grupo A e em nenhum caso no grupo B (p < 0,05). No grupo B observou-se formação de uma camada de fibroblastos ao redor do material, protegendo a medula, caracterizando a formação de uma \"neoduramater\". Conclusão: A utilização da película de celulose biossintética parece ser mais adequada como substituto de dura-máter para cobertura e proteção do tecido nervoso que a matriz dérmica humana acelular. Ela parece promissora na correção intra-uterina da meningomielocele, evitando a aderência do tecido nervoso aos planos superficiais (\"medula presa\") minimizando os efeitos deletérios do ambiente intra-uterino sobre a medula espinhal. / Purpose: The aim of this study was to compare the effectiveness of two dura-mater substitutes, namely human acellular dermal matrix (HADM) and biosynthetic cellulose (BC), in repairing, in utero, surgically-induced meningomyelocele (MMC) in fetal sheep. Methods: A neural tube defect was created at 74-77 days gestation in 36 fetal sheep. They were divided into 3 groups, the control group that did not receive pre-natal corrective surgery, and the other two groups that received corrective surgery using HADM (Group A) or BC (Group B). Both materials were used as a dura-mater substitutes between the neural tissue and the sutured skin. Correction was performed at gestation day 100 and the fetuses were maintained in utero until term. Sheep were sacrificed on gestation day 140. The fetal spine was submitted to macro and microscopic analysis. At microscopy, adherence of the material to the skin and neural tissue was analyzed. Results: In the initial phase (pilot), experimentally-induced MMC was performed on 11 fetuses and 4 survived (37%). In the second phase (study), 25 fetuses received surgery and 17 survived (68%). In the study group, 6 fetuses did not undergo repair (control group), 11 cases were submitted to corrective surgery (experimental group) and one fetal loss occurred. Of the surviving cases in the experimental group, 4 constituted Group A and 6 in Group B. Macroscopically, skin and underlying tissues where easily displaced from the BC in all cases it was used; in contrast, HADM adhered to these tissues. To compare the adherence, 4 cases from Group A and 4 in Group B were studied. We observed adherence, host cell migration and vessel proliferation into the HADM all sections from Group A and this aspect was not present in any cases in Group B (p < 0.05). In Group B, we also observed that a new fibroblast layer formed around the BC thus protecting the medulla and constituting a \"neoduramater\". Conclusion: The use of BC seems to be more adequate as a dura-mater substitute to cover the damaged neural tissue than HADM. It seems promising for use in the in utero correction of MMC because to does not adhere to neural tissue of superficial and deep layers (\"tethered spinal cord\"). Thus, BC minimizes the mechanical and chemical intrauterine damage to the spinal medulla.

O crescente aumento da resistência microbiana aos antibióticos disponíveis impulsiona a busca por novas substâncias, com características superiores às correntemente usadas. Neste sentido, este trabalho propôs investigar as propriedades terapêuticas do xilitol visando a sua aplicação no controle da dermatite atópica, patologia que acomete a pele e que é agravada pela presença da bactéria Staphylococcus aureus. No presente estudo foram executados ensaios in vitro de atividade antimicrobiana do xilitol e verificado se este composto atua na aderência bacteriana, sobre a bactéria Staphylococcus aureus ATCC 25923. Foi avaliada a ação do xilitol produzido tanto pela via química quanto pela biotecnológica, sendo este último obtido a partir de fermentação do hidrolisado hemicelulósico da palha de trigo, nas concentrações de 1, 5 e 10 % (p/ v). A seguir, foram executados testes de toxicidade dérmica aguda com doses repetidas com xilitol nas concentrações de 5 e 10 % (p/ p), nas formas farmacêuticas de creme e de gel, em coelhos albinos da raça Nova Zelândia e testes de fototoxicidade, na concentração de 10 % (p/ p), nas formas farmacêuticas de creme e de gel, utilizando cobaias albinas da raça Durkin-Hartley. Em relação aos ensaios in vitro, observou-se que o xilitol, nas concentrações testadas, não impediu o crescimento bacteriano, mas inibiu a aderência da bactéria a uma superfície de prova, evidenciando ser este o provável mecanismo de ação desta substância sobre as bactérias. Em testes toxicológicos realizados, todas as formulações contendo xilitol foram classificadas como não irritantes quando foram avaliadas quanto à toxicidade dérmica aguda com doses repetidas. Entretanto, nos testes da fototoxicidade, as formulações testadas apresentaram certa fototoxicidade, sugerindo ser a formulação a base de creme mais fototóxica do que aquela a base de gel. Estes resultados evidenciam a aplicabilidade do xilitol no controle da dermatite atópica, como princípio ativo de formulações seguras, observando que a aplicação deve ser realizada com o uso de protetor solar. Este estudo buscou contribuir de maneira expressiva na elucidação do mecanismo de ação do xilitol e verificar os cuidados que devem ser considerados quando realizada sua aplicação pela via dérmica. / Since the microorganisms\' resistance to antibiotics increases, it is imperative to look for different substances that can combat these pathogens growth, with greater advantages. The propose of this work was to study therapeutic properties of xylitol in order to control atopic dermatitis, a dermal disease characterized by the presence of Staphylococcus aureus bacterium. Xylitol is a substance that can be obtained by chemical and biotechnological means, being the latter a relevant alternative that produces high-value compounds obtained by fermentation of lignocelullosic hydrolysates. In the present study in vitro assays were performed in order to check if wxylitol (obtained by chemical and biotechnological means) has antimicrobial activity at 1, 5 and 10 % (w/ v) concentrations. Other assays were also performed to verify if xylitol properties, at the same concentrations, hinder the adherence of Staphylococcus aureus ATCC 25923 bacterium. Xylitol was produced by biotechnological means using wheat straw