Cellular and Molecular Tissue Response to Triple Antibiotic Intracanal Dressing

Introduction

The aim of this study was to characterize the response of mouse subcutaneous tissue to triple antibiotic paste (TAP) using conventional light microscopy and real-time PCR (qRT-PCR).

Methods

Polyethylene tubes containing TAP or calcium hydroxide (CH) (ie, the control group) were implanted in mouse subcutaneous tissue. Animals that received empty tubes or no tubes were used as additional controls. After periods of 7, 21, and 63 days postimplantation, the specimens were removed and subjected to histologic processing. The number of inflammatory cells and vessels, vessel areas, vascular density, and relative percentage of collagen were evaluated. Gene expression of proinflammatory (interleukin-1 beta, tumor necrosis factor alpha, and interleukin 17) and anti-inflammatory (transforming growth factor beta) cytokines and angiogenic factors (vascular endothelial growth factor and hypoxia-inducible factor-1 alpha) was quantified by 7 and 21 days postimplantation. Results were analyzed using the Student t test, analysis of variance, and the Tukey test (α = 0.05).

Results

TAP induced an exuberant inflammatory and angiogenic response, with higher numbers of inflammatory cells, higher vascular area and density, and lower relative percentage of collagen compared with CH. In general, the expression of genes involved in inflammation and angiogenesis was higher in the TAP group compared with animals that received CH or empty tubes.

Conclusions

The response of mouse subcutaneous tissue to TAP was characterized by exuberant and persistent inflammatory and angiogenic responses with no repair and high gene expression of biomarkers associated with inflammation and angiogenesis.     

Sunscreen use and skin protection behavior on the Belgian beach

BACKGROUND: Public health campaigns encourage the public to protect themselves against skin cancer by using sunscreens and taking other protective measures. However, it is difficult to estimate the level of awareness among the general public. METHODS: This study explores the prevalence and predictors of solar protection behavior in a community sample of beachgoers. During the months of May, June, July and August 2001 a total of 360 participants (145 men and 215 women) were randomly selected from several Belgian beaches in and around the city of Ostend, Belgium. The solar protection behavior of each participant was assessed by direct observation and interview. RESULTS: The risk awareness percentages were 70.6% for skin cancer, 60.8% for sunburn and 25.0% for skin aging. These percentages were considerably higher in the female participant group than in the male group. Sunscreen cream was the most popular preventive behavior, especially in the female population, whereas the alternative protective measures (limited exposure during peak sun hours, the use of shade and the use of protective clothing and hats) were more popular in the male group. CONCLUSIONS: While solar protection has become part of routine beach behavior, there is room for improvement by more frequent application of sunscreen cream, the use of a higher sun protection factor (SPF) (15+), timed sunbathing, more use of clothing and hats and more seeking of shade. The results of this study can assist in evaluating the effectiveness of current sun-protection campaigns and health education programs.     

Impact of obesity on autoimmune arthritis and its cardiovascular complications

Obesity can instigate and sustain a systemic low-grade inflammatory environment that can amplify autoimmune disorders and their associated comorbidities. Metabolic changes and inflammatory factors produced by the adipose tissue have been reported to aggravate autoimmunity and predispose the patient to cardiovascular disease (CVD) and metabolic comorbidities. Rheumatoid arthritis (RA) and psoriatic arthritis (PsA) are autoimmune arthritic diseases, often linked with altered body mass index (BMI). Severe joint inflammation and bone destruction have a debilitating impact on the patient's life; there is also a staggering risk of cardiovascular morbidity and mortality. Furthermore, these patients are at risk of developing metabolic symptoms, including insulin resistance resulting in type 2 diabetes mellitus (T2DM). In addition, arthritis severity, progression and response to therapy can be markedly affected by the patient's BMI. Hence, a complex integrative pathogenesis interconnects autoimmunity with metabolic and cardiovascular disorders. This review aims to shed light on the network that connects obesity with RA, PsA, systemic lupus erythematosus and Sj?gren's syndrome. We have focused on clarifying the mechanism by which obesity affects different cell types, inflammatory factors and traditional therapies in these autoimmune disorders. We conclude that to further optimize arthritis therapy and to prevent CVD, it is imperative to uncover the intricate relation between obesity and arthritis pathology.     

Recurrence of blackwater fever: triggering of relapses by different antimalarials

Five cases of blackwater fever (BWF) are described, all of whom had a history of recent quinine therapy. In two cases a second haemolytic crisis was induced by halofantrine, in one case also a third. Increasing frequency of this syndrome with its dramatic clinical presentation is to be expected as imported P. falciparum infection, parasite resistance to chloroquine and the use of quinine and other related antimalarials become more frequent.     

