The Experts below are selected from a list of 243 Experts worldwide ranked by ideXlab platform
Paul L Mcneil - One of the best experts on this subject based on the ideXlab platform.
-
antibody neutralization of vascular endothelial growth factor inhibits wound Granulation Tissue formation
Journal of Surgical Research, 2001Co-Authors: Thomas R Howdieshell, Dianne Callaway, Whitney Webb, Michael D Gaines, Charles Procte, Jennife S Pollock, Tommy L Ock, Paul L McneilAbstract:Abstract Objective. The goal of this work was to test the functional role of vascular endothelial growth factor (VEGF) in promoting the vigorous Granulation Tissue formation, wound fluid accumulation, and angiogenic responses characteristic of this wound model. Background. Formation of vessel-rich Granulation Tissue is central to wound repair and is thought to be regulated by locally liberated angiogenic factors. Despite the clinical importance of Granulation Tissue formation in the early stage of wound healing, surprisingly little is known about the molecular identity of signals leading to Granulation Tissue invasion of a wound space. Methods. A ventral hernia, surgically created in the abdominal wall of 15 swine, was repaired using silicone sheeting and skin closure. An osmotic minipump, inserted in a remote subcutaneous pocket, delivered saline (n = 5), an irrelevant control antibody (n = 5), or neutralizing anti-VEGF antibody (n = 5) into the wound environment. Serial ultrasonography on Days 2, 4, 7, 9, 11, and 14 was used to determine the dimensions of the subcutaneous Granulation Tissue and wound fluid compartment. VEGF and transforming growth factor β1 (TGF-β1) levels in serial wound fluid samples were quantitated by ELISA. On Day 14, animals were sacrificed and the abdominal wall was harvested for histologic, biochemical, and molecular analyses. Results. In animals receiving saline or an irrelevant antibody, a nearly linear 4-fold increase in Granulation Tissue thickness and 7-fold increase in wound fluid volume were measured over the 14-day study interval. In contrast, in animals receiving anti-VEGF neutralizing antibody, Day 14 Granulation Tissue thickness and wound fluid volume measurements were essentially unchanged from Day 2 values. Moreover, in the anti-VEGF animals, ultrasonography was unable to resolve the “angiogenic zone” typical of both controls, and correspondingly, wound vessel count and vascular surface area estimates derived from image analysis of histological sections were 3-fold lower in the anti-VEGF animals compared with the saline and antibody controls. Finally, VEGF levels in wound fluid detectable by ELISA analysis were strikingly (10-fold) reduced in anti-VEGF animals on Postsurgery Days 7–14. In contrast, TGF-β1 levels were unaffected by the anti-VEGF treatment. Conclusion. Functional VEGF is a key mediator in wound angiogenesis, fluid accumulation, and Granulation Tissue formation.
H P Ehrlich - One of the best experts on this subject based on the ideXlab platform.
-
effects of interleukin 8 on Granulation Tissue maturation
Journal of Cellular Physiology, 2002Co-Authors: Kurtis E Moye, Gregory C Saggers, G M Alliso, Donald R Mackay, H P EhrlichAbstract:The inflammatory alpha-chemokine, interleukin-8 (IL-8), affects the function and recruitment of various inflammatory cells, fibroblasts, and keratinocytes. Gap junctions are anatomical channels that facilitate the direct passage of small molecules between cells. The hypothesis is that IL-8 enhances gap junctional intercellular communication (GJIC) between fibroblasts in Granulation Tissue, which increases the rate of Granulation Tissue maturation. In vitro, human dermal fibroblasts were incubated with IL-8 prior to scrape loading, a technique that quantifies GJIC. Polyvinyl alcohol (PVA) sponges were implanted within subcutaneous pockets in rats and received local injections of either IL-8 or saline and were harvested on day 11. In vitro, IL-8 treated fibroblasts demonstrated an increase in GJIC by scrape loading compared to saline treated controls. In vivo, IL-8 treated PVA sponges demonstrated a decrease in cell density and an increase in vascularization compared to saline controls by H&E staining. Polarized light viewed Sirius red-stained specimens demonstrated greater collagen birefringence intensity, indicating thicker, more-mature collagen fibers. IL-8 increases GJIC in cultured fibroblasts and induces a more rapid maturation of Granulation Tissue.
