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      1. Author :
        Dai, T.; Tegos, G. P.; Burkatovskaya, M.; Castano, A. P.; Hamblin, M. R.
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2009
      5. Publication :
        Antimicrobial Agents and Chemotherapy
      6. Products :
      7. Volume :
        53
      8. Issue :
        N/A
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        IVIS, Xenogen, Xen5, Xen44
      12. Abstract :
        An engineered chitosan acetate bandage preparation (HemCon) is used as a hemostatic dressing, and its chemical structure suggests that it should also be antimicrobial. We previously showed that when a chitosan acetate bandage was applied to full-thickness excisional wounds in mice that had been infected with pathogenic bioluminescent bacteria (Pseudomonas aeruginosa, Proteus mirabilis, and Staphylococcus aureus), it was able to rapidly kill the bacteria and save the mice from developing fatal infections. Wound healing was also stimulated. In the present study, we asked whether a chitosan acetate bandage could act as a topical antimicrobial dressing when it was applied to third-degree burns in mice contaminated with two of these bacterial species (P. aeruginosa and P. mirabilis). Preliminary experiments established the length of burn time and the number of bacteria needed to produce fatal infections in untreated mice and established that the chitosan acetate bandage could adhere to the infected burn for up to 21 days. In the case of P. aeruginosa infections, the survival rate of mice treated with the chitosan acetate bandage was 73.3% (whereas the survival rate of mice treated with a nanocrystalline silver dressing was 27.3% [P = 0.0055] and that of untreated mice was 13.3% [P < 0.0002]). For P. mirabilis infections, the comparable survival rates were 66.7%, 62.5%, and 23.1% respectively. Quantitative bioluminescent signals showed that the chitosan acetate bandage effectively controlled the growth of bacteria in the burn and prevented the development of systemic sepsis, as shown by blood culture. These data suggest that chitosan acetate bandage is efficacious in preventing fatal burn infections.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/19015341
      14. Call Number :
        137209
      15. Serial :
        5713
      1. Author :
        Kirby, A. C.; Beattie, L.; Maroof, A.; Rooijen, N. van; Kaye, P. M.
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2009
      5. Publication :
        American Journal of Pathology
      6. Products :
      7. Volume :
        175
      8. Issue :
        N/A
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        IVIS, Xenogen, Xen10
      12. Abstract :
        Marginal zone macrophages in the murine spleen play an important role in the capture of blood-borne pathogens and are viewed as an essential component of host defense against the development of pneumococcal sepsis. However, we and others have previously described the loss of marginal zone macrophages associated with the splenomegaly that follows a variety of viral and protozoal infections; this finding raises the question of whether these infected mice would become more susceptible to secondary pneumococcal infection. Contrary to expectations, we found that mice lacking marginal zone macrophages resulting from Leishmania donovani infection have increased resistance to Streptococcus pneumoniae type 3 and do not develop sepsis. Using biophotonic imaging, we observed that pneumococci are rapidly trapped in the spleens of L. donovani-infected mice. By selective depletion studies using clodronate liposomes, depleting monoclonal antibodies specific for Ly6C/G and Ly6G, and CD11c-DTR mice, we show that the enhanced early resistance in L. donovani-infected mice is entirely due to the activity of SIGNR1? red pulp macrophages. Our data demonstrate, therefore, that the normal requirement for SIGNR1+ marginal zone macrophages to protect against a primary pneumococcal infection can, under conditions of splenomegaly, be readily compensated for by activated red pulp macrophages.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/19644016
      14. Call Number :
        139699
      15. Serial :
        7610
      1. Author :
        Xie, Chao; Liang, Bojian; Xue, Ming; Lin, Angela S.P.; Loiselle, Alayna; Schwarz, Edward M.; Guldberg, Robert E.; O'Keefe, Regis J.; Zhang, Xinping
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2009
      5. Publication :
        Am J Pathol
      6. Products :
      7. Volume :
        175
      8. Issue :
        N/A
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        Xen10, Xen 10, Streptococcus pneumoniae Xen10, IVIS
      12. Abstract :
        Although the essential role of cyclooxygenase (COX)-2 in fracture healing is known, the targeted genes and molecular pathways remain unclear. Using prostaglandin E2 receptor (EP)2 and EP4 agonists, we examined the effects of EP receptor activation in compensation for the lack of COX-2 during fracture healing. In a fracture-healing model, COX-2-/- mice showed delayed initiation and impaired endochondral bone repair, accompanied by a severe angiogenesis deficiency. The EP4 agonist markedly improved the impaired healing in COX-2-/- mice, as evidenced by restoration of bony callus formation on day 14, a near complete reversal of bone formation, and an approximately 70% improvement of angiogenesis in the COX-2-/- callus. In comparison, the EP2 agonist only marginally enhanced bone formation in COX-2-/- mice. To determine the differential roles of EP2 and EP4 receptors on COX-2-mediated fracture repair, the effects of selective EP agonists on chondrogenesis were examined in E11.5 long-term limb bud micromass cultures. Only the EP4 agonist significantly increased cartilage nodule formation similar to that observed during prostaglandin E2 treatment. The prostaglandin E2/EP4 agonist also stimulated MMP-9 expression in bone marrow stromal cell cultures. The EP4 agonist further restored the reduction of MMP-9 expression in the COX-2-/- fracture callus. Taken together, our studies demonstrate that EP2 and EP4 have differential functions during endochondral bone repair. Activation of EP4, but not EP2 rescued impaired bone fracture healing in COX-2-/- mice.
