Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P00750 (PLA)
 16,800 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We investigated the ability of recombinant tissue plasminogen activator to inhibit post-radical pelvic surgery adhesions formation in 40 adult female canines undergoing radical hysterectomy, bilateral salpingo-oophorectomy, omentectomy, resection of pelvic and abdominal peritoneum, and placement of a peritoneal access catheter. Immediately after operation one half of animals received either recombinant tissue plasminogen activator, 1 mg/kg weight, diluted in 9 ml sterile normal saline solution per milligram of the plasminogen activator or 10 ml vehicle per kilogram intraperitoneally every 12 hours for a total of 10 doses. A single control animal died postoperatively of complications of intestinal obstruction. No bleeding abnormalities were noted in either group of animals. Four weeks after surgery, animals underwent reexploration and adhesions were quantified. Adhesion scores for the animals treated with recombinant tissue plasminogen activator (n = 20; mean score, 1.29 +/- 1.97; median, 0.6) were significantly less than for control animals (n = 19; mean score, 4.64 +/- 3.71; median, 3.86; p = 0.03). Whereas recombinant tissue plasminogen activator appears to effectively prevent post-radical pelvic surgery adhesions in this canine model, phase I and II trials in humans will be required to determine safety and clinical benefit.
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PMID:The ability of recombinant tissue plasminogen activator to inhibit post-radical pelvic surgery adhesions in the dog model. 195 91

Adhesions are the leading cause of small bowel obstruction and a frequent cause of failure of infertility operations. Fibrinolysis is involved in the formation and resolution of adhesions. Although intravenous dextran (Macrodex) is known to augment intravascular fibrinolysis, the effects of intraperitoneal dextran (Hyskon) on fibrinolysis have not been extensively studied. A fibrin plate assay system was used to assess plasminogen activator activity of rabbit peritoneum and plasma after treatment with intraperitoneal or intravenous dextran 70. Hyskon significantly reduced the ability of severe trauma to depress plasminogen activator activity of visceral peritoneum and was capable of direct plasminogen activation. Untraumatized or minimally traumatized peritoneum was not affected, nor was plasminogen activator activity of plasma. Pulmonary effusions and perioperative deaths were significantly associated with the use of Hyskon.
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PMID:Intravenous versus intraperitoneal administration of dextran in the rabbit: effects on fibrinolysis. 242 47

Damage to the fibrinolytic system preventing the resolution of temporary fibrinous adhesions was repeatedly mentioned as an etiological factor in the process of adhesion formation. We experimentally induced abdominal adhesions in rats by gentle scraping of the entire small bowel. Severe adhesions, sometimes accompanied by intestinal obstruction, developed in all of the control animals. Urokinase, a commonly used and potent fibrinolytic agent and a known plasminogen activator, was administered intragastrically, intraperitoneally, or intravenously at various doses ranging from 5,000 to 100,000 U/kg. Urokinase had no effect on the prevention of abdominal adhesions, nor did it reduce the severity or frequency of adhesion formation.
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PMID:Urokinase does not prevent abdominal adhesion formation in rats. 404 58

The increased incidence of postoperative adhesions and their complications have refocused attention on our understanding of adhesions, their clinical consequences and prevention. Postsurgical adhesions have four major negative impacts on health care outcomes. First, adhesions cause significant morbidity, including intestinal obstruction, infertility and pelvic pain. Second, adhesions are associated with multiple surgical complications. Third, these complications lead to greater surgical workload and utilization of hospital and other health care resources. Fourth, all these negative impacts result in significant economic burden to society. The complexities of adhesion formation and limitations in their understanding and research have hampered the development of satisfactory preventive treatments. Adhesions are highly differentiated, formed through an intricate process and associated with a complex organ, the peritoneum. The surface lining of the peritoneum is the key site in adhesion formation and prevention. Two unique properties of the peritoneal surface play key roles in these processes: its delicacy and its uniform, relatively rapid rate of re-epithelialization, irrespective of the size of injury. A suitable barrier that separates damaged peritoneal surfaces for the entire five to seven days of re-epithelialization is likely to prove effective in reducing adhesion formation. Postsurgical peritoneal repair begins with coagulation, which releases a variety of chemical messengers that bring about a cascade of events. Some of the principal cellular elements in this cascade are leukocytes, including polymorphonuclear neutrophils and macrophages, mesothelial cells, and fibrin. Following surgical injury, macrophages exhibit increased phagocytic, respiratory burst and secretory activity, and after day 5, are the major component of the leukocyte population. Macrophages also recruit new mesothelial cells onto the surface of the injury. These cells form small islands throughout the injured area which proliferate into sheets of mesothelial cells and accomplish re-epithelialization, usually five to seven days after surgical injury. The progenitor to adhesions is the fibrin gel matrix which develops in several steps. These include the formation and insolubilization of fibrin polymer and its interaction with fibronectin and a series of amino acids. Protective fibrinolytic enzyme systems of the peritoneal mesothelium, such as the tissue plasminogen activator (tPA) system, can remove the fibrin gel matrix. However, surgery dramatically diminishes fibrinolytic activity. This occurs in at least two ways: first, by increasing levels of plasminogen activator inhibitors and second, by reducing tissue oxygenation. Peritoneal re-epithelialization and adhesion formation thus can be seen as alternative pathways following peritoneal injury. The pivotal events determining the pathway are the apposition of two damaged surfaces and the extent of fibrinolysis. Development of strategies to separate damaged peritoneal surfaces and to foster an appropriate degree of fibrinolysis appears to be among the most promising avenues of adhesion prevention research. Hopefully, these efforts will lead to adhesion-free peritoneal healing following abdominal surgery.
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PMID:Biochemical events in peritoneal tissue repair. 907 47

