Effects of platelet activating factor (PAF) and other vasoconstrictors on a model of angiogenesis in the mouse.
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The combination of sponge implant and 133Xe washout technique described in this paper provides a model to study neovascularization in mice which can be observed over several days in the same animal. The local blood flow within the ingrowing granulation tissue has been determined by measuring the washout rate of 133Xe injected into the implants. Tissue infiltration of the sponges was assessed by histological examination and by measurement of sponge wet weight, protein and glycosaminoglycans (GAG) content. The newly formed blood vessels, despite having abnormal configuration, responded to platelet activating factor (PAF) and to endothelin-1 (ET-1) similarly to the normal mature vessels in adjacent skin. However, the sponge blood vessels were more sensitive to angiotensin II than the skin blood vessels. Using this model we have also demonstrated an angiogenic activity of PAF substantiated by increased blood flow and biochemical variables in the implanted sponges. (+info)
Histologic evaluation of wound healing in experimental intestinal anastomoses: effects of antineoplastic agents.
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Histologic evaluation of intestinal wound healing with and without cytostatics was performed in 36 rats. Variables were the relative position of the wound edges in mucosa and muscularis, necrosis, exudate, granulation tissue, granulocytes, macrophages, fibroblasts, restoration of the mucosal epithelium, and repair of the muscularis propria. The relative position of the wound edges in the mucosa and the muscularis in the initial phase of wound healing depended on technique but appeared to improve in the later phases of wound healing. It was not affected by the administration of antineoplastic agents; neither were muscularis repair, epithelial restoration of the mucosa, necrosis, nor exudate. Granulation tissue, fibroblasts and macrophages were present in maximal amounts after 7 days appearing later or showing this maximum at a different moment in time when antineoplastic agents were given. The processes of epithelial and muscularis repair were not influenced by the relative position of the wound edges. Granulation tissue, macrophages, and fibroblasts were the best parameters for measuring the histologic evolution of intestinal wound healing, and the effects of antineoplastic agents upon it. (+info)
PRODUCTION OF AN ANTI-INFLAMMATORY SUBSTANCE AT A SITE OF INFLAMMATION.
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The anti-inflammatory effect of various substances was measured in rats implanted with cotton wool pellets. Injection or implantation of irritant materials decreased the deposition of granulation tissue on the pellets. As the amount of irritant material increased there was a corresponding decrease in the amount of tissue deposited on the pellets. There is evidence that this could not be explained by a limit to the amount of granulation tissue available within the body, and competition for it between the cotton pellets and the implanted substances. An alternative hypothesis that an anti-inflammatory substance is produced at the site of irritation (the site of implantation of the irritant substance, such as polyester sponges) was investigated. The evidence obtained supports this hypothesis. Inflammatory exudate, squeezed from polyester sponges which had been implanted subcutaneously in the backs of adrenalectomized rats. The substance responsible for this effect is probably not a steroid, and is not normally present in the plasma of adrenalectomized animals. There is, however, some (although not conclusive) evidence that it is present in the plasma of animals in which sponges have been implanted. It does not appear to be produced by incubation in vitro of plasma with sponge. The significance of these observations is discussed. (+info)
THE ARCHITECTURE OF CASEOUS NODULES IN THE LUNG AND THE PLACE OF THE WORD "ACINAR" IN DESCRIBING TUBERCULOUS LESIONS.
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In a study of caseous pulmonary nodules, it was found possible to identify the cellular and connective tissue background of the caseous material. In the absence of liquefaction, the connective tissues were found to retain their reaction to special stains indefinitely, and fibrin could be identified for periods up to one year after the onset of caseation. This allowed recognition of the part of lung involved and of pathological changes which had preceded caseation. Identification of the site of the suppurative "focus" in the respiratory bronchiole was important because bacilli could be found there most readily. Though lesions often outlined the acinus with clarity, the only value of the term "acinar" was to define the limits of one particular lesion. (+info)
Intratumoral distribution of fluorine-18-fluorodeoxyglucose in vivo: high accumulation in macrophages and granulation tissues studied by microautoradiography.
