Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 61
Filtrar
1.
Dev Cell ; 56(13): 1917-1929.e9, 2021 07 12.
Artigo em Inglês | MEDLINE | ID: mdl-34129836

RESUMO

During development, quiescent airway basal stem cells are derived from proliferative primordial progenitors through the cell-cycle slowdown. In contrast, basal cells contribute to adult tissue regeneration by shifting from slow cycling to proliferating and subsequently back to slow cycling. Although sustained proliferation results in tumorigenesis, the molecular mechanisms regulating these transitions remain unknown. Using temporal single-cell transcriptomics of developing murine airway progenitors and genetic validation experiments, we found that TGF-ß signaling decelerated cell cycle by inhibiting Id2 and contributed to slow-cycling basal cell specification during development. In adult tissue regeneration, reduced TGF-ß signaling restored Id2 expression and initiated regeneration. Id2 overexpression and Tgfbr2 knockout enhanced epithelial proliferation; however, persistent Id2 expression drove basal cell hyperplasia that resembled a precancerous state. Together, the TGF-ß-Id2 axis commonly regulates the proliferation transitions in basal cells during development and regeneration, and its fine-tuning is critical for normal regeneration while avoiding basal cell hyperplasia.


Assuntos
Proliferação de Células/genética , Proteína 2 Inibidora de Diferenciação/genética , Regeneração/genética , Fator de Crescimento Transformador beta/genética , Animais , Diferenciação Celular/genética , Células Epiteliais/citologia , Humanos , Pulmão/crescimento & desenvolvimento , Camundongos , Sistema Respiratório/crescimento & desenvolvimento , Células-Tronco/citologia
2.
J Anat ; 238(2): 426-445, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-32974934

RESUMO

A morphological and morphometric study of the skin development in the eastern quoll (Dasyurus viverrinus) was conducted to follow the transition from cutaneous to pulmonary gas exchange in this extremely immature marsupial species. Additionally, the development of the cardiac and respiratory system was followed, to evaluate the systemic prerequisites allowing for cutaneous respiration. The skin in the newborn D. viverrinus was very thin (36 ± 3 µm) and undifferentiated (no hair follicles, no sebaceous and perspiratory glands). Numerous superficial cutaneous capillaries were encountered, closely associated with the epidermis, allowing for gaseous exchange. The capillary volume density was highest in the neonate (0.33 ± 0.04) and decreased markedly during the first 4 days (0.06 ± 0.01). In the same time period, the skin diffusion barrier increased from 9 ± 1 µm to 44 ± 6 µm. From this age on the skin development was characterized by thickening of the different cutaneous layers, formation of hair follicles (day 55) and the occurrence of subcutaneous fat (day 19). The heart of the neonate D. viverrinus had incomplete interatrial, inter-ventricular, and aortico-pulmonary septa, allowing for the possibility that oxygenated blood from the skin mixes with that of the systemic circulation. The fast-structural changes in the systemic circulations (closing all shunts) in the early postnatal period (3 days) necessitate the transition from cutaneous to pulmonary respiration despite the immaturity of the lungs. At this time, the lung was still at the canalicular stage of lung development, but had to be mature enough to meet the respiratory needs of the growing organism. The morphometric results for the skin development of D. viverrinus suggest that cutaneous respiration is most pronounced in neonates and decreases rapidly during the first 3 days of postnatal life. After this time a functional transition of the skin from cutaneous respiration to insulation and protection of the body takes place.


Assuntos
Marsupiais/crescimento & desenvolvimento , Troca Gasosa Pulmonar , Pele/crescimento & desenvolvimento , Animais , Animais Recém-Nascidos , Sistema Cardiovascular/crescimento & desenvolvimento , Marsupiais/metabolismo , Sistema Respiratório/crescimento & desenvolvimento , Pele/metabolismo
3.
Respir Physiol Neurobiol ; 270: 103263, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31386914

RESUMO

Longer term respiratory morbidity is a frequent concern for former preterm infants. Increased airway reactivity and wheezing disorders are extremely common in this population, both in infants who meet diagnostic criteria for bronchopulmonary dysplasia [BPD], and in the absence of this diagnosis. It is, therefore, imperative to gain a better understanding of normal and abnormal postnatal development of the immature airway. Airway hyperreactivity may be secondary to abnormal bronchoalveolar attachments in the face of parenchymal lung injury, or secondary to an imbalance between constrictor and dilator neural pathways. Finally, the airway itself may undergo functional and/or structural changes, including increased airway smooth muscle mass, and changes in airway extracellular matrix which may, in turn, modulate downstream signaling pathways to hyperoxia or pressure exposed vulnerable airways.


