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PubMed1986

Abnormalities of granulation tissue and collagen formation in experimental diabetes, uraemia and malnutrition.

The formation of granulation tissue and collagen was studied in rats made diabetic with streptozotocin. Granulation tissue was harvested from the inside of steelmesh cylinders implanted in the back of diabetic and control animals. Four weeks after implantation there was a reduction in the quantity of granulation tissue and its collagen content in diabetic animals compared to controls. Rats with renal failure or malnutrition but no diabetes also formed less granulation tissue but in these animals the content of collagen in the granulation tissue was normal. These results suggest that the decrease of collagen, but not granulation tissue, in diabetes is a relatively specific phenomenon which was not due to the toxic effects of streptozotocin as the changes were prevented by insulin treatment. The hydroxyproline/proline ratio of diabetic collagen was found to be normal, excluding defective hydroxylation of proline as an important factor in the reduction of collagen in diabetes. Treatment with an aldose reductase inhibitor did not prevent the abnormalities of granulation tissue and collagen in diabetes, making it unlikely that increased activity of this enzyme played an important pathogenetic role. The observed reduction of granulation tissue mass and collagen content in diabetes may be important factors in the impairment of wound healing in diabetes.

Aldehyde Reductase↗
PubMed1996

Microbiology of tracheal granulation tissue associated with silicone airway prostheses.

Granulation tissue formation and contraction is inevitable during the healing of open wounds. The presence of infection and a foreign body, such as a silicone airway prosthesis or other tracheotomy tube, magnifies this response. In airway reconstruction, wound contraction secondary to chronic inflammation is a liability. Cultures of granulation tissue were taken from 12 patients with silicone cannulas of T-Tubes. Polymicrobial colonization predominated, with variable combinations of gram-positive, gram-negative, and anaerobic organisms being present. On the basis of sensitivity data, amoxicillin-clavulanate potassium and ciprofloxacin hydrochloride were chosen as empirical antimicrobials. Anecdotally, impressive decreases in the quantity of granulation tissue were seen. We recommend a prospective trial to more accurately define the role of antibiotics in this setting.

Adult↗
PubMed1975

Deamination of biogenic amines and other nitrogenous compounds in granulation tissue from experimental wounds.

In the granulation tissue of skin wounds an increase in the content of hydroxyproline was accompanied by changes in lipid peroxidation products. At the same time deamination of 5-hydroxytryptamine, tyramine or adenosine-5'-monophosphate decreased, but the ability to deaminate histamine, putrescine and lysine appeared. Pargyline prevented the appearance of these new deaminating properties. Adenosine-3'-monophosphate slowed down to the weight increase and lowered the content of hydroxyproline in the growing granulation tissue; it also changed the dynamics of deamination of tyramine or 5-hydroxytryptamine and significantly inhibited the deamination of histamine, lysine and adenosine-5'-monophosphate. The patterns of changes in deamination of nitrogenous compounds and the effects caused by pargyline and adenosine-3'-monophosphate suggest that qualitative alteration (transformation) in catalytic properties of monoamine oxidases may occur in the growing granulation tissue from wounds.

Adenosine Monophosphate↗
PubMed2006

Bacteriology of granulation tissue in laryngotracheal stenosis patients.

BACKGROUND: The formation of granulation tissue is an important factor promoting recurrence after surgical treatment of laryngotracheal stenosis. Bacterial infection was claimed to be the cause. OBJECTIVE: The present study aimed to identify the bacteriology of granulation tissue in laryngotracheal stenosis patients. MATERIAL AND METHOD: Data was collected prospectively. Granulation tissue found in the site of laryngotracheal stenosis was removed and sent to the microbiologic study to identify the organisms. RESULTS: Twenty-four specimens from 17 patients were included in the present study. Coagulase-positive Staphylococcus (45.8%) was the most common gram-positive organism and Pseudomonas aeruginosa as well as Enterobacter species (16.7%) were the most common gram-negative bacteria. Ciprofloxacin may be the oral antibiotic that should be recommended. CONCLUSION: Coagulase-positive Staphylococcus, Pseudomonas aeruginosa as well as Enterobacter species were the common organisms identified from the granulation tissue in recurrent laryngotracheal stenosis. Oral antibiotics, such as ciprofloxacin, may have benefit in reducing the formation of this granulation tissue.

