Expression and Potential Role of MMP-9 in Intrauterine Adhesion.

OBJECTIVE: Intrauterine adhesions affect menstruation and fertility, and endometrial fibrosis is the final manifestation of IUA. MMP-9 is closely related to fibrosis. The purpose of the study was to assess the role of MMP-9 in intrauterine adhesion (IUA) in rats and patients. METHODS: 40 rats and 24 women were enrolled in this study. 40 rats were randomly divided into 3 groups: IUA group (n = 20), sham group (n = 10), and control group (n = 10). Rat IUA models were established by intrauterine mechanical and chemical injured. In this study, 12 patients of intrauterine adhesions were detected and underwent TCRA (transcervical resection of adhesion) surgery, and endometrial tissue specimens were obtained during operation. One month later, an office hysteroscopy procedure was performed, and endometrial tissue specimens were obtained during operation again (postoperative group). A group of 12 normal age-matched control individuals served as controls underwent hysteroscopy and endometrial sampling. We used immunohistochemistry to detect MMP-9 expressions in rats and human endometrial tissues and to detect MMP-9 protein levels by Western blotting. In addition, we detected mRNA expression levels with qRT-PCR. RESULTS: The expression of MMP-9 in the IUA rats was reduced compared with that in the sham group and Ctrl group (P < 0.05), and the expression of MMP-9 was also reduced in the IUA patients compared with that in the Ctrl group (P < 0.05). The mRNA levels of MMP-9 in the endometrium reflected similar results (P < 0.05). The MMP-9 clearly increased even in the endometrium after TCRA surgery (P < 0.05). CONCLUSION: Our study suggests that MMP-9 may play an important role in IUA. In the future, more in-depth research should be conducted on MMP-9.

Localized delivery of miRNAs targets cyclooxygenases and reduces flexor tendon adhesions.

The formation of adhesions during healing of an injured tendon remains a difficult problem in clinical practice. Local anti-inflammation gene delivery provides high local gene concentration, reduces the inflammatory response of the injured tendon microenvironment, and decreases systemic side effects to enhance in vivo efficacy. In this study, we designed a novel local sustained gene delivery system by using cyclooxygenase (COX-1 and COX-2)-engineered miRNA plasmid/nanoparticles embedded in hyaluronic acid (HA) hydrogel to reduce flexor tendon adhesions. The local sustained gene delivery system significantly downregulates COX-1 and COX-2 expression in the tendon tissue and the surrounding subcutaneous tissue. More importantly, this plasmid/nanoparticle hydrogel system significantly reduced tissue adhesion formation. This approach offers an effective therapeutic strategy to reduce tendon adhesions by directly targeting the down-regulation of COX-1 and COX-2 expression within the microenvironment of the injured tendon. STATEMENT OF SIGNIFICANCE: A local sustained gene delivery system was developed to regulate the expression of targeted genes in the specific time and location for tendon adhesion treatment. The engineered miRNA plasmid/nanoparticles embedded in hyaluronic acid hydrogel were synthesized to downregulate the expression of cyclooxygenases in the tendon tissue during the early stage of tendon healing with inflammatory response. This plasmid/nanoparticle hydrogel system offers an effective therapeutic strategy to attenuate the formation of tendon adhesion through direct downregulation of COX-1 and COX-2 expression within the microenvironment of the injured tendon.

Low-Dose and Short-Duration Matrix Metalloproteinase 9 Inhibition Does Not Affect Adhesion Formation during Murine Flexor Tendon Healing.