Assuntos
Transtornos Respiratórios/epidemiologia , Sistema Respiratório/crescimento & desenvolvimento , Adulto , Asma/epidemiologia , Displasia Broncopulmonar/fisiopatologia , Feminino , Humanos , Lactente , Recém-Nascido , Recém-Nascido Prematuro , Gravidez , Sons Respiratórios
4.
Respirology ; 24(11): 1053-1062, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-30801930

RESUMO

Bronchiectasis has historically been considered to be irreversible dilatation of the airways, but with modern imaging techniques it has been proposed that 'irreversible' be dropped from the definition. The upper limit of normal for the ratio of airway to arterial development increases with age, and a developmental perspective is essential. Bronchiectasis (and persistent bacterial bronchitis, PBB) is a descriptive term and not a diagnosis, and should be the start not the end of the patient's diagnostic journey. PBB, characterized by airway infection and neutrophilic inflammation but without significant airway dilatation may be a precursor of bronchiectasis, and there are many commonalities in the microbiology and the pathology, which are reviewed in this article. A high index of suspicion is essential, and a history of chronic wet or productive cough for more than 4-8 weeks should prompt investigation. There are numerous underlying causes of bronchiectasis, although in many cases no cause is found. Causes include post-infectious, especially after tuberculosis, adenoviral or pertussis infection; aspiration syndromes; defects in host defence, which may solely affect the airways (cystic fibrosis, not considered in this review, and primary ciliary dyskinesia); and primary ciliary dyskinesia or be systemic, such as common variable immunodeficiency; genetic syndromes; and anatomical defects such as intraluminal airway obstruction (e.g. foreign body), intramural obstruction (e.g. complete cartilage rings) and external airway compression (e.g. by tuberculous lymph nodes). Identification of the underlying cause is important, because some of these conditions have specific treatments and others genetic implications for the family.


Assuntos
Bronquiectasia , Sistema Respiratório , Adulto , Bronquiectasia/diagnóstico , Bronquiectasia/etiologia , Criança , Diagnóstico Diferencial , Humanos , Sistema Respiratório/diagnóstico por imagem , Sistema Respiratório/crescimento & desenvolvimento , Sistema Respiratório/imunologia , Sistema Respiratório/fisiopatologia
5.
Pesqui. vet. bras ; 38(1): 154-166, Jan. 2018. ilus
Artigo em Inglês | LILACS, VETINDEX | ID: biblio-895553

RESUMO

The rhea (Rhea americana) is an important wild species that has been highlighted in national and international livestock. This research aims to analyse embryo-foetal development in different phases of the respiratory system of rheas. Twenty-three embryos and foetuses were euthanized, fixed and dissected. Fragments of the respiratory system, including the nasal cavity, larynx, trachea, syrinx, bronchi and lungs, were collected and processed for studies using light and scanning electron microscopy. The nasal cavity presented cubic epithelium in the early stages of development. The larynx exhibited typical respiratory epithelium between 27 and 31 days. The trachea showed early formation of hyaline cartilage after 15 days. Syrinx in the mucous membrane of 18-day foetuses consisted of ciliated epithelium in the bronchial region. The main bronchi had ciliated epithelium with goblet cells in the syringeal region. In the lung, the parabronchial stage presented numerous parabronchi between 15 and 21 days. This study allowed the identification of normal events that occur during the development of the rhea respiratory system, an important model that has not previously been described. The information generated here will be useful for the diagnosis of pathologies that affect this organic system, aimed at improving captive production systems.(AU)


A ema (Rhea americana) representa importante espécie silvestre que vem se destacando na pecuaria nacional e internacional. Esta pesquisa objetiva analisar o desenvolvimento embrionário-fetal, em diferentes fases, do sistema respiratório de emas. Vinte e três embriões e fetos foram eutanasiados, fixados e dissecados. Fragmentos do sistema respiratório: cavidade nasal, laringe, traqueia, siringe, brônquios e pulmões, foram coletados e processados para estudos por meio de microscopia de luz e microscopia eletrônica de varredura. A cavidade nasal apresentou, nas primeiras fases de desenvolvimento, epitélio estratificado cúbico. A laringe exibiu epitélio respiratório típico entre 27 e 31 dias. A traqueia aos 15 dias apresentou início de formação da cartilagem hialina. Na siringe a túnica mucosa de fetos de 18 dias e formada por epitélio estratificado ciliado na região bronquial. Os brônquios principais apresentavam epitélio estratificado ciliado com células caliciformes na região siringeal. No pulmão, o estágio parabronquial apresentou numerosos parabrônquios entre 15 a 21 dias. Este estudo permitiu a identificação de eventos normais que ocorrem durante o desenvolvimento do sistema respiratório de emas, importante modelo ainda não descrito. As informações geradas serão úteis para o diagnóstico de patologias que acometem este sistema orgânico, visando a melhoria dos sistemas de produção em cativeiro.(AU)


