Submitted by Caroline Periotto (carol@ufscar.br) on 2016-09-12T13:51:14Z No. of bitstreams: 1 DissBCF.pdf: 2364500 bytes, checksum: 0724cfda8e723ca02a3836a52f064450 (MD5) / Approved for entry into archive by Marina Freitas (marinapf@ufscar.br) on 2016-09-13T14:22:12Z (GMT) No. of bitstreams: 1 DissBCF.pdf: 2364500 bytes, checksum: 0724cfda8e723ca02a3836a52f064450 (MD5) / Approved for entry into archive by Marina Freitas (marinapf@ufscar.br) on 2016-09-13T14:22:21Z (GMT) No. of bitstreams: 1 DissBCF.pdf: 2364500 bytes, checksum: 0724cfda8e723ca02a3836a52f064450 (MD5) / Made available in DSpace on 2016-09-13T14:22:31Z (GMT). No. of bitstreams: 1 DissBCF.pdf: 2364500 bytes, checksum: 0724cfda8e723ca02a3836a52f064450 (MD5) Previous issue date: 2015-07-07 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) / Prematurity has been considered a public health problem. It is a condition, associated with complications, that is among the three leading causes of death in children under age five. It is a risk factor for the development of retinopathy of prematurity (ROP), a vascularization disorder of the immature retina that occurs in eighteen thousand premature infants annually in Brazil, ten percent of which develop visual impairment. Having a premature child with visual impairment due to the retinopathy of prematurity impacts family dynamics. This study aims to analyze the influence of interactions between parents (mother and father) and health professionals in the care of the child with ROP. The theoretical reference is Symbolic Interactionism and the methodological framework is Narrative Research. The data was collected through individual, in depth interviews led by two moments: characterization of the subjects, with elaboration of genogram and eco-map and obtaining the narrative of the phenomenon in focus, through the following proposition: 'I believe that, in function of the prematurity and ROP of your child, you have met with various health professionals. Tell me about your relationship with them and how it interfere in nurturing (child's name). The location of the subjects, parents (father and mother) of children with retinopathy of prematurity, was performed by the snow ball strategy. Questions concerning the characterization of the subjects were an opportunity to create a table with demographic data of both parents and obstetric data from mothers. In addition to a second table concerning children‟s demographics, conditions of birth and received diagnoses during hospitalization in the neonatal intensive care unit. The analysis of parental narratives allowed to list "Walking despite the limits" as the central storyline, supported by the themes "Child‟s Partner" and "(Un)welcoming" (subdivided into Informational and Emotional). These depict the struggle of the parents to nurture the child with ROP before the interactional context with professionals in the studied scenario. We conclude that the interactions with professionals characterized as mostly limited to parental care, especially for the lack of communication and information affecting the creation of bonds, emotional care and the development of parenting skills. On the other hand, interactions with the child and internalized reflections acted as motivating, resulting in partnership actions and stimulating their development. Limitations pointed solely to bringing only parental perspective with almost homogeneous characterization of participants, probably due to the use of snow ball strategy ( probability sampling technique that involves indication of potential subject).The study expands the qualitative evidence in the context of retinopathy of prematurity, with innovative character for lean events inherent to the experience of having / caring for a child with ROP, contemplating the perception of parents (women and men), a fact that breaks the tendency to hear only mothers. The emphasis on interaction has strengthened the value and role of dialogue, of language, of intersubjective interactions as care constituents and thus deserving investment, being still a challenge en route to qualification of Health. / A prematuridade tem sido considerada problema de saúde pública. Trata-se de uma condição que, associada às complicações decorrentes, está entre as três primeiras causas de morte em crianças menores de cinco anos. É fator de risco para o desenvolvimento da retinopatia da prematuridade (ROP), um distúrbio de vascularização anormal da retina imatura que acomete, anualmente no Brasil, dezoito mil recém-nascidos prematuros, dos quais dez por cento desenvolvem deficiência visual. Ter um filho prematuro, com deficiência visual em função da retinopatia da prematuridade impacta a dinâmica familiar. O presente estudo objetivou analisar as influências das interações entre pais (mãe e pai) e profissionais de saúde no cuidado parental junto ao filho com ROP. Elencou-se como referencial teórico o Interacionismo Simbólico e como referencial metodológico a Pesquisa de Narrativa. A coleta de dados ocorreu por meio de entrevista em profundidade individual, conduzida por dois momentos: caracterização dos sujeitos, com elaboração de genograma e ecomapa, e obtenção de narrativa sobre o fenômeno em foco, por meio da seguinte proposição: „Acredito que, em função da prematuridade e da ROP de seu(sua) filho(a), você tenha se encontrado com diversos profissionais de saúde. Conte-me sobre sua relação com eles e como ela interferiu no cuidado do(a) (nome da criança). A localização dos sujeitos, pais (pai e mãe) de crianças com retinopatia da prematuridade, foi realizada por meio da estratégia snow ball (bola de neve – técnica de amostragem probabilística que envolve indicação de potenciais sujeitos). As questões concernentes à caracterização dos sujeitos oportunizaram a criação de quadro com dados sociodemográficos de ambos os pais e de obstétricos das mães. Além de um segundo quadro, relativo às crianças, com dados