Turkey knockdown in successive flocks.

Turkey knockdown was diagnosed in three of five flocks of hen turkeys on a single farm within a 12-mo period. The age of birds in the flocks affected ranged from 6 wk 2 days to 7 wk 4 days. The attack rate ranged from 0.02% to 0.30% with a case fatality rate in affected birds ranging from 0 to 74%. The diagnosis was made on the basis of clinical signs and histopathologic lesions associated with knockdown. The feed in all flocks contained bacitracin methylene disalicylate and monensin (Coban). Affected birds were recumbent, demonstrated paresis, and were unable to vocalize. Postmortem examination revealed few significant lesions although pallor of the adductor muscles and petechiation in adductor and gastrocnemius muscles were noted. Birds that had been recumbent for extended periods were severely dehydrated. Consistent microscopic lesions included degeneration, necrosis, and regeneration of adductor, gastrocnemius, and abdominal muscles. No lesion in cardiac tissue was noted. Results of our investigation indicated that changes in water consumption, vitamin E status, and brooder to finisher movement correlated with the occurrence of knockdown. Turkey knockdown was defined in 1993 as any condition identified in a turkey flock that has affected the neuromuscular system to a degree that a turkey is unable to walk or stand. This definition was later modified to...neuromuscular or skeletal systems to a degree that a turkey is unable to walk or stand properly. Knockdown may be associated with numerous feed, management, or disease factors alone or in combination. Dosage of monensin, feed restriction/gorging, water restriction, heat stress, copper, mycotoxins, sodium chloride in feed, and sulfa drugs have all been suggested as contributing factors; however, laboratory studies to duplicate this have not been successful. This report presents observations from a single farm at which three of five hen flocks in a single year experienced knockdown. When a flock was reported as affected, a detailed investigation was initiated within 3 hr. The fifth flock was followed on a twice weekly basis from 0 to 8 wk of age to determine if initiating events were evident, but knockdown did not occur.

Alterations in levels of various host antioxidant factors in turkey knockdown syndrome.

Five components (selenium, glutathione peroxidase, copper, superoxide dismutase, and vitamin E) of the antioxidant system of turkey poults were examined to determine if they play any role in the knockdown (KD) syndrome. All flocks were provided with feed formulated to contain monensin at 54-60 g/ton. Flock data were analyzed as a case-control study with three treatment groups (KD-affected and unaffected turkey poults from a KD flock and poults from an unaffected flock [control]). Affected turkey poults had lower (P < 0.001) serum vitamin E levels compared with unaffected poults from KD flocks or poults from unaffected flocks. No significant differences were observed for the other parameters evaluated but there was a trend towards lower copper and superoxide dismutase values in affected birds. It appears that serum vitamin E concentrations in turkey poults may play a significant role in susceptibility to or protection against KD syndrome. Other components of the antioxidant system may also be involved, and complex interactions among several body systems may be critical.

Influence of floor space allowance and dietary selenium and zinc on growth performance, clinical pathology measurements and liver enzymes, and adrenal weights of weanling pigs.

Crossbred weanling pigs (n = 96, average initial weight, 8.4 kg) were used in a 6-wk trial using a 2 x 2 x 3 factorial arrangement of treatments to determine the effects of floor space allowance (.28 and .14 m2/pig), dietary Se (40 and 200 ppb), and dietary Zn (30, 80, and 250 ppm) on growth performance, clinical pathology measurements, serum minerals, and enzymes, liver enzymes, and adrenal weights. Pigs (four/pen) were given ad libitum access to feed and water. Body weight and feed consumed were recorded weekly, and heparinized blood samples were taken for the various assays. Three pigs per pen were killed at the end of the trial for gross examination of organs and tissues and for liver enzymes assays. Pigs housed with restricted floor space ate 21% less (P < .001) and grew 18% more slowly (P < .001) than pigs housed with adequate floor space, but their gain:feed ratio was 4% higher (P < .08). Growth performance was not influenced by dietary Se and Zn treatments. There was no mortality in any of the treatments, and no visible gross abnormalities in organs and tissues at necropsy examination, except that more musculoskeletal bruising was observed for pigs housed with adequate floor space. This finding is supported by higher serum K concentration and creatine phosphokinase activity for pigs housed with adequate floor space. Corticosteroid activity and adrenal weights were similar for all treatments. Concentrations of blood Se and glutathione peroxidase were positively related to dietary Se levels, and serum Zn concentration was related to dietary Zn levels. Other effects of dietary Se and Zn on clinical pathology measurements were minimal and usually unexplained. Most two-way interactions of Se and Zn with floor space allowance were nonsignificant, which suggests that the main effects of Se, Zn and floor space were independent. Some hematologic values, serum metabolites, serum minerals, and serum and liver enzymes were decreased or increased, which is suggestive of stress of pigs housed with restricted floor space. However, most values were unchanged, and a few changed in the direction to suggest benefits of restricting space; all values were within an expected normal range.