Assuntos
Animais , Sistema Respiratório/anatomia & histologia , Sistema Respiratório/crescimento & desenvolvimento , Sistema Respiratório/embriologia , Reiformes/embriologia , Organogênese
6.
Paediatr Anaesth ; 28(1): 13-22, 2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-29148119

RESUMO

BACKGROUND: There is disagreement regarding the anatomy of the pediatric airway, particularly regarding the shape of the cricoid cartilage and the location of the narrowest portion of the larynx. AIMS: The aim of this review is to clarify the origin and the science behind these differing views. METHODS: We undertook a review of published literature, University Libraries, and authoritative textbooks with key search words and phrases. RESULTS: In vivo observations suggest that the narrowest portion of the airway is more proximal than the cricoid cartilage. However, in vitro studies of autopsy specimens measured with rods or calipers, confirm that the nondistensible and circular or near circular cricoid outlet is the narrowest level. These anatomic studies confirmed the classic "funnel" shape of the pediatric larynx. In vivo studies are potentially misleading as the aryepiglottic, vestibular, and true vocal folds are in constant motion with respiration. These studies also do not consider the effects of normal sleep, inhalation agents, and comorbidities such as adenoid or tonsil hypertrophy that cause some degree of pharyngeal collapse and alter the normal movement of the laryngeal tissues. Thus, the radiologic studies suggesting that the narrowest portion of the airway is not the cricoid cartilage may be the result of an artifact depending upon which phase of respiration was imaged. CONCLUSION: In vivo studies do not take into account the motion of the highly pliable laryngeal upper airway structures (aryepiglottic, vestibular, and vocal folds). Maximal abduction of these structures with tracheal tubes or bronchoscopes always demonstrates a larger opening of the glottis compared to the outlet of the cricoid ring. Injury to the larynx depends upon ease of tracheal tube or endoscope passage past the cricoid cartilage and not passage through the readily distensible more proximal structures. The infant larynx is funnel shaped with the narrowest portion the circular or near circular cricoid cartilage confirmed by multiple in vitro autopsy specimens carried out over the past century.


Assuntos
Manuseio das Vias Aéreas , Laringe/anatomia & histologia , Sistema Respiratório/anatomia & histologia , Criança , Pré-Escolar , Cartilagem Cricoide/anatomia & histologia , Cartilagem Cricoide/crescimento & desenvolvimento , Humanos , Lactente , Recém-Nascido , Laringe/crescimento & desenvolvimento , Sistema Respiratório/crescimento & desenvolvimento
7.
PLoS Genet ; 13(7): e1006882, 2017 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-28678789

RESUMO

Development is governed by a few conserved signalling pathways. Amongst them, the EGFR pathway is used reiteratively for organ and tissue formation, and when dysregulated can lead to cancer and metastasis. Given its relevance, identifying its downstream molecular machinery and understanding how it instructs cellular changes is crucial. Here we approach this issue in the respiratory system of Drosophila. We identify a new role for EGFR restricting the elongation of the tracheal Dorsal Trunk. We find that EGFR regulates the apical determinant Crb and the extracellular matrix regulator Serp, two factors previously known to control tube length. EGFR regulates the organisation of endosomes in which Crb and Serp proteins are loaded. Our results are consistent with a role of EGFR in regulating Retromer/WASH recycling routes. Furthermore, we provide new insights into Crb trafficking and recycling during organ formation. Our work connects cell signalling, trafficking mechanisms and morphogenesis and suggests that the regulation of cargo trafficking can be a general outcome of EGFR activation.


Assuntos
Amidoidrolases/genética , Proteínas de Drosophila/genética , Receptores ErbB/genética , Proteínas de Membrana/genética , Organogênese/genética , Receptores de Peptídeos de Invertebrados/genética , Sistema Respiratório/crescimento & desenvolvimento , Traqueia/crescimento & desenvolvimento , Animais , Polaridade Celular/genética , Drosophila melanogaster/genética , Drosophila melanogaster/crescimento & desenvolvimento , Matriz Extracelular/genética , Regulação da Expressão Gênica no Desenvolvimento , Transporte Proteico/genética , Traqueia/metabolismo
8.
Anaesth Crit Care Pain Med ; 36(5): 285-290, 2017 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-27481692

