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Vasconcelos, P. R. L. de. "Hepatic metabolism during sepsis." Thesis, University of Oxford, 1987. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.233530.
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Lattuada, Marco. "Effect of Ventilatory Support on Abdominal Fluid Balance in a Sepsis Model." Doctoral thesis, Uppsala universitet, Klinisk fysiologi, 2013. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-207218.
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In patients affected by acute respiratory failure or acute respiratory distress syndrome (ARDS) the leading cause of death is failure of different vital organs other than the lungs, so called multiple organ dysfunction syndrome (MODS). The abdominal organs have a crucial role in the pathogenesis of this syndrome. There is a lack of knowledge regarding the mechanisms by which mechanical ventilation can affect the abdominal compartment. One hypothesis is that mechanical ventilation can interfere with abdominal fluid balance causing edema and inflammation. We addressed the question whether different levels of ventilatory support (mechanical ventilation with different levels of positive end-expiratory pressure, PEEP, and spontaneous breathing with or without PEEP) can influence abdominal edema and inflammation in both healthy and endotoxin-exposed animals. The effect on lymphatic drainage from the abdomen exerted by different degrees of ventilatory support was evaluated (paper I). We demonstrated that endotoxin increases abdominal lymph production, that PEEP and mechanical ventilation increase lymph production but also impede lymphatic drainage; spontaneous breathing improves lymphatic drainage from the abdomen. By adapting a non-invasive nuclear medicine imaging technique and validating it (paper II), we have been able to evaluate extravascular fluid accumulation (edema formation) in the abdomen over time (paper III) demonstrating that edema increases during endotoxemia, mimicking a sepsis-like condition, and that spontaneous breathing, compared to mechanical ventilation, reduces extravascular fluid. Pro-inflammatory cytokines TNF-α and IL-6 in intestinal biopsies are reduced during spontaneous breathing compared to mechanical ventilation. Abdominal edema results in increased intra-abdominal pressure (IAP): in paper IV we analyzed the effect of increased intra-abdominal pressure on the respiratory system. Pulmonary shunt fraction increased with high IAP both in healthy and LPS animals, resulting in decreased level of oxygenation. These changes are only partially reversible by reducing IAP. In conclusion, mechanical ventilation is a life-saving tool but the possible side effect at the extra-pulmonary level should be considered, and the introduction of some degree of spontaneous breathing when clinically possible is a suggested choice.
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Bleszynski, Michael Sean. "Impact of open abdomen and Vacuum Assisted Closure Device in surgical abdominal sepsis." Thesis, University of British Columbia, 2017. http://hdl.handle.net/2429/61001.
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Introduction: Surgical abdominal sepsis has traditionally been managed with by a single staged procedure, otherwise known as primary abdominal closure (PAC). An on demand laparotomy may be performed for post-operative clinical deterioration. Open abdomen and a planned re-laparotomy with vacuum assisted closure (VAC) is an alternate method to single staged procedure. Inflammatory cytokines can potentially help stratify severity of sepsis and guide surgical management. The objective of the study was to identify if inflammatory cytokines could differentiate between PAC and VAC. Secondary objectives were to see if cytokines could predict mortality and characterize longitudinal cytokine profiles during open abdomen management. Severity of disease between surgical groups was compared using the Acute Physiology and Chronic Health Assessment (APACHE)-IV predictive mortality rate (PMR) calculator.
Methods: Prospective case series between December 2011 to June 2013. Patients were included if they met criteria of severe abdominal sepsis/septic shock requiring urgent source control laparotomy (SCL). Blood and peritoneal samples were obtained pre- and post-operatively at primary SCL in patients who underwent PAC and VAC management. Peritoneal fluid (PF) samples were obtained once the peritoneum was entered. Blood and peritoneal samples were obtained for re-look laparotomies in the VAC group. Samples were centrifuged within 1 hour and stored at -70 degrees Celsius. Samples were analyzed with a Human Cytokine 30-plex Panel and concentrations were reported as pg/ml.
Results: 12 patients were included (4 PAC and 8 VAC). PF cytokine concentrations of IL 6, IL-17, IL-5 and HGF were significantly higher in VAC compared to PAC. Peritoneal fluid at primary SCL did not differentiate between survivors and non-survivors. Pre-operative serum RANTES was significantly elevated in survivors compared to non-survivors. Pre operative serum VEGF, IL-1b, FGF-b, IL-5, IL-4, IL-7 and post-operative serum VEGF, IL-7 differentiated between VAC survivors and non-survivors at second SCL.
Conclusion: VAC management was utilized in patients with elevated peritoneal cytokines compared to single staged procedures. Increased peritoneal inflammatory cytokine concentrations in VAC represent a more severe degree of local sepsis. Pro and anti-inflammatory cytokines are both elevated in the early and late phases of surgical abdominal sepsis.Medicine, Faculty of
Surgery, Department of
Graduate
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Perry, Sara Elizabeth. "The phenotypic characterization of the monocyte in human sepsis." Thesis, University of Liverpool, 2003. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.268902.
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Sartelli, M., F. M. Abu-Zidan, L. Ansaloni, M. Bala, M. A. Beltran, W. L. Biffl, F. Catena, et al. "The role of the open abdomen procedure in managing severe abdominal sepsis: WSES position paper." BioMed Central, 2015. http://hdl.handle.net/10150/610338.
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The open abdomen (OA) procedure is a significant surgical advance, as part of damage control techniques in severe abdominal trauma. Its application can be adapted to the advantage of patients with severe abdominal sepsis, however its precise role in these patients is still not clear. In severe abdominal sepsis the OA may allow early identification and draining of any residual infection, control any persistent source of infection, and remove more effectively infected or cytokine-loaded peritoneal fluid, preventing abdominal compartment syndrome and deferring definitive intervention and anastomosis until the patient is appropriately resuscitated and hemodynamically stable and thus better able to heal. However, the OA may require multiple returns to the operating room and may be associated with significant complications, including enteroatmospheric fistulas, loss of abdominal wall domain and large hernias. Surgeons should be aware of the pathophysiology of severe intra-abdominal sepsis and always keep in mind the option of using open abdomen to be able to use it in the right patient at the right time.
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Januszkiewicz, Anna. "In vivo protein synthesis determinations in human immune cells /." Stockholm, 2005. http://diss.kib.ki.se/2005/91-7140-219-5/.
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Cajander, Sara. "Dynamics of Human Leukocyte Antigen-D Related expression in bacteremic sepsis." Doctoral thesis, Örebro universitet, Institutionen för medicinska vetenskaper, 2017. http://urn.kb.se/resolve?urn=urn:nbn:se:oru:diva-56125.
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Monocytic human leukocyte antigen-D related (mHLA-DR) expression determined by flow cytometry has been suggested as a biomarker of sepsisinduced immunosuppression. In order to facilitate use of HLA-DR in clinical practice, a quantitative real-time PCR technique measuring HLA-DR at the transcription level was developed and evalutated. Levels of HLA-DR mRNA correlated to mHLADR expression and were robustly measured, with high reproducibility, during the course of infection. Dynamics of mHLA-DR expression was studied during the first weeks of bloodstream infection (BSI) and was found to be dependent on the bacterial etiology of BSI. Moreover, mHLA-DR was shown to be inversely related to markers of inflammation. In patients with unfavourable outcome, sustained high C-reactive protein level and high neutrophil count were demonstrated along with low mHLA-DR expression and low lymphocyte count. This supports the theory of sustained inflammation in sepsis-induced immunosuppression. The association between mHLA-DR and bacterial etiology may be linked to the clinical trajectory via differences in ability to cause intractable infection. Staphylococcus aureus was the dominating etiology among cases with unfavourable outcome. With focus on patients with S. aureus BSI, those with complicated S. aureus BSI were found to have lower HLA-DR mRNA expression during the first week than those with uncomplicated S. aureus BSI. If these results can be confirmed in a larger cohort, HLA-DR measurement could possibly become an additional tool for early identification of patients who require further investigation to clear infectious foci and achieve source control. In conclusion, PCR-based measurement of HLA-DR is a promising method for measurements of the immune state in BSI, but needs further evaluation in the intensive care unit setting to define the predictive and prognostic value for deleterious immunosuppression. The etiology of infection should be taken into consideration in future studies of translational immunology in sepsis.
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González, Lisorge Ada. "Estudio sobre la sepsis grave de origen abdominal. Utilidad de la procalcitonina y otros marcadores pronósiticos." Doctoral thesis, Universidad de Murcia, 2013. http://hdl.handle.net/10803/128673.
