Bioactivation of cyanide to cyanate in sulfur amino acid deficiency: relevance to neurological disease in humans subsisting on cassava.

Neurological disorders have been reported from parts of Africa with protein-deficient populations and attributed to cyanide (CN-) exposure from prolonged dietary use of cassava, a cyanophoric plant. Cyanide is normally metabolized to thiocyanate (SCN-) by the sulfur-dependent enzyme rhodanese. However, in protein-deficient subjects where sulfur amino acids (SAA) are low, CN may conceivably be converted to cyanate (OCN-), which is known to cause neurodegenerative disease in humans and animals. This study investigates the fate of potassium cyanide administered orally to rats maintained for up to 4 weeks on either a balanced diet (BD) or a diet lacking the SAAs, L-cystine and L-methionine. In both groups, there was a time-dependent increase in plasma cyanate, with exponential OCN- increases in SAA-deficient rats. A strongly positive linear relationship between blood CN- and plasma OCN- concentrations was observed in these animals. These data are consistent with the hypothesis that cyanate is an important mediator of chronic cyanide neurotoxicity during protein-calorie deficiency. The potential role of thiocyanate in cassava-associated konzo is discussed in relationship to the etiology of the comparable pattern of motor-system disease (spastic paraparesis) seen in lathyrism.

Sodium cyanate alters glutathione homeostasis in rodent brain: relationship to neurodegenerative diseases in protein-deficient malnourished populations in Africa.

Sodium cyanate, a neurotoxic chemical in rodents, primates and humans, is implicated in neurodegenerative disorders in protein-deficient populations subsisting in parts of Africa on the cyanogenic plant cassava. The molecular and cellular mechanisms of cyanate neurotoxicity are not understood. This study investigates the effect of sodium cyanate on glutathione (GSH) homeostasis in rodent brain and liver in vitro and in vivo. GSH levels in mouse brain were rapidly, time- and dose-dependently decreased following intraperitoneal administration of 100, 200 or 300 mg/kg sodium cyanate. By contrast, GSH disulfide (GSSG) levels were increased and GSH/GSSG ratios were decreased in a dose-dependent manner in rat brain. Sodium cyanate depleted GSH levels in all regions of mouse brain. Brain glutathione reductase activity was dose-dependently inhibited, while glutathione peroxidase activity was not affected by sodium cyanate. The disruption of GSH homeotasis, as evidenced by reduced tissue GSH/GSSG ratios, likely results from cyanate-induced inhibition of glutathione reductase activity. The results of this study suggest that cyanate neurotoxicity, and perhaps cassava-associated neurodegenerative diseases, are mediated in part by disruption of glutathione homeostasis in neural tissue.

Dietary deficiency of cystine and methionine in rats alters thiol homeostasis required for cyanide detoxification.

Nutritional status is an important factor in modulating the metabolic fate of xenobiotics. Sulfur amino acid (SAA) deficiency has been proposed as a risk factor for human neurological diseases among protein-poor populations subsisting on the cyanophoric plant cassava. Female Sprague-Dawley rats were used to develop and define a model of SAA deficiency for use in future studies examining cassava-related neurotoxicity. Rats were kept in metabolic cages for 7-21 d and fed a balanced diet (BD) of known composition or a comparable diet selectively deficient in methionine and cystine (SAA-free diet). Animals fed the SAA-free diet failed to thrive, lost body weight, excreted porphyrinic materials, and showed a steep and persistent reduction of urinary inorganic sulfate. In contrast, animals on the BD gained body weight and maintained baseline output of urinary inorganic sulfate. Urinary thiocyanate excretion did not differ between groups, but plasma thiocyanate concentrations reached double that in SAA-deficient rats. Increased plasma thiocyanate suggests mobilization of sulfur amino acids from endogenous sources. Liver glutathione and blood cyanide concentrations were similar in animals on the BD and the SAA-deficient diet. In summary, a diet free of methionine and cystine results in increased retention of inorganic sulfur as thiocyanate and a near absence of inorganic sulfur excretion in urine.