demográficos, de condições de nascimento e diagnósticos recebidos durante a internação na unidade de terapia intensiva neonatal. A análise das narrativas parentais permitiu elencar “Caminhando apesar dos limites” como enredo central, sustentado pelos temas “Parceiro do filho” e “(Des)acolhimento” (subdividido em Informacional e Emocional). Esses retratam a luta dos pais em prover cuidado ao filho com ROP diante do contexto interacional com os profissionais no cenário estudado. Conclui-se que as interações com os profissionais caracterizam-se majoritariamente enquanto limite ao cuidado parental, principalmente por incipiências comunicacionais e informacionais, afetando a criação de vínculo, o acolhimento emocional e o desenvolvimento das competências parentais. Por outro lado, as interações com o filho e as reflexões internalizadas agiam de maneira motivacional, resultando em ações de parceria com ele e de estimulação ao seu desenvolvimento. Aponta-se como limites, trazer unicamente a perspectiva parental, com caracterização quase homogênea dos participantes, provavelmente devido à utilização da estratégia snow ball. O estudo amplia as evidências qualitativas no âmbito da retinopatia da prematuridade, com caráter inovador por enfocar eventos inerentes à experiência de ter/ cuidar de uma criança com ROP, contemplando inclusive a percepção de pais (mulheres e homens), fato que rompe com a tendência de ouvir apenas mães. A ênfase na interação permitiu reforçar o valor e papel do diálogo, da linguagem, das interações intersubjetivas como constituintes do cuidado e, assim, de merecimento de investimentos, constituindo-se ainda como um desafio na caminhada rumo à qualificação da Saúde.

In recent years, concern about a new epidemic of retinopathy of prematurity (ROP) has focused attention on the increasing incidence of the disease and the factors responsible for its most severe consequences. Two studies designed to address these issues were done using data from three sources: the B.C. Health Surveillance Registry (Registry), Physicians's Notices of Livebirth (PNOB), and the Vancouver General Hospital (VGH). In the first study, Registry and PNOB records were used to determine crude annual birth weight-specific incidence rates for ROP in infants liveborn in the Province of British Columbia (B.C.) in the period 1952-1983. These rates showed that, in B.C., the original epidemic of the disease ended in 1954. Linear regression lines fitted for each of four birth weight categories showed that, in the 29 year period after 1954, there was a significant increase in the incidence of ROP-induced blindness in infants weighing less than 1000 grams at birth. To refine this observation, the data were sub-divided: the 29 year period, to two smaller periods, 1955-1964 and 1965-1983; the less than 1000 gram birth weight category to two sub-categories, 500-749 and 750-999 grams. Since the inter-period incidence should have been similar if the birth weight-specific incidence had not changed since the end of the original epidemic, the crude weight-specific rates for ROP-induced blindness in the early period were used to calculate the expected number of cases in the later period. When weight-standardized incidence ratios (SIR's) and 95% confidence limits were calculated, the results showed that, in the 750-999 gram sub-category, the SIR was significantly increased. Infants born in the period 1965-1983 were 3.07 times more likely to be ROP: blind than their equal weight counterparts in the earlier period. In infants weighing 500-749 and 1000 grams or more, there was no evidence to suggest an increase in incidence after 1954. The second study was done to determine the cofactors that differentiate infants who are blinded by ROP from those who are not. Infants were included if (i) they were born in B.C. between 1955 and 1983, (ii) they were known to the Registry as being ROP: blind (cases) or not blind (controls), and (iii) they were born in or admitted to the VGH within 28 days of birth. When the data from all three data sources were dichotomized and analyzed using univariate techniques, two variables, respiratory distress syndrome (RDS) and neonatal weight loss, showed a significantly protective effect. The effect of RDS disappeared when the data were stratified by birth interval indicating that the observed association was confounded by time. When the variables were reanalyzed in continuous form, none were significantly associated with visual outcome. However, since the power of the cofactor study was extremely low, none of the variables that were included can be eliminated as potential cofactors for the induction of blindness in infants with ROP. / Medicine, Faculty of / Population and Public Health (SPPH), School of / Graduate

Die Frühgeborenenretinopathie (Retinopathia praematurorum (RPM)) ist eine Erkrankung der Netzhaut, die vor allem sehr unreife Frühgeborene betrifft und in ihrem Endstadium zur Erblindung führen kann. Ein gesicherter Risikofaktor für die Entwicklung einer RPM ist die Gabe von hohen Konzentrationen an Sauerstoff nach der Geburt. Gegenstand dieser Arbeit war die Frage, ob nach der Einführung eines Sauerstoffprotokolls 2007 das Auftreten höherer Stadien der RPM reduziert werden konnte. Das Sauerstoffprotokoll hatte zum Ziel die Gabe von inspiratorischem Sauerstoff nach Möglichkeit zu senken und übermäßige Fluktuationen zu vermeiden. Hierfür wurden 268 Frühgeborene mit einem Gestationsalter < 32Wochen bei Geburt, welche in den Jahren von 2005 bis 2006 (pre-Gruppe) und 2008 bis 2009 (post-Gruppe) in der Universitätsklinik Leipzig geboren und einem RPM-Screening unterzogen wurden, verglichen. Es konnte gezeigt werden, dass die Inzidenz der RPM nach 2007 signifikant niedriger war. So erkrankten in der pre-Gruppe 12 von 102 Kinder an einer höhergradigen RPM (>Stadium 3), wohingegen diese Stadien in der post-Gruppe nicht mehr beobachtet wurden. Demzufolge reduzierte sich