No description available.

Universiẗat, Diss., 2006--Giessen.

Universiẗat, Diss., 2006--Giessen.

Zugl.: Giessen, Univ., Diss., 2006

Univ., Diss., 2007--Frankfurt (Main).

München, Techn. Univ., Diss., 2004.

Em cães, os estudos experimentais comparativos dos diferentes tipos de sutura para a síntese do brônquio principal são escassos, quando não ausentes nesta espécie. Além disso, existem possíveis complicações decorrentes da má cicatrização do brônquio. O objetivo deste estudo foi realizar um estudo experimental comparando-se sob o ponto de vista anatomo-patológico, paramétrico, radiológico e broncoscópico as suturas manual e mecânica em brônquio principal após pneumonectomia esquerda em cães. Foram utilizados 18 cães, sadios, machos e fêmeas, adultos, sem raça definida, pesando entre 9 e 27,5 kg. Os cães foram submetidos à intubação seletiva e toracotomia esquerda no 5º espaço intercostal, onde foi feita a pneumonectomia. Foram separados em 2 grupos de 9 cães, de acordo com o tipo de sutura empregada: Grupo A - sutura manual do coto brônquico principal esquerdo com pontos separados \"em 8\" com fio polipropileno 5-0; Grupo B - sutura mecânica do coto brônquico principal esquerdo com grampeador mecânico modelo TL-30 com grampos dispostos em fileira dupla. Cada grupo foi subdividido em 3 subgrupos de 3 animais, sendo estabelecido estudo temporal aos 7, 15 e 36 dias de pós-operatório, onde foi realizado a avaliação anatomo-patológica da cicatrização das suturas manual e mecânica, bem como, a avaliação paramétrica (antes da indução da anestesia, imediatamente após o final do ato cirúrgico, 48 horas, 7, 15 e 36 dias após o procedimento cirúrgico), avaliação radiológica ( 24 horas antes e com 7, 15 e 36 dias após o procedimento cirúrgico) e avaliação broncoscópica (após indução anestésica e com 7, 15 e 36 dias após o procedimento cirúrgico), consideradas importantes para avaliar possíveis complicações decorrentes deste tipo de procedimento cirúrgico. Estas avaliações foram realizadas de acordo com o estudo temporal nos diferentes subgrupos. A avaliação paramétrica foi realizada através da mensuração da temperatura, hematócrito, hemoglobina, freqüências cardíaca e respiratória. Na avaliação histopatológica foram avaliados qualitativamente e semi-quantitativamente a intensidade da inflamação, fibrose, vasos neoformados e a presença ou não de tecido de granulação, granuloma tipo corpo estranho e necrose. Os resultados encontrados foram analisados estatisticamente. Apesar das alterações dos índices paramétricos, todos os cães apresentaram evolução pós-operatória satisfatória. Com relação à análise histopatológica, ocorreu a formação de granuloma tipo corpo estranho no coto brônquico esquerdo em 88,9% dos cães submetidos à sutura manual e em nenhum dos cães submetidos à sutura mecânica. Houve ainda, diferença estatística significativa nos cães dos Grupos A e B em relação à intensidade da inflamação, sendo de maior intensidade nos cães submetidos à sutura manual. Os resultados obtidos mostraram não haver diferença estatística significativa nas avaliações radiográficas e broncoscópicas entre os Grupos A e B. Não foram observadas intercorrências no trans e pós-operatório. Concluiu-se que os 2 tipos de sutura promoveram cicatrização adequada do coto brônquico principal esquerdo, embora tenha ocorrido maior intensidade de inflamação e maior ocorrência de granuloma tipo corpo estranho nos cães submetidos à sutura manual, permitindo evolução paramétrica, radiológica, broncoscópica