Vários materiais têm sido injetados ou inseridos nas pregas vocais na tentativa de solucionar a incompetência ou insuficiência glótica. Contudo, poucos são os estudos que avaliam o processo cicatricial decorrente da enxertia destes materiais. O objetivo desta pesquisa foi quantificar e comparar as fibras colágenas no músculo vocal das laringes dos coelhos que foram submetidos a enxerto unilateral de gordura ou fáscia muscular com a prega vocal contra-lateral, que foi submetida ao mesmo procedimento, com exceção da enxertia. Estudamos 24 coelhos, divididos em dois grupos com 12 coelhos em cada um. No primeiro grupo, denominado F (Fáscia), os coelhos foram submetidos à inserção de enxerto de fáscia lata autóloga na prega vocal direita. No outro grupo, denominado G (Gordura), os coelhos foram submetidos a implante de gordura autóloga \"em bloco\" também na prega vocal direita. Todos os coelhos foram também submetidos ao mesmo procedimento na prega vocal esquerda, com exceção da colocação do enxerto. A prega vocal esquerda, desta forma, constituiu o \"controle\" para cada coelho. Metade dos coelhos, de cada um dos grupos (F e G), foi sacrificada após 90 dias do procedimento cirúrgico. A outra metade dos coelhos dos grupos G e F foi sacrificada após 180 dias do procedimento cirúrgico. As laringes foram removidas e as pregas vocais, direita e esquerda, foram preparadas histologicamente. Os cortes corados pelo método da picrosírius-polarização foram utilizados para a visualização e análise das fibras colágenas. O colágeno foi analisado morfometricamente através do método da Picrossírius-polarização com a utilização do software Image Pro Plus. Houve aumento do colágeno em todos grupos enxertados quando comparados com o grupo controle. A concentração do colágeno encontrada nos coelhos submetidos a enxerto de gordura foi significativamente maior quando comparados à concentração do colágeno nos coelhos submetidos a enxerto de fáscia muscular, tanto com 90 quanto com 180 dias. A enxertia de gordura e fáscia lata na prega vocal de coelho promoveu maior deposição de colágeno do que no grupo controle, sendo mais exuberante na inserção de gordura / Several materials have been injected or inserted in the vocal fold, in attempt to solve glottic insufficiency. Nevertheless, there is just a few papers that evaluates the inflammatory process resulted from these materials incorporation. The objective of this study was to quantify and compare the collagen fibers in the vocal muscle of the larynx from the rabbits in which unilateral fat and muscular fascia were introduced, to the contralateral vocal fold, in which the same procedure have taken place, except be the grafting. Twenty four rabbits were used in this study, divided into two groups, 12 rabbits each. In the first group, named F (from Fascia), the rabbits underwent the insertion of fascia lata into the right vocal fold. In the other group, named G (from Grease), the rabbits underwent implantation of autologous fat \"en bloc\" in the right vocal fold, as well. All rabbits have undergone the same procedure in the left vocal fold, except for the graft insertion. The left vocal fold, therefore, formed the control group for each rabbit. Half the rabbits, form each group (F and G), was sacrificed after 90 days, while the other half was sacrificed after 180 days from the surgical procedure. The larynxes were removed and the vocal folds, right and left, were prepared for histology, using the method of picrosirius-polarization for the coloration. The collagen fibers in the samples were analyzed using a computer software called Image Pro Plus. An increasing of the collagen was found in all the groups in which grafts have been placed, when compared to the control group. The collagen density found in those rabbits which underwent fat insertion was significantly higher than in those with muscular fascia insertion, for both periods of 90 and 180 days, as well. Fat and muscular fascia insertion in rabbits vocal fold resulted in a higher collagen deposition, when compared to the control group, being

Anti-inflamatórios não esteroidais (AINEs) de uso tópico ocular são amplamente utilizados por um número crescente de médicos e veterinários, clínicos gerais e oftalmologistas. A crescente utilização de AINEs tópicos é motivada pela busca de fármacos que não apresentem os conhecidos efeitos adversos tópicos e sistêmicos dos corticosteróides. Desta forma, os profissionais envolvidos no cuidado destes pacientes devem estar cientes de que fármacos AINEs tópicos não são livres de efeitos adversos. Este trabalho objetivou investigar os potenciais efeitos adversos locais e sistêmicos da utilização de colírios contendo diclofenaco sódico 0,1% e cetorolaco de trometamina 0,5% em coelhos tratados por 90 dias. Desta forma buscou-se elucidar questões relacionadas à segurança do seu uso como agente terapêutico, que poderiam restringir a sua aplicação clínica em pequenos animais. Para isso, 18 coelhos foram divididos em três grupos. Os animais foram tratados três vezes ao dia por 90 dias com colírio de cetorolaco de trometamina 0,5%, diclofenaco sódico 0,1% e solução fisiológica (NaCl 0,9%). Foi realizada a mensuração diária do consumo de água e ração, assim como exames clínicos semanais e coleta de sangue a cada 30 dias. Ao final do tratamento os animais foram eutanasiados e necropsiados. A superfície da córnea foi analisada por microscopia eletrônica de varredura (MEV). Não houve alterações clínicas e diferenças entre os grupos quanto aos valores de hemograma, leucograma, contagem de plaquetas, tempo de protrombina e tromboplastina, proteínas totais, albumina, creatinina, sódio e potássio. Dados de necropsia não apontaram alterações macro ou microscópicas no sistema gástrico, hepático e renal. Após noventa dias de tratamento com ambos os colírios contendo AINEs, pôde ser identificado os princípios ativos no plasma por extração em fase sólida e detecção por espectrometria de massas. Valendo-se da MEV foi comprovado que ambos os AINEs causaram alterações no padrão celular do epitélio corneano. Os resultados desta tese foram apresentados no formato de artigos, sendo que no primeiro artigo foram descritas as implicações da absorção sistêmica dos colírios contendo cetorolaco de trometamina 0,5% e de diclofenaco sódico 0,1%; e o segundo artigo referiu-se à avaliação ultraestrutural do epitélio corneano de coelhos tratados por 90 dias com os colírios de sem cons cetorolaco de trometamina 0,5% e de diclofenaco sódico 0,1% sem conservantes. / The use of topical ophthalmic nonsteroidal anti-inflammatory drugs (NSAIDs) is widely adopted by an increasing number of physicians and veterinarians, general practitioners and ophthalmologists. The increasing use of topical NSAIDs is motivated by the need of administer drugs that do not present the well-known adverse effects of topical and systemic corticosteroids. Thus, the professionals involved in the care of these patients should be aware that topical NSAIDs drugs are not free of adverse effects. This study aimed to investigate the potential local and systemic adverse effects of eye drops administration containing diclofenac sodium 0.1% and ketorolac tromethamine 0.5% in rabbits treated during a period of 90 days. In this manner we sought to clarify issues related to the safety of their use as a therapeutic agent, which could restrict its clinical application in small animals. The 18 rabbits were separated into three groups. The animals were treated three times daily during a period of 90 days with ketorolac tromethamine 0.5% eye drop, sodium diclofenac and 0.1% saline (0.9% NaCl). It was carried out a daily measurement of water and food consumption as well as a weekly clinical examination and blood sampling every 30 days. At the end of the treatment the animals were euthanized and necropsied. The corneal surface was analyzed by scanning electron microscopy (SEM). There were no clinical alterations and differences between the three groups in terms of blood count values, white blood cell count, platelet count, prothrombin time and thromboplastin, total protein, albumin, creatinine, sodium and potassium. Necropsy data showed no macroscopic or microscopic changes in gastric, hepatic and renal system. Ninety days after treatment with both eye drops containing NSAIDs, it could be identified the active ingredients in the plasma by solid phase extraction and detection by mass spectrometry. Taking advantage of SEM has been proven that both NSAIDs caused changes in cellular pattern of the corneal epithelium. The results from the thesis were presented in these two articles, in the first, we described the implications of the systemic absorption of eyedrops diclofenac sodium 0,1% and ketorolac tromethamine 0,5%; and in the second article which refers to the ultrastructural evaluation of the corneal epithelium of rabbits treated for 90 days with eyedrops diclofenac sodium 0,1% and ketorolac tromethamine 0,5% preservative-free.

