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PubMed1989

Evidence that 1 per cent Meshushit ointment prevents progressive dermal ischaemia of experimental deep partial skin thickness burns: a preliminary, quantitative controlled study.

This study quantitatively assessed the topical effects of Meshushit, a new herbal compound, on the healing process of experimental deep partial skin thickness burns over 27 days. To symmetrical circular burns were inflicted on the back of 15 animals by aluminium templates. The Meshushit and its control vehicle containing 0.1 per cent gentamycin or the control vehicle plus antibiotic alone, were applied topically to randomly selected burns at equal time intervals. Epithelialization and contraction were assessed on postburn days 6, 10, 15, 18, 22 and 27 using a computerized planimeter. The newly formed granulation tissue was assessed histologically on postburn day 27, while the hair follicles were counted in the same sections. Student's t test was used to differentiate the rates of contraction and epithelialization; hair follicle counts and the thickness of the newly formed granulation tissue. None of the animals died during the experiment. The epithelialization and contraction rates did not differ significantly between the test groups. The Meshushit-treated wounds showed a significantly thicker granulation tissue layer as compared to its control (828.72 +/- 46.39 microns vs. 540.78 +/- 37.81 microns, P less than 0.01). The count of hair follicles was significantly higher in the Meshushit-treated burns (23.38 +/- 1.84 vs. 3.76 +/- 0.35, P less than 0.001). It is concluded that the herbal Meshushit ointment enhanced the newly formed granulation tissue and preserved better the hair follicles in the present burn wound model. It is suggested that these findings are due to the preservation of the dermal microcirculation.

Animals↗
PubMed1990

[Immunohistochemical studies on the peptidergic nerve distribution in hard palate mucosa and gingiva of the rat. 2. Responses of calcitonin gene-related peptide (CGRP)-containing nerve fibers on wound healing of the mucosa].

This study investigated morphological changes of CGRP-containing nerve fibers during wound healing of the rat oral mucosa following resection of the transverse palatine ridge and gingivectomy. The tissue was immunohistochemically examined at 0, 3, 7, 14, 21, 28 and 70 days after surgical injury. The following results were obtained. 1) The Transverse Palatine Ridge. At shorter survival periods (0 and 3 days), CGRP-containing nerve fibers adjacent to the surgical defect degenerated and decreased in number. By 7 days, tissue repair had advanced and the defect had been filled with granulation tissue. Thin nerve fibers were found in and around the granulation tissue, especially nearby newly proliferating blood vessels. At 14 days, extensive regeneration of thin nerve fibers was observed in the repaired tissue. Many of them were found singularly in deeper layers of the repaired tissue, and some in bundles reaching the base of the epithelium. Some of these sprouts appeared to have existed only transiently because their number somewhat reduced by 21 days. The defect was filled with scar tissue at 28 days and mucous structure did not return to normal even at 70 days. Nerve fibers neither regenerated to regain the original density nor formed subepithelial plexuses. 2) The Gingiva. At 0 and 3 days, CGRP-containing nerve fibers near the cut surface of gingiva degenerated and their number decreased. At 7 days, a few thin regenerating fibers were found entering the epithelium on the oral side. Sprouts were also seen around small blood vessels deep in the granulation tissue. By 14 days, the nerve fibers had gradually increased with progress of tissue repair. However, rapid, transient increase in number of fibers, like that observed for the palatine ridge, was not noted. By 21 days, the junctional epithelium had regenerated, and regenerating fibers had redistributed into and beneath the sulcal epithelium. At 28 and 70 days, the repaired marginal gingiva were indistinguishable from normal (and control) marginal gingiva as regards the histology and CGRP-innervation. There were, however, a few exceptions in which junctional epithelium did not fully recover. In these animals, regeneration of CGRP-containing fibers was barely discernible in or around the sulcal epithelium.

Animals↗
PubMed2000

Heme oxygenase-1 is upregulated in the rat heart in response to chronic administration of angiotensin II.