pós-operatória satisfatória e sem diferença nos cães dos Grupos A e B. / In dogs, comparative experimental studies of the different types of sutures for the synthesis of the main bronchus are scarce, when not all available in this species. Furthermore, there are possible complications due to the poor healing of the bronchus. The objective of this study was to perform an experimental study to be compared under the pathological-anatomic, parametric, radiological and bronchoscopic point of views, the manual and mechanical sutures in the main bronchus after left pneumonectomy in dogs. Eighteen adult mongrel, healthy dogs, both male and female, were utilized weighing from 9 to 27.5 kg. The dogs were submitted to a selective intubation and left thorax incision in the 5 th intercostal space where a pneumonectomy was performed. Were separated into 2 groups of 9 dogs according to the type of suture employed: Group A - a manual suture of the main left bronchial stump with separate stitches \"in 8\" with polypropylene 5-O; Group B - a mechanical suture of main left bronchial stump with a mechanical stapler, model TL-30 arranged in a double file. Each group was subdivided into 3 subgroups of 3 animals and a temporal postoperative study was established at 7, 15 and 36 days where an pathological-anatomic evaluation was made on the healing of the manual and mechanical sutures as well as a parametric evaluation (before the induction of anesthesia, immediately after the final surgical act, 48 hours, 7, 15 and 36 days after the surgical procedure), radiological evaluation (24 hours before and with 7, 15 and 36 days after the surgical procedure), and bronchoscopic evaluation (after the induction of anesthesia and with, 7, 15 and 36 days after the surgical procedure), considered important to evaluate possible complications due to this type of surgical procedure. These evaluations were made according to the temporal study in the subgroups. The parametric evaluation was made through the mensuration of temperature, hematocrit, hemoglobin, heart and respiratory rate. During the histopathological evaluation, the intensity of inflammation, fibrosis, neoformed vessels, and the presence or absence of granulation tissue, foreign body reaction and necrosis were evaluated qualitatively and semi-quantitatively. The results found were analyzed statistically. Although the difference observed in the parametric evaluations, all the dogs showed good recovery postoperative. Regarding the histopathologic analysis, foreign body reaction occured in the left bronchial stump in 88,9% of the dogs submitted to a manual suture and in none of the dogs submitted to a mechanical suture. There is still, significant statistical difference in the dogs in Groups A and B in relation to the intensity of the inflammation, the greatest intensity being in the dogs submitted to the manual suture. The results obtained showed that there was no significant statistical difference in the radiographic and bronchoscopic evaluations between Groups A and B. No intercurrences were observed in the trans and postoperative period. It is concluded that both types of sutures brought an adequate healing of the main left bronchial stump, although there was a greater intensity of inflammation and a greater occurence of foreign body reaction in the dogs submitted to the manual suture, permitting satisfactory parametric, radiological and bronchoscopic postoperative evolution and there is no difference in all of the dogs in Groups A and B.

