Orientador: João Roberto Gonçalves / Resumo: O espectro oculoauriculovertebral (EOAV), também conhecido como Síndrome de Goldenhar, afeta o desenvolvimento de estruturas dos 1º e 2º arcos branquiais que envolvem alterações mandibulares, oculares, vertebrais, auriculares e estruturas extracranianas. A maioria dos estudos sobre o EOAV são relatos clínicos e aqueles com populações significativas são descrições fenotípicas. Os estudos que avaliaram a morfologia tiveram seus resultados limitados ao incluir indivíduos com envolvimento unilateral, bilateral, leve, moderado e grave, na mesma amostra. Dessa forma, os objetivos do presente estudo foram de caracterizar a morfologia craniofacial e da via aérea e suas possíveis correlações em uma amostra homogênea (n = 18) composta apenas por indivíduos com EOAV unilateral grave. A análise da via aérea foi realizada por meio do Software Dolphin Imaging®. Para avaliar a morfologia craniofacial, sete medidas morfométricas foram realizadas com Software Materialize Mimics®. Para comparar as variáveis das vias aéreas e morfométricas, foi utilizado um grupo controle pareado por idade e sexo. Pelo teste de Shapiro-Wilk, observou-se que 13 das 35 variáveis não apresentaram distribuição normal. O teste t de Student foi aplicado para as variáveis de distribuição normal e Mann-Whitney para aquelas sem distribuição normal. Comparando os grupos Controle e OAVS para medidas craniofaciais, 16 das 26 variáveis foram estatisticamente significantes e, para as medidas das vias aéreas, todas foram esta... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: The Oculoauriculovertebral spectrum (OAVS), also known as Goldenhar Syndrome, affects the development of structures of the 1st and 2nd branchial arches that involve mandibular, ocular, vertebral, auricular changes, as well as extracranial structures. Most OAVS studies are clinical reports, and those with significant populations are phenotypic description. Studies that evaluated morphology had their results limited by including individuals with unilateral, bilateral, mild, moderate and severe involvement in the same sample. The objectives of this study were to characterize the craniofacial and airway morphology and its possible correlations in a homogeneous sample (n = 18) composed only of unilateral severe OAVS individuals. Airway analysis was performed using Dolphin Imaging® software. To evaluate craniofacial morphology, seven morphometric measurements were performed by Materialize Mimics® Software. To compare airway and morphometric variables, a control group matched by age and sex was used. Through the Shapiro-Wilk test, it was observed that 13 of the 35 variables did not have normal distribution. Student's t-test was applied for the normal distribution variables and Mann-Whitney for those without normal distribution. Comparing the Control and OAVS groups for craniofacial measurements, 16 of the 26 variables were statistically significant, and for airway measurements all were statistically significant except for the RG Area variable. Pearson and Spearman's correlation coef... (Complete abstract click electronic access below) / Mestre

Apesar de bem estabelecido em termos morfológicos, a repercussão funcional do envolvimento das pequenas vias aéreas nas pneumopatias intersticiais fibrosantes (PIF) permanece controversa. O presente estudo avaliou de maneira invasiva e não-invasiva (espirometria, volume de fechamento, variação da complacência dinâmica com a freqüência respiratória) a função das pequenas vias aéreas em portadores de PIF, comparando com grupo controle e correlacionando com índices morfométricos de biópsias. Os testes funcionais não diferenciaram portadores da doença dos controles quanto ao acomentimento das pequenas via aéreas e não se correlacionaram com os dados morfométricos / Although well known involvement of small airway in fibrosing interstitial lung disease based on morfologic issues, its functional consequences remains controversial. We present an invasive and non-invasive physiologic study for small airway function (pulmonary function tests, closing volume and frequency dependence of dynamic compliance) in patients with lung fibrosis. The physiological data were compared with normal controls and correlated with morfometric measurements from biopsies. Specific small airway function data could not show obstructive pattern when compared with normals, and did not correlate with morofmetric data

