Fibrosis In Rabbits Research Articles

Study on effect of cordyceps sinensis on early-stage silicotic pulmonary fibrosis in rabbits

To establish a rabbit model of silicotic pulmonary fibrosis and to investigate the effect of cordyceps sinensis in this model. Thirty healthy male white rabbits were randomly divided into control group, silicosis model group, and intervention group. The rabbits in silicosis model group and intervention group received endotracheal perfusion of silicon dioxide suspension (120 mg/kg), and the control group was treated with the same volume of saline. All the rabbits were sacrificed 30 days later. The lung coefficient was calculated by comparing the lung weight and body weight; the right lung tissue was stained with hematoxylin-eosin (HE). The content of hydroxyproline in lung tissue was measured by alkaline hydrolysis. The mRNA levels of transforming growth factor beta 1 (TGF-β₁) and mothers against decapentaplegic homolog 7 (Smad7) in rabbit lung sections were determined by real-time PCR. No abnormalities were observed by HE staining in the lung tissues of control group, while fibrosis and silicotic nodules were discovered in the silicosis model group and intervention group. The lung coefficient and the content of hydroxyproline in lung tissue were significantly higher in the silicosis model group than in the control group and intervention group (P < 0.05 or P < 0.01). Compared with the control group, the silicosis model group and intervention group had significantly increased TGF-β₁ mRNA levels but significantly reduced Smad7 mRNA levels (P < 0.02). Compared with the silicosis model group, the intervention group had a significantly reduced TGF-β₁ mRNA level but a significantly increased Smad7 mRNA level (P < 0.05). Cordyceps sinensis is able to reduce the expression of TGF-β₁ mRNA and increase the expression of Smad7 mRNA in lung tissues of rabbits with silicotic pulmonary fibrosis, and thus postpone the progression of fibrosis.

Evaluation of fatty liver fibrosis in rabbits using real-time shear wave elastography.

The aim of the present study was to detect the elastic modulus (stiffness) of the livers of rabbits with non-alcoholic and alcoholic fatty liver disease using real-time shear wave elastography (SWE), and to investigate the fibrosis development process in the formation of fatty liver. The stiffness of the fatty livers in rabbit models prepared via feeding with alcohol or a high-fat diet were measured using a real-time SWE ultrasound system and a 4–15-MHz linear array probe, and the liver stiffness was compared with the pathological staging of the disease. The stiffness of the liver was positively correlated with the degree of pathological change in fatty liver disease (P<0.01). The stiffness of the liver in the alcoholic fatty liver group was higher compared with that in the non-alcoholic fatty liver and control groups, and the stiffness in the non-alcoholic fatty liver group was higher than that in the control group (P<0.01). Real-time SWE objectively identified the trend in the changing stiffness of the liver and noninvasively detected the development of fibrosis in the progression of non-alcoholic and alcoholic fatty liver disease.

Effect of Chinese herbal compound on liver fibrosis in rabbits with schistosomiasis by B-ultrasound

ObjectiveTo explore the value of B-ultrasound on the evaluation of the effects of traditional Chinese medicine compound of Radix astragali, Salvia miltiorrhiza and Angelica sinensis, and TCM + praziquantel on liver fibrosis in rabbits with schistosomiasis. MethodsThe hepatic fibrosis model in rabbits with schistosomiasis was established. The experimental animals (24 rabbits) were randomly divided into four groups (group A, B, C and D, n=6). Group A (control group) was only treated by praziquantel; Group B was treated by mixture of Radix astragali and Salvia miltiorrhiza + praziquantel; Group C was treated by mixture of Radix astragali and Angelica sinensis + praziquantel; Group D was treated by mixture of Radix astragali, Salvia miltiorrhiza and Angelica sinensis + praziquantel. Then B-ultrasonogram was used to evaluate the effects. ResultsEach group showed certain curative effect on liver fibrosis in rabbits with schistosomiasis. The efficacy of group B, C and D was better than group A, and that of group D was the best. The differences in long diameter, thickness diameter, transverse diameter and portal vein inner diameter of liver before and after treatment were statistically significant (P<0.05). The liver function indexes and liver fibrosis indexes were significantly improved after treatment (P<0.05). ConclusionsThe mixture of Radix astragali, Salvia miltiorrhiza and Angelica sinensis combined with Western medicine treatment can obviously improve the efficacy on liver fibrosis of schistosomiasis.