Com o objetivo de se avaliar a importância do \"clearance\" do dietilenotriamino-pentacetato marcado com Tecnécio 99m (DTPA-Tecnécio-99m) em portadores de pneumopatia por amiodarona foram estudados 40 indivíduos, em quatro grupos. Grupo I: 10 voluntários normais, assintomáticos e não fumantes (8 homens e 2 mulheres), com média de idade de 56,80 anos. Grupo II: 10 voluntários normais, assintomáticos e fumantes (6 homens e 4 mulheres ), com média de idade de 27,50 anos. Grupo III: 10 pacientes não fumantes ( 4 homens e 5 mulheres ), com média de idade de 52,90 anos. Todos faziam uso crônico de amiodarona por via oral. Grupo IV: 10 pacientes portadores de pneumopatia por amiodarona, quatro ex-fumantes, dois fumantes e quatro não fumantes ( 8 homens e 2 mulheres) com média de idade de 52,90 anos. Todos faziam uso de amiodarona por via oral e nenhum fumou nas 4 semanas que precederam o estudo. Após espirometria que constou do registro da curva volume-tempo, todos inalaram 4 ml de solução salina contendo 740 MBq de DTPA Tecnécio-99m, durante cinco minutos. Através de uma c~mara de cintilação computadorizada foram obtidas imagens pulmonares, definindo-se 9 áreas de interesse. Para cada região escolhida foi determinada uma curva de \"clearance\" extraindo-se o valor de meia-vida biológica em minu- tos ( T 1/2 ) e a taxa percentual de \" clearance\" alvéolo capilar do radioaerossol por minuto (K%/min). Observamos que, das variáveis espirométricas consideradas, a capacidade vital forçada (CVF) e o volume expiratório forçado no 1 segundo (VEF1) mostraram diferenças significantes entre os grupos I e IV. A contagem total de radioatividade de ambos os pulmões não mostrou relação com a CVF e o VEF1. O \" clearance \" pulmonar do DTPA Tecnécio-99m foi maior nos grupos 11 e IV, porém não permitindo sua diferenciação. Estes resultados permitem concluir: Os pacientes portadores de pneumonite por amiodaro- na apresentam\" clearance \" alvéolo-capilar de DTPA Tecnécio-99m significativamente maior que os indivíduos do grupo de normais não fumantes. Este fato também se verificou em relação aos pacientes em uso crônico de amiodarona mas sem evidências de pneumopatia. Não é possível diferenciar os fumantes dos portadores de pneumonite por amiodarona através da análise da integridade da barreira alvéolo-epitelial com DTPA Tecnécio-99m. Comparativamente, o estudo da integridade alvéolo-epitelial pelo \"clearance\" pulmonar de DTPA Tecnécio-99m é mais sensível que a espirometria na avaliação da pneumonite por amiodarona, permitindo diferenciar estes pacientes dos que fazem uso crônico da droga / In order to evaluate the role of the clearance of 99m Technetium chelated to diethylenetriamine-penta-acetate ( 99mTc-DTPA) in amiodarone induced pulmonary disease, 40 individuaIs were studied in four groups. Group I: 10 normal non smoking volunteers (8 men and 2 women ), whose mean age was 56.80 years. Group lI: 10 normal smoking volunteers ( 6 men and 4 women ), aging 27.50 years in average. Group III: 10 non smoking patients ( 4 men and women ), aging 52.90 years in average, who were chronically taking oral amiodarone. Group IV: 10 patients with amiodarone induced pul- monary disease (8 men and 2 women), four non-smokers, two smokers and four previous smokers. Their mean age was 62.90 years. AIl of them were taking oral amiodarone and none has smoked in the 4 weeks previous to the study. After spirometry, where a volume-time curve was registered, alI individuaIs inhaled 740 MBq of 99mTc-DTPA diluted in 4 ml of saline, for five minutes. Pulmonary images were obtained in a computadorized scintillation camera and 9 regions of interest were selected. A clearance curve of each region was determined, from which the effective half-life in minutes (T 1/2 ) and the alveolar-capilar clearance rate per minute ( k%/min ) of the radiolabeled aerosol were mea- sured. The spirometric analys disclosed a statistically lower value of the forced vital capacity ( FVC ) and forced expiratory volume in the first second ( FEV1 ) in the patients of group IV when compared to group I. The total radioactivity count for both lungs were not influenced by FVC and FEV1. The 99mTc-DTPA clearance rate was higher in groups 11 and IV, but these two groups could not be statistically differentiated. Based on these results it 1s concluded: patients with amiodarone induced pulmonary pneumonitis have higher clearance rates of 99m Tc-DTPA than normal non smoking controls and than patients taking amiodarone but with no lung toxicity. It is not possible to separate patients with amiodarone induced disease from normal smokers by determining 99m Tc-DTPA clearance rates. The determination of the alveolar-epithelial barrier integrity by 99m Tc-DTPA clearance rate is a more sensitive test than spirometry in the evaluation of amiodarone induced pneumonitis making it possible to differentiate these patients from those who take the drug and have no lung toxicity

Lau Hoi Yan. / Thesis (M.Phil.)--Chinese University of Hong Kong, 2003. / Includes bibliographical references (leaves 134-157). / Abstracts in English and Chinese. / PUBLICATIONS BASED ON WORK IN THIS THESIS --- p.I / ABSTRACT --- p.II / ACKNOWLEDGEMENTS --- p.VI / TABLE OF CONTENTS --- p.VIII / Chapter CHAPTER 1 --- INTRODUCTION --- p.1 / Chapter 1.1 --- General Introduction --- p.1 / Chapter 1.2 --- Emesis --- p.3 / Chapter 1.2.1 --- Introduction --- p.3 / Chapter 1.2.2 --- Retching & Vomiting --- p.3 / Chapter 1.2.3 --- Nausea --- p.4 / Chapter 1.2.4 --- Motor Components of Emetic Reflex --- p.5 / Chapter 1.2.4.1 --- Pre-ejection Phase --- p.5 / Chapter 1.2.4.2 --- Ejection Phase --- p.5 / Chapter 1.2.4.3 --- Post-ejection Phase --- p.6 / Chapter 1.2.5 --- Components of Emetic Reflex --- p.6 / Chapter 1.2.5.1 --- Area Postrema (AP) --- p.6 / Chapter 1.2.5.2 --- Nucleus Tractus Solitarius (NTS) --- p.7 / Chapter 1.2.5.3 --- Vomiting Centre --- p.8 / Chapter 1.2.5.4 --- Vestibular System --- p.10 / Chapter 1.2.5.5 --- Abdominal Visceral Afferents --- p.10 / Chapter 1.2.5.6 --- Forebrain --- p.11 / Chapter 1.2.6 --- Neurotransmitters & Receptors --- p.12 / Chapter 1.2.7 --- Anti-emetics --- p.13 / Chapter 1.3 --- Models of Nausea --- p.16 / Chapter 1.3.1 --- Introduction --- p.16 / Chapter 1.3.2 --- Conditioned Taste Aversion --- p.18 / Chapter 1.3.3 --- Pica Behaviour --- p.20 / Chapter 1.3.4 --- Studies of the Involvement of Vasopressin --- p.21 / Chapter 1.3.5 --- Tachygastria --- p.24 / Chapter 1.3.6 --- Locomotor Activity --- p.26 / Chapter 1.4 --- Markers of Neuronal Activity --- p.27 / Chapter 1.4.1 --- General Comments --- p.27 / Chapter 1.4.2 --- c-fos Expression as a Marker of Neuronal Activity --- p.28 / Chapter 1.4.2.1 --- What is c-fos? --- p.28 / Chapter 1.4.2.2 --- Regulation of c-fos Expression --- p.30 / Chapter 1.4.2.2.1 --- Calcium Response Element --- p.31 / Chapter 1.4.2.2.2 --- Serum Response Element --- p.32 / Chapter 1.4.2.3 --- Types of Receptors Involved in c-fos Expression --- p.32 / Chapter 1.4.2.4 --- Feasibility of Using c-fos Expression as Marker of Cellular Activity --- p.36 / Chapter 1.4.2.5 --- Identification of Emetic Pathway by c-fos Immunohistochemistry --- p.36 / Chapter 1.5 --- Aims & Objectives --- p.37 / Chapter CHAPTER 2 --- METHODS --- p.42 / Chapter 2.1 --- Animals --- p.42 / Chapter 2.1.1 --- Ferrets --- p.42 / Chapter 2.1.2 --- Suncus murinus --- p.42 / Chapter 2.2 --- Measurement of Animal Behaviour --- p.43 / Chapter 2.2.1 --- Experiment Design --- p.43 / Chapter 2.2.2 --- Recording of Animal Behaviour --- p.43 / Chapter 2.2.3 --- Calibration of Equipment Used to Record Spontaneous Locomotor Activity --- p.44 / Chapter 2.2.4 --- Behaviour Recorded by the Observer --- p.45 / Chapter 2.3 --- Administration of Drugs --- p.46 / Chapter 2.3.1 --- Ferrets --- p.46 / Chapter 2.3.1.1 --- General Comments --- p.46 / Chapter 2.3.1.2 --- Drug Antagonism Studies --- p.47 / Chapter 2.3.2 --- Suncus murinus --- p.47 / Chapter 2.3.2.1 --- General Comments --- p.47 / Chapter 2.3.2.2 --- Dose-Response Studies --- p.48 / Chapter 2.3.2.3 --- Drug Antagonism Studies --- p.48 / Chapter 2.4 --- c-fos Expression Studies in Ferret Brainstems --- p.50 / Chapter 2.4.1 --- Animals and Anaesthesia --- p.50 / Chapter 2.4.2 --- Perfusion and fixation --- p.50 / Chapter 2.4.3 --- Dehydration of brains --- p.51 / Chapter 2.4.4 --- Embedding of tissue --- p.52 / Chapter 2.4.5 --- Sectioning --- p.52 / Chapter 2.4.6 --- Staining --- p.52 / Chapter 2.4.7 --- Antibodies used --- p.55 / Chapter 2.4.8 --- Positive Control Slides --- p.55 / Chapter 2.5 --- Experimental Design and Statistics --- p.56 / Chapter 2.5.1 --- Randomization of Treatments --- p.56 / Chapter 2.5.2 --- Statistics --- p.57 / Chapter 2.5.2.1 --- Ferrets --- p.57 / Chapter 2.5.2.2 --- Suncus murinus --- p.59 / Chapter 2.6 --- Drugs and Chemicals Used --- p.60 / Chapter 2.6.1 --- Drugs Used --- p.60 / Chapter 2.6.2 --- Chemicals Used --- p.62 / Chapter CHAPTER 3 --- RESULTS --- p.63 / Chapter 3.1 --- Ferret --- p.63 / Chapter 3.1.1 --- "The Effect of Ondansetron and CP-99,994 on Emesis and Locomotor Activity Changes Induced by Cisplatin in the Ferret" --- p.63 / Chapter 3.1.2 --- The Effect of Domperidone on Emesis and Locomotor Activity Changes Induced by Apomorphine in the Ferret --- p.69 / Chapter 3.1.3 --- "The Effect of CP-99,994 on Emesis and Locomotor Activity Changes Induced by Apomorphine in the Ferret" --- p.74 / Chapter 3.1.4 --- c-fos Expression Studies in Ferret Brainstems --- p.79 / Chapter 3.1.4.1 --- Cisplatin-treated Ferrets --- p.79 / Chapter 3.1.4.2 --- Positive Control Slides --- p.84 / Chapter 3.2 --- Suncus murinus --- p.88 / Chapter 3.2.1 --- The Emetic Potential of Nicotine and its Effects on the Spontaneous Locomotor Activity of Suncus murinus --- p.88 / Chapter 3.2.2 --- "The Effect of CP-99,994 on Emesis and Locomotor Activity Changes Induced by Nicotine in Suncus murinus" --- p.92 / Chapter 3.2.3 --- The Emetic Potential of Copper Sulphate and its Effects on the Spontaneous Locomotor Activity of Suncus murinus --- p.95 / Chapter 3.2.4 --- "The Effect of CP-99,994 on Emesis and Locomotor Activity Changes Induced by Copper Sulphate in Suncus murinus" --- p.98 / Chapter 3.2.5 --- The Emetic Potential of Cisplatin and its Effects on the Spontaneous Locomotor Activity of Suncus murinus --- p.101 / Chapter 3.2.6 --- The Effect of Ondansetron on Emesis and Locomotor Activity Changes Induced by Cisplatin in Suncus murinus --- p.104 / Chapter 3.2.7 --- "The Effect of CP-99,994 on Emesis and Locomotor Activity Changes Induced by Cisplatin in Suncus murinus" --- p.107 / Chapter 3.2.8 --- "The Effects of Ondansetron and CP-99,994 on Locomotor Activity in Suncus murinus" --- p.110 / Chapter CHAPTER 4 --- DISCUSSION --- p.113 / Chapter CHAPTER 5 --- GENERAL SUMMARY --- p.130 / REFERENCES --- p.134

Although ACC exerted a strong effect on the haemodynamic changes after SA, SA per se did not have much influence on ACC. The incidence and severity of ACC remained unchanged compared with the pre-spinal state. As long as maternal blood pressure were well controlled, the uterine blood flow indices were not affected by ACC. / Although there are many publications on ACC, most publications have considered ACC as a single entity, or reported its effects in terms of just a few end-point measures. The information published so far on ACC remains fragmented. This will be readdressed by taking a multidisciplinary approach with input from the fields of anaesthesia, obstetrics and radiology to non-invasively assess the haemodynamic changes associated with ACC. / Aortocaval compression occurs when parturients lie in the supine position with the gravid uterus compressing the aorta and the inferior vena cava. This interferes with venous return to the heart to reduce cardiac output, resulting in hypotension, uterine hypo-perfusion and fetal acidosis. Under neuraxial anaesthesia when the compensatory mechanisms via the sympathetic nervous outflow are blocked, the effects from ACC are exaggerated and results in maternal and fetal morbidity. / Intermittent IVC compression