No description available.

No description available.

No description available.

No description available.

No description available.

No description available.

No description available.

No description available.

In this thesis I examined the role of circulating monocytes and lung macrophages in the pathogenesis of the early fibrotic, progressive fibrotic and resolution phases of pulmonary fibrosis. Pulmonary fibrosis with destruction of lung architecture and consequent respiratory failure and death represents a massive worldwide health burden. Although idiopathic pulmonary fibrosis (IPF) is the archetypal and most common cause of lung fibrosis, numerous respiratory diseases can progress to pulmonary fibrosis, and this usually signifies a worse prognosis. Importantly, the incidence and prevalence of IPF continue to rise and it remains one of the few respiratory conditions for which there are no effective therapies. The mechanisms resulting in pulmonary fibrosis are controversial. Early work in the 1980s and 1990s suggested that lung macrophages were important. However, at the turn of the 21st century there was a shift to a belief that pulmonary fibrosis resulted from aberrant wound healing as a consequence of repetitive epithelial injury from an as yet unknown cause. However, with the ever expanding knowledge of the importance of macrophages in other fibrotic conditions such as the kidney and liver, the potential importance of macrophages in pulmonary fibrosis has become more pertinent. Using an in vivo depletional strategy in several murine models of lung fibrosis, in conjunction with human studies, I sought to characterise the role of circulating monocytes and lung macrophages in the pathogenesis of pulmonary fibrosis. I have established that circulating monocytes and lung macrophages are not critical for the development of early lung fibrosis. In contrast, circulating monocytes and lung macrophages are important during the progressive fibrotic phase of lung fibrosis. Furthermore, my data suggest that the pro-fibrotic alternatively activated macrophages may be the sub-class of macrophages that mediate this fibrogenic effect. In addition and in contrast, I have established that lung macrophages are required for the resolution of fibrosis. This finding is in keeping with important work performed in the field of liver fibrosis. There is an ever increasing literature examining the role of matrix metalloproteinases (MMPs) during tissue fibrosis and repair. My work has suggested that during lung fibrosis there may be compartmental specific functions of MMPs that regulate lung fibrogenesis, although more work is required before this exciting finding can be properly defined.

OBJETIVO: Determinar los predictores no invasivos de la severidad de la fibrosis hepática en pacientes con infección crónica por hepatitis C del Servicio de Gastroenterología del Hospital IV Alberto Sabogal (EsSALUD), durante el período diciembre 2000 – diciembre 2002. MATERIAL Y MÉTODOS: Se incluyeron a 30 pacientes con serología positiva para HCV que fueron sometidos a Laparoscopia más biopsia hepática. Estudio observacional, descriptivo, retrospectivo y de corte transversal. Se usó la base de datos del programa SPSS versión 10.0, y se evaluó la asociación mediante el test de Chi cuadrado (_i2), con una significancia estadística del 5%. RESULTADOS: La edad promedio fue de 56.27 ± 12.55 años, Se demostró asociación entre fibrosis severa y radio TGO/TGP mayor de 1 y esplenomegalia(p=0.018 y 0.001, respectivamente) en forma estadísticamente significativa,mientras que la plaquetopenia menor de 150,000 no mostró asociación con fibrosis hepática severa en el grupo de pacientes estudiados (p=0.136). CONCLUSIONES: El radio TGO/TGP mayor de 1 y la esplenomegalia pueden ser considerados como predictores de fibrosis avanzada en pacientes con infección crónica por hepatitis c. En estos pacientes quizás no sea necesaria una biopsia hepática. / --- OBJETIVE: To Determine the non-invasive predictors from Hepatic Fibrosis severity in patients with Hepatitis C chronic infection at Gastroenterology Service from Alberto Sabogal Hospital (EsSALUD), since december 2000 – december 2002. MATERIAL AND METHODS: 30 patients were included with positive HCV serology who had Laparoscopy and hepatic biopsy. This is an observational, descriptive, retrospective and transversal study. It was used SPSS 10.0 database program, and was evaluated its association with chi-square test (_i2), with 5% statistical significance. RESULTS: The age average was 56.27 ± 12.55 years old. A TGO/TGP ratio of major of 1 and splenomegaly correlated significantly with advance stage of fibrosis (p=0.018 and 0.001 respectively) but there wasn’t correlation between platelet count major of 150,000 and severe fibrosis (p=0.136). CONCLUSIONS: A TGO/TGP ratio of major of 1 and splenomegalia can predict advance stage of fibrosis in patients with chronic hepatitis C infection .In these patients, a liver biopsy may not be necessary. Key words: Hepatitis C chronic infection, Hepatic Fibrosis.