RESUMO

BACKGROUND: One of the requirements of laryngoscopy is to determine which head position will result in optimal visualization. Our hypothesis was that parameters derived from magnetic resonance imaging (MRI) can help quantify the effect of age on airway modifications due to head extension during development. METHOD: In children undergoing planned MRI, additional sequences on the upper airways were performed: one in a near-neutral position, the other with the head extended at 35°. The axis of the face, the pharynx, the larynx, the trachea, and the line of glottic visualization were determined. The following angles were calculated: the Visu-Lar angle, formed by the line of glottic visualization and the laryngeal axis, and the Phar-Lar angle, formed by the pharyngeal and laryngeal axes. RESULTS: One hundred and fifty-five patients (1 to 222 months of age [25-145] months) were included and 54% were under general anaesthesia. Age had no effect on the variation in the Visu-Lar angle, which diminished as a function of head extension, nor on the variation in the Phar-Lar angle, which was minimal in the neutral position. During extension, anatomical axes rotated similarly, and the visualization axis rotated the most, followed by the pharyngeal and laryngeal axes. These results were not correlated with general anaesthesia. CONCLUSION: Regardless of age, head extension diminished the Visu-Lar angle, and increased the Phar-Lar angle. This study supports that, as in adults, head extension is probably the key factor for good visualization conditions during laryngoscopy on children, but clinical data is needed to confirm this result.


Assuntos
Manuseio das Vias Aéreas/métodos , Cabeça , Imageamento por Ressonância Magnética/métodos , Posicionamento do Paciente/métodos , Sistema Respiratório/anatomia & histologia , Sistema Respiratório/crescimento & desenvolvimento , Envelhecimento , Anestesia Geral , Criança , Pré-Escolar , Feminino , Humanos , Intubação Intratraqueal , Laringoscopia/métodos , Laringe/anatomia & histologia , Masculino , Faringe/anatomia & histologia
9.
Ann Glob Health ; 82(1): 119-31, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27325070

RESUMO

Evidence has accumulated that exposure to widespread environmental toxicants, such as heavy metals, persistent organic pollutants, and tobacco smoke adversely affect fetal development and organ maturation, even after birth. The developing immune and respiratory systems are more sensitive to environmental toxicants due to their long-term physical development, starting from the early embryonic stage and persisting into early postnatal life, which requires complex signaling pathways that control proliferation and differentiation of highly heterogeneous cell types. In this review, we summarize the effect of early-life exposure to several widespread environmental toxicants on immune and lung development before and after birth, including the effects on immune cell counts, baseline characteristics of cell-mediated and humoral immunity, and alteration of lung structure and function in offspring. We also review evidence supporting the association between early-life exposure to environmental toxicants and risk for immune-related diseases and lung dysfunction in offspring in later life.


Assuntos
Exposição Ambiental/efeitos adversos , Desenvolvimento Fetal/fisiologia , Substâncias Perigosas/toxicidade , Sistema Imunitário/efeitos dos fármacos , Pulmão/embriologia , Pulmão/crescimento & desenvolvimento , Sistema Respiratório/efeitos dos fármacos , Meio Ambiente , Desenvolvimento Fetal/efeitos dos fármacos , Humanos , Hipersensibilidade , Sistema Imunitário/crescimento & desenvolvimento , Pulmão/efeitos dos fármacos , Sistema Respiratório/crescimento & desenvolvimento , Doenças Respiratórias/induzido quimicamente , Doenças Respiratórias/fisiopatologia
10.
PLoS Genet ; 11(1): e1004929, 2015 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-25615601

RESUMO

The tubular networks of the Drosophila respiratory system and our vasculature show distinct branching patterns and tube shapes in different body regions. These local variations are crucial for organ function and organismal fitness. Organotypic patterns and tube geometries in branched networks are typically controlled by variations of extrinsic signaling but the impact of intrinsic factors on branch patterns and shapes is not well explored. Here, we show that the intersection of extrinsic hedgehog(hh) and WNT/wingless (wg) signaling with the tube-intrinsic Hox code of distinct segments specifies the tube pattern and shape of the Drosophila airways. In the cephalic part of the airways, hh signaling induces expression of the transcription factor (TF) knirps (kni) in the anterior dorsal trunk (DTa1). kni represses the expression of another TF spalt major (salm), making DTa1 a narrow and long tube. In DTa branches of more posterior metameres, Bithorax Complex (BX-C) Hox genes autonomously divert hh signaling from inducing kni, thereby allowing DTa branches to develop as salm-dependent thick and short tubes. Moreover, the differential expression of BX-C genes is partly responsible for the anterior-to-posterior gradual increase of the DT tube diameter through regulating the expression level of Salm, a transcriptional target of WNT/wg signaling. Thus, our results highlight how tube intrinsic differential competence can diversify tube morphology without changing availabilities of extrinsic factors.