Em condições basais a inspiração é um fenômeno ativo enquanto a expiração é um fenômeno passivo. Em condições de desafios metabólicos, como aumento da pressão parcial de CO2 e da [H+] no sangue arterial (hipercapnia/acidose), ocorre aumento da atividade inspiratória, a expiração passa a ser ativa, produzindo aumentos da atividade dos músculos abdominais, e a resistência das vias aéreas superiores reduz. O Locus Coeruleus (LC) contém neurônios noradrenérgicos (NE) que aumentam sua frequência de potenciais de ação quando expostos a elevados níveis de CO2/[H+] e se comunicam com os neurônios respiratórios do tronco encefálico para fazer ajustes compensatórios na ventilação pulmonar durante a hipercapnia/acidose. Utilizando preparações in situ de ratos avaliamos a contribuição dos neurônios NE do LC na geração central das atividades inspiratória e expiratória e no controle da resistência das vias aéreas superiores em condições basais e em resposta a hipercapnia/acidose. Neurônios NE do LC foram seletivamente silenciados de maneira aguda e reversível pela aplicação do peptídeo de inseto alatostatina (Alst) após a transfecção celular utilizando um vetor lentiviral para expressão de receptores de Drosophila para a Alst acoplados a proteína G inibitória (AlstR). Dez a doze dias após, realizamos a abordagem dorsal da preparação in situ de ratos. Os nervos frênico (PN), abdominal (AbN), hipoglosso (HN) e vago cervical (cVN) foram registrados e analisados em diferentes fases do ciclo respiratório. Registros extracelulares single unit dos neurônios do LC também foram realizados. A frequência respiratória (fR), a duração da inspiração (DI) e da expiração (DE), a expiração ativa, a magnitude da modulação respiratória e a frequência de potenciais de ação dos neurônios do LC também foram avaliadas. A inibição seletiva dos neurônios NE do LC usando Alst não provocou alterações significativas na atividade dos motores nervos respiratórios, na fR, DI e DE em normocapnia. A inibição desses neurônios antes e/ou durante à hipercapnia/acidose reduziu significantemente a amplitude do AbN e em alguns momentos, eliminou a expiração ativa, além de reduzir as respostas inspiratórias do PN e HN (amplitude) e a atividade pós-inspiratória (adução da glote) do cVN. Quandoda ausência da expiração ativa após a inibição dos neurônios NE do LC, a DI, DE e a duração da atividade pré-inspiratória do cVN (abdução da glote) e HN (protusão da língua) foram normalizadas. A adição de Alst em preparações in situ de ratos que não expressavam o AsltR durante a hipercapnia/acidose não causou alterações no padrão dos nervos motores respiratórios registrados, na incidência da expiração ativa e na fR, DI e DE. Entre os neurônios do LC registrados, encontramos três populações com diferentes padrões de modulação pela respiração e uma com atividade tônica. A hipercapnia/acidose aumentou a magnitude da modulação respiratória e a frequência de potenciais de ação destas populações neuronais. Esses dados demonstram que os neurônios NE do LC exercem importante papel modulatório excitatório na geração central da inspiração, expiração ativa e no controle da resistência das vias aéreas superiores evocados pela hipercapnia/acidose em preparações in situ de ratos / In basal conditions, inspiration is an active phenomenon while expiration is a passive phenomenon. Under conditions of high metabolic demands, such as increased in partial pressure of CO2 and [H+] in arterial blood (hypercapnia/acidosis), there is an increase in inspiratory activity, expiration becomes active, producing increases in abdominal muscle activity, and the resistance of the upper airways reduces. The Locus Coeruleus (LC) contains noradrenergic (NE) neurons that increase their firing frequency when exposed to elevated CO2/[H+] levels and communicate with respiratory brainstem neurons to make compensatory adjustments in lung ventilation during hypercapnia/acidosis. Using in situ preparations of rats, we evaluated the contribution of LC NE neurons in the central generation of inspiratory and expiratory activities, as well as in the control of upper airway resistance in basal conditions and in response to hypercapnia/acidosis. LC NE neurons were selectively acutely and reversibly silenced by application of the insect allatostatin peptide (Alst) after cellular transfection using a lentiviral vector for expression of Alst Drosophila receptors coupled to inhibitory G protein (AlstR). Ten to twelve days after, we performed the dorsal approach of the in situ preparation of rats. The phrenic (PN), abdominal (AbN), hypoglossal (HN) and cervical vagus (cVN) nerves were recorded and analyzed in different phases of the