BACKGROUND: After flexor tendon injury and repair, adhesion formation is a substantial concern, as it can result in loss of motion and functional disability. Matrix metalloproteinase 9 (Mmp9) is a gelatinase that contributes to degradation of extracellular matrix and is expressed during flexor tendon healing. Mmp9(-/-) mice have accelerated remodeling of adhesions during flexor tendon healing, relative to wild-type mice. The purpose of this study was to investigate whether Ro 32-3555, an Mmp9 inhibitor, can improve flexor tendon healing by limiting adhesion formation or enhancing remodeling of scar tissue during murine flexor tendon healing. METHODS: Flexor digitorum longus laceration and repair was performed in female C57BL/6J mice. Mice were treated with vehicle or the Mmp9 inhibitor Ro 32-3555 for 8 days. Analysis was performed for digit range of motion and gliding function, biomechanics, gene expression, and Mmp9 activity. RESULTS: An Mmp9 activity assay and zymography confirmed suppression of Mmp9 activity in mice treated with Ro 32-3555. There was no significant difference in tendon gliding or range of motion between vehicle and Ro 32-3555-treated mice. There was also no difference in tendon biomechanical properties between the two groups. CONCLUSION: Local inhibition of Mmp9 gelatinolytic activity at the flexor tendon repair site is insufficient to alter adhesion formation, remodeling of adhesions, or mechanical properties of healing murine flexor tendons.

Molecular implication of ADAM-15 and -17 in intrauterine adhesions.

OBJECTIVES: To investigate the regulation of the proteins ADAM-15 and ADAM-17 in intrauterine adhesions (IUA). STUDY DESIGN: 68 patients were found to have IUA in a study performed at our Department of Gynecology, and 18 control volunteer participants were recruited in the study. The patients with IUA were assigned to three groups according to the classification of March et al.: IUA-I (n=28), IUA-II (n=22), and IUA-III (n=18). All the volunteers were assigned to the control group (Con, n=18). The expression of ADAM-15 and ADAM-17 in the adhesive band tissue in patients and the endometrium in volunteers was detected by western blot, real-time PCR, and immunohistochemistry. RESULTS: The expression of ADAM-15 and ADAM-17 was significantly upregulated in both protein level and transcript level in IUA patients compared to that in controls. ADAM-15 expression was significantly higher in IUA-III (4.59±0.15) compared to IUA-II (3.18±0.12) and IUA-I (2.11±0.17; P<0.01). ADAM-17 expression was also significantly higher in IUA-III (3.25±0.11) compared to IUA-II (2.21±0.15) and IUA-I (1.78±0.21; P<0.01). The transcript levels of ADAM-15 and ADAM-17 showed similar patterns, and were markedly higher in grade III IUA patients compared to grade II and grade I. The severity of IUA was positively correlated to the protein and transcript expression level of ADAM-15 and ADAM-17 in uterine tissue. CONCLUSIONS: The development of IUA is associated with regulation of ADAM15 and ADAM-17, which may be potential biological markers for evaluating the severity of intrauterine adhesions.

Intraabdominal adhesion formation is associated with differential mRNA expression of metabolic genes PDHb and SDHa.

PURPOSE: Intraabdominal adhesions represent a major cause of postoperative morbidity potentially causing pain, small bowl obstruction and infertility. The process of adhesion formation might be regarded as an ischemic disease. Under hypoxic conditions, metabolic enzymes are regulated via hypoxic responsive elements by the hypoxia-inducible factor 1 (HIF-1). We therefore investigated the gene expression of HIF-1 and two pivotal metabolic genes, pyruvate-dehydrogenaseß (PDHb) and succinate-dehydrogenase-complex-subunit-A (SDHa) in a validated ischemia model of adhesion formation. METHODS: Peritoneal adhesions were created using an ischemic button model in female Wistar rats. Expression levels of HIF-1α/ß, PDHb and SDHa in adhesiogenic versus native peritoneum were analyzed using quantitative PCR on the third post-operative day. RESULTS: Gene expression of HIF-1α was up-regulated by 10 % (p = 0.003), PDHb was up-regulated by 23 % (p = 0.0004) and SDHa (p = 0.0005) was up-regulated by 24 % in the adhesiogenic peritoneum compared to native peritoneum. The expression level of HIF-1ß was not significantly influenced by adhesion formation. CONCLUSION: The increased expression level of HIF-1α in the peritoneal tissue of ischemic buttons associated with postsurgical adhesions supports the major role for hypoxia in influencing peritoneal expression patterns of genes involved in the process of adhesion formation. As pivotal metabolic genes are upregulated, this seems to be an anabolic process associated with increased cellular metabolism.