Adolescent↗
PubMed2000

Covered expandable tracheal stents in the management of benign tracheal granulation tissue formation.

BACKGROUND: Tracheal obstruction secondary to benign proliferation of granulation tissue is a difficult problem to address if tracheal resection is contraindicated. Some patients may benefit from Nd:YAG (neodymium: yttritium-aluminum garnet) laser fulguration or tracheal stenting. If uncovered expandable metallic stents are employed granulation tissue can regrow and proliferate through the mesh, thereby obstructing the lumen once again. Covered metallic stents confer the advantage of preventing granulation tissue proliferation and therefore maintain patency of the tracheal lumen. METHODS: Two patients who developed tracheal obstruction secondary to proliferating granulation tissue formation after tracheostomy and who were medically unfit for prolonged general anesthesia were successfully treated using covered expandable metallic tracheal stents. RESULTS: Each patient demonstrated a significant improvement in respiratory status, and in both patients, at 6 and 9 months' follow-up, stent position has not changed, tracheal lumen remains patent, and there has been no proliferation of granulation tissue through the stent. CONCLUSIONS: Covered expandable metallic stents should be considered in the management of patients with proliferating tracheal granulation tissue when tracheal resection is contraindicated.

Adult↗
PubMed1984

The contractile properties of wound granulation tissue.

A systematic examination of the contractile properties of wound granulation tissue is presented. Shortening of and tension generated by granulation tissue in the presence of 30 mM diphenhydramine HCl have been measured. Analysis of the stress (load per unit area)/strain (extent of shortening) results from isotonic shortening studies showed that over the range of 0 to 2.5% shortening there was an approximately linear relationship between stress and strain with a high modulus of elasticity. At lower stresses, wide variations in the amount of shortening occurred with little change in stress. Our interpretation of these findings is that diphenhydramine HCl caused an active shortening of the granulation tissue by 2.5% of its length and contractions greater than this were the result of secondary effects such as coiling and bending of the strips. It is shown that the granulation tissue would have to shorten by 2% once every 3 days to account for observed in vivo rates of contraction for large human wounds and once every 13 hr for rapidly contracting experimental rabbit wounds. The time course of the development of isometric tension by the granulation tissue is shown to be consistent with the proposal that each contractile cell contributes equally to the overall tension developed and that each cell is individually activated by a critical concentration of diphenhydramine HCl which is transported through the tissue by diffusion.

Animals↗
PubMed1994

Altered interaction of human granulation-tissue fibroblasts with fibronectin is regulated by alpha 5 beta 1 integrin.

Granulation-tissue fibroblasts express an unique phenotype distinct from normal fibroblasts. Due to the importance of the cell-matrix interactions in the regulation of cell morphology and behavior, we have compared the cell adhesion apparatus, especially integrin-type receptors, in fibroblasts cultured from healthy human periodontal connective tissues and from chronic and wound granulation tissues. The spreading of granulation-tissue cells on fibronectin, but not on type I collagen or laminin, was slower when compared with the normal fibroblasts. Cell spreading on fibronectin could be inhibited by RGD-containing peptide, suggesting integrin-mediated interaction. Both cell types expressed beta 1 integrin subunit, which associated with several integrin alpha subunits, namely alpha 1, alpha 2, alpha 3, alpha 5 and alpha v. In addition to beta 1 subunit, alpha v chain formed heterodimers with beta 3 and beta 5 subunits. Thus, these cells have multiple putative fibronectin, laminin, collagen, and vitronectin receptors. Cell spreading of both cell types on fibronectin was inhibited with anti-beta 1 and anti-alpha 5 antibodies, but antibodies against other putative FN-binding integrins (alpha 3, alpha v, and alpha v beta 3) had no effects. Furthermore, granulation-tissue fibroblasts showed delayed spreading on substrates coated with anti-beta 1 or anti-alpha 5 integrin antibodies. On substrates coated with anti-alpha 3 antibody, both cell types spread equally well. By FACS analysis, the amount of beta 1 and alpha 5 integrin subunits expressed on the cell surfaces was slightly elevated in GTFs compared with HGFs. Thus, the findings in this study indicate that the weakened interaction of granulation-tissue fibroblasts with fibronectin is regulated by altered function of alpha 5 beta 1 integrin.

