Ruminal and plasma concentrations of 3-methylindole associated with tryptophan-induced pulmonary edema and emphysema in cattle.

Five Hereford cows were given an intraruminal dose of L-tryptophan (0.35 g/kg of body weight), and 2 cows were used as controls. Of the 5 treated cows, 3 developed clinical signs of interstitial pul monary edema, and emphysema and severe pulmonary lesions were seen at necropsy after 96 hours. Another cow developed moderate clinical signs and pulmonary lesions, and the remaining cow had few clinical signs and mild pulmonary lesions. The severity of clinical signs in each cow was related to the severity of pulmonary lesions at necropsy. The 3-methylindole (3MI) was present in ruminal fluid and plasma within 6 hours after administration of tryptophan, and the concentrations increased to 3.0 and 9.0 mug/ml within 12 to 24 hours. Severity of pulmonary lesions was related to maximal concentration and duration of 3MI in the plasma. At necropsy, gross lesions were characterized by diffuse, pulmonary edema and interstital emphysema; and the lungs were dark red, firm, and heavier than normal. Predominant microscopic changes included accumulation of proteinaceous residue, hypertrophy and hyperplasia of alveolar lining epithelium, thickening of alveolar septums, and emphysematous thickening of interstitial tissues. These changes were similar to previously reported 3MI-induced pulmonary lesions. The presence of 3MI in ruminal fluid and plasma after administration of tryptophan and the relationship between concentration of 3MI and severity of clinical signs indicate that 3MI is the principal metabolite of ruminal fermentation which leads to the development of acute pulmonary edema and emphysema in cattle given tryptophan.     

Pulmonary edema and emphysema in cattle after intraruminal and intravenous administration of 3-methylindole.

Intraruminal and intravenous administration of 3-methylindole (3MI; skatole) caused interstitial pulmonary edema and emphysema in cattle. In 3 adult heifers given the intraruminal dose of 0.2 g of 3 MI per kilogram of body weight, clinical signs of respiratory disease appeared between 6 and 12 hours after dosing, and death due to pulmonary edema and emphysema occurred at 33, 69, and 72 hours. The mean plasma concentration of 3MI became maximal (18.5 mug/ml) at 3 hours and then decreased to low concentrations by 48 hours. In 2 heifers given an intraruminal dose of 0.1 g of 3MI/kg, clinical signs developed, but they did not die during the 96-hour experiment. The mean plasma concentration of 3 MI became maximal (16.8 mug/ml) at 3 hours and decreased to 1.6 and 0.4 mug/ml at 12 and 36 hours, respectively. At necropsy of the heifers, the lung were large, firm, dark red, and heavier than normal. Diffuse pulmonary edema was the predominant change in cattle which died early, and interstitial emphysema was more severe at later stages of the disease. During the early stages, alveoli were overdistended, and a few more ruptured. Most alveolar spaces were filled with proteinaceous residue, but the alveolar septums were smooth and of normal thickness. At later stages, proliferation of alveolar cells was observed, and alveolar septums were thickened. In 3 cows given 0.06 g of 3MI/kg by jugular infusion, clinical signs appeared in all cows, and 1 cow died of pulmonary edema and emphysema 56 hours after the infusion was started. Severe pulmonary lesions seen in all of the cows given a 3MI infusion were similar to those in the cows given an intraruminal dose of 3MI. The mean plasma concentration of 3MI increased to 10.7 mug/ml at 9 hours after starting the infusion and decreased to 0.5 mug/ml at 18 hours. The results indicate that 3MI, a product of ruminal tryptophan fermentation, can cause pulmonary edema and interstitial emphysema in cattle and support the hypothesis that 3MI is the causative agent in tryptophan-induced pulmonary disease.     

