Sepse bacteriana é a maior causa de morbimortalidade na faixa etária pediátrica e neonatal. A detecção precoce do quadro séptico é difícil, devido os sinais iniciais da doença serem inespecíficos. A possibilidade da existência de exame laboratorial capaz de identificar precocemente quadros sépticos melhoraria o prognóstico desses pacientes. Várias proteínas de fase aguda foram estudadas como marcadores de infecção sendo a proteína C reativa (PCR) a mais utilizada. A procalcitonina (PCT), um pró-hormônio, encontra-se elevado precocemente em quadros sépticos em crianças e adultos. Estudo prospectivo com 14 crianças submetidas à cirurgia cardíaca com circulação extra-corpórea (CEC), com dosagens seriadas de procalcitonina e proteína C reativa, serviram como modelo de resposta inflamatória sistêmica sem infecção com dosagens antes da CEC, após a CEC no primeiro, segundo e terceiro dia após cirurgia, enquanto 14 crianças com sepse/choque séptico dosagens seriadas de PCT e PCR foram obtidas sequencialmente antes do tratamento antibioticoterápico e a cada dia até o terceiro dia. Em crianças sépticas a PCT demonstrou ser superior a PCR como marcador de sepse assim como para diferenciar quadros inflamatórios sistêmicos. / Bacterial sepsis is a major cause of morbidity and mortality in neonates and children. Early detection of bacterial sepsis is difficult because the first signs of this disease may be minimal or nonspecific. The availability of a laboratory test to accurately and rapidly identify septic neonates and children would be of great value in improving the outcome of these patients. Several acute-phase proteins have been used for the diagnosis of bacterial sepsis and C reactive protein (CRP) is the usual marker. It has been reported that the concentration of procalcitonin (PCT), a pro-hormone, is markedly higher in children and adults with sepsis. In a prospective study, 14 children were enrolled after cardiac surgery with cardiopulmonary bypass (CPB), these group represent the non infected children with inflammatory response. Blood samples were obtained before CPB, after CPB, on the first, second and third day after surgery. Another group with 14 children with sepsis or septic shock were enrolled, and blood samples were obtained before antibiotic start, on the first, second and third days. In septic children PCT concentration is a better diagnostic marker of sepsis and to differentiate inflammatory response than CRP.

Os genes de choque térmico groES e groEL de Caulobacter crescentus foram isolados utilizando-se os genes homólogos de E.coli como sonda e por sequenciamento demonstrou-se que estes genes estão organizados na forma de um operon em um fragmento de DNA de aproximadamente 2,5 kb, contendo também sua região regulatória. \"Northern blots\" de RNA total de células crescidas a 300C ou submetidas a choque térmico mostraram a presença de um único RNA de tamanho aproximado de 2,3kb, altamente induzido por choque térmico, permanecendo em altos níveis mesmo após longos períodos de choque térmico. Amostras de RNA total de células sincronizadas, de diferentes estágios do ciclo celular de Caulobacter, foram também analisadas mostrando que os níveis do mRNA groESL variam durante o ciclo, apresentando um máximo na célula prédivisional. Análises através de \"Western blot\" mostraram uma pequena variação nos níveis da proteína GroEL ao longo do ciclo celular, sendo os tempos 60 e 120 minutos, respectivamente, os pontos de mínimo e máximo acúmulo da proteína concordando com os resultados obtidos em \"N orthern blots\". O mesmo tipo de análise foi feito com extratos totais obtidos a partir uma população mista de células crescidas a 300C e submetidas a choque térmico, observando-se o acúmulo da proteína até 60 minutos depois do choque térmico, com aumento da ordem de 5 