Enhanced glucocorticoid receptor signaling in T cells impacts thymocyte apoptosis and adaptive immune responses

To study the effect of enhanced glucocorticoid signaling on T cells, we generated transgenic rats overexpressing a mutant glucocorticoid receptor with increased ligand affinity in the thymus. We found that this caused massive thymocyte apoptosis at physiological hormone levels, which could be reversed by adrenalectomy. Due to homeostatic proliferation, a considerable number of mature T lymphocytes accumulated in the periphery, responding normally to costimulation but exhibiting a perturbed T-cell repertoire. Furthermore, the transgenic rats showed increased resistance to experimental autoimmune encephalomyelitis, which manifests in a delayed onset and milder disease course, impaired leukocyte infiltration into the central nervous system and a distinct cytokine profile. In contrast, the ability of the transgenic rats to mount an allergic airway response to ovalbumin was not compromised, although isotype switching of antigen-specific immunoglobulins was altered. Collectively, our findings suggest that endogenous glucocorticoids impact T-cell development and favor the selection of Th2- over Th1-dominated adaptive immune responses.     

Anti‐Aspergillus human host defence relies on type 1 T helper (Th1), rather than type 17 T helper (Th17), cellular immunity

Both interferon‐γ‐producing type 1 T helper (Th1)‐ and interleukin‐17 (IL‐17)‐producing Th17 cells have been proposed to be involved in anti‐fungal host defence. Although invasive aspergillosis is one of the most severe human fungal infections, little is known regarding the relative importance of the Th1 versus Th17 cellular immune pathways for the human anti‐Aspergillus host defence. Using human peripheral blood mononuclear cells and a system consisting of monocyte‐derived macrophages with lymphocytes, we found that Aspergillus fumigatus is a weak inducer of human IL‐17 but induces a strong Th1 response. These data were validated by the very low IL‐17 levels in bronchoalveolar lavage fluid and serum of patients with invasive aspergillosis. Surprisingly, live A. fumigatus reduced IL‐17 production induced by mitogenic stimuli. This effect was mediated through the propensity of A. fumigatus to metabolize tryptophan and release kynurenine, which modulates the inflammatory response through inhibition of IL‐17 production. In conclusion, A. fumigatus does not stimulate production of IL‐17 and human host defence against aspergillosis may not rely on potent Th17 responses.     

CXCR3 determines strain susceptibility to murine cerebral malaria by mediating T lymphocyte migration toward IFN-gamma-induced chemokines

Cerebral malaria (CM) results from the binding of infected erythrocytes and leukocytes to brain endothelia. The precise mechanisms underlying lymphocyte recruitment and activation in CM remain unclear. Therefore, the expression of various chemokines was quantified in brains of mice infected with Plasmodium berghei ANKA (PbA). Several chemokines attracting monocytes and activated T-lymphocytes were expressed at high levels. Their expression was almost completely abrogated in IFN-gamma ligand and receptor KO mice, indicating that IFN-gamma is an essential chemokine inducer in vivo. Surprisingly, the expression levels of chemokines, IFN-gamma and also adhesion molecules in the brain were not lower in CM-resistant Balb/c and DBA/2 mice compared to CM-sensitive C57BL/6 and DBA/1 mice, although T lymphocyte sequestration in the brain was significantly less in CM-resistant than in CM-sensitive mice. This difference correlated with a higher up-regulation of the CXC chemokine receptor (CXCR)-3 on splenic T cells and a higher chemotactic response to IFN-gamma-inducible protein-10 (IP-10) in C57BL/6 compared to Balb/c mice. In conclusion, parasite-induced IFN-gamma in the brain results in high local expression levels of specific chemokines for monocytes and lymphocytes. The strain-dependent susceptibility to develop CM is more related to the expression of CXCR3 in circulating leukocytes than to the chemokine expression levels in the brain.     

Respective roles of inflammation and axonal breakdown in the regulation of peripheral nerve hemopexin: an analysis in rats and in C57BL/Wlds mice

We have previously demonstrated that one of the peripheral nerve responses to injury is the overexpression of hemopexin (HPX). Here, we demonstrate that Wallerian degeneration is required for this response, since HPX does not increase in C57BL/Wlds mice, which display a severely impaired Wallerian degeneration. We also show that HPX synthesis is dramatically increased in macrophages during their activation or after IL-6 stimulation. However, IL-6-driven HPX overexpression occurs in vivo and in vitro in the absence of substantial macrophage invasion. We conclude that, after nerve injury, HPX overexpression occurs first in Schwann cells as a result of axotomy and is subsequently regulated by inflammation. Furthermore, our results and those already described suggest that IL-6, synthesized by the various cell types producing HPX, control nerve HPX expression via paracrine and autocrine mechanisms.