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INTRODUCCIÓN: La sepsis es una de las principales causas de morbimortalidad en las unidades de cuidados intensivos (UCIs). La sepsis grave de origen abdominal es uno de los cuadros más frecuentes en las UCIs Posquirúrgicas. Su mortalidad es elevada y oscila entre 40% y el 70% según las series. Sin embargo, es un cuadro que suele tener poco protagonismo en la literatura científica. Los biomarcadores son elementos fundamentales para el diagnóstico, seguimiento y pronóstico de la sepsis. Uno de los biomarcadores más estudiados en las últimas décadas ha sido la procalcitonina. Muchos autores consideran que su cinética se relaciona con la evolución, el pronóstico o con un tratamiento correcto de diversas patologías. Las escalas de gravedad, como el Acute Physiology And Chronic Health Evaluation II (APACHE II) y la escala Sequential Organ Failure Assessment (SOFA) tienen utilidad pronóstica en pacientes críticos. El APACHE II no es específico para pacientes sépticos, pero identifica pacientes con gravedad aumentada. La escala SOFA es un sistema específico de valoración de la gravedad del paciente séptico. Se diseñó para evaluar la afectación orgánica secundaria a la sepsis, aunque posteriormente, también se ha empleado con fines pronósticos. El objetivo principal de esta Tesis Doctoral es identificar los factores que influyen en la evolución (Éxitus o supervivencia) de los pacientes con sepsis grave de origen abdominal. Analizamos la utilidad de la procalcitonina como marcador de supervivencia y evaluamos si las escalas de gravedad, APACHE II y SOFA, permiten predecir la mortalidad de estos pacientes. MATERIAL Y MÉTODO: Se incluyeron en el estudio todos los pacientes con diagnóstico de sepsis grave de origen abdominal ingresados en una Unidad de Cuidados Críticos Posquirúrgicos entre los años 2007 y 2008. Se recogieron datos demográficos, los valores de la procalcitonina en los días primero, tercero y séptimo de ingreso y se calcularon las puntuaciones de las escalas APACHE II y SOFA al ingreso y de la escala SOFA en los días tercero y séptimo. RESULTADOS: Estudiamos 69 pacientes. La mortalidad de nuestra serie fue del 23,19% (IC95%: 13,19;33,19%). La edad media de estos pacientes fue 64,94 años (IC95%: 61;69 años). La mayoría de los pacientes (57,97%) presentó sepsis de origen comunitario (p<0,05). La patología previa más frecuente fue la hipertensión arterial (49,27%; IC95%: 37,27;61,27%), seguida de la diabetes mellitus (24,63%; IC95%: 14,43;34,83%) El foco de infección más frecuente fue el intestino grueso (40,57%; IC95%: 28,57;52,57%). La puntuación APACHE II media al ingreso fue de 16,43 puntos (IC95%: 14,95;17,91puntos) y fue superior entre los Éxitus (p<0,00001). La puntuación SOFA media al ingreso fue de 6,46 puntos (IC95%: 5,71;7,2puntos). En el estudio de regresión logística binario, los dos factores que más influyeron en la mortalidad de estos pacientes fueron la edad y el ascenso de las puntuaciones de la escala SOFA entre los días primero y séptimo. La procalcitonina presentó una dinámica diferente entre Éxitus, cuyos valores se mantuvieron elevados y Supervivientes, en los que los valores disminuyeron con el tiempo (p<0,05). El valor de procalcitonina que mejor identificó pronóstico fue el del día séptimo (AUC-ROC 0,768), niveles mayores o iguales a 3,5ng/mL detectaron mortalidad con una sensibilidad del 55% y una especificidad del 73%. CONCLUSIONES: En nuestra serie de pacientes con sepsis grave posquirúrgica de origen abdominal, el valor de procalcitonina en el séptimo día de observación se relaciona con el pronóstico. El ascenso en la puntuación de la escala SOFA entre los días primero y séptimo, junto con la edad, fueron los elementos que mejor identificaron el pronóstico de los pacientes con sepsis grave de origen abdominal.Sepsis represents a major cause of morbidity and mortality in Intensive Care Units (ICU). Severe sepsis of intraabdominal origin is a frequent pathology in Surgical ICU. It presents a high mortality rate, 40% in some series, but even 70% has been reported. Nevertheless, it has little prominence in scientific literature. Biomarkers are main elements in the battery of diagnostic, monitoring and prognostic tests. Procalcitonin has been one of the most studied markers in lasts decades. Many authors consider its dynamics well related with evolution, outcome or a correct treatment of different pathologies. Severity scales, such as Acute Physiology and Chronic Health Evaluation II (APACHE II) and Sequential Organ Failure Assessment score (SOFA) are some of the prognostic tools used in critical patients. APACHE II is not specific for septic patients, but has utility identifying patients with augmented severity. SOFA score is a specific system for severity assessment in septic patients. It identifies and allows the monitoring of organ failure secondary to sepsis. Initially it was design for the evaluation of organ dysfunction during the ICU stay of these patients, though its prognostic value has also been proved. The purpose of this Doctoral Thesis is to study which elements characterize patients with severe sepsis of intraabdominal origin, and try to identify which factors can influence the outcome of these patients. We assess the utility of procalcitonin and severity scores, APACHE II and SOFA, as outcome predictors in patients with severe sepsis of intraabdominal origin. PATIENTS AND METHOD: We included all patients admitted in a Surgical Intensive Care Unit with the diagnosis of severe sepsis of intraabdominal origin, between 2007 and 2008. We recorded demographic data, procalcitonin levels at days one, three and seven, and APACHE II and SOFA scores on admission, as well as SOFA score on days three and seven. RESULTS: 69 patients were included in the study. Mortality rate of our series was 23.19% (95%ic, 13.19-33.19%). Mean age of these patients was 64.94 (95%ic, 61;69y). More than 55% of patients had community acquired sepsis (p<0.05). Most frequent previous pathologies were hypertension (49.27%; 95%ci, 37.27;61.27%), followed by mellitus diabetes (24.63%; 95%ci, 14.43;34.83%). The most frequent focus of infection was colonic (40.57%; 95%ci, 28.57;52.57%). Mean APACHE II score on admission was 16.43 points (95%ci, 14.95;17.91points) and was higher in those patients who finally died (p<0.00001). Mean SOFA score on admission was 6.46 points (95%ci, 5.71;7.2points). In the binary regression logistic study, those factors identified as more related with outcome were age and the increase in SOFA score between days one and seven. Procalcitonin presented a different dynamic among Nonsurvivors (levels maintained or increased) and Survivors (whose levels decreased)(p<0.05). Procalcitonin levels on day seven identified better the outcome of these patients (AUC-ROC 0.768). Levels equal or higher than 3.5ng/mL identified mortality with 55% sensibility and 73% specificity. CONCLUSIONS: In our series of patients with severe sepsis of intraabdominal origin, procalcitonin does not identify outcome of patients on admission, but on day seven of observation. Increase on SOFA score between days one and seven and age were the factors that identified outcome in a more accurate way on patients with severe sepsis of intraabdominal origin.
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Smith, Laura Ann. "Effects of Bacterial Products on Human Blood Leukocytes." University of Toledo Health Science Campus / OhioLINK, 2006. http://rave.ohiolink.edu/etdc/view?acc_num=mco1164046331.
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Lima, Erica Silva. "Efeito da suplementação dietética com L-glutamina na sepse abdominal induzida em rato." Universidade do Estado do Rio de Janeiro, 2012. http://www.bdtd.uerj.br/tde_busca/arquivo.php?codArquivo=5869.
