Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0001511 (Adhesion)
 5,955 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Epicardial adhesions are believed to form secondarily to impaired pericardial fibrinolytic activity. This activity was reconstituted in a rabbit pericardial adhesion model with single doses of the fibrinolytic agents tissue plasminogen activator (t-PA), t-PA analog (Fb-Fb-CF), and streptokinase (SK), resulting in reductions in the extent and tenacity of adhesion formation. Adhesions of the median strip of the anterior cardiac surface were reduced in area from 89% (n = 22) in controls, to 28% (n = 5) by treatment with Fb-Fb-CF (0.94 mg), and to 49% (n = 7) by treatment with SK (93,750 IU). A modified fabric of oxidized regenerated cellulose (mTC7) used to deliver the agent to the cardiac surface did not interfere with the activity of these agents (Fb-Fb-CF 19%, n = 14; SK 33%, n = 7). t-PA (0.94 mg) was also found to reduce adhesion formation in combination with mTC7 (4%, n = 4), although the appearance of significant postoperative bruising and bleeding resulted in a decision to terminate the treatment of further animals with t-PA with and without mTC7. Postoperative bruising, bleeding, and swelling, to a lesser extent, were associated with SK and Fb-Fb-CF. Despite the efficacy of the these fibrinolytic drugs further work is required to assess their safety before they are used clinically.
 ...
PMID:Fibrinolytic drugs prevent pericardial adhesions in the rabbit. 140 17

Previous reports have shown the benefits of calcium channel blockers and recombinant tissue plasminogen activator to prevent postoperative adhesion formation in animal models. To assess the potential benefit of synergistic therapy for the prevention of postoperative adhesion formation, these agents were studied in a rabbit uterine horn model. Four groups of New Zealand White rabbits (n = 8 per group) had a bilateral devascularization injury to the uterine horns. Before closure saline solution, verapamil hydrochloride (2.5 mu/kg/hour), recombinant tissue plasminogen activator (4 mg total dose), or a combination of verapamil and recombinant tissue plasminogen activator at the stated doses were instilled by means of an Alzet osmotic pump x 200 hours. Adhesion scores were evaluated after this time period by estimating the total uterine horn surface involved in adhesions at a terminal laparotomy and by clinically grading the response to determine whether minimal adhesions formed. Results of the total uterine horn surface scores were (mean score +/- SE): saline solution, 44% +/- 3.7%; verapamil, 19% +/- 4.8%; recombinant tissue plasminogen activator, 11% +/- 3.6%; combined, 3% +/- 1% (p less than 0.01 to control and p less than 0.05 to single-drug therapy). Results of the number of animals per group with minimal adhesions were as follows: saline solution, 0; verapamil, 1; recombinant tissue plasminogen activator, 3; combined, 8 (P less than 0.01). These results show a synergistic benefit of verapamil and recombinant tissue plasminogen activator to prevent postsurgical adhesion formation when delivered via the intraperitoneal route.
 ...
PMID:Synergistic effect of intraperitoneally administered calcium channel blockade and recombinant tissue plasminogen activator to prevent adhesion formation in an animal model. 190 94

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.
 ...
PMID:The ability of recombinant tissue plasminogen activator to inhibit post-radical pelvic surgery adhesions in the dog model. 195 91

To evaluate the potential benefit of recombinant tissue plasminogen activator (rt-PA) as an agent for reducing postoperative adhesions, a rabbit uterine horn model was studied. Fifty-five rabbits underwent laparotomy, at which time the uterus was abraded with scalpel and a thermal injury was induced with electrocautery. Before abdominal closure, rt-PA was applied topically in various dosages. Adhesions were evaluated at a second laparotomy performed 2 weeks later. Treatment significantly reduced both adhesion quantity (P less than 0.001) and adhesion density (P less than 0.001). In the second phase of the study, the efficacy of rt-PA as an adjunct to surgical adhesiolysis was investigated. Again, a dose-related treatment effect was observed (P less than 0.001). No wound healing or bleeding complications were seen.
 ...
PMID:Recombinant tissue plasminogen activator reduces adhesion formation in a rabbit uterine horn model. 249 5

