Dwayne W. Hamar

In vivo indicators of pathologic ruminal sulfide production in steers with diet-induced polioencephalomalacia.

Two groups of 3 120–160-kg Holstein steers were fed a diet high in carbohydrate and low in long fiber and either with or without added sodium sulfate. Prior to and during the course of feeding the experimental diet, the concentrations of rumen hydrogen sulfide gas and rumen fluid sulfide were determined by a simple sulfide detector tube method and by sulfide-selective electrode, respectively. Other measurements included rumen fluid pH, blood creatine kinase, and blood sulfhemoglobin. Two of the 3 steers fed the high-sulfate diet developed signs and lesions of polioencephalomalacia. Clinical signs included episodic ataxia and blunted or absent menace reaction. Increased ruminal H2S gas concentrations occurred in all 3 steers consuming the diet with added sulfate. The onset of clinical signs coincided with the onset of elevated H2S concentrations. These increases were 40–60 times the values measured in the steers consuming the diet without added sulfate. In contrast, increases in rumen fluid sulfide concentrations usually rose to 4 times that of control steers. The steers fed an identical diet but without added sulfate exhibited no signs or lesions of polioencephalomalacia and no elevations of sulfide in rumen gas or fluid. All steers had a modest decrease in rumen fluid pH associated with the transition to the concentrate diet. No significant changes were observed in any of the blood measurements of any of the steers. An additional pair of steers was fed the experimental diet with or without added sulfate to compare the ruminal H2S gas concentrations estimated by H2S detector tubes with those estimated by a different method of analysis utilizing charcoal trapping of H2S, conversion to sulfate, and measurement of the sulfate. Both methods yielded comparable estimates of H2S concentration. Overall, these data indicate that changes in rumen gas cap H2S concentrations are larger than changes in rumen fluid sulfide concentration and that estimation of rumen gas cap H2S concentration may be a practical approach to detecting pathologic increases in ruminal H2S gas. This simple, rapid, minimally invasive method should be useful for estimating the H2S content of ruminal gas under field conditions.

Trace elements and prion diseases: a review of the interactions of copper, manganese and zinc with the prion protein

Transmissible spongiform encephalopathies (TSEs) are a family of neurodegenerative diseases characterized by their long incubation periods, progressive neurological changes, and spongiform appearance in the brain. There is much evidence to show that TSEs are caused by an isoform of the normal cellular surface prion protein PrPC. The normal function of PrPC is still unknown, but it exhibits properties of a cupro-protein, capable of binding up to six copper ions. There are two differing views on coppers role in prion diseases. While one view looks at the PrPC copper-binding as the trigger for conversion to PrPSc, the opposing viewpoint sees a lack of PrPC copper-binding resulting in the conformational change into the disease causing isoform. Manganese and zinc have been shown to interact with PrPC as well and have been found in abnormal levels in prion diseases. This review addresses the interaction between select trace elements and the PrPC.

Brain enzyme and clinical alterations induced in rats and mice by nitroaliphatic toxicants

The effects of a single subcutaneous (s.c.) injection of the nitroaliphatic toxicants 3-nitropropanol (NPOH) and 3-nitropropionic acid (NPA) dissolved in physiological saline solution were studied in mice and rats, respectively. Clinical signs observed in both NPOH-treated mice and NPA-treated rats included depression, abnormal motor activity, and recumbency. Succinate dehydrogenase (SDH) activity, demonstrated histochemically in frozen brain sections, was markedly reduced in intoxicated mice and rats. The SDH activity of mitochondrial preparations from brains of intoxicated mice and rats was diminished to 18-24% of control values, although the activity of another mitochondrial flavoprotein enzyme, alpha-glycerophosphate dehydrogenase (alpha-GPDH), was not altered.