Heme oxygenase (HO) is a heme-catabolizing enzyme that converts heme into biliverdin, iron, and carbon monoxide. HO-1, an inducible form of HO, is thought to act as an endogenous antioxidant defense mechanism. To determine whether chronic administration of angiotensin II affects HO-1 expression in the heart, expression and localization of HO-1 were investigated in the heart of rats receiving angiotensin II infusion (0.7 mg. kg(-1). day(-1)) via osmotic minipump for up to 7 days. Angiotensin II induced formation of granulation tissue, characterized by myofibroblast proliferation, fibrous deposition, and inflammatory cell migration. Angiotensin II also upregulated cardiac HO-1 expression. Immunohistochemistry revealed that HO-1 was intensively expressed in the granulation tissue. The selective AT(1)-receptor antagonist, losartan, completely, but hydralazine only partially, suppressed angiotensin II-induced granulation tissue formation and HO-1 upregulation. Chronic norepinephrine infusion (2.8 mg. kg(-1). day(-1)) did not induce granulation tissue formation or HO-1 upregulation. Our data suggest that angiotensin II upregulates cardiac HO-1 expression in the newly formed inflammatory lesion, which may represent an adaptive response to angiotensin II-induced cardiac damage.

Angiotensin II↗
PubMed1988

[Excluding a recurrence of cholesteatoma using high resolution computerized tomography. Can one dispense with the second-look operation?].

In a prospective study 20 patients were examined by high-resolution computed tomography of the temporal bone (HR-CT) before an early or late second-look operation. One year earlier 8 of the patients had undergone a posterior tympanotomy ("intact canal wall" technique) for a cholesteatoma and if necessary a one-stage ossicular reconstruction. In 4 other patients a two-stage ossicular reconstruction was carried out. In the remaining 8 patients a one stage operation had been carried out several years before. After a cholesteatoma operation three typical X-ray findings can be observed in HR-CT: 1. Normal findings (no granulation tissue in the middle ear space, antrum or mastoid) 2. Granulation tissue without destruction 3. Cholesteatoma recurrence (homogeneous soft tissue mass with bony destruction) Based on previous experience we forego an early second-look 1 year later and suggest the following plan: 1. Providing the post-operative follow up proves normal, a HR-CT examination is carried out 2 years, after a cholesteatoma operation. 1.1 If the HR-CT, the clinical and audiological examinations are normal a HR-CT investigation is necessary a further 2 years later. 1.2 In the case of granulation tissue a further HR-CT must be carried out 1 year later. Should the granulations become progressively worse a second-look is mandatory. 1.3 Homogeneous soft tissue mass and destruction are signs of cholesteatoma recurrence. Immediate operation is necessary. 2. If audiological or clinical findings suggest a recurrent cholesteatoma within the first 2 years after the operation, HR-CT should be carried out at once.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1995

Cellular mechanisms, interactions, and dynamics of gastric ulcer healing.

An ulcer is a deep, focal defect in the gastric or duodenal wall penetrating through the entire thickness of mucosa and muscularis mucosae. Ulcer healing (i.e., the reconstruction of the muscularis mucosae and mucosal architecture) is an active process of filling the mucosal defect with proliferating and migrating epithelial cells and connective tissue. Mucosa adjacent to the ulcer creater forms a healing zone. Gastric glands in this zone dilate and the epithelial cells lining these glands dedifferentiate, express epidermal growth factor (EGF) receptor, and proliferate. The proliferation is triggered by local activation of genes encoding for EGF and its receptor. From the ulcer margin, proliferating epithelial cells migrate onto the granulation tissue to cover (re-epithelialize) the ulcer and bud into granulation tissue to reconstruct gastric glands in the ulcer scar. Re-epithelialization and reconstruction of epithelial structures are under control of EGF and related peptides produced locally by regenerating cells. Granulation tissue at the ulcer base (whose growth is regulated, at least in part, by fibroblast growth factors) supplies microvessels for restoration of the microvascular network and connective tissue for restoration of the lamina propria within the mucosal scar. The ulcer healing reflects a dynamic interaction between the epithelial component from the healing zone at the ulcer margin and the connective tissue component (including microvessels) originating from the granulation tissue.