Assuntos
Proteínas de Drosophila/genética , Drosophila melanogaster/genética , Proteínas Hedgehog/genética , Proteínas de Homeodomínio/genética , Sistema Respiratório/crescimento & desenvolvimento , Proteína Wnt1/genética , Animais , Padronização Corporal/genética , Proteínas de Drosophila/biossíntese , Drosophila melanogaster/crescimento & desenvolvimento , Embrião não Mamífero , Regulação da Expressão Gênica no Desenvolvimento , Proteínas Hedgehog/biossíntese , Proteínas Repressoras/biossíntese , Proteínas Repressoras/genética , Via de Sinalização Wnt/genética , Proteína Wnt1/biossíntese
11.
Tissue Eng Part B Rev ; 21(4): 323-44, 2015 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-25587703

RESUMO

Currently, lung disease and major airway trauma constitute a major global healthcare burden with limited treatment options. Airway diseases such as chronic obstructive pulmonary disease and cystic fibrosis have been identified as the fifth highest cause of mortality worldwide and are estimated to rise to fourth place by 2030. Alternate approaches and therapeutic modalities are urgently needed to improve clinical outcomes for chronic lung disease. This can be achieved through tissue engineering of the respiratory tract. Interest is growing in the use of airway tissue-engineered constructs as both a research tool, to further our understanding of airway pathology, validate new drugs, and pave the way for novel drug therapies, and also as regenerative medical devices or as an alternative to transplant tissue. This review provides a concise summary of the field of respiratory tissue engineering to date. An initial overview of airway anatomy and physiology is given, followed by a description of the stem cell populations and signaling processes involved in parenchymal healing and tissue repair. We then focus on the different biomaterials and tissue-engineered systems employed in upper and lower respiratory tract engineering and give a final perspective of the opportunities and challenges facing the field of respiratory tissue engineering.


Assuntos
Sistema Respiratório/crescimento & desenvolvimento , Engenharia Tecidual/métodos , Engenharia Tecidual/tendências , Materiais Biocompatíveis/farmacologia , Humanos , Sistema Respiratório/anatomia & histologia , Sistema Respiratório/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Células-Tronco/citologia , Células-Tronco/efeitos dos fármacos
12.
Curr Opin Anaesthesiol ; 28(1): 2-9, 2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-25517623

RESUMO

PURPOSE OF REVIEW: The mean age of patients presenting for thoracic surgery is rising steadily, associated with an increased demand for thoracic surgical treatments by geriatric patients. With increasing age, physiologic changes and comorbidities have to be considered. Thoracic anesthesia for elderly patients requires greater specific knowledge. RECENT FINDINGS: Respiratory mechanics change progressively during aging, and the pharmacology of different drugs is also altered with increasing age. This has implications for the preoperative, intraoperative and postoperative management of elderly patients scheduled for thoracic surgery. Special focus has to be placed on preoperative evaluation, the ventilation regime and general intraoperative management. Effective postoperative pain treatment after geriatric thoracic surgery requires careful pain assessment and drug titration. SUMMARY: Considering key points of physiology and pharmacology can help to provide best possible care for the increasing number of elderly patients in thoracic surgery. Management of geriatric patients in thoracic surgery offer opportunities for anaesthetic interventions including protective ventilation, use of different anesthetics, anaesthesia monitoring, fluid management and pain therapy.


Assuntos
Idoso de 80 Anos ou mais/fisiologia , Idoso/fisiologia , Anestesia/métodos , Procedimentos Cirúrgicos Torácicos/métodos , Humanos , Cuidados Pós-Operatórios , Respiração Artificial , Sistema Respiratório/crescimento & desenvolvimento , Sistema Respiratório/fisiopatologia
13.
Am J Physiol Lung Cell Mol Physiol ; 307(4): L295-301, 2014 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-24951774

RESUMO

Wheezing is a major long-term respiratory morbidity in preterm infants with and without bronchopulmonary dysplasia. We hypothesized that mild vs. severe hyperoxic exposure in neonatal mice differentially affects airway smooth muscle hypertrophy and resultant airway reactivity. Newborn mice were exposed to 7 days of mild (40% oxygen) or severe (70% oxygen) hyperoxia vs. room air controls. Respiratory system resistance (Rrs), compliance (Crs), and airway reactivity were measured 14 days after oxygen exposure ended under ketamine/xylazine anesthesia. Baseline Rrs increased and Crs decreased in both treatment groups. Methacholine challenge dose dependently increased Rrs and decreased Crs in 40% oxygen-exposed mice, whereas Rrs and Crs responses were similar between 70% oxygen-exposed and normoxic controls. Airway smooth muscle thickness was increased in 40%- but not 70%-exposed mice, whereas collagen increased and both alveolar number and radial alveolar counts decreased after 40% and 70% oxygen. These data indicate that severity of hyperoxia may differentially affect structural and functional changes in the developing mouse airway that contribute to longer-term hyperreactivity. These findings may be important to our understanding of the complex role of neonatal supplemental oxygen therapy in postnatal development of airway responsiveness.