The role of myeloperoxidase in the pathogenesis of postoperative adhesions.

Hypoxia induces the adhesion phenotype, characterized by enhanced extracellular matrix molecule and cytokine expression. Additionally, hypoxia reduces myeloperoxidase (MPO) activity in normal peritoneal fibroblasts to basal levels of adhesion fibroblasts indicating the importance of this enzyme in the development of the adhesion phenotype and also in tissue fibrosis. Immunohistochemistry was used to detect and localize MPO and inducible nitric oxide synthase (iNOS) in fibroblasts. Silencing of these genes was performed using siRNA technology. Levels of iNOS, MPO, type I collagen, and transforming growth factor were detected using real-time reverse transcription-polymerase chain reaction (RT-PCR), while HPLC was used to measure nitrate/nitrite levels. Our results show a unique interaction between MPO and iNOS, which are colocalized in both cell lines. Silencing iNOS reduced MPO and nitric oxide levels while silencing MPO had similar results, but to a lesser extent in both cell types. Additionally, silencing iNOS reduced type I collagen and transforming growth factor-beta in adhesion fibroblasts, but to a lesser extent in peritoneal fibroblasts. These studies identify MPO and iNOS as key enzymes in the cellular response to hypoxia and consequent development of tissue fibrosis.

Cilostazol and pentoxifylline decrease angiogenesis, inflammation, and fibrosis in sponge-induced intraperitoneal adhesion in mice.

AIMS: Adhesion formation following abdominal intervention is an abnormal peritoneal healing process. Our aim was to investigate the effects of controlling adhesion development by inhibiting its key components (angiogenesis, inflammation and fibrosis) using phosphodiesterase (PDE) inhibitors. MAIN METHODS: Two PDE inhibitors including cilostazol a PDE3 inhibitor (40 and 400 mg/kg), and pentoxifylline (PTX), a PDE 1-5 inhibitor (50 and 500 mg/kg) were used for a period of 7 days to inhibit angiogenesis, inflammation, and fibrosis in a murine model of sponge-induced peritoneal adhesion. Angiogenesis was assessed by hemoglobin content, vascular endothelial growth factor (VEGF) levels, and morphometric analysis. Accumulation of neutrophils and macrophages was determined by measuring myeloperoxidase (MPO) and N-acetylglucosaminidase (NAG) activities, respectively. Levels of TNF-alpha were also determined. Fibrosis was assessed by determining the amount of collagen in the implant; TGF-beta1 levels in the implant were also measured. KEY FINDINGS: Our results show that the treatments attenuated the main components of the adhesion tissue by reducing the amount of fibrovascular tissue that infiltrated the sponge matrix (wet weight). Hemoglobin content and VEGF levels were also decreased by approximately 40%. Neutrophil accumulation was unaffected by the compounds. However, NAG activity was reduced by pentoxifylline, but not by cilostazol. These compounds also decreased the levels of the pro-inflammatory and pro-fibrogenic cytokines TNF-alpha and TGF-beta1, respectively, and collagen synthesis. SIGNIFICANCE: Our results suggest that cilostazol and PTX decreased the development of peritoneal adhesions in the model, which might be associated with cyclic nucleotide modulation. Therapies to intervene in these pathways may be beneficial for the prevention of these lesions.

[Matrix metalloproteinase 9 presence in adhesive intraperitoneal processes]. / Studiul prezentei metaloproteinazei 9 la nivelul proceselor aderentiale cronice intraperitoneale.