Animals↗
PubMed1979

[Effect of silicoorganic compounds on protein biosynthesis in granulation-fibrous tissue].

The authors studied the effect of propoxysilatran (POS) on the biosynthesis of the main connective tissue biopolymeres. The use of POS in the form of 0.5 and 2.0% ointments on lanolin-vaseline base caused stimulation of cellular proliferation in the granulation fibrous tissue developing in the open skin defects of albino rats. Stimulation of cellular proliferation in these animals was accompanied by increase of collagen biosynthesis and of noncollagen proteins. In concentrations of 10(-3)--10(-4) M POS caused intensification of collagen biosynthesis (formation of peptide-bound nondialyzed 14C-oxyproline) in vitro in the cartilage tissue of chick embryos. Thus, silatrans are biologically-active substances producing a regulating effect on the course of the reparative-proliferative processes in the connective tissue.

Animals↗
PubMed1991

Sodium hyaluronate increases vascular ingrowth in the rabbit ear chamber.

The rabbit ear-chamber model was used to study the effect of sodium hyaluronate (NaHe, Healon) on the rate of ingrowth of vascular structures of healing granulation tissue. The chamber area covered by granulation tissue was determined by in-vivo microscopy at regular intervals during a period of 32 days. Daily injections of 1% NaHe into the ear chamber, 50 microliters from day 0 to day 7 and 25 microliters from day 8 to day 21, significantly inhibited ingrowth as observed between days 20 and 26, compared with buffer-injected controls. There was no difference between the latter and non-injected chambers. Intermittent injections of 1% NaHe, 50 microliters on days 1 and 5 and 25 microliters on days 9, 13 and 22 significantly increased the ingrowth as observed between days 6 and 18. It was noted that wound macrophages internalized fluorescein-labelled NaHe. The inhibitory effect of daily injections on angiogenesis was probably due to physical hindrance caused by the NaHe. The stimulatory effect of intermittent administration of NaHe on angiogenesis may have several explanations, including activation of macrophages and their release of angiogenetic factors.

Animals↗
PubMed2001

Impaired wound healing in mice deficient in a matricellular protein SPARC (osteonectin, BM-40).

BACKGROUND: SPARC is a matricellular protein involved in cell-matrix interactions. From expression patterns at the wound site and in vitro studies, SPARC has been implicated in the control of wound healing. Here we examined the function of SPARC in cutaneous wound healing using SPARC-null mice and dermal fibroblasts derived from them. RESULTS: In large (25 mm) wounds, SPARC-null mice showed a significant delay in healing as compared to wild-type mice (31 days versus 24 days). Granulation tissue formation and extracellular matrix protein production were delayed in small 6 mm SPARC-null wounds initially but were resolved by day 6. In in vitro wound-healing assays, while wild-type primary dermal fibroblasts showed essentially complete wound closure at 11 hours, wound closure of SPARC-null cells was incomplete even at 31 hours. Addition of purified SPARC restored the normal time course of wound closure. Treatment of SPARC-null cells with mitomycin C to analyze cell migration without cell proliferation showed that wound repair remained incomplete after 31 hours. Cell proliferation as measured by 3H-thymidine incorporation and collagen gel contraction by SPARC-null cells were not compromised. CONCLUSIONS: A significant delay in healing large excisional wounds and setback in granulation tissue formation and extracellular matrix protein production in small wounds establish that SPARC is required for granulation tissue formation during normal repair of skin wounds in mice. A defect in wound closure in vitro indicates that SPARC regulates cell migration. We conclude that SPARC plays a role in wound repair by promoting fibroblast migration and thus granulation tissue formation.

Animals↗
PubMed1995

Dose response profiles of human growth hormone in subcutaneous wound chambers in rats.