Assuntos
Hiperóxia/fisiopatologia , Oxigênio/toxicidade , Sistema Respiratório/crescimento & desenvolvimento , Animais , Animais Recém-Nascidos , Displasia Broncopulmonar/fisiopatologia , Colágeno/metabolismo , Feminino , Complacência Pulmonar/efeitos dos fármacos , Masculino , Cloreto de Metacolina , Camundongos , Sistema Respiratório/fisiopatologia
14.
Integr Comp Biol ; 54(2): 307-22, 2014 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-24812329

RESUMO

The scaling laws governing metabolism suggest that we can predict metabolic rates across taxonomic scales that span large differences in mass. Yet, scaling relationships can vary with development, body region, and environment. Within species, there is variation in metabolic rate that is independent of mass and which may be explained by genetic variation, the environment or their interaction (i.e., metabolic plasticity). Additionally, some structures, such as the insect tracheal respiratory system, change throughout development and in response to the environment to match the changing functional requirements of the organism. We discuss how study of the development of respiratory function meets multiple challenges set forth by the NSF Grand Challenges Workshop. Development of the structure and function of respiratory and metabolic systems (1) is inherently stable and yet can respond dynamically to change, (2) is plastic and exhibits sensitivity to environments, and (3) can be examined across multiple scales in time and space. Predicting respiratory performance and plasticity requires quantitative models that integrate information across scales of function from the expression of metabolic genes and mitochondrial biogenesis to the building of respiratory structures. We present insect models where data are available on the development of the tracheal respiratory system and of metabolic physiology and suggest what is needed to develop predictive models. Incorporating quantitative genetic data will enable mapping of genetic and genetic-by-environment variation onto phenotypes, which is necessary to understand the evolution of respiratory and metabolic systems and their ability to enable respiratory homeostasis as organisms walk the tightrope between stability and change.


Assuntos
Drosophila melanogaster/fisiologia , Gafanhotos/fisiologia , Manduca/fisiologia , Animais , Metabolismo Basal , Drosophila melanogaster/crescimento & desenvolvimento , Gafanhotos/crescimento & desenvolvimento , Homeostase , Manduca/crescimento & desenvolvimento , Sistema Respiratório/crescimento & desenvolvimento
15.
Paediatr Anaesth ; 24(1): 10-21, 2014 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-24152199

RESUMO

This review article focuses on neonatal respiratory physiology, mechanical ventilation of the neonate and changes induced by anesthesia and surgery. Optimal ventilation techniques for preterm and term neonates are discussed. In summary, neonates are at high risk for respiratory complications during anesthesia, which can be explained by their characteristic respiratory physiology. Especially the delicate balance between closing volume and functional residual capacity can be easily disturbed by anesthetic and surgical interventions resulting in respiratory deterioration. Ventilatory strategies should ideally include application of an 'open lung strategy' as well avoidance of inappropriately high VT and excessive oxygen administration. In critically ill and unstable neonates, for example, extremely low-birthweight infants surgery in the neonatal intensive care unit might be an appropriate alternative to the operating theater. Best respiratory management of neonates during anesthesia is a team effort that should involve a joint multidisciplinary approach of anesthetists, pediatric surgeons, cardiologists, and neonatologists to reduce complications and optimize outcomes in this vulnerable population.


Assuntos
Recém-Nascido/fisiologia , Pulmão/fisiologia , Mecânica Respiratória/fisiologia , Fenômenos Fisiológicos Respiratórios , Abdome/cirurgia , Anestesia/efeitos adversos , Humanos , Hipercapnia/fisiopatologia , Intubação Intratraqueal , Óxido Nítrico/administração & dosagem , Óxido Nítrico/uso terapêutico , Oxigênio/efeitos adversos , Respiração Artificial/instrumentação , Respiração Artificial/métodos , Síndrome do Desconforto Respiratório do Recém-Nascido , Sistema Respiratório/crescimento & desenvolvimento , Procedimentos Cirúrgicos Operatórios/efeitos adversos , Procedimentos Cirúrgicos Torácicos , Vasodilatadores/administração & dosagem , Vasodilatadores/uso terapêutico
16.
Dev Biol ; 370(2): 198-212, 2012 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-22885335