The human bronchial epithelium is composed of multiple, discrete cell types that cooperate to perform mucociliary clearance. While previous studies have shown that cigarette smoke can alter bronchial epithelial gene expression, the underlying effects of this exposure on specific cell types are not well understood. In this thesis, single-cell RNA sequencing was used to profile bronchial epithelial cells from six current smokers and six never smokers. Thirteen cell clusters were identified that were defined by expression of unique combinations of nineteen distinct gene sets. This clustering revealed that smoke exposure induced expression of a toxin metabolism program that specifically associated with ciliated cells. Extensive airway remodeling was also observed, in which smoking was associated with loss of club cells as well as goblet cell expansion and hyperplasia. Additionally, a previously uncharacterized CEACAM5+ KRT8+ epithelial subpopulation was identified in the airways of smokers. While it has been shown that most smoking-associated gene expression alterations can be reversed upon smoking cessation, a subset of these alterations persists in former smokers. The basal layer of the bronchial epithelium is comprised of a multipotent progenitor subpopulation. When abnormalities persist in the bronchial epithelium despite normal tissue turnover, the source of these abnormalities may be traced to this progenitor population and its program of differentiation. Therefore, basal cells were procured from three current smokers and three never smokers, differentiated in vitro, and profiled by RNA sequencing at eight time points spanning the differentiation procedure. Twenty-seven unique sets of co-expressed genes associated with differentiation were identified and functionally characterized, a subset of which were abnormally expressed in smoker cells. Robust expression of genes involved with the unfolded protein response was specifically detected in smoker basal cells. Additionally, a smoking-associated delay in the onset of expression of genes involved with ciliogenesis was observed. These data therefore indicate that smoking has long-term consequences on the differentiated state of the airway epithelium. Collectively, the observations outlined in this thesis demonstrate that smoking drives a complex landscape of alterations that affects the function and composition of the human bronchial epithelium. / 2020-10-24T00:00:00Z

