Novel inhibitors of sterol C-14 demethylase and Δ14 Reductase/Δ8 → Δ7 isomerase for cereal disease control

The activity of five experimental fungicides combining structural elements responsible for sterol C-14 demethylase inhibition and sterol nuclear double-bond transformations has been investigated by examining sterol accumulation in Ustilago maydis (DC.) Corda, inhibition of sterol-biosynthesis enzymes in Saccharomyces cerevisiae Meyer using a cell-free system and protective activity in cereals against Erysiphe graminis DC. and Puccinia coronata Corda. Combining the fenpropidin/fenpropimorph basic structure with a pyridine moiety offered no advantage in fungicidal activity. However, the combination of the pyrifenox structure with a morpholine moiety yielded a compound which was a good inhibitor of C-14 demethylase and Δ⁸ → Δ⁷ isomerase in vitro and gave good cereal protection.     

The dietary toxicity of flocoumafen to hens: Elimination and accumulation following repeated oral administration

In a dietary toxicity study, laying hens received a diet containing the rodenticide flocoumafen at concentrations of 1.5, 5, 10 and 50 mg kg^?1 for five consecutive days. The LC₅₀ at termination following a 28-day observation period was 16.4 mg kg^?1. Livers of birds which received doses of flocoumafen between 5 and 50 mg kg^?1 had concentrations of flocoumafen (1.5 nmol g^?1) that were independent of dose. The data indicate the presence in hen liver of a saturable high-affinity flocoumafen binding site with similar characteristics and capacity to that of the quail and rat. Residues of flocoumafen in samples of breast and leg muscle were low in all exposure groups. Higher, dose-related residues were found in samples of abdominal fat and skin-associated fat and there was a clear demonstration of the transfer of dose-related residues into eggs. In a separate study in which hens were dosed with [¹⁴C]flocoumafen for five consecutive days at a daily rate of 1 and 4 mg kg^?1 body weight, the majority (68 %) of the daily radioactive dose was eliminated over the following 24 hours via excreta. Residues in liver at death or when killed accounted for < 1 % of the cumulative administered radioactivity. Residues in eggs were located primarily in the yolk with maximum concentrations 1.0 mg kg^?1 or 0.18% of the low dose; 2.1 mg kg^?1 or 0.06% of the high dose as [¹⁴C]flocoumafen equivalents were observed at 10 days after start of dosing. Some 40 % of the total activity in the yolk was unchanged flocoumafen.     

Serum total and ionized magnesium concentrations and urinary fractional excretion of magnesium in cats with diabetes mellitus and diabetic ketoacidosis

OBJECTIVE: To determine magnesium (Mg) status in cats with naturally acquired diabetes mellitus (DM) and diabetic ketoacidosis (DKA), evaluate changes in Mg status after treatment for DKA, and correlate Mg status with systemic blood pressure and degree of glycemic control. DESIGN: Case series and cohort study. ANIMALS: 12 healthy cats (controls), 21 cats with DM, and 7 cats with DKA. PROCEDURE: Serum total magnesium (tMg) and ionized magnesium (iMg) concentrations and spot urinary fractional excretion of magnesium (FEmg) were determined, using serum and urine samples obtained from all cats when they were entered in the study and from cats with DKA 12, 24, and 48 hours after initiating treatment. Indirect blood pressure and degree of glycemic control were determined in 10 and 21 cats with DM, respectively. RESULTS: Initially, 2 and 13 cats with DM and 1 and 4 cats with DKA had serum tMg and iMg concentrations, respectively, less than the low reference limit (mean-2 SD) determined for controls. In cats with DKA, serum tMg concentration decreased significantly over time after initiating treatment. Urinary FEmg was significantly higher in cats with DM or DKA, compared with controls. Systemic hypertension was not detected nor was there a correlation between Mg status and degree of glycemic control in cats with DM. CONCLUSIONS AND CLINICAL RELEVANCE: Hypomagnesemia was a common finding in cats with DM and DKA and was more readily identified by measuring serum iMg concentration than tMg concentration. The clinical ramifications of hypomagnesemia in such cats remain to be determined.     

ULTRASONOGRAPHIC FINDINGS IN CHOLECYSTOKININ-INDUCED PANCREATITIS IN DOGS

Pancreatitis can be induced in dogs by intravenous infusion of supraphysiologic doses of synthetic cholecystokinin octapeptide (CCK-8). Eight anesthetized female beagles were given either CCK-8 or saline in a randomized, blinded fashion and had abdominal ultrasonography to study the development of pancreatic lesions. Pancreatic lesions were apparent 2 hours after the start of CCK-8 infusion and included swelling, interlobular and subcapsular fluid accumulation and patchy hypoechogenicity of the gland parenchyma. CCK-8 had a variable effect on gallbladder emptying. No signs of biliary obstruction or duodenal lesions were identified. Dogs given CCK-8 had severe edematous pancreatitis at necropsy six hours after the start of the infusion. Compared to the oleic acid model of pancreatitis, CCK-8 infusion induces a rapid onset of pancreatitis and an ultrasonographic appearance that reflects diffuse edema of the gland. The short time-scale of the experiment may account for the relative absence of secondary lesions affecting the biliary tract or duodenum compared to the naturally-occurring disease.     