auch die Notwendigkeit einer Therapie von 7,4 % auf 0 % (jeweils p = 0.0005). In Hinblick auf die Kerndaten wie Gestationsalter, Geburtsgewicht, Körpergröße, sowie dem Auftreten schwerer Begleiterkrankungen wie u.a. der nekrotisierenden Enterokolitis oder der bronchopulmonalen Dysplasie fanden sich keine Unterschiede zwischen den Gruppen. Allerdings wies die post-Gruppe eine höheren Anteil an männlichen Frühgeborenen auf. Die Mortalität zeigte keine signifikante Veränderung nach der Intervention und lag bei 7.8 % in der pre- bzw. 6.6 % in der post-Gruppe (p = 0.81). Die Auswertung der pulsoximetrisch gemessenen Sauerstoffsättigung (SpO2) und der inspiratorischen Sauerstofffraktion (FiO2) zeigte, dass der SpO2 leicht und der FiO2 deutlich reduziert werden konnte. Ein signifikanter Unterschied ergab sich hier jedoch lediglich für den FiO2, insbesondere in den ersten 14 Lebenstagen. Die logistische Regressionsanalyse legt nahe, dass hohe SpO2- und FiO2-Werte sowie das Auftreten von intrakraniellen Blutungen mit schwerwiegenden ROP-Stadien korrelieren. Ein bedachter Umgang in der Sauerstofftherapie Frühgeborenen könnte in der Lage sein das Auftreten der Frühgeborenenretinopathie zu reduzieren ohne eine Erhöhung der Mortalitätsrate zu riskieren.

Background/Aims: This study aimed to analyze the effects of perinatal history on tear film properties and lid geometry in adults born preterm. Methods: The Gutenberg Prematurity Eye Study (GPES) is a German prospective examination of adults born preterm and term aged 18 to 52 years with Keratograph® 5M and Schirmer test I. Main outcome measures were first non-invasive tear film break-up time (F-NITBUT), bulbar redness (BR), Schirmer test, and nasal palpebral angle measurement. The associations with gestational age (GA), birth weight (BW), and BW percentile, retinopathy of prematurity (ROP), ROP treatment, and other perinatal factors were evaluated using regression analyses. Results: 489 eyes of 255 preterm and 277 eyes of 139 full-term individuals (aged 28.6 +/− 8.8 years, 220 females) were included. Of these, 33 participants (56 eyes) had a history of spontaneously regressed ROP and 9 participants (16 eyes) had a history of ROP treatment. After adjustment for age and sex, lower F-NITBUT (<20 s) was associated with ROP treatment (OR = 4.42; p = 0.025). Lower GA correlated with increased bulbar redness (B = −0.02; p = 0.011) and increased length of wetting in the Schirmer test (B = −0.69; p = 0.003). Furthermore, low GA was associated with narrowing of the nasal palpebral angle (B = 0.22; p = 0.011) adjusted for age and sex, but not when considering ROP in the multivariable model. Conclusion: Our analyses indicate that perinatal history affects ocular surface properties, tear production and lid geometry in adults born term and preterm. This might indicate that affected persons have a predisposition to diseases of the corneal surface such as the dry eye disease.

No description available.

Background: Optical coherence tomography (OCT), multifocal electroretinography (mfERG) and full-field electroretinography (ffERG) give important information about retinal structure and function. Purpose: To collect normative data of macular Cirrus Spectral domain (SD)-OCT assessments and of mfERG measurements of healthy children (papers I and II). To assess the macular thickness with Cirrus SD-OCT and the retinal function with ffERG in 6.5-year-old children born extremely preterm and in children born at term (papers III and IV). Methods: Study participants aged 5-15 years and living in Uppsala County were randomly chosen from the Swedish Birth Register (papers I and II). In papers III and IV, the study participants consisted of children born extremely preterm and children born at term – all were aged 6.5 years. In paper III, the children were living in Stockholm and Uppsala health care regions and, in paper IV, in Uppsala health care region only. Macular thickness was assessed with Cirrus SD-OCT and macular function with mfERG, using the Espion Multifocal system and DTL-electrodes. The retinal function was assessed with ffERG and DTL-electrodes, using the Espion Ganzfield system. Results: Altogether, 58 children participated in paper I and 49 children in paper II. In paper I, the repeatability and reproducibility of the OCT assessments were good. In paper II, the results of the mfERG measurements were in accordance with retinal cone density and there were no significant differences between the right and left eyes. In paper III, 134 preterm children and 145 children born at term constituted the study population. The central macular thickness was significantly thicker in the preterm group than in the control group. Within the preterm group, gestational age (GA), former retinopathy of prematurity (ROP) and male gender were all important risk factors for an increased macular thickness. In paper IV, 52 preterm children and 45 control children constituted the study population. Significantly lower amplitudes and prolonged implicit times of the combined rod and cone responses, as well as of the isolated cone responses, were found in the preterm group when compared with the control group. In paper IV, there was no association between GA, ROP or male gender and the ffERG assessments. Conclusion: Normative data of Cirrus SD-OCT and mfERG assessments were reported. The results of the assessments were reliable. Children aged 6.5 years, born extremely preterm, had a significantly thicker central macula and both rod and cone function were significantly reduced in comparison to children born at term. ROP had an influence on retinal structure but not retinal function in the present cohorts. Our results suggest that retinal development is abnormal in children born extremely preterm. Long-term follow-up studies are necessary in order to evaluate the functional ophthalmological outcome in this vulnerable population of children growing up today.