was responsible for most of the haemodynamic effects, presenting mainly as a reduction in cardiac output. Blood pressure or heart rate changes are poor indicators for IVC compression, and most patients were asymptomatic. Patients who have moderate to severe ACC have a higher incidence of hypotension after SA and consume a higher amount of phenylephrine for maintaining BP. / The research was conducted on non-labouring term parturients presenting for elective Caesarean section under spinal anaesthesia. Measurements were performed to assess the patency of blood vessels and haemodynamic responses to lateral tilts, using ultrasound and non-invasive haemodynamic monitors. / This research has achieved the following: (1) Qualitative measurements of compression of the aorta and IVC with US imaging and Doppler US; (2) Development of a new simple bedside method for detecting ACC using US; (3) Quantitative measurements of physiological responses in the maternal and fetal circulation associated with ACC; (4) Investigation of the effects of spinal anaesthesia per se on ACC. / Lee, Wee Yee Shara. / Adviser: Khaw Kim Sun. / Source: Dissertation Abstracts International, Volume: 70-06, Section: B, page: 3446. / Thesis (Ph.D.)--Chinese University of Hong Kong, 2008. / Includes bibliographical references (leaves 234-254). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Electronic reproduction. [Ann Arbor, MI] : ProQuest Information and Learning, [200-] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Abstracts in English and Chinese. / School code: 1307.

Yeung Sai Mo, Simon. / "June 2002." / Thesis (Ph.D.)--Chinese University of Hong Kong, 2002. / Includes bibliographical references (p. 255-278). / Electronic reproduction. Hong Kong : Chinese University of Hong Kong, [2012] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Electronic reproduction. Ann Arbor, MI : ProQuest Information and Learning Company, [200-] System requirements: Adobe Acrobat Reader. Available via World Wide Web. / Mode of access: World Wide Web. / Abstracts in English and Chinese.

一氧化二氮，俗稱笑氣，是現代臨床麻醉最為常用的一種麻醉劑。然而，關於一氧化二氮效能及安全性的研究至今仍存在爭議。近來，一個稱為ENIGMA的臨床研究項目對2,050個施行大手術的病人接受麻醉情況及術後併發癥進行了研究。研究發現手術中施行一氧化二氮麻醉的病人術後傷口感染率較之對照組上升了35%。另一方面，對423個ENIGMA病人的長期隨訪研究發現，在術中接受一氧化二氮麻醉的病人中慢性術後痛的發病率相對對照組降低了56%。 對於這些臨床發現的分子機制，目前知之甚少。 因此我們進行了一系列實驗來研究一氧化二氮導致術後感染以及預防慢性痛的分子機制。 / 一氧化二氮對基因穩定性的影響 / 在對93個接受直腸結腸大型外科手術的病人進行的隨機對照試驗中，我們比較了接受一氧化二氮麻醉及其對照組病人的外周白細胞脫氧核糖核酸（DNA）損傷情況和術後傷口感染率。通過單細胞凝膠電泳（彗星實驗），我們發現術中一氧化二氮麻醉顯著增加了手術24小時后病人的DNA損傷情況 （p < 0.001）。且這種變化是劑量依賴的，r = 0.33; p = 0.03。並且，在DNA損傷程度及術後傷口感染率間存在顯著相關。術後DNA損傷程度每增加十個單位，傷口感染率則隨之增加17%。 / 一氧化二氮對DNA損傷應答及修復的影響 / 利用大鼠模型，我們對一氧化二氮導致基因不穩定的機制進行了研究。Sprague Dawley大鼠暴露於一氧化二氮中2小時後，我們對其DNA損傷應答及修復基因的轉錄情況進行了檢測。脂多糖（LPS）注射大鼠模擬了圍手術期的炎癥反應。我們發現LPS刺激的白細胞經一氧化二氮處理后，其編碼DNA連接酶IV的LIG4基因的轉錄量顯著降低（p < 0.05）。LIG4基因的下調導致了一氧化二氮麻醉後圍手術期的免疫抑制效應。 / NMDA受體抑制在一氧化二氮預防性鎮痛中的作用 / 在大鼠慢性神經痛模型中，我們檢測了一氧化二氮鎮痛作用的機制。我們發現一氧化二氮處理組的機械痛覺過敏相較對照組顯著降低（p = 0.001）。一氧化二氮處理后，神經痛大鼠脊髓背角中的c-Fos表達量也顯著降低，這表明了一氧化二氮對神經元活性的影響。該影響可能是NMDA受體抑制的結果。另外，我們還觀察到一氧化二氮的鎮痛特徵與NMDA受體非競爭性拮抗劑MK-801的鎮痛效果相似。 / 基因表達改變在一氧化二氮預防性鎮痛中的作用 / 一氧化二氮鎮痛效果的遲發性和延續性提示了除受體拮抗之外的其他作用機制的存在。我們發現在大鼠坐骨神經壓迫損傷模型中，一氧化二氮處理顯著降低了同側脊髓背角組織中LIG4基因的轉錄及表達（p = 0.006）。同時一氧化二氮處理降低了星形膠質細胞在同側脊髓背角中的活化。我們的研究表示一氧化二氮影響DNA修復， 抑制脊髓背角基因的表達，從而起到預防性鎮痛的作用。 / 總而言之，一氧化二氮通過抑制鉀硫氨酸合成酶，削弱DNA修復和基因組穩定性，從而成為導致術后傷口感染的危險因素。另一方面，這一機制也阻止了脊髓背角中異常突觸的建立，從而預防了神經損傷導致的慢性神經痛的建立。另外，一氧化二氮的鎮痛機制也和NMDA受體抑制作用有關。 / Nitrous oxide is a commonly administered anesthetic and analgesic agent in contemporary clinical anesthesia. However, the efficacy and safety of nitrous oxide delivery remains a subject of debate. The recent Evaluation of Nitrous oxide In a Gas Mixture for Anaesthesia (ENIGMA) Trial found that nitrous oxide administration, in 2,050 patients undergoing major surgery, increased the incidence of wound infection by 35%. On the other hand, in a long term follow-up study of 423 ENIGMA patients in Hong Kong, the risk of chronic postsurgical pain was reduced by 56% in patients who received nitrous oxide in the index surgery. Little is known about the mechanisms associated with these clinical observations; we therefore conducted a series of experiments to determine the molecular changes after nitrous oxide administration leading to postoperative wound infection and preventive analgesia. / Genomic Instability after Nitrous Oxide Administration / In a randomized controlled trial of 93 patients undergoing major colorectal surgery, we compared the changes of deoxyribonucleic acid (DNA) damage in circulating leukocytes and rates of wound infection in patients who were exposed to nitrous oxide or not. Using single cell gel electrophoresis (CometAssay), we found that intraoperative nitrous oxide administration produced significant DNA damage, 24 hours after surgery, compared with controls, p < 0.001. The changes were dose-dependent, r = 0.33; p = 0.03. In addition, there was a significant correlation between DNA damage and postoperative wound infection. For every 10 units increase in the percentage of DNA in tail after surgery compared with baseline, there was 17% increase in the risk of wound infection. / DNA Damage Response and Repair / In a rat model, we explored the mechanism of genomic instability after nitrous oxide administration. In Sprague Dawley rats exposed to nitrous oxide anesthesia for 2 hours, we tested the transcription of an array of DNA damage response and repair genes. Lipopolysaccharide (LPS) was added to mimic postoperative inflammation. In the mRNA that were extracted and analyzed by real-time polymerase chain reaction (RT-PCR), we found the transcription of gene encoding for DNA Ligase IV (LIG4 gene) was significantly reduced after nitrous oxide administration in LPS-stimulated leukocytes (p < 0.05). The down regulation of LIG4 gene contributed to perioperative immunosuppression following nitrous oxide exposure. / Role of N-methyl-D-aspartate receptor (NMDAR) Blockade for Preventive Analgesia with Nitrous Oxide / Using a rat model of chronic neuropathic pain, we tested the mechanisms underlying nitrous oxide analgesia. In