OBJECTIVE: To investigate dose response profiles of human growth hormone in soft connective tissue healing when it is given locally in subcutaneous wound chambers. DESIGN: Placebo controlled parallel study. SETTING: Institute of Medical Anatomy, Denmark. MATERIAL: 36 male Sprague Dawley rats, in three group of 12. INTERVENTIONS: Stainless steel wire mesh cylinders 7 mm in diameter and 20 mm long were implanted subcutaneously in pairs in the upper and lower back on either side of the midline in three groups of male Sprague Dawley rats. Two groups were each given two different doses of growth hormone (group 1, 0.2 and 0.7 IU; and group 2, 0.02 and 2 IU) in two cylinders and vehicle alone in the two cylinders on the opposite side. Group 3 were given vehicle alone in two cylinders and needle puncture (sham) on the opposite side. Injections of growth hormone or vehicle (placebo) were given every three days for 16 days. MAIN OUTCOME MEASURES: Body weight, weight of granulation tissue, and concentrations of hydroxyproline and aminoterminal propeptide of procollagen type III. RESULTS: The dose response curves for weight of granulation tissue and deposition of collagen were upward convex (ANOVA p < 0.001 and 0.001, respectively). Growth hormone in doses of 0.2 and 0.7 IU stimulated formation of granulation tissue to means of 180% (95% confidence interval (Cl) 149% to 210%) and 174% (95% Cl 148% to 200%) more than in the placebo treated cylinders (group 3) (p < 0.05 and < 0.01, respectively). Doses of 0.2 and 2 IU, however, had less effect. The placebo cylinders in animals in groups 1 and 2 contained a mean of 157% (95% Cl 137% to 177%) more granulation tissue than the cylinders in group 3, indicating that locally applied growth hormone also had a systemic effect. CONCLUSION: The clinical use of topical growth hormone in wound healing may be complicated by the relatively narrow therapeutic interval.

Animals↗
PubMedDate not supplied

Percutaneous cholangioscopy in obstructed biliary metal stents.

PURPOSE: To reevaluate the reasons for the occlusion of self-expanding biliary metal stents, on the basis of cholangioscopic findings. METHODS: Percutaneous transhepatic cholangioscopy (PTCS) was performed in 15 patients with obstructed biliary Wallstents. The reason for stent insertion was a malignant obstruction in 14 patients; 1 had a benign biliary stricture. Conventional noncovered stents had been inserted in 12 patients; in 3 cases a polyurethanecovered prototype Wallstent had been used. Stent occlusions occurred after 1-55 months. PTCS was performed with a 2.3-mm endoscope through an 11 Fr sheath. Biopsies were taken via the working channel of the endoscope. RESULTS: In all patients with noncovered stents the inner surface of the stent was highly irregular with seaweed-like protrusions (biopsy-proven granulation tissue). Stent incorporation varied from absent (n = 1) to subtotal (n = 8), but was always incomplete, no matter how long the stent had been in place. Tumor ingrowth was histologically proven in 2 patients. One patient had a large occluding concrement at the proximal end of the stent. In patients with covered stents, the inner surface appeared more regular; however, viable granulation tissue was found inside two stents and tumor ingrowth in one of them. CONCLUSION: PTCS showed that incorporation of the stent is virtually always incomplete. The factors contributing most to stent occlusion are the buildup of granulation tissue, bile sludge, and tumor overgrowth. Stone formation and tumor ingrowth can also be important, although less common causes of occlusion. A polyurethane stent covering could not prevent tumor ingrowth in one patient and the buildup of viable granulation tissue inside the stent in two further patients; mean stent patency in the three patients with such a stent was 3 months.

Aged↗
PubMed1984

Inflammatory reaction in an experimental model of open wounds in the rat. The role of polymorphonuclear leukocytes.