A light and electron microscopic study of sarcocysts in a horse.

The structure of sarcocysts in a horse is presented. Light microscopic examination revealed that the maximum cyst dimensions were 136 X 990 micrometers and the cyst walls were striated and 1 to 3 micrometers thick. Electron microscopic examination revealed that the "cyst wall" was formed by villuslike protrusions of the parasitophorous vacuole's primary wall. A unique feature was the presence and arrangement of microtubules within the parasitophorous vacuole. Thirty-four to 55 microtubules extended from the apical tips and sides of each villus and passed through the ground matrix to form junctions with the outer pellicle membrane of bradyzoites and metrocytes located at the margins of the cyst. The average dimensions of the bradyzoites were 3.2 X 14.2 micrometers.

Megaesophagus in 15 llamas: a retrospective study (1985-1993).

Megaesophagus was diagnosed in 15 llamas on the basis of survey and contrast radiography. Age of onset ranged from 13 months to 9.5 years. Clinical signs varied, with salivation being the most common; regurgitation or dysphagia were noted in only 33% of the cases. Duration of the disorder ranged from 1 week to 5 years. Organophosphate toxicity was the cause of megaesophagus in 1 llama. While most cases were of unknown etiology, the 3 with histological abnormalities included 1 with vagal neuropathy and 2 with a degenerative myopathy of esophageal muscles. The causes in most were undetermined.

Electrophysiologic studies of the thoracic limb of the horse.

The cutaneous innervation of the thoracic limb was investigated in 18 barbiturate-anesthetized horses, using electrophysiologic techniques. The cutaneous area (CA) innervated by each cutaneous nerve was delineated in at least 4 horses by stroking the hairs with a small watercolor brush while recording from the nerve. Mapping of adjacent CA revealed areas of considerable overlap. The part of a CA of a given nerve supplied only by that nerve is referred to as its autonomous zone (AZ). In contrast to the standard textbook illustrations cutaneous branches of the axillary, radial, musculocutaneous, and ulnar nerves overlapped extensively in the antebrachium. Clinically testable AZ were found in the antebrachium for the caudal cutaneous antebrachial nerve of the ulnar nerve and in the carpus and manus for the cutaneous branches of the median, ulnar, and musculocutaneous nerves; AZ were not found for the cutaneous branches of the radial and axillary nerves.

Comparison of sensory nerve conduction velocities in horses versus ponies.

Normal sensory nerve conduction velocity (SNCV) values in 8 ponies and 8 horses were compared by use of a percutaneous signal-averaging technique. Nerve fibers evaluated included those in the medial and lateral palmar and plantar digital nerves. Mean SNCV values were significantly slower (P less than 0.0002) for horses, compared with those values for ponies. Animal height and nerve segment length were inversely related to SNCV consistently. The SNCV values were affected by surface skin temperature by a factor of approximately 1.2 m/s change for 1 degree C change in temperatures from 35 C. The ability to calculate warning limits to define those SNCV values in normal and abnormal ranges were developed from these data for both ponies and horses.

Variations of serum vitamin E, cholesterol, and total serum lipid concentrations in horses during a 72-hour period.

Fluctuations of serum vitamin E (alpha-tocopherol), cholesterol, and total lipids were monitored in 12 horses at 3-hour intervals for 72 hours. Mean coefficients of variation were 12, 5, and 15%, respectively. Statistical analyses were used to conclude that instrumentation error was accountable for only a small portion of the vitamin E variation. Results indicated that a single serum sample assay is an unsatisfactory indicator of vitamin E status in horses. These data have clinical application in the evaluation of horses suspected to be affected with equine degenerative myeloencephalopathy. The large variance of serum total lipids and the lack of correlation of it with serum vitamin E over time preclude the use of vitamin E/serum total lipids ratio in assessing vitamin E status.

Serially determined plasma alpha-tocopherol concentrations and results of the oral vitamin E absorption test in clinically normal horses and in horses with degenerative myeloencephalopathy.