Influence of supplemental selenium on humoral immune responses in weaned beef calves.

Influence of supplemental Se on humoral immune response was measured in 60 weaned beef calves with marginal blood Se status. Calves were fed a Se-deficient diet consisting of corn silage, corn grain, and soybean meal. Blood Se concentrations, primary and secondary humoral immune responses to hen egg lysozyme inoculation, and weight gain were determined in a 70-day trial. Calves fed 20 mg of Se/kg of mineral mixture ad libitum had lower antibody responses (P less than 0.02), compared with calves fed 20 mg of Se/kg of mineral mixture and given 0.1 mg of Se and 0.22 IU of vitamin E/kg of body weight, IM, or with calves fed 80, 120, 160, or 200 mg of Se/kg of mineral mixture. Calves fed 80, 120, 160, or 200 mg of Se/kg of mineral mixture had higher (P less than 0.001) blood Se concentrations on day 70, compared with calves fed 20 mg of Se/kg of mineral mixture and given 0.1 mg of Se and 0.22 IU of vitamin E/kg of body weight, IM. Selenium supplementation had no effect on weight gain.

Effect on blood, liver, and kidney variables of age and of dosing rats with lead acetate orally or via the drinking water.

Levels of lead in the livers and kidneys of rats increased in proportion to the dose of lead acetate that the rats were given orally or in the drinking water. The activities of delta-aminolevulinic acid dehydratase (DALAD) in blood and liver decreased when the rats were dosed with lead, whereas glutathione levels in the blood increased. The decrease in the activity of blood DALAD was the most sensitive indicator of lead toxicity. Levels of lead in the livers and kidneys decreased after 3, 7, and 14 d of lead withdrawal. The activities of blood DALAD increased after 3 d of lead withdrawal. Groups of rats that initially weighted an average of 140 g were killed at weekly intervals for 6 wk. Blood hematocrits and liver glutathione levels increased, and blood DALAD and activated DALAD from blood decreased with increasing age of the rats. Activated DALAD activities from liver increased after the first week of the study.

Effect of diet on the response in rats to lead acetate given orally or in the drinking water.

Liver lead levels were higher for rats that were orally dosed with 100 mg lead acetate/kg body wt and fed a semipurified diet than those fed a pelleted diet. The activities of delta-aminolevulinic acid dehydratase in blood were decreased in the group given 10 micrograms lead acetate/mL in their drinking water and fed the semipurified diet, but not in the blood from the group treated with lead and fed the pelleted diet. The levels of glutathione in the liver decreased in response to lead acetate in the drinking water of rats fed the semipurified diet, but not in the livers from the group fed the pelleted diet and treated with lead. The levels of lead in the kidneys were higher in the group given lead acetate in their drinking water and fed the semipurified diet than in the lead treated group fed the pelleted diet. Rats dosed orally with lead or given lead in the drinking water and fed the semipurified diet were more sensitive to lead treatment than those fed the pelleted diet.

Repletion of blood selenium concentrations in weaned beef calves.

Eighty-three weaned beef calves severely deficient (less than 20 micrograms/L) in blood selenium (Se) were allotted by sex, weight and breed to one of six regimens of Se supplementation for 108 days to examine the efficacy of various Se supplementation programs and to monitor the repletion rate of blood Se concentrations. Cattle in treatment 1 received an IM injection of sodium selenite and an ad libitum feeding of 20 mg Se/kg salt-mineral mixture. Salt-mineral mixtures (treatments 2, 3, 4 and 5) were formulated to contain 20, 40, 80 and 160 mg Se/kg supplement, respectively, and were offered free-choice. Treatment 2 served as the selenium-treated control because 20 mg Se/kg supplement was the maximum permissible by FDA in commercial salt-mineral preparations at the time of this study. Cattle in treatment 6 received a salt-mineral supplement which contained no Se but dried brewers grain (434 micrograms Se/kg) was incorporated in the ration as an organic source of Se and fed at a rate of 1.1 kg/head/day. There was a within group time/treatment interaction (P less than 0.01) among all treatments as blood Se concentrations significantly increased over time. Final mean whole blood Se concentrations for treatments 1-6 were 87.8, 60.6, 95.1, 123.1, 154.2 and 91.4 micrograms/L, respectively. Treatments 1, 3, 4, 5 and 6 effectively increased and maintained whole blood Se concentrations at adequate levels (greater than 70 micrograms/L) by day 84. Treatment 2 (control) increased blood Se during the 108-day study, but blood Se concentrations never exceeded marginal levels (50-70 micrograms/L). Cattle consumed less salt-mineral supplement as the concentration of Na selenite increased from 20 to 160 mg Se/kg supplement.