respiratory cycle. Single unit extracellular records of LC neurons were also performed. Respiratory frequency (fR), duration of inspiration (DI) and expiration (DE), active expiration, the magnitude of respiratory modulation and the firing frequency of LC neurons were also evaluated. Selective inhibition of LC NE neurons using Alst did not produce significant changes in the activity of respiratory motor nerves, fR, DI and DE in normocapnia. Inhibition of these neurons before and/or during hypercapnia/acidosis significantly reduced AbN amplitude and its incidence, as well as the inspiratory responses of PN and HN (amplitude) and post-inspiratory activity (glottal adduction) of the cVN. In the absence of active expiration after the inhibition of LC NE neurons, the DI, DE and the pre-inspiratory activity of cVN (glottal abduction) and HN (tongue protrusion) were normalized. The perfusion of Alst in in situ preparations of rats withoutthe expression of the AsltR during hypercapnia/acidosis did not change the pattern of the recorded respiratory motor nerves, the incidence of active expiration, fR, DI and DE. Among the registered LC neurons, we found three populations with different patterns of respiratory modulation and one with tonic activity. Hypercapnia/acidosis increased the magnitude of the respiratory modulation and their firing frequency. These data demonstrate that LC NE neurons exert an important excitatory modulatory role in the central generation of inspiration, active expiration and in the control of upper airway resistance evoked by hypercapnia/acidosis in in situ preparations of rats

Des techniques d’exploration de la fonction respiratoire nécessitant une coopération minimale, réalisables en ventilation spontanée, sans anesthésie, sont nécessaires chez les jeunes enfants asthmatiques. De telles méthodes sont la mesure de l’impédance respiratoire par la technique des oscillations forcées, la mesure de la résistance spécifique des voies aériennes par pléthysmographie ou la capnographie qui mesure la concentration de CO2 dans le gaz expiré. L’objectif principal de travail a été l’amélioration du diagnostic de l’asthme infantile en utilisant des études cliniques et fondamentales. Une étude clinique incluant des enfants asthmatiques et témoins a montré que la spécificité de la résistance est améliorée en expiration par rapport à l’inspiration du au fait que la fermeture de la glotte à l’expiration est proportionnelle au degré de l’obstruction bronchique. Une autre étude a démontré que le diagnostic de l’asthme est amélioré par le calcul des variations d’admittance respiratoire à un bronchodilatateur, ce calcul n’étant pas influencé par l’artefact des voies aériennes supérieures. Une étude a montré que la mesure de la résistance spécifique des voies aériennes en ventilation spontanée est surestimée par rapport à la mesure en halètement. La capnographie est une méthode noninvasive qui donne des renseignements sur l’inhomogénéité de la ventilation pendant une obstruction bronchique aigue. Toutefois, elle peut être limitée chez le jeune enfant par une fréquence ventilatoire élevée. Une étude expérimentale a été menée chez le lapin pour valider les indices capnographiques à différentes fréquences ventilatoires pour identifier la présence d’une obstruction aigue / Shorter lung function testing methods are needed in young asthmatic children, requiring minimal cooperation, performed in spontaneous breathing, without anaesthesia. Such methods are measurement of respiratory impedance by forced oscillations technique, measurement of specific airway resistance by plethysmography or capnography, measurement of CO2 concentration in expired air. The main objective of this work was to improve pediatric asthma diagnosis by using clinical and experimental studies. A study including asthmatic and control children showed that the specificity of resistance was improved in expiration compared to inspiration due to the fact that the glottis closure during expiration was proportional to the degree of airway obstruction. Another clinical study demonstrated that asthma diagnosis was improved by computation of respiratory admittance response to a bronchodilator because this computation is not affected by upper airways artifact. A study showed that specific airway resistance measured during spontaneous breathing was overestimated compared to panting metthod. Capnography is a non invasive technique. The shape of the expired CO2 time course is altered by the non homogenous distribution of ventilation resulting from bronchoconstriction. But its clinical usefulness in young children may be limited by the relatively high respiratory rate. An experimental study was conducted in rabbits to validate capnogram shape indices at different rates of breathing during airway constriction by methacholine. The indices have detected the acute airway obstruction even at high frequencies, frequencies usually presented by infants during an acute bronchoconstriction

Apesar de bem estabelecido em termos morfológicos, a repercussão funcional do envolvimento das pequenas vias aéreas nas pneumopatias intersticiais fibrosantes (PIF) permanece controversa. O presente estudo avaliou de maneira invasiva e não-invasiva (espirometria, volume de fechamento, variação da complacência dinâmica com a freqüência respiratória) a função das pequenas vias aéreas em portadores de PIF, comparando com grupo controle e correlacionando com índices morfométricos de biópsias. Os testes funcionais não diferenciaram portadores da doença dos controles quanto ao acomentimento das pequenas via aéreas e não se correlacionaram com os dados morfométricos / Although well known involvement of small airway in fibrosing interstitial lung disease based on morfologic issues, its functional consequences remains controversial. We present an invasive and non-invasive physiologic study for small airway function (pulmonary function tests, closing volume and frequency dependence of dynamic compliance) in patients with lung fibrosis. The physiological data were compared with normal controls and correlated with morfometric measurements from biopsies. Specific small airway function data could not show obstructive pattern when compared with normals, and did not correlate with morofmetric data

Decorin, is an extracellular matrix proteoglycan with important biological functions. Decorin deficiency affects collagen fibrillogenesis, airway mechanics, airway-parenchymal interdependence, and airway smooth muscle proliferation and apoptosis. We questioned whether decorin deficiency would alter allergen-induced asthma in a mouse model. Decorin-/- and decorin+/+ mice (C57Bl/6) were sensitized and challenged with ovalbumin. Control animals received saline. Responsiveness was assessed at baseline and after delivery of increasing concentrations of methacholine. Histological analyses were also performed. Decorin deficiency resulted in more modest hyperresponsiveness. Respiratory resistance and elastance along with tissue damping and tissue elastance, were increased in ovalbumin decorin +/+ and decorin-/-, but more so in decorin+/+ . Airway resistance was increased in ovalbumin decorin+/+ only. Inflammation and collagen staining within the airway wall, were increased in ovalbumin decorin+/+ mice only; whereas biglycan was significantly increased in ovalbumin decorin-/- mice only. These results reflect the role of decorin in the development of allergen-induced asthma.

Untersuchung zur Wirkung von intranasal verabreichtem Xylometazolin bei brachy- und normozephalen Hunden: Impuls-Oszillometrie und akustische Rhinometrie P. Franco, J. P. Hueber, G. U. Oechtering Klinik für Kleintiere, Arbeitsgruppe Brachyzephalie, Universität Leipzig Einleitung: Die zuchtbedingte Verkürzung des Gesichtsschädels brachy - zephaler Hunderassen hat zu einer Reihe klinisch relevanter morphologischer und physiologischer Veränderungen geführt. Hierzu zählen stenotische Naseneingänge, eine durch fehlgebildete Conchen obstruierte Nasenhöhle sowie ein verdicktes und verlängertes Gaumensegel. Diese Einengung der oberen Atemwege führt zu Atemnot und ausgeprägter Belastungsintoleranz, was als Brachyzephales Atemnotsyndrom (BAS) bezeichnet wird. Xylometazolin ist ein für den Menschen zugelassenes Alpha-Sympathomime - tikum. Topische und systemische Sympathomimetika werden beim Menschen zur Behandlung nasaler Kongestionen zum Abschwellen der Nasenschleimhaut eingesetzt. Zielstellung: Ausgehend von der Hypothese, dass Xylometazolin auch bei Hunden zu einem Abschwellen der Nasenschleimhaut führt und dass die Morphologie der Nasenmuscheln sich zwischen den zwei Zielgruppen unterscheidet, sollte der intranasale Strömungswiderstand bei brachy- und normozephalen Hunden vor und nach Xylometazolingabe mit Impuls- Oszillometrie untersucht werden. Zusätzlich wurden in der Beaglegruppe mit akustischer Rhinometrie das Nasenhöhlenvolumen und die minimale Querschnittsfläche bestimmt. Methodik: Die Messungen erfolgten nach dem Prinzip der Impuls-Oszillometrie (IOS) und akustischer Rhinometrie. In einer prospektiven klini - schen Studie wurden 10 brachyzephale Hunde (5 Möpse, 5 Französische Bulldoggen) und 6 Beagles untersucht. Bei den anästhesierten, spontan atmenden Tieren wurde der intranasale Strömungswiderstand mit Impuls- Oszillometrie unmittelbar vor und 30 Minuten nach intranasal verabreichtem Xylometazolin gemessen. Messungen mit akustischer Rhinometrie erfolgten zusätzlich vor und nach Xylometazolingabe. Bei allen Tieren wurden die oberen Atemwege endoskopisch und computertomographisch untersucht. Ergebnisse: Der aus drei Messungen gemittelte intranasale Strömungswiderstand bei Patienten mit BAS betrug vor Xylometazolingabe 0,87 ± 0,097 kPa/(L/s). Nach Xylometazolingabe reduzierte sich der intranasale Strömungswiderstand um etwa 48% auf 0,42 ± 0,55 kPa/(L/s). Vergleich - bare Ergebnisse ermittelten wir in der Beaglegruppe. Nach Xylometazolingabe ergab sich bei den Beagles eine Zunahme des Nasenvolumens und der minimalen Querschnittsfläche. Schlussfolgerungen: Wir konnten erstmals zeigen, dass Xylometazolin auch bei Hunden zum Abschwellen der Nasenschleimhaut führt und sich das Abschwellverhalten zwischen brachy- und normozephalen Hunden kaum voneinander unterscheidet. A13 Abstracts 18. Jahrestagung der DVG-FG InnLab © Schattauer 2010 Tierärztliche Praxis Kleintiere 1/2010

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La fréquence de l’asthme augmente au Vietnam, mais les moyens de diagnostic et d’évaluation fonctionnelle sont limités. Une étude précédente utilisant la technique des oscillations forcées a montré une différence de résistance des voies aériennes entre enfants français et vietnamiens à l’âge de 10 ans mais pas à 6 ans. Si l’hypothèse d’une différence ethnique significative est correcte, alors des différences semblables devraient aussi exister à l’âge adulte. Pour tester l’hypothèse, une étude par pléthysmographie a été mise en place pour mesurer la résistance des voies aériennes et la résistance spécifique des voies aériennes chez de jeunes adultes sains en France et au Vietnam. Nous avons profité de l’étude pour établir des valeurs de référence pour les volumes pulmonaires dans ces populations. La résistance des voies aériennes est significativement plus grande chez les sujets vietnamiens que chez les caucasiens, mais il n’y a aucune différence de résistance spécifique des voies aériennes. Au final, l’étude ne montre pas de différence de calibre des voies aériennes normalisé pour le volume pulmonaire liée l’ethnie, à l’âge adulte. La taille debout est le facteur prédictif le plus important pour la capacité pulmonaire totale, tandis que l’ethnicité est un facteur important pour la capacité vitale et le rapport du volume résiduel à la capacité pulmonaire totale. Cette étude est la première qui fournit des valeurs de référence pour la résistance des voies aériennes, la résistance spécifique des voies aériennes et les volumes pulmonaires par pléthysmographie chez l’adulte vietnamien. La pléthysmographie a été validée à Hanoi et l’étude a permis la formation d’un nouveau groupe de travail sur le diagnostic et la prise en charge de l’asthme au Vietnam / Despite the increasing prevalence of asthma in Viet Nam, the country has limited means for respiratory function testing. A previous study using the forced oscillation technique suggested lower respiratory resistance between French and Vietnamese children at 10 years but not 6 years of age. If the hypothesis of a significant ethnic difference in airway caliber is correct, then similar differences should exist at adult age. To test the hypothesis, a plethysmographic study was set up to measure airway resistance and specific airway resistance in healthy young adults in France and Viet Nam. We took advantage of the study to provide reference values for lung volume in these populations. Airway resistance is significantly larger in Vietnamese than in Caucasians but there is no difference in specific airway resistance. Altogether the study does not support the consequence of a putative ethnic difference in childhood airway caliber on airway resistance normalized for lung volume at adult age. The standing height is the best predictor of the total lung capacity, while ethnicity is an important predictor of vital capacity and of the residual volume to total lung capacity ratio. This is the first study which provides reference values for airway resistance, specific airway resistance and lung volumes by plethysmography in healthy young Vietnamese adults. Plethysmography was validated in the north of Viet Nam, and the study allowed initiating a young working group on asthma diagnosis in Vietnam