The accumulation of polymorphonuclear leukocytes (PMNLs) and the concentration of prostaglandin E2 in full thickness open skin wounds, created in the back of the rat, were studied. The quantity of PMNLs in the granulation tissue, assessed by analysis of wound exudate myeloperoxidase activity, increased from 0.45 units/ml on day 1 after wounding to 0.8 units/ml on day 2 and then remained constant throughout the 5 days of observation. The prostaglandin E2 concentration in wound exudate was measured by radioimmunoassay increased progressively from 70 ng/ml on day 1 to 290 ng/ml on day 5. The lack of correlation between these two variables indicates that PMNLs were not the major source of prostaglandin E2. To study the relation between PMNL accumulation, blood flow, and albumin extravasation in the granulation tissue, rats were treated with an antineutrophil serum. This resulted in an 83% decrease in circulating PMNLs and a 61% decrease in granulation tissue myeloperoxidase activity on the 5th day, as compared with rats treated with normal rabbit serum. No relationship was observed between myeloperoxidase activity and blood flow (r = 0.37) or between myeloperoxidase activity and albumin extravasation (r = -0.34) when absolute values were compared. However, when interindividual variation in the absolute levels of the variable measured was eliminated, by calculating in each rat a left to right wound ratio, good correlations (r = 0.81 and r = 0.65, respectively) were found. It is suggested that blood flow and albumin extravasation in the granulation tissue are influenced by local PMNL accumulation.

Animals↗
PubMed1994

Developmental stages in experimental liver metastases: relation to invasiveness.

We have previously reported that an invasive morphotype can be evoked in a rat colon carcinoma by transplanting it into pre-induced subcutaneous granulation tissue. We have now studied the interaction of the same tumor with liver tissue, which is extremely poor in connective tissue in comparison with the subcutaneous site. Tumor cells were injected into the portal system and the resulting experimental liver metastases were examined by electron microscopy and immunohistochemistry. Early metastases consisted of well-differentiated acini, fully surrounded by connective tissue that was derived from the periportal stroma. In a later stage, this connective tissue was overgrown by tumor cells and, almost immediately, acinar differentiation was lost. Most metastases eventually reached the liver capsule, which reacted by forming a layer of granulation tissue. Only in this layer, we observed invasion by thin tumor cell strands, which were often intimately associated with fibroblasts or with blood capillaries. The tumor cells remained smooth and rounded during this process. After fully penetrating the granulation tissue, the tumor cell strands reached the liver surface, where they formed poorly structured papillary masses that were nearly devoid of stroma. Our observations indicate that, even in a relatively homogeneous organ like the liver, the tumor-host interaction is highly complex and dynamic. They also confirm the notion that granulation tissue stimulates tumor invasiveness. Finally, they show that tumor cells can actively invade host tissues without exhibiting a "fibroblastic" morphology.

Animals↗
PubMed2002

Effect of substance P released from peripheral nerve ending on endogenous expression of epidermal growth factor and its receptor in wound healing.

OBJECTIVE: To explore the relationship between substance P (SP) released from peripheral nerve endings and the expression of epidermal growth factor (EGF) and epidermal growth factor receptor (EGFR) during wound healing. METHODS: Fifty Wistar rats were randomly divided into 2 groups, injury group and capsaicin group. In the injury group, a full-thickness skin wound on the back of the rat was taken. The wound edge and granulation tissues were taken on the 1st, 3rd, 6th, 9th, 12th days after injury, respectively. In the capsaicin group, capsaicin was injected subcutaneously on the back of the rats to destroy the sensory nerve to prevent the secretion of SP, then a wound and sample was made in the same way. Immunohistochemistry and in situ hybridization were employed to detect the expression of SP, EGF/EGFR, and EGF mRNA/EGFR mRNA in the granulation tissues. RESULTS: In the injury group, immunohistochemical stain of SP and EGF/EGFR was located on the hair follicles and sebaceous glands at the 1st day. And the stain of SP was obvious at the 3rd day in the granulation tissues, then decreased gradually. EGF/EGFR was at low level at the 3rd day, then increased gradually and reached the peak at the 9th day, then declined. In the capsaicin group, the immunohistochemical stain of SP and EGF/EGFR was faint and without obvious change during the wound healing process. The tendency of the EGF mRNA/EGFR mRNA expression was similar to that of EGF/EGFR. CONCLUSIONS: During wound healing, SP may promote the healing process by affecting the expression of EGF/EGFR in the granulation tissues.