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Conselho Nacional de Desenvolvimento Científico e TecnológicoApós o estímulo deflagrador de um trauma ou infecção, a liberação de citocinas na circulação sanguínea desempenha um importante papel efetor e também modulador da resposta imune sistêmica. Essas citocinas podem ser pró-inflamatórias, que estimulam a liberação de diversos tipos celulares e de outras citocinas, como fator de necrose tumoral-alfa (TNF-α), interleucina 1 (IL-1), IL-2, IL-6, IL-8, IL-12 e interferon-gama (INF-); ou citocinas com efeitos antiinflamatórios, que inibem o processo inflamatório, em parte pela redução da produção de diversas citocinas que regulam positivamente a resposta, minimizando o comprometimento orgânico resultante, como IL-4, IL-10, IL-13. A L-glutamina é o aminoácido mais abundante no organismo, com importante papel no metabolismo protéico. Sua ação trófica sobre a mucosa do intestino delgado é bastante conhecida, o que o torna componente essencial para a manutenção estrutural e funcional do intestino. O objetivo deste trabalho foi avaliar o efeito da suplementação dietética com L-glutamina na modulação da resposta inflamatória em animais submetidos a sepse abdominal induzida por ligadura e perfuração cecal. Foram utilizados 24 ratos Wistar machos adultos, com peso inicial entre 200 e 230 g, distribuídos em três grupos, cada um com oito animais, da seguinte forma: grupo I (controle) submetidos a operação simulada (laparotomia e manipulação de alças intestinais); grupo II submetidos a laparotomia, com indução de sepse abdominal; e grupo III receberam suplementação dietética com L-glutamina por sete dias e, após, foram submetidos a indução de sepse abdominal. Foram coletadas amostras sanguíneas de todos os animais antes (tempo 0) e duas e quatro horas (tempos 1 e 2) após a indução da sepse abdominal. Foram verificados o número de leucócitos, a dosagem da concentração plasmática de citocinas pró- e antiinflamatórias (INF-γ, IL-6 e IL-10) e análise microbiológica de líquido peritoneal. A glicemia apresentou aumento significativo em todos os grupos, comparando-os ao início e ao final do experimento (p<0,05). No que concerne à IL-10, observou-se aumento significativo nos animais do grupo III entre os tempos 0 e 2, e entre os tempos 1 e 2 (p=0,0331 e p=0,0155, respectivamente). Não se observou qualquer outra diferença ao serem analisadas as demais citocinas (IFN- e IL-6), em todos os grupos e em todos os momentos analisados. Nossos achados sugerem que a suplementação dietética com L-glutamina em animais submetidos à indução de sepse abdominal com modelo CLP parece potencializar a resposta antiinflamatória, aumentando a concentração plasmática de IL-10, enquanto as concentrações de INF-γ e IL-6 não apresentaram variação significativa.
After the triggering stimulus of trauma or infection, the release of cytokines into the bloodstream plays an important effector and modulator role on the systemic immune response. These cytokines may be pro-inflammatory, stimulating the release of several cell types and other cytokines, such as tumor necrosis factor-alpha (TNF-α), interleukin 1 (IL-1), IL-2, IL-6, IL-8, IL-12 and interferon-gamma (IFN-); or cytokines with anti-inflammatory effects that inhibit the inflammatory process, in part by reducing the production of several cytokines that positively regulate the response, minimizing the resulting organic damages, such as IL-4 , IL-10, IL-13. L-Glutamine is the most abundant amino acid in the body, with an important role in protein metabolism, acting as a vehicle for nitrogen transport. Its trophic action on the small intestinal mucosa is well known, which makes it an essential component in the maintenance of the bowel structure and function. This study aimed at evaluating the effect of the dietary supplementation with L-glutamine in modulating the inflammatory response in animals submitted to the induction of abdominal sepsis by cecal ligation and puncture (CLP). We used 24 adult male Wistar rats, initially weighing between 200 and 230 g, divided into three groups, each with eight animals as follows: group I (control) sham operation (laparotomy and manipulation of the bowel); group II laparotomy with induction of abdominal sepsis; and group III dietary supplementation with L-glutamine for seven days and after submitted to the induction of abdominal sepsis. Blood samples were collected from all animals before (time 0) and two and four hours (times 1 and 2) after the induction of abdominal sepsis. We verified white blood cell (WBC) count, the plasmatic concentration of pro- and anti-inflammatory cytokines (INF-γ, IL-6 and IL-10), and the microbiological analysis of peritoneal fluid. Blood glucose increased significantly in all groups, comparing them in the beginning and in the end of the experiment (p<0.05). Concerning to IL-10, we observed a significant increase in the animals of group III between times 0 and 2, and times 1 and 2 (p=0.0331 and p=0.0155, respectively). We did not observe any difference in the analysis of the other cytokines (IFN- and IL-6) in all groups and at all times. Our findings suggest that dietary supplementation with L-glutamine in animals submitted to the induction of abdominal sepsis with CLP model seems to enhance the anti-inflammatory response, increasing the plasmatic concentration of IL-10, while the concentration of INF-γ and IL-6 did not present significant change.
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Al-Bahrani, Ahmed Z. "An Investigation of Intra-Abdominal Pressure and the Potential Impact of Intra-Abdominal Hypertension on Gut Barrier and Other Organ Functions in Patients With Severe Acute Pancreatitis and in Patients with Abdominal Sepsis." Thesis, University of Manchester, 2009. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.501974.
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Soop, Anne. "Experimental studies on endotoxin infusion in human : evaluation of pharmacological immunomodulation by adenosine and nicotinamide /." Stockholm, 2003. http://diss.kib.ki.se/2003/91-7349-716-9/.
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Vesali, Rokhsareh Farrah. "Amino acid and protein turnover in human skeletal muscle /." Stockholm, 2005. http://diss.kib.ki.se/2005/91-7140-285-3/.
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O'Leary, Michael James. "Tissue protein catabolism in sepsis : mechanisms, and modulation by nutrition, glutamine and recombinant human growth hormone." Thesis, Queen Mary, University of London, 2004. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.415158.
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Youssef, Nermeen. "Assessment of manual and robotic miRNAs extraction methods with optimization of the two-tailed RT-qPCR technology for miRNAs detection as biomarkers from human plasma for early sepsis diagnosis : Future diagnostics of sepsis." Thesis, Högskolan i Skövde, Institutionen för biovetenskap, 2021. http://urn.kb.se/resolve?urn=urn:nbn:se:his:diva-20233.
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Sepsis is a life-threatening syndrome that occurs due to dysregulated body response to pathogenic infections. More than 30 million cases are recorded annually worldwide, with a high mortality rate of up to 40% of the recorded cases. Early diagnosis of sepsis will help clinicians to start proper therapy as early as possible and save lives. Circulating miRNAs in biofluids were found previously as potential biomarkers that can be used in a multi-marker panel to develop a rapid, friendly user diagnostic kit for the early sepsis diagnosis. This study assessed miRNAs from healthy donors’ human plasma by two extraction methods, manually and robotically via QIAcube. In addition to optimizing two-tailed RT-qPCR (TATAA Biocenter) technology for miRNAs detection and quantification. The extraction of miRNAs was using miRNeasy® Serum/Plasma Advanced kit (Qiagen) for the two methods. Plasma was spiked in with synthetic miRNA-210 to ensure miRNA detection and was used as a positive control for the study. The concentration and the purity of the RNA eluates were measured and statistically analyzed to identify which method could be better in conventional laboratory practice. QIAcube results showed its ability to compete with manual RNA extraction protocols. However, more studies are required for RNA extractions with different kits using QIAcube. The two-tailed RT-qPCR technology successfully detected many miRNAs, but more samples are required to be tested for accurate conclusions. The results emphasize the ability of two-tailed RT-qPCR to detect and quantify miRNAs from human plasma as potential biomarkers in a multi-marker panel for early sepsis diagnosis.
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Krüger, Anne [Verfasser], and Carsten Jürgen [Akademischer Betreuer] Kirschning. "Towards understanding bacterial induced sepsis : RNA recognition by murine TLR13 and human TLR8 / Anne Krüger. Betreuer: Carsten Jürgen Kirschning." Duisburg, 2016. http://d-nb.info/1109745583/34.
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Merino, Chávez Oscar Miguel. "Estudio comparativo de la evolución de la sepsis abdominal con relaparotomía a demanda y relaparatomía planeada. Hospital Alberto Sabogal Sologuren – Callao - Perú, enero 2004 a diciembre 2005." Bachelor's thesis, Universidad Nacional Mayor de San Marcos, 2006. https://hdl.handle.net/20.500.12672/15869.
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La sepsis abdominal es una de las patologías con alta mortalidad y costos elevados. A pesar de los avances en antibioticoterapia y manejo intensivo se registran valores de hasta un 70 % de mortalidad, estancias hospitalarias prolongadas y gran número de complicaciones. El estudio tiene como finalidad la comparación entre la evolución de los pacientes con sepsis de origen abdominal sometidos a relaparotomías a demanda y la de aquellos tratados con relaparotomías planeadas. Se contó con una muestra total de 137 pacientes con sepsis abdominal, de los cuales 63 fueron sometidos a Relaparotomía Planeada y 74 a Relaparotomía a Demanda. Cabe señalar que el origen más frecuente de la sepsis fue el tracto gastrintestinal (69.3 %). La mortalidad global por sepsis abdominal fue 29.9 %. Al comparar ambas técnicas quirúrgicas resultó que la mortalidad con Relaparotomía a Demanda (21.6 %) fue significativamente menor que con la Relaparotomía Planeada (39.7 %). De igual manera con la técnica a Demanda los pacientes presentaron menor estancia hospitalaria en cuidados críticos (8 días en promedio), menor índice de complicaciones (9.5 %) y menor número promedio de reintervenciones por paciente (3 cirugías por caso en promedio) que aquellos sometidos a Relaparotomías Planeadas. Resumiendo lo planteado, se puede afirmar que los pacientes evolucionaron mejor cuando fueron sometidos a Relaparotomía a Demanda, recomendándose la aplicación de esta técnica en realidades semejantes a la del hospital.
