Leung, Wan Lun Fiona. / Thesis (M.Phil.)--Chinese University of Hong Kong, 2011. / Includes bibliographical references (leaves 179-204). / Abstracts in English and Chinese. / Abstract --- p.i / 中文摘要 --- p.v / Acknowledgement --- p.viii / List of Abbreviations and Symbols x --- p.vi / List of Tables --- p.xx / List of Figures --- p.xxi / Chapter CHAPTER ONE --- Introduction --- p.1 / Chapter 1.1 --- General Overview --- p.1 / Chapter 1.2 --- Necrotizing Enterocolitis (NEC) --- p.3 / Chapter 1.2.1 --- Epidemiology of NEC --- p.3 / Chapter 1.2.2 --- "Clinical Presentation, Diagnosis and Management of NEC" --- p.5 / Chapter 1.2.3 --- Pathophysiology of NEC --- p.9 / Chapter 1.2.3.1 --- Prematurity --- p.9 / Chapter 1.2.3.2 --- Bacterial Colonization --- p.12 / Chapter 1.2.3.3 --- Enteral Feeding --- p.15 / Chapter 1.2.3.4 --- Hypoxia and Ischemia --- p.16 / Chapter 1.2.3.5 --- Genetic Polymorphism --- p.17 / Chapter 1.2.3.6 --- Inflammatory Mediators --- p.20 / Chapter 1.3 --- Spontaneous Intestinal Perforation (SIP) --- p.24 / Chapter 1.3.1 --- Epidemiology of SIP --- p.24 / Chapter 1.3.2 --- "Clinical Presentation, Diagnosis and Management of SIP" --- p.26 / Chapter 1.3.3 --- Risk Factors of SIP --- p.28 / Chapter 1.3.3.1 --- Prematurity --- p.29 / Chapter 1.3.3.2 --- Use of Drugs --- p.30 / Chapter 1.4 --- Comparison between NEC and SIP --- p.32 / Chapter 1.5 --- Role of Cytokines in Pathogenesis of NEC and SIP --- p.38 / Chapter 1.6 --- Immunoregulatory Molecules of Interest in This Study --- p.46 / Chapter 1.6.1 --- Angiopoietin-2 (Ang-2) --- p.46 / Chapter 1.6.2 --- v-erb-b2 Erythroblastic Leukemia Viral Oncogene Homolog 2 (avian) (ErbB3) --- p.48 / Chapter 1.6.3 --- Type II Interleukin-1 Receptor (IL-1RII) --- p.52 / Chapter 1.6.4 --- Urokinase Plasminogen Activator Receptor (uPAR) --- p.54 / Chapter CHAPTER TWO --- Objectives --- p.57 / Chapter CHAPTER THREE --- Materials and Methodology --- p.58 / Chapter 3.1 --- Overview of the Experimental Procedures --- p.58 / Chapter 3.1.1 --- Investigation on the Profile of Circulatory Immunoregulatory Proteins in Plasma of NEC and SIP High Risk Neonates --- p.58 / Chapter 3.1.2 --- Investigation on the mRNA Expression Level of Targeted Immunoregulatory Molecules on Resected Intestinal Tissues in NEC and SIP Neonates --- p.58 / Chapter 3.1.3 --- Investigation on the mRNA and Protein Expression Levels of Targeted Immunoregulatory Molecules in Human Intestinal Cell Lines --- p.60 / Chapter 3.2 --- Reagents and Lab-wares with Their Sources --- p.61 / Chapter 3.3 --- Study Population --- p.63 / Chapter 3.4 --- Collection of Neonatal Whole Blood Samples --- p.65 / Chapter 3.5 --- Cytokine Antibody Array Analyses --- p.67 / Chapter 3.6 --- Enzyme-linked Immunosorbant Assays (ELISA) --- p.69 / Chapter 3.6.1 --- Angiopoietin-2 --- p.69 / Chapter 3.6.2 --- sErbB3 --- p.71 / Chapter 3.6.3 --- sIL-lRII --- p.72 / Chapter 3.6.4 --- suPAR --- p.74 / Chapter 3.7 --- Collection of Neonatal Resected Intestinal Tissues --- p.76 / Chapter 3.8 --- Resected Intestinal Tissue RNA Isolation --- p.78 / Chapter 3.9 --- Purity Assessment of the Purified Tissue RNA Samples --- p.80 / Chapter 3.10 --- Integrity Assessment of the Purified Tissue RNA Samples --- p.81 / Chapter 3.11 --- In vitro Stimulation of Human Enterocytes by Lipopolysaccharides (LPS) and/or Platelet Activating Factor (PAF) --- p.84 / Chapter 3.12 --- mRNA Expression Level