-
wound healing the role of gap junctional communication in rat Granulation Tissue maturation
Experimental and Molecular Pathology, 2002Co-Authors: Kurtis E Moye, Gregory C Saggers, Donald R Mackay, A Davis, H P EhrlichAbstract:Granulation Tissue maturation is dependent upon the orientation of collagen fibers and cell differentiation. Gap junctions are intercellular membrane gated channels that facilitate direct communication between cells known as gap junctional intercellular communication (GJIC). The hypothesis is that GJIC modulates the maturation of Granulation Tissue during wound repair. In vitro, GJIC optimizes fibroblast-populated collagen lattice contraction and influences cell morphology. It is reported that LiCl increases GJIC in cultured cardiac myocytes. Polyvinyl alcohol (PVA) sponge implants with central reservoirs were placed within separate subcutaneous pockets on the backs of adult male Sprague-Dawley rats. Each PVA implant received either 20 mM LiCl or saline injections on days 5, 7, and 10 after implantation. On day 11 implants were harvested and processed for light microscopy. By H&E staining LiCl-treated implants showed increased vascularization and decreased cell density compared to saline controls. Polarized light microscopy of Sirius red-stained specimens revealed more intense collagen fiber birefringence secondary to dense, parallel-organized collagen fiber bundles after LiCl treatment. This suggests that LiCl enhancement of GJIC between fibroblasts advances the maturation of Granulation Tissue. It is proposed that the degree of GJIC between Granulation Tissue fibroblasts influences both the quantity and the quality of Granulation Tissue deposited during the wound healing process.
Kurtis E Moye - One of the best experts on this subject based on the ideXlab platform.
-
effects of interleukin 8 on Granulation Tissue maturation
Journal of Cellular Physiology, 2002Co-Authors: Kurtis E Moye, Gregory C Saggers, G M Alliso, Donald R Mackay, H P EhrlichAbstract:The inflammatory alpha-chemokine, interleukin-8 (IL-8), affects the function and recruitment of various inflammatory cells, fibroblasts, and keratinocytes. Gap junctions are anatomical channels that facilitate the direct passage of small molecules between cells. The hypothesis is that IL-8 enhances gap junctional intercellular communication (GJIC) between fibroblasts in Granulation Tissue, which increases the rate of Granulation Tissue maturation. In vitro, human dermal fibroblasts were incubated with IL-8 prior to scrape loading, a technique that quantifies GJIC. Polyvinyl alcohol (PVA) sponges were implanted within subcutaneous pockets in rats and received local injections of either IL-8 or saline and were harvested on day 11. In vitro, IL-8 treated fibroblasts demonstrated an increase in GJIC by scrape loading compared to saline treated controls. In vivo, IL-8 treated PVA sponges demonstrated a decrease in cell density and an increase in vascularization compared to saline controls by H&E staining. Polarized light viewed Sirius red-stained specimens demonstrated greater collagen birefringence intensity, indicating thicker, more-mature collagen fibers. IL-8 increases GJIC in cultured fibroblasts and induces a more rapid maturation of Granulation Tissue.
-
wound healing the role of gap junctional communication in rat Granulation Tissue maturation
Experimental and Molecular Pathology, 2002Co-Authors: Kurtis E Moye, Gregory C Saggers, Donald R Mackay, A Davis, H P EhrlichAbstract:Granulation Tissue maturation is dependent upon the orientation of collagen fibers and cell differentiation. Gap junctions are intercellular membrane gated channels that facilitate direct communication between cells known as gap junctional intercellular communication (GJIC). The hypothesis is that GJIC modulates the maturation of Granulation Tissue during wound repair. In vitro, GJIC optimizes fibroblast-populated collagen lattice contraction and influences cell morphology. It is reported that LiCl increases GJIC in cultured cardiac myocytes. Polyvinyl alcohol (PVA) sponge implants with central reservoirs were placed within separate subcutaneous pockets on the backs of adult male Sprague-Dawley rats. Each PVA implant received either 20 mM LiCl or saline injections on days 5, 7, and 10 after implantation. On day 11 implants were harvested and processed for light microscopy. By H&E staining LiCl-treated implants showed increased vascularization and decreased cell density compared to saline controls. Polarized light microscopy of Sirius red-stained specimens revealed more intense collagen fiber birefringence secondary to dense, parallel-organized collagen fiber bundles after LiCl treatment. This suggests that LiCl enhancement of GJIC between fibroblasts advances the maturation of Granulation Tissue. It is proposed that the degree of GJIC between Granulation Tissue fibroblasts influences both the quantity and the quality of Granulation Tissue deposited during the wound healing process.