      13. URL :
        http://ajp.amjpathol.org/cgi/content/abstract/175/2/772
      14. Call Number :
        PKI @ kd.modi @ 2
      15. Serial :
        10401
      1. Author :
        Kozloff, K. M.; Quinti, L.; Patntirapong, S.; Hauschka, P. V.; Tung, C. H.; Weissleder, R.; Mahmood, U.
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2009
      5. Publication :
        Bone
      6. Products :
      7. Volume :
        44
      8. Issue :
        N/A
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        OsteoSense, IVIS Animals; Animals, Newborn; Bone Development; Bone Resorption/enzymology; Calcification, Physiologic; Cathepsin K; Cathepsins/genetics/*metabolism; Cell Survival; Cells, Cultured; Cryoultramicrotomy; Female; Femur/pathology; Fluorescence; Humans; Mice; Mice, Inbred BALB C; *Molecular Probe Techniques; Molecular Probes/metabolism; Osteoclasts/cytology/*enzymology; Ovariectomy; RNA, Messenger/genetics/metabolism; Up-Regulation
      12. Abstract :
        Osteoclasts degrade bone matrix by demineralization followed by degradation of type I collagen through secretion of the cysteine protease, cathepsin K. Current imaging modalities are insufficient for sensitive observation of osteoclast activity, and in vivo live imaging of osteoclast resorption of bone has yet to be demonstrated. Here, we describe a near-infrared fluorescence reporter probe whose activation by cathepsin K is shown in live osteoclast cells and in mouse models of development and osteoclast upregulation. Cathepsin K probe activity was monitored in live osteoclast cultures and correlates with cathepsin K gene expression. In ovariectomized mice, cathepsin K probe upregulation precedes detection of bone loss by micro-computed tomography. These results are the first to demonstrate non-invasive visualization of bone degrading enzymes in models of accelerated bone loss, and may provide a means for early diagnosis of upregulated resorption and rapid feedback on efficacy of treatment protocols prior to significant loss of bone in the patient.
      13. URL :
        http://www.ncbi.nlm.nih.gov/pubmed/19007918
      14. Call Number :
        PKI @ kd.modi @ 1
      15. Serial :
        10466
      1. Author :
        Bondareva, A.; Downey, C. M.; Ayres, F.; Liu, W.; Boyd, S. K.; Hallgrimsson, B.; Jirik, F. R.
      2. Title :
      3. Type :
        Journal Article
      4. Year :
        2009
      5. Publication :
        PLoS One
      6. Products :
      7. Volume :
        4
      8. Issue :
        N/A
      9. Page Numbers :
        N/A
      10. Research Area :
        N/A
      11. Keywords :
        IVIS, Xenogen
      12. Abstract :
        Lysyl oxidase (LOX), an extracellular matrix remodeling enzyme, appears to have a role in promoting breast cancer cell motility and invasiveness. In addition, increased LOX expression has been correlated with decreases in both metastases-free, and overall survival in breast cancer patients. With this background, we studied the ability of beta-aminopropionitrile (BAPN), an irreversible inhibitor of LOX, to regulate the metastatic colonization potential of the human breast cancer cell line, MDA-MB-231. BAPN was administered daily to mice starting either 1 day prior, on the same day as, or 7 days after intracardiac injection of luciferase expressing MDA-MB-231-Luc2 cells. Development of metastases was monitored by in vivo bioluminescence imaging, and tumor-induced osteolysis was assessed by micro-computed tomography (microCT). We found that BAPN administration was able to reduce the frequency of metastases. Thus, when BAPN treatment was initiated the day before, or on the same day as the intra-cardiac injection of tumor cells, the number of metastases was decreased by 44%, and 27%, and whole-body photon emission rates (reflective of total tumor burden) were diminished by 78%, and 45%, respectively. In contrast, BAPN had no effect on the growth of established metastases. Our findings suggest that LOX activity is required during extravasation and/or initial tissue colonization by circulating MDA-MB-231 cells, lending support to the idea that LOX inhibition might be useful in metastasis prevention.
      13. URL :
        http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=19440335
      14. Call Number :
        136327
      15. Serial :
        7869
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