Hepatic (64)Cu excretion in Dobermanns with subclinical hepatitis

To investigate whether Dobermanns have impaired copper excretion an intravenous radioactive copper isotope ((64)Cu) was used as a tracer. Five patients and eight normal dogs (5 normal Dobermanns and 3 Beagles) were studied. The five female Dobermann patients had a subclinical hepatitis and an increased hepatic copper concentration (median 822mg/kg, range 690-1380mg/kg dry matter). The normal dogs, five Dobermanns and three Beagles, had no abnormal liver histopathology and hepatic copper concentrations were considered normal (Dobermanns; median 118mg/kg, range 50-242mg/kg dry matter; Beagles; median 82mg/kg, range 50-88mg/kg dry matter). Cholestasis was excluded in all dogs by means of a (99m)Tc-Bis-IDA hepatobiliary scintigraphy. Plasma clearance of (64)Cu was comparable in all dogs with no statistically significant differences. The excretion of (64)Cu into the bile, although not statistically significant, was less for the Dobermanns with subclinical hepatitis compared to the normal dogs. The findings suggest that impaired copper excretion may play a role in the aetiology of chronic hepatitis in the Dobermann.     

Tear copper and its association with liver copper concentrations in six adult ewes.

Tear and liver copper concentrations from 6 clinically healthy adult mixed-breed ewes were measured by Atomic Absorption Electrothermal Atomization (graphite furnace) Spectrometry and Flame Absorption Spectrometry, respectively, 7 times over 227 d to determine if their tears contained copper and if so, whether tear copper concentrations could reliably predict liver copper concentrations. To produce changes in liver copper concentration, the diet was supplemented with copper at concentrations that increased from 23 mg to 45 mg Cu/kg feed/day/sheep during the study. This regimen raised liver copper for all sheep to potentially toxic hepatic tissue concentration of greater than 500 mg/kg dry (DM) matter (tissue). The results of the study showed that copper was present in the tears of all sheep. The mean tear copper concentration showed a positive correlation with liver copper concentration (P = 0.003), increasing from 0.07 mg/kg DM at the start to 0.44 mg/kg DM at the end of the study, but could not reliably predict liver copper concentration (R2 = 0.222).     

Chemotherapy of T b brucei infection: Use of DFMO, diminazene aceturate, alone and in combination

The therapeutic activity of diminazene aceturate, difluoromethylornithine (DFMO) and a combination of the two agents was investigated in experimental Trypanosoma brucei brucei infections in mongrel dogs. The criteria used in the assessment of the trypanocidal effect of these compounds included the examination of the blood for the parasite, as well as clinical and haematological changes at intervals following treatment. Diminazene aceturate (7 mg/kg intramuscularly), DFMO (300 mg/kg/day orally in three divided doses for six days) and the combination of diminazene aceturate (7 mg/kg intramuscularly) and DFMO (300 mg/kg/day orally for six days) produced an intermittent aparasitemia in the dogs. Relapse infection occurred in all the three groups, but the period of aparasitemia produced by the combination of the agents was longest. The packed cell volume, haemoglobin concentration and red cell count values decreased after the dogs were inoculated with the parasite. The values improved slightly following the treatments with the agents or their combination. The total white blood cell counts in the infected dogs indicated leucocytosis, but this improved with drug treatment.     

Dietary Management of Labrador Retrievers with Subclinical Hepatic Copper Accumulation

Background

Genetic and environmental factors, including dietary copper intake, contribute to the pathogenesis of copper‐associated hepatitis in Labrador retrievers. Clinical disease is preceded by a subclinical phase in which copper accumulates in the liver.

Objective

To investigate the effect of a low‐copper, high‐zinc diet on hepatic copper concentration in Labrador retrievers with increased hepatic copper concentrations.

Animals

Twenty‐eight clinically healthy, client‐owned Labrador retrievers with a mean hepatic copper concentration of 919 ± 477 mg/kg dry weight liver (dwl) that were related to dogs previously diagnosed with clinical copper‐associated hepatitis.

Methods

Clinical trial in which dogs were fed a diet containing 1.3 ± 0.3 mg copper/Mcal and 64.3 ± 5.9 mg zinc/Mcal. Hepatic copper concentrations were determined in liver biopsy samples approximately every 6 months. Logistic regression was performed to investigate effects of sex, age, initial hepatic copper concentration and pedigree on the ability to normalize hepatic copper concentrations.

Results

In responders (15/28 dogs), hepatic copper concentrations decreased from a mean of 710 ± 216 mg/kg dwl copper to 343 ± 70 mg/kg dwl hepatic copper after a median of 7.1 months (range, 5.5–21.4 months). Dogs from a severely affected pedigree were at increased risk for inability to have their hepatic copper concentrations normalized with dietary treatment.

Conclusions and Clinical Importance

Feeding a low‐copper, high‐zinc diet resulted in a decrease in hepatic copper concentrations in a subset of clinically normal Labrador retrievers with previous hepatic copper accumulation. A positive response to diet may be influenced by genetic background. Determination of clinical benefit requires further study.     

Tissue retention and adverse reaction after intravenous injection of hematoporphyrin derivatives in dogs

We evaluated changes in hematology and chemical profile, and the tissue retention of hematoporphyrin derivative (HpD) following the intravenous injection in dogs. HpD at concentrations of 1, 5, 10, and 15 mg/kg was intravenously injected to 16 dogs (n=4 each) and complete blood count (CBC) and blood chemistry were performed on days 1, 3, 5, and 7 after the injection. To examine tissue retention, HpD (5 mg/kg) was administered to 15 dogs and 3 dogs were euthanized on days 1, 2, 7, 14, and 28 after the injection, respectively, to collect the skin, muscle, small intestine, spleen, kidney and liver as tissue samples. There were no significant changes in CBC and blood chemical profile except for an increase in LDH concentrations in dogs given 10 and 15 mg/kg of HpD at day 3. The levels of HpD retention in the tissues were ranked in the following order: liver > kidney > spleen > intestine > muscle > skin.     

Vitamin A concentrations in commercial foods for dogs and cats

The vitamin A concentration was determined in 89 Australian brands of commercial foods for dogs and cats. It was found that 8% of the dog foods and 14% of the cat foods had concentrations of vitamin A below the minimum recommended 1.1 mg/kg dry matter (dm) for dogs and 1.8 mg/kg dm for pregnant or lactating cats. Canned and fish-labelled cat foods were the only varieties with less than the minimum recommended concentration of Vitamin A, of which 71% were the same brand. The minimum recommended concentration of vitamin A was exceeded in all canned dog food tested. Concentrations of vitamin A in dry (ca. 6% moisture) dog and cat foods and semi-moist dog foods (ca. 23% moisture) never exceeded 10 mg vitamin A/kg dm. In contrast, canned pet foods stated to contain liver or kidney showed vitamin A concentrations from 13 to 284 mg/kg dm.     

Case study of copper poisoning in a British dairy herd

Following the initial diagnosis of chronic copper poisoning (CCP), the copper (Cu) status of a British