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Mommert, Marine. "Modulation de l'expression des rétrovirus endogènes humains dans des contextes d'inflammation et d'immunosuppression." Thesis, Lyon, 2018. http://www.theses.fr/2018LYSEN044.
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Le sepsis est défini par l’apparition de dysfonctions d’organes, multiples et mortelles, causées par une réponse de l’hôte dérégulée suite à une infection. L’hétérogénéité de la maladie représente un défi clinique majeur au regard de la prise en charge thérapeutique, et à ce jour les marqueurs proposés ne suffisent pas à stratifier les patients. Les rétrovirus endogènes humains (HERV) pourraient être des marqueurs pertinents,compte tenu des propriétés immunosuppressives de leurs enveloppes et de leur expression dans des maladies inflammatoires et auto-immunes. Cette thèse a pour objectif de savoir dans quelle mesure les HERV sont exprimés et modulés, dans des conditions d’inflammation et d’immunosuppression. Pour cela,nous avons utilisé une puce à ADN haute densité permettant (i) l’analyse de la transcription de 363 689HERV et 1500 gènes, et (ii) une lecture fonctionnelle de l’activité des LTR. L’expression des HERV a été objectivée (i) dans un modèle ex-vivo de tolérance à l’endotoxine sur des cellules mononuclées du sang périphérique (PBMC) d’individus sains et (ii) sur sang total provenant d’individus sains et de patients en choc septique, stratifiés ou non en fonction du statut immunitaire. (1) De 5,6% à 6,9% des HERV sont exprimés dans le compartiment sanguin et environ 20% des LTR possèdent une fonction promotrice ou polyA, les deux fonctions étant mutuellement exclusives. (2) Le contenu du transcriptome HERV est modulé ex vivo dans le contexte de tolérance à l’endotoxine laissant apparaitre deux grands phénotypes transcriptionnels. L’expression de certains loci HERV est corrélée au statut immunitaire de patient septique.L’évaluation d’une signature moléculaire complexe sur une cohorte de validation, permet la séparation en deux groupes présentant des critères de sévérité distincts, suggérant les HERV/MaLR comme biomarqueurs de stratification. (3) L’analyse de la co-expression des gènes et des HERV a permis d’intégrer ceux-ci au sein de réseaux associées à la réponse de l’hôte et de proposer des hypothèses fonctionnellesSepsis is defined as a life-threatening organ dysfunction caused by a dysregulated host response to infection.The heterogeneity of the disease present a major clinical challenge with regard to the therapeutic coverage,and this day the proposed markers are not enough to stratify patients. The human endogenous retrovirus(HERV) could be relevant markers, considering the immunosuppressives properties of their envelopes andtheir expression in inflammatory and autoimmune disease. The aim of this thesis is to know to what extentthe HERVs are expressed and modulated, in inflammatory and immunocompromised contexts. For this, weused a high density DNA chip allowing (i) the transcription analysis of 363,689 HERV and 1500 genes,and (ii) a functional reading of LTRs activities. The HERVs expression was objectified (i) in endotoxintolerance ex vivo model in peripheral blood mononuclear cells (PBMCs) of healthy volunteers and (ii) inwhole blood of healthy volunteers and septic shock patients, stratified or not according to immunity state.(1) Of 5,6% at 6,9% of HERVs are expressed in the blood compartment and around 20% of LTRs have apromoter or polyA function, both functions being mutually exclusive. (2) The HERV transcriptome ismodulated in ex vivo endotoxin tolerance model letting appear two higher transcriptional phenotypes. Theexpression of some HERVs loci are correlated of the immunity state of the septic shock patients. Theevaluation of molecular signature in validation cohort, allowed to separate in two patients groupspresenting different severity criteria, suggesting HERV/MaLR as biomarkers of stratification. (3) The coexpressedanalysis of genes and HERVs allowed to integrate these within signaling pathways associated atthe host immune response and to provide functional hypothesis
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Ara?jo, Filho Irami. "Influ?ncia da laparoscopia e da laparotomia na gasometria, leucometria diferencial e citocinas em modelo de sepse abdominal em ratos." Universidade Federal do Rio Grande do Norte, 2005. http://repositorio.ufrn.br:8080/jspui/handle/123456789/13419.
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Previous issue date: 2005-10-27Laparoscopic surgery is associated with reduced surgical trauma, and less acute phase response, as compared with open surgery. Cytokines are important regulators of the biological response to surgical and anesthetic stress. The aim of this study was to determine if CO2 pneumoperitoneum would change cytokine expression, gas parameters and leukocyte count in septic rats. Methods: Wistar rats were randomly assigned to five groups: control (anesthesia only), laparotomy, CO2 pneumoperitoneum, cecum ligation and puncture by laparotomy, and laparoscopic cecum ligation and puncture. After 30 min of the procedures, arterial blood samples were obtained to determine leukocytes subpopulations by hemocytometer. TNFα, IL-1β, IL-6 were determined in intraperitoneal fluid (by ELISA). Gas parameters were measured on arterial blood, intraperitoneal and subperitoneal exsudates. Results: Peritoneal TNFα, IL-1β and IL-6 concentrations were lower in pneumoperitoneum rats than in all other groups (p<0.05). TNFα, IL-1β and IL-6 expression was lower in the laparoscopic than in laparotomic sepsis (p<0.05). Rats from laparoscopic cecum ligation and puncture group developed significant hypercarbic acidosis in blood and subperitoneal fluid when compared to open procedure group. Total white blood cells and lymphocytes were significantly lower in laparoscopic cecum ligation and puncture rats than in the laparotomic (p<0.01). Nevertheless, the laparotomic cecum ligation rats had a significant increase in blood neutrophils and eosinophils when compared with controls (p<0.05). Conclusions: This study demonstrates that the CO2 pneumoperitoneum reduced the inflammatory and immune response in an animal model of peritonitis with respect to intraperitoneal cytokines, white blood cell count and clinical correlates of sepsis. The pneumoperitoneum produced hypercarbic acidosis in septic animals
A cirurgia laparosc?pica est? associada com trauma reduzido e baixa resposta metab?lica na fase aguda do trauma, quando comparada com a cirurgia aberta. As citocinas e o balan?o ?cido-base s?o fatores importantes da resposta biol?gica ao trauma cir?rgico-anest?sico. O objetivo deste estudo foi determinar se o pneumoperit?nio com CO altera a express?o das citocinas intraperitoneais, a gasometria do sangue arterial, dos exsudatos intraperitoneal e subperitoneal, e a contagem diferencial de leuc?citos em ratos com sepse abdominal. M?todo: Ratos Wistar foram aleatoriamente distribu?dos em cinco grupos: controle (somente 2anestesia), laparotomia, pneumoperit?nio com CO2, ligadura e pun??o do ceco por laparotomia, ligadura e pun??o do ceco por laparoscopia. Ap?s 30 minutos dos procedimentos, sangue arterial foi colhido para leucometria em hemocit?metro. FNTα, IL-1β e IL-6 foram dosadas no lavado intraperitoneal (por ELISA). Os par?metros gasosos foram medidos no sangue arterial e nos exsudatos intraperitoneal e subperitoneal. Resultados: Os valores de FNTα, IL-1β e IL-6 foram significantemente menores nos ratos submetidos ao pneumoperit?nio do que em todos os outros grupos (p<0.05). Express?o de FNTα, IL-1β e IL-6 foi menor no grupo sepse induzida por laparoscopia do que por laparotomia (p<0.05). Os ratos submetidos ? ligadura e pun??o do ceco por via laparosc?pica desenvolveram acidose hiperc?rbica no sangue arterial e exsudato subperitoneal, mais intensa do que no grupo sepse laparot?mica. Leucopenia e linfopenia foram mais acentuadas no grupo sepse laparosc?pica (p<0.01). Entretanto, os animais submetidos a sepse laparot?mica desenvolveram significante aumento de neutr?filos e eosin?filos quando comparados com os controles (p<0.05). Conclus?es: Este estudo demonstrou que o pneumoperit?nio com CO contribuiu para reduzir a resposta inflamat?ria e imunol?gica em ratos submetidos a modelo de sepse abdominal, no que diz respeito a citocinas intraperitoneais e leucometria diferencial. O pneumoperit?nio tamb?m contribuiu para instala??o de acidose hiperc?rbica nos ratos s?pticos
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Von, Ehr Michelle. "Optimization of the Two-Tailed RT qPCR method with synthetic miR-16 and miR-210 in human plasma for future diagnostics of sepsis." Thesis, Högskolan i Skövde, Institutionen för biovetenskap, 2020. http://urn.kb.se/resolve?urn=urn:nbn:se:his:diva-18844.