UNLABELLED: Matrix metalloproteinases (MMP) represents a zinc-dependent proteolytic enzyme multigenic family, directly involved in embryogenesis, some physiological and pathological processes, occurring in the adult organism. For physiological processes, MMP play roles in proliferation, tissue remodeling, wound healing, angiogenesis. AIM: The aim of the study was to analyze the MMP9 presence in chronic peritoneal adherences, following the correlation between the presence of this metalloproteinase and the evolution of the connective tissue remodeling process from intraperitoneal adherences. MATERIAL AND METHODS: 6 women formed the study group: 5 operated for gynecological pathologies (with harvested tissue fragments from the adherences) and one patient with harvested tissue from normal peritoneum. Fragments were fixed in 10% formalin and processed for the microscopic exam in routine staining and immunohistochemistry, using anti-MMP9 antibodies and a technique based on peroxidaze-antiperoxidase system. The immunohistochemical reaction was quantified by using image analysis software. RESULTS: The morphological structure of the adherences was mainly represented by fibrous tissue, sometimes associated with elements of muscle and adipose tissues. For the fibrous connective tissue, the collagen component was characterized by a fascicular organization with different orientations and with fibrillar aspect. Semiquantitative analysis showed increased levels for MMP9 in adherences by comparison with normal peritoneum (mean ration for the MMP9-positive area: 26.5% for the adherences versus 15.93% normal peritoneum). CONCLUSION: The intraperitoneal adherences with more than 1 year of evolution show an extension of the remodeling processes that can lead to the possible resolution.

Regulation of inducible nitric oxide synthase in post-operative adhesions.

BACKGROUND: The deficiency of the inducible nitric oxide synthase (iNOS) substrate, L-arginine (L-Arg), the co-factor tetrahydrobiopterin (H4B) or molecular oxygen may lead to lower NO levels, which enhances the development of adhesion phenotype. METHODS: We utilized high-performance liquid chromatography (HPLC) and immunoprecipitation with nitrotyrosine antibody to determine the levels of H4B, citrulline and protein nitration in fibroblasts established from normal peritoneal and adhesion tissues. RESULTS: The level of H4B was dramatically attenuated in adhesion fibroblasts. The immunoprecipitation with nitrotyrosine antibody revealed higher protein nitration in adhesion compared with normal fibroblasts. There were higher accumulations of citrulline in adhesion fibroblasts as compared with normal fibroblasts. In addition, peritoneal fibroblasts treated with 2% oxygen for 24 h and implanted back into the peritoneal cavity of the rats exhibited marked increase in severity of adhesion as well as extensive distribution involving many sites and organs. CONCLUSIONS: Control of the catalytic activity of iNOS in adhesion fibroblasts may be because of subsaturating amounts of L-Arg and H4B which allow iNOS to generate a combination of reactive oxygen species in addition to NO, thereby influencing NO bioavailability and function.

The effect of inducible nitric oxide synthase on postoperative adhesion formation in rats.

OBJECTIVE: To evaluate the effect of iNOS on adhesion formation and to assess whether inhibition of iNOS expression affected adhesion formation according to adhesion maturation days. STUDY DESIGN: Forty Wistar Albino rats were subjected to standardized lesion by cecal abrasion and parietal peritoneal defect and were randomly divided into four groups. Group I (control) received no treatment; groups II-IV received N-acetyl-cystein (NAC) 15 mg/100 g per day intramuscularly on days 4-14, 0-14 and 0-3, respectively, after surgery. On the postoperative 14th day adhesion score, tissue iNOS expression, inflammatory cell reaction (ICR) and tissue fibrosis score were determined. RESULTS: Inflammation score of groups I and II was lower than that of groups III and IV (P < 0.05). Adhesion scores and tissue fibrosis of group II were significantly lower than that of the other groups (P < 0.001). CONCLUSION: iNOS inhibition during the first 3 days postoperatively caused a delay in the resolution of inflammatory cell reaction. On the other hand, when inhibited after the first 3 days, adhesion formation and fibrosis were reduced both clinically and histopathologically.

Significance of chymase inhibition for prevention of adhesion formation.