Recent work shows that a common pathway in adhesion production is a reduction in local plasminogen activator activity (PAA). This deficit permits deposited surface fibrin to become organized to fibrous adhesions. A rabbit model for adhesion formation was used to assess the effect of replacing the deficit with recombinant tissue plasminogen activator (rt-PA). Adhesions were produced by stripping peritoneum from corresponding parietal and visceral areas. One week later the adhesions were divided. Either rt-PA or placebo was applied to the divided adhesion. After a further week the animal was killed and the adhesions assessed. Sixty strips were performed. Fifty-five adhesions were produced (92%). Placebo gel was applied to 28 sides and rt-PA applied to 27. Twenty-two of the placebo group recurred (79%). Two of the rt-PA group reformed (7%, chi 2 = 20.883, P less than 0.001). Recombinant tissue plasminogen activator is an effective inhibitor of adhesion formation in the experimental animal.
 ...
PMID:Intra-abdominal adhesions and their prevention by topical tissue plasminogen activator. 250 82

Monocytes and endothelial cell interactions play a key role in the development of vascular lesion, inflammation and atherosclerosis. Leukocyte adhesion is mediated through specific molecules CD11/CD18 complexes on the leukocyte side and the ELAM (Leukocyte Adhesion Molecule) ICAM (Intercellular Adhesion Molecule) on the endothelium cell surface. Several monocyte products damage endothelial cells such as free radicals, oxygen peroxides, proteases, hydrolases, lipases... Various monokines alter endothelial cell function and proliferation. Interleukin 1, gamma interferon, alpha tumor necrosis factor increase ELAM, further more they induce the synthesis of procoagulant activity by endothelial cells. Monocyte derived growth factor stimulates endothelial cells proliferation while transforming growth factors, beta (TGF beta) and TNF alpha inhibit endothelial cell growth. Lipid products of monocyte origins such as leukotrienes induce an activation of endothelial cells which results in a production of prostacyclin. Monocytes may also participate in the coagulation process by producing thromboplastin and coagulation factors and facilitating the tenase (activation of factor X) complex formation. On the other hand, monocyte also synthesize tissue plasminogen activator and inhibitor. The numerous factor produced by monocytes may affect in different ways the endothelial cell behavior.
 ...
PMID:[Monocyte-endothelium relations]. 265 10

Intra-abdominal adhesions have been shown to result from the impairment of peritoneal fibrinolysis by inhibitors present in ischemic tissue. A reproducible model for the formation of intra-abdominal adhesions was utilized for the evaluation of the effectiveness of intraperitoneal applications of recombinant tissue plasminogen activator (rtPA) in adhesion prevention. Concentrations of rtPA required to overcome the inhibition of fibrinolysis in this model were estimated by titration of that amount of rtPA required to lyse blood clot in the presence of a measured amount of ischemic tissue. Adhesions were graded, and the hydroxyproline content of the abdominal wounds was analyzed. The effect of intraperitoneal administration of rtPA on adhesion formation was strongly dose related. Levels of rtPA of 0.01 mg/mL showed no effect (p < 0.75) on adhesion formation, whereas levels of 0.1 mg/mL either prevented or significantly modified the formation of intra-abdominal adhesions (p < 0.05). Concomitantly, wound hydroxyproline content was significantly reduced (p = 0.004). Prior investigations have shown a strong correlation between wound bursting strength and hydroxyproline content. The results of this study indicated that the levels of rtPA required to alter or prevent intra-abdominal adhesion formation also produce a significant impairment of the early phase of wound healing as measured by the wound content of hydroxyproline.
 ...
PMID:Dose dependency and wound healing aspects of the use of tissue plasminogen activator in the prevention of intra-abdominal adhesions. 842 2