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Every year, around 6 million people lose the fight against sepsis. Sepsis is a dysregulated response from the host to an infection, leading to life-threatening organ dysfunction. The gold-standard diagnostics of sepsis to date is blood culturing and the results take up to three days to be validated Therefore, it is important to focus on biomarkers like MicroRNA [miRNA] to develop faster diagnostics tools as they have previously shown to be potential minimally-invasive biomarkers for many diseases of different origin. RT-qPCR is known to amplify DNA, while a new primer, called the two-tailed primer, was developed by TATAA Biocenter to specialize on miRNA amplification. The aim of this study is to perform the two-tailed RT-qPCR method manually with two synthetic miRNAs, miR-210 and miR-16, reduce the amount of plasma to a minimum of 100 μl and optimize this method for the use in conventional labs. Whole blood was drawn, centrifuged and the resulting plasma underwent RNA extraction. Synthetic miRNAs were used for spiking and the two-tailed RT-qPCR method was performed and both melt curve analysis, standard curve analysis and absolute quantification were performed. Amplification was detected in all samples, allowing to conclude that the two-tailed primers work. The amplification efficiencies and the linearity for both synthetic miRNAs were determined at 77% and 0.99, respectively. Absolute quantification showed promising quantification for all spiked samples while it needs to be taken into account that the amplification efficiencies were rather low and the standard curves used for absolute quantification should be diluted with care.
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Souza, Yglesio Luciano Moyses Silva de. "Avaliação dos efeitos da ozonioterapia no tratamento da infecção intra-abdominal em ratos." Universidade de São Paulo, 2009. http://www.teses.usp.br/teses/disponiveis/5/5160/tde-05032010-164441/.
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INTRODUÇÃO: O ozônio (O3) é encontrado na natureza e também pode ser produzido no corpo humano através da ativação de anticorpos. Seus efeitos anti-bactericidas são descritos na literatura, mas esses dados são controversos quanto a um potencial efeito benéfico da ozonioterapia no tratamento de certos tipos de infecção. OBJETIVO: Avaliar os efeitos da aplicação intraperitoneal (i.p.) de uma mistura gasosa de ozônio em um modelo de ligadura e punção de ceco (LPC) em ratos, através da dosagem de interleucinas (IL)-6, IL-10 e da quimiocina CINC-1 (cytokine-induced neutrophil chemoattractant), da lesão pulmonar aguda (LPA) e da análise das taxas de sobrevida. MÉTODO: Quatro grupos de ratos Wistar foram utilizados para análise de cada objetivo (CTR, LPC, LPC+O2 e LPC+O3). Os animais do grupo CTR foram submetidos somente a laparotomia. O grupo LPC foi submetido aos procedimentos de LPC. Os outros grupos foram submetidos à LPC e receberam injeção (i.p.) da mistura gasosa correspondente, administrada a cada 12 horas durante o período de observação. Os níveis séricos de IL-6, CINC-1 e IL-10 foram determinados por imuno- ensaio (enzyme linked immunosorbent assay- ELISA). A LPA foi avaliada através da histologia pulmonar e quantificada através do método do extravasamento pulmonar do Azul de Evans. Os animais da análise de sobrevivência foram observados por cinco dias. Os valores obtidos foramexpressos como médias ± erro-padrão da média (EP) ou medianas mais percentis 25 e 75(P25; P75), de acordo com a distribuição dos dados. Considerou-se significante p<0,05. RESULTADOS: Os ratos do grupo CTR exibiram os menores níveis de CINC-1 (p<0,01). O grupo LPC+O3 teve níveis menores de CINC-1 comparado a LPC+O2 e LPC (p<0,05). Os níveis de IL-10 do grupo CTR foram menores do que nos outros 3 grupos(p=0,02) . Não houve diferenças entre os outros 3 grupos (p=0,85). IL-6 foi significativamente menor para o grupo CTR (30,8± 4,8) quando comparado a todos os outros grupos (p<0,001). LPC+O3 e LPC+O2 exibiram níveis menores quando comparados ao grupo LPC (p<0,01). Não houve diferença entre os grupos LPC+O3 e LPC+O2 (p=0,54). O escore de histologia pulmonar foi menor para CTR (p=0,02). Os outros grupos não apresentaram diferenças significantes intergrupos (p=0,3). Os valores dos coeficientes de extravasamento pulmonar do Azul de Evans foram menores para LPC+O3 quando comparado aos grupos LPC+O2 e LPC (p=0,02), porém não houve diferença na comparação com CTR O grupo CTR teve o maior tempo de sobrevida (110±10h) comparado com os outros grupos, ou seja, LPC (57,3± 10,4h), LPC+O2 (71 ± 12,9h) e LPC+O3 (52,1 ± 8), os quais não apresentaram diferenças entre si quanto à sobrevida (p=0,4). CONCLUSÃO: No presente estudo experimental em ratos, a ozonioterapia teve um benefício potencial na modulação da resposta inflamatória e na LPA, mas não influenciou as taxas de sobrevida dos animais.INTRODUCTION: Ozone (O3) is found in nature and also can be produced in the human body through activation of antibodies. Its antibacterial effect has been described in the literature, but these data are controversial regardi ng a benefic role of O3 therapy in the treatment of certain types of infection. OBJECTIVE: To evaluate the effects of intraperitoneal (i.p.) application of an O3 gas mixture in a rat model of cecal ligation and puncture (CLP), by analyzing interleukin (IL)-6, IL-10 and cytokine-induced neutrophil chemoattractant (CINC)-1 levels, acute lung injury (ALI) and survival rates. METHOD: Four animal groups were used (SHAM, CLP, CLP+O2 and CLP+O3). SHAM animals were submitted solely to laparotomy. CLP group was submitted to cecal ligation and puncture. The other groups were submitted to CLP and received injections (i.p.) of the corresponding gas mixture every 12 hours during the observation period. The serum concentrations of IL-6, CINC-1 and IL-10 were determined by the enzyme-linked immunosorbent assay (ELISA). ALI was evaluated with pulmonary histology and quantitated by means of the Evans blue dye (EBD) lung leakage method. For survival analysis, animals were observed for 5 days. Values were expressed as means ± SEM or medians (P25; P75), according to the data distribution. A p<0,05 was considered significant.RESULTS: SHAM rats had the lowest levels of CINC-1 compared to all other groups (p<0,01). CLP+O3 group had lower levels of CINC-1 compared to CLP+O2 and CLP (p<0,05). SHAM IL-10 levels were the lowest compared to the 3 other groups (p=0,02). There were no differences between the other 3 groups (p=0,85). IL-6 was significantly lower for SHAM compared to all groups (p<0,001). CLP+O3 and CLP+O2 had lower levels when compared to CLP (p<0,01). Comparison between groups CLP+O3 and CLP+O2 showed no significant difference (p=0,54). Pulmonary histology score was lower for SHAM (p=0,02). The other groups presented no statistical difference when compared to each other (p=0,3). EBD lung leakage values were lower to CLP+O3 compared to CLP+O2 and CLP (p=0,02). SHAM group had the longest survival time (110±10h) compared to all other groups (p=0,002). CLP (57,3± 10,4h), CLP+O2 (71 ± 12,9h) and CLP+O3 (52,1 ± 8h), which did not show difference on survival compared to each other (p=0,4). CONCLUSION: In this rat model of sepsis, ozone therapy had a potential benefit in the modulation of inflammatory response and ALI, but no improvement on survival rates was observed.
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Stephens, Alick Christopher. "Studies on human monocyte tissue factor expression and inhibition following endotoxin exposure : plasma measurement of tissue factor and tissue factor pathway inhibitor in sepsis." Thesis, Imperial College London, 2000. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.393656.
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Oliveira, Luciana Mello de. "Frequência reduzida de genes KIR ativadores em pacientes com sepse." reponame:Biblioteca Digital de Teses e Dissertações da UFRGS, 2016. http://hdl.handle.net/10183/149582.
