Intralesional cytokines in chronic oxazolone-induced contact sensitivity suggest roles for tumor necrosis factor alpha and interleukin-4.

An analysis was conducted of the cytokine profile and inflammatory response in oxazolone sensitized mouse skin. Following exposure to oxazolone, the intralesional production of inflammatory cytokines was demonstrable at the levels of both mRNA and protein. An initial challenge led to a transient increase in tumor necrosis factor-alpha production followed predominately by the T helper (Th)1 cytokine, interferon-gamma. There was a minimal production of interleukin-4, a Th2 cytokine. Continued exposure to oxazolone led to a downregulation of interferon-gamma and an upregulation of interleukin-4 production. A strong relationship was found between interleukin-4 and the inflammatory response, as measured by ear thickness. Similar experiments conducted in mast cell-deficient mice revealed reduced neutrophil influx but only minor changes in cytokine profile. An irritant response induced by chronic exposure of mouse skin to phorbol ester did not reveal any significant interferon-gamma or interleukin-4 response but was characterized by a tumor necrosis factor-alpha response that correlated with the inflammatory response. These observations suggest that the major source of interferon-gamma and interleukin-4 in the oxazolone response may be the infiltrating lymphocytes; whereas the tumor necrosis factor-alpha may result from the local irritation seen with both oxazolone and phorbol ester. At the end of 4 wk of chronic exposure to oxazolone, it was found that serum IgE levels had significantly increased. Histologic analysis of the skin lesion revealed that a mixed infiltrate including eosinophils developed upon repeat exposure to oxazolone. These findings are consistent with an early predominate Th1 response that is reduced and largely replaced with a Th2 response upon chronic T cell activation.

cAMP-specific phosphodiesterase inhibitor, rolipram, reduces eosinophil infiltration evoked by leukotrienes or by histamine in guinea pig conjunctiva.

The effect of rolipram, an isozyme IV-selective inhibitor of cAMP-specific phosphodiesterase, was evaluated in a guinea pig eye model of tissue eosinophilia. (R)-rolipram was administered by gavage to guinea pigs 1 h prior to topical ocular challenge with a mixture of leukotrienes (LTs) (10 ng LTB4 + 1000 ng LTD4/eye) or with histamine dihydrochloride (1 mg/eye). Conjunctivae were evaluated histologically 6 h after challenge. Eosinophil counts per millimeter of conjunctival epithelium in LT-challenged animals that received (R)-rolipram at dosages of 0.1, 0.3, 1, 3, or 10 mg/kg were reduced by 63, 63, 84, 81 and 90% respectively, compared to LT-challenged controls. Reduction was statistically significant (P < 0.05) at all dosages. Eosinophil counts per millimeter of epithelium in histamine-challenged animals that received 10 mg/kg (R)-rolipram were reduced by 79% compared to histamine-challenged controls (P < 0.01). The results indicate that (R)-rolipram inhibits the response to two distinct classes of mediator in this model of eosinophil infiltration, adding support to the contention that isozyme IV-selective cAMP phosphodiesterase inhibitors offer therapeutic potential for human asthma.

Myopathy with core-like structures in a dog.

Core-like structures were seen histologically in many of the fibres of the triceps and biceps femoris muscles of an 18-months-old male Great Dane with muscle weakness and moderate proximal muscular atrophy. The structures were lightly staining and lacked cross-striations. Some contained vacuoles and nuclei. Scattered necrotic and presumably regenerating fibres were also present. Ultrastructurally, the cores contained disarrayed filament bundles attached to thickened Z-lines which were compatible with the rods of rod myopathies. The condition was not fully characterized, but has certain similarities to a group of rare human congenital muscular disorders which includes central core disease.

Technique for physiological examination of canine skeletal muscle in vivo.

A technique is described for studying the physiological function of canine skeletal muscle in vivo. The contractile properties of the tarsal flexor muscles were examined in three beagle dogs under general anaesthesia. The force responses to electrical stimulation of the common peroneal nerve were measured at various frequencies to determine the frequency:force relationship for this muscle group. Fatigue characteristics were also examined during intermittent stimulated activity delivered in a set pattern of frequencies. The results provide quantitative characterisation of muscle function which is repeatable. The technique described could be applied to other animals and is a potentially powerful tool for evaluating the effects of drugs on muscle performance.