Plasma alpha-tocopherol (vitamin E) values were monitored serially in 9 foals sired by a stallion with equine degenerative myeloencephalopathy (EDM) and in 5 age-matched control foals (sired by a clinically normal stallion) raised in the same environment for the first year of life. Clinical evaluation determined that 8 of the 9 foals sired by the stallion with EDM had neurologic deficits consistent with the disease on one or more occasions during the study period, whereas control foals had normal gait. From 6 weeks to 10 months of age, plasma alpha-tocopherol values in foals with signs of EDM were significantly (P less than 0.001) lower than those in control foals. An oral vitamin E absorption test was performed, and results for 8 of the affected horses and the affected stallion were compared with results for 4 of the monitored control horses and 4 additional control horses. Significant differences were not evident in any of the absorption indices. On the basis of data from this study and supported by reported prophylactic and therapeutic benefits of supplemented vitamin E, low plasma concentration of vitamin E is concluded to be a factor in the development of EDM in the first year of life of hereditarily predisposed foals. It was also concluded that the significantly lower alpha-tocopherol values seen in the foals in this study did not reflect a primary gastrointestinal tract absorption problem.

Evaluation of the oral vitamin E absorption test in horses.

An oral vitamin E absorption test used in human beings was modified for use in horses. The most appropriate techniques with which to measure gastrointestinal tract absorption of vitamin E (alpha-tocopherol) in horses were developed. Vitamin E was administered orally, and serum values of alpha-tocopherol were measured by use of high-performance liquid chromatography at 0, 3, 6, 9, 12, and 24 hours after vitamin E administration. Variables included comparison of 2 dosages (45 and 90 IU/kg of body weight), routes of administration, and absorption dynamics of 3 preparations of dl-alpha-tocopherol. Absorption of the 2 doses of dl-alpha-tocopherol acetate indicated a dose response; the area under the curve at 24 hours (AUC24) was 4.3 micrograms.h/ml for the 45-IU/kg dose and 32.2 micrograms.h/ml (P less than 0.01) for the 90-IU/kg dose. Maximal absorption was apparent when vitamin E was naturally consumed in grain, compared with administration of identical preparations by stomach tube or paste. In the same horses, dl-alpha-tocopherol and dl-alpha-tocopherol acetate plus polyethylene glycol had statistically similar absorption curves and both had significantly greater AUC24, compared with dl-alpha-tocopherol acetate; values for the 3 compounds were 23.6, 25.8, and 12.6 micrograms.h/ml, respectively. The AUC24 varied between individual horses, but time of peak value was consistently observed between 6 and 9 hours.(ABSTRACT TRUNCATED AT 250 WORDS)

Sensory nerve conduction velocities in forelimb of ponies.

Normal nerve conduction velocity values in 10 ponies were determined for sensory nerve fibers in the median and ulnar nerves. A percutaneous signal-averaging technique was developed and used. Medial and lateral palmar digital nerves on the abaxial surface of the proximal sesamoid bones were used as the sites for percutaneous stimulation, whereas recording sites included the medial and lateral palmar nerves just distal to the carpus and the median and ulnar nerves in the middle of the radius. Sensory nerve conduction velocities can be evaluated simply and clinically in the limbs of horses, using percutaneous signal-averaging techniques.

Pharmacokinetic disposition of dimethyl sulfoxide administered intravenously to horses.