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Base teórica: A sepse é uma síndrome heterogênea, definida como disfunção orgânica que ameaça à vida, causada por uma resposta desregulada do hospedeiro à infecção. É um problema de saúde mundial, graças à sua alta prevalência, morbimortalidade associada, além de custos para seu tratamento. As células Natural Killer (NK) fazem parte do sistema imune inato reconhecendo moléculas de HLA de classe I em células alvo, através de seus receptores de membrana killer cell immunoglobulin-like receptors (KIR). A intensidade da resposta à infecção pode variar entre indivíduos, logo pode-se considerar que esta seja determinada por bases genéticas, e estas influenciem na ocorrência de sepse e variabilidade nos desfechos. Objetivos: Avaliar a associação entre os genes KIR e os ligantes HLA em pacientes críticos, comparando pacientes com sepse e controles não sépticos internados na mesma UTI. Métodos: Foi examinado o polimorfismo de 16 genes KIR e seus ligantes HLA em 271 pacientes críticos, caucasóides, sendo 211 pacientes com sepse e 60 controles, pela técnica de PCR-SSO e PCR-SSP, respectivamente. Resultados: Os genes ativadores KIR2DS1 e KIR3DS1 foram mais frequentes nos controles que nos pacientes com sepse (41,23% versus 55,00%, e 36,49% versus 51,67%; p = 0.041 e 0,025, respectivamente). Estes resultados fornecem informação inicial sobre o papel de polimorfismos de KIR na sepse, sugerindo que este possa ser um potencial marcador diagnóstico ou prognóstico da doença.Background: Sepsis is a heterogeneous syndrome, defined a life-threatening organic dysfunction caused by a dysregulated host response to infection. Sepsis is a global health problem, due to its high prevalence, associated morbidity and mortality, and costs for its treatment. Cells Natural Killer (NK) cells are part of the innate immune system that recognize HLA class I molecules on target cells via membrane receptors called killer cell immunoglobulin-like receptors (KIR). The intensity of the response to an infection may vary among individuals and might be influenced genetic features affecting sepsis occurrence and variability in outcomes. Objectives: To evaluate the association between KIR genes and HLA ligands in critically ill patients, comparing patients with sepsis and without sepsis admitted to the same ICU. Methods: We examined the polymorphism of 16 KIR genes and their HLA ligands in 271 critically ill patients, Caucasians, and 211 patients with sepsis and 60 controls by PCR-SSO and PCR-SSP, respectively. Results: Activating KIR2DS1 and KIR3DS1 genes were more common in controls than in patients with sepsis (41.23% versus 55.00% and 36.49% versus 51.67%, p = 0.041 and 0.025, respectively). These results provide initial information on the role of polymorphism of KIR in sepsis, suggesting that this may be a potential diagnostic or prognostic marker of the disease.
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Costa, Luciane Pires da. "Consumo de óleo de peixe na resposta inflamatória em ratos submetidos a esplenectomia total isolada ou combinada com autoimplante esplênico e à indução de sepse abdominal." Universidade do Estado do Rio de Janeiro, 2012. http://www.bdtd.uerj.br/tde_busca/arquivo.php?codArquivo=4858.
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Em órgãos potencialmente importantes na resposta imune, como o baço, alternativas como o autoimplante de segmentos esplênicos, quando a esplenectomia total torna-se necessária, e a utilização de nutrientes com funcionalidade imunomoduladora vêm sendo estudadas, objetivando minimizar o efeito pró-inflamatório persistente da sepse abdominal. O objetivo deste trabalho foi avaliar o efeito do consumo de óleo de peixe na modulação da resposta inflamatória em animais submetidos a esplenectomia total isolada ou combinada com autoimplante esplênico e à indução de sepse abdominal, verificando a possível otimização na resposta pró-inflamatória e a regeneração funcional do autoimplante. Utilizamos 64 ratos machos da linhagem Wistar, com peso variando entre 140-200 g, aleatoriamente distribuídos em oito grupos: quatro grupos-controle (100% óleo de soja) e quatro grupos-intervenção (35% de óleo de peixe), cada um com oito animais. Os dos grupos-controle (animais alimentados com ração purificada, segundo AIN-93, com conteúdo lipídico constituído por 100% óleo de soja) foram: I sem intervenção cirúrgica e, 16 semanas após, submetidos à indução de sepse abdominal; II esplenectomia total isolada e, 16 semanas após, submetidos à indução de sepse abdominal; III esplenectomia total combinada com autoimplante esplênico e, 16 semanas após, submetidos à indução de sepse abdominal; e IV esplenectomia total combinada com autoimplante esplênico e, oito semanas após, submetidos à indução de sepse abdominal. Os dos grupos-intervenção (V a VIII) foram submetidos a procedimentos similares aos executados nos grupos I a IV, respectivamente, sendo a única modificação fundamentada na substituição de 35% do conteúdo lipídico da alimentação dos animais por óleo de peixe. Todos os animais foram submetidos a sepse induzida por ligadura e perfuração cecal (CLP). Coletamos amostras sanguíneas de todos os animais antes da indução da sepse (período 1) e 2 e 4 horas (períodos 2 e 3) após a indução da sepse abdominal. Verificou-se, a cada três dias, massa corporal (MC) e ingestão alimentar (IA). Analisamos as citocinas INF-γ, IL-6 e IL-10 por meio da tecnologia Luminex. Utilizamos o teste T de Student para análise estatística, considerando significativo com p≤0,05. Os dos grupos V, VI e VIII apresentaram maior consumo alimentar que seus controles. Os do grupo V apresentaram menores concentrações de IFN-γ em todos os períodos e maior IL-10 nos períodos 2 e 3. Os do grupo VI apresentaram menores concentrações de todas as citocinas: IFN-γ nos períodos 2 e 3; IL-6 nos períodos 1 e 2; e maior IL-10 nos períodos 1 e 2. Os do grupo VIII apresentaram menor IFN-γ no período 3, IL-6 no período 2, e maior IL-10 no período 1. Não observou-se diferenças nos do grupo VII em nenhuma das citocinas estudadas. Este estudo demonstrou que a utilização do óleo de peixe em pequena dose, consumido cronicamente, como parte do teor lipídico total da dieta e não de forma suplementar, é capaz de manter a massa corporal adequada e reduzir a resposta inflamatória à sepse abdominal induzida por CLP, aumentando a IL-10 plasmática em ratos que não sofreram intervenção cirúrgica, e parece favorecer a regeneração funcional precoce do autoimplante esplênico.In organs potentially important in the immune response, like the spleen, alternatives such as autotransplantation of splenic segments, when the total splenectomy becomes necessary, and the use of nutrients with immunomodulatory function have been studied, trying to minimize the effect of pro-inflammatory persistent abdominal sepsis. The aim of this study was to evaluate the effect of consumption of fish oil in modulating the inflammatory response in animals submitted to total splenectomy alone or combined with spleen autotransplantation and the induction of sepsis, verifying the possible optimization in the proinflammatory response and the functional regeneration of the autotransplant. We used 64 male Wistar rats, weighing between 140-200 g, were randomly distributed into eight groups: four control-groups (100% soybean oil) and four intervention-groups (35% fish oil), each one with ten animals. The rats in control groups (animals fed with purified according to the AIN-93 with lipid content consisting of 100% soybean oil) : I without surgical intervention, and 16 weeks after, submitted to the induction of abdominal sepsis II total spleenectomy alone, and 16 weeks after, submitted to the induction of abdominal sepsis; III total splenectomy combined with spleen autotransplantation, and 16 weeks after, submitted to the induction of abdominal sepsis; and IV total splenectomy combined with spleen autotransplantation, and 8 weeks after, submitted to the induction of abdominal sepsis. The rats in intervention groups (V to VIII) were subjected to similar procedures performed in groups I to IV, respectively, being the only modification based on the substitution of 35% of the lipid content of animal feed for fish oil. All animals were subjected to sepsis induced by cecal ligation and puncture (CLP). We collected blood samples from all animals before the induction of sepsis (period 1) and 2 and 4 hours (periods 2 and 3) after the induction of abdominal sepsis. We checked every 3 days corporal mass (MC) and alimentary ingestion (AI). We analyzed the cytokines IFN-γ, IL-6 and IL-10 by Luminex technology. We used the T-test of Student for statistical analysis, considering significant with a p ≤ 0.05. The animals in groups V, VI, and VIII showed higher food intake than their controls. The animals in group V showed lower IFN-γ in all, IL-6 in periods 1 and 2; and higher IL-10 in periods 2 e 3. The animals in group VI showed lower concentration of all cytokines: IFN-γ in periods 2 and 3; IL-6 in periods 1 and 2 and higher IL-10 in periods 1 e 2. The animals in group VIII showed lower IFN-γ in period 3, IL-6 in period 2, and higher IL-10 in period 1. No differences were observed with the concentration of cytokines in those of group VII. This study demonstrated that the use of fish oil in small doses, chronically consumed as part of total dietary fat and not as a supplement, is able to maintain the adequate corporal mass and to reduce the inflammatory response to abdominal sepsis induced by CLP, increasing IL-10 concentration in health rats and seems to promote early functional regeneration of the spleen autotransplants.