Em cães, os estudos experimentais comparativos dos diferentes tipos de sutura para a síntese do brônquio principal são escassos, quando não ausentes nesta espécie. Além disso, existem possíveis complicações decorrentes da má cicatrização do brônquio. O objetivo deste estudo foi realizar um estudo experimental comparando-se sob o ponto de vista anatomo-patológico, paramétrico, radiológico e broncoscópico as suturas manual e mecânica em brônquio principal após pneumonectomia esquerda em cães. Foram utilizados 18 cães, sadios, machos e fêmeas, adultos, sem raça definida, pesando entre 9 e 27,5 kg. Os cães foram submetidos à intubação seletiva e toracotomia esquerda no 5º espaço intercostal, onde foi feita a pneumonectomia. Foram separados em 2 grupos de 9 cães, de acordo com o tipo de sutura empregada: Grupo A - sutura manual do coto brônquico principal esquerdo com pontos separados \"em 8\" com fio polipropileno 5-0; Grupo B - sutura mecânica do coto brônquico principal esquerdo com grampeador mecânico modelo TL-30 com grampos dispostos em fileira dupla. Cada grupo foi subdividido em 3 subgrupos de 3 animais, sendo estabelecido estudo temporal aos 7, 15 e 36 dias de pós-operatório, onde foi realizado a avaliação anatomo-patológica da cicatrização das suturas manual e mecânica, bem como, a avaliação paramétrica (antes da indução da anestesia, imediatamente após o final do ato cirúrgico, 48 horas, 7, 15 e 36 dias após o procedimento cirúrgico), avaliação radiológica ( 24 horas antes e com 7, 15 e 36 dias após o procedimento cirúrgico) e avaliação broncoscópica (após indução anestésica e com 7, 15 e 36 dias após o procedimento cirúrgico), consideradas importantes para avaliar possíveis complicações decorrentes deste tipo de procedimento cirúrgico. Estas avaliações foram realizadas de acordo com o estudo temporal nos diferentes subgrupos. A avaliação paramétrica foi realizada através da mensuração da temperatura, hematócrito, hemoglobina, freqüências cardíaca e respiratória. Na avaliação histopatológica foram avaliados qualitativamente e semi-quantitativamente a intensidade da inflamação, fibrose, vasos neoformados e a presença ou não de tecido de granulação, granuloma tipo corpo estranho e necrose. Os resultados encontrados foram analisados estatisticamente. Apesar das alterações dos índices paramétricos, todos os cães apresentaram evolução pós-operatória satisfatória. Com relação à análise histopatológica, ocorreu a formação de granuloma tipo corpo estranho no coto brônquico esquerdo em 88,9% dos cães submetidos à sutura manual e em nenhum dos cães submetidos à sutura mecânica. Houve ainda, diferença estatística significativa nos cães dos Grupos A e B em relação à intensidade da inflamação, sendo de maior intensidade nos cães submetidos à sutura manual. Os resultados obtidos mostraram não haver diferença estatística significativa nas avaliações radiográficas e broncoscópicas entre os Grupos A e B. Não foram observadas intercorrências no trans e pós-operatório. Concluiu-se que os 2 tipos de sutura promoveram cicatrização adequada do coto brônquico principal esquerdo, embora tenha ocorrido maior intensidade de inflamação e maior ocorrência de granuloma tipo corpo estranho nos cães submetidos à sutura manual, permitindo evolução paramétrica, radiológica, broncoscópica pós-operatória satisfatória e sem diferença nos cães dos Grupos A e B. / In dogs, comparative experimental studies of the different types of sutures for the synthesis of the main bronchus are scarce, when not all available in this species. Furthermore, there are possible complications due to the poor healing of the bronchus. The objective of this study was to perform an experimental study to be compared under the pathological-anatomic, parametric, radiological and bronchoscopic point of views, the manual and mechanical sutures in the main bronchus after left pneumonectomy in dogs. Eighteen adult mongrel, healthy dogs, both male and female, were utilized weighing from 9 to 27.5 kg. The dogs were submitted to a selective intubation and left thorax incision in the 5 th intercostal space where a pneumonectomy was performed. Were separated into 2 groups of 9 dogs according to the type of suture employed: Group A - a manual suture of the main left bronchial stump with separate stitches \"in 8\" with polypropylene 5-O; Group B - a mechanical suture of main left bronchial stump with a mechanical stapler, model TL-30 arranged in a double file. Each group was subdivided into 3 subgroups of 3 animals and a temporal postoperative study was established at 7, 15 and 36 days where an pathological-anatomic evaluation was made on the healing of the manual and mechanical sutures as well as a parametric evaluation (before the induction of anesthesia, immediately after the final surgical act, 48 hours, 7, 15 and 36 days after the surgical procedure), radiological evaluation (24 hours before and with 7, 15 and 36 days after the surgical procedure), and bronchoscopic evaluation (after the induction of anesthesia and with, 7, 15 and 36 days after the surgical procedure), considered important to evaluate possible complications due to this type of surgical procedure. These evaluations were made according to the temporal study in the subgroups. The parametric evaluation was made through the mensuration of temperature, hematocrit, hemoglobin, heart and respiratory rate. During the histopathological evaluation, the intensity of inflammation, fibrosis, neoformed vessels, and the presence or absence of granulation tissue, foreign body reaction and necrosis were evaluated qualitatively and semi-quantitatively. The results found were analyzed statistically. Although the difference observed in the parametric evaluations, all the dogs showed good recovery postoperative. Regarding the histopathologic analysis, foreign body reaction occured in the left bronchial stump in 88,9% of the dogs submitted to a manual suture and in none of the dogs submitted to a mechanical suture. There is still, significant statistical difference in the dogs in Groups A and B in relation to the intensity of the inflammation, the greatest intensity being in the dogs submitted to the manual suture. The results obtained showed that there was no significant statistical difference in the radiographic and bronchoscopic evaluations between Groups A and B. No intercurrences were observed in the trans and postoperative period. It is concluded that both types of sutures brought an adequate healing of the main left bronchial stump, although there was a greater intensity of inflammation and a greater occurence of foreign body reaction in the dogs submitted to the manual suture, permitting satisfactory parametric, radiological and bronchoscopic postoperative evolution and there is no difference in all of the dogs in Groups A and B.

