Dermal collagen degradation and phagocytosis. Occurrence in a horse with hyperextensible fragile skin.

A 2-year-old female horse had large areas of hyperextensible, fragile skin that were interspersed with areas of normal skin. Affected skin tore easily and contained reduced amounts of dermal collagen. Collagen fibers were fragmented and disorganized, and in trichrome-stained sections, many fibers had abnormal red-stained centers. Electron microscopy showed that many collagen fibers had discrete foci of degradation in which the fibrils were fragmented, loosely packed, and widely separated by granular material. Collagen fibril fragments were present in secondary lysosomes in dermal fibroblasts, but there were no degranulated mast cells or inflammatory cells in these areas. This suggested that a noninflammatory degradation and phagocytosis of collagen had occurred in the areas of hyperextensible fragile skin in this horse. Unaffected skin had no signs of collagen degradation or phagocytosis; uniformly cylindrical collagen fibrils were densely packed into morphologically normal fibers.

Functional and morphological characterization of neuropathy induced with 5-lipoxygenase inhibitor CGS 21595.

Peripheral toxic neuropathy induced in rats with a 5-lipoxygenase inhibitor CGS 21,595 was characterized using special functional tests and pathological procedures. Functional tests included measurement of grip strength, landing foot splay, assessment of sensorimotor and autonomic functions and monitoring of motor activity. Pathological procedures consisted of perfusion fixation, embedding in plastic, teasing of isolated nerve fibers, and light and electron microscopy. Male and female albino rats received the test article orally by gavage on 5 days per week. To characterize the development of the lesion animals treated with 1000 mg/kg were examined and sacrificed at 2-week intervals until termination at 10 weeks. In a separate study, the dose-effect relationship was examined in groups of animals treated with 50,200 or 1000 mg/kg for 10 weeks. Neurotoxicity occurred only in animals treated with 1000 mg/kg and was first detected following 4 weeks of treatment. Although there were no overt clinical signs of neurotoxicity, functional examination detected a reduction of grip strength, increased landing foot splay and reduced motor activity. Neuropathological examination revealed peripheral segmental demyelination affecting predominantly the Schwann cells in the ventral spinal nerve roots. Owing to its unusual localization in the nervous system and to subtlety of functional signs, peripheral segmental demyelination represents a special diagnostic challenge in toxicological safety studies.

Collagen in normal and abnormal tissues.

Despite being a very widespread protein, collagen is an unusual molecule possessing a great tensile strength conferred by a rope-like structure and intermolecular crosslinks. Our current knowledge of the biosynthesis of collagen is providing some insights into certain diseases of connective tissue and is also helping us to understand the healing processes of wounds and diseased tissues.

Branchial cyst in a heifer.

A branchial cyst in a heifer was removed surgically. Diagnosis was based on clinical signs, analysis of cyst contents, and histologic examination of the cyst wall. Biochemically, the cyst fluid resembled a transudate. The cyst lining consisted of nonciliated, pseudostratified columnar epithelium and pigmented, keratinized, stratified squamous epithelium. The embryologic origin was thought to be endoderm of the 2nd pharyngeal pouch and adjacent ectoderm.

Sudden death attributable to exercise-induced pulmonary hemorrhage in racehorses: nine cases (1981-1983).

Pathologic changes are described in 11 horses that died during racing or training; 9 died of acute pulmonary hemorrhage (exercise-induced pulmonary hemorrhage), 1 died of exsanguination, and 1 died of CNS trauma. Cardiac lesions were not found in any horse. Severe engorgement of pulmonary vessels, with hemorrhage into alveoli, airways, interstitium, and subpleural tissues, was observed in all 9 horses that died of exercise-induced pulmonary hemorrhage. Infiltration of eosinophils and/or lymphocytes around vessels and airways was seen in 6 horses. Focally extensive fibrosis was observed in the pleura and interstitium of 6 horses, and collections of siderophages were seen in the fibrous tissue and in the airways. Focal occlusion of bronchioles with inspissated mucus, such as that associated with small airway disease, was found in 4 horses. Underlying respiratory tract lesions, particularly those associated with small airway disease or bronchiolitis, may have a role in fatal pulmonary hemorrhage.

Environmental zinc and cadmium pollution associated with generalized osteochondrosis, osteoporosis, and nephrocalcinosis in horses.

Several suspect causes of chronic zinc/cadmium toxicosis in horses near a zinc smelter were investigated following observations of lameness, swollen joints, and unthriftiness, particularly in foals. Two foals born and raised near the smelter were lame and had joint swellings that were attributable to severe generalized osteochondrosis. Zinc and cadmium concentrations were markedly increased in the pancreas, liver, and kidney. The serum of 1 foal, zinc and potassium concentrations were high, whereas calcium and magnesium concentrations were low. Marked nephrocalcinosis and osteoporosis were observed in this foal. Nephrocalcinosis also was observed in his dam, who died of a punctured lung following rib fractures, though there was no history of trauma. The joint cartilage lesions were similar to those induced experimentally in animals fed high-zinc diets and may have been the result of zin-induced abnormality of copper metabolism. The osteoporosis and nephrocalcinosis were consistent with chronic cadmium toxicosis.

The role of allergy in chronic pulmonary disease of horses.

Twenty-five horses with chronic pulmonary disease were skin tested with allergenic extracts of 24 molds, 4 thermophilic actinomyces, barn dust, hay dust, soya-bean mill dust, and grain mill dust. The results were compared with those obtained on 25 normal horses. Between the 2 groups of horses, there was a highly significant difference in positive skin test results at 30 minutes and 4 hours.

