mRNA-based therapy in a rabbit model of variegate porphyria offers new insights into the pathogenesis of acute attacks

SummaryThe aim of this study was to determine the effects of intra-articular hyaluronic acid on meniscal healing. Circular defects, 1.0 mm in diameter, were made in the anterior third of the medial meniscus in rabbits. In one joint, 0.4 ml hyaluronic acid (Healon®) was instilled, and in the contralateral (control) joint, 0.4 ml Ringer’s saline. Four rabbits were killed after four, eight and 12 weeks and the menisci examined histologically. By eight weeks most of the lesions had healed by filling with hyaline-like cartilage. Healing was not improved by hyaluronic acid treatment. The repair tissue stained strongly with alcian blue, and the presence of type II collagen, keratan sulphate, and chondroitin sulphate was demonstrated by immunohistochemical localisation. In contrast to the circular defects, longitudinal incisions made in the medial menisci of a further six rabbits did not show any healing after 12 weeks, indicating that the shape of the lesion largely determined the potential for healing.The effect of hyaluronic acid on meniscal healing was tested in a rabbit model. With one millimeter circular lesions in the medial meniscus, healing by filling with hyalinelike cartilage was not significantly affected by the application of hyaluronic acid intra-articularly at the time of surgery, compared to saline controls, as assessed histologically four, eight and 12 weeks after the operation.

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Inhibition of Leucocyte and Platelet Adhesion Reduces Neointimal Hyperplasia after Arterial Injury

Thrombosis and Haemostasis ◽

10.1055/s-0038-1656050 ◽

1997 ◽

Vol 77 (04) ◽

pp. 783-788 ◽

Cited By ~ 28

Author(s):

Paolo Golino ◽

Giuseppe Ambrosio ◽

Massimo Ragni ◽

Plinio Cirillo ◽

Nicolino Esposito ◽

...

Keyword(s):

Coronary Angioplasty ◽

Neointimal Hyperplasia ◽

Rabbit Model ◽

Arterial Injury ◽

Platelet Glycoprotein ◽

Beneficial Effects ◽

Von Willebrand ◽

Willebrand Factor ◽

Factor Interaction ◽

Adhesion Complex

SummaryRestenosis following coronary angioplasty is thought to result from migration and proliferation of medial smooth muscle cells. However, the factors that initiate this proliferation are still unknown. In a rabbit model of carotid artery injury, we tested the hypothesis that activated platelets and leucocytes might contribute to the development of neointimal hyperplasia. Following arterial injury, rabbits received either no treatment, R15.7, a monoclonal antibody against the leucocyte CD ll/CD 18 adhesion complex, aurintricarboxylic acid (ATA), a sub stance that inhibits platelet glycoprotein Ib-von Willebrand factor interaction, or the combination of R15.7 and ATA. After 21 days, the extent of neointimal hyperplasia was evaluated by planimetry on histological arterial sections. The area of neointima averaged 0.51 ±0.07 mm2 in control animals and it was significantly reduced by administrationof either R15.7 or ATA alone to 0.12 ± 0.05 and 0.20 ±0.01 mm2, respectively (p <0.05 vs controls for both groups). The animals that received the combination of R15.7 and ATA showed a further reduction in neointimal hyperplasia, as compared to animals that received ATA alone (p <0.05 vs ATA alone). These data indicate that platelets and leucocytes play animportant role in the pathophysi ology of neointimal hyperplasia in this experimental model. Interven tions that reduce platelet and leucocyte adhesion to vessel wall might have beneficial effects in reducing restenosis following coronary angioplasty.

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Acyl-Enzymes as Thrombolytic Agents in a Rabbit Model of Venous Thrombosis

Thrombosis and Haemostasis ◽

10.1055/s-0038-1657183 ◽

1982 ◽

Vol 47 (03) ◽

pp. 269-274 ◽

Cited By ~ 32

Author(s):

R A G Smith ◽

R J Dupe ◽

P D English ◽

J Green

Keyword(s):

Venous Thrombosis ◽

Active Site ◽

Fibrinolytic Activity ◽

Rabbit Model ◽

Fibrinolytic Agent ◽

Essential Nature ◽

Thrombolytic Agents

SummaryA derivative of human lys-plasmin in which the active site has been reversibly acylated (BRL 26920; p-anisoyl human lys-plasmin) has been examined as a fibrinolytic agent in a previously described rabbit model of venous thrombosis and shown to be significantly more active and less fibrinogenolytic than free plasmin. A p-anisoylated derivative of a streptokinase (SK)-activated plasmin preparation was significantly less fibrinogenolytic in vivo than the non-acylated enzyme. Acylation increased the fibrinolytic activity of preparations of SK-plasmin activator complexes. BRL 26921, the active site anisoylated derivative of the primary 2-chain SK-plasminogen complex was the most potent fibrinolytic agent studied. SK-Val442-plasminogen complexes, free or acylated, were biologically inactive in this model and confirm the essential nature of fibrin binding processes for effective thrombolysis in vivo.

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