Les cellules souches pluripotentes (CSP) incluent les cellules souches embryonnaires (ES) et les celles souches pluripotentes induites (iPS). Elles sont définies par deux propriétés fondamentales : l’auto-renouvellement et la capacité à se différencier dans tous les types cellulaires. Les ES sont dérivées de la masse cellulaire de l’embryon. Elles soulèvent l’intérêt de la communauté scientifique du fait de leur capacité à générer tous les tissus. Il s’agit d’un outil biotechnologique majeur dont les applications thérapeutiques et pharmacologiques comporteront notamment la médecine régénératrice, la modélisation in vitro de maladies humaines et le criblage de candidat-médicaments. Cependant l’utilisation d’embryons humains pour générer les ES soulève des problèmes éthiques. Les iPS contournent ces difficultés car elles sont dérivées de cellules somatiques différenciées. En effet, S. Yamanaka, qui a reçu le prix Nobel en 2012, a découvert en 2006 une technique simple de reprogrammation cellulaire. L’expression transitoire de quatre gènes (OCT4, SOX2, c-MYC and KLF4) est suffisante pour reprogrammer des fibroblastes murins en iPS. Ces cellules iPS ont la même morphologie et les mêmes propriétés que les cellules ES. L’année suivante, S. Yamanaka a appliqué avec succès son cocktail à des fibroblastes humains pour produire des iPS humaines (hiPS). Les hiPS peuvent également dépasser les problèmes immunologiques soulevés par l’utilisation d’ES dans la thérapie cellulaire, par le simple fait que les hiPS pourront être dérivées du patient à traiter. De plus, parce qu’il est possible de choisir les cellules du donneur à reprogrammer selon son génotype, il est plus facile de modéliser des maladies génétiques à partir d’hiPS que d’ES. Enfin, d’un point de vue pharmaceutique, les hiPS peuvent fournir une plateforme quasi-infinie pour le criblage de molécules afin de traiter diverses pathologies. Le but de mon projet de recherche est l’utilisation de la technologie hiPS afin de modéliser le développement de l’épithélium bronchique. Premièrement, in vivo, des tératomes ont été générés après injection d’hiPS dans des souris immunodéficientes. Les tératomes démontrent la capacité de nos hiPS à se différencier en épithélium bronchique. Secondairement, in vitro, reproduire le développement embryonnaire et fœtal permet d’offrir une méthode simple pour modéliser l’épithélium bronchique dans un puits. Cette technologie ouvre la voie vers de nombreuses recherches, du criblage de molécules à la production de cellules souches pour réparer l’épithélium bronchique, et in fine à la promotion de nouveaux traitements pharmacologiques ou de thérapie innovante pour les maladies respiratoires. / Pluripotent stem cells (PSC) include embryonic stem cells (ES) and induced pluripotent stem cells (iPS). They are defined by two fundamental properties: self-renewal and the capacity to differentiate into all cell types. ES cells are derived from the inner cell mass of embryos. They arouse the interest of the scientific community in particular for their ability to generate all tissues. They provide major therapeutic and pharmacological applications, including regenerative medicine, in vitro modelling of human diseases and molecular screening. However, the use of human blastocysts to generate ES cells raises many ethical problems. iPS circumvent these ethical issues as they can be derived from differentiated somatic tissues. Indeed, S. Yamanaka, Nobel Prize in 2012, discovered in 2006 a simple technique of cellular reprogramming. The transient expression of four genes (OCT4, SOX2, c-MYC and KLF4) is sufficient to reprogram mouse fibroblasts into iPS. These iPS cells have the same morphology and the same properties than ES cells. The following year, S. Yamanaka applied successfully his cocktail to human fibroblasts to produce human iPS (hiPS). hiPS may also overcome immunological problems raised by the use of ES cell for cellular therapy, as hiPS can be derived from the patient to be treated. In addition, it is easier to model genetic diseases from hiPS than ES, because it is possible to choose the donor cells to reprogram according to its genotype. Finally, from a pharmacological point of view, hiPS can provide a broad platform of molecular screening to treat various diseases. The aim of my research project is to use the hiPS technology to model the development of bronchial epithelium. First, in vivo, teratomas were formed by the injection of hiPS into immunodeficient mice. Teratomas highlight the ability of differentiation of our hiPS into bronchial epithelium. Second, in vitro, reproducing embryonic and foetal bronchial development provides a way to model bronchial epithelium in a dish.These techniques open the door to many potential research avenues from screening small molecules to engineering stem cells to repair bronchial epithelium, and will in fine promote new pharmacologic or cell-based treatments for respiratory diseases.