Canine Liver Iron, Copper, and Zinc Concentrations and Association with Histologic Lesions

Concentrations of iron, copper, and zinc were measured in livers of 95 dogs that were suspected of having liver disease. Iron concentrations ranged from 177 to 7,680 ppm (dry weight basis); 54 dogs had iron concentrations greater than the normal concentration of 1,200 ppm. Iron stores were present in Kupffer cells and macrophages but not hepatocytes. The dogs did not have lesions of hemochromatosis. Dogs with high liver iron tended to have high liver copper and inflammatory lesions. High liver copper concentrations usually were associated with hepatocellular necrosis and fibrosis. High liver zinc was found in only 5 animals and was accompanied by histologic inflammatory lesions in one. In humans, increased iron concentration in the liver exacerbates liver damage caused by a variety of insults, and the same may be true for dogs.

Safety and efficacy of high-dose fomepizole compared with ethanol as therapy for ethylene glycol intoxication in cats.

OBJECTIVE To determine the safety and efficacy of high-dose fomepizole compared with ethanol (EtOH) in cats with ethylene glycol (EG) toxicosis. DESIGN Prospective study. SETTING University veterinary research laboratory. ANIMALS Thirteen cats. INTERVENTIONS Two cats received injections of high-dose fomepizole (Study 1). Three cats received lethal doses of EG and fomepizole treatment was initiated 1, 2, or 3 hours later (Study 2). Eight cats received a lethal dose of EG and were treated with fomepizole or EtOH (Study 3). Cats treated with fomepizole received 125 mg/kg IV initially, then 31.25 mg/kg at 12, 24, and 36 hours. Cats treated with EtOH received 5 mL of 20% EtOH/kg IV initially, then every 6 hours for 5 treatments, then every 8 hours for 4 treatments. Cats also received fluids and supportive therapy as needed. MEASUREMENTS AND MAIN RESULTS Clinical signs were monitored and serial blood analyses performed. Cats receiving fomepizole experienced mild sedation but no biochemical evidence of toxicity. Cats receiving fomepizole for EG intoxication survived if therapy was initiated within 3 hours of EG ingestion. One of the 6 developed acute renal failure (ARF) but survived. Only 1 of the 3 cats treated with EtOH 3 hours following EG ingestion survived; 2 developed ARF and were euthanized. Cats treated 4 hours following EG ingestion developed ARF, whether treated with EtOH or fomepizole. CONCLUSIONS Fomepizole is safe when administered to cats in high doses, prevents EG-induced fatal ARF when therapy is instituted within 3 hours of EG ingestion, and is more effective than treatment with EtOH.

Iatrogenic Copper Toxicosis Induced by Administering Copper Oxide Boluses to Neonatal Calves

Iatrogenic copper toxicosis is often a problem in adult sheep but may also occur in cattle.10 Copper poisoning has been reported in veal calves fed milk replacer with various copper-containing hematinics.14 Calves from 3 to 45 days of age fed milk replacer containing 10 or 50 ppm copper on a dry matter basis had similar average daily weight gain, while those fed 200 and 500 ppm copper had decreased weight gain. Some calves fed 1,000 ppm copper milk replacer died, while those that survived demonstrated poor weight gain.9 This paper reports copper toxicosis in calves, aged 6–8 weeks, from 8 cow-calf herds where copper oxide bolusesa were administered to calves within the first 48 hours after birth. Seven herds in western Nebraska and 1 herd in northern Wyoming reside in areas where forages are generally considered to be copper deficient.5 In previous years, supplementation included access to a high-copper mineral supplement and copper glycinate injections administered to newborn calves. The producers injected newborn calves with copper glycinate, believing that copper enhanced general health and decreased neonatal disease. Since copper glycinate was no longer available, the administration of copper oxide boluses was recommended to the producers in lieu of copper glycinate injections. The product’s label states, ‘‘Copper Supplement for Calves from 150 to 500 lbs. bodyweight.’’ In the 8 herds, 7.1% of the neonatal calves supplemented with copper oxide boluses as neonates died of apparent copper toxicosis at 6–8 weeks of age. Ratios of the number of deaths to the total number of calves given the copper oxide boluses for each of the eight herds are as follows: 69/243, 20/550, 16/498, 11/75, 6/175, 9/48, 2/50, and 11/385. Clinical signs, reported by the producers or practitioners, varied from none to lethargy, pale or icteric mucous membranes, and bloody urine. Necropsy findings revealed mild to severe jaundice, dark kidneys, and bloody urine. Histologic lesions in the liver were consistent with acute copper toxicosis. The most prominent change was extensive