Pathophysiologic studies of calves given 3-methylindole intraruminally

Intraruminal administration of 0.25 g of 3-methylindole (3MI; skatole/kg of body weight) to seven young calves generally caused mild respiratory signs and lesions, accompanied by only slight changes in cardiopulmonary function. Moderate depression, trembling, and irregular respiratory rate were observed between postadministration hours (PAH) 6 and 12. By PAH 24 at this dosage, abnormal clinical signs were not present. Statistically significant (P less than or equal to 0.05) changes observed in blood gas data from the seven calves were a decrease in aortic oxygen tension at PAH 12, increases in free-flowing venous oxygen tension in the intervals between PAH 6 and 12 and between PAH 6 and 24, and an increase in occluded venous oxygen tension at PAH 24. All calves had increases (although generally not statistically significant) in heart rate, cardiac output, cardiac index, stroke volume, and stroke index after 3MI administration. Mean aortic and pulmonary arterial pressure changes were generally small and variable. At necropsy, the lungs of the calves did not collapse when the thorax was opened. Patchy areas of consolidation (0.5 cm in diameter) were scattered throughout the parenchyma. Pulmonary edema or emphysema was not observed grossly. Microscopically, the alveolar septae were irregularly thickened because of edema, infiltration by polymorphonuclear and mononuclear cells, and vascular congestion. Interstitial lesions were patchy in distribution and severity and corresponded to the areas of consolidation observed grossly. Alveolar epithelial hypertrophy and hyperplasia were present, and an occasional focus of alevoli contained fluid of edema. Degeneration of individual hepatocytes was observed in scattered areas of the liver, especially in the periportal areas. It was concluded that differences in 3MI dosage response may exist between young calves and adult cattle in which calves are more resistant to the pulmonary cytotoxicity of 3MI.     

Evaluation of the ability of orally administered aspirin to mitigate effects of 3-methylindole in feedlot cattle

OBJECTIVE: To evaluate the ability of orally administered aspirin to mitigate 3-methylindole (3MI)-induced respiratory tract disease and reduced rate of gain in feedlot cattle. ANIMALS: 244 beef cattle. PROCEDURE: In a masked, randomized, controlled field trial, calves were untreated (controls) or received a single orally administered dose of aspirin (31.2 g) on entry into a feedlot. Serum 3MI concentrations were measured on days 0, 3, and 6. Rumen 3MI concentration was measured on day 3. Cattle were observed daily for clinical signs of respiratory tract disease. Lungs were evaluated at slaughter for gross pulmonary lesions. RESULTS: Mean daily gain (MDG) in cattle treated with aspirin, compared with control cattle, was 0.06 kg greater in the backgrounding unit and 0.03 kg greater for the overall feeding period. Neither serum nor rumen 3MI concentrations appeared to modify this effect. Cattle treated with aspirin were more likely to be treated for respiratory tract disease. Mortality rate, gross pulmonary lesions, and serum and rumen 3MI concentrations were similar between groups. Increased rumen 3MI concentration was associated with a small difference in risk of lung fibrosis. CONCLUSIONS AND CLINICAL RELEVANCE: Cattle given a single orally administered dose of aspirin on feedlot entry had higher MDG in the backgrounding unit and for the overall feeding period, but this finding could not be attributed to mitigation of effects of 3MI. This may have been influenced by low peak 3MI production and slow rates of gain.     

Histologic and immunochemical study of the pathogenesis of heartwater (Cowdria ruminantium infection) in goats and mice

Eleven adult goats and 32 adult outbred mice were inoculated IV with Cowdria ruminantium-infected blood (Kwanyanga isolate), monitored clinically, then serially euthanatized. Predominant clinical signs of disease in goats were depression, head tremors, seizures, and dyspnea. In mice, dyspnea and depression were the only clinical signs of disease noticed. Tissues were examined histologically and immunohistochemically for C ruminantium colonies or antigen. In goats, C ruminantium was detected only in endothelial cells of the brain, even though gross and microscopic lesions were confined to the thorax. In mice, C ruminantium was detected only in endothelial cells of the heart and lungs.     

Pulmonary artery banding for ventricular septal defect in dogs and cats

Five dogs and 1 cat had pulmonary artery banding for ventricular septal defect and congestive heart failure. An umbilical tape band constricted the pulmonary artery to one-third its original diameter, increased the right ventricular pressure, and decreased the left ot right shunt. Five animals had remission of clinical signs; 1 dog died of right ventricular failure due to a band that had been applied too tightly. The results indicated pulmonary artery banding is helpful in reduction of clinical signs, due to increased flow to the lungs from ventricular septal defect.     

Synergistic effects of concurrent challenge with bovine respiratory syncytial virus and 3-methylindole in calves.

