Biomedical subjects
C L McGuinness
Publications and source records attributed to C L McGuinness.
Monocyte chemotactic protein-1 (MCP-1) accelerates the organization and resolution of venous thrombi.
PURPOSE: Organization, recanalization, and contraction are common to wound healing and thrombus resolution. Monocytes are essential to wound healing and are also found in venous thrombi. We measured endogenous levels of the monocyte chemotactic protein-1 (MCP-1) in naturally resolving venous thrombi and determined the effect of injecting MCP-1 into newly formed thrombus. METHODS: Endogenous MCP-1 levels were estimated in rat blood, thrombi, and the adjacent vessel wall after thrombus formation, in cohorts of eight animals at 1, 7, and 14 days. In another group (n = 10), 1 microgram of MCP-1 was injected into newly formed thrombi. Carrier was injected into the thrombi of control animals (n = 10). Thrombi and adjacent vein walls were obtained for histology at 7 days. Thrombi were given an arbitrary organization score based on erythrocyte and extracellular matrix content, which was assessed by means of computerized and observer analysis. Specimen weight, thrombus area, and cellular and monocyte content were measured. RESULTS: Endogenous MCP-1 increased between days 1 and 7 in the thrombus (1-day median, 1.1 ng/g wet wt; 1-day range, 0.8 to 1.4 ng/g wet wt; 7-day median, 5.4 ng/g wet wt; 7-day range, 1.5 to 7.4 ng/g wet wt; P <.0001) and vein wall (1-day median, 1.5 ng/g wet wt; 1-day range, 0.8 to 4.3 ng/g wet wt; 7-day median, 3.3 ng/g wet wt; 7-day range, 2.7 to 8.3 ng/g wet wt; P <. 05). At 14 days, thrombus was incorporated in the vein wall, and total MCP-1 levels remained high (median, 3.9 ng/g wet wt; range, 1.1 to 7.4 ng/g wet wt). Less MCP-1 was found in the thrombus than the adjacent vessel wall at day 1 (P <.05), but there was no difference at day 7. MCP-1 could not be detected in the blood. MCP-1 injection into thrombus increased the computer (P =.016) and observer (P =.004) organization scores, reduced the thrombus area (from median, 3. 4 mm(2), and range, 1.5 to 5.7 mm(2), to median, 0.2 mm(2), and range, 0.02 to 2.6 mm(2); P =.048), and increased the surrounding vessel wall monocyte content (P =.008). Specimen weights of treated animals were lower than those of control animals (P <.02). CONCLUSION: Venous thrombus MCP-1 levels increase during natural resolution. MCP-1 treatment increased the organization and resolution of thrombi. MCP-1 may therefore be of therapeutic use.
The role of the monocyte in the generation and dissolution of arterial and venous thrombi.
Monocyte infiltration into forming thrombus has been demonstrated in experimental models of venous thrombosis developed in our laboratories. These cells produce and release plasminogen activators as the thrombus organises and resolves. Monocytes are also capable of assembling and releasing procoagulant factors and the evidence for their importance in thrombogenesis is reviewed. The ability of monocytes to maintain this fibrinolytic balance suggests that they may have a role in both thrombosis and thrombus resolution. Control of the mechanisms which regulate these activities may therefore be important in preventing thrombus formation or stimulating its resolution.
High and constant plasma levels of tissue plasminogen activator and PEG-hirudin can be achieved by subcutaneous delivery.
Intramural thrombosis is a consistent finding in the arteries of patients who die following coronary angioplasty. This thrombosis is thought to have a role in restenosis, which is a common complication of coronary angioplasty. It has been hypothesised that antithrombotics such as hirudin or tissue-type plasminogen activator (tPA), may be therapeutically useful following angioplasty. This report describes the bioavailability of both agents following subcutaneous (sc) injection in cholesterol-fed rabbits. Intravenously delivered tPA has a half-life of 3-5 minutes. The half-life of intravenously administered hirudin is less than one hour in many species. In order to prolong the duration of action recombinant hirudin was conjugated to polyethylene glycol (PEG). Polyethylene glycol conjugated recombinant hirudin (PEG-rH) (0.7 mg/kg) antigen and activity were measurable after just 1 hr, reaching a maximum (663 and 884 ng/ml respectively) at 12 hours. Significant levels were present in rabbit plasma 24 hours after injection. Subcutaneously delivered recombinant (r-tPA) (1 mg/kg) was present in significant amounts 1 hr after injection, reaching a maximum (92 IU/ml) at 2 hours. Levels of tPA at 9 hours were approximately 80x normal circulating levels. High and constant levels of functional activity of both PEG-rH and r-tPA in rabbit plasma are achieved by subcutaneous delivery.
Research in the training of general surgeons: results of a survey.
Explore the source record for details and available documents.
Percutaneous transluminal angioplasty of the internal carotid artery.
Explore the source record for details and available documents.
Stapling technique for annular pancreas.
Explore the source record for details and available documents.