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.
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PMID:Role of plasminogen activators in peritoneal adhesion formation. 1202 39

Postoperative adhesion development remains a very frequent occurrence, which is often unrecognized by surgeons because of limited ability to conduct early second-look laparoscopies. The consequences include infertility, pelvic pain, bowel obstruction, and difficult reoperative procedures. To date, approaches to limit adhesions primarily have involved barriers to separate tissue during reepithelization. Future progress in regulating adhesion development and tissue fibrosis likely will require an improved understanding of the molecular processes involved in normal peritoneal repair and its aberrations leading to adhesion development. We hypothesize that tissue hypoxia (in part resulting from tissue incision, fulguration, suture ligation, etc.) is the major inciting event, which leads to a coordinated series of molecular events that promote an inflammatory response leading to enhanced tissue fibrosis. These events are reduced plasminogen activator activity, extracellular matrix deposition, increased cytokine production, increased angiogenesis, and reduced apoptosis (programmed cell death). Improved understanding of these events and their regulation will provide the opportunity to regulate better postoperative adhesion development and tissue fibrosis, thereby reducing the morbidity and mortality they cause.
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PMID:Molecular characterization of postoperative adhesions: the adhesion phenotype. 1555 39

Most surgical procedures performed by obstetrician-gynecologists are associated with pelvic adhesions that cause subsequent serious sequelae, including small bowel obstruction, infertility, chronic pelvic pain, and difficulty in postoperative treatment, including complexity during subsequent surgical procedures. This study was conducted to determine if gonadotropin-releasing hormone analogues (GnRHa) affect the expressing tissue-type plasminogen activator (t-PA) and its inhibitor-1 (PAI-1) in peritoneal cells in culture. Human peritoneal Met5A cells were used to examine the effects of GnRHa leuprolide, buserelin and goserelin on the levels of t-PA and PA-1. Antigen concentrations were measured in conditioned media and cell lysates by real-time PCR and ELISA. GnRH receptor (GnRHR) mRNA was determined by RT-PCR. GnRHR mRNA was detected in Met5A cells. Exposure of Met5A cells to GnRHa induced a rapid decrease of PAI-1 level in cultured medium but not in cell lysate (protein and mRNA). These effects of GnRHa on PAI-1 were not associated with any changes in t-PA level. These results suggest that GnRHa may be an effective stimulator of local peritoneal fibrinolytic activity, as it decreases PAI-1 secretion in peritoneal Met5A cells by a mechanism linked to GnRHR.
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PMID:GnRH receptor and peritoneal plasmin activity. 2023 28

Post-operative peritoneal adhesions are serious consequences of abdominal or pelvic surgery and cause severe bowel obstruction, chronic pelvic pain and infertility. In this study, a novel nano-hydrogel system based on a monomethoxy poly(ethylene glycol)-poly(lactic acid) (MPEG-PLA) di-block copolymer was studied for its ability to prevent abdominal adhesion in rats. The MPEG-PLA hydrogel at a concentration of 40% (w/v) was injected and was able to adhere to defect sites at body temperature. The ability of the hydrogel to inhibit adhesion of post-operative tissues was evaluated by utilizing a rat model of abdominal sidewall-cecum abrasion. It was possible to heal wounded tissue through regeneration of neo-peritoneal tissues ten days after surgery. Our data showed that this hydrogel system is equally as effective as current commercialized anti-adhesive products.
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PMID:Biodegradable and thermosensitive monomethoxy poly(ethylene glycol)-poly(lactic acid) hydrogel as a barrier for prevention of post-operative abdominal adhesion. 2473 Feb 38