OBJECTIVE: To evaluate the potential synergy between bovine respiratory syncytial virus (BRSV) and 3-methylindole (3MI) in inducing respiratory disease in cattle. ANIMALS: 20 mixed-breed beef calves. PROCEDURE: A 2 X 2 factorial design was used, with random assignment to the following 4 treatment groups: unchallenged control, BRSV challenge exposure (5 X 10(4) TCID50 by aerosolization and 5.5 X 10(5) TCID50 by intratracheal inoculation), 3MI challenge exposure (0.1 g/kg of body weight, PO), and combined BRSV-3MI challenge exposure. Clinical examinations were performed daily. Serum 3MI concentrations, WBC counts, PCV, total plasma protein, and fibrinogen concentrations were determined throughout the experiment. Surviving cattle were euthanatized 7 days after challenge exposure. Pulmonary lesions were evaluated at postmortem examination. RESULTS: Clinical respiratory disease was more acute and severe in cattle in the BRSV-3MI challenge-exposure group than in cattle in the other groups. All 5 cattle in this group and 3 of 5 cattle treated with 3MI alone died or were euthanatized prior to termination of the experiment. Mean lung displacement volume was greatest in the BRSV-3MI challenge-exposure group. Gross and histologic examination revealed that pulmonary lesions were also most severe for cattle in this group. CONCLUSIONS AND CLINICAL RELEVANCE: Feedlot cattle are commonly infected with BRSV, and 3MI is produced by microflora in the rumen of all cattle. Our results suggest that there is a synergy between BRSV and 3MI. Thus, controlling combined exposure may be important in preventing respiratory disease in feedlot cattle.     

Pulmonary artery pressures in normal horses and in horses affected with chronic obstructive pulmonary disease

Horses clinically affected with chronic obstructive pulmonary disease (COPD) were found to have pulmonary artery hypertension which was associated with systemic arterial hypoxia. The pulmonary hypertension in symptomatic COPD-affected horses was partially reversible upon remission of clinical signs or by oxygen administration. The induction of acute hypoxaemia caused an increase in pulmonary artery pressure in both normal and COPD-affected horses.     

Acute Atypical Bovine Pneumonia Caused by Ascaris Lumbricoides

A case of acute atypical pneumonia (bovine asthma, pulmonary emphysema, or pulmonary adenomatosis) occurred in a group of cross-bred beef type yearlings in late autumn. Clinical signs included a forced expiratory grunt, excessive salivation, ruminal stasis and, on auscultation over the lungs, pulmonary emphysema and oedema. The cattle had been brought in from a poor summer pasture and housed in a pig pen heavily contaminated with Ascaris lumbricoides eggs as it had contained unwormed feeder pigs all summer.

Fifteen out of seventeen head were affected ten days following housing and all within twenty-four hours. One steer of the group died and at necropsy fourth stage A. lumbricoides larvae were isolated from lungs showing profuse oedema and some emphysema. Histopathological examinations of the lungs showed a diffuse interstitial pneumonia. All remaining animals appeared clinically normal six days following the outbreak.

     

Site of 3-methylindole and indole absorption in steers after ruminal administration of L-tryptophan

To determine the site of 3-methylindole (3MI) and indole absorption in cattle after ruminal administration of L-tryptophan (TRP), 4 Holstein steers were given 0.4 g of TRP/kg of body weight directly into the rumen through ruminal cannulas. Chromium EDTA and ruthenium phenanthroline were added to feedings of orchard grass hay twice a day for measurement of fluid and particulate flow to the duodenum, respectively. Passage of 3MI and indole (products of ruminal fermentation of TRP) to the duodenum was determined by the products of digesta flow rate and concentration in duodenal contents. Ruminal fluid, duodenal contents, and jugular blood were sampled at postdosing hours (PDH) 0, 6, 12, 18, 24, 36, and 72 for analysis of 3MI, indole, and digesta flow markers. Ruminal, duodenal, and jugular plasma concentrations of 3MI and indole peaked at PDH 12 to 24 at 152.4 and 25.9; 15.5 and 1.0; and 8.7 and 2.2 mg/L, respectively. Most 3MI and indole reaching the duodenum were associated with the particulate phase of the digesta. On a molar basis, total passage of 3MI to the duodenum during 72 hours amounted to 1.0% of the TRP dose for 3MI and 0.1% of the TRP dose for indole. Absorption of 3MI and indole in these steers was almost entirely proximal to the duodenum.     

Pulmonary lesions induced by 3-methylindole and bovine respiratory syncytial virus in calves

Our objectives were to describe the ultrastructural morphogenesis of pulmonary lesions induced by 3-methylindole in 30- to 45-day-old Holstein calves and to determine whether toxic exposure to 3-methylindole exacerbates pulmonary lesions induced by bovine respiratory syncytial virus. Administration of 3-methylindole (0.25 g/kg) to calves resulted in interstitial edema and ultrastructural swelling of type-I alveolar epithelial cells and nonciliated bronchiolar epithelial cells as early as 4 to 6 hours after intraruminal administration. More severe alveolar edema containing protein was associated with swelling of capillary endothelial cells at 2 days after administration. Proliferation of type-II alveolar epithelial cells was first observed at 2 days after 3-methylindole administration, and marked hyperplasia of type-II epithelial cells and nonciliated bronchiolar epithelial cells was evident by 4 days after administration. Pulmonary cytochrome P-450 monooxygenase concentrations decreased significantly (P less than 0.001) by 12 hours after administration and did not increase significantly again by 8 days after administration. Calves were inoculated with bovine respiratory syncytial virus 3 days after administration of 3-methylindole, and pulmonary lesions were assessed 5 days after viral inoculation. Viral replication was demonstrated by fluorescence microscopy for viral antigen or by transmission electron microscopy in ciliated and nonciliated airway epithelial cells. Viral antigen was identified infrequently in alveolar macrophages and in type-II alveolar epithelial cells. 3-Methylindole exposure in calves did not result in more widespread distribution of viral antigen in alveolar tissue of respiratory syncytial virus-inoculated calves or in significant enhancement of viral pneumonia.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effects of 3-methylindole production and immunity against bovine respiratory syncytial virus on development of respiratory tract disease and rate of gain of feedlot cattle

OBJECTIVE: To determine whether immunity against bovine respiratory syncytial virus (BRSV) mitigates the effects of 3-methylindole (3MI) on occurrence of bovine respiratory tract disease (BRD) and rate of gain in feedlot cattle. ANIMALS: 254 mixed-breed beef cattle. PROCEDURE: Cattle were randomly assigned to 1 of 3 groups at the time of arrival at the feedlot. One group was vaccinated with an inactivated BRSV vaccine, another was vaccinated with a modified-live BRSV vaccine, and the third was maintained as unvaccinated control cattle. On days 0 and 28, serum BRSV antibody concentrations were measured, using serum neutralizing and ELISA techniques. Serum 3MI concentrations were measured at feedlot arrival and 3 days later. Cattle were monitored for development of BRD. At slaughter, lungs were evaluated grossly for chronic lesions. RESULTS: Higher serum 3MI concentrations early in the feeding period were associated with lower mean daily gain. Control cattle were more likely to be treated for BRD after day 3, compared with cattle vaccinated with the modified-live BRSV vaccine. Humoral immunity against BRSV did not appear to modify the effect of 3MI on development of BRD or mean daily gain. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that abrogating the effects of 3MI and BRSV infection may improve the health and growth performance of feedlot cattle. However, in this study, immunity against BRSV did not appear to protect against the potential synergism between 3MI and BRSV infection, possibly because of the slow rates of gain of cattle included in the study or timing of sample collection.     

Pulmonary function changes in goats given 3-methylindole orally

Six adult goats were given 0.2 g of 3-methylindole (3MI)/kg of body weight orally. Lung mechanics and ventilatory function were obtained before 3MI and 2, 4, 6, 24, 48, and 72 hours after 3MI administration. Clinical signs were also monitored. Lungs were removed for gross and microscopic examination and for morphometric analysis from goats that died spontaneously or were killed with an overdose of pentobarbital after 72 hours. The major pulmonary function changes observed included a marked decrease in dynamic lung compliance with a moderate increase in airway resistance, a concomitant hypoxemia, sustained increase in respiratory frequency, a progressive decrease in tidal volume and alveolar ventilation, and increased dead space to tidal volume ratio. A mild metabolic acidosis was also noticed.     

A clinical trial to assess the use of sodium hypochlorite and oxytetracycline on the healing of digital dermatitis lesions in cattle

The increased frequency of diseases, especially those of the hoof, cause economic losses, such as premature culling of affected animals, decreased milk production, weight loss, reduced fertility, and the high costs of treatment. A great variety of hoof conditions may affect cattle, one of them is digital dermatitis. These conditions are probably due to multiple factorial diseases and present with similar clinical signs. Bovine lameness is typically treated by foot trimming and debridment of the lesions, coupled when necessary with systemic antibiotics and therapeutic footbaths, which results in a clinical cure in the majority of the cases. The objective of this study was to evaluate the topical action of sodium hypochlorite associated with the systemic use of oxytetracycline for the treatment of wounds clinically diagnosed as bovine digital dermatitis. One hundred and twenty Holstein cattle varying ages from 1 to 9 y and presenting the clinical signs of digital dermatitis, were used in this study. Group 1 (G1) received topical treatment with a 1% sodium hypochlorite footbath twice a day for 30 d and 4 treatments of parenteral oxytetracycline (10 mg/kg bodyweight, IM, q48h). Group 2 (G2) received only the topical treatment with 1% sodium hypochlorite, as described for G1. Group 3 (G3) received only with parenteral oxytetracycline, as described for G1. Group 4 (G4) was treated exclusively with a dicloro divynil pirrolidona, ortoiododimetil, para-nitofenil-fosforotioato in a vegetal tar-based ointment, immediately after the surgery. After 45 d, the recovery rates were as follows: G1, 86.67%; G2, 73.33%; G3, 56.67%; and G4, 50%. The surgical treatment of digital dermatitis with subsequent treatment with oxytetracycline systemically and 1% sodium hypochlorite topically was the most effective for the convalescence of cattle bearing wounds similar to digital dermatitis.     

3-Methylindole-induced pulmonary injury in lambs. A comparison with acute respiratory distress syndrome (ARDS)

Five to six month-old lambs of two different Norwegian breeds (Dala and Rygja) were dosed with 3-methyl indole (3MI) and DL-tryptophan (DL-T), and examined clinically, hematologically and post mortem. Results were compared with the findings in Acute Respiratory Distress Syndrome (ARDS), a condition of acute dyspnea occurring in 5-6 month-old lambs (of Dala and Spael breeds) after they have been moved from mountain pastures onto lush aftermath in September. The results show that such young Norwegian lambs are susceptible to 3MI-dosing, and that the symptoms and lesions were similar to those described earlier in connection with 3MI-dosing in cattle and adult sheep. The results clearly demonstrate that 3-MI-induced pulmonary injury in lambs differs from ARDS as far as both symptoms, hematology and pathology are concerned.     

Role of mixed-function oxidase in 3-methylindole-induced acute pulmonary edema in goats

The relationship between the pulmonary toxicity of 3- methylindole (3MI, skatole) and the mixed-function oxidase (MFO) system was investigated. Nine goats assigned to three groups were given a jugular infusion of [14C]3MI (0.02 to 0.03 g of 3MI/kg of body weight containing 0.5 muCi/kg of body weight) for 1.5 hours to induce acute pulmonary edema. Two groups of three goats each were treated with phenobarbital (PB) or piperonyl butoxide (BT) prior to 3MI infusion to induce or to inhibit the MFO system. Three goats were used as 3MI controls. During a 72-hour test period, blood was collected for determination of plasma 3MI concentration and radioactivity. Urine was collected and was fractionated by column chromatography. The severity of pulmonary lesions was evaluated by gross and microscopic examination. Pretreatment with BT prevented the onset of acute pulmonary edema. Goats pretreated with PB had more severe lung lesions than did 3MI controls. Plasma of goats pretreated with BT had a longer half-life (2.1 hours) of radioactivity, whereas plasma of goats pretreated with PB had a shorter half-life (1.0 hour) when compared with plasma of 3MI control goats (1.5 hours) given the same dosage of [14C]3MI (P less than 0.025). The plasma half-life of 3MI was longer (P less than 0.025) in BT-pretreated goats (0.45 hour) than that in PB-pretreated goats (0.26 hour). At 72 hours, 70% to 98% of the infused radioactivity had been excreted in the urine. The pattern of urinary metabolites of 3MI was altered in BT-pretreated goats compared with patterns in control and PB-pretreated goats. Results indicate that the MFO system is one of the pathways involved in the metabolism of 3MI and that pulmonary toxicosis results from metabolism of 3MI by this enzyme system.     