vezes nos níveis de GroEL, níveis estes que diminuem lentamente a partir deste ponto. Os inícios de transcrição foram determinados em experimentos de \"primer extension\" utilizando-se RNA total de células incubadas 300C e de células submetidas a diferentes condições de choque térmico. Dois possíveis sítios de início de transcrição foram determinados nas posições -119 e -88 do ATG da metionina iniciadora de groES, sendo as regiões -10 e -35 dos promotores correspondentes (P 1 e P2) identificadas. Somente a transcrição iniciando a partir de P2, que apresenta características de um promotor transcrito pelo σ32, aumenta durante o choque térmico. Fusões de transcrição com o vetor repórte placZ/290 e a região 5\' regulatória do operon groESL foram construídas para identificar as sequências responsáveis pelo controle por choque térmico e pelo controle temporal. Fusões de transcrição contendo deleções na região 5\' do operon mostraram que sequências a montante do promotor P2 não são necessárias para a indução por choque térmico ou para o controle temporal. Fusões de transcrição contendo mutações sítio-dirigidas na repetição invertida, encontrada a 3\' do promotor P2, antes do gene groES, revelaram que este elemento, conhecido como CIRCE, regula negativamente a expressão de groESL a 300C e mutações neste elemento levam à perda do controle temporal deste operon. / The heat shock genes groES and groEL of Caulobacter crescentus were isolated using the homologous genes of E.colí as a probe. DNA sequence analysis has shown that these genes are organized as an operan in a fragment of about 2.5kb, which includes the 5\' regulatory region. Northern blot analysis of total RNA from cells grown at 300C or heat shocked treated has shown the presence of a single mRNA species for groESL, of approximately 2.3kb in size, which presented increased leveis even after long periods of heat shock. Samples of total RNA from synchronized cells, corresponding to different stages of the Caulobaaer cell cycle, were also analysed, showing that the amount of groESL mRNA varies during the cycle, with maximum leveis in predivisional cells. Western blot analysis of GroEL leveis in Caulobaaer has shown that the amount of the protein decreases during the first 60 minutes of C.crescentus cell cycle and then starts to increase again. These results corroborate the data obtained with Northern blot analysis. A similar experiment was performed after exposing a mixed population of C.crescentus cells to different times of heat shock at 400C. Western blot of extracts of these cells showed a fivefold increase in the leveis of GroEL after 60 minutes of heat shock, which then begins to decrease. Primer extension experiments were performed using total RNA from cells incubated at normal growth temperature or after heat shock treatment. Two possible transcription start sites were determined at positions -119 and -88 from the ATG of the groES initiator methionine and the -10 and -35 regions of the corresponding promoters (P 1 and P2) were identified. Only trancription initiating from the P2 promoter, which has caracteristics of a σ32 promoter, I ncreases during heat shock .Transcription fusions with the reporter vector placZ/290 and the 5\' regulatory region of the groESL operan were contructed in order to identify the sequences responsible for heat shock and cell cycle contral. Deletion analysis in the 5\' region of the operon showed that no sequences upstream of the P2 promoter are necessary for heat shock induction or for temporal contral. Site-directed mutagenesis in the inverted repeat found 3\' of the P2 promoter, in front of the groES gene, revealed that this element, also known as CIRCE, negatively regulates groESL expression at 300C and mutations in it lead to loss of temporal control of this heat shock operon.