Thomas R Howdieshell - One of the best experts on this subject based on the ideXlab platform.
-
antibody neutralization of vascular endothelial growth factor inhibits wound Granulation Tissue formation
Journal of Surgical Research, 2001Co-Authors: Thomas R Howdieshell, Dianne Callaway, Whitney Webb, Michael D Gaines, Charles Procte, Jennife S Pollock, Tommy L Ock, Paul L McneilAbstract:Abstract Objective. The goal of this work was to test the functional role of vascular endothelial growth factor (VEGF) in promoting the vigorous Granulation Tissue formation, wound fluid accumulation, and angiogenic responses characteristic of this wound model. Background. Formation of vessel-rich Granulation Tissue is central to wound repair and is thought to be regulated by locally liberated angiogenic factors. Despite the clinical importance of Granulation Tissue formation in the early stage of wound healing, surprisingly little is known about the molecular identity of signals leading to Granulation Tissue invasion of a wound space. Methods. A ventral hernia, surgically created in the abdominal wall of 15 swine, was repaired using silicone sheeting and skin closure. An osmotic minipump, inserted in a remote subcutaneous pocket, delivered saline (n = 5), an irrelevant control antibody (n = 5), or neutralizing anti-VEGF antibody (n = 5) into the wound environment. Serial ultrasonography on Days 2, 4, 7, 9, 11, and 14 was used to determine the dimensions of the subcutaneous Granulation Tissue and wound fluid compartment. VEGF and transforming growth factor β1 (TGF-β1) levels in serial wound fluid samples were quantitated by ELISA. On Day 14, animals were sacrificed and the abdominal wall was harvested for histologic, biochemical, and molecular analyses. Results. In animals receiving saline or an irrelevant antibody, a nearly linear 4-fold increase in Granulation Tissue thickness and 7-fold increase in wound fluid volume were measured over the 14-day study interval. In contrast, in animals receiving anti-VEGF neutralizing antibody, Day 14 Granulation Tissue thickness and wound fluid volume measurements were essentially unchanged from Day 2 values. Moreover, in the anti-VEGF animals, ultrasonography was unable to resolve the “angiogenic zone” typical of both controls, and correspondingly, wound vessel count and vascular surface area estimates derived from image analysis of histological sections were 3-fold lower in the anti-VEGF animals compared with the saline and antibody controls. Finally, VEGF levels in wound fluid detectable by ELISA analysis were strikingly (10-fold) reduced in anti-VEGF animals on Postsurgery Days 7–14. In contrast, TGF-β1 levels were unaffected by the anti-VEGF treatment. Conclusion. Functional VEGF is a key mediator in wound angiogenesis, fluid accumulation, and Granulation Tissue formation.
-
Nitric oxide synthase isoform expression in a porcine model of Granulation Tissue formation.
Surgery, 2001Co-Authors: Jennifer S. Pollock, Dianne Callaway, Whitney L. Webb, Sathyanarayana, William E. O'brien, Thomas R HowdieshellAbstract:Background. This study was designed to determine whether the nitric oxide (NO) pathway is involved in wound Granulation Tissue formation. Methods. A section of the pig abdominal wall (excluding the skin) was excised, creating an incisional hernia. The resulting defect was repaired with silicone sheeting in a manner that mimics a temporary abdominal wall closure. During the 14-day experimental period, porcine omentum adhered to the peritoneal edges of the defect and a highly vascularized Granulation Tissue formed on both sides of the sheeting. Granulation Tissue thickness and wound fluid volume were monitored by ultrasonography and epigastric artery flow velocity was monitored by color Doppler flow analysis at days 2, 4, 7, 9, 11, and 14. Fluid was serially harvested from the wound compartment at days 2, 4, 7, 9, 11, and 14 for nitrite/ nitrate (NOx) analysis. Finally, Granulation Tissue was harvested at day 14 for immunohistochemical and molecular analyses. Results. There was a significant increase in Granulation Tissue thickness and wound fluid volume during the 14-day study period. Blood flow to the wound increased significantly by day 4 and returned toward baseline by day 14. Wound fluid NOx levels significantly increased from days 7 to 11 and then decreased to near baseline values by day 14. Wound fluid arginine levels significantly decreased when compared with peritoneal fluid and plasma levels at day 14, while wound fluid ornithine levels significantly increased. Immunohistochemical analysis of Granulation Tissue at day 14 revealed nitric oxide synthase (NOS) 2 was present in the majority of the cells in the Granulation Tissue. NOS 3 was expressed in endothelial cells only, and NOS 1 expression was not observed in the Granulation Tissue. Conclusions. This study suggests that NO, NOS 2, and arginine may play critical roles in Granulation Tissue formation and wound healing. Arginase and NOS 2 may compete for available arginine as a substrate, thereby limiting later NO production in favor of sustained ornithine synthesis. (Surgery 2001;129:341-50.)