Quantitative Measurement of Bleomycin-induced Lung Fibrosis in Rabbits Using Sequential in vivo Regional Analysis and High-Resolution Computed Tomography:: Correlation with Pathologic Findings

To examine the feasibility of quantitative high-resolution computed tomography (HRCT) findings to monitor the stage of bleomycin-induced pulmonary fibrosis in rabbits by correlating HRCT and pathologic scores and analyzing sequential changes on HRCT images using regional volume histograms. Lung fibrosis was induced by injecting bleomycin intratracheally into 23 Japanese white rabbits. Rabbits were randomly separated into seven groups depending on follow-up period (12-hour, 24-hour, 3-day, 7-day, 14-day, 21-day, and 28-day). Four-row HRCT examinations were performed at any of the seven time points in each follow-up period and just after bleomycin administration in addition to pre-bleomycin administration as the baseline scan. Scores of consolidation, homogenous ground-glass opacity (GGO), inhomogeneous GGO, reticulolinear shadow, and honey-comb formation were recorded as ratio of affected area to total cross-section in four transaxial planes. Inflammatory and fibrous changes were scored histopathologically. Correlations between HRCT and pathologic findings were assessed. Sequential changes on HRCT images in areas with pathologically confirmed fibrosis were assessed on volume histograms of cubic regions of interest (ROI) using quantitative parameters. Consolidation and inhomogeneous GGO exhibited fair correlations with inflammation scores (r = 0.273, P = .009, and r = 0.393, P < .001); reticulolinear shadow and inhomogeneous GGO had a fair and good correlation, respectively, with fibrous scores (r = 0.327, P = .001, and r = 0.579, P < .001). Inhomogeneous GGO was hardly detected on regional images at 21 and 28 days after bleomycin administration. As to mean computed tomography attenuation, skewness, and kurtosis, inhomogeneous GGO differed from reticulolinear shadow and consolidation. Using appropriate ROI settings, quantitative assessment of inhomogeneous GGO with regional volume histograms enables us to monitor the progression of lung fibrosis by sequential observations.

Chemical composition and inhibitory effect on hepatic fibrosis of Danggui Buxue Decoction

The present study was carried out to investigate chemical components and therapeutic effects on hepatic fibrosis of Danggui Buxue Decoction (DBD) in rabbits. The chemical components of DBD were analyzed by LC-DAD-MS. Schistosomiasis hepatic fibrosis was employed as models of hepatic fibrosis. The rabbits were divided into treatment and control groups. DBD was orally administered at a dose of 50 g/kg rabbit's weight in treatment group. We evaluated the therapeutic effects of DBD on hepatic fibrosis in rabbits using B-ultrasound images, histopathologic examination, and hyaluronic acid content in serum. The results indicated that DBD had good therapeutic effects for hepatic fibrosis.

Biochemical studies on experimental pulmonary fibrosis in rabbits treated with N-methyl-N-nitrosourethane (author's transl)

Biochemical studies on experimental pulmonary fibrosis in rabbits treated with N-methyl-N-nitrosourethane (author's transl)