Abortion and stillbirth associated with Chlamydia psittaci var ovis in dairy goats with high titers to Toxoplasma gondii.

During two consecutive breeding seasons in a brucellosis-free dairy goat herd, approximately 40% to 70% of the does (mean herd size, 14.5) had stillbirths or aborted. None of the does aborted or had stillbirths twice. In the first breeding season, 9 of 13 does aborted in the last 2 months of gestation. Three fetuses and 2 fetal placentas from 2 does were examined. Microscopic findings included severe multifocal hepatic necrosis, mild pneumonia, and mild multifocal necrosis in the brain. Cultures for Listeria monocytogenes, Chlamydia psittaci, and Coxiella burnetii were negative. Paired sera from 3 of the does that had aborted or had stillbirths were tested for antibodies to Toxoplasma gondii. On the basis of high titers, a tentative diagnosis of toxoplasmosis was made. During the following breeding season, 6 of 16 does aborted during the last 2 months of gestation. A total of 6 fetuses and 4 fetal placentas from 5 of these does were examined. Microscopic findings included infiltration of mononuclear cells around hepatic vessels and multifocal necrosis and gliosis in the brain. Chlamydia psittaci was isolated from the tissues of 1 fetus, 2 aborting does had persistent, high antibody titers against C psittaci (1:160 and 1:320), and all except 2 other does in the herd had C psittaci titers of 1:20 to 1:40. All but 2 does had T gondii titers of 1:32 to 1:4096. Evidently there was mixed infection with C psittaci and T gondii in this herd, but the former organism probably was responsible for the abortions and stillbirths.

Anaphylactoid purpura in a horse.

An 8-year-old gelding with a long-standing, streptococcal respiratory infection developed dyspnoea and colic. Laparotomy disclosed numerous, discrete, hemorrhagic, thick areas of necrosis throughout the intestinal tract. At postmortem examination similar lesions were seen in the laryngeal mucosa and in many skeletal muscles. Microscopically these lesions had massive necrosis and hemorrhage with a leucocytoclastic vasculitis in adjacent tissue. This condition resembled anaphylactoid purpura (Henoch-Schönlein disease) in man. Fungal infection was ruled out by special stains which failed to show fungal elements.

Percutaneous lung biopsy in the horse.

Percutaneous lung biopsies with a cutting needle (Vim Tru Cut) were obtained from 20 horses. The procedure was performed in standing horses under a local anesthesia without sedation. All lung tissue specimens were suitable for histologic examinations and contained both pulmonary parenchyma and large airways. The only complication was hemoptysis in 2 (10%) horses which required no therapy. All horses were subsequently killed, and no gross abnormalities were present at the biopsy site.

The use of the radioimmunoassay in the characterization of antibodies to basement membrane collagen.

This study describes the use of the radioimmunoassay for the characterization of antibodies to basement membrane (type IV) collagen from bovine anterior lens capsule. The immunogen was extracted from calf anterior lens capsules by limited pepsin digestion and injected into rabbits. The antisera were characterized using gel diffusion, haemagglutination and the radioimmunoassay in which 125I-labelled types I, II, III, and IV bovine collagen were employed. In the direct radioimmunoassay there was no reaction with either native or denatured types I, II or III bovine collagen, whereas there were high titres towards both native and denatured type IV bovine collagen. Radioimmune inhibition studies using unlabelled types I, II, III and IV bovine collagen, collagenase digested and repepsinized type IV collagen showed that there was marked inhibition by either native, denatured or repepsinized type IV collagen, and slight inhibition by native type I collagen; native type II and type III, denatured types I, II and III, and collagenase digested type IV collagen had no inhibitory effects.

Renal papillary necrosis in horses after phenylbutazone and water deprivation.

Acute renal papillary necrosis occurred in five horses given normal therapeutic doses of phenylbutazone and deprived of water for 36 to 48 hours prior to euthanasia. Five horses given phenylbutazone alone and four horses subjected to water deprivation alone did not develop papillary necrosis. Urinalyses were normal prior to water deprivation, and also after water deprivation in the horses that did not receive phenylbutazone, but the water-deprived, phenylbutazone-treated horses had many red blood cells, transitional epithelial cells, and large numbers of oxalate crystals in their urine. Ulceration of the alimentary tract was seen in more than 50% of these horses. Tongue ulceration was present in one of five horses given phenylbutazone and one of five horses which had phenylbutazone and water deprivation. Ulceration of the gastric mucosa was seen in two of the five phenylbutazone-treated horses, four of five horses with phenylbutazone treatment and water deprivation, and one of four horses with water deprivation alone. Severe colonic ulceration with perforation and peritonitis was present in one horse given phenylbutazone for three months. No other significant changes in the small or large intestine were seen in the other 13 horses.

Prevention of spontaneous tumours in female rats by fadrozole hydrochloride, an aromatase inhibitor.

Mammary tumours are oestrogen dependent in female Sprague-Dawley rats and in a significant proportion of women, so pharmacological treatment to inhibit oestrogen production is a valuable therapeutic measure to prevent or slow the progression of disease. Here we show that a non-steroidal aromatase inhibitor, which competitively inhibits the conversion of androstenedione to oestrone, prevents the development of both benign and malignant spontaneous mammary neoplasms in female Sprague-Dawley ats. It also slows the spontaneous development of pituitary pars distalis adenomas in female rats, and reduces the incidence of spontaneous hepatocellular tumours in male and female rats.