A campanha dos refratários magnesianos aplicados como revestimento de trabalho de panelas de aciaria depende da soma de diversos fatores como resistência à corrosão, resistência à oxidação do carbono, estabilidade termomecânica, entre outros. A concepção microestrutural do refratário pode influenciar de forma benéfica ou deletéria no desempenho do refratário in situ. Nesta tese de doutorado os refratários magnesianos comerciais de panela de aciaria foram estudados sob três diferentes aspectos: redução da oxidação prematura do carbono, formação da fase espinélio de alumina e magnésio e resistência ao choque térmico e ao dano por choque térmico. Para reduzir a oxidação precoce do carbono foi desenvolvido um coating cerâmico que atua como uma eficiente barreira física, reduzindo o contato do oxigênio da atmosfera de aquecimento com o carbono presente no refratário. Como resultado reduz-se a oxidação prematura do carbono e eleva-se a vida útil do revestimento. A formação da fase espinélio de magnésia e alumina também influencia o desempenho termomecânico destes refratários, principalmente devido ao incremento volumétrico decorrente de sua formação. Nesta tese foram estudados os mecanismos de formação desta fase in situ, demonstrando experimentalmente o caminho preferencial que leva à formação desta fase mineralógica. O comportamento termomecânico dos refratários magnesianos foi determinado em função da resistência ao choque térmico (parâmetros R, R\'\'\') e quanto à resistência ao dano por choque térmico (parâmetro R\'\'\'\' e Rst). Estes parâmetros foram correlacionados com as respectivas características microestruturais destes refratários. Os resultados apresentados por esta tese de doutorado compõe uma importante ferramenta técnica para as indústrias produtoras de aço e de refratários por fornecer subsídio técnico e científico para fundamentar alterações em refratários já existentes e colaborar com o desenvolvimento de novos refratários de engenharia com elevado desempenho e maior vida útil. / The campaign of magnesium based refractories of steel ladles depends on the sum of many factors, such as corrosion resistance, carbon oxidation resistance, thermomechanical stability, among others. The microstructural conception of the refractory can influence the performance in situ in a beneficially or deleterious way. In this doctoral thesis, the commercial magnesium refractory of steel ladles were studied under three different aspects: reducing the premature oxidation of carbon present into the refractory matrix, formation of the spinel MgAl2O4 and the resistance to thermal shock and thermal shock damage. To reduce the premature oxidation of carbon, it was developed a ceramic coating that acts as an effective physical barrier, reducing the contact of the atmosphere\'s oxygen with the carbon in the refractory. As a result, the premature oxidation of carbon was reduced and the refractory system\'s lifespan increased. The formation of the MgAl2O4 spinel also influences the thermomechanical performance of these refractories, mainly due to increase of volume due to its formation. In this thesis were studied the mechanisms of formation of this phase in situ, experimentally showing the mechanism that leads to the formation of this mineral phase. The thermomechanical behavior of refractories MgO-C, Al2O3-MgO-C and MgO-Al2O4-C was determined according to the thermal shock resistance (R, R\'\'\' parameters) and the resistance to thermal shock damage (R\'\'\'\' and Rst parameters). Those parameters were correlated with their respective microstructural characteristics of refractories. The results presented in this doctoral thesis make up an important technical tool for steelworks and refractory industries by providing technical and scientific aid to support changes in existing refractories and collaborate with the development of new refractory engineering with higher performance and longer life.