Sprague Dawley rats undergoing unilateral constrictive injury to the sciatic nerve, we found that mechanical hyperalgesia was significantly reduced with nitrous oxide compared with controls (p = 0.01). In addition, c-Fos expression was decreased in spinal dorsal horn suggesting that neuron excitability was reduced after nitrous oxide administration which could be caused by blockade of the NMDA receptor. Interestingly, the characteristics of analgesia were similar to that provided by MK-801, a noncompetitive antagonist of NMDA receptors. / Transcriptional Changes for Nitrous Oxide Analgesia / The onset of nitrous oxide analgesia was delayed and outlasted actual receptor antagonism. We therefore explored mechanisms, other than NMDA receptor blockade, for nitrous oxide analgesia. Specifically, in rats undergoing sciatic nerve constrictive injury, we found that transcription of LIG4 gene was down-regulated in the ipsilateral spinal dorsal horn after nitrous oxide administration (p = 0.006). There was a decrease in DNA ligase IV expression and a reduction in the activation of astrocytes. Our data suggested that regulation of DNA repair and suppression spinal dorsal horn gene transcription is one of the alternative mechanisms for nitrous oxide analgesia. / In summary, nitrous oxide administration is a risk factor for postoperative wound infection. This is related to irreversible inhibition of the enzyme methionine synthase, impaired DNA repair and genomic instability. The same mechanism however prevented aberrations of synaptic regeneration in the spinal dorsal horn and could therefore prevent the development of chronic neuropathic pain after direct nerve injury. Nitrous oxide analgesia was also related to NMDA receptor blockade. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Detailed summary in vernacular field only. / Chen, Yan. / Thesis (Ph.D.)--Chinese University of Hong Kong, 2012. / Includes bibliographical references (leaves 126-157). / Abstract also in Chinese. / Declaration of origination --- p.I / Abstract: --- p.II / Acknowledgements --- p.VIII / Table of Contents --- p.X / List of Tables --- p.XV / List of Figures --- p.XVI / List of Abbreviations --- p.XVIII / Chapter Part I: --- Literature Review --- p.1 / Chapter Chapter 1 --- A review of nitrous oxide: Historical, clinical and mechanistic Perspectives --- p.2 / Chapter 1.1 --- History of Nitrous Oxide --- p.2 / Chapter 1.2 --- Clinical Pharmacology of Nitrous Oxide --- p.4 / Chapter 1.3 --- Evaluation of Nitrous oxide In the Gas Mixture for Anesthesia (ENIGMA) Trial --- p.9 / Chapter 1.4 --- Efficacy and Toxicity of Nitrous Oxide: Biochemical and Molecular Mechanisms --- p.14 / Chapter 1.4.1 --- Immunosuppression Following Nitrous Oxide Administration --- p.14 / Chapter 1.4.2 --- Analgesia with Nitrous Oxide - Molecular Mechanisms --- p.17 / Chapter 1.4.2.1 --- Direct molecular target --- p.17 / Chapter 1.4.2.2 --- Interaction with γ aminobutyric acid type A (GABAA) receptors --- p.19 / Chapter 1.4.2.3 --- Regulation of opioid system --- p.20 / Chapter 1.4.2.4 --- Regulation of noradrenergic neurons --- p.21 / Chapter 1.4.2.5 --- N-methyl-d-aspartate (NMDA) receptor inhibition --- p.22 / Chapter 1.4.2.6 --- Long-term Preventive Analgesia with Nitrous Oxide --- p.23 / Chapter 1.4.3 --- Summary --- p.24 / Chapter Part II: --- Experiments --- p.26 / Chapter Chapter 2 --- Study Hypothesis and Objectives --- p.27 / Chapter 2.1 --- Genomic Instability after Nitrous Oxide Administration --- p.27 / Chapter 2.2 --- DNA Damage Response and Repair --- p.28 / Chapter 2.3 --- NMDA Receptor Blockade for Preventive Analgesia with Nitrous Oxide --- p.28 / Chapter 2.4 --- Transcriptional Changes for Nitrous Oxide Analgesia --- p.28 / Chapter Chapter 3 --- Genomic Instability After Nitrous Oxide Administration: A Randomized Controlled Trial --- p.32 / Chapter 3.1 --- Introduction --- p.32 / Chapter 3.2 --- Methods and Materials --- p.36 / Chapter 3.2.1 --- Study Participants --- p.36 / Chapter 3.2.2 --- Study Procedures --- p.36 / Chapter 3.2.3 --- Randomization --- p.37 / Chapter 3.2.4 --- Anesthetic Care --- p.37 / Chapter 3.2.5 --- Postoperative Care --- p.38 / Chapter 3.2.6 --- Measurement of Genomic Instability --- p.44 / Chapter 3.2.7 --- Statistical Analysis --- p.47 / Chapter 3.2.8 --- Sample Size Calculation --- p.47 / Chapter 3.3 --- Results --- p.48 / Chapter 3.4 --- Discussion --- p.61 / Chapter 3.4.1 --- Principal Findings --- p.61 / Chapter 3.4.2 --- Comparison to Other Studies --- p.61 / Chapter 3.4.3 --- Strengths and Limitations --- p.63 / Chapter 3.4.4 --- Implications --- p.64 / Chapter 3.4.5 --- Conclusions --- p.64 / Chapter Chapter 4 --- DNA Damage Response and Repair After Nitrous Oxide Administration / Chapter 4.1 --- Introduction --- p.65 / Chapter 4.1.1 --- DNA Damage Response and Repair Pathways --- p.65 / Chapter 4.1.2 --- Nitrous oxide and DNA Damage Response and Repair --- p.69 / Chapter 4.2 --- Materials and Methods --- p.70 / Chapter 4.2.1 --- Animals --- p.70 / Chapter 4.2.2 --- Nitrous Oxide Administration --- p.70 / Chapter 4.2.3 --- Lipopolysaccharide-Induced Infection Model --- p.72 / Chapter 4.2.4 --- Sample Collection and Preparation --- p.72 / Chapter 4.2.5 --- Single Cell Gel Electrophoresis (CometAssay) --- p.72 / Chapter 4.2.6 --- RNA Extraction for Gene Transcription Study --- p.72 / Chapter 4.2.7 --- Reverse Transcription Polymerase Chain Reaction (RT PCR) --- p.73 / Chapter 4.2.8 --- Quantitative RT PCR --- p.74 / Chapter 4.2.9 --- Statistical Analysis --- p.76 / Chapter 4.3 --- Results --- p.76 / Chapter 4.3.1. --- Genome Instability in Rat Leukocytes after Nitrous Oxide Administration --- p.76 / Chapter 4.3.2. --- Effect of Nitrous Oxide on the Transcription of DNA Damage Response Genes --- p.78 / Chapter 4.3.3. --- Effects of Nitrous Oxide on DNA Damage Response Genes in Animals Treated with Lipopolysaccharide --- p.80 / Chapter 4.4 --- Discussion --- p.84 / Chapter 4.4.1 --- Principal Findings --- p.84 / Chapter 4.4.2 --- Implications --- p.84 / Chapter 4.4.3 --- Limitation of our Study --- p.85 / Chapter 4.4.4 --- Conclusions --- p.87 / Chapter Chapter 5 --- Preventive Analgesia with Nitrous Oxide: Role of NMDA Receptor Blockade / Chapter 5.1. --- Introduction --- p.88 / Chapter 5.1.1. --- The ENIGMA Trial: Long Term Follow-up --- p.89 / Chapter 5.1.2. --- Nitrous oxide prevents chronic postsurgical pain: putative mechanisms --- p.89 / Chapter 5.1.3. --- Hypothesis --- p.90 / Chapter 5.2. --- Materials and methods --- p.91 / Chapter 5.2.1. --- Animals --- p.91 / Chapter 5.2.2. --- Chronic constriction injury (CCI) to induce neuropathic pain --- p.91 / Chapter 5.2.3. --- Behavioral test --- p.93 / Chapter 5.2.4. --- Nitrous oxide administration --- p.93 / Chapter 5.2.5. --- Dizocilpine (MK-801) pretreatment --- p.94 / Chapter 5.2.6. --- Tissue Collection, Preparation and Western Blot --- p.94 / Chapter 5.2.7. --- Statistical Analysis --- p.96 / Chapter 5.3. --- Results --- p.96 / Chapter 5.3.1. --- Preventive Analgesia with Nitrous oxide --- p.96 / Chapter 5.3.2. --- Nitrous oxide analgesia via NMDA receptors block --- p.99 / Chapter 5.3.3. --- Preventive analgesia with NMDA receptors Blockade --- p.101 / Chapter 5.4. --- Discussion --- p.103 / Chapter 5.4.1 --- Principal Findings --- p.103 / Chapter 5.4.2 --- Our Findings compared with Other Studies --- p.103 / Chapter 5.4.3 --- Limitations of the Study --- p.104 / Chapter 5.4.4 --- Conclusions --- p.105 / Chapter Chapter 6 --- Transcriptional Changes for Nitrous Oxide Analgesia --- p.106 / Chapter 6.1 --- Introduction --- p.106 / Chapter 6.1.1 --- Neuro-immune Interactions in the Development of Chronic Neuropathic Pain --- p.106 / Chapter 6.1.2 --- Nitrous Oxide Interferes Astrocytes and Glial Responses --- p.107 / Chapter 6.2 --- Materials and methods --- p.109 / Chapter 6.2.1 --- Chronic Constriction Injury Pain Model and Nitrous Oxide Administration --- p.109 / Chapter 6.2.2 --- Lumbar Dorsal Horn Tissue Collection, Preparation and Immunoflurescence --- p.109 / Chapter 6.2.3 --- RNA Extraction and Quantitative RT PCR for Gene Transcription Study --- p.110 / Chapter 6.2.4 --- Protein Extraction and Western Blot for protein Expression Study --- p.110 / Chapter 6.2.5 --- Statistical Analysis --- p.111 / Chapter 6.3 --- Results --- p.112 / Chapter 6.3.1 --- Time Course of LIG4 Gene Transcription after Constrictive Nerve Injury --- p.112 / Chapter 6.3.2 --- Nitrous oxide reduced DNA ligase IV expression in spinal dorsal horn --- p.114 / Chapter 6.3.3 --- Nitrous oxide Reduced Astrocytes Activation in Spinal Dorsal Horn --- p.116 / Chapter 6.4 --- Discussions --- p.119 / Chapter 6.4.1 --- Principal Findings --- p.119 / Chapter 6.4.2 --- Our Findings in Relation to Other Studies --- p.119 / Chapter 6.4.3 --- Limitations of Our Study --- p.120 / Chapter 6.4.4 --- Conclusions --- p.120 / Chapter Part III: --- Conclusions --- p.122 / Chapter Chapter 7 --- Conclusions and Future Perspectives --- p.123 / Chapter 7.1 --- Conclusions --- p.123 / Chapter 7.2 --- Future Perspectives --- p.124 / Chapter Part IV --- References --- p.126

Introdução: Os efeitos da radiação ultravioleta sobre o sistema imunológico humano são altamente complexos e alteram alguns componentes da resposta imunológica. Objetivo: O objetivo deste estudo foi avaliar os efeitos clínicos, histopatológicos e imunológicos da radiação solar em pescadores do sexo masculino com mais de dez anos de atividade ininterrupta. Métodos: Um estudo prospectivo, transversal, observacional e analítico, foi realizado para determinar as lesões dermatológicas diagnosticadas pelo exame físico, comparando grupos, para a análise de marcadores imunológicos na pele e no sangue, assim como alterações histológicas na pele. Este estudo foi realizado numa comunidade de pescadores, no Pina, no estado de Pernambuco, Brasil. Dezenove pescadores, com tempo médio de profissão de 29,0 ± 10,3 anos, foram incluídos no estudo. As variáveis desta amostra foram: idade, sexo, tipo da pele (segundo classificação de Fitzpatrick) estado civil, grau de instrução, número de filhos, tipo e tempo de atividade profissional, índice de massa corpórea, exposição diária à radiação solar e qualquer tipo de doença atual ou prévia (nos 12 meses anteriores à coleta de dados). As variáveis dermatológicas foram quaisquer alterações em pele, mucosa e anexos. Para comparar a subpopulação de linfócitos no sangue, foram empregados 10 indivíduos não pescadores, vivendo na mesma região e exercendo profissão ao abrigo do sol. As idades médias igualaram-se a 42,5 ± 16,1 anos. Os marcadores imunológicos da pele foram determinados por imuno-histoquímica e os do sangue, por citômetro de fluxo. O teste de Mann-Whitney, para a hipótese de igualdade, entre os grupos expostos e não expostos ao sol, foi usado. O teste de Fisher foi empregado para análise de independência dos grupos e o teste de Wilcoxon, para comparação dos achados imunológicos e histopatológicos em pele exposta e coberta, todos em igual nível de significância (0,05). Resultados: Comparando pele exposta à coberta, elastose (73,7% contra 23,1%, respectivamente; p=0,03), vasos ectásicos dérmicos (78,9% contra 31,6%, respectivamente; p=0,012) e número de células nos segmentos da epiderme entre os cones (5,8 ± 1,08 contra 5,2 ± 0,42; p=0,029) foram significantemente mais freqüentes na pele exposta. Também os marcadores CD45RO+, CD68+ e mastócitos (p=0,040, p<0,001 e p=0,001) foram estatisticamente significantes na pele exposta. O aumento de CD3CD8CD45RO+ no sangue periférico foi mais freqüente em pescadores do que em não pescadores (p=0,016). Conclusões: O efeito barreira à penetração da radiação solar, representado por elastose, aumento do número de células nas camadas entre os cones, aumento de melanócitos e da vasculatura dérmica, representada pela ectasia, sugere a existência de um efeito de tolerância ao dano da radiação solar, o qual provavelmente inibe a instalação da imunodepressão. Esse efeito é reforçado pelo aumento do CD3CD8CD45RO+ e pelo aumento da expressão da linhagem CD28+, capaz de proteger as células