Taurine

Taurine, a sulfur-containing amino acid (Figure), has been termed a functional nutrient that could be used to protect against, among others, diabetes mellitus and atherosclerosis.1 Indeed, an increasing body of literature supports the use of taurine supplements. Because taurine has very diverse functions, notably, intracellular osmoregulation and bile acid formation, and is abundantly present in several organs, multiple pathways could be involved. Some of these are discussed in this editorial. Figure. A simplified biosynthesis pathway from methionine to taurine. Methionine is converted to homocysteine in 3 steps. Homocysteine is used as a substrate to form cysteine in 2 steps but can also be converted back to methionine by 2 different mechanisms. Cysteine, precursor for the important antioxidant glutathione and the gaseous transmitter/signaling molecule H2S, can be further converted to cysteine sulfinate. Cysteine sulfinate is converted to taurine in 2 steps via 2 different pathways. Taurine can decrease methionine by decreasing uptake. Whether taurine decreases homocysteine directly or via a reduction of methionine is unclear. Of the 20 canonical amino acids, 18 are composed of carbon, hydrogen, nitrogen, and oxygen only. The remaining 2, methionine and cysteine, also contain 1 atom of sulfur. Because sulfur is not as electronegative as oxygen, the sulfur-containing amino acids play a key role in protein structure and synthesis.2 Methionine and cysteine also play important roles in cell metabolism. For instance, methionine serves as a substrate for S-adenosylmethionine, which is vital for methylation of nucleic acids, proteins, lipids, etc. In proteins, cysteine easily forms double bonds with other cysteine residues, thus determining tertiary structure and binding sites. Moreover, cysteine is substrate for glutathione, an important intracellular antioxidant, and H2S, a gas that can induce endothelial-dependent relaxation.3 Cysteine is considered a nonessential amino acid because it is synthesized …

Successive observation of laminin and hyaluronic acid on the formation of non-alcoholic fatty liver fibrosis in rabbits

Successive observation of laminin and hyaluronic acid on the formation of non-alcoholic fatty liver fibrosis in rabbits

Evaluation of DuraGen in preventing peridural fibrosis in rabbits

Peridural fibrosis is the scar tissue formed over the dura mater after a laminectomy. It has been implicated as a cause of persistence of pain after spinal surgery and associated with increased risk of complications during revision surgery. The application of a mechanical barrier to cover the peridural space to block the migration of inflammatory cells from superficial layers to the epidural space can potentially prevent or decrease scar formation. The authors evaluated the use of DuraGen for this purpose. Seventeen New Zealand White rabbits underwent bilateral L-4 and L-7 laminectomies. Each space was randomly assigned to either receive DuraGen, fat graft, or no (sham) treatment. At a mean 18 +/- 4 weeks after surgery, the animals underwent magnetic resonance (MR) imaging with and without Gd enhancement, and the area of the scar tissue overlying the middle of the laminectomy was measured. The rabbits were killed and the spinal cords with an intact dural covering were harvested. The midsection of each treated level was evaluated histologically and the scar area was measured. In rabbits in which a fat graft was placed, MR imaging of the epidural space demonstrated a significant (p < 0.05) increase in the mean area (0.9713 mm2) of scar tissue compared with those in which DuraGen was used (0.687 mm2) or those receiving sham treatment (0.6661 mm2). The same correlation was observed when the histological sections were measured at the middle of the laminectomy site where the mean areas of both DuraGen (1008 mm2) and control (2249 mm2) groups were significantly lower than that in the fat graft group (6007 mm2) (p < 0.01 and 0.05, respectively). No significant differences between the DuraGen and control groups were observed. The authors demonstrated that peridural scarring formed in all groups. The mean area of scar deposition was significantly higher in the fat graft group than in the DuraGen or control group both on MR imaging and histological analysis. DuraGen was more effective than a fat graft in preventing epidural fibrosis but not significantly different from that occurring in control animals.

