Interstitial lung disease with chronic fibrosis is a frequent cause of reduced performance in horses. The aim of this study was to establish a model of acute alveolar damage and interstitial lung disease in horses that could be used to monitor the histopathological lesions and changes in expression levels of genes relevant to pulmonary fibrosis. Six adult horses were given a single intravenous injection (6 mg per kg body weight) of perilla mint ketone (PMK). Transthoracic lung biopsy samples (1 x 0.2 x 0.2 cm) were collected before and after (days 1, 4, 8, 11, 15, 18, 22, 25 and 29) the administration of PMK. Light and electron microscopy revealed severe acute alveolar damage (days 1 to 4), proliferation of type II pneumocytes (days 4 to 11) and finally complete healing at about day 18. However, unexpectedly severe clinical signs necessitated euthanasia in two horses on days 9 and 11. The expression levels of the collagen genes COL1AI and COL3AI as well as transforming growth factor (TGF)-beta were examined in the biopsy samples by reverse transcription-real time quantitative polymerase chain reaction. COL1AI and COL3AI gene expressions were upregulated (3- and 17-fold, respectively) between days 1 and 29 in all six horses, whereas TGF-beta was upregulated in two horses (2- and 4-fold, respectively), between days 4 and 18. Although the gene expression analyses indicated a strong activation of the pro-fibrotic pathway, no interstitial fibrosis was seen in any horse. A complete necropsy performed on day 60 revealed complete recovery of the lungs of the four surviving horses, with no evidence of fibrosis. Unidentified compensatory mechanisms may have prevented pulmonary fibrosis, despite strong upregulation of pro-fibrotic genes.

Animals↗

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Percutaneous lung biopsy in the horse: comparison of two instruments and repeated biopsy in horses with induced acute interstitial pneumopathy.

The aim of the study reported here was to compare complications of lung biopsy in horses and the quality of the lung specimens after biopsy using the manual Tru-Cut biopsy needle (TC) and an automated biopsy needle (ABN). For experiment 1, lung biopsy was performed in 50 horses with one instrument on one side of the thorax, and then with the other instrument on the other side. Postmortem examination was performed in 20 of the 50 horses. Coughing was detected in 10 of 50 horses and epistaxis was observed in 6 of the 50 horses. Endoscopy revealed bleeding into the airways in 16 of 49 horses and in 5 of 49 horses after biopsy with the TC or the ABN, respectively. Use of the ABN induced a significantly smaller amount of bleeding. Pneumothorax was detected by radiography in 1 of 50 horses. Hematoma diameter determined in 7 of 20 horses at postmortem examination, was significantly larger after biopsy with the TC than with the ABN. The quality of the lung specimen was good. In experiment 2, complications after repeated and multiple lung biopsies in 6 horses were evaluated. Moderate epistaxis was observed on 13 of 104 occasions. Bleeding into the airways was detected at endoscopy on 41 of 104 occasions, and pneumothorax was detected during 4 of 104 occasions. Complications such as hematoma at the biopsy site and bleeding into the airways were greater after biopsy with the TC than after use of the ABN. Lung biopsy specimens obtained with the ABN were fairly safe for the animal.

Animals↗

PubMedDate not supplied

[Enzyme, enzyme-histochemical and immunohistological studies in chronic erysipelas polyarthritis of swine].

The chronic Erysipelas-polyarthritis in pigs has been considered an animal model resembling human rheumatoid arthritis. Fifteen specifically pathogenfree (SPF) pigs 45 days old were experimentally infectec with strain T 28 of Erysipelothrix rhusiopathiae-bacteria. During the subsequent 32 weeks several enzymatic, immunohistological and microbiological parameters were monitored. Compared to 5 age and sex matched healthy controls the infected pigs showed increased activity of plasma acid phosphatase starting 4 weeks after the infection. Acid phosphatase activity was usually enhanced in synovial fluid of chronically ill animals. Histochemically increased activity of acid phosphatase, beta-glucuronidase and beta-acetylglucosaminidase was found in lining cells and fibroblasts of the synovial membrane of chronically diseased joints. Immunohistochemically Erysipelas-antigen was demonstrated in the synovial membrane even of those inflamed joints from which no living bacteria had been isolated. The microbiological and immunohistochemical results correlated positively with the enzymehistochemical data. The release of lysosomal enzymes from cells of the synovial membrane in chronically diseased joints due to the influence of Erysipelas-bacteria and the possible implications of persistent bacteria on the perpetuation of chronic Erysipelas-polyarthritis are discussed.