O objetivo geral deste estudo foi investigar o efeito do leite humano na redução de respostas biocomportamentais de dor em RNPTs submetidos ao exame de fundo de olho para diagnóstico precoce da retinopatia da prematuridade, em comparação com a sacarose 25%. Trata-se de ensaio clínico randomizado, realizado na unidade neonatal de um hospital universitário de Ribeirão Preto-SP, com 48 prematuros distribuídos randomicamente em dois grupos: leite humano e sacarose, administrados por via oral 2 minutos antes do procedimento doloroso. As variáveis dimensionadas foram mímica facial da escala de dor NFCS, choro, frequência cardíaca e cortisol salivar. A coleta de dados foi realizada em cinco períodos para a mímica facial e o NFCS: basal (05 minutos), olho direito e olho esquerdo, recuperação imediata (05 minutos após o procedimento) e recuperação tardia (05 minutos após a recuperação imediata); quatro períodos para a frequência cardíaca e o choro: basal (05 minutos), procedimento, recuperação imediata e tardia. O cortisol salivar foi coletado antes do início do exame de fundo de olho (basal), após 30 (cortisol resposta) e 60 (cortisol recuperação) minutos do término do exame. O projeto foi aprovado pelo Comitê de Ética em Pesquisa da instituição e foi registrado no Australian and New Zeland Clinical Trials. O Teste de Kolmogorov-Smirnov e o Teste t-student mostraram que os grupos são comparáveis. Para análise das variáveis de desfecho, utilizou-se a Análise de Variância com Medidas Repetidas (RM-ANOVA). Após testar a homogeneidade das variáveis (teste de Levene), foi avaliado o pressuposto da esfericidade das matrizes de variância (teste de Mauchly). Assumindo-se a esfericidade, adotaram-se a análise multivariada, com valor de épsilon < 0,75, e a estatística de Wilk´s Lambda. Para valores de épsilon > 0,75, adotaram-se a análise univariada e a estatística de Hunh-Feldt (HF) ou Greenhouse-Geisser. Para as variáveis categóricas, foi utilizado o teste Qui-quadrado ou Teste exato Fisher. O efeito do leite humano no alívio da dor, decorrente do exame de fundo de olho, não diferiu estatisticamente da sacarose 25%, ao avaliarmos a duração da presença de fronte saliente [Wilk\'s Lamba=0,918, F=0,960, p=0,241], do sulco nasolabial [Wilk\'s Lambda=0,883; F=1,43; p=0,241] e do choro [Wilk\'s Lambda=0,964; F=3,44; p=0,656], e o escore médio do NFCS adaptado ao considerarmos essas duas ações da mímica facial [Wilk\'s Lambda=0,924; F=0,884; p=0,481], a FC [Wilk\'s Lambda=0,977; F=3,44; p=0,792] e a concentração de cortisol salivar [Wilk\'s Lambda=0,978; F=2,45; p=0,612]. A comparação intrasujeitos mostrou diferença significativa nos períodos de coleta dos dados, com aumento nos escores do NFCS, na duração da fronte saliente e do sulco nasolabial, durante o exame do fundo de olho direito e esquerdo, como também no aumento do choro, durante o procedimento doloroso, em comparação com os períodos basal, recuperação inicial e tardia. A concentração do cortisol salivar aumentou significativamente aos 30 e 60 minutos após o procedimento, em comparação com os valores do cortisol basal; não houve diferença entre o cortisol resposta (30 minutos) e recuperação (60 minutos). A duração do sulco nasolabial, do choro e os escores do NFCS no basal não diferiram significativamente dos valores encontrados na recuperação inicial e tardia. Na FC, houve diferença no basal em relação à recuperação imediata, e na duração da fronte saliente houve diferença nas duas recuperações. Concluímos que o efeito do leite humano, na redução das respostas biocomportamentais de dor em prematuros submetidos ao exame de fundo de olho para diagnóstico da retinopatia da prematuridade, não é superior ao efeito obtido com a sacarose 25%, rejeitando-se a hipótese alternativa. / The general aim of this study was to investigate the effect of human milk on reducing biobehavioral pain responses in PN\'s undergoing the ocular fundus examination for the early diagnosis of retinopathy of prematurity, compared with 25% sucrose. This is a randomized clinical trial conducted in the neonatal unit of a university hospital of Ribeirão Preto-SP, with 48 premature newborns randomly distributed into two groups: human milk and sucrose, orally administered 2 minutes before the painful procedure. The variables investigated were the facial movements of the NFCS pain scale, crying, heart rate (HR) and salivary cortisol levels. Data collection was conducted in five periods for the facial movements and NFCS: baseline (05 minutes), right eye and left