Effects of Dietary Protein Concentration on Growth, Survival, and Body Composition of Muskellunge Esox musquinongy and Tiger Muskellunge Esox masquinongy × E. luscius Fingerlings

Growth rate, survival and body composition of muskellunge Esox musquinongy (initial mean total length = 125 mm) and tiger muskellunge E. masquinongy × E. lucius (initial mean total length = 115 mm) fed semi-purified diets differing in protein level from 31 to 40% and 34 to 45%, respectively, were evaluated in 8-wk trials. The minimum protein level that yielded satisfactory growth rates for muskellunge was 37%, whereas tiger muskellunge growth rates were highest for fish fed a 45% protein diet. Growth differences were caused by changes in protein quantity, not quality, as amino acid ratios were similar for test diets and showed no imbalances among diets. Condition factors for both fishes increased with dietary protein. Survival of muskellunge (73%) and tiger muskellunge (97%) was not pffected by diet type. Body protein increased and fat content decreased in both fishes when fed higher dietary protein. Results suggest that both fishes respond similarly to dietary changes, but that substantial differences exist in protein requirements.     

Heinz Body Formation Associated With Ketoacidosis in Diabetic Cats

Oxidative damage plays an important role in the pathophysiology of diabetes and diabetic complications. Feline hemoglobin is uniquely susceptible to oxidative denaturation; therefore, Heinz body formation is a highly sensitive indicator of in vivo oxidative stress in this species. Heinz bodies also contribute to anemia. We investigated hematological and clinical biochemical changes in 30 cats with spontaneous diabetes mellitus (as compared to 15 healthy control cats) and evaluated the relationship of these changes to erythrocyte oxidative damage. Cats were categorized as ketoacidotic or nonketoacidotic based on their clinical presentation and the presence of urine ketones. Ketoacidotic cats had significantly ( P = .0009) more Heinz bodies (28.3% ± 9.1 %) than nonketotic diabetic cats (6.5% ± 1.60%) and healthy control cats (0.6% ± 0.2%). Percent Heinz bodies in diabetic cats directly correlated with plasma β-hydroxy-butyrate concentration ( r = .622; P = .0002), as well as with serum chloride concentration ( r = -0.576; P = 0.0009) and the number of monocytes ( r = .536; P = .0023). Percent Heinz bodies were negatively correlated with erythrocyte glutathione concentrations. Erythrocyte membrane lipid peroxidation was slightly but not significantly increased in diabetic cats. There were no significant associations between percent Heinz bodies and degree of anemia, hyperglycemia, or glycohemoglobin. These data indicate that ketones are associated with oxidative hemoglobin damage in cats, and suggest that ketone metabolism, ie by cytochrome P450 2E1, may be a potential source of in vivo oxygen radical generation in animals with ketosis.     

Influence of glucosamine on matrix metalloproteinase expression and activity in lipopolysaccharide-stimulated equine chondrocytes

OBJECTIVE: To characterize potential mechanisms of action of glucosamine inhibition of matrix metalloproteinase (MMP) expression and activity in lipopolysaccharide (LPS)-stimulated equine chondrocytes. SAMPLE POPULATION: Chondrocytes cultured from samples of metacarpophalangeal articular cartilage collected from cadaveric limbs of horses. PROCEDURE: The effect of glucosamine on MMP activity in conditioned medium from LPS-stimulated cartilage explants was determined by a colorimetric assay with azocoll substrate. Treatments consisted of negative and positive controls, glucose (50 mM), and glucosamine (50, 25, 6.25, 3, and 1.5 mM). The influence of glucosamine on MMP synthesis was determined in chondrocytes in pellet culture incubated with LPS (20 microg/mL). Concentration of MMP-13 was quantified in spent medium via ELISA; nonspecific MMP activity was determined via azocoll digestion in organomercurial-activated medium. Effects of glucosamine on MMP mRNA concentration in similarly treated chondrocytes were determined by northern blot hybridization with MMP-1, -3, and -13 probes. Statistical analyses were performed with 2-way ANOVA. RESULTS: Glucosamine had no effect on activated MMP activity but inhibited MMP protein expression, as determined by azocoll digestion (glucosamine, 3 to 50 mM) and MMP-13 ELISA (glucosamine, 1.5 to 50 mM). Resting mRNA concentrations for MMP-1, -3, and -13 mRNA were significantly lower in cultures exposed to glucosamine at concentrations of 50 and 25 mM than those of positive controls. CONCLUSIONS AND CLINICAL RELEVANCE: Glucosamine appears capable of pretranslational, and possibly also translational, regulation of MMP expression; data suggest a potential mechanism of action for chondroprotective effects of this aminomonosaccharide.     