by Lam Wai Yip. / Thesis (M.Phil.)--Chinese University of Hong Kong, 1995. / Includes bibliographical references (leaves 184-195). / Contents --- p.I - IV / Abstract --- p.V / Abbreviations --- p.VI / List of Tables and Figures --- p.VII - XV / Chapter Chapter One: --- Introduction / Part I / Chapter 1.1 --- Human genome project --- p.1 / Chapter 1.2 --- Progress of human genome project --- p.2 / Chapter 1.3 --- Human heart cDNA sequencing --- p.3 / Chapter 1.4 --- Significance of the human heart cDNA library project --- p.5 / Chapter 1.5 --- Homology search tools for cDNA sequences alignment --- p.5 / Part II / Chapter 1.6 --- Investigation of a human heart cDNA clone A076 --- p.7 / Chapter 1.7 --- General introduction of Heat Shock Proteins (HSPs) --- p.7 / Chapter 1.7.1 --- Definition of HSP --- p.8 / Chapter 1.7.2 --- Discovery of HSP --- p.10 / Chapter 1.7.3 --- Transcriptional regulation of heat shock genes --- p.11 / Chapter 1.7.4 --- Nomenclature of HSPs --- p.13 / Chapter 1.7.5 --- HSP110 --- p.13 / Chapter 1.7.6 --- HSP90 --- p.14 / Chapter 1.7.7 --- HSP70 --- p.15 / Chapter 1.7.8 --- HSP60 --- p.17 / Chapter 1.7.9 --- Ubiquitin - HSP8 --- p.19 / Chapter 1.7.10 --- HSP27 --- p.20 / Chapter 1.8 --- The theme of this thesis --- p.28 / Chapter Chapter Two: --- Method and Materials / Chapter 2.1 --- The human heart cDNA library --- p.29 / Chapter 2.2 --- Plating out the cDNA library --- p.29 / Chapter 2.3 --- DNA amplification --- p.31 / Chapter 2.4 --- DNA sequencing reaction - Cycle sequencing reaction --- p.32 / Chapter 2.5 --- Operation of the A.L.F. DNA sequencer --- p.33 / Chapter 2.5.1 --- Preparation of the gel cassette --- p.33 / Chapter 2.5.2 --- Preparation of the acrylamide gel --- p.34 / Chapter 2.5.3 --- Fitting the gel cassette into the electrophoresis unit --- p.35 / Chapter 2.5.4 --- Settings of electrophoresis --- p.36 / Chapter 2.6 --- Comparison of DNA sequences to databases --- p.37 / Chapter 2.7 --- Programming for sending cDNA sequences to NCBI --- p.38 / Chapter 2.8 --- Storage of sequence data --- p.39 / Chapter 2.9 --- Synthesis and purification of primers --- p.40 / Chapter 2.10 --- Connection of cDNA clones using Polymerase Chain Reaction (PCR) --- p.41 / Chapter 2.11 --- Purification of DNA fragment from agarose gels by GENECLEAN´ёØ --- p.42 / Chapter 2.12 --- "Preparation of competent Escherichia coli for transformation (Hanahan, 1986)" --- p.43 / Chapter 2.13 --- Transformation of Plasmid into Competent Escherichia coli --- p.44 / Chapter 2.14 --- "Small scale preparation of plasmid DNA (Sambrook et al.,1989" --- p.45 / Chapter 2.15 --- Large scale plasmid preparation by QIAGEN´ёØ --- p.46 / Chapter 2.16 --- DNA sequencing reaction - Unicycle sequencing reaction --- p.48 / Chapter 2.17 --- Synthesis of Radiolabeled DNA probe --- p.49 / Chapter 2.18 --- "Isolation of genomic DNA from human blood cells (Thomas A. Ciulla, 1988)" --- p.51 / Chapter 2.19 --- Southern blotting --- p.52 / Chapter 2.20 --- Prehybridization and hybridization procedure for Southern blot analysis --- p.54 / Chapter 2.21 --- "AGPC-RNA extraction method (Chomczynski and Sacchi 1987, modifed)" --- p.56 / Chapter 2.22 --- Electrophoresis of RNA through gels containing formaldehyde --- p.58 / Chapter 2.23 --- First-Strand cDNA synthesis --- p.59 / Chapter 2.24 --- Use of T7 RNA polymerase to direct expression of the cloned hsp27b gene (A076&B490) --- p.60 / Chapter 2.25 --- "Sodium Dodecyl Sulphate Polyacrylamide Gel Electrophoresis (Laemmli, 1970)" --- p.61 / Chapter 2.26 --- Staining of the Gel by the Commassie Blue Method --- p.63 / Chapter Chapter Three: --- Results / Part I / Chapter 3.1 --- Sample results of Sequencing a few clones --- p.64 / Chapter 3.2 --- A Catalogue of 497 cDNA clones obtained from human heart cDNA sequencing --- p.71 / Chapter 3.3 --- Submission of novel sequences to genbank --- p.81 / Chapter 3.4 --- A Catalogues