Amino Acid Sequence↗
PubMed1976

Collagen and myofibroblasts of granulation tissue. A chemical, ultrastructural and immunologic study.

In granulation tissue produced in the rat by subcutaneous injection of turpentine oil or polyvynile sponge implantation, the great majority of fibroblasts (myofibroblasts) possess a contractile apparatus which makes them similar to smooth-muscle cells. Chemical analysis shows that these granulation tissues contain a high proportion of Type III collagen, a genetically distinct collagen normally associated with embryonic dermal tissue. Type III collagen may persist up to 9 months after sponge implantation and myofibroblasts are seen in granulation tissue by means of electron microscopy and immunofluorescence. When granulation tissue is resorbed 50 days after turpentine oil injection, myofibroblasts disappear and the dermis contains Type I collagen. The concurrent presence of myofibroblasts and Type III collagen suggests that myofibroblasts, in addition to their contractile activity, synthetize, at least in part, type III collagen.

Animals↗
PubMed1975

Oxygen consumption by granulation tissue in bipedicle tube flaps.

The oxygen consumption rate (QO2) of granulation tissue from cylinders implanted in bipedicle tube flaps of rabbits was measured weeks 2 to 7 in vitro in a Biological Oxygen Monitor. Granulation tissue from cylinders implanted in skin folds was used as control. The QO2 of granulation tissue decreased slowly as the oxygen tension in the medium fell. All measurements were made at an oxygen tension of 75 mmHg. At week 2 the QO2 of granulation tissue in flaps was high and a decrease occurred between week 2 and week 4. A further decrease took place between weeks 6 and 7 and a very low QO2 was found at week 7. Control granulation tissue showed a higher QO2 than skin flap granulation tissue at weeks 3, 4, 5 and 7.

Animals↗
PubMed2003

Bacteria and granulation tissue associated with Montgomery T-tubes.

OBJECTIVES: Although complications (infection, development of granulation tissue) of silicone Montgomery T-tubes have been reported, the microbiological consequences and the origin of granulation tissue have not yet been evaluated. STUDY DESIGN: A prospective trial. METHODS: Twenty-three Montgomery T-tubes from 10 patients were analyzed with regard to the development of granulation tissue, bacterial growth (including genotyping with polymerase chain reaction), and results of sensitivity testing. Furthermore, stent sterilization (n = 6) was investigated. RESULTS: Granulation tissue occurred with 74% of the stents, and all specimens showed signs of infection but no foreign body reaction. The predominant organisms were Staphylococcus aureus (35%) and Pseudomonas aeruginosa (17%). The differences between groups with and without granulation tissue were significant for P aeruginosa. Polymerase chain reaction fingerprinting of the S aureus obtained from 15 stents (n = 3 patients) revealed a total of seven different genotypes. Whereas two of these patients harbored six different genotypes of S aureus, the third patient was persistently colonized by S aureus over a 15-month period with the identical genotype. Susceptibility testing showed most commonly (65%) sensitivity to a combination of amoxicillin-clavulanate and ofloxacin. After sterilization, 92% of analyzed stent segments showed no bacterial growth. CONCLUSIONS: Granulation tissue commonly occurred next to the silicone (subglottic area, stoma) where S aureus and P aeruginosa were commonly isolated. A combination of mechanical irritation and bacterial infection seems to account for the development of granulation tissue. Polymerase chain reaction fingerprinting showed both prolonged persistence and a change of colonizing strains after multiple stent replacements. A combination of amoxicillin-clavulanate and ofloxacin is the most effective antibiotic therapy. Sterilization of the cost-intensive silicone stents is feasible, and reuse in the same patient is justifiable from economic aspects.

Adult↗
PubMed2005

Granulation tissue formation by nonspecific inflammatory agent occurs independently of macrophage galactose-type C-type lectin-1.

The role of a macrophage galactose-type calcium-type lectin-1 (MGL1) in antigen-independent granulation tissue formation was investigated. Granulation tissue was induced by injection of carrageenan in an air pouch and distribution of macrophages expressing MGL1/2 was histologically examined. MGL1/2-positive cells were not observed in the granulation tissue induced by carrageenan though these cells were present in dermis. This was distinct from the fact that MGL1/2-positive cells were abundant in granulation tissue induced by antigenic stimulation. CD11b-positive cells were in dermis and carrageenan-induced granulation tissue. Because antigen-induced granulation tissue formation was previously shown to decrease in MGL1-deficient mice or after treatment with anti-MGL1 antibody, we investigated the effects of MGL1-deficient status on carrageenan-induced granulation tissue formation. The thickness of granulation tissue was almost identical between wild-type and MGL1-deficient mice. It is highly likely that MGL1-positive cells are not involved in tissue remodeling when inflammation is driven by nonspecific stimuli.