Assessment of Selected Target Genes in Resected Intestinal Tissues and Human Intestinal Cell Lines --- p.86 / Chapter 3.12.1 --- Synthesis of First Strand cDNA --- p.86 / Chapter 3.12.2 --- Quantitative Polymerase Chain Reaction (qPCR) --- p.87 / Chapter 3.13 --- Statistical Analysis --- p.89 / Chapter CHAPTER FOUR --- Screening of Immunoregulatory Target Protein Molecules in Plasma of NEC and SIP Patients by Cytokine Array Analyses --- p.104 / Chapter 4.1 --- Results --- p.104 / Chapter 4.1.1 --- Screening of Detectable Immunoregulatory Target Molecules --- p.104 / Chapter 4.1.2 --- Selection of Target Molecules Based on the Fold Change in NEC or SIP Compared with Control Samples --- p.105 / Chapter 4.1.2.1 --- Similar Regulation of Target Molecules in Both NEC and SIP patients --- p.105 / Chapter 4.1.2.2 --- Differential regulation of Target Molecules in NEC and SIP Patients --- p.106 / Chapter 4.1.2.3 --- "Relative Normalized Expressions of Selected Circulatory Immunoregulatory Protein Molecules in NEC, SIP and Control Neonates" --- p.108 / Chapter 4.1.2.3.1 --- Anti-inflammation --- p.108 / Chapter 4.1.2.3.2 --- Pro-inflammation --- p.109 / Chapter 4.1.2.3.3 --- Cell Growth --- p.110 / Chapter 4.1.2.3.4 --- Wound Healing --- p.110 / Chapter 4.1.2.3.5 --- Angiogenesis --- p.111 / Chapter 4.1.2.3.6 --- "Anti-apoptosis, Cell Adhesion and Extracellular Matrix Organization" --- p.112 / Chapter 4.1.3 --- Further Selection of Novel Target Molecules Based on Statistical Significance and Fold Change of NEC versus SIP --- p.113 / Chapter 4.2 --- Discussion --- p.115 / Chapter CHAPTER FIVE --- Validation of Target Proteins in Plasma of NEC and SIP Patients by Enzyme-linked Immunosorbant Assay --- p.132 / Chapter 5.1 --- Results --- p.133 / Chapter 5.1.1 --- Demographic Data of the Study Group --- p.133 / Chapter 5.1.2 --- "Comparison of Plasma Levels of Target Proteins between NEC, SIP and Respective Controls" --- p.134 / Chapter 5.1.3 --- Longitudinal Study of the Pre- and Post-operative Target Proteins Levels in Plasma --- p.136 / Chapter 5.2 --- Discussion --- p.138 / Chapter CHAPTER SIX --- Investigation on mRNA Expression Levels of Target Immunoregulatory Protein Molecules in Intestinal Tissue and Intestinal Cell Lines --- p.151 / Chapter 6.1 --- Results --- p.152 / Chapter 6.1.1 --- mRNA Expression Levels of Target Molecules in the Diseased Margin of Resected Intestinal Tissues of NEC and SIP patients --- p.152 / Chapter 6.1.2 --- mRNA Expression Levels of Target Molecules in the Macroscopically Normal and Diseased Margin of Resected Intestinal Tissues of NEC and SIP patients --- p.154 / Chapter 6.1.3 --- mRNA Expression Levels of Target Molecules in Human Intestinal Cell Lines upon LPS and PAF Challenge --- p.156 / Chapter 6.1.3.1 --- FHs-74 Int Cell Line --- p.156 / Chapter 6.1.3.2 --- Caco-2 Cell Line --- p.157 / Chapter 6.2 --- Discussion --- p.158 / Chapter CHAPTER SEVEN --- General Discussion --- p.171 / Chapter 7.1 --- Overall Findings --- p.171 / Chapter 7.2 --- Limitations of Study --- p.174 / Chapter 7.3 --- Future Investigations --- p.177 / References --- p.179