CD4+ da apoptose induzida pelo CD95 (Faz). SUMMARY Introduction: The ultraviolet radiation effects on the human immunological system are highly complex, disturbing some components of immune response. Objective: The objective of this study was to evaluate the clinical, histopathological and immunological effects from solar radiation in male fishermen with more than 10 years of uninterrupted activity. Methods: A prospective, transversal, observational and analytical study was done observing the dermatological lesions diagnosed by a physical exam, comparing groups, for the analysis of immunologic markers on the skin and in the blood, as well as histological alterations on the skin. This study was developed at a fishing community in Pina, in the state of Pernambuco, Brazil. Nineteen fishermen with an average professional working time of 29,0 ± 10,3 years were included in this study. The variable of this sample was: age, sex, skin type (according to Fitzpatrick classification), civilian status, degree of instruction, number of children, type and time of professional activity, body mass index, daily sun radiation exposure and any kind of current or past (12 months prior of the collection of data) illness. The dermatological variable was any alterations on the skin, mucosa and annexes. In order to compare the lymphocytes subpopulation in the blood, we used 10 non fishermen living in the same region with an indoor profession. The average ages ranged 42,5 ± 11,6 years. The immunological markers of the skin were determined by immune-histochemistry and those of blood, by flow cytometer. The Mann-Whitney test had been used, for equality hypothesis, between the sun-exposed and non-exposed group. The Fisher test was used for independence group analyzing and Wilcoxon test, as a comparison between the immunological and histopathological findings on exposed and non-exposed skin, all in equal level of significance (0,05). Results: Comparing exposed and non-exposed skin, elastosis (73,7% against 23,1% respectively; p = 0,03) dermis ectasic vases (78,9% against 31,6% respectively; p=0,012) and number of cells in epidermis segments between cones(5,8 ± 1,08 against 5,2 ± 0,42; p=0,029) were significantly more frequent in the exposed skin. Also, the CD45RO+, Cd68+ markers and mastocytes (p=0,040, p<0,001 and p=0,001) had been significantly statistic on exposed skin. The increase of CD3CD8CD45RO+, in peripheral blood, was more frequent in fishermen than the non fishermen workers (p=0,016) Conclusions: The barrier effect to the penetration of the solar radiation established by elastosis, the increase of cellular number of cell layers between the cones, increase of melanocytes and increase of dermal vasculature, represented for the ectasy, suggests the existence of a tolerance effect to sun radiation damage, which probably inhibits the installation of immunodepression. This effect is endorsed by the increasing of CD3CD8CD45RO+ and increase in trend of CD28+ expression, capable to protect Cd4+ cells apoptosis induced from CD95 (Fas). / Introduction: The ultraviolet radiation effects on the human immunological system are highly complex, disturbing some components of immune response. Objective: The objective of this study was to evaluate the clinical, histopathological and immunological effects from solar radiation in male fishermen with more than 10 years of uninterrupted activity. Methods: A prospective, transversal, observational and analytical study was done observing the dermatological lesions diagnosed by a physical exam, comparing groups, for the analysis of immunologic markers on the skin and in the blood, as well as histological alterations on the skin. This study was developed at a fishing community in Pina, in the state of Pernambuco, Brazil. Nineteen fishermen with an average professional working time of 29,0 ± 10,3 years were included in this study. The variable of this sample was: age, sex, skin type (according to Fitzpatrick classification), civilian status, degree of instruction, number of children, type and time of professional activity, body mass index, daily sun radiation exposure and any kind of current or past (12 months prior of the collection of data) illness. The dermatological variable was any alterations on the skin, mucosa and annexes. In order to compare the lymphocytes subpopulation in the blood, we used 10 non fishermen living in the same region with an indoor profession. The average ages ranged 42,5 ± 11,6 years. The immunological markers of the skin were determined by immune-histochemistry and those of blood, by flow cytometer. The Mann-Whitney test had been used, for equality hypothesis, between the sun-exposed and non-exposed group. The Fisher test was used for independence group analyzing and Wilcoxon test, as a comparison between the immunological and histopathological findings on exposed and non-exposed skin, all in equal level of significance (0,05). Results: Comparing exposed and non-exposed skin, elastosis (73,7% against 23,1% respectively; p = 0,03) dermis ectasic vases (78,9% against 31,6% respectively; p=0,012) and number of cells in epidermis segments between cones(5,8 ± 1,08 against 5,2 ± 0,42; p=0,029) were significantly more frequent in the exposed skin. Also, the CD45RO+, Cd68+ markers and mastocytes (p=0,040, p<0,001 and p=0,001) had been significantly statistic on exposed skin. The increase of CD3CD8CD45RO+, in peripheral blood, was more frequent in fishermen than the non fishermen workers (p=0,016) Conclusions: The barrier effect to the penetration of the solar radiation established by elastosis, the increase of cellular number of cell layers between the cones, increase of melanocytes and increase of dermal vasculature, represented for the ectasy, suggests the existence of a tolerance effect to sun radiation damage, which probably inhibits the installation of immunodepression. This effect is endorsed by the increasing of CD3CD8CD45RO+ and increase in trend of CD28+ expression, capable to protect Cd4+ cells apoptosis induced from CD95 (Fas).