RESUMO

Respiratory epithelial cells are derived from cell progenitors in the foregut endoderm that subsequently differentiate into the distinct cell types lining the conducting and alveolar regions of the lung. To identify transcriptional mechanisms regulating differentiation and maintenance of respiratory epithelial cells, we conditionally deleted Foxm1 transcription factor from the conducting airways of the developing mouse lung. Conditional deletion of Foxm1 from Clara cells, controlled by the Scgb1a1 promoter, dramatically altered airway structure and caused peribronchial fibrosis, resulting in airway hyperreactivity in adult mice. Deletion of Foxm1 inhibited proliferation of Clara cells and disrupted the normal patterning of epithelial cell differentiation in the bronchioles, causing squamous and goblet cell metaplasia, and the loss of Clara and ciliated cells. Surprisingly, conducting airways of Foxm1-deficient mice contained highly differentiated cuboidal type II epithelial cells that are normally restricted to the alveoli. Lineage tracing studies showed that the ectopic alveolar type II cells in Foxm1-deficient airways were derived from Clara cells. Deletion of Foxm1 inhibited Sox2 and Scgb1a1, both of which are critical for differentiation and function of Clara cells. In co-transfection experiments, Foxm1 directly bound to and induced transcriptional activity of Scgb1a1 and Sox2 promoters. Foxm1 is required for differentiation and maintenance of epithelial cells lining conducting airways.


Assuntos
Diferenciação Celular , Proliferação de Células , Fatores de Transcrição Forkhead/metabolismo , Sistema Respiratório/citologia , Sistema Respiratório/crescimento & desenvolvimento , Animais , Células Epiteliais/citologia , Proteína Forkhead Box M1 , Fatores de Transcrição Forkhead/genética , Deleção de Genes , Pulmão/citologia , Pulmão/crescimento & desenvolvimento , Camundongos , Alvéolos Pulmonares/citologia , Fatores de Transcrição SOXB1/metabolismo , Transcriptoma , Uteroglobina/metabolismo
17.
Semin Fetal Neonatal Med ; 17(2): 73-6, 2012 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-22300711

RESUMO

Many very prematurely born infants develop bronchopulmonary dysplasia (BPD), remaining oxygen dependent for many months and requiring frequent rehospitalisations. Troublesome, recurrent respiratory symptoms requiring treatment and lung function abnormalities at follow-up are common. The most severely affected may remain symptomatic with evidence of airways obstruction even as adults. Data from adolescents and adults on the respiratory outcome of extreme prematurity, however, are usually from patients who have had 'classical' BPD with severe respiratory failure in the neonatal period. Nowadays, infants have 'new' BPD developing chronic oxygen dependence despite initially minimal or even no respiratory distress. Affected patients do suffer chronic respiratory morbidity and their lung function may deteriorate during the first year after birth. Infants who suffer respiratory syncytial virus lower respiratory tract infections are most likely to require rehospitalisation and suffer chronic respiratory morbidity, but this may reflect greater abnormal premorbid lung function.


Assuntos
Displasia Broncopulmonar/epidemiologia , Desenvolvimento Infantil , Deficiências do Desenvolvimento/epidemiologia , Recém-Nascido de muito Baixo Peso , Sistema Respiratório/crescimento & desenvolvimento , Sistema Respiratório/fisiopatologia , Humanos , Bem-Estar do Lactente/estatística & dados numéricos , Recém-Nascido , Recém-Nascido Prematuro , Prognóstico , Fenômenos Fisiológicos Respiratórios , Fatores de Risco , Índice de Gravidade de Doença
18.
Braz. oral res ; 25(3): 241-247, May-June 2011. ilus, graf, tab
Artigo em Inglês | LILACS | ID: lil-590042

RESUMO

The aim of the present retrospective study was to evaluate the influence of age and gender on upper and lower airway width and upper lip length. In this study, 390 lateral cephalograms were divided into 13 age groups (ranging from 6 to 18 years) and were analyzed. The intergroup differences were analyzed using a MANOVA (Multivariate Analysis of the Variance), and the intragroup differences were analyzed using an ANOVA (Analysis of the Variance) and Tukey's test. The results of the present study indicated that although the airway width and the upper lip length increased with age, the lower airway width exhibited variable growth between the ages of six and eighteen years. The airway width was significantly greater in females than males, whereas the upper airway width was similar between these two genders. The lip length was significantly shorter in females than males. The lower airway width and upper lip length were significantly different between males and females, whereas the upper airway width was similar for the genders. The upper airway width and upper lip exhibited incremental growth between the ages of six and eighteen years. The upper lip closely followed the growth pattern of the upper airway width; the growth plateaued between the ages of 6 and 9 years, increased from 9 to 16 years and plateaued from 16 to 18 years.