Orientador: José Guilherme Cecatti / Dissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Ciências Médicas / Made available in DSpace on 2018-08-26T11:44:16Z (GMT). No. of bitstreams: 1 Santos_JulianaPaulaFerrazdos_M.pdf: 1715906 bytes, checksum: f5ae24f0025dda816672cb4f1b773f8c (MD5) Previous issue date: 2015 / Resumo: Antecedentes: O conceito de near miss neonatal tem sido proposto como ferramenta para avaliação da qualidade da atenção aos recém-nascidos que sofreram alguma condição ameaçadora à vida. No entanto, não existem conceitos nem critérios internacionalmente aceitos que definam ou identifiquem esses casos de near miss. O objetivo do estudo é fazer uma revisão dos marcadores que possam identificar casos de near miss neonatal, bem como predizer a mortalidade neonatal. Métodos: Foram realizadas buscas eletrônicas nas bases de dados Pubmed, Embase e Scielo, sem restrição de período ou língua. Para isso foi utilizado o termo "neonatal near miss" isolado ou em associação com termos relativos à morbidade e mortalidade neonatais e aos escores de gravidade neonatal. A primeira etapa da seleção foi baseada no título, a segunda no resumo e a terceira no artigo completo. A seleção dos estudos e a extração de seus dados foram realizadas de forma independente por dois pesquisadores. O tipo dos dados não permitiu a realização de metanálise. Resultados: Pelos critérios de inclusão e exclusão definidos, apenas 4 artigos foram selecionados. Prematuridade e asfixia perinatal foram utilizados como marcadores de near miss em todos os estudos. Observou-se que a razão de near miss neonatal foi entre 2.6 a 8 vezes maior que a de mortalidade neonatal. Conclusões: O desenvolvimento do conceito e critérios para o near miss neonatal parece ser uma ferramenta importante na avaliação dos cuidados prestados ao recém-nascido e o primeiro passo para se criar estratégias de manejo que contribuam na redução de mortalidade e de sequelas na vida futura dessas crianças / Abstract: Background: The concept of neonatal near miss has been proposed as a tool to assess the quality of care to neonates suffering any life-threatening condition. However, there are still no internationally accepted concepts or criteria to define or identify these cases of neonatal near miss. The purpose of this study is to perform a systematic review on markers that are able to identify cases of neonatal near miss and to predict neonatal mortality. Methods: Electronic searches were performed in the databases of Pubmed, Embase and Scielo, with no restriction of time period or language. For that, the term "neonatal near miss" was used alone or in association with terms related to neonatal morbidity and mortality and to the scores of neonatal severity. The first step of selection was based on the titles of articles, the second on their abstracts and the third on the full article. Two researchers independently performed the study selection and data extraction. The characteristics of data did not allow for proceeding with a metanalysis. Results: Using the predefined inclusion and exclusion criteria, only four articles were selected. Preterm and perinatal asphyxia were used as markers of near miss in all of them. It was observed that the neonatal near miss ratio was between 2.6 to 8 times higher than the neonatal mortality. Conclusions: The development of concept and criteria for neonatal near miss neonatal seems to be an important tool for the assessment of health care provided to neonates and the first step to build management strategies to contribute for decreasing mortality and sequelae in the future life of these children / Mestrado / Saúde Materna e Perinatal / Mestra em Ciências da Saúde