Procurou-se confirmar a existência de alterações estruturais em corpos carotídeos de ratos expostos à hiperóxia que pudessem explicar a atenuação da resposta fisiológica à hipóxia nessas condições descrita na literatura. Também testamos a hipótese de haver um desvio de fluxo sanguíneo para os capilares intraglômicos em situações de hiperoxigenação hiperbárica.15 ratos machos Wistar adultos foram divididos em 3 grupos e expostos a 2,4 ATA por 6 horas, a 3,0 ATA por 6 horas e a ar ambiente (grupo controle). Os resultados obtidos através de análise histológica e morfométrica mostraram: a) nenhuma alteração da arquitetura dos corpos carotídeos, mas as células expostas à dose mais elevada apresentaram-se com citoplasma desarranjado, confirmado pela microscopia eletrônica; b) um aumento significativo da densidade volumétrica de capilares preenchidos por hemácias, mas não do estroma intersticial, no grupo exposto à dose mais elevada de O2 c) uma vasoconstricção significativa das arteríolas maiores em todas as doses de oxigênio empregadas no estudo e das arteríolas menores na dose mais elevada de O2; d) variações significativas na proporção das variantes de células glômicas no grupo exposto a menor dose de O2; e) mitocôndrias com poucas cristas, tanto nas células glômicas quanto nas terminações nervosas, embora nas primeiras apresentem-se bem deformadas; f) proliferação membranosa citoplasmática com aumento de REG e Golgi nas células glômicas e sustentaculares. Esses resultados sugerem um desvio do fluxo dos vasos mais calibrosos em direção aos capilares intraglômicos, confirmando nossa hipótese inicial e indicam que o oxigênio, dependendo da dose utilizada, exerce um efeito tóxico importante sobre os corpos carotídeos, com alterações significativas da ultraestrutura das células glômicas e terminações nervosas. / We sough to confirm the existence of structural alterations in rat carotid bodies exposed to hyperoxia that could explain the attenuation of the ventilatory hypoxic drive (HD) by hyperoxic conditions described in the literature. We also tested the hypothesis of there being a deviation of blood flow toward intraglomic capillaries in situations of hyperbaric oxygenation (HBO).15 adult male Wistar rats were divided in 3 groups and exposed to O2 at 2.4 ATA for 6 hours, at 3.0 ATA for 6 hours and to air at 1.0 ATA (control group). The results obtained through histological and morphometric analysis showed: a) no alteration in the architecture of the carotid bodies, but the cytoplasm of the cells exposed to the highest dose were disarranged, a feature confirmed by electron microscopy; b) a significant increase in volume density of capillaries filled out by red blood cells but not of interstitial stroma in the group exposed to O2 at the highest dose; c) a significant vasoconstriction of larger arterioles in all doses of oxygen employed in the study and of smaller arterioles at the highest dose of O2; d) significant variations in the proportion of glomic cell variants in the group exposed to the lowest dose of O2; e) mitochondria with few cristae, so in glomic cells as in nerve-endings, although in the former they were very deformed; f) cytoplasmic membranous proliferation with an increase of endoplasmic reticulum and Golgi apparatus in glomic and sustentacular cells. These results suggest a deviation of blood flow from more calibrated vessel toward intraglomic capillaries, confirming our initial hypothesis and indicate that oxygen, depending on the dose used, exerts an important toxic effect on rat carotid body with significant alterations of glomic cell and nerve-endings ultrastructure.

Objetivos: Avaliar a segurança e a eficácia do midazolam intranasal (MIN) para sedação para tomografia em crianças, bem como a qualidade dos estudos radiológicos obtidos com esta técnica. Material e métodos: Entre dezembro de 2011 e julho de 2012, este estudo prospectivo avaliou o MIN como sedativo para crianças submetidas à tomografia sem acesso venoso. Após aprovação do Comitê de Ética em Pesquisa e consentimento dos responsáveis, 0,4 mg/kg de MIN foi administrado, sendo feita dose adicional de 0,1 mg/kg se o nível de sedação avaliado pela Escala de Sedação de Ramsay não fosse atingida após 15 minutos da primeira dose. Os desfechos relacionados à sedação incluíram tempo para sedação e para atingir os critérios de alta; parâmetros fisiológicos como oximetria de pulso e frequência cardíaca foram registrados a cada cinco minutos até a alta. A qualidade dos exames tomográficos foi avaliada quanto à presença de artefatos de imagem e movimento. Resultados: 60 eventos de sedação foram realizados em 58 pacientes. A idade média foi de 15,5 meses, sendo 90,9% dos exames tomográficos de crânio. O tempo médio para sedação foi de 15,2 minutos (5-40) e o tempo médio para atingir os critérios de alta foi de 74,7 minutos. Eventos adversos foram observados em 5 crianças (8,4%), incluindo reação paradoxal (3), tempo de recuperação prolongado (1) e vômitos (1). Apenas 4 pacientes (6,7%) não foram adequadamente sedados com MIN. Imagens consideradas excelentes, sem artefatos, foram obtidas em 56 (93,3%) sedações. Não houve eventos como bradicardia, hipoxemia ou hipotensão. Conclusões: O midazolam intranasal, administrado via atomizador nasal, é um método simples e não-invasivo para sedação segura, eficaz e previsível para crianças na obtenção de estudos tomográficos de qualidade / Objective: To evaluate the safety, efficacy and image quality of sedation with aerosolized intranasal midazolam for pediatric CT studies. Materials and Methods: Between December 2011 to May 2012, this prospective study evaluated aerosolized intranasal (AIN) midazolam as a sedative for CT of children without intravenous access. After IRB approval and parental consent, 0,4 mg/kg of AIN midazolam was administered, and repeated with 0.1 mg/kg if adequate sedation evaluated by Ramsay Sedation Scale not achieved in 15 minutes after the first dose. Sedation outcome variables which included time to achieve sedation, to meet discharge criteria and physiological vital signs of pulse oximetry and heart rate, were recorded every five minutes until discharge. The quality of CT images was reviewed and graded for presence of motion and imaging artifacts, Results: 60 sedation encounters were performed in 58 children. Mean age was 15.5 months, and 90.9% of CT scans were brain scans. Mean time to sedation was 15.2 minutes (range 5-40) and mean time to achieve discharge criteria was 74.7 minutes. Adverse events were recorded in 5 children (8.4%) that underwent sedation - paradoxical reaction (3), prolonged recovery time (1) and vomiting (1). Only 4 patients (6.7%) failed to sedate. Excellent CT imaging, with no artifacts, were obtained in 56 (93.3%) of sedation encounters. No adverse events like bradycardia, hypoxia or hypotension were documented. Conclusions: The aerosolized route of administration of midazolam is a simple and noninvasive approach for predictable, effective and safe sedation of children for quality CT imaging studies