hemicellulosic hydrolysate. Afterwards, in vivo assays were performed to investigate if xylitol is safe for skin application. Acute dermal toxicity tests with repeated doses were done with New Zealand rabbits using concentrations of 5 and 10 % (w/ w) xylitol, in either cream or gel. Phototoxicity assays were also performed with Durkin-Hartley guinea pigs, using only 10 % (w/ w) xylitol, in cream and gel forms. It was observed that xylitol does not have antimicrobial properties on S. aureus at all tested concentrations, but this compound has the capability of inhibiting this bacterium adherence on a surface, at all tested concentrations. In relation to toxicity assays, formulations contaning xylitol are nonirritative. However, xylitol has phototoxicity properties, mainly when cream is the base. Xylitol is an adequate alternative to be applied for atopic dermatitis control, and its application on the skin should be done with sunscreen. This study aimed to clarify xylitol action mechanism and to check the cares that should be taken when xylitol is applied on skin.

The concept of immunosurveillance suggests that the innate and adaptative immune system eliminate developing tumors. However, tumor development is associated with important modifications of the stroma which, by multiple mechanisms, restrain the immune response notably by affecting dendritic cells (DC) recruitment and functions. My thesis project aims at deciphering how the tumor environment alters the mechanisms and pathways of DC recruitment and impairs their functions. First, we determine if the site of tumor transplantation affects tumor immunogenicity. We show that tumors transplanted in the dermis (i.d.), an environment containing multiple DC subsets, induce a protective anti-tumoral immune response and tumor rejection. By contrast, the same tumor implanted in the subcutaneous tissue (s.c), mainly containing monocytes, is not rejected. Rejection of i.d. tumor is associated with a rapid (within 2 days) recruitment of DC within the tumor and rapid migration of DC towards tumor draining lymph nodes (dLN) where they present the tumor antigens (TAA) to CD4 and CD8 T lymphocyte. These events also occur for s.c. tumors but with a delayed kinetic. Thus the kinetic of DC mobilisation is decisive for tumor immunogenicity. Analysis of the DC subpopulations (TIDC) infiltrating the i.d. or s.c. tumors at 4 days (D4) and 8 days (D8) post-tumor transplantation, revealed that the different DC subpopulations are present at similar frequencies. Based on these findings, we proposed that i.d. tumor are rapidly infiltrated by dermal DC (DDC), whereas in s.c. tumor, the absence of inflammatory signals would limit DDC recruitment. In this latter case, DC would mainly come from local differentiation of blood-born precursors of DC (pre-cDC). Local differentiation of pre-cDC within the immunosuppressor tumor environment may affect their differentiation program and functions. We found that pre-cDC infiltrate i.d. and s.c. tumors starting at D4 and their frequency increases at D8. To determine the DC origin in tumors, we use CD11c-DTR-GFP mice in which CD11c+ cells express a fusion protein constituted by the diphtheria toxin receptor (DTR) and GFP. To track DDC trafficking within tumors, we injected anti-MHCII antibody before tumor implantation and analysed MHCII+ CD11c+ DDC infiltration in tumor by biphotonic microscopy. At D3 post-tumor transplantation, the DDC infiltration was higher in i.d. than s.c. tumors. To analyse the impact of this early DDC recruitment on anti-tumor immunity, we inhibit early recruitment of DC by injection of pertussis toxin (PTX), a chemokine receptor protein G inhibitor, during the three first days of tumor development. For i.d. tumors, PTX treatment induced 60% reduction of DC recruitment starting at D4. In s.c. tumor, while this effect was observable at D3 (60% reduction) and increased to 80% at D4. These results suggest that early recruitment of DDC to i.d. tumors may be be chemokine independent. PTX treatment, which inhibits DDC migration from tumors to dLN inhibits the early TAA presentation to CD4 and CD8 T cells but did not impaired i.d. tumor rejection. Collectively, these results suggest that a first wave of DDC may infiltrate i.d. tumor. The initial wave of DDC may rapidly activate the adaptive immune system and induce protective anti-tumoral immune response. For s.c. tumor, this first wave in delayed or limited. Tumor neoangioenesis would permit an input of pre-cDC which would differentiate locally into cDC1 and cDC2. To consolidate this model we are developing new protocols to efficiently inhibit early recruitment of DDC in i.d. tumor. Moreover, to determine the DC origin and pathways of DC recruitment in tumors, we exploit several experimental approaches to directly analyse DDC migration toward i.d. and s.c. tumor. / Le concept d’immunosurveillance postule que le système immunitaire inné et adaptatif élimine les tumeurs naissantes. Cependant, le développement de tumeurs est associé à des modifications importantes du stroma qui, par des mécanismes multiples, inhibent la réponse immunitaire en affectant notamment le recrutement et la fonction des cellules dendritiques (DC). Mon projet de thèse vise à préciser comment l’environnement tumoral affecte les mécanismes et les voies de recrutement des DC dans les tumeurs et leurs fonctions. Tout d’abord, nous avons déterminé si la composition en DC du tissu d’implantation affecte l’immunogénicité tumorale. Nous avons montré que les tumeurs implantées dans le derme (i.d.), un environnement riche en DC dermales (DDC), induisent une réponse anti-tumorale protectrice. En revanche, une même tumeur transplantée dans le tissu sous-cutané (s.c.), contenant principalement des monocytes, n’est pas rejetée. Le rejet des tumeurs i.d. est associé à un recrutement précoce et rapide des DC dans la tumeur (dès 2 jours post-injection) et une migration, dans les ganglions drainants (dLN), de DC qui présentent les antigènes tumoraux (TAA) aux lymphocytes T (LT) CD4+ et CD8+. Dans les tumeurs s.c. ces événements sont présents mais retardés. Ceci indique que la cinétique de mobilisation des DC est déterminante pour l’immunogénicité tumorale.