Animals↗
PubMed1987

Modulation of fibroblast growth and glycosaminoglycan synthesis by interleukin-1.

Cellular response to inflammatory mediators is central to the regulation of new scar tissue formation. Fibroblasts derived from normal dermis and from 14-day old skin wound granulation tissue were compared with regard to production of non-collagenous extracellular matrix and response to interleukin-1 (IL-1). Following a serum-free 48 hour labeling with [3H]-glucosamine, the cellular, pericellular and medium fractions from the two cell types were collected, precipitated with cetylpyridinium chloride (CPC), and analyzed by cellulose acetate electrophoresis. In addition, susceptibility of precipitates to the polysaccharidases Streptomyces hyaluronidase and chondroitinase ABC was determined. Labeled conditioned medium from both cell types contained dermatan sulfate (DS) and hyaluronate (HA), although the relative amounts of these glycosaminoglycans (GAGs) were different. Medium from normal dermal fibroblasts contained more DS than HA, while 14-day granulation tissue culture medium contained a proportionately larger amount of HA. The amount of HA in the medium fraction of normal dermal fibroblasts was increased approximately 10-fold in the presence of 5 U/ml IL-1, while HA in the medium of wound-derived fibroblasts was quantitatively unaffected by addition of the mediator. Pericellular GAG consisted of heparan sulfate (HS) and chondroitin sulfate (CS), with no observable differences between the two cell types and no effect of IL-1 on this profile for either cell type. Conditioned medium from both cell types contained IL-1 activity (measured by thymocyte proliferation assay), with medium from 14-day granulation tissue fibroblasts containing 10-fold higher activity than normal dermal fibroblast medium.

Animals↗
PubMed1999

Maturation of the pediatric tracheostomy stoma: effect on complications.

The pediatric tracheostomy stoma can be matured via a technique that places 4-quadrant sutures from the tracheal cartilage to the dermis. This has the potential of decreasing the risk of accidental decannulation and the formation of granulation tissue. A retrospective analysis of 149 tracheostomies performed between January 1989 and December 1996 was done for the following factors: age, underlying diagnosis, indication for tracheostomy, type of tracheal incision, maturation of stoma, duration of tracheostomy, and early and late (>7 days) complications. Maturation of the stoma was performed in 88 (59.1%) of the 149 tracheostomies. There was an overall complication rate of 21.5% (32/149, not including granulation tissue formation). There were 9 (6.0%) early complications and 23 (15.4%) late complications. The overall incidence of tracheocutaneous fistulas occurred in 11 (11.2%) of the 98 decannulated patients: 6 (10.2%) of the 59 matured stomas and 5 (12.8%) of the 39 nonmatured stomas. Granulation tissue was found on subsequent laryngoscopy in 24 (27.3%) of the 88 matured stomas versus 23 (37.7%) of the 61 nonmatured stomas. There were no tracheostomy-related mortalities. Maturing the tracheostomy stoma resulted in a decreased morbidity from accidental decannulations and did not increase the incidence of tracheocutaneous fistulas or granulation tissue formation.

Adolescent↗
PubMed2000

Effect of amniotic fluid cellular content on attic aeration pathways: histologic observations of infants aged 2 to 4 months.