Kazuo Ohuchi - One of the best experts on this subject based on the ideXlab platform.
-
Analysis of the Leukotriene D4 Receptor in the Granulation Tissue of Allergic Inflammation in Rats
International Archives of Allergy and Immunology, 2009Co-Authors: Noriyasu Hirasawa, Tomonori Hoshi, Michiko Kudoh, Suetsugu Mue, Susumu Tsurufuji, Masako Watanabe, Kazuo OhuchiAbstract:Leukotriene (LT) D4 receptor in the Granulation Tissue formed in the air pouch-type allergic inflammation model in rats was analyzed. Membrane preparation of the Granulation Tissue obtained
-
defective angiogenesis in the inflammatory Granulation Tissue in histidine decarboxylase deficient mice but not in mast cell deficient mice
Journal of Experimental Medicine, 2002Co-Authors: Ajoy Kuma Ghosh, Noriyasu Hirasawa, Takehiko Watanabe, Hiroshi Ohtsu, Kazuo OhuchiAbstract:We have analyzed the role of histamine in the angiogenesis of the Granulation Tissue in histidine decarboxylase–deficient (HDC−/−) mice, mast cell–deficient mice (WBB6F1-W/WV), and their corresponding wild-type mice (HDC+/+ and WBB6F1+/+). In HDC+/+ mice, subcutaneous implantation of a cotton thread in the dorsum induced Granulation Tissue formation with angiogenesis, while the topical injection of antivascular endothelial growth factor (VEGF) IgG strongly suppressed them. In HDC−/− mice which showed lower VEGF levels in the Granulation Tissue, there was notably less angiogenesis and Granulation Tissue formation than in HDC+/+ mice. The topical injection of histamine or the H2 agonist dimaprit rescued the defective angiogenesis and Granulation Tissue formation in HDC−/− mice. There was no significant difference in the Granulation Tissue formation and angiogenesis between WBB6F1-W/WV and WBB6F1+/+ mice. In addition, macrophages in the Granulation Tissue were found to express HDC. Our findings indicate that histamine derived from nonmast cells plays a significant role in the angiogenesis of the inflammatory Granulation Tissue.
-
cyclooxygenase 2 mediated angiogenesis in carrageenin induced Granulation Tissue in rats
Journal of Pharmacology and Experimental Therapeutics, 2000Co-Authors: Ajoy Kuma Ghosh, Noriyasu Hirasawa, Hisae Niki, Kazuo OhuchiAbstract:The possible participation of cyclooxygenase (COX)-2 in angiogenesis in Granulation Tissue was analyzed using an air pouch-type carrageenin-induced inflammation model in rats. Injection of carrageenin solution into an air pouch induced gradual increases in the pouch fluid volume and Granulation Tissue weight as well as angiogenesis in Granulation Tissue. NS-398 (10–100 μg) inhibited all of these parameters in a dose-dependent manner. NS-398 (100 μg), indomethacin (100 μg), and dexamethasone (10 μg) markedly reduced prostaglandin (PG) E2 levels in the pouch fluid at day 6. NS-398 and indomethacin did not affect protein levels of COX-1 and COX-2 but dexamethasone significantly reduced the level of COX-2 in Granulation Tissue at day 6. Protein levels of vascular endothelial growth factor (VEGF) in Granulation Tissue and in the pouch fluid were higher at day 6 than at day 3, and the levels were decreased by treatment with NS-398 (10–100 μg) in a dose-dependent manner. The inhibitory effects of NS-398 (100 μg) were almost the same as those of indomethacin (100 μg). Dexamethasone (10 μg) also reduced VEGF protein levels in Granulation Tissue at day 6. To clarify the role of PGE2 in VEGF production, minced Granulation Tissue obtained 3 days after carrageenin injection from the indomethacin-treated rats was incubated in the presence of various concentrations of PGE2. It was shown that VEGF mRNA and protein levels in the minced Granulation Tissue were increased by PGE2 in a concentration-dependent manner. These findings suggest that COX-2-derived PGE2 plays a significant role in angiogenesis in the carrageenin-induced Granulation Tissue through VEGF formation.
