Fibrosis In Rabbits Research Articles

Hepatic fibrosis in rabbits infected with Japanese and Philippine strains of Schistosoma japonicum.

Symmers' clay pipestem fibrosis of the liver was produced by Schistosoma japonicum infection in the rabbit. Gross and microscopic portal fibrosis and portal vascular lesions resembled those in hepatosplenic schistosomiasis in man. Portal obstruction caused dilation of portal-systemic collateral veins but only minimal portal hypertension. The rapidity of development and prevalence of Symmers' fibrosis were related to the intensity of the schistosome infection. A mixed macronudular and micronodular cirrhosis of the liver was also present in most animals with Symmers' fibrosis, and other differences from the disease in man were present as well. Hepatic fibrosis regressed after the 30th week of infection, as judged from gross and microscopic observations and from measurement of hepatic collagen. The prevalence of Symmers' fibrosis and cirrhosis also decreased after the 30th week in the less heavily infected rabbits. The S. japonicum-infected rabbit is an imperfect model of human Symmers' fibrosis, but the rabbit is the only experimental model available other than the schistosome infected chimpanzee. The rapid production of severe fibrosis without the use of hepatotoxic agents, and the reversibility of the lesions, make this model of general interest for the study of hepatic fibrosis.

Paraquat lung injury in rabbits.

An aerosol model for the study of paraquat (PQ) toxicity was developed using a 134 litre chamber and an ultrasonic nebuliser. Three groups of New Zealand white rabbits weighing 2-3 kg were studied. Group I (n = 6) was exposed to 10 g PQ/100 ml double-distilled water (DDW), Group II (n = 24) was exposed to 200 mg PQ/100 Ml DDW and a control group (n = 6) was exposed to 100 ml DDW. In a second experiment ten animals (Group III) were exposed to 10 mg PQ/100 ML DDW over a three-month period together with a control group (n = 5). Group I animals died with extensive haemorrhagic pneumonitis 38 hours after the last challenge. Most animals in Group II surviving more than three exposures had a significant reduction (P less than 0.001) in arterial oxygen tension (PaO2) and an increase (P less than 0.001) in the alveolar-arterial O2 gradient. Specific compliance decreased (P less than 0.005) and functional residual capacity and breathing frequency increased (P less than 0.05). Tissue PQ values showed even pulmonary distribution, with evidence of PQ accumulation after repeated inhalation. The lungs showed focal interstitial fibrosis, interstitial thickening, proliferation of macrophages in the alveoli, epithelioid changes in the interstitium, Type II cell hyperplasia, and foci of acute inflammation with consolidation. Controls and Group III animals were normal. This indicates that repeated inhalation of paraquat aerosol induces dose-related interstitial pneumonitis and fibrosis in rabbits.

Schistosoma japonicum: Semiquantitative assessment of circulating immune complexes, serum Clq and C3, and their relationship to renal pathology and hepatic fibrosis in rabbits

Ten New Zealand white rabbits were infected either once or four times with variable numbers of Schistosoma japonicum cercariae. Four animals served as the uninfected controls. All rabbits were bled at semimonthly intervals. Serum samples were examined for circulating immune complexes using an [ 125I]Clq assay, or for Clq and C3 levels by single radial immunodiffusion. Control and experimental animals were necropsied at 32–39 weeks postinfection, and the kidneys and livers were removed. Some kidney specimens were quick-frozen in isopentane-liquid nitrogen, cut with a cryostat, and examined by direct or indirect immunofluorescent techniques for immunoglobulin, complement (C3), or parasite antigen glomerular localization. Other kidney specimens were fixed in formalin, sectioned, stained with H&E or PAS, and examined for evidence of histopathology. Liver specimens were treated in a similar manner. Diffuse renal lesions appeared in only 2 of 10 rabbits in the present study. However, each of these two animals had prominent and persistent levels of circulating [ 125I]Clq material (immune complex), and the animal with the highest concentration of immune complex had the most severe nephropathologic changes. C3 levels were consistently depressed in the animal with severe renal pathology but were elevated in all other animals at some point in the infection. Circulating immune complex and serum C3 and Clq values moved in concert for most of the infected rabbits with the principal exception being the animals with diffuse renal lesions. It is of considerable interest and potential etiological significance that the four rabbits with the highest levels of circulating immune complex had the most extensive hepatic fibrosis.

Insulin release in cystic fibrosis.

Early insulin response to rapid intravenous injection of glucose was studied in 7 cases of cystic fibrosis aged 8 months to 9 1/2 years. Plasma insulin was measured with a radioimmunological method. Blood glucose values were determined and the glucose disappearance rate (kG) calculated. In all children except the youngest one the early insulin response values were low compared with normal children. The kG-values were normal and correlated neither to the duration of clinical symptoms, nor to the patients' actual clinical condition measured by means of the Shwachman score. The explanation of the decreased insulin response is probably the progressive fibrosis of the pancreas. This may also explain the reported increased incidence of diabetes mellitus in cystic fibrosis. Comparison is made with the condition in pancreatic fibrosis in rabbits, produced through duct ligation.

Experimental Pneumoconiosis

This book reviews experimental pneumoconiosis from the 1920's to the early 1960's. An introductory chapter recounts the ancients' awareness of the dangers of dust to miners. A description of the minerals causing pneumoconiosis and of the related industries is valuable. Experimental methods for studying silicosis are described minutely. Variations in species reactions are noted; perfect silicotic nodules are found in the white rat, diffuse fibrosis in rabbits. Species vary in effectiveness of nasal filtration of dust and metabolic rate and phagocytic activity in the experimental animal should match that of man. The pathology of silicosis is superficially discussed but there is an excellent account of experimental silicosis. Theories of pathogenesis of various pneumoconioses are reviewed, as are the many suggested treatments. Insufficient emphasis is made of the nonspecificity of the asbestos body. The few cases where pure carbon could have been fibrogenic are reviewed. Many would dispute the dogma that