HYPOTHESIS: The tissue-fixed amniotic fluid cellular content (AFCC) in the middle ear and mastoid antrum causes foreign body type reactions that may later severely restrict the aeration pathways to the main attic and to Prussak's space. BACKGROUND: It was shown by Aschoff 100 years ago that AFCC remained in the neonate ears and caused sterile otitis media. Recent data show that children born through thick meconium are at risk for large quantities of AFCC entering the middle ear cleft, the ensuing inflammatory reaction being related to the amount of AFCC. Spread of AFCC in the neonate occurred along the aeration pathways with corresponding tissue fixation but further systematic data in young infants are lacking. METHODS: Five temporal bones of three infants aged 2 to 4 months were embedded in celloidin, serially sectioned at 20 microns, and every 10th section stained with Hematoxylin and eosin and mounted on slides. All slides were studied and relevant details of aeration pathways and all compartments photographed. RESULTS: The histologic changes were characterized by the development of masses of pseudocystic granulation tissue, with some remnants of the original AFCC, mainly in the form of fragments of hair. The tympanic isthmus was involved to varying extent, maximally to half of its size. Posterior tympanum and the stapes region had masses of fresh granulation tissue, the maturing of which might cause marked indrawing of the posterior pars tensa and further reduction of the tympanic isthmus. Aeration of Prussak's space was severely involved in two bones, favored by the narrow pathway through the posterior pouch. Features of recent acute or secretory otitis media were associated with the early changes caused by AFCC. CONCLUSIONS: The granulation tissue in this age group is immature and its final fate is decided by the nature of the future ear disease. If the AFCC contamination is slight, the granulation tissue after maturing may appear only in the form of thin cords and sheets, a frequent chance finding in ear surgery. Large amount of AFCC may lead to chronic inflammation, which may predispose the child to recurring middle ear infections during infancy. Further histologic and clinical studies in older infants and young children are needed to find out the final outcome after a massive AFCC contamination of the new-born middle ear.

Amniotic Fluid↗
PubMed2000

Molecular mechanisms of ulcer healing.

An ulcer in the gastrointestinal tract is a deep necrotic lesion penetrating the entire mucosal thickness and muscularis mucosae. Ulcer healing is an active process of filling the mucosal defect with proliferating and migrating epithelial and connective tissue cells. At the ulcer margin, epithelial cells proliferate and migrate onto the granulation tissue to cover (reepithelialize) the ulcer and also invade granulation tissue to reconstruct glandular structures within the ulcer scar. The reepithelialization and reconstruction of glandular structures is controlled by growth factors: trefoil peptides, EGF, HGF, bFGF and PDGF; and locally produced cytokines by regenerating cells in an orderly fashion and integrated manner to ensure the quality of mucosal restoration. These growth factors, most notably EGF, trigger cell proliferation via signal transduction pathways involving EGF-R, adapter proteins (Grb2, Shc and Sos), Ras, Raf1 and MAP (Erk1/Erk2) kinases, which, after translocation to nuclei, activate transcription factors and cell proliferation. Cell migration requires cytoskeletal rearrangements and is controlled by growth factors via Rho/Rac and signaling pathways involving PLC-gamma, PI-3 K and phosphorylation of focal adhesion proteins. Granulation tissue develops at the ulcer base. It consists of connective tissue cells: fibroblasts, macrophages and proliferating endothelial cells forming microvessels under the control of angiogenic growth factors: bFGF, VEGF and angiopoietins, which all promote angiogenesiscapillary vessel formation, essential for the restoration of microvascular network in the mucosa and thus crucial for oxygen and nutrient supply. The major mechanism of activation of angiogenic growth factors and their receptor expression appears to be hypoxia, which activates hypoxia-inducible factor, which binds to VEGF promoter.

Journal Article↗
PubMed1992

The use of cytosine arabinoside in glaucoma filtering surgery.

Posterior lip sclerectomies were performed in rabbits and cytosine arabinoside (Ara-C) was applied by topical instillation or subconjunctival injection. In both groups, the mean intraocular pressure (IOP) of the treated eyes was significantly lowered at postoperative week 1 and 2, but there was no significant difference between the mean IOP of the control eyes and that of the treated eyes at postoperative week 3 and 4. In both groups, at postoperative week 2, the sclerectomy sites of the control eyes were totally occluded by granulation tissue, but those of the treated eyes were partially replaced by granulation tissue. At postoperative week 4, the sclerectomy sites of the treated eyes were totally occluded by the granulation tissue ultimately in both groups. There were no differences in the mean IOP and the histologic finding of the treated eyes between the topical instillation group and the subconjunctival injection group. We concluded that either topical instillation or subconjunctival injection of Ara-C can delay wound healing at the surgical site after glaucoma filtering surgery in rabbits.

Administration, Topical↗