Evaluation of severe disease induced by aerosol inoculation of calves with bovine respiratory syncytial virus

OBJECTIVE: To develop a model of bovine respiratory syncytial virus (BRSV) infection that induces severe disease similar to that seen in some cattle with naturally acquired BRSV infection. ANIMALS: 25 male Holstein calves, 8 to 16 weeks old. PROCEDURE: 17 calves were given a low-passage field isolate of BRSV by aerosolization; 8 control calves were given supernatant from noninfected cell culture. Disease was characterized by evaluating clinical signs, virus isolation and pulmonary function tests, and results of blood gas analysis, gross and histologic postmortem examination, and microbiologic testing. RESULTS: Cumulative incidence of cough, harsh lung sounds, adventitious sounds, and dyspnea and increases in rectal temperature and respiratory rate were significantly greater in infected calves. Three infected calves developed extreme respiratory distress and were euthanatized 7 days after inoculation. Virus was isolated from nasal swab specimens from all infected calves but not from mock infected calves. On day 7 after inoculation, mean PaO2 and PaCO2 were significantly lower, and pulmonary resistance was significantly higher, in infected calves. During necropsy, infected calves had varying degrees of necrotizing and proliferative bronchiolitis and alveolitis with syncytial formation. The 3 calves euthanatized on day 7 had emphysematous bullae in the caudal lung lobes; 1 had unilateral pneumothorax. CONCLUSION AND CLINICAL RELEVANCE: Severe disease similar to that seen in some cattle with naturally acquired BRSV infection can be induced in calves with a single aerosol exposure of a low-passage clinical isolate of BRSV. Our model will be useful for studying the pathogenesis of BRSV infection and for evaluating vaccines and therapeutics.     

Aerosolized Micropolyspora faeni antigen as a cause of pulmonary dysfunction in ponies with recurrent airway obstruction (heaves)

Ponies with recurrent airway obstruction (principal ponies) and their controls were given aerosolized Micropolyspora faeni antigen via endotracheal tube during a period when the principal ponies were in disease remission. In both groups of ponies, we performed bronchoalveolar lavage (BAL) and measured pulmonary function at base line, and 5 hours after aerosol administration of 30 ml of 0.9% NaCl solution or 30 ml of 1% w/v particulate M faeni antigen in 0.9% NaCl solution. In both groups of ponies, aerosolized M faeni antigen increased WBC count, neutrophil numbers, and albumin concentration in BAL fluid, but macrophage numbers decreased. In the principal ponies, BAL mast cell numbers were decreased 5 hours after administration of M faeni antigen. The M faeni antigen had no effect on the mechanical properties of the lungs or on gas exchange in the control ponies, but did increase respiratory frequency minute ventilation and pulmonary resistance, and decreased arterial oxygen tension in the principal ponies. Changes in pulmonary function were apparent only in the principal ponies, which suggests that neutrophils, per se, do not cause pulmonary dysfunction and that M faeni may be one of the etiologic agents involved in chronic obstructive pulmonary disease.     

The efficacy of valnemulin (Econor) in the control of disease caused by experimental infection of calves with Mycoplasma bovis

Mycoplasma bovis infection was experimentally induced in groups of six young calves. A further group was uninfected and served as a control. Ten days after infection, medication with either enrofloxacin (Baytril, Bayer) or valnemulin (Econor, Novartis) was instituted via the milk replacer for a further 10 days, after which all calves were killed. Infection resulted in depression, pyrexia, inappetance and prominent respiratory signs. Arthritis occurred in two animals and two (unmedicated) animals died. At post-mortem examination extensive lesions were present in the lungs and M. bovis was re-isolated from infected unmedicated calves' lungs. Medication with either enrofloxacin or valnemulin resulted in a rapid diminution of clinical signs, restoration of appetite and reversal of weight loss. Isolation of Pasteurella multocida from the calves' lungs was suppressed by both medicaments. Valnemulin resulted in a more rapid reduction of clinical scores and eliminated M. bovis from the lungs more effectively than enrofloxacin.     

Copper toxicosis in cattle fed chicken litter

Cattle from 2 herds developed copper toxicosis after the ingestion of chicken litter. The affected animals were adult Holstein cows and crossbred steers that ate 9 to 16 kg of litter/day. These cattle developed a sudden onset of weakness, depression, anorexia, icteric mucous membranes, and dark reddish brown urine. Liver copper concentrations in 2 cattle (1 from each herd) were 436 and 730 ppm. Results of copper analyses of chicken litter ranged from 620 to 920 ppm. Sodium molybdate and sodium thiosulfate were added to the ration of the dairy herd. Two cows with clinical signs of copper toxicosis recovered after being given additional sodium molybdate and thiosulfate supplements, orally.