Animals↗
PubMed1988

Collagen degradation by experimentally-induced subcutaneous granulation tissue in the rat.

Granulation tissue provoked by implantation of cellulose sponge or a nylon bag degraded a powder of homologous collagen. This activity was located in a non-filtrable tissue fraction and was associated with the appearance of mononuclear and histiocytic giant cells, following an early polymorphonuclear-cell infiltration. The activity could be manipulated experimentally, indicating that this model can be used in investigations of inflammation-induced collagen degradation.

Animals↗
PubMed1981

Selective inhibition of collagen breakdown by proteinase inhibitors in granulation tissue in rats.

A rapid breakdown of collagen was found in granulation tissue induced by carrageenin in rats; the half-life of collagen in both growing and resorbing tissues was about 3.5 days, whereas that in non-resorbing tissue was about 7 days. On the other hand, the half-life of noncollagen protein in the growing, resorbing and non-resorbing tissues was about 2-3 days. epsilon-Amino-n-caproic acid n-hexyl ester, an inhibitor of plasmin and trypsin, selectively inhibited collagen breakdown in vivo without affecting the degradation of noncollagen protein or the syntheses of collagen and noncollagen protein in granulation tissues. A similar selective inhibition of collagen breakdown was also found upon treatment with soybean trypsin inhibitor. Collagenase activity was assayed directly in the insoluble 6,000 X g pellet of granulation tissue homogenates. epsilon-Amino-n-caproic acid n-hexyl ester and soybean trypsin inhibitor markedly inhibited the collagen breakdown in granulation tissue pellets in vitro. The results are consistent with those from in vivo experiments and suggest that both the inhibitors indirectly inhibit the collagen breakdown in granulation tissue through the inhibition of a latent collagenase-activating proteinase(s), because none of the inhibitors directly inhibit collagenase. It may be argued, therefore, that a proteinase(s) which activates a latent collagenase plays an important role in the rapid breakdown of collagen in granulation tissues.

Aminocaproates↗
PubMed1979

Ribonuclease activities in developing experimental granulation tissue with reference to polysomes.

The Mg2+-precipitable polysomes in experimental granulation tissue increase up to three weeks and decrease slowly thereafter. Polysomes from young granulation tissue are, on a weight basis, more active in cell-free protein synthesis than polysomes from old granulation tissue. RNase activity is highest in polysomes from 1-week tissue. The polysomes contain both acid and alkaline RNase, but the alkaline RNase is the latent form, manifested by the addition of p-chloromercuribenzoate (pCMB). The high RNase activity of granulation tissue renders the analysis of polysomal patterns and functions of the polysomes difficult. In the post-polysomal supernatant of granulation tissue the RNase activity is highest in 2-4 week old tissue; it is maximal at pH 7-8 and only slightly influenced by pCMB.

Animals↗
PubMed1993

Transplantation of colon carcinoma into granulation tissue induces an invasive morphotype.

The stroma surrounding many malignant tumors resembles granulation tissue. To test the hypothesis that such stroma stimulates tumor invasiveness, we compared, by electron microscopy and immunohistochemistry, the growth patterns of CC531 rat colon adenocarcinoma in 2 experimental situations: (i) after transplantation into the undisturbed subcutaneous connective tissue of rats, and (ii) after transplantation into experimentally induced subcutaneous granulation tissue in rats. For the latter experimental situation, a subcutaneous "tissue chamber" was designed allowing fragments of tumor tissue to be transplanted into the very center of developing granulation tissue. In the undisturbed subcutaneous tissue, the whole tumor was generally encapsulated, and the tumor cells were arranged in compact groups with a strong tendency to form acini. In the pre-formed granulation tissue, on the other hand, the tumor tissue closely matched descriptions of invasive colon carcinomas in the literature and met the criteria for the "invasive morphotype". In this situation, the tumor consisted of thin, unorganized, widely dispersed strands of irregular tumor cells with numerous protrusions that deeply penetrated the surrounding matrix. Our results show that an invasive morphotype can be evoked by pre-inducing granulation tissue at the transplantation site.