The combination of high dietary methionine plus cholesterol induces myocardial fibrosis in rabbits

Limited evidence suggests that myocardial fibrosis might be associated with dietary cardiovascular risk factors. Objective To investigate the effects of high dietary cholesterol, methionine (the precursor to homocysteine), and the combination of the two diets on myocardial fibrosis. Methods Rabbits were randomly allocated into four dietary groups for 12 weeks: control (Con), 1% methionine (Meth), 0.5% cholesterol (Chol) or 1% methionine plus 0.5% cholesterol (MethChol). Results Myocardial fibrosis was not significantly increased in Chol or Meth. However, interstitial fibrosis increased by 85% ( p = 0.03) and perivascular fibrosis 28-fold ( p < 0.01) in the MethChol group compared to Con. Conclusions These results suggest that high levels of dietary cholesterol or methionine alone do not significantly increase myocardial collagen content. However, the combination of the two diets does cause myocardial fibrosis. Therefore, excessive cholesterol and methionine intake may be an important pathogenic factor in the development of myocardial fibrosis.

Prevention of Postlaminectomy Epidural Fibrosis Using Bioelastic Materials

The use of elastic protein-based polymers for the prevention of epidural fibrosis following lumbar spine laminectomy was investigated in a rabbit model. To determine the safety and efficacy of two bioelastic polymers in matrix and gel forms as interpositional materials in preventing postlaminectomy epidural fibrosis. Postlaminectomy epidural fibrosis complicates revision spine surgery and is implicated in cases of "failed back syndrome." Materials employed as mechanical barriers to limit tethering of neural elements by the fibrosis tissue have met with little success. A recent family of protein-based polymers, previously reported to prevent postoperative scarring and adhesions, may hold promise in treating this condition. Sixteen female New Zealand White rabbits underwent laminectomy at L4 and L6. Two polymer compositions, each in membrane and gel forms, were implanted at a randomly assigned level in four rabbits each, with the remaining level serving as an internal control. The animals were killed at 8 weeks, and qualitative and quantitative histology and gross pathologic examination were performed for both the control and the experimental sites to assess the polymers' efficacy in preventing dorsal epidural fibrosis. The use of the polymers caused no adverse effects. Compared to the control sites, both polymers in either gel or membrane form significantly reduced the formation of epidural fibrosis and its area of contact with the dura postlaminectomy. However, no significant difference in efficacy was detected between either the polymers or their respective forms in preventing epidural fibrosis. The selected compositions of biosynthetic, bioelastic polymers were safe and effective in the limiting the direct contact and consequent tethering of the underlying neural elements by the postlaminectomy epidural fibrosis in rabbits.

Topical mitomycin C-induced inhibition of postlaminectomy peridural fibrosis in rabbits.

The authors conducted a study to determine the effectiveness of mitomycin C in preventing postlaminectomy peridural fibrosis in rabbits. Laminectomies were performed at L-4 in 12 rabbits. Color-coded cotton pads soaked either with 0.02% mitomycin C or saline were applied in a blinded fashion to the operative sites, with saline-treated laminectomy sites serving as controls. The rabbits were killed 30 days after surgery. The extent of peridural fibrosis was evaluated by histological analysis. The mitomycin C-treated sites showed significantly decreased peridural fibrosis. Peridural fibrosis can be a devastating condition that develops after laminectomy. Topical application of mitomycin C may be a successful method of preventing postlaminectomy peridural fibrosis.

Immunohistochemical and gelatin zymography studies for matrix metalloproteinases in bleomycin-induced pulmonary fibrosis.

The role of various matrix metalloproteinases (MMP) and tissue inhibitor of metalloproteinases-2 (TIMP-2), and the gelatinolytic activities of MMP involved in the process of bleomycin-induced pulmonary fibrosis in rabbits were investigated. Male Japanese white rabbits were intubated with tracheal tubes under anesthesia, and bleomycin hydrochloride in sterile saline or only sterile saline was administered through the tracheal tubes. The animals were killed 1, 3, 7, 14 and 28 days after the administration of bleomycin (n = 3) or saline (n = 2). Light microscopic immunohistochemistry for MMP-1 (interstitial collagenase), MMP-2 (gelatinase A), MMP-9 (gelatinase B) and TIMP-2 was performed. The gelatinolytic activities of lung tissue homogenates were studied by gelatin zymography. In the early stages, the gelatinolytic activity of MMP-9 was predominant. MMP-9 localized in the infiltrating neutrophils, macrophages, bronchial and bronchiolar epithelial cells. The alveolar epithelial basement membrane was frequently disrupted in the early stages, where MMP-9 possibly contributed to the disruption. In the late stages, the gelatinolytic activities of the latent and active forms of MMP-2 were predominant, and MMP-2 localized in the regenerated alveolar epithelial cells in addition to the bronchial epithelial cells. MMP-2, especially its active form, possibly plays a role in alveolar epithelial cell regeneration. The localization of MMP-1 was similar to that of MMP-9. TIMP-2 localized in the epithelial cells and in some fibroblasts in fibrotic lesions. TIMP-2 possibly plays a role in extracellular matrix deposition in balance with MMP.