of genes that are expressed in the adult human heart --- p.83 / Chapter 3.5 --- The use of the programmes to assist the sending and receiving of sequence data E-mail message --- p.90 / Chapter 3.5.1 --- The use of the SENDMAIL.EXE programme --- p.91 / Chapter 3.5.2 --- "The use of the EDITBLN.EXE, ALLFILE.EXE and DATABASE.EXE" --- p.95 / Part II / Chapter 3.6 --- DNA sequence profiles of cDNA clones A076 and B490 --- p.105 / Chapter 3.7 --- Ligation of cDNA clones using Polymerase Chain Reaction (PCR) --- p.112 / Chapter 3.8 --- Cloning of the PCR product A076&B490 into the pAED4 expression vector --- p.117 / Chapter 3.9 --- Unicycle sequencing of the subcloned insert A076&B490 --- p.121 / Chapter 3.10 --- Southern hybridization of hsp27b (A076&B490) --- p.125 / Chapter 3.11 --- Results of RT-PCR and PCR --- p.127 / Chapter 3.12 --- Expression pAED4-A076&B490 in E.coli --- p.133 / Chapter Chapter Four: --- Discussion / Part I / Chapter 4.1 --- EST characterization --- p.138 / Chapter 4.2 --- Further investigation --- p.140 / Chapter 4.3 --- Disadvantage of randomly picked cDNA sequencing --- p.141 / Chapter 4.4 --- Problem of GenBank database searching --- p.141 / Part II / Chapter 4.5 --- The DNA sequence of A076 and B490 --- p.143 / Chapter 4.6 --- Ligation of HSP27B by using PCR --- p.144 / Chapter 4.7 --- Analysis of the DNA and protein sequence ofhsp27b (A076&B490) --- p.145 / Chapter 4.8 --- Southern hybridization of human hsp27b --- p.153 / Chapter 4.9 --- "RT-PCR and PCR of first strand cDNA with primers A076-ATG, A076-mid and oligo dT" --- p.153 / Chapter 4.10 --- Expression of human hsp27b --- p.154 / Chapter 4.11 --- The possible roles of human hsp27b --- p.156 / Chapter 4.12 --- Further analysis --- p.160 / Appendix I --- p.161-182 / Appendix II --- p.183 / References --- p.184-195

Chen, Chao. / Thesis (M.Phil.)--Chinese University of Hong Kong, 2009. / Includes bibliographical references (leaves 43-46). / Abstract also in Chinese. / Abstract --- p.i / Acknowledgement --- p.iii / Chapter 1 --- Introduction --- p.1 / Chapter 2 --- Preliminaries --- p.7 / Chapter 3 --- The mathematical formulation of the problem and main results --- p.11 / Chapter 4 --- Reformulation of the problem --- p.17 / Chapter 5 --- Proof of the main theorems --- p.23 / Chapter 5.1 --- Proof of uniqueness --- p.23 / Chapter 5.2 --- Proof of non-existence --- p.31 / Chapter 6 --- Work in future --- p.40 / Chapter 7 --- Appendix --- p.41 / Bibliography --- p.43

Le choc septique est défini par une hypotension persistante malgré un remplissage vasculaire adéquat en présence d’une réponse inflammatoire systémique suite à une infection. Il est responsable de 10% des admissions en réanimation et malgré des progrès thérapeutiques constants, la mortalité liée au sepsis varie entre 30% et 60% dans les cas de choc septique. Dans 50% des cas, le choc septique est associé à une insuffisance surrénale relative ce qui diminue la probabilité de survie des patients. Les patients sont alors traités avec de l’hydrocortisone et de la fludrocortisone, mais ce traitement est très controversé. Pour la première fois, nous avons pu mettre au point et valider une technique de quantification de la fludrocortisone plasmatique après une prise de 50 μg. Cette technique a pu ensuite être utilisée pour l’obtention de l’étude pharmacocinétique/pharmacodynamique de la fludrocortisone chez le volontaire sain et le patient septique avec insuffisance surrénale relative. Enfin, nous avons étudié la distribution et l’élimination de cette molécule chez la souris saine et deux modèles de sepsis. Les paramètres pharmacocinétiques montrent que la demi-vie de la fludrocortisone est d’environ 1 h, avec un délai d’absorption d’environ 50 minutes. Nos travaux ont permis de mettre en évidence qu’il existe deux populations de patients : les absorbants et les non-absorbants la fludrocortisone, qui représentent 30 % des