Dimethyl sulfoxide (DMSO) was administered IV to 6 Thoroughbred horses at 2 dosages: 1.0 g/kg and 0.1 g/kg. The pharmacokinetics seemed linear, with biological half-lives of 8.6 +/- 0.3 hours and 9.8 +/- 2.2 hours for the 1.0 g/kg and 0.1 g/kg dosages, respectively. This was further substantiated by mean residence times of 9.8 +/- 0.44 hours and 13.8 +/- 4.25 hours, areas under the curve of 12.55 +/- 1.42 mg/ml/hr and 1.63 +/- 0.49 mg/ml/hr, and the clearances of 0.081 +/- 0.009 L/kg/hr and 0.066 +/- 0.022 L/kg/hr for the large and small dosages, respectively. At 12 hours after 1.0 g/kg was administered, 26.6% of the DMSO dose was excreted unchanged into the urine; at 12 hours after 0.1 g/kg was administered, 25.3% of the DMSO dose was excreted unchanged into the urine. It was predicted that 29.4% and 40.6% of the total DMSO dose would be excreted into the urine for the 1.0 g/kg and 0.1 g/kg dosages, respectively. A 10% DMSO concentration in normal saline solution was safe to give as rapid IV infusion. Slow administration is recommended for more concentrated solutions. Based on the half-life, DMSO should be administered 2 times a day IV for the treatment of increased intracranial pressure and/or cerebral edema in horses.

Variability of alpha-tocopherol values associated with procurement, storage, and freezing of equine serum and plasma samples.

Recent evidence concerning the pathogenesis of equine degenerative myeloencephalopathy indicated that low blood alpha-tocopherol values are a factor in the disease process. Variables that could be introduced by a veterinarian procuring, transporting, or storing samples were evaluated for effects on alpha-tocopherol concentration in equine blood. These variables included temperature; light; exposure to the rubber stopper of the evacuated blood collection tube; hemolysis; duration of freezing time, with and without nitrogen blanketing; and repeated freeze/thaw cycles. It was found that hemolysis caused the greatest change in high-performance liquid chromatography-measured serum alpha-tocopherol values, with mean decrease of 33% (P < 0.001). Lesser, but significant (P < 0.01) changes in serum alpha-tocopherol values were an approximate 10% decrease when refrigerated blood was left in contact with the red rubber stopper of the blood collection tube for 72 hours and an approximate 5% increase when blood was stored at 20 to 25 C (room temperature) for 72 hours. Repeated freeze/thaw cycles resulted in a significant (P < 0.05) 3% decrease in alpha-tocopherol values in heparinized plasma by the third thawing cycle. Freezer storage for a 3-month period without nitrogen blanketing resulted in slight (2%) decrease in mean serum alpha-tocopherol values, whereas values in serum stored for an identical period under nitrogen blanketing did not change. A significant (P < 0.001) mean decrease (10.3%) in alpha-tocopherol values was associated with freezer (-16 C) storage of nitrogen blanketed serum for 6 months.(ABSTRACT TRUNCATED AT 250 WORDS)

Cervical dorsal spondylosis with spinal cord compression in a black swan (Cygnus atratus).

Cervical dorsal spondylosis with spinal cord compression in a black swan (Cygnus atratus) was confirmed radiographically and morphologically. Clinically ataxia was associated. Noninflammatory, degenerative changes of the synovial joint cartilage were associated with the spondylosis.

Factors affecting prerace dehydration and performance of racing greyhounds.

Several factors, including age, sex, race number, post position, and race class, were evaluated for relationships to prerace percentage body weight loss and performance in all Greyhounds racing during August 1983 in Oregon. The incidence of percentage body weight loss greater than or equal to 2.5% was low (5%). Race number had a direct effect on weight loss; the later the dogs raced, the more weight loss they experienced. Female dogs were 3 times more likely to lose greater than 2.4% of body weight than males. All dogs experiencing greater than 2.4% body weight loss were 2 times more likely to finish in the first 3 places when racing in the first 5 races overall. In addition, males losing greater than 2.4% of body weight performed better than females when racing together in the final 6 races. Males appeared to be better performers than females, as they were twice as likely to be in class A races. However, once in the race, males and females performed equally.

Chronic encephalomyelitis caused by canine distemper virus in a Bengal tiger.

A chronic progressive neurologic disease was observed and monitored for 18 months in a young, tamed Bengal tiger. Clinical, serologic, and neuropathologic evidence of canine distemper virus infection was seen. Clinical signs included convulsions, myoclonus, and slowly progressive ataxia. Marked increases in neutralizing antibodies against canine distemper virus were seen in the serum and cerebrospinal fluid. Neuropathologic findings were nonsuppurative meningoencephalomyelitis, with perivascular cuffing, demyelination, and inclusion bodies typical of canine distemper virus. It was concluded that, in light of this case and an earlier report of canine distemper in lion cubs, vaccination of this subgroup of carnivores with a killed vaccine may be beneficial if exposure to other animals susceptible to canine distemper is anticipated.

Use of electromyography in a cow with esophageal paralysis.

Electromyography of the esophageal musculature of a cow that had been regurgitating and losing weight after correction of an esophageal obstruction was suggestive of unilateral denervation. Radiography before and after oral administration of barium sulfate revealed a dilated terminal portion of the thoracic esophagus, suggestive of a focal motility problem. Electromyography was performed on the esophageal musculature by positioning the electrode through the rumen fistula and into the thoracic esophagus and by positioning the electrode percutaneously with the aid of a tube placed in the cervical esophagus. Numerous fibrillation potentials and sharp epsilon-positive waves were detected in the muscles of the left side of the distal portions of the cervical and thoracic esophagus. During hospitalization, the cow was given alfalfa pellets, ground corn, and sodium bicarbonate through the rumen fistula 3 times each day for several weeks to maintain body weight.

Effects of racing on hematologic and serum biochemical values in greyhounds.

Blood samples were collected on nonracing days from 57 racing Greyhounds at 2 weeks, 8 weeks, 13 weeks, and 16 weeks after the beginning of the racing season. Hematologic and biochemical tests were performed to detect marked changes induced by stress of racing. In general, these Greyhounds were healthy. Rhabdomyolysis was detected in one dog. In several other dogs, possible subclinical muscle injury was identified by increased serum creatine kinase activities. Mean serum Ca concentrations tended to decrease during the racing season. None of the tests was a good predictor of racing performance. Mean values for several hematologic and biochemical tests were different from those of other breeds of dogs.

Atypical pneumonia associated with ryegrass staggers in calves.

A group of 6- to 8-month-old calves developed head tremors, stiff gait, and staggering after consuming ryegrass straw that contained 3,711 micrograms of lolitrem-B/ kg. Signs were consistent with ryegrass staggers syndrome. At necropsy, all calves examined had atypical interstitial pneumonia, with marked emphysema and bullae. Infectious organisms and pneumotoxins were not identified. Experimentally, feeding the same ryegrass straw to age-matched calves induced similar neurologic signs, but did not result in pneumonic lesions. The high concentration of lolitrem-B in the straw or other, undefined factors, such as feed changes, may have contributed to the atypical interstitial pneumonia in the naturally exposed calves.

Palatal myositis in horses with dorsal displacement of the soft palate.

The histologic and histochemical features of palatine muscles from 53 horses were studied; 25 of the horses were racehorses that had upper airway obstruction associated with dorsal displacement of the soft palate and 28 of the horses did not have any respiratory disorders and served as controls. Pathologic features observed included myonecrosis, phagocytosis, mononuclear cell infiltration of perimysial connective tissue, alkaline phosphatase-positive myofibers, and myofibers with cytoarchitectural changes that included irregular staining of the intermyofibrillar sarcoplasm and sarcoplasmic masses. These histopathologic features were judged to be indicative of myositis. Those features were found in both control horses and horses with dorsal displacement of the soft palate; however, their prevalence was higher in horses with dorsal displacement of the soft palate. For the control horses as well as the horses with dorsal displacement of the soft palate, the inflammatory changes were more prevalent in older horses. The finding of myositis suggests that palatal muscle weakness may contribute to the development of dorsal displacement of the soft palate; however, the myositis might have been secondary to trauma associated with displacement of the soft palate. We could not distinguish between these 2 possibilities. A large number of horses with dorsal displacement of the soft palate also had concurrent pharyngeal lymphoid hyperplasia. Extension of the mucosal inflammatory changes associated with pharyngeal lymphoid hyperplasia into the underlying palatine muscle might have accounted for the myositis.