To clarify the role of chymase in adhesion formation, we investigated whether a chymase inhibitor could prevent adhesion formation after surgery in hamsters. Hamsters received a lesion produced by uterus scraping. A specific chymase inhibitor, 2-[4-(5-fluoro-3-methylbenzo[b]thiophen-2-yl)sulfonamido-3-methanesulfonylphenyl]oxazole-4-carboxylicacid (TY-51184), or placebo was injected into the abdomen before closing and scores for adhesion formation were assessed at 1, 4, and 12 weeks. A single peritoneal administration of TY-51184 significantly decreased the adhesion scores even at 12 weeks (placebo, 2.80+/-0.20; chymase inhibitor, 1.60+/-0.31). Thus, chymase inhibitors may be a novel strategy to prevent adhesion formation.

Cyclooxygenase-2 is expressed in human fibroblasts isolated from intraperitoneal adhesions but not from normal peritoneal tissues.

OBJECTIVE: To determine whether the COX-2 gene is expressed in human fibroblasts isolated from normal peritoneal and adhesion tissues. DESIGN: Prospective experimental study. SETTING: University medical center. PATIENT(S): Five patients undergoing laparotomy for pelvic pain. Primary cultures of fibroblasts were taken from both peritoneum and adhesion tissues. INTERVENTION(S): Hypoxia treatment of the primary cultured fibroblasts. MAIN OUTCOME MEASURES: We used the multiplex reverse transcription-polymerase chain reaction (RT-PCR) and immunohistochemistry techniques to determine whether COX-2 mRNA and its protein were present in normal peritoneal and adhesion fibroblasts from the same patients. Total RNA was extracted from cultured fibroblasts and subjected to multiplex RT-PCR to detect the presence of COX-2 mRNA in these cells. Cultured fibroblasts from all tissues were also fixed on slides and stained with COX-2 monoclonal antibody labeled with immunofluorescence. RESULT(S): COX-2 mRNA and its protein were absent in normal peritoneal fibroblasts from all five subjects but were present in adhesion fibroblasts from the same patients, as indicated by the multiplex RT-PCR and immunohistochemistry techniques. Hypoxia treatment significantly induced the mRNA and COX-2 protein levels in normal peritoneal fibroblasts to levels seen in adhesion fibroblasts under normoxic conditions. However, hypoxia had no effects on COX-2 expression by adhesion fibroblasts. CONCLUSION(S): Adhesion fibroblasts develop a specific phenotype, an adhesion phenotype, which is in part characterized by the expression of COX-2. The expression of COX-2 mRNA in adhesion fibroblasts and the induction of COX-2 in peritoneal fibroblasts in response to hypoxia indicate a possible inflammatory response. Regulation of COX-2 may alter peritoneal healing and may provide the opportunity to reduce postoperative adhesion development.

Role of plasminogen activators in peritoneal adhesion formation.

Intra-abdominal adhesion formation is a major complication of serosal repair following surgery, ischaemia or infection, leading to conditions such as intestinal obstruction and infertility. It has been proposed that the persistence of fibrin, due to impaired plasminogen activator activity, results in the formation of adhesions between damaged serosal surfaces. This study aimed to assess the role of fibrinolysis in adhesion formation using mice deficient in either of the plasminogen activator proteases, tissue-type plasminogen activator (tPA) or urokinase-type plasminogen activator (uPA). We hypothesize that, following serosal injury, mice with decreased peritoneal fibrinolytic activity will be more susceptible to adhesion formation. Adhesion formation was induced in tPA- and uPA-deficient and wild-type mice following either surgical trauma to the serosa with haemorrhage and acute or chronic intraperitoneal inflammation. Adhesion formation was assessed from 1 to 4 weeks post-injury. Mice deficient in tPA were more susceptible to adhesion formation following both a surgical insult and a chronic inflammatory episode compared with uPA-deficient and wild-type mice. In addition, the time of maximal adhesion formation varied depending on the nature of the initial insult. It is proposed that the persistence of fibrin due to decreased tPA activity following surgery or chronic inflammation plays a major role in peritoneal adhesion formation.

Matrix metalloproteinase (MMP-1) and tissue inhibitor of MMP in peritoneal fluids and sera and correlation with peritoneal adhesions.