Adenocarcinoma↗
PubMed2001

Nitric oxide synthase isoform expression in a porcine model of granulation tissue formation.

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.

Abdominal Injuries↗
PubMed2003

Regulation by prostaglandin E2 and histamine of angiogenesis in inflammatory granulation tissue.

In an air pouch-type carrageenin-induced inflammation model in rats, the selective cyclooxygenase (COX)-2 inhibitor NS-398 dose dependently inhibited the granulation tissue formation, angiogenesis and the level of vascular endothelial growth factor (VEGF) in the granulation tissue. In culture of the minced granulation tissue, PGE2 induced VEGF production in a concentration-dependent manner. Histamine also induced VEGF production in the granulation tissue in vitro. The H2 receptor antagonist cimetidine, the cAMP antagonist Rp-cAMP and the protein kinase A inhibitor H-89 suppressed the histamine-induced VEGF production in the granulation tissue. However, the H1 receptor antagonist pyrilamine maleate, the H3 receptor antagonist thioperamide, the protein kinase C inhibitors Ro 31-8425 and calphostin C or the tyrosine kinase inhibitor genistein showed no effect. Subcutaneous implantation of a cotton thread in the dorsum of histidine decarboxylase-deficient (HDC-/-) mice, but not in mast cell-deficient (WBB6F1-W/Wv) mice, induced less angiogenesis with lower levels of VEGF in the granulation tissue than in their corresponding wild-type (HDC+/+ and WBB6F1(-)+/+) mice. In HDC-/- mice, the topical injection of histamine or the H2 receptor agonist dimaprit rescued the defective angiogenesis and granulation tissue formation. In addition, cimetidine but not pyrilamine maleate and thioperamide inhibited the histamine-induced angiogenesis in the granulation tissue in HDC-/- mice. These findings suggest that PGE2 and histamine augment angiogenesis in the inflammatory granulation tissue by inducing VEGF production, and histamine induces VEGF production possibly through the H2 receptor--cAMP--protein kinase A pathway.

Animals↗
PubMed1993

Collagen metabolism during wound healing in rats. The aminoterminal propeptide of type III procollagen in serum and wound fluid in relation to formation of granulation tissue.

The aminoterminal propeptide of type III procollagen (PIIINP) in serum has been shown to correlate with fibrillogenesis, and thus to be a potential direct marker of type III collagen deposition. The aim of the study was to investigate the correlation between changes in serum PIIINP and formation of granulation tissue during pharmacological suppression. Granulation tissue was induced in rats by the implantation of viscose cellulose sponges. Pharmacological suppression was achieved by cyclophosphamide treatment. To distinguish between the isolated effect of cyclophosphamide and the influence of the weight loss caused by treatment, weight loss caused by starvation was investigated. In untreated rats, serum PIIINP and wound fluid PIIINP were related to formation of granulation tissue (serum: r = 0.58, p < 0.05; wound fluid: r = 0.56, p < 0.05). In rats treated with cyclophosphamide, collagen deposition and formation of granulation tissue were markedly reduced, as compared within the untreated rats (6% vs 33%, p = 0.01). Wound fluid PIIINP reflected the sparse collagen deposition (r = 0.48, p < 0.05), whereas serum PIIINP decreased (-35%, p < 0.01) and was not correlated with the formation of granulation tissue. In starved rats, with a weight loss of 8%, formation of granulation tissue, vascular density, and collagen deposition were not reduced. Wound fluid PIIINP reflected the formation of granulation tissue (r = 0.52, p < 0.05), whereas serum PIIINP remained unchanged despite normal formation of granulation tissue. Starvation of rats without implants caused a decrease in serum PIIINP (-33%(-)-48%, p < 0.01). We conclude that during cyclophosphamide treatment and after a moderate weight loss, serum PIIINP is not a valid marker of fibrillogenesis. However, in normal rats with free access to food, changes in serum PIIINP mirror fibrillogenesis. Furthermore, our study provides experimental evidence consistent with the hypothesis that wound fluid PIIINP directly mirrors the local formation of granulation tissue, independent of weight loss and cyclophosphamide treatment.

Animals↗