patients testés, ce qui pourrait être à l’origine de la controverse sur les effets bénéfiques de cette molécule sur la survie des patients. Cependant nous n’avons pu mettre en évidence aucun effet hémodynamique de cette molécule sur les patients septiques. / The septic shock is defined by persistent hypotension despite fluid resuscitation with systemic inflammation due to infection. This is the cause of 10% of the admission in intensive care unit. Despite steady progress in therapeutics, the mortality of patients with sepsis varies between 30% to 60% for a septic shock. In 50%, the septic shock is associated to relative adrenal insufficiency which decrease survival probability of the patients. The patients receive hydrocortisone and fludrocortisone but this treatment is still controversial. For the first time, we developped and validated a quantification method of low concentration fludrocortisone in plasma. This method were used for the pharmacokinetic/pharmacodynamic study of fludrocortisone in healthy volunteers and patients with septic shock associated with relative adrenal insufficiency. Then we studied the distribution and elimination of this molecule in two mice models of sepsis. The pharmacokinetic parameters show that the half-life of fludrocortisone is about 1h and the delay of absorption is about 50min. Our study shows two groups of patients : absorbent patients and non-absorbent patients which have no detectable fludrocortisone concentrations in plasma. This population represents 30% of the population. This could be the reason of the controversial results. No hemodynamic effetc were found in patients with septic shock due to fludrocortisone after low-dosage administration.

Healthy cells continuously produce proteins to accomplish various functions, including immune responses, reaction catalyses, transmitting signals, structural supports and molecular transport. Protein needs to fold correctly into three-dimensional shape in order to function well, using the information stored in the amino acid sequence. Proteins may fold spontaneously in solution, but the situation in living cells can be complicated. Cells are filled with nucleic acids and proteins thus they are usually in a stressful environment. Under such circumstances, proteins can be unfolded or misfolded, leading to non-function or even toxicity. Cells employ molecular chaperones to solve protein folding problems. Among the many types of chaperones, heat shock proteins of approximately 70KDa (Hsp70s) act as a hub, because its functions feed into other members of the chaperone network. Hsp70s help to stabilize nascent polypeptides, facilitate cross-membrane translocation, refold the misfolded proteins, and guide non-recoverable denatured proteins to degradation. Hsp70s have explicit role in cancer cells, because elevated metabolism requires increased Hsp70s’ activity to avoid apoptosis and ensure survival. Hsp70s also help to prevent neurodegenerative diseases, and decreased level of Hsp70s is found in age-related symptoms and diseases. In general, it is well understood what Hsp70s can do, but little is known how Hsp70s do the job. Hsp70s are present and highly conserved in all living species, comprised of two structural domains. The nucleotide binding domain (NBD) binds and hydrolyzes ATP, while the substrate binding domain (SBD) binds and releases hydrophobic peptides. Although Hsp70s are known to act as an allosteric molecular machine, the details are elusive about how the domains are regulated. Besides, how nucleotide binding affects the Hsp70s’ function, and how ATP hydrolysis is performed are also unknown. In this thesis, I first introduce salient background on the Hsp70 subject, then explore previously unclear aspects of Hsp70 allosteric regulation and catalytic activity in two chapters describing my dissertation research, and finally conclude with my perspectives on future directions.