OBJECTIVE: To assess the presence of matrix metalloproteinase (MMP-1) and tissue inhibitor of MMP (TIMP-1) in peritoneal fluid and serum of subjects with and without adhesions. DESIGN: Cross-sectional study. SETTING: Academic research centers. PATIENT(S): Sixty-three patients who underwent abdominal/pelvic surgery. INTERVENTION(S): MMP-1, TIMP-1, and MMP-1-TIMP-1 complex content. MAIN OUTCOME MEASURE(S): ELISA. RESULT(S): Peritoneal fluids (PF) and sera of subjects with and without peritoneal adhesions contain MMP-1, TIMP-1, and MMP-1-TIMP-1 complex at varying levels with 10- to 100-fold higher TIMP-1 than MMP-1. Compared with serum, PF contains a lower level of MMP-1 in subjects with mild adhesions and without adhesions, higher TIMP-1 in subjects with extensive adhesions, and lower MMP-1-TIMP-1 complex in subjects with moderate adhesions. However, the serum and PF content of MMP-1, TIMP-1, and MMP-1-TIMP-1 complex was not statistically different among subjects with or without adhesions, with the exception of TIMP-1 in PF of subjects with extensive adhesions. MMP1-TIMP-1 ratio indicates that a major portion of MMP-1 is in complex with TIMP-1. There was no age- or gender-dependent difference in MMP-1 and TIMP-1 content in serum or PF. CONCLUSION(S): Despite differences in MMP-1 and TIMP-1 levels in serum and PF of subjects with extensive and moderate adhesions, there is no correlation between MMP-1 and TIMP-1, with the exception of higher TIMP-1 in PF of subjects with extensive adhesions.

Expression of matrix metalloproteinase (MMP-1) and tissue inhibitor of MMP in serosal tissue of intraperitoneal organs and adhesions.

OBJECTIVE: To compare expression of matrix metalloproteinase (MMP-1) and tissue inhibitor of MMP (TIMP-1) in serosal tissue of intraperitoneal organs and adhesions. DESIGN: Prospective and cross-sectional study. SETTING: Academic research centers. PATIENT(S): Patients undergoing abdominal or pelvic surgery. INTERVENTION(S): MMP-1 and TIMP-1 expression. MAIN OUTCOME MEASURE(S): Expression of messenger ribonucleic acid (mRNA) and protein was measured by using quantitative reverse transcription polymerase chain reaction (RT-PCR) and enzyme-linked immunosorbent assay. RESULT(S): Serosal tissue of intraperitoneal organs and adhesions express MMP-1 and TIMP-1 mRNA and protein at levels that are consistently varied with 10- to 10,000-fold and 2- to 10-fold higher TIMP, mRNA and protein, respectively. Parietal peritoneum, fallopian tubes and ovaries express higher MMP-1 mRNA levels compared with uterus and adhesions; the lowest expression is found in small and large bowels, subcutaneous tissue. and omentum. Expression of TIMP-1 mRNA was less variable; the highest level was found in the uterus and the lowest in subcutaneous tissue and small bowels. There was less variability in MMP-1 and TIMP-1 protein content than mRNA expression; ovaries and adhesions contained the highest MMP-1 and TIMP-1 levels, respectively, and peritoneum contained the lowest. The MMP-1 and TIMP-1 content and ratios further indicate limited MMP-1 proteolytic activity. Although tissues from premenopausal women express more MMP-1 and TIMP-1, expression did not differ by sex or age. CONCLUSION(S): Because MMP-1 and TIMP-1 expression varies consistently among the serosal tissues of peritoneal organs and adhesions, and because tissue injury alters their expression, site-specific variations in expression of these substances may predispose a particular organ to develop more adhesions.

Postoperative exposure to glove powders modulates production of peritoneal eicosanoids during peritoneal wound healing.