eye, immediate recovery (05 minutes after the procedure) and delayed recovery (05 minutes after immediate recovery); and in four periods for heart rate and crying: baseline (05 minutes), procedure, immediate and delayed recovery. Salivary cortisol was collected before the start of the fundus examination (baseline), and at 30 minutes (cortisol response) and 60 minutes (cortisol recovery) after the end of the examination. The project was approved by the Research Ethics Committee and was registered in the Australian and New Zealand Clinical Trials. The Kolmogorov-Smirnov test and Student\'s t-test showed that the groups were comparable. For the analysis of the outcome variables, the Analysis of Variance with Repeated Measures (RM-ANOVA) was used. After testing the homogeneity of the variables (Levene\'s test) the assumption of sphericity of the variance matrices was evaluated (Mauchly\'s test). Assuming sphericity, multivariate analysis was adopted, with a < 0.75 value of epsilon and Wilk\'s Lambda statistic. For values of epsilon > 0.75, univariate analysis and the Hunh-Feldt (HF) or Greenhouse-Geisser statistic were adopted. For the categorical variables, the chi-square test or Fisher exact test was used. The effect of human milk on pain relief, arising from the ocular fundus examination, did not differ statistically from 25% sucrose, when the duration of the presence of brow lowering [Wilk\'s Lambda=0.918; F=0.960; p=0.241], of deepening of the naso-labial furrow [Wilk\'s Lambda=0.883; F=1.43; p=0.241] and of crying [Wilk\'s Lambda=0.964; F=3.44; p=0.656] were evaluated, as well as the mean score of the NFCS adapted to consider these two facial movement actions [Wilk\'s Lambda=0.924; F=0.884; p=0.481], the HR [Wilk\'s Lambda=0.977; F=3.44; p=0.792] and the salivary cortisol concentration [Wilk\'s Lambda=0.978; F=2.45; p=0.612]. The intra-subject comparison showed a significant difference in the data collection periods, with an increase in the NFCS scores, in the duration of brow lowering and naso-labial furrow deepening, during the examination fundus of the right and left eyes, as well as increased crying during the painful procedure, compared with the baseline period, immediate and delayed recovery. The concentration of salivary cortisol increased significantly at 30 and 60 minutes after the procedure, compared with the baseline cortisol values; there was no difference between cortisol response (30 minutes) and recovery (60 minutes). The duration of naso-labial furrow deepening, of crying and the NFCS scores at the baseline did not differ significantly from the values found in the immediate and delayed recovery. In the HR, there was no difference between the baseline and the immediate recovery, and in the duration of brow lowering there was no difference in the two recoveries. We conclude that the effect of human milk, on the reduction of biobehavioral responses to pain in preterm infants undergoing the ocular fundus examination for the diagnosis of retinopathy of prematurity, is not greater than the effect obtained with 25% sucrose, rejecting the alternative hypothesis.

Dans les pays industrialisés, les pathologies oculaires à composante vasculaires, que ce soit la rétinopathie du prématuré (ROP), la rétinopathie du diabétique ou la dégénérescence lié à l’âge, représentent la première cause de cécité respectivement chez l’enfant, l’adulte et la personne âgée. Plusieurs études sur l’homme ou sur des modèles animaux ont souligné le rôle crucial joué des acides gras polyinsaturés (AGPI) au cours de ces rétinopathies et notamment l’action préventive des acides gras polyinsaturés oméga 3 (AGPI n-3) sur l’angiogenèse pathologique. Ces AGPI sont estérifiés dans les glycérophospholipides constituant les membranes cellulaires. On les retrouve également dans une classe particulière de glycérophospholipides, les plasmalogènes. La particularité des plasmalogènes réside dans leur liaison vinyl-éther en position sn-1 au lieu d’une liaison ester dans les autres glycérophospholipides. Les AGPI sont libérés des plasmalogènes par une phospholipase indépendante au calcium, la iPLA2, pour devenir des métabolites actifs. Les plasmalogènes via la libération des AGPI joueraient un rôle dans la mise en place et la maturation du réseau vasculaire rétinien et ce, notamment grâce à la bonne mise en place du réseau astrocytaire. Les astrocytes et les cellules de Müller sont les cellules macrogliales qui servent de soutien physique et métabolique à la rétine. De plus, les cellules de Müller