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While 2-deoxy-2-[18F]fluoro-D-glucose ([18F]FDG) is a useful tumor imaging agent, its intratumoral distribution has not been described well at the cellular level. In order to demonstrate cellular localization of [18F]FDG and 2-deoxy-D-[3H]glucose (3H-DG) uptake by the tumor in vivo, C3H/He mice transplanted subcutaneously with FM3A tumors were studied 1 hr after intravenous injection of [18F]FDG or 3H-DG using micro- and macro-autoradiography. Fluorine-18-FDG and 3H-DG showed the same distribution pattern in the tumor with both autoradiographic methods. The newly formed granulation tissue around the tumor and macrophages, which were massively infiltrating the marginal areas surrounding necrotic area of the tumor showed a higher uptake of [18F]FDG than the viable tumor cells. A maximum of 29% of the glucose utilization was derived from nontumor tissue in this tumor. The comparison of double-tracer autoradiographic distribution patterns of [18F]FDG and [6-3H]-thymidine showed the differences and the similarities between glucose utilization and the DNA synthesis. Whole proliferating tissue metabolizes [18F] FDG but not vice versa. High accumulation of [18F]FDG in the tumor is believed to represent high metabolic activity of the viable tumor cells. Our results showed that one should consider not only the tumor cells proper but also the non-neoplastic cellular elements, which appear in association with growth or necrosis of the tumor cells, for precise analysis of [18F]FDG uptake in tumor-bearing subjects, especially after anti-neoplastic treatment. (+info)
Nutritional support for wound healing.
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Healing of wounds, whether from accidental injury or surgical intervention, involves the activity of an intricate network of blood cells, tissue types, cytokines, and growth factors. This results in increased cellular activity, which causes an intensified metabolic demand for nutrients. Nutritional deficiencies can impede wound healing, and several nutritional factors required for wound repair may improve healing time and wound outcome. Vitamin A is required for epithelial and bone formation, cellular differentiation, and immune function. Vitamin C is necessary for collagen formation, proper immune function, and as a tissue antioxidant. Vitamin E is the major lipid-soluble antioxidant in the skin; however, the effect of vitamin E on surgical wounds is inconclusive. Bromelain reduces edema, bruising, pain, and healing time following trauma and surgical procedures. Glucosamine appears to be the rate-limiting substrate for hyaluronic acid production in the wound. Adequate dietary protein is absolutely essential for proper wound healing, and tissue levels of the amino acids arginine and glutamine may influence wound repair and immune function. The botanical medicines Centella asiatica and Aloe vera have been used for decades, both topically and internally, to enhance wound repair, and scientific studies are now beginning to validate efficacy and explore mechanisms of action for these botanicals. To promote wound healing in the shortest time possible, with minimal pain, discomfort, and scarring to the patient, it is important to explore nutritional and botanical influences on wound outcome. (+info)
The essential involvement of cross-talk between IFN-gamma and TGF-beta in the skin wound-healing process.
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Several lines of in vitro evidence suggest the potential role of IFN-gamma in angiogenesis and collagen deposition, two crucial steps in the wound healing process. In this report, we examined the role of IFN-gamma in the skin wound healing process utilizing WT and IFN-gamma KO mice. In WT mice, excisional wounding induced IFN-gamma mRNA and protein expression by infiltrating macrophages and T cells, with a concomitant enhancement of IL-12 and IL-18 gene expression. Compared with WT mice, IFN-gamma KO mice exhibited an accelerated wound healing as evidenced by rapid wound closure and granulation tissue formation. Moreover, IFN-gamma KO mice exhibited enhanced angiogenesis with augmented vascular endothelial growth factor mRNA expression in wound sites, compared with WT mice, despite a reduction in the infiltrating neutrophils, macrophages, and T cells. IFN-gamma KO mice also exhibited accelerated collagen deposition with enhanced production of TGF-beta1 protein in wound sites, compared with WT mice. Furthermore, the absence of IFN-gamma augmented the TGF-beta1-mediated signaling pathway, as evidenced by increases in the levels of total and phosphorylated Smad2 and a reciprocal decrease in the levels of Smad7. These results demonstrate that there is crosstalk between the IFN-gamma/Stat1 and TGF-beta1/Smad signaling pathways in the wound healing process. (+info)
Sponge-induced angiogenesis and inflammation in PAF receptor-deficient mice (PAFR-KO).
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1. To determine biological functions of platelet-activating factor (PAF) in chronic inflammation, we have investigated the kinetics of angiogenesis, inflammatory cells recruitment and cytokine production in sponge-induced granuloma in wild type and PAF receptor-deficient mice (PAFR-KO). 2. Angiogenesis as determined by morphometric analysis and hemoglobin content was significantly higher in the implants of PAFR-KO mice at all time points. Treatment with PAF receptor antagonist UK74505 (30 mg kg(-1)) also increased angiogenesis in sponge implants. 3. Neutrophils and macrophages accumulation, as determined by myeloperoxidase and N-acetylglucosaminidase activities in the supernatant of implanted sponges were markedly decreased in PAFR-KO mice. Surprisingly, the levels of the proinflammatory chemokines, keratinocyte-derived chemokine and chemokine monocyte chemoattractant protein 1 were higher in the implants of the transgenic animals. 4. We have shown that angiogenesis was stimulated in PAFR-KO mice whereas inflammation was decreased, indicating that PAF is an endogenous regulator of new blood vessels formation in the inflammatory microenvironment induced by the sponge implant. (+info)