Hepatic sinusoidal fibrosis induced by cholesterol and stilbestrol in the rabbit: 1. Morphology and inhibition of fibrogenesis by dipyridamole

This study documents the hepatic morphology and the ultrastructure of a model of hepatic fibrosis in rabbits. Rabbits were given a cholesterol-supplemented diet (1%), a stilbestrol diet (10 mg subcutaneously twice a week), or both treatments simultaneously for 7 weeks. Rabbits given the combined treatment developed sinusoidal and portal fibrosis with only a mild disturbance of acinar vascular relationships. Ultrastructurally, there was marked widening of the spaces of Disse by collagen fibers, basement membrane material adjacent to endothelial cells and hepatocytes, blunted hepatocellular microvilli, activated stellate cells, lipid droplets in endothelial cells and hepatocytes, and degranulated platelets in sinusoids. The hepatic hydroxyproline content was markedly increased (12.0 +/- 5.2 vs. 4.8 +/- 1.5 mmol/g of liver dry weight; P < .001). Plasma bile acids were markedly increased (222 +/- 180 vs. 12 +/- 5 in controls; P < .001). Dipyridamole (25 mg every 12 hours) that was given in addition to cholesterol and stilbestrol decreased the hepatic collagen content (-49% and -48%, in two experiments; P < .05 in both) and splenomegaly. This model provides a reliable method for the production of extensive sinusoidal fibrosis with capillarization of sinusoids. Hepatocellular degeneration is only mild to moderate, and fibrosis occurs slowly without the sudden pathological changes that occur with other models of hepatic fibrosis, such as with the administration of CCl4 or galactosamine. The mechanism of injury may involve the accumulation of bile salts or the generation of free radicals from cholesterol oxidation products. The possibility that the sinusoidal release of platelet-derived factors may have a role in the activation of stellate cells (lipocytes) is supported by the suppression of fibrogenesis by dipyridamole.

Centrolobular liver fibrosis in the hypercholesterolemic rabbit.

During a study on the development of atheromatous lesions in rabbits fed a diet with a low or high cholesterol supplement, we found a moderate to pronounced centrolobular liver fibrosis. This fibrosis developed in three stages. Early after supplementation of cholesterol, we observed increased immunoreactivity of collagen types I, III, and IV, and fibronectin, around central veins and in adjacent sinusoids. In the second stage, we observed further increase of collagen and fibronectin immunoreactivity, together with the appearance of alpha-smooth muscle actin (alpha-SM actin)-positive cells and anti-rabbit macrophage monoclonal antibody (RAM 11)-positive cells. In the third stage, we observed large numbers of alpha-SM actin-positive cells, together with heavy deposition of connective tissue proteins in pericentral sinusoids, in addition to focal atrophy of parenchymal cells. By transmission electron microscopy (TEM), fat-storing cells in the pericentral regions were shown to be enlarged, to lose their lipid-droplets, and to acquire dilated rough endoplasmic reticulum corresponding to an activated phenotype. Parenchymal cells were either normal or contained numerous small lipid-droplets. They sometimes were smaller and distorted. Northern hybridization performed on total RNA of whole liver showed an increased level of collagen alpha1(I), alpha1(III), and alpha1(IV) messenger RNA (mRNA) after 24 weeks of low dietary cholesterol supplementation. These data show enhanced expression of extracellular matrix proteins. We conclude that cholesterol overload induces pericentral liver fibrosis in rabbits. The diet clearly activates fat-storing cells to become fibrogenic effector cells. At present, we have no explanation why hypercholesterolemia induces phenotypic transition of fat-storing cells.

