Impaired Immune Tolerance to Porphyromonas gingivalis Lipopolysaccharide Promotes Neutrophil Migration and Decreased Apoptosis.

Periodontitis, a chronic inflammatory disease of the tissues supporting the teeth, is characterized by an exaggerated host immune and inflammatory response to periopathogenic bacteria. Toll-like receptor activation, cytokine network induction, and accumulation of neutrophils at the site of inflammation are important in the host defense against infection. At the same time, induction of immune tolerance and the clearance of neutrophils from the site of infection are essential in the control of the immune response, resolution of inflammation, and prevention of tissue destruction. Using a human monocytic cell line, we demonstrate that Porphyromonas gingivalis lipopolysaccharide (LPS), which is a major etiological factor in periodontal disease, induces only partial immune tolerance, with continued high production of interleukin-8 (IL-8) but diminished secretion of tumor necrosis factor alpha (TNF-) after repeated challenge. This cytokine response has functional consequences for other immune cells involved in the response to infection. Primary human neutrophils incubated with P. gingivalis LPS-treated naïve monocyte supernatant displayed a high migration index and increased apoptosis. In contrast, neutrophils treated with P. gingivalis LPS-tolerized monocyte supernatant showed a high migration index but significantly decreased apoptosis. Overall, these findings suggest that induction of an imbalanced immune tolerance in monocytes by P. gingivalis LPS, which favors continued secretion of IL-8 but decreased TNF- production, may be associated with enhanced migration of neutrophils to the site of infection but also with decreased apoptosis and may play a role in the chronic inflammatory state seen in periodontal disease.

Verteporfin Photodynamic Therapy Cohort Study Report 2: Clinical Measures of Vision and Health-Related Quality of Life

Purpose: To quantify decreases in health-related quality of life (HRQoL) for given deterioration in clinical measures of vision; to describe the shape of these relationships; and to test whether the gradients of these relationships change with duration of visual loss.

Will Antiangiogenic Agents be a Future for Mesothelioma Therapy?

Background: Malignant mesothelioma (MM) is an aggressive disease that is diagnosed mostly in locally advanced or metastatic stage. In this condition chemotherapy with the combination cisplatin and pemetrexed or ralitrexed represents the standard treatment as supported by a phase III study. However, chemotherapy has very limited effect on the improvement of survival of patients and very few of the MM patients survive more than 2 years. A better understanding of molecular mechanisms and pathways involved in angiogenesis in MM is the basis for the development of new drugs targeted against these pathways responsible for the proliferation and survival of tumor cells.

A longitudinal observational study of insulin therapy and glycaemic control in Scottish children with Type 1 diabetes: DIABAUD 3

Objective/background Our objective was to investigate glycaemic control in children with Type 1 diabetes in Scotland and to analyse the effect of changing 'conventional' insulin regimen strategies on outcome. DIABAUD 2 ( 1997 - 1998) (D2) demonstrated that average glycaemic control in young people with Type 1 diabetes in Scotland was poor, with mean HbA(1c) of 9.0%. Over 90% were then treated with a twice-daily insulin regimen. The aim of DIABAUD 3 ( 2002 2004) (D3) was to determine if control had improved, and to examine changes in insulin regimen and effects on glycaemic control.