OBJECTIVE: To assess the effect of postsurgical exposure of peritoneal cavity to glove powders, Hydrocote, latex proteins, and lipopolysaccharide (LPS) on eicosanoid production in peritoneal fluid and cellular distribution of eicosanoid enzymes in peritoneal wound during healing. DESIGN: Randomised experimental study. SETTING: Institute for Wound Research, USA. ANIMALS: 360 mice randomised into six groups of 60 each. INTERVENTION: Abrasion of peritoneal cavity followed by instillation of 500 microl of sterile phosphate buffered saline (PBS) alone (Control) or containing 100 microg/ml of Biosorb, Keoflo, Hydrocote, 1 mg/ml of latex proteins, or 12.5 microg/ml of LPS. Mice were killed at 1, 2, 4, 7, 14 and 28 days, and the peritoneal washing obtained from each animal and concentration of eicosanoids measured. Tissue were immunostained for cyclooxygenases and 5-lipoxygenase and thromboxane A2 (TXA2) synthetase. RESULTS: Peritoneal fluid from uninjured controls contained 3.9 (0.8), 5.2 (0.3) and 0.2 (0.02) ng/ml of thromboxane B2 (TXB2), prostaglandin E2 (PGE2) and leukotriene B4 (LTB4), respectively. These increased significantly during the first week to 6.3 (0.3), 11.7 (0.8) and 2.6 (0.1) ng/ml, p<0.05, before returning to baseline by day 14. In all the treated groups the values were significantly higher than in controls (p<0.05). Immunoreactive cyclo-oxygenases, 5-lipoxygenase and TXA2 synthetase proteins were present in various cell types in uninjured skin and peritoneum, incisional and peritoneal wounds and adhesion tissues. Staining was more intense at the site of wounds and paralleled eicosanoid concentrations during healing. There was no difference between exposed and unexposed groups. CONCLUSION: The presence of glove powders, latex proteins and LPS in peritoneal cavity cause increased eicosanoid production and aggravate the normal inflammatory reaction to tissue injury. This may contribute to the inflammatory or immune reactions and development of adhesions caused by glove powders.

Lysyl oxidase transcripts in peritoneal adhesions and incisional scars.

OBJECTIVE: To evaluate the role of lysyl oxidase in postsurgical adhesion formation and incision wound repair. STUDY DESIGN: Female New Zealand rabbits underwent a pelvic-peritoneum adhesion-inducing operation under sterile conditions. In brief, the uterine horns were removed from the abdomen and abraded with surgical gauze and a scalpel blade. The horns were then replaced into the abdominal cavity, the incision was sutured, and the animals were allowed to recover. The animals were killed before lesion development and after 2, 4, 8, and 14 days of postsurgical recovery. The abraded uterine horns, abdominal wall incisional wound and a portion of the sidewall peritoneum were then removed. Total RNA was extracted using the guanidinium thiocyanate-phenol-chloroform method. Northern blot analysis was performed with an [alpha-32P]-labeled lysyl oxidase probe. RESULTS: Lysyl oxidase was expressed during abdominal wall incision repair on days 2 and 4 of postsurgical recovery, declining thereafter (days 8 and 14). In contrast, no increase in lysyl oxidase expression was noted in the uterine horns as compared to the control sidewall peritoneum. CONCLUSION: Lysyl oxidase plays a differential role in the early stages of abdominal wall and uterine horn repair.

Reduced human peritoneal plasminogen activating activity: possible mechanism of adhesion formation.

A unifying pathophysiological hypothesis states that the plasminogen activating activity (PAA) of the peritoneal mesothelium determines whether the fibrin which forms after peritoneal injury is either lysed or organized into permanent fibrous adhesions. The PAA of human peritoneal biopsies was measured using a fibrin plate lysis technique to assess the changes that occur in inflammation and ischaemia, conditions which both produce fibrous adhesions. Activity was found in all biopsies from normal parietal and visceral (appendix, bowel and omentum) peritoneum with no significant site-to-site variation. Inflamed peritoneum (parietal, appendicular and mesenteric) had significantly less PAA compared with normal peritoneum; visceral ischaemia also resulted in a significant decrease of PAA. These reductions in human peritoneal PAA observed in inflammation and ischaemia support the view that mesothelial PAA plays a key part in the prevention of events leading to the production of fibrous adhesions.