Hepatic sinusoidal fibrosis induced by cholesterol and stilbestrol in the rabbit: 1. Morphology and inhibition of fibrogenesis by dipyridamole

This study documents the hepatic morphology and the ultrastructure of a model of hepatic fibrosis in rabbits. Rabbits were given a cholesterol- supplemented diet (1%), a stilbestrol diet (10 mg subcutaneously twice a week), or both treatments simultaneously for 7 weeks. Rabbits given the combined treatment developed sinusoidal and portal fibrosis with only a mild disturbance of acinar vascular relationships. Ultrastructurally, there was marked widening of the spaces of Disse by collagen fibers, basement membrane material adjacent to endothelial cells and hepatocytes, blunted hepatocellular microvilli, activated stellate cells, lipid droplets in endothelial cells and hepatocytes, and degranulated platelets in sinusoids. The hepatic hydroxyproline content was markedly increased (12.0 +/- 5.2 vs. 4.8 +/- 1.5 mmol/g of liver dry weight; P < .001). Plasma bile acids were markedly increased (222 +/- 180 vs. 12 +/- 5 in controls; P < .001). Dipyridamole (25 mg every 12 hours) that was given in addition to cholesterol and stilbestrol decreased the hepatic collagen content (-49% and -48%, in two experiments; P < .05 in both) and splenomegaly. This model provides a reliable method for the production of extensive sinusoidal fibrosis with capillarization of sinusoids. Hepatocellular degeneration is only mild to moderate, and fibrosis occurs slowly without the sudden pathological changes that occur with other models of hepatic fibrosis, such as with the administration of CCl4 or galactosamine. The mechanism of injury may involve the accumulation of bile salts or the generation of free radicals from cholesterol oxidation products. The possibility that the sinusoidal release of platelet-derived factors may have a role in the activation of stellate cells (lipocytes) is supported by the suppression of fibrogenesis by dipyridamole. (Hepatology 1996 Oct;24(4):855-64)

Centrolobular liver fibrosis in the hypercholesterolemic rabbit

During a study on the development of atheromatous lesions in rabbits fed a diet with a low or high cholesterol supplement, we found a moderate to pronounced centrolobular liver fibrosis. This fibrosis developed in three stages. Early after supplementation of cholesterol, we observed increased immunoreactivity of collagen types I, III, and IV, and fibronectin, around central veins and in adjacent sinusoids. In the second stage, we observed further increase of collagen and fibronectin immunoreactivity, together with the appearance of alpha-smooth muscle actin (alpha-SM actin)-positive cells and anti-rabbit macrophage monoclonal antibody (RAM 11)-positive cells. In the third stage, we observed large numbers of alpha-SM actin-positive cells, together with heavy deposition of connective tissue proteins in pericentral sinusoids, in addition to focal atrophy of parenchymal cells. By transmission electron microscopy (TEM), fat-storing cells in the pericentral regions were shown to be enlarged, to lose their lipid-droplets, and to acquire dilated rough endoplasmic reticulum corresponding to an activated phenotype. Parenchymal cells were either normal or contained numerous small lipid-droplets. They sometimes were smaller and distorted. Northern hybridization performed on total RNA of whole liver showed an increased level of collagen alpha1(I), alpha1(III), and alpha1(IV) messenger RNA (mRNA) after 24 weeks of low dietary cholesterol supplementation. These data show enhanced expression of extracellular matrix proteins. We conclude that cholesterol overload induces pericentral liver fibrosis in rabbits. The diet clearly activates fat-storing cells to become fibrogenic effector cells. At present, we have no explanation why hypercholesterolemia induces phenotypic transition of fat-storing cells. (Hepatology 1996 Oct;24(4):939-46)

Reversal of advanced liver fibrosis in rabbits with Schistosomiasis japonica.