The depression of focal fibrinolytic activity in mesothelial or serosal tissues which results from a surgical ischemic insult can lead to the formation of permanent fibrinous adhesions. To assess the time course for the prevention of adhesion formation by recombinant tissue plasminogen activator (rt-PA), infusions of rt-PA were administered to rabbits every 12 hr for a total of 1, 2, 4, or 8 days. Animals in each rt-PA treatment group received a total cumulative dose of 16 mg. Control animals received saline with the same corresponding dosing regimens as the treated groups. Prior to dosing, all animals had a devascularizing injury to the uterine horns performed bilaterally by bipolar cauterization of the uterine mesenteric vascular arcade below the horns. A catheter was then placed from a subcutaneous port to the intraperitoneal space. rt-PA, or saline, was instilled intraperitoneally via the subcutaneous port. Adhesions were scored at the second laparotomy by assessing the percentage of the involvement of the uterine horns in adhesions. Mean score for adhesion formation in each placebo group was 35 to 40%. Mean score (+/- standard error of the mean) for rt-PA after 1 day of therapy was 13.1% +/- 3.89; after 2 days of therapy, 6.3% +/- 1.57; after 4 days of therapy, 3.8% +/- 1.57; and after 8 days of therapy, 6.9% +/- 2.3 (P < 0.01 compared to the control grouped mean for each day of treatment).(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Effect of varying days of tissue plasminogen activator therapy on the prevention of postsurgical adhesions in a rabbit model. 847 40

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.
 ...
PMID:Biochemical events in peritoneal tissue repair. 907 47

Adhesions, which occur after 67% to 93% of abdominal operations, represent a major clinical problem, resulting in intestinal obstruction, infertility, and pain and incurring considerable economic costs. The magnitude and seriousness of the problem of adhesions have been underappreciated. Moreover, efforts to prevent or reduce adhesions largely have been unsuccessful, hindered by their empirical basis, the lack of good predictive animal models, and the biochemical complexities of adhesiogenesis. The two major strategies for adhesion prevention or reduction are adjusting surgical technique and applying adjuvants. Modifications in technique that all surgeons should implement include minimizing the invasiveness of surgery, minimizing surgical trauma, such as ischemia from peritoneal suturing, and avoiding the introduction of foreign material, e.g., starch glove powder, into the body. Given the adhesiogenic nature of peritoneal repair, however, improvements in surgical technique alone will help decrease but not prevent adhesion formation. Adjuvant therapy is necessary. Adjuvants fall into two main categories, drugs and barriers. Nonsteroidal anti-inflammatory drugs have shown questionable clinical efficacy, possibly because of difficulties in drug delivery. Corticosteroids, alone or with antihistamines, also have had equivocal clinical results and may be immunosuppressive and delay wound healing. Experimentally, fibrinolytics such as tissue plasminogen activator (tPA), administered systemically or intraperitoneally (i.p.), have demonstrated conflicting results and hemorrhagic complications. However, recently, tPA, administered topically in a carboxymethylcellulose (CMC) gel, has been effective in reducing and preventing adhesions in rabbits. Phosphatidylcholine, given i.p. or orally, also has shown promise in animal studies. Barriers, by separating traumatized surfaces for the critical first five to seven days of peritoneal re-epithelialization, are useful adjuvants, and include macromolecular solutions and mechanical devices. Dextran, a macromolecular solution, has been studied widely, but has not demonstrated consistent clinical efficacy and has been largely abandoned as an anti-adhesion barrier. A newly developed hyaluronic acid-phosphate-buffered saline solution applied intraoperatively to protect peritoneal surfaces from indirect surgical trauma effectively and safely reduced adhesions in a large multicenter study of women undergoing gynecological laparotomy. Three recently developed mechanical barriers also have demonstrated clinical progress in adhesion prevention. A bioresorbable membrane consisting of hyaluronic acid and CMC has gained regulatory approval for clinical use in both general and gynecological surgery following demonstration of efficacy and safety in reducing adhesions. A barrier made of expanded polytetrafluoroethylene and another developed from oxidized regenerated cellulose are currently available for gynecological surgery. With continued research, new and improved approaches hopefully will become available to prevent adhesion formation.
 ...
PMID:Adhesions: preventive strategies. 907 50


1 2 Next >>