Diese Habilitationsschrift konzentriert sich auf die Evolution osteologischer Korrelate, anhand derer Rückschlüsse auf die Struktur der Haut sowie die Art der Atmung und der Nahrungsaufnahme früher Tetrapoden gezogen werden können. Die äußere Skulptur der Hautknochen früher Tetrapoden trug zur Konsolidierung der darüber liegenden Dermis bei; dies und die zahlreichen Hautverknöcherungen deuten darauf hin, dass Hautatmung im Gegensatz zu heutigen Lissamphibien keinen wesentlichen Teil des Gasaustausches ausmachen konnte. Es wird die Hypothese aufgestellt, dass eine weitere Funktion der Knochenskulptur in der Pufferung von CO2-induzierter Azidose bestand, wenn sich die Tiere an Land aufhielten. Mehrere Gruppen früher Tetrapoden entwickelten unabhängig voneinander Osteoderme im Rumpf, die unter anderem die Wirbelsäule bei der Fortbewegung an Land unterstützen konnten oder als Kalzium-Reservoir dienten. Die Veränderungen in der Morphologie, Histologie und Anordnung der Dermalschuppen während des Fisch-Tetrapoden-Überganges erfolgte etwa simultan zur Entwicklung der Tetrapodenextremität und ermöglichte eine größere Flexibilität des Körpers und der Beine. Der Bau des Kiemenskeletts ihrer Fischvorfahren wurde bei einer unerwartet großen Anzahl früher Tetrapoden beibehalten. Dies zeigt, dass viele frühe Tetrapoden sowohl der Stamm- als auch der Kronengruppe als Adulte über innere Kiemen atmeten, während ihre Larven äußere Kiemen besaßen. Das Kiemenskelett und die Rekonstruktion assoziierter Muskeln zeigen, dass viele aquatische frühe Tetrapoden ihre Nahrung durch akinetisches Saugschnappen erbeuteten. Trotz spärlicher Fossilüberlieferung gibt es Hinweise darauf, dass die ersten an Land fressenden Tetrapoden noch keine bewegliche Zunge besaßen. Ein ontogenetischer Umbau des larvalen, kiementragenden Kiemenskelets in einen zungenstützenden Apparat kann bei frühen Tetrapoden nur in Ausnahmefällen belegt werden. / This habilitation thesis focuses on the evolution of skeletal correlates from which the integumentary structure and the mode of breathing and feeding in early tetrapods can be inferred. Sculpture on the external surface of dermal bones contributed to the consolidation of a dense integument; this and numerous dermal ossifications render substantial cutaneous respiration as in extant lissamphibians unlikely. It is hypothesised that a further function of dermal bone sculpture was to buffer CO2-induced acidosis while the animals were on land. Numerous early tetrapods independently developed osteoderms in the trunk that may have served among other things for support of the vertebral column in terrestrial locomotion or as a physiological calcium reservoir. The alterations in morphology, histology and arrangement of dermal scales during the fish-to-tetrapod transition occurred at roughly the same time when digits appeared and enabled greater flexibility of body and limbs. The structure of the hyobranchium of their fish-like ancestors was retained in an unexpected large number of early tetrapods, showing that many early tetrapods of both the stem- and crown-group breathed via the associated internal gills as adults, and via external gills as larvae. The hyobranchial apparatus and reconstruction of the associated musculature indicate that many aquatic early tetrapods fed by akinetic suction feeding. There is evidence that the earliest terrestrial tetrapods captured prey on land by jaw prehension rather than by tongue based feeding. Ontogenetic remodelling into a tongue supporting adult hyobranchium in early tetrapods can only be demonstrated in exceptional cases.