Animals↗

PubMedDate not supplied

[Immunopathologic aspects of chronic erysipelas polyarthritis in swine].

Chronic erysipelas polyarthritis in pigs is considered to be an animal model closely resembling human rheumatoid arthritis. In an experimental study using SPF pigs infected with Erysipelothrix rhusiopathiae several immunopathological aspects were studied for up to 14 months after infection. After an initial febrile phase a progressive polyarthritis and discospondylitis developed at 2 weeks after infection. Quantitative determination of IgG and IgM revealed a significant increase in these immunoglobulins both in the serum and the synovia from arthritic joints. Arthritic joints containing viable Erysipelothrix bacteria at termination of the experiment have a higher content of IgG and IgM than bacteriologically negative joints. During the entire experiment the rheumatoid factor titer, determined by the Waaler Rose test, remained relatively low with increases and decreases. The Erysipelothrix antibody titers are highly significant. The total complement activity in the serum increases discontinuously and shows fluctuations similar to those of the rheumatoid factor titer. The highest enzyme activities of acid phosphatase and lactate dehydrogenase are demonstrable in the synovial fluid of arthritic joints with positive bacteriological or immunohistological findings. These joints also have the greatest numbers of IgG-producing plasma cells. By means of immunohistological methods Erysipelothrix antigen can be demonstrated in macrophages of the proliferating synovial membrane. Finally, there is a discussion of the pathogenic significance for the perpetuation of chronic polyarthritis of Erysipelothrix persisting in arthritic joints in spite of focal immune reactions.

Acid Phosphatase↗

PubMedDate not supplied

[Immunopathology and pathogenesis of chronic erysipelas polyarthritis of swine].

Several immuno-pathological aspects of polyarthritis following experimental infection with erysipelas in pigs were studied for two years. Aseptic and specifically pathogenfree animals were infected subcutaneously and intravenously-intraarticularly with living erysipeals bacteria (erysipelothrix rhusiopathiae) of serotype B. After an initial febrile phase a progressive polyarthritis and disco-spondylitis developed. Some animals also developed thrombo-endocarditis. Hypergammaglobulinemia and high titers of specific antibodies were observed during the whole experimental period. Antiglobulin factors, however, were not detected in the serum or the synovium. In some animals collagen antibodies were demonstrated in synovial tissue. Bacterial examination of the synovium showed that erysipelas bacteria were present in arthritic joints for months. Living erysipelas bacteria were isolated 24 months after the experimental infection from synovial tissue of two pigs. The polyarthritis was characterised by exudates rich in fibrin, villous proliferation, pannus formation, cartilage erosions, and peri-articular fibrosis. IgG and specific erysipelas antibodies were demonstrated in plasma cells from synovial tissue by immuno-histological methods. The findings emphasize the morphological resemblance of the erysipelas induced chronic polyarthritis in pigs to human rheumatoid arthritis.

Animals↗

PubMedDate not supplied

[Significance of coagulation disorders and inflammatory immune reaction in an infectious model of rheumatoid arthritis. I. Systemic, shock-like coagulopathy and fibrin incorporation as indicators of rheumatoid manifestations in the erysipelas model].

A combined study employing plethysmographical, scintillation counting and coagulation methods indicates that a coagulation crisis in combination with fibrin overproduction may be an indicator of a beginning arthritis of rheumatoid character. Rats which received a single subcutaneous infection with erysipelas bacteria exhibit a shock resembling crisis two days post inoculation as substantiated by the consumption of coagulation factors II, V, VIII, XII and decrease of platelets. This consumption of coagulation factors is characterized by a rapid compensatory increase of platelets, antihaemophilic factor VIII and fibrin, 5 times more in the pig and 3 1/2 times more in the rat than in control animals. In adult rats the overproduction of fibrin is combined with an intense concealed consumption of fibrin in all organs of manifestation. Only in young rats an absolute consumption of fibrin is observed. The incorporation of fibrin into connective tissue is accompanied by fibrin consumption as demonstrated by immunofluorescence, by oedema of the paw, and by mesenchymal proliferation as substantiated by scintillation counting of incorporated 35SO4 and 3H-Proline, as markers for the beginning synthesis of ground substances and collagen. This model supports the importance of an initial vascular phase for the subsequent phase of manifestation in chronic rheumatoid diseases. It is discussed whether the organ specific permeability of the affected organs (joints, heart, arteries and eyes) may be a localizing factor of organ manifestation, parallel to the hormonal mesenchymal reaction.

Animals↗