Moment arms about the carpal and metacarpophalangeal joints for flexor and extensor muscles in equine forelimbs

OBJECTIVE: To determine whether muscle moment arms at the carpal and metacarpophalangeal joints can be modeled as fixed-radius pulleys for the range of motion associated with the stance phase of the gait in equine forelimbs. SAMPLE POPULATION: 4 cadaveric forelimbs from 2 healthy Thoroughbreds. PROCEDURE: Thin wire cables were sutured at the musculotendinous junction of 9 forelimb muscles. The cables passed through eyelets at each muscle's origin, wrapped around single-turn potentiometers, and were loaded. Tendon excursions, measured as the changes in lengths of the cables, were recorded during manual rotation of the carpal (180 degrees to 70 degrees) and metacarpophalangeal (220 degrees to 110 degrees) joints. Extension of the metacarpophalangeal joint (180 degrees and 220 degrees) was forced with an independent loading frame. Joint angle was monitored with a calibrated potentiometer. Moment arms were calculated from the slopes of the muscle length versus joint angle curves. RESULTS: At the metacarpophalangeal joint, digital flexor muscle moment arms changed in magnitude by < or = 38% during metacarpophalangeal joint extension. Extensor muscle moment arms at the carpal and metacarpophalangeal joints also varied (< or = 41% at the carpus) over the range of joint motion associated with the stance phase of the gait. CONCLUSIONS AND CLINICAL RELEVANCE: Our findings suggest that, apart from the carpal flexor muscles, muscle moment arms in equine forelimbs cannot be modeled as fixed-radius pulleys. Assuming that muscle moment arms at the carpal and metacarpophalangeal joints have constant magnitudes may lead to erroneous estimates of muscle forces in equine forelimbs.     

Antegrade pyelography for suspected ureteral obstruction in cats: 11 cases (1995-2001)

OBJECTIVE: o determine sensitivity and specificity of radiography, ultrasonography, and antegrade pyelography for detection of ureteral obstructions in cats. DESIGN: Retrospective study. ANIMALS: 11 cats. PROCEDURE: Medical records of cats that had radiography, ultrasonography, and antegrade pyelography performed for suspected ureteral obstructions were examined. Ultrasound-guided pyelocentesis and fluoroscopic-assisted antegrade pyelography were performed on 18 kidneys in 11 cats. Obstructive ureteral lesions were confirmed in all cats by surgical or necropsy examination. Sensitivity and specificity of survey radiography, ultrasonography, and antegrade pyelography for identification of ureteral obstructions were calculated. Surgical or necropsy findings were used as the standard for comparison. RESULTS: All cats were azotemic. Mean +/- SD serum creatinine and BUN concentrations were 10.2 +/- 6.1 and 149 +/- 82 mg/dL, respectively. Fifteen of 18 ureters were found to be obstructed at surgery or necropsy. Sensitivity and specificity were 60 and 100% for radiography and 100 and 33% for ultrasonography, respectively, in identification of ureteral obstructions. Leakage of contrast material developed in 8 of 18 kidneys during antegrade pyelography and prevented diagnostic interpretation in 5 of 18 studies. For the 13 diagnostic studies, specificity and sensitivity were 100% by use of the antegrade pyelography technique. Correct identification of the anatomic location of the ureteral obstruction was obtained in 100% of diagnostic antegrade pyelography studies and in 60% of radiography or ultrasonography studies. CONCLUSIONS AND CLINICAL RELEVANCE: Antegrade pyelography can be a useful alternative in the diagnosis and localization of ureteral obstructions in azotemic cats, although leakage of contrast material may prevent interpretation of the study.     

Outcome of and complications associated with prophylactic percutaneous laser disk ablation in dogs with thoracolumbar disk disease: 277 cases (1992-2001)

OBJECTIVE: To determine outcome of and complications associated with prophylactic percutaneous laser disk ablation in dogs with thoracolumbar disk disease. DESIGN: Retrospective study. ANIMALS: 277 dogs. PROCEDURE: Medical records of dogs with a history of thoracolumbar disk disease in which the 7 intervertebral disks from T10-11 through L3-4 were ablated with a holmium-yttrium-aluminum-garnet laser inserted through percutaneously placed needles were reviewed. Complications and episodes of a recurrence of neurologic signs (eg, paresis or paralysis) were recorded. Owners were contacted by telephone for follow-up information. RESULTS: Nine of 262 (3.4%) dogs for which follow-up information was available had a recurrence of paresis or paralysis. Follow-up time ranged from 1 to 85 months (mean, 15 months); signs recurred between 3 and 52 months (mean, 15.1 months) after laser disk ablation. Acute complications occurred in 5 dogs and included mild pneumothorax in 1 dog, an abscess at a needle insertion site in 1 dog, and proprioceptive deficits in 3 dogs, 1 of which required hemilaminectomy within 1 week because of progression and severity of neurologic signs. One dog developed diskospondylitis. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that prophylactic percutaneous laser disk ablation is associated with few complications and may reduce the risk of recurrence of signs of intervertebral disk disease in dogs.