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Berthet, Julien. "Rôle fonctionnel du Toll-Like Receptor 4 exprimé par les plaquettes sanguines en tant que cellules inflammatoires de l'immunité." Phd thesis, Université Jean Monnet - Saint-Etienne, 2010. http://tel.archives-ouvertes.fr/tel-00673243.
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Les plaquettes jouent un rôle majeur dans l'hémostase primaire ainsi que dans l'inflammation. Elles contiennent et sécrètent une grande variété de facteurs solubles et parmi les nombreux récepteurs qu'elles expriment à leur surface, les plaquettes expriment les " Toll-Like Receptor " (TLR), récepteurs clés de l'interaction entre l'immunité innée et adaptative. En réponse à un stimulus infectieux, comme le lipopolysaccharide (LPS) des bactéries Gram-négative, ligand naturel du TLR4, ou des peptides issus d'une partie de la protéine d'enveloppe du VIH (gp41), les plaquettes vont s'activer de manière différentielle. L'activation plaquettaire est variable en fonction de leur activation par à un stimulus hémostatique (exemple : la thrombine) vs. infectieux (exemple : le LPS) ; le panel de cytokines libérées dans le surnageant plaquettaire semble en fait finement régulé. De plus, nous avons démontré la présence intra-plaquettaire de la majorité des protéines composant les voies de signalisation du TLR4 eucaryote. Nous avons ensuite montré que ces voies pouvaient être modulées. L'engagement du TLR4 plaquettaire par deux types biochimiques de LPS entraîne un relargage différentiel des facteurs solubles immunomodulateurs dans le surnageant de culture et que ce surnageant dernier génère une activation différentielle des cellules cibles, comme les cellules mononucléées du sang circulant. Ces travaux montrent que la réponse inflammatoire plaquettaire est régulée en fonction du stimulus. Ainsi, mes travaux s'inscrivent dans la ré-exploration de la fonction inflammatoire des plaquettes sanguines et l'étude du rôle des plaquettes comme cellules de l'immunité innée et inflammatoire
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Bürfent, Benedikt [Verfasser]. "The immunomodulatory capacity of helminths on inflammation: Impact of eosinophils on E. coli-induced sepsis and genome-wide transcriptome profiling of human monocytes stimulated with helminth extract and LPS implicate immune functions and diseases / Benedikt Bürfent." Bonn : Universitäts- und Landesbibliothek Bonn, 2017. http://d-nb.info/1149154284/34.
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Manzoli, Talita Freitas. "Dosagem de HLA-DR (Human Leukocyte antigen DR) de mononucleares para avaliação de imunoparalisia em pacientes sépticos na Unidade de Terapia Intensiva Pediátrica (UTIP) de um Hospital Terciário." Universidade de São Paulo, 2017. http://www.teses.usp.br/teses/disponiveis/5/5141/tde-09082017-114631/.
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O presente estudo avaliou a ocorrência de imunoparalisia e sua associação com pior prognóstico em pacientes pediátricos internados em uma UTI de hospital terciário. Para determinar a presença de imunoparalisia procedeu-se a dosagem da expressão de mHLA-DR usando o QuantiBRITE TM Anti HLA-DR/ Anti- Monocyte, um novo reagente que padroniza os valores da citometria de fluxo para o mHLA-DR. Determinamos a expressão de mHLA-DR em 30 pacientes com sepse grave ou choque sépticos admitidos na UTI Pediátrica no período do estudo, mHLA-DR foi quantificado por duas vezes: entre os dias 3 a 5 (mHLA-DR1) e 5 a 7 (mHLA-DR2) após o inicio do quadro séptico. Também foi calculado o deltamHLA-DR (mHLA-DR2 - mHLA-DR1). Dosamos, ainda, o mHLA-DR em vinte e um controles hígidos. O objetivo do estudo foi determinar se a expressão de mHLA-DR correlaciona-se com a mortalidade em pacientes sépticos pediátricos. Os resultados mostram que o mHLA-DR foi significativamente menor nos pacientes sépticos do que nos controles (p = 0.0001). A mortalidade foi de 46% nos pacientes com valores negativos ou < 1000 mAb/cell de deltaHLA-DR, e 7% em pacientes com valores positivos ou > 1000 mAb/cell de deltaHLADR. O deltamHLA-DR médio foi significativamente diferente entre sobreviventes e pacientes que foram a óbito (p = 0.023). Dessa forma, após a análise estatística dos resultados concluímos que o deltaHLA-DR correlaciona-se com a mortalidade em pacientes pediátricos com sepse grave e choque sépticoThis study analysis the presence of Immunoparalysis and its association with prognosis in pediatric septic patients of a Tertiary Intensive Care Unit. To determine the presence of immunoparalysis we performed the mHLA-DR dosage using the QuantiBRITE TM Anti HLA-DR/ Anti- Monocyte, a novel reagent that standardizes flow cytometry values. We determined mHLA-DR expression in 30 patients with severe sepsis or septic shock admitted to PICU, mHLA-DR expression was quantified between days 3-5 and 5-7 after the onset of sepsis and calculated the deltamHLA-DR (mHLA-DR2 - mHLADR1). We also measured mHLA-DR levels in twenty-one healthy patients. The objective of this study was to determine if mHLA-DR values correlate with mortality in pediatric septic patients. The results showed that the mean mHLA-DR expression was significantly lower in septic patients compared with controls (p = 0.0001). Mortality was 46% in patients with negative deltaHLA-DR or < 1000 mAb/cell and 7% in patients with positive deltaHLA-DR or > 1000 mAb/cell. Mean deltamHLA-DR levels were significantly different between survivors and non-survivors (p = 0.023). After statistical analysis we concluded that deltaHLA-DR correlates with mortality in pediatric patients with septic shock or severe sepsis
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Monteiro, Norberto de K?ssio Vieira. "Avalia??o das atividades anti-inflamat?ria, anticoagulante e antiproliferativa do inibidor de quimotripsina das sementes de erythrina velutina (EvCI)." Universidade Federal do Rio Grande do Norte, 2011. http://repositorio.ufrn.br:8080/jspui/handle/123456789/12579.