Turkey poult tolerance to diets containing deoxynivalenol (vomitoxin) and salinomycin.

Feed taken from a commercial turkey farm where poults had refused to eat the feed and high mortality had occurred was analyzed and found to contain .81 mg/kg vomitoxin and 2.2 mg/kg salinomycin. The present four experiments investigated the effects of diets containing salinomycin at 0, 2.2, 5.5, 11, and 22 mg/kg and vomitoxin at 0, 2.2, and 4.4 mg/kg. A factorial design with vomitoxin at 0 and 4.4 mg/kg and salinomycin at 0 and 22 mg/kg was used in Experiment 4. Poults fed the suspect commercial diet had significantly lower feed consumption and higher motality than poults fed a control diet (P less than .05). Poults (0 to 3 wk of age) fed diets containing vomitoxin (4.4 mg/kg), salinomycin (22 mg/kg), or both showed no significant decrease in feed consumption, body weight gain, or viability.

Lack of influence of nursery temperature on the response of weanling pigs to supplemental vitamins C and E.

Three trials using 240 weanling pigs were conducted during winter months to determine the influence of nursery temperature ("comfortable" vs "cold") on the response of weanling pigs to added vitamin C (700 ppm) or E (55 IU/kg) to a corn-soybean meal diet. A "comfortable" temperature schedule (27 C initially with a weekly 2 C drop) was maintained in one nursery, with the temperature schedule in the "cold" nursery about 8 C lower. Plasma concentrations of vitamin C and vitamin E were elevated when the respective vitamins were added to the diet, but were not consistently influenced by nursery temperatures. Daily gain, daily feed intake and feed efficiency were not improved with the added C or E. Daily feed intake was increased and feed-to-gain ratios were larger for pigs housed in the "cold" nursery compared with pigs housed in the "comfortable" nursery; however, daily gains were similar in the two environments. Pigs housed in the "cold" nursery were slightly stressed, as indicated by heavier adrenal glands, but the antibody response and serum glucocorticoid concentrations were not significantly affected by either diet or temperature.

Toxicologic and antitumor studies on 5-hydroxymethyldeoxyuridine.

Toxic effects of 5-hydroxymethyldeoxyuridine (HMUdR) were studied in white Swiss mice. Pathological, hematological, and clinical chemistry parameters were examined. Systemic toxicity was not observed in mice after ip administration of HMUdR in single doses up to 2000 mg/kg. Mice administered HMUdR daily for 15 days at 200 mg/kg, ip, manifested loss of weight, rough hair coat, diarrhea, swollen abdomens, weakness, lethargy, and a 20% mortality rate. Hematological and clinical chemistry parameters of all mice receiving HMUdR were within normal limits. At necropsy, all organs were grossly normal but microscopic examination of tissues of treated mice revealed the presence of shortened, thickened villi in the small intestine, nuclear vacuolation and necrosis of intestinal crypt epithelial cells, and some cytoplasmic vacuolation causing nuclear margination in hepatocytes. All histological lesions were reversible with cessation of treatment. HMUdR was active against murine L1210 and L5178Y leukemias in cell culture. The concentrations required to inhibit cell growth 50% compared to untreated cells was 2 and 4 microM, respectively. When HMUdR was administered ip at 50, 100, or 200 mg/kg in five daily doses to mice implanted with L1210 cells, life spans increased 20, 30, or 33% over placebo-treated controls.

Arsenic toxicosis and suspected chromium toxicosis in a herd of cattle.

Arsenic toxicosis and suspected chromium toxicosis were diagnosed in a herd of cattle that ingested ashes from lumber treated with copper, chromium, and arsenic. Findings included peracute death, depression, ataxia, weakness, recumbency, and watery diarrhea. Chemical analyses of liver, kidney, abomasal contents, rumen contents, and ashes revealed high concentrations of arsenic and chromium. Histologically, specimens of abomasum and duodenum had diffuse mucosal degeneration and engorged capillaries. Epithelial cells of the proximal convoluted tubules and distal collecting tubules of the kidney were swollen and had mild granular cytoplasmic degeneration. Burning lumber treated with copper, chromium, and arsenic does not remove the heavy metals from them, and ingestion of the ashes from the wood constitutes a hazard to livestock health.