Assuntos
Adolescente , Criança , Feminino , Humanos , Masculino , Lábio/crescimento & desenvolvimento , Sistema Respiratório/crescimento & desenvolvimento , Fatores Etários , Cefalometria , Lábio/anatomia & histologia , Análise Multivariada , Tamanho do Órgão , Respiração , Estudos Retrospectivos , Sistema Respiratório/anatomia & histologia , Caracteres Sexuais , Fatores Sexuais
19.
J Perinatol ; 31(5): 302-10, 2011 May.
Artigo em Inglês | MEDLINE | ID: mdl-21127467

RESUMO

Apnea of prematurity (AOP) is a significant clinical problem manifested by an unstable respiratory rhythm reflecting the immaturity of respiratory control systems. This review will address the pathogenesis of and treatment strategies for AOP. Although the neuronal mechanisms leading to apnea are still not well understood, recent decades have provided better insight into the generation of the respiratory rhythm and its modulation in the neonate. Ventilatory responses to hypoxia and hypercarbia are impaired and inhibitory reflexes are exaggerated in the neonate. These unique vulnerabilities predispose the neonate to the development of apnea. Treatment strategies attempt to stabilize the respiratory rhythm. Caffeine remains the primary pharmacological treatment modality and is presumed to work through blockade of adenosine receptors A(1) and A(2). Recent evidences suggest that A(2A) receptors may have a greater role than previously thought. AOP typically resolves with maturation suggesting increased myelination of the brainstem.


Assuntos
Apneia , Cafeína/uso terapêutico , Hipercapnia/metabolismo , Hipóxia/metabolismo , Doenças do Prematuro , Taxa Respiratória/efeitos dos fármacos , Apneia/etiologia , Apneia/metabolismo , Apneia/fisiopatologia , Apneia/terapia , Arritmias Cardíacas/induzido quimicamente , Tronco Encefálico/efeitos dos fármacos , Tronco Encefálico/crescimento & desenvolvimento , Estimulantes do Sistema Nervoso Central/uso terapêutico , Pressão Positiva Contínua nas Vias Aéreas , Maturidade dos Órgãos Fetais , Humanos , Hipercapnia/complicações , Hipóxia/complicações , Recém-Nascido , Recém-Nascido Prematuro/metabolismo , Doenças do Prematuro/etiologia , Doenças do Prematuro/metabolismo , Doenças do Prematuro/fisiopatologia , Doenças do Prematuro/terapia , Prognóstico , Receptores Purinérgicos P1/metabolismo , Sistema Respiratório/efeitos dos fármacos , Sistema Respiratório/crescimento & desenvolvimento
20.
Ann Otol Rhinol Laryngol ; 119(8): 541-6, 2010 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-20860280

RESUMO

OBJECTIVES: The purpose of this study was to establish the largest magnetic resonance imaging study so far, by including 292 cases in a prospective fashion, to investigate the normative values of the upper airway and surrounding tissues during development. METHODS: We enrolled in the study 448 children who underwent cranial magnetic resonance imaging. We included 292 patients who had no sleep disorders or any associated symptom that could be related to breathing disorders. Using midsagittal and axial images, we evaluated the variations in size of the upper airway tissues. RESULTS: On images from the midsagittal plane, the normative values of the length and the thickness of the soft palate, the length and height of the tongue, the distance between the mental spine and the clivus, the thickness of the adenoid pad and the nasopharyngeal area, the adenoid pad oblique width, the soft palate oblique width, and the tongue oblique width were obtained for several age groups. Using images from the axial plane at the level of maximal tonsillar cross-sectional area, we measured the normative values of the mean tonsillar width and intertonsillar space. CONCLUSIONS: Magnetic resonance imaging is an excellent method of assessing upper airway structures. Knowledge of variations in size of the upper airway and surrounding tissues is essential in determining the significance of incidental findings in this area.


Assuntos
Desenvolvimento Infantil/fisiologia , Sistema Respiratório/anatomia & histologia , Sistema Respiratório/crescimento & desenvolvimento , Adolescente , Fatores Etários , Pesos e Medidas Corporais , Criança , Pré-Escolar , Estudos de Coortes , Tecido Conjuntivo/anatomia & histologia , Feminino , Humanos , Lactente , Tecido Linfoide/anatomia & histologia , Imageamento por Ressonância Magnética , Masculino , Boca/anatomia & histologia , Valores de Referência
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA