Diagnosis of primary ciliary dyskinesia / Diagnóstico de discinesia ciliar primária

Primary ciliary dyskinesia (PCD) is a genetic disorder of ciliary structure or function. It results in mucus accumulation and bacterial colonization of the respiratory tract which leads to chronic upper and lower airway infections, organ laterality defects, and fertility problems. We review the respiratory signs and symptoms of PCD, as well as the screening tests for and diagnostic investigation of the disease, together with details related to ciliary function, ciliary ultrastructure, and genetic studies. In addition, we describe the difficulties in diagnosing PCD by means of transmission electron microscopy, as well as describing patient follow-up procedures.

Discinesia ciliar primária (DCP) é uma doença genética que compromete a estrutura e/ou a função ciliar, causando retenção de muco e bactérias no trato respiratório e levando a infecções crônicas nas vias aéreas superiores e inferiores, defeitos de lateralidade visceral e problemas de fertilidade. Revisamos os sinais e sintomas respiratórios da DCP, os testes de triagem e a investigação diagnóstica, bem como detalhes relacionados ao estudo da função, ultraestrutura e genética ciliar. Descrevemos também as dificuldades em diagnosticar a DCP por meio de microscopia eletrônica de transmissão, bem como o seguimento dos pacientes.

Prognóstico da videocirurgia da região frontal com técnica modificada de fixação / Prognosis of frontal region video surgery with a modified fixation technique

INTRODUÇÃO: A videoendoscopia tem se estabelecido como procedimento de escolha no tratamento da ptose do supercílio e das rugas da região frontal. O acesso minimamente invasivo produz vantagens em relação à tradicional incisão coronal. Diversos métodos de fixação são relatados na literatura, apresentando resultados semelhantes. Nesta série de casos, descrevemos a fixação direta com agulha. OBJETIVO: Avaliar o prognóstico da videocirurgia, utilizando-se a técnica direta com agulha. MÉTODO: Avaliação fotográfica computadorizada de 37 pacientes submetidos à videoendoscopia da região frontal com a fixação direta com agulha, realizada em dois hospitais privados na cidade de Porto Alegre-RS. Resultados: A elevação média do supercílio foi de 5,7 mm no terço lateral e de 4,4 mm no terço medial. Após um pequeno descenso da elevação, no primeiro mês pós-operatório, o reposicionamento do supercílio permaneceu inalterado nas medidas subsequentes até 24 meses. CONCLUSÃO: A fixação direta com agulha é capaz de produzir resultados duráveis, seguros e reprodutíveis no período em que foram realizadas as medições.

INTRODUCTION: Video endoscopy has become a procedure of choice for the treatment of eyebrow ptosis and forehead wrinkles. This minimally invasive technique has several advantages over traditional coronal incision. Several fixation methods are reported in the literature, with similar results. In this study, we describe direct needle fixation. OBJECTIVE: To evaluate the prognosis of video endoscopic surgery using a direct needle technique. METHOD: Computerized photographic evaluations of 37 patients undergoing video endoscopy of the frontal region with needle direct fixation were conducted in two private hospitals in the city of Porto Alegre in Rio Grande do Sul, Brazil. RESULTS: The mean eyebrow elevations were 5.7 and 4.4 mm in the lateral and middle third measurements. After a small dip in elevation in the first month after surgery, the repositioning of the eyebrow remained unchanged in subsequent measurements up to 24 months later. CONCLUSION: Direct needle fixation produced lasting, reliable, and reproducible results during the period in which measurements were made.

Dinámica y patología del barrido mucociliar como mecanismo defensivo del pulmón y alternativas farmacológicas de tratamiento / Mucociliary clearance system in lung defense

The first line of defense to maintain the sterility of the intrapulmonary airways is the mucociliary clearance system. This rapidly responding, non-specific, immune defensive system is challenged by approximately 12,000 liters of air filtered by the lungs each day, containing millions of particles like spores, environmental and eventually toxic pollutants. The main components of this system are the floating mucus "blanket", the underlying mucus propelling cilia with periciliary fluid, and the airway epithelium with secretory and ciliated type of cells. The fine and coordinated regulation of these three components is critical for an effective performance. Deregulation resulting from continuous insults, inherited ion channel disease, infections or abnormal immune response may lead to mucus alterations, goblet cell hyperplasia and metaplasia, airway obstruction, air trapping and chronic lung disease. Options for treatment are limited. Understanding this system may reveal new targets for treatment of lung disease.

TNF alfa modifica la respuesta de la frecuencia de batido ciliar a la carga viscosa, asociado a alteraciones en el calcio intracelular en células ciliadas respiratorias humanas / TNF alpha modifies ciliary beat frequency in response to viscous overload, associated to changes in intracellular calcium in human respiratory ciliated cells

Introducción: Secreciones sinonasales patológicas y elevados niveles de factor de necrosis tumoral alfa (TNF alfa) se han encontrado en mucosa sin usal de pacientes con sinusitis crónica. Las células ciliadas respiratorias tienen una reserva funcional que les permite autorregular su frecuencia de batido ciliar (FBC) en respuesta a cambios en la viscosidad, modificando los niveles de calcio intraacelular [Ca+²]ic. Objetivo: Nuestro objetivo es determinóar si TNFalfa afecta el mecanismo de autorregulación y la homeostasis del calcio intraacelular frente a cambios en la viscosidad. Material y método: Cultivos primarios de explantes de tejido adenoideo. Registro de FBC mediante microfotodensitometría. Cultivos tratados con TNFalfa (10 ng/ml) o control durante 24 y 48 horas. Se in crementó la viscosidad agregando dextrano 500 al 10 por ciento y 20 por ciento. Se midió [Ca+²]ic en células cargadas con Fura 2AM. Resultados: El tratamiento con TNFalfa por 48 horas produjo una significativa disminución de la FBC a baja viscosidad, aumento significativo de [Ca+²]ic y caída mayor de FBC en cultivos tratados con tapsigargina (bloqueador bomba calcio-ATPasa retículo). in o se encontró diferencia a alta viscosidad. Conclusión: Después de 48 horas de exposición a TNFalfa se observa un efecto negativo en el mecanismo de adaptación de las células ciliadas a un medio con baja viscosidad, probablemente secundario a cambios en la homeostasis del [Ca+²]ic.

Introduction: Pathologic sinonasal secretions and elevated levels of tumor necrosis factor alpha (TNFalpha) have been in oted in sin us mucosa ofpatients with chronic sinusitis. Respiratory ciliated cells have a functional reserve that allows them to autoregulate their ciliary beat in response to the changesin viscosity, modify in g intraacellular calcium levels [Ca+²]ic. Aim: Our goal was to determinate if TNFalpha affect this autoregulation to viscosity and calcium homeostasis. Material and Method: Primary cultures from adenoid tissue expiants. Ciliary beat frequency (CBF) was recorded usin g microphotodensitometry Cultures viere treated with TNF alpha (10 ng/ml) or control during 24 and 48 hours. Viscosity was increased by add in g dextran 500 10 percent and 20 percent. [Ca+²]ic was determined in cells loaded with Fura-2AM. Results: 48 hours treatment with TNFalpha produced a significant decrease in CBF at low viscosity significant increase in [Ca+²]ic and greater decrese in CBF in cultures treated with thapsigargin (endoplasmic calcium-ATPase pump blocker). Conclusions: After 48 hours of exposure to TNF alpha a negative effect in the adaptation mechanism to a low viscous media is observed in ciliated cells, probably secondary to changesin homeostasis of [Ca+²]ic.

Cultivo primario de células ciliadas de adenoides humanos: un modelo experimental para evaluar la actividad ciliar in vitro / Primary culture of human adenoid ciliated cells: an experimental model to evaluate ciliar activity in vitro

Introducción: El clearance mucociliar normal es el mecanismo de defensa básico de las vías respiratorias. Sin embargo, los mecanismos de control ciliar aún se desconocen. Con el fin de entenderlo mejor, se han desarrollado diferentes técnicas de cultivo de células ciliadas. Objetivos: Desarrollar un modelo experimental a partir de cultivos primarios de tejido adenoideo y cornete medio. Caracterizarla respuesta a adenosin trifosfato (ATP), agonista conocido de la frecuencia de batido ciliar (FBC). Material y método: Cultivos primarios a partir de explantes de epitelio adenoideo y cornete medio humano. Medición de FBC, con técnica de microfotodensitometría, en condición basal y en respuesta a ATP a diferentes concentraciones. Resultados: La FBC basal (promedio (X) + - desv estándar (DE)) para los cultivos de cornete medio fue 11,9 + -1,5 Hz y para tejido adenoideo fue 10,9 + - 1,9 (p >0,05). Se observó un aumento en la FBC en respuesta a ATP, dosis dependiente. No hubo diferencia significativa en la FBC basal ni en la respuesta a ATP entre cultivos de cornete medio y adenoides. Conclusión: El cultivo primario de células ciliadas nasales a partir de explantes de adenoides, es un modelo experimental reproducible, en el que es posible observar actividad ciliary una respuesta funcional concordante con lo descrito en la literatura.

Introduction. Mucociliary clearance constitutes the main defense mechanism of the airway, but the mechanisms of ciliary control are still unknown. With the aim of a better understanding of this process, many ciliated cells culture techniques have been developed. Aims. 1. To develop an experimental model based on primary cultures from adenoid and middle turbinate tissue. 2. To characterize in this model the response to ATP, a known agonist of ciliary beat frequency (CBF). Material and Method. Primary cultures derived from human adenoid tissue and middle turbinate epithelial explants were obtained. CFB was measured by microphotodensitometry, both in basal conditions and in response to ATP at different concentrations. Results. Basal CFB (average (X) +- standard deviation (SD)) for middle turbinate cultures was 11.9 +-1.5 Hz, and for adenoid tissue was 10.9 +-1.9 Hz (p< 0.05). A CBF increase was observed in response to ATP, in a dose-dependent manner. No significant difference in basal CFB or in response to ATP was found between middle turbinate and adenoid cultures. Conclusion. Primary culture of nasal ciliated cells derived from adenoid explants is a reproducible experimental model, in which it is possible to observe both ciliary activity and a functional response in accordance to what has been reported in the literature.

Discinesia ciliar primária / Primary ciliary diskinesia

Discinesia ciliar primária (DCP) é uma doença genética autossômica recessiva, caracterizada por defeito da motilidade de estruturas ciliadas. A propulsäo do espermatozóide e o clearance do muco estäo prejudicados. As manifestaçöes clínicas de interesse para o otorrinolaringologista säo: sinisite, otomastoidite, problemas na fala e olfato. O diagnóstico é feito por uma cascata de investigaçöes, iniciando com o teste de sacarina, frequência do batimento ciliar e microscopia eletrônica para verificar a morfologia e a orientaçäo ciliar. É importante que o diagnóstico seja precoce para previnir o desenvolvimento de bronquiectasia e para evitar qualquer procedimento otorrinolaringológico desnecessário. O tratamento da DCP é essencialmente sintomático. Os pilares säo a antibioticoterapia e a fisioterapia torácica. O seguimento contínuo é essencial, e o acompanhamento deve ser multidisciplinar, com o apoio de centros com interesse em DCP. O prognóstico é bom, mas a morbidade é considerável se a DCP for manuseada incorretamente.

Effects of formaldehyde on the frog's mucociliary epithelium as a surrogate to evaluate air pollution effects on the respiratory epithelium

The increasing use of alcohol as an alternative fuel to gasoline or diesel can increase emission of formaldehyde, an organic gas that is irritant to the mucous membranes. The respiratory system is the major target of air pollutants and its major defense mechanism depends on the continuous activity of the cilia and the resulting constant transportation of mucous secretion. The present study was designed to evaluate the effects of formaldehyde on the ciliated epithelium through a relative large dose range around the threshold limit value adopted by the Brazilian legislation, namely 1.6 ppm (1.25 to 5 ppm). For this purpose, the isolated frog palate preparation was used as the target of toxic injury. Four groups of frog palates were exposed to diluted Ringer solution (control, N = 8) and formaldehyde diluted in Ringer solution at three different concentrations (1.25, 2.5 and 5.0 ppm, N = 10 for each group). Mucociliary clearance and ciliary beat frequency decreased significantly in contact with formaldehyde at the concentrations of 2.5 and 5.0 ppm after 60 min of exposure (P<0.05). We conclude that relatively low concentrations of formaldehyde, which is even below the Brazilian threshold limit value, are sufficient to cause short-term mucociliary impairment

Población celular del pulmón: primera de dos partes / Cell population of the lung: first part

Este trabajo de revisión incluye los principales aspectos anatómicos, histológicos, ultraestructurales, bioquímicos y fisiológicos del pulmón. El epitelio de las vías aéreas está formado por las siguientes células: ciliadas, caliciformes, serosas, en cepillo, intermedias, oncocitos, neuroendocrinas, de Kultschitzky y de Clara. Las más abundantes son las ciliadas, sus cilios poseen nueve pares de microtúbulos periféricos y dos centrales, y los brazos de dineína interno y extrerno y ATP-asa, responsables de su movilidad. Las segundas células más frecuentes son las caliciformes. Son las encargadas de la producción de moco. La célula de Clara se localiza en la vía aérea pequeña, posee gran actividad metabólica, con función destoxificadora de sustancias extrañas, y participa en la formación del surfactante. El alvéolo está compuesto por los neumocitos tipos I y II. El primero forma, junto con la célula endotelial, la membrana alvéolocapilar, que es la unidad anatómica-funcional del pulmón donde se lleva a cabo el intercambio gaseoso. El neumocito tipo II se encarga de la restitución del epitelio alveolar y es el principal productor del surfactante. El intersticio está formado por fibras, principalmente de colágena y elastina, por diversas sustancias como los proteoglicano y por células, siendo la más común el fibroblasto. Se mencionan también las células de la inflamación y la respuesta inmunitaria

Transplante de múltiplos enxertos cilíndricos de couro cabeludo para correção de madarose superciliar da hanseníase / ?

A hanseníase ainda representa um grave flagelo em nosso meio onde o estigma decorrente da doença é forte o suficiente para marginalizar os portadores de suas següelas. A madarose superciliar é uma alteração muito freqüente, caracterizada mas não patognomônica desta doença, sendo geralmente bilateral e definitiva. Neste estudo procuramos corrigir a madarose superciliar decorrente da hanseníase pela aplicação de tranplante de múltiplos enxertos cilíndricos de couro cabeludo removidos com auxílio de "punch". Um conjunto de características capazes de determinar o resultado final das cirurgias foi observado em um dos 17 pacientes operados por meio desta técnica, após o 8§ mês pós-operatório. O aspecto isolado de cada supercílio foi considerado BOM em 22 (64,70 por cento), ACEITÁVEL em 6 (17,65 por cento) e RUIM em 6 (17,65 por cento). A aparência estética final de cada paciente foi considerada SATISFATÓTIA em 14 (82,35 por cento) e INSATISFATÓRIA em 3 (17,65 por cento). Os enxertos cilíndricos incorporaram com sucesso aos orifícios receptores. O procedimento estudado demonstrou ser simples, seguro e eficaz e isento de complicações significativas reunindo todas as qualidades necessárias para a sua execução em um grande número de pacientes. O autor destacou ainda importantes aspectos relativos a reinserção psico-social completa destes pacientes na sociedade.

Development of the mucociliary system in the eustachian tube and middle ear: murine model

In order to describe the developmental anatomy of the murine eustachian tube and its related structures, seventy six mice of ages ranging from gestational day 11 to postnatal day 21 were investigated through the light and electron microscopic observations. Development of the ciliated cells was seen concurrently in both the eustachian tube and middle ear on the 16 th gestation day, one day earlier than the epithelial secretory cells appeared in both the eustachian tube and middle ear. The number of ciliated cells and secretory cells increased rapidly after birth. Tubal glands were well identified with evidence of secretory activity around the time of birth. Thus, the findings of this study indicate that the mucociliary defense system starts to develop during the fetal stage and is well established immediately after birth.

Measurement of nasal mucociliary transportation rate in healthy aged persons

The measurement of the nasal mucociliary transportation rate [MTR] is useful not only in the fundamental research but also in clinical evaluation of the patients as well .We have used the radioisotope 113m In-DTPA as the tracer combined with gamma scintigraphy in measuring this rate in 40 healthy aged persons. The mean value is 3.47mm/min. It is significantly slower than that of the adults and youths [5.71mm/min] [p<0.01]