Encephalomalacia associated with hypovitaminosis E in turkey poults.

Four-to-five-week-old turkey poults fed a diet markedly deficient in vitamin E (alpha-tocopherol) abruptly developed neurologic signs such as tremor, incoordination, and recumbency shortly after being moved to new quarters. Serum concentrations of alpha-tocopherol in birds on this diet were significantly lower than control values. Associated lesions included recent ischemic necrosis of the cerebellum and spinal cord. The condition closely resembled nutritional encephalomalacia of chicks. This report represents the initial published description of that entity in turkeys.

Trace element levels in liver and kidney from cattle, swine and poultry slaughtered in Canada.

Levels of arsenic, cadmium, copper, mercury and lead were determined in approximately 650 samples of liver and kidney from cattle, swine and poultry slaughtered in Canada during 1979-81. In addition zinc levels were determined in livers and kidneys from swine, and selenium and zinc levels were determined in the livers and kidneys from cattle. Depending on the element several methods of atomic absorption spectroscopy were used to analyze samples including flame, hydride generation, cold vapour generation and graphite furnace atomization. Analyses were also done by plasma emission spectroscopy. Levels of arsenic over 2.0 micrograms/g were detected in 0.9% of swine livers and 0.3% of swine kidneys. Cadmium levels higher than 1.0 micrograms/g were detected in 0.3% of cattle livers, 10.8% of cattle kidneys, 1.8% of swine kidneys, 0.4% of poultry livers and 0.3% of poultry kidneys. Levels of copper over 150 micrograms/g were detected in 0.4% of cattle and swine livers. Levels of lead over 2.0 micrograms/g were detected in 1.4% of poultry livers and 1.6% of poultry kidneys. The highest level of mercury detected in all species was 0.25 micrograms/g and the highest level of selenium was 1.9 micrograms/g. Zinc levels of over 100 micrograms/g were detected in 1.7% of cattle livers, 0.2% of cattle kidneys and 5.0% of swine livers.

Comparison of the antiviral effects of 5-methoxymethyldeoxyuridine-5'-monophosphate with adenine arabinoside-5'-monophosphate.

Methoxymethyldeoxyuridine-5'-monophosphate (MMUdR-MP) and arabinofuranosyladenine-5'-monophosphate (Ara-AMP) had significant antiviral activity against herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2) in RK-13 and Vero cells. MMUdR-MP and Ara-AMP were more potent than methoxymethyldeoxyuridine (MMUdR) and arabinofuranosyladenine (Ara-A) against the MS strain of HSV-2. MMUdR-MP inhibited replication of HSV-1r (mutant resistant to MMUdR). MMUdR in combination with Ara-AMP showed additive activity; whereas the MMUdR-MP and Ara-AMP combination was antagonistic against herpes viruses. MMUdR in combination with Ara-A was synergistic in reducing the log virus yield. Cytotoxicity (microscopic lesions) was observed on exposure to MMUdR-MP and Ara-AMP at 450 and 90 microM, respectively. Rapidly proliferating RK-13 cells exposed to Ara-AMP (64 microM) were killed. In the same system, the cells surviving after incubation with MMUdR-MP (650 microM), multiplied at an almost normal rate.

Pharmacological studies on 5-methoxymethyl-2'-deoxyuridine: a new antiviral agent.

Pharmacokinetic and pharmacodynamic properties of 5-methoxymethyl-2'-deoxyuridine (MMUdR), a drug with potent antiviral activity against herpes simplex virus, were investigated. After i.v. administration of [2-14C]MMUdR at 50 and 25 mg/kg to rats, the overall half life of the drug (T 1/2 Kel) was calculated to be 32 to 35 min. The biological half life of the drug (T 1/2 beta) was 89 min and the distribution half life (T1/2 alpha) was 6 min. The specific volume of distribution was calculated to be 1.28 to 1.35 liters/kg and the total body clearance rate of the drug was 10 ml/min/kg. The data were analyzed on the basis of a two-compartment open pharmacokinetic model. After i.p. administration of 50 mg/kg of [2-14C]MMUdR to mice, peak plasma levels of 35.6 micrograms/ml were attained in 10 min. The highest tissue concentrations of [2-14C]MMUdR in mice were 63 micrograms/g in kidneys (30 min) followed by 36 micrograms/g in liver and spleen and 30 to 32 micrograms/g in lungs and gut (20 min). MMUdR did not undergo biotransformation in plasma but urine was found to contain MMUdR (greater than 80%) and a small amount of radioactivity which comigrated with MMUdR monophosphate. Administration of 500 mg/kg of MMUdR i.v. to New Zealand White rabbits did not produce any observable effects on the heart rate, ECG pattern or respiration rate. Vasodilation of 39-sec duration was observed immediately after administration of MMUdR.

Combination chemotherapy: interaction of 5-methoxymethyldeoxyuridine with adenine arabinoside, 5-ethyldeoxyuridine, 5-iododeoxyuridine, and phosphonoacetic acid against herpes simplex virus types 1 and 2.

The antiviral activity of 5-methoxymethyl-2'-deoxyuridine (MMUdR) was compared with that of 5-iodo-2'-deoxyuridine (IUdR), 5-ethyl-2'-deoxyuridine (EtUdR), adenine arabinoside (Ara-A), and phosphonoacetic acid (PAA) against herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2). MMUdR was more potent than Ara-A and PAA but less active than EtUdR and IUdR against HSV-1 in rabbit kidney (RK-13) cells. In Vero cells, the antiviral activities of MMUdR, Ara-A, and PAA against HSV-1 were of the same order of magnitude. The antiviral potency against HSV-2 varied with the strain of virus used. All strains of HSV-2 were markedly inhibited by EtUdR and IUdR and to a lesser degree by PAA. However, considerable variation was noticed in the susceptibility of HSV-2 strains to Ara-A and MMUdR. Interaction of MMUdR with Ara-A, EtUdR, IUdR, and PAA was investigated by the method of response isobolograms. MMUdR showed synergistic activity in combination with Ara-A and PAA but antagonistic activity in combination with EtUdR and IUdR against herpesviruses. Minimum toxic dose (concentration required to produce definite evidence of microscopic cytotoxicity in rapidly growing RK-13 cells) was determined for each compound and was found to be 512, 172, 64, 8, and less than 0.5 microgram/ml for MMUdR, PAA, Ara-A, EtUdR, and IUdR, respectively. MMUdR was found to have the maximum antiviral index against HSV-1 (512) and HSV-2 strains X-265 (102) and ATCC (85). Antiviral index was defined as the minimum toxic dose divided by the dose that reduced plaque numbers by 50%.

Comparative efficacy of 5-methoxymethyl-2'-deoxyuridine, 9 beta-D-arabinofuranosyladenine and 5-iodo-2'-deoxyuridine in the treatment of experimental herpes simplex keratitis.

The relative efficacy of 5-methoxymethyldeoxyuridine (MMUdR), adenine arabinoside (Ara-A), 5-iododeoxyuridine (IUdR) and the combination of MMUdR and Ara-A in the treatment of experimental herpes simplex keratitis was investigated in rabbits. Treatment was initiated either at 4 or 24 h post virus inoculation. The parameter used to evaluate effectiveness was lesion size. Each eye was graded daily for the first 5 days and on alternate days thereafter to day 11. At concentrations of 2 or 5% both MMUdR and Ara-A were found to have potent antikeratitis activity. At 5% concentration, Ara-A provided essentially the same protection against herpes keratitis as 0.1% IUdR, while MMUdR was slightly less effective. The simultaneous application of 2% MMUdR and 2% Ara-A in combination was more effective than 5% MMUdR alone and was effective as 5% Ara-A or 0.1% IUdR in controlling the viral keratitis.

Synthesis and cell culture studies on the antiviral activity of 5-mercaptomethyl-2'-deoxyuridine.

Treatment of 5-mercaptomethyluracil (I) with trimethylsilyl chloride in the presence of triethylamine gave 2,4,5-tris-(trimethylsilyl)-5-mercaptomethyluracil (II) which, upon coupling with 2-deoxy-3,5-di-O-(p-toluoyl)-D-erythro-pentofuranosyl chloride, furnished as anomeric mixture of fully substituted 2'-deoxy ribonucleosides. The nucleoside with beta configuration (III) was predominantly formed and was isolated as a crystalline solid. The free nucleoside IV was obtained by removal of blocking groups by sodium methoxide catalyzed deacylation, deionization under reducing atmosphere, and chromatography on neutral alumina. IV is oxidized to the corresponding disulfide V in solution in the absence of thiols. IV was found to be markedly inhibitory against the herpes virus of infectious bovine rhinotracheitis (IBR). Against this virus, IV was found to be as potent as 5-iododeoxyuridine and cytosine arabinoside when added 18 hr before virus infection.