The main objectives of this study are to determine how various physical and chemical properties of geologic samples can be investigated by Fourier Transform InfraRed (FTIR) spectral analyses, and determine how each of these individual properties uniquely alter the mid-infrared spectrum. Of particular interest is how extraterrestrial samples differ (spectrally) from terrestrial samples, and how such findings can be applied to current and future missions to airless planetary bodies (such as Diviner Lunar Radiometer, aboard the Lunar Reconnaissance Orbiter, and the Mercury Thermal Radiometer on BepiColombo). As such, a range of geological samples have been analysed including terrestrial rocks (anorthosite, granite, grabbro etc.), mineral standards (common rock-forming minerals), lunar meteorites (from Miller Range, Antarctica), and Apollo 14, 15, and 16 soils. A new technique to analyse such samples has been developed and implemented as part of this study: FTIR spectral imaging of unconsolidated samples (powders and soils) to obtain modal mineralogy estimates. Such estimates are comparable to QEMSCAN analyses and spot point counting of the same samples. This is particularly relevant for the non-destructive analysis of Apollo soil samples (bulk and sieved fractions). Individual spectra of polished terrestrial and extraterrestrial samples have been obtained in preparation for the creation of a spectral database. Such samples also have coupled chemical composition information via Electron Probe MicroAnalysis (EPMA). To have a spectrum and an associated chemical composition for each mineral in a database is unique compared to other spectral databases. Analyses of lunar meteorites resulted in an understanding of how shock (caused by hypervelocity impacts) alters the physical and spectral properties of lunar minerals. FTIR microscopy of individual minerals and phases in the meteorites were coupled with optical and cathodoluminescence (CL) imaging to identify the level of shock obtained by each mineral and phase. The FTIR reflectance bands of plagioclase merge with increasing shock pressure until a single, low-reflectance broad peak is displayed by the most highly shocked plagioclase (>45 GPa), and a dark-red colour is present in CL images. FTIR and QEMSCAN analyses of Apollo regolith samples have provided an understanding of the spectral effects of bulk mineralogy, maturity (a measure of the time spent at the lunar surface), grain size, and mineral chemistry. Using such information, the modal mineralogy of each sample has been estimated, one of which had not previously been analysed for its modal mineralogy. Samples from the same Apollo missions present similar spectral features, meaning FTIR spectroscopy can be used to identify the origin of lunar soils. A weak correlation in maturity with a spectral feature termed the Christiansen Feature has been found for lunar samples. Related to maturity, FTIR spectra of individual agglutinates (a product of space weathering) have been obtained and the spectral properties of agglutinates (decreased %Reflectance values of the region sensitive to geological materials) resemble those of highly mature lunar soils.

Made available in DSpace on 2014-06-11T19:22:21Z (GMT). No. of bitstreams: 0 Previous issue date: 2002Bitstream added on 2014-06-13T19:48:37Z : No. of bitstreams: 1 meletti_jfa_me_botfm.pdf: 304572 bytes, checksum: 2aa2c2ff89fef69f6ae6c470cdfdfd03 (MD5) / Diversos modelos experimentais têm sido utilizados para ilustrar as alterações hemodinâmicas e metabólicas que ocorrem durante o choque hemorrágico. O objetivo da pesquisa é observar os comportamentos hemodinâmicos e metabólicos que acontecem em um modelo seqüencial e progressivo de choque hemorrágico em cão, verificando quais índices alteram-se mais precocemente. Metodologia: O estudo foi realizado em 13 cães sob anestesia intravenosa total com pentobarbital sódico, em normoventilação e previamente esplenectomizado. Os animais não foram hidratados e a velocidade do sangramento foi ditada pela pressão arterial em que o animal se encontrava. Os atributos estudados foram divididos em hemodinâmicos (freqüência cardíaca – FC, pressão arterial média – PAM, índice de resistência vascular sistêmica – IRVS, índice sistólico – IS, índice cardíaco – IC, índice de choque – I. choque, índice de trabalho sistólico do ventrículo esquerdo – ITSVE, pressão capilar pulmonar – PCP, pressão venosa central – PVC) e metabólicos (saturação venosa mista – SvO2, pressão venosa de oxigênio – PvO2, transporte de oxigênio – DO2, consumo de oxigênio – VO2, Extração de oxigênio – TEO2, lactato sérico – Lactato). A coleta de dados e os atributos foram estudados em 6 momentos distintos: M1 – controle, M2 – sangramento de 10% da volemia calculada para o animal, M3 – sangramento de... / Many experimental models have been used to elucidate hemodynamic and metabolic alterations that occur during the hemorrhagic shock. The aim of this research is to observe hemodynamic and metabolic behaviours present in a sequential and progressive model of hemorrhagic shock in dogs, verifying which indexes change more precociously. Methods: This study was performed in 13 dogs under total intravenous anesthesia with sodic pentobarbital, with standart ventilation and formerly splenectomized. The animals were not hydrated and the bleeding velocity was according to the blood pressure of the animal. The studied parameters were divided into hemodynamics (heart rate – HR, mean arterial blood pressure – MAP, sistemic vascular resistance index – SVRI, sistolic index – SI, cardiac index – CI, shock index – S index, sistolic function of the left ventricle index – SFLVI, pulmonary capillary pressure – PCP, central venous pressure – CVP) and metabolics (mixed venous saturation – MVS, venous oxigen pressure – VOP, oxygen transport – OT, oxygen consumption – OC, oxygen extraction – OE and seric lactate). The results and parameters were evaluated in 6 different moments: M1 – control, M2 – bleeding of 10% of calculated volemic for the animal, M3 – increase of 10% in bleeding, M4 – increase of 10% in bleeding, M5 - increase... (Complete abstract, click electronic access below)

Sepse bacteriana é a maior causa de morbimortalidade na faixa etária pediátrica e neonatal. A detecção precoce do quadro séptico é difícil, devido os sinais iniciais da doença serem inespecíficos. A possibilidade da existência de exame laboratorial capaz de identificar precocemente quadros sépticos melhoraria o prognóstico desses pacientes. Várias proteínas de fase aguda foram estudadas como marcadores de infecção sendo a proteína C reativa (PCR) a mais utilizada. A procalcitonina (PCT), um pró-hormônio, encontra-se elevado precocemente em quadros sépticos em crianças e adultos. Estudo prospectivo com 14 crianças submetidas à cirurgia cardíaca com circulação extra-corpórea (CEC), com dosagens seriadas de procalcitonina e proteína C reativa, serviram como modelo de resposta inflamatória sistêmica sem infecção com dosagens antes da CEC, após a CEC no primeiro, segundo e terceiro dia após cirurgia, enquanto 14 crianças com sepse/choque séptico dosagens seriadas de PCT e PCR foram obtidas sequencialmente antes do tratamento antibioticoterápico e a cada dia até o terceiro dia. Em crianças sépticas a PCT demonstrou ser superior a PCR como marcador de sepse assim como para diferenciar quadros inflamatórios sistêmicos. / Bacterial sepsis is a major cause of morbidity and mortality in neonates and children. Early detection of bacterial sepsis is difficult because the first signs of this disease may be minimal or nonspecific. The availability of a laboratory test to accurately and rapidly identify septic neonates and children would be of great value in improving the outcome of these patients. Several acute-phase proteins have been used for the diagnosis of bacterial sepsis and C reactive protein (CRP) is the usual marker. It has been reported that the concentration of procalcitonin (PCT), a pro-hormone, is markedly higher in children and adults with sepsis. In a prospective study, 14 children were enrolled after cardiac surgery with cardiopulmonary bypass (CPB), these group represent the non infected children with inflammatory response. Blood samples were obtained before CPB, after CPB, on the first, second and third day after surgery. Another group with 14 children with sepsis or septic shock were enrolled, and blood samples were obtained before antibiotic start, on the first, second and third days. In septic children PCT concentration is a better diagnostic marker of sepsis and to differentiate inflammatory response than CRP.