participent au métabolisme des lipides. L’objectif de ce travail de thèse a été d’évaluer l’implication des plasmalogènes dans le métabolisme des cellules de Müller et des astrocytes mais aussi dans la communication entre ces cellules macrogliales. Nous avons également étudié le profil lipidique d’enfants prématurés pour mettre en évidence de potentielles altérations du métabolisme des plasmalogènes chez des nouveau-nés développant une rétinopathie à composante vasculaire, la rétinopathie du prématuré (ROP). Pour ce faire nous avons étudié les effets d’une diminution en plasmalogènes et/ou en iPLA2 sur des cellules de Müller en culture primaire après avoir préalablement vérifié l’expression de l’enzyme clef de la biosynthèse des plasmalogènes. Nous avons ensuite étudié les effets d’une diminution des teneurs en plasmalogènes sur la communication calcique entre les cellules de Müller et les astrocytes. Nos résultats ont montré que les cellules de Müller expriment l’enzyme-clé de synthèse des plasmalogènes et que ces cellules sont plus riches en plasmalogènes que la rétine entière. Les plasmalogènes seraient impliqués dans le contrôle de la migration des cellules de Müller par l’action de la voie ERK1/2 MAPK. Ces effets ne semblent pas passer par la libération des AGPI. De plus nos résultats suggèrent une dégradation de la communication entre les astrocytes et les cellules de Müller en cas de diminution des teneurs en plasmalogènes dans les cellules de Müller. Enfin chez l’homme nous avons mis en évidence une accumulation des AGPI n-6 au détriment des AGPI n-3 dans les érythrocytes des enfants développant une rétinopathie du prématuré et inversement dans le groupe d’enfants prématuré contrôle. L’ensemble de ces travaux confirme l’importance du métabolisme lipidique, et plus particulièrement celui des plasmalogènes, sur le fonctionnement de la rétine. / Retinal vascular disorders such as retinopathy of prematurity (ROP), diabetic retinopathy or age-related macular degeneration represent the first cause of vision loss at all ages in industrialized countries. Many epidemiological or animal studies have shown the involvement of polyunsaturated fatty acids (PUFA) in the regulation of vascular development and more specifically the beneficial properties of omega 3 PUFA (n-3 PUFA) against pathological vascularization. Those PUFA are esterified on glycerophospholipids (GP). GP are the primary constituents of the lipid bilayer of cell membranes. PUFA can be also esterified on a specific class of GP, called plasmalogens. Plasmalogens are characterized by the presence of a vinyl ether linkage at the sn-1 position of glycerol instead of an ester linkage as seen in other GP. PUFA are released from plasmalogens by a calcium-independent phospholipase (iPLA2). Free PUFA can be converted into biologically active metabolites. Plasmalogens may have an impact on the development and the maturation of retinal vascular network through the PUFA they release through the control of astrocyte template formation prior to vessel formation. Astrocytes and Müller cells are macroglials cells providing physical and metabolic supports to the retina. Müller cells are key actors of the retinal lipid metabolism. The aim of this work was to evaluate the involvement of plasmalogens in Müller cells and astrocytes metabolism as well as in the ability of these cells to communicate. On one hand, we have studied the effects of a decrease in plasmalogen biosynthesis and/or in iPLA2 activity on Müller cell physiology. Müller cells express a biosynthesis key enzyme of plasmalogen and reducing the biosynthesis of plasmalogens affects Müller cell ability to migrate through the ERK1/2 MAPK signalling. In a second series of studies, we studied the repercussions of such modifications on Müller cell physiology on their ability to communicate with retinal astrocytes through calcium signalling. Our results suggest that affecting plasmalogen metabolism in Müller cells alters the communication between astrocytes and Müller cells. Finally, and in order to investigate whether plasmalogen metabolism may be modified in a human disease displaying abnormal retinal vascular development, we performed a lipidomic study of circulating lipids in infants affected by retinopathy of prematurity. ROP was characterized by the accumulation of n-6 PUFA at the expense of n-3 PUFA, these changes being associated to plasmalogens. All these experiments confirm the importance of lipid metabolism, and especially plasmalogens, on the retina functioning.