Advanced liver fibrosis is generally considered to be irreversible. We studied the reversibility of marked liver fibrosis in rabbits infected with Schistosoma japonicum. We determined liver collagen content, collagen biosynthesis, and collagenase activity using serial biopsy specimens obtained 20, 40, and 60 weeks after infection. Reversibility of this process was investigated in rabbits cured of infection at 21 weeks; control rabbits not cured of infection were also studied. At 20 weeks, liver collagen content was 16-fold greater than normal, with accumulation of collagen types I, III, and V. Synthesis of collagen within fibrotic liver slices was 10-fold greater than normal. Liver collagenolytic activity for a type I substrate was 19-fold greater than normal. After parasitologic cure, a striking morphologic reversal of fibrosis occurred during the subsequent 40 weeks, with the return of liver collagen content to three-fold greater than normal and a 75% decrease in synthetic rates compared with those at 20 weeks (P < 0.01). Collagenolytic activity remained elevated to the same degree noted at 20 weeks. A similar but lesser resolution of fibrosis also occurred in untreated control rabbits, coincident with a spontaneous decrease in new egg deposition known to occur in this model system. We conclude that advanced liver fibrosis in S. japonicum-infected rabbits is slowly reversible after cure or senescence of the infection. A possible mechanism for this reversal is persistently increased collagenolysis as collagen synthesis diminishes.

The reduction of postlaminectomy peridural fibrosis in rabbits by a carbohydrate polymer.

Spinal peridural fibrosis following total laminectomy in New Zealand White rabbits was significantly decreased by the intraoperative application of GT1587, a semi-synthetic carbohydrate polymer. The application of a similar polymer, GT1043, or phosphate-buffered saline (PBS) was not as effective. Laminectomies were performed at L-2 and L-4 in 25 rabbits. Absorbable gelatin sponge soaked with GT1043, GT1587, or PBS was applied in a blinded fashion to the operative sites, with untreated (sham) laminectomy sites serving as controls. Animals were sacrificed after 2 or 4 weeks. The extent of peridural fibrosis was evaluated by gross microdissection and histological analysis. Dense scar formation and dural adhesions were evident at both time intervals in the sham- and PBS-treated laminectomy sites. The sites treated with GT1587 showed significantly decreased peridural scar formation and dural adhesions, whereas GT1043 treatment caused modest reduction of scar formation at only the 2-week examination. The healing of skin and lumbosacral fascia was not affected by treatment of the laminectomy site with GT1587. These results suggest that GT1587 may prove beneficial in preventing postlaminectomy dural adhesions and peridural fibrosis in humans.

Animal model of grain worker's lung.

We examined the light microscopic changes in the lungs of rabbits exposed to grain dust for variable periods of time, to determine whether an animal model of grain worker's lung could be developed. Experimental animals were exposed to grain dust at a concentration of 20 mg/m3 for 7 hr/day, 5 days/week, for up to 6 months. The lungs of these rabbits demonstrated a granulomatous interstitial pneumonitis associated with exudation of mononuclear cells into the alveoli and conducting airways. These changes appeared within 5 days of the onset of exposure and reached a peak at 3 weeks but were sustained through the longest exposure interval. No abnormalities were observed in the lungs of control rabbits. These results show three points of consistency with those obtained in epidemiologic studies of grain elevator workers. First, the rapid appearance of the experimental changes suggests that the mechanism of tissue injury may not be immunologic. Second, the occurrence of the histopathologic alterations in the interstitium, alveoli, and airways corresponds with the combined restrictive and obstructive ventilatory defect described in the human epidemiologic studies. Third, the absence of lung fibrosis in rabbits exposed to dust for 6 months suggests that the pneumonitis is reversible. Thus this experimental model shows promise of helping to clarify the nature and mechanism of the adverse pulmonary effects of grain dust.