A morphological study of the lesions of African horsesickness.

Gross, histological and ultrastructural findings are described in 6 natural cases and in 2 experimental cases of African horsesickness. From the gross lesions the cases were divisible into 2 groups which represented the previously described pulmonary and mixed forms of the disease. Histologically, abundance of fibrin and inflammatory cells in oedematous lung suggests that the pulmonary lesion is an exudative pneumonia. Lymphoid depletion and necrosis in germinal centres were consistently present. Electron microscopy failed to demonstrate virus particles or virus-associated structures in the tissues. Ultrastructural evidence of vascular injury was not apparent in oedematous tissues. Possible mechanisms in the development of the lung oedema are considered and a comparison is made with oedema induced by alpha-naphthyl-thiourea. Lack of structural evidence of vascular injury revealed by this study extends some hope for therapy in African horsesickness.

Resistance of sheep to poisoning by The plant, Marticaria nigellifolia DC.

The plant, Matricaria nigellifolia, was dosed to 2 sheep to reinvestigate whether or not sheep are susceptible to pushing disease ("stootsiekte"). Each sheep received a total dose of 370 g/kg of the milled, dried plant from a batch that had caused pushing disease in cattle when given at doses as low as 10 g/kg. Neither of the sheep developed clinical disease over the trial period of 60 days, and necropsies revealed no macro- or microscopical lesions. Sheep are apparently resistant to pushing disease, which supports previous findings.

Cerebral mycosis in a dog caused by Cladosporium trichoides Emmons 1952.

The fungus, Cladosporium trichoides, was isolated and cultured from a lesion in the cerebellum and from smaller lesions in the liver, kidney and spleen of a dog which had a history of behavioural changes, ataxia and collapse. Histopathological examination showed the cerebellar lesion to be a purulant granuloma which contained brown, septate hypae and structures resembling conidia. The source of infection was not traced and no predisposing factors were apparent. As far as is known, this is the first record of the condition in animals in southern Africa and the first report anywhere of this condition in the dog.

A suspected lipofuscin storage disease of sheep associated with ingestion of the plant, Trachyandra divaricata (Jacq.) Kunth.

Paresis afflicted 85 out of a flock of 770 young Merino ewes kept on old wheat lands in the western Cape during a period of drought. Many of the paretic ewes died. The vegetation was sparse and was dominated by Trachyandra divaricata. At necropsy, yellowish-brown discoloration of the grey matter throughout the brain and spinal cord and mild brown discoloration of the liver, renal cortex and lymph nodes were consistently seen. Light microscopical examination revealed abundant, yellowish-brown pigment granules in the cytoplasm of most of the larger neurons. Similar pigment also occurred in some non-nervous tissues. Shrinkage and loss of a few randomly scattered axons were observed in the white matter of the spinal cord in 2 sheep. Histochemical and ultrastructural features of the pigment were consistent with those of lipofuscin. T. divaricata failed to reproduce the condition when dosed to a sheep, but the paresis and pigmentation shown to be caused by the closely related plant, T. laxa, are strikingly similar. Trachyandra poisoning appears to be the first documented example in farm animals of an acquired lipofuscin storage disease involving nervous and non-nervous tissues for which a specific plant has been causally implicated.

Bovine skin lesions of possible filarial origin associated with heavy hornfly infestations (Haematobia meridiana).

Circumscribed, ulcerative skin lesions, usually situated caudal to the scapula, affected cattle in the Republic of Venda during the summer of 1981-82. The occurrence of the lesions was associated with heavy infestations of the hornfly. Haematobia meridiana. Microscopically the lesions were characterized by intense eosinophilic dermatitis. Microfilariae were seen in histological sections of one lesion, but a species identification could not be made. The possible cause of the lesions is discussed.

Measurements of mass, length and valve diameters from normal formalin-fixed ovine hearts.

Hearts from 60 Merino sheep of known age, sex and live mass and with no known history of disease were collected and fixed in buffered 10% formalin. Systematic light microscopical examination did not indicate any abnormality in hearts of any of the sheep. The mass of various parts of the hearts, the length of the hearts and the diameters of the heart valves were measured to establish a basis for quantitative assessment of possible pathological changes associated with the ingestion of cardiotoxic plants. The mass measurements and, to a lesser degree, the lengths of the hearts varied considerably, but the ratio of the mass of the left ventricle plus ventricular septum divided by the right ventricular free wall mass was remarkably stable, and is promising as an indicator of right ventricular hypertrophy.

Pathology of a nervous disorder (pushing disease or "stootsiekte") in cattle caused by the plant Matricaria nigellifolia DC. (Asteraceae).

Brains from 10 bovine field cases of pushing disease, a nervous disorder caused by the plant, Matricaria nigellifolia, were examined by light microscopy. Moderate to marked encephalitis, characterized by predominantly perivascular microgliosis, perivascular lymphocytic infiltrates and reactive changes in astrocytes, was present in all the brains. The lesion was concentrated in the white matter throughout the forebrain and midbrain. Dried, milled M. nigellifolia was dosed to 6 steers. Clinical signs of pushing disease, which included docility, clumsiness and pushing against objects, appeared abruptly in 5 of the steers after a latent period that varied from 16-44 days. The lowest total dose of plant that proved toxic was 10 g/kg. The length of the latent period appeared to be related inversely to the total dose. Encephalitis, which was similar in nature and distribution to those in the field cases, was demonstrated in the 5 affected steers. The lesion was minimal in the brain of the steer that did not develop pushing disease. The cerebral lesion is sufficiently consistent and distinctive to be useful in establishing a diagnosis of pushing disease. The perivascular distribution of microgliosis suggests that the site of the toxic insult is the cerebral vasculature. Botanical information is presented.

Intoxication of cattle on kikuyu grass following army worm (Spodoptera exempta) invasion.

Clinical features and pathological and mycological findings in a field outbreak of intoxication in dairy cattle grazing kikuyu grass are reported. The outbreak followed invasion of the grass by the army worm (Spodoptera exempta). Clinical signs included drooling of saliva, depression, apparent inco-ordination, sunken eyes, ruminal distension and atony, recumbency, moderate diarrhoea and "sham drinking". Seventy-seven cows (64%) were clinically affected over a period of 12 days. Of these, 37 died. Necropsies performed on 4 affected cattle revealed necrosis of the epithelium of the forestomach, which was consistently more severe in the omasum. Light microscopy showed extensive necrosis of the epithelium of the forestomach with associated fibrinopurulent inflammation. The stratum spinosum and s. granulosum were selectively involved, but the s. basale was generally preserved. Electron microscopical examination of ruminal and omasal epithelium from 2 of these cattle revealed cytopathological features in the s. spinosum and s. granulosum which were consistent with stages in an acute, anoxic type of injury. Mycological examination of the pastures revealed sparse growth of a mixed fungal population, which included Myrothecium verrucaria. There was no evidence of heavy fungal infestation. Previous evidence that M. verrucaria, or other fungi, may be involved in the aetiology of kikuyu grass poisoning of cattle in New Zealand is addressed. It appears improbable that any of the fungi isolated in this investigation could have played an important role in the aetiology of this outbreak.

A tremorgenic mycotoxicosis of cattle caused by maize sprouts infested with Aspergillus clavatus.

An outbreak of disease affecting a herd of 16 dairy cattle which were fed mouldy, sprouted maize is described. Eight of the cattle were affected, 5 of which died. The clinical signs included muscular tremors, hypersensitivity, ataxia, anorexia and salivation. Aspergillus clavatus was the only fungus isolated from the sprouts. Clinical signs that were indistinguishable from those in the field outbreak were reproduced by dosing the mouldy maize sprouts to a steer and a sheep, and by dosing another sheep with maize inoculated with a pure culture of A. clavatus isolated from the mouldy maize on the farm. Light microscopical examination revealed neuronal degeneration and necrosis in the midbrain, medulla oblongata and spinal cord of all 3 of these animals. The disease is clinically and pathologically indistinguishable from the disease caused by the ingestion of sorghum beer residue, and in certain respects it is similar to toxicoses caused by the ingestion of wheat sprouts and malt sprouts infested with A. clavatus.

Reaction patterns in myocardium in response to injury.

Some reactions and their components at a microscopical level in myocardium are described using evidence obtained from natural and experimental cardiac conditions. Necrosis of different types, hypertrophy, mineralization, and other changes in myocytes, changes in myocarditis, and patterns involving conductive tissue are considered. A short summary of some collected values concerning the chronology of myocardial reactions is presented. The pathogenesis of myocardial reactions is complex and is influenced by diverse factors. Although certain patterns are recognizable, firm aetiological interpretation from the pattern alone is rarely justifiable.

Kikuyu grass poisoning of cattle in Natal.

The clinical findings in six natural and two experimental cases of Kikuyu grass poisoning in Natal, South Africa, are described and compared with findings in cases of toxicity reported elsewhere. The toxic factor has not been identified but a mycotoxin is suspected.

Unilateral hindleg spasticity: outbreak of a specific clinical condition in suckling piglets.

A specific clinical condition of unilateral hindleg spasticity is described which affected all the piglets of 8 litters in one piggery. Histopathological examination of 3 of the piglets revealed changes involving some of the large neurons in the red nucleus, cerebellar nuclei and lumbar spinal cord. These changes were absent from 2 control piglets of the same age which were studied. The clinical and histopathological findings are discussed in relation to the possible aetiology of the condition.

Myocardial pathology of domestic ruminants in southern Africa.

Myocardial pathology of ruminants in southern Africa, including lesions associated with toxic plants, other toxic agents, infectious agents and nutritional deficiency, is discussed with regard to recognition and to aetiological diagnosis. Findings are included which have not been published elsewhere. The importance and difficulties in recognition of myocardial lesions at an early stage are emphasized. Further research into the pathology of cardiac failure caused by toxic plants is clearly needed.

A mycobacteriosis in a sheep resembling paratuberculosis (Johne's disease).

In a sheep which was euthanased because of severe emaciation and weakness, slight thickening of the ileum was seen grossly. Microscopically there was a granulomatous ileitis with obliterative lymphangitis and lymphangiectasis. Granulomatous lesions were also present in the liver and some mesenteric lymph nodes. Large numbers of acid-fast bacilli were present within epithelioid macrophages in the lamina propria of the ileum. Although the identity of the Mycobacterium spp. involved was not established, the possibility of paratuberculosis is discussed. The apparent rarity of this disease in sheep in South Africa is considered. Particular attention is drawn to the absence of diarrhoea in this case, to the slightness of the gross changes and to the importance of submitting material for mycobacterial culture.

An outbreak of cerebrocortical necrosis (polioencephalomalacia) in goats.

In a herd of 30 Boer goats, 3 young goats developed nervous signs including apparent blindness. In 2 of the goats a diagnosis of cerebrocortical necrosis was confirmed by the demonstration of lesions typical of the disease on histopathological examination. Lead concentrations in the renal cortex were well below the level regarded as indicative of lead poisoning in ruminants. The reason for the outbreak was not clear, but the feeding of concentrate and poor quality roughage may have been contributory factors. Cerebrocortical necrosis appears to be unusual in goats, compared to cattle and sheep, but it should be entertained in the differential diagnosis of caprine nervous diseases.

A haemorrhagic syndrome in recently weaned pigs ascribed to hypovitaminosis K.

An outbreak of a haemorrhagic syndrome involved recently weaned, mixed-breed pigs in a large piggery. The pigs were fed a pelleted complete ration containing antibacterial drugs. Affected pigs failed to grow, became pale and developed large, subcutaneous haematomas. Some pigs became lame and one had epistaxis. The monthly mortality rate in the weaner house, which was previously less than 2%, exceeded 6% during the outbreak. Coagulation time, activated partial thromboplastin time and prothrombin time were prolonged in blood from some of the pigs. The outbreak resolved promptly after supplementation of the diet with vitamin K3.