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Studies indicate that several components were isolated from medicinal plants, which have antibacterial, antifungal, antitumor and anti-inflammatory properties. Sepsis is characterized by a systemic inflammation which leads to the production of inflammatory mediators exacerbated by excessive activation of inflammatory cells and disseminated intravascular coagulation (DIC), in which the human neutrophil elastase plays an important role in its pathogenesis. Several epidemiological studies suggest that components of plants, especially legumes, can play a beneficial role in reducing the incidence of different cancers. A chymotrypsin inhibitor of Kunitz (Varela, 2010) was purified from seeds of Erythrina velutina (Mulungu) by fractionation with ammonium sulfate, affinity chromatography on Trypsin-Sepharose, Chymotrypsin-Sepharose and ion exchange chromatography on Resource Q 1 ml (GE Healthcare) in system FPLC / AKTA. The inhibitor, called EvCI, had a molecular mass of 17 kDa determined by SDS-PAGE. The purified protein was able to inhibit human neutrophil elastase (HNE), with an IC50 of 3.12 nM. The EvCI was able to inhibit both pathways of HNE release stimulated by PAF and fMLP (75.6% and 65% respectively). The inhibitor also inhibited leukocyte migration in septic mice about 87% and prolonged the time of coagulation and inhibition factor Xa. EvCI showed neither hemolytic activity nor cytotoxicity. EvCI showed a selective antiproliferative effect to HepG2 cell lines with IC50 of 0.5 micrograms per milliliter. These results suggest EvCI as a molecule antagonist of PAF / fMLP and a potential use in fighting inflammation related disorders, disseminated intravascular coagulation (DIC) and cancer
Estudos indicam que v?rios componentes medicinais foram isolados de vegetais, os quais apresentam atividades antibacterianas, antif?ngicas, antitumorais e anti-inflamat?rias. Sepse ? caracterizada por uma inflama??o sist?mica que tem como conseq??ncia a produ??o exarcebada de mediadores inflamat?rios, pela excessiva ativa??o de c?lulas inflamat?rias e coagula??o intravascular disseminada (CIVD), na qual a elastase neutrof?lica humana exerce um papel importante na sua patog?nese. Diversos estudos epidemiol?gicos sugerem que componentes de vegetais, especialmente de leguminosas, podem desempenhar um papel ben?fico na redu??o da incid?ncia de diferentes tipos de c?ncer. Um inibidor de quimotripsina do tipo Kunitz (Varela, 2010) foi purificado de sementes de Erythrina velutina (Mulungu) por fracionamento com sulfato de am?nio, cromatografias de afinidade em Tripsina-Sepharose e Quimotripsina-Sepharose e cromatografia de troca i?nica em Resource Q 1 mL (GE Healthcare), em sistema FPLC/AKTA. O inibidor, denominado EvCI, apresentou uma massa molecular de 17 kDa, determinada por SDS-PAGE. A prote?na purificada foi capaz de inibir a elastase de neutr?filos humanos (ENH), apresentando um IC50 de 3,12 nM. O EvCI foi capaz de inibir ambas as vias de libera??o de ENH estimuladas por PAF e fMLP (75,6% e 65%, respectivamente). O inibidor tamb?m inibiu a migra??o leucocit?ria em camundongos s?pticos em cerca de 87% e prolongou o tempo de coagula??o com inibi??o do fator Xa. EvCI n?o apresentou atividade hemol?tica nem citot?xica. EvCI apresentou um efeito antiproliferativo seletivo para linhagens de c?lulas HepG2 com IC50 de 0,5 μg /mL. Estes resultados sugerem o EvCI como uma mol?cula antagonista dos receptores PAF/fMLP e um potencial emprego no combate a dist?rbios relacionados a inflama??o, coagula??o intravascular disseminada (CIVD) e cancer
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Boontham, Pisake. "Significant and selective modulation of function and survival in vitro of human dendritic cells (DCs) and T cell subsets by N-(3-oxododecanoyl)-L-homoserine lactones : a paradigm for understanding dysfunction of host defences in vivo in sepsis in man." Thesis, University of Nottingham, 2005. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.422764.
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Préau, Sébastien. "Implication du cytosquelette dans les dysfonctions myocardiques : exemple de la cardiomyopathie septique." Phd thesis, Université du Droit et de la Santé - Lille II, 2013. http://tel.archives-ouvertes.fr/tel-01018473.
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Le cytosquelette se compose de microfilaments (polymères d'actine), de microtubules (polymères de tubuline) et de filaments intermédiaires (polymères de desmine, de lamines ...). Le sepsis défini par une infection associée à une réaction inflammatoire systémique est responsable de dysfonctions myocardiques de mauvais pronostique. Cette cardiomyopathie apparait dans les premières heures du sepsis et guérit en moins de deux semaines chez les survivants. Même si certaines études démontrent l'implication d'éléments du cytosquelette dans la cardiomyopathie septique, les rôles des microfilaments et des microtubules ne sont pas clairement établis.Macrophage migration inhibitory factor (MIF) est une cytokine pro-inflammatoire sécrétée en excès dans le sepsis qui serait responsable d'un ralentissement de la récupération myocardique. Dans un premier temps, notre travail a consisté à caractériser l'implication des microtubules dans la dysfonction musculaire cardiaque induite par MIF. Dans un modèle de trabécules auriculaires droites humaines nous avons démontré que MIF induit une hyperpolymérisation des microtubules responsable d'une hyperviscosité intracellulaire, d'une dysfonction mitochondriale et d'une dysfonction contractile. Nos résultats suggèrent qu'une hyperpolymérisation des microtubules induite par MIF pourrait être responsable d'un ralentissement de la récupération myocardique à la phase tardive de la myocardiopathie septique. Dans un second temps, nous avons évalué l'implication des microfilaments dans un modèle murin de dysfonction myocardique inflammatoire induite par l'injection d'une endotoxine bactérienne, le lipopolysaccharide. Nos résultats suggèrent qu'à la phase précoce de la cardiomyopathie inflammatoire il existe une hyperpolymérisation des microfilaments responsable de dysfonctions contractile et mitochondriale.Les connaissances fondamentales acquises au cours de ce travail de thèse suggèrent une implication directe des microtubules et des microfilaments dans la physiopathologie des cardiomyopathies inflammatoires.
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Grimaldi, David. "Mécanismes cellulaires et moléculaires de l'immunodépression post-infectieuse." Phd thesis, Université René Descartes - Paris V, 2013. http://tel.archives-ouvertes.fr/tel-00924659.
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Les infections graves entraînent une dysrégulation de la réaction inflammatoire associée à une immunodépression complexe associée à la survenue d'infections nosocomiales. Les mécanismes cellulaires et moléculaires qui régulent ces phénomènes demeurent largement incompris. A l'interface entre système immunitaire inné et adaptatif, les cellules dendritiques et les lymphocytes innés pourraient être impliqués dans l'immunodépression post-infectieuse. Par ailleurs, les récepteurs de type Toll (TLR) déterminent l'amplitude de la réponse inflammatoire initiale, mais leur contribution dans le développement de l'immunodépression post-infectieuse n'a pas été établie. Les objectifs de ce projet de recherche étaient d'investiguer le rôle des cellules dendritiques, des lymphocytes de type innés et des voies de signalisation dépendantes des TLRs dans l'immunodépression induite par le sepsis. Nous avons mené ce programme de recherche en combinant une double approche translationnelle et expérimentale. Nous avons étudié la cinétique des cellules dendritiques circulantes chez le patient septique et montré que leur déplétion était associée à la survenue d'infections nosocomiales. L'analyse des trois souspopulations de lymphocytes T innés (lymphocytes γδ, NKT et MAIT) chez le patient septique a montré que seuls les lymphocytes MAIT présentaient une déplétion associée au sepsis sévère, dont la persistance était également corrélée à la survenue d'infections nosocomiales. Enfin, à l'aide de souris knockout nous avons étudié le rôle de TLR2, TLR4 et TLR5 sur la réponse anti-bactérienne dans un modèle murin de pneumonie secondaire à P. aeruginosa à distance d'un sepsis polymicrobien sublétal. Nous avons montré que les souris déficientes pour TLR2 étaient protégées de l'infection secondaire grâce à une meilleure clairance bactérienne. Ce travail introduit des perspectives nouvelles dans la physiopathologie de l'immunodépression post-infectieuse et suggère des applications thérapeutiques potentielles.
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Navarro, Xavier. "Analysis of cerebral and respiratory activity in neonatal intensive care units for the assessment of maturation and infection in the early premature infant." Phd thesis, Université Rennes 1, 2013. http://tel.archives-ouvertes.fr/tel-00979727.
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This Ph.D. dissertation processes and analyzes signals from the neonatal intensive care units (NICUs) for the study of maturity, systemic infection (sepsis) and the influence of immunization in the premature newborn. A special attention is payed to the electroencephalography and the breathing signal. The former is often contaminated by several sources of noise, thus methods based on the signals decomposition and optimal noise cancellation, adapted to the characteristics of the immature EEG, were proposed and evaluated objectively on real and simulated signals. By means of the EEG and delta burst analysis, detected automatically by a proposed classifier, infant's maturation and the effects of vaccination are studied. Concerning the second signal, breathing, non-linear and fractal methods are adapted to evaluate maturity and sepsis. A robustness study of estimation methods is also conducted, showing that the Hurst exponent, estimated on respiratory variability signals, is a good detector of infection.
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Yang, Q., M. Zhang, Dean J. Harrington, G. W. Black, and I. C. Sutcliffe. "A proteomic investigation of Streptococcus agalactiae reveals that human serum induces the C protein β antigen and arginine deiminase." 2011. http://hdl.handle.net/10454/11568.
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NoStreptococcus agalactiae is a major neonatal pathogen. Disease progression is characterised by bacterial adaptation from commensal maternal vaginal colonisation to environments associated with neonatal disease, including exposure to blood. To explore this adaptation in vitro, we have used proteomics to identify proteins differentially expressed following growth on Todd Hewitt agar in the presence or absence of 10% v/v human serum. Twelve differentially expressed proteins were identified. Notably, the C protein β antigen and arginine deiminase proteins were upregulated following growth in the presence of human serum, consistent with previous studies implicating these two proteins in the pathogenesis of S. agalactiae disease.