Studies on urolithiasis: XII. Association of urine polyelectrolytes

Abstract The property of molecular association of urine polyelectrolytes (UPE) consisting of proteins and peptides isolated from the urine of lambs fed on calculus- and non-calculus-provoking rations has been investigated. The UPE showed a variation in degree of association according to the ration and the ionic media in which they were dissolved. There was a greater degree of association in: (1) the UPE in the presence of calcium than magnesium ions, (2) the UPE of the calculus-provoking than the non-calculus-provoking rations, and (3) the UPE of the small molecular weight fraction (less than 5000) than the larger molecular weight fraction (greater than 5000). The UPE seemed to be in more dissociated forms in the presence of NaCl, KCl, and Na 2 HPO 4 . Dimethyl sulfoxide, which is effective in reducing the incidence of urolithiasis, appeared to be able either to prevent the further association of UPE molecules or to keep the associated molecules in solution. The results of this study showed that the highly associated urine polyelectrolytes, proteins as well as peptides, had apparently contributed to the cause of urinary calculus formation by serving as the calculus matrix.

Comparison of Four Methods for Forage Nitrate Analysis

Twenty forage samples were collected and selected for variation in nitrate content. Each forage sample was analyzed 4 times by 4 different methods: diphenylamine spot plate, spectrophotometric, nitrate-selective electrode, and high-performance liquid chromatographic. Five feed extracts were spiked with 2 different amounts of nitrate and analyzed by each method. The spectrophotometric and nitrate-selective electrode had similar percent recoveries, which were close to 100%. The nitrate-selective electrode method had the least variation of the 4 methods. The diphenylamine spot plate method had the poorest average recovery, greatest variation, and was the least accurate. The average coefficients of variation for all samples within a method were 15%, 12%, 6.4%, and 16% for the diphenylamine spot plate, spectrophotometric, nitrate-selective electrode, and high-performance liquid chromatographic methods, respectively. The variation in the nitrate-selective electrode method was lower (P < 0.05) than the other methods. The results from this study suggest that the nitrate-selective electrode method is more accurate and precise than the other methods of analysis tested.

Alanine: a toxicity study

Male and female rats of weanling age were fed a basal ration containing 0, 5, 10, or 20% alanine for 26 weeks. When alanine intake increased, urinary alanine increased approximately 100- to 1000-fold and serum alanine increased approximately 50-fold. Increased alanine intake also caused changes in the blood chemistry as follows (p < 0.05). Plasma pyruvate and triglycerides were decreased in both male and female cats. Blood ammonia was increased in the males, but there was no change in the females. Plasma lactate was decreased in the females, while there was no changes in the males. The opposite was true for plasma cholesterol, which was decreased in the males and remained unchanged in the females. Rats fed rations with alanine added had steady body weight gains. However, the weight gain of the groups fed 20% alanine was 20–30% less than those fed 5 and 10% alanine. Pathological changes were not observed upon examination of the rats at termination of the study. Feeding of alanine up to 20% in the ration to male and female rats for 26 weeks did not appear to affect their general physical condition.

Alcohols and Glycols

Ethanol and methanol are primary alcohols, and isopropanol is a secondary alcohol. Glycols have two hydroxyl groups in their molecules and are dihydric. Ethylene glycol (EG) is the most common glycol responsible for poisonings, and EG poisoning is significantly more common in domestic animals than is alcohol toxicosis. Propylene glycol and butylene glycol are much less toxic than EG. The chemical and metabolic properties of the previously mentioned alcohols and glycols are discussed in this chapter. Diagnoses and treatment options are also given for each. Ethylene glycol toxicity is covered extensively, and its treatment with fomepizole is discussed.