Induction of M2 Macrophages Prevents Bone Loss in Murine Periodontitis Models.

Periodontitis is characterized by the progressive destruction of tooth-supporting alveolar bone, which is mainly caused by chronic inflammation in response to persistent bacterial insult. It has recently become clear that the pathogenesis of periodontitis is associated with a high ratio of proinflammatory M1 (classically activated) macrophages to anti-inflammatory M2 (alternatively activated). To decrease the inflammatory activity, we locally delivered the C-C motif chemokine ligand 2 (CCL2) using controlled-release microparticles (MPs). CCL2 is known to promote chemotaxis of M0 or M2 phenotype macrophages to the inflamed site and induce M2 phenotype polarization locally. Our in vitro data showed that CCL2 increased the number of M2 phenotype macrophages, decreased TNF-α secretion, and enhanced chemotaxis of RAW264.7 cells toward CCL2 MPs. Moreover, we induced periodontal disease in 2 animal models through inoculation of Porphyromonas gingivalis and ligature around the murine molar. Micro-computed tomography analysis showed significant reduction of alveolar bone loss in the CCL2 MP treatment group when compared with a blank MP group and a no-treatment periodontitis group in both models. Immunohistologic analysis showed a significant increase in the M2 phenotype subset and a decrease in the M1 phenotype subset in the CCL2 MP group of the P. gingivalis-induced model. Also, in both models, tartrate-resistant acidic phosphatase staining showed significantly fewer numbers of osteoclasts in the CCL2 MP group in alveolar bone area. Moreover, quantitative polymerase chain reaction results showed a significant increase in IL-1RA (interleukin 1 receptor antagonist) mRNA expression and a decrease in RANKL (receptor activator of nuclear factor kappa-Β ligand) mRNA expression in the CCL2 MP group in the ligature model. In summary, manipulation of endogenous M2 phenotype macrophages with CCL2 MPs decreased the M1 phenotype:M2 phenotype ratio and prevented alveolar bone loss in mouse periodontitis models. The delivery of CCL2 MPs provides a novel approach to treat periodontal disease.

The impact of a contaminated city water supply on an emergency department.

In March 2007 Galway City and County's water supply was officially contaminated by cryptosporidiosis. The medical and nursing staff at the city's only Emergency Department had noted a rise in an atypical form of gastroenteritis in the preceding months. A retrospective audit of 11,723 charts from January 1st 2007 to 22nd March (day after contamination was confirmed) was performed to identify these patients. The number of potential gastroenteritis cases was 185 (incidence 1.6%), with a peak five weeks before the outbreak was confirmed. Half the patients were aged between 20 and 34. Pain (80%), nausea or vomiting (74%) and diarrhoea (66.5%) were the most frequent symptoms. The mean duration of symptoms at presentation was 2 days. Stool samples were sent for nine patients and four of these were tested for Cryptosporidium. Over a quarter (28.6%) of patients were admitted and almost three-quarters (69.7% +/- 7%) had a residential address in the affected area. Difficulty exists in the early identification of new outbreaks and many of the affected patients are not detected using routine surveillance or current capture methods.