Submitted by Erika Demachki (erikademachki@gmail.com) on 2015-02-20T15:09:52Z No. of bitstreams: 2 Dissertação - Tatiana Vieira de Brito Marquez - 2010.pdf: 2722177 bytes, checksum: d3f571bcc9c3e44cf51b9d4539e6191d (MD5) license_rdf: 23148 bytes, checksum: 9da0b6dfac957114c6a7714714b86306 (MD5) / Approved for entry into archive by Erika Demachki (erikademachki@gmail.com) on 2015-02-20T15:10:12Z (GMT) No. of bitstreams: 2 Dissertação - Tatiana Vieira de Brito Marquez - 2010.pdf: 2722177 bytes, checksum: d3f571bcc9c3e44cf51b9d4539e6191d (MD5) license_rdf: 23148 bytes, checksum: 9da0b6dfac957114c6a7714714b86306 (MD5) / Made available in DSpace on 2015-02-20T15:10:12Z (GMT). No. of bitstreams: 2 Dissertação - Tatiana Vieira de Brito Marquez - 2010.pdf: 2722177 bytes, checksum: d3f571bcc9c3e44cf51b9d4539e6191d (MD5) license_rdf: 23148 bytes, checksum: 9da0b6dfac957114c6a7714714b86306 (MD5) Previous issue date: 2010-07-06 / OBJECTIVES: To compare the response of bevacizumab and the response of the laser photocoagulation with indirect binocular ophthalmoscope (IBO) in infants with retinopathy of prematurity (ROP) stages II or III. METHODS: Data collection was performed in the neonatal intensive care unit of the Hospital Materno Infantil, from May to November 2009. Preterm infants with ROP stages II or III, with or without the plus disease were included. They were divided into two groups: on group I, an intra-vitreous injection of bevacizumab was performed and on group II, laser photocoagulation with IBO was performed. RESULTS: In group I, from the 20 eyes that underwent the application of bevacizumab, there was total regression of ROP with one application in 14 eyes, being 4 eyes with complete regression with two doses of bevacizumab, and 2 eyes with total regression after two applications of bevacizumab and one application of laser. On group II, from the 20 eyes treated with laser photocoagulation with IBO, there was total regression of ROP with laser therapy in 14 eyes and there was total regression with two laser sessions in 6 eyes. CONCLUSION: Bevacizumab is effective if compared to laser photocoagulation in ROP stages II and III. / OBJETIVOS: Comparar a resposta terapêutica do bevacizumabe intravítreo com à resposta da fotocoagulação a laser com oftalmoscópio binocular indireto, em prematuros portadores de retinopatia da prematuridade estágios II ou III. MÉTODOS: A coleta de dados foi realizada na UTI neonatal do Hospital Materno Infantil, no período de maio a novembro de 2009. Foram incluídos os prematuros com retinopatia da prematuridade graus II ou III, com ou sem doença plus. Estes foram divididos em dois grupos: no grupo I foi realizada a injeção intra-vitrea de bevacizumabe, no grupo II foi realizada a fotocoagulação a laser com oftalmoscópio binocular indireto. RESULTADOS: No grupo I, dos 20 olhos incluídos, houve regressão total da retinopatia da prematuridade com uma aplicação de bevacizumabe em 14 olhos, regressão total com duas aplicações em 4 olhos e regressão total após duas aplicações de bevacizumabe e uma aplicação de laser em 2 olhos. No grupo II, dos 20 olhos tratados com fotocoagulação a laser com oftalmoscópio binocular indireto, houve regressão total da retinopatia da prematuridade com uma sessão em 14 olhos e houve regressão total com duas sessões em 6 olhos. CONCLUSÃO: O bevacizumabe é tão eficiente quanto a fotocoagulação a laser na retinopatia da prematuridade nos estágios II e III.

O objetivo geral deste estudo foi investigar o efeito do leite humano na redução de respostas biocomportamentais de dor em RNPTs submetidos ao exame de fundo de olho para diagnóstico precoce da retinopatia da prematuridade, em comparação com a sacarose 25%. Trata-se de ensaio clínico randomizado, realizado na unidade neonatal de um hospital universitário de Ribeirão Preto-SP, com 48 prematuros distribuídos randomicamente em dois grupos: leite humano e sacarose, administrados por via oral 2 minutos antes do procedimento doloroso. As variáveis dimensionadas foram mímica facial da escala de dor NFCS, choro, frequência cardíaca e cortisol salivar. A coleta de dados foi realizada em cinco períodos para a mímica facial e o NFCS: basal (05 minutos), olho direito e olho esquerdo, recuperação imediata (05 minutos após o procedimento) e recuperação tardia (05 minutos após a recuperação imediata); quatro períodos para a frequência cardíaca e o choro: basal (05 minutos), procedimento, recuperação imediata e tardia. O cortisol salivar foi coletado antes do início do exame de fundo de olho (basal), após 30 (cortisol resposta) e 60 (cortisol recuperação) minutos do término do exame. O projeto foi aprovado pelo Comitê de Ética em Pesquisa da instituição e foi registrado no Australian and New Zeland Clinical Trials. O Teste de Kolmogorov-Smirnov e o Teste t-student mostraram que os grupos são comparáveis. Para análise das variáveis de desfecho, utilizou-se a Análise de Variância com Medidas Repetidas (RM-ANOVA). Após testar a homogeneidade das variáveis (teste de Levene), foi avaliado o pressuposto da esfericidade das matrizes de variância (teste de Mauchly). Assumindo-se a esfericidade, adotaram-se a análise multivariada, com valor de épsilon < 0,75, e a estatística de Wilk´s Lambda. Para valores de épsilon > 0,75, adotaram-se a análise univariada e a estatística de Hunh-Feldt (HF) ou Greenhouse-Geisser. Para as variáveis categóricas, foi utilizado o teste Qui-quadrado ou Teste exato Fisher. O efeito do leite humano no alívio da dor, decorrente do exame de fundo de olho, não diferiu estatisticamente da sacarose 25%, ao avaliarmos a duração da presença de fronte saliente [Wilk\'s Lamba=0,918, F=0,960, p=0,241], do sulco nasolabial [Wilk\'s Lambda=0,883; F=1,43; p=0,241] e do choro [Wilk\'s Lambda=0,964; F=3,44; p=0,656], e o escore médio do NFCS adaptado ao considerarmos essas duas ações da mímica facial [Wilk\'s Lambda=0,924; F=0,884; p=0,481], a FC [Wilk\'s Lambda=0,977; F=3,44; p=0,792] e a concentração de cortisol salivar [Wilk\'s Lambda=0,978; F=2,45; p=0,612]. A comparação intrasujeitos mostrou diferença significativa nos períodos de coleta dos dados, com aumento nos escores do NFCS, na duração da fronte saliente e do sulco nasolabial, durante o exame do fundo de olho direito e esquerdo, como também no aumento do choro, durante o procedimento doloroso, em comparação com os períodos basal, recuperação inicial e tardia. A concentração do cortisol salivar aumentou significativamente aos 30 e 60 minutos após o procedimento, em comparação com os valores do cortisol basal; não houve diferença entre o cortisol resposta (30 minutos) e recuperação (60 minutos). A duração do sulco nasolabial, do choro e os escores do NFCS no basal não diferiram significativamente dos valores encontrados na recuperação inicial e tardia. Na FC, houve diferença no basal em relação à recuperação imediata, e na duração da fronte saliente houve diferença nas duas recuperações. Concluímos que o efeito do leite humano, na redução das respostas biocomportamentais de dor em prematuros submetidos ao exame de fundo de olho para diagnóstico da retinopatia da prematuridade, não é superior ao efeito obtido com a sacarose 25%, rejeitando-se a hipótese alternativa. / The general aim of this study was to investigate the effect of human milk on reducing biobehavioral pain responses in PN\'s undergoing the ocular fundus examination for the early diagnosis of retinopathy of prematurity, compared with 25% sucrose. This is a randomized clinical trial conducted in the neonatal unit of a university hospital of Ribeirão Preto-SP, with 48 premature newborns randomly distributed into two groups: human milk and sucrose, orally administered 2 minutes before the painful procedure. The variables investigated were the facial movements of the NFCS pain scale, crying, heart rate (HR) and salivary cortisol levels. Data collection was conducted in five periods for the facial movements and NFCS: baseline (05 minutes), right eye and left eye, immediate recovery (05 minutes after the procedure) and delayed recovery (05 minutes after immediate recovery); and in four periods for heart rate and crying: baseline (05 minutes), procedure, immediate and delayed recovery. Salivary cortisol was collected before the start of the fundus examination (baseline), and at 30 minutes (cortisol response) and 60 minutes (cortisol recovery) after the end of the examination. The project was approved by the Research Ethics Committee and was registered in the Australian and New Zealand Clinical Trials. The Kolmogorov-Smirnov test and Student\'s t-test showed that the groups were comparable. For the analysis of the outcome variables, the Analysis of Variance with Repeated Measures (RM-ANOVA) was used. After testing the homogeneity of the variables (Levene\'s test) the assumption of sphericity of the variance matrices was evaluated (Mauchly\'s test). Assuming sphericity, multivariate analysis was adopted, with a < 0.75 value of epsilon and Wilk\'s Lambda statistic. For values of epsilon > 0.75, univariate analysis and the Hunh-Feldt (HF) or Greenhouse-Geisser statistic were adopted. For the categorical variables, the chi-square test or Fisher exact test was used. The effect of human milk on pain relief, arising from the ocular fundus examination, did not differ statistically from 25% sucrose, when the duration of the presence of brow lowering [Wilk\'s Lambda=0.918; F=0.960; p=0.241], of deepening of the naso-labial furrow [Wilk\'s Lambda=0.883; F=1.43; p=0.241] and of crying [Wilk\'s Lambda=0.964; F=3.44; p=0.656] were evaluated, as well as the mean score of the NFCS adapted to consider these two facial movement actions [Wilk\'s Lambda=0.924; F=0.884; p=0.481], the HR [Wilk\'s Lambda=0.977; F=3.44; p=0.792] and the salivary cortisol concentration [Wilk\'s Lambda=0.978; F=2.45; p=0.612]. The intra-subject comparison showed a significant difference in the data collection periods, with an increase in the NFCS scores, in the duration of brow lowering and naso-labial furrow deepening, during the examination fundus of the right and left eyes, as well as increased crying during the painful procedure, compared with the baseline period, immediate and delayed recovery. The concentration of salivary cortisol increased significantly at 30 and 60 minutes after the procedure, compared with the baseline cortisol values; there was no difference between cortisol response (30 minutes) and recovery (60 minutes). The duration of naso-labial furrow deepening, of crying and the NFCS scores at the baseline did not differ significantly from the values found in the immediate and delayed recovery. In the HR, there was no difference between the baseline and the immediate recovery, and in the duration of brow lowering there was no difference in the two recoveries. We conclude that the effect of human milk, on the reduction of biobehavioral responses to pain in preterm infants undergoing the ocular fundus examination for the diagnosis of retinopathy of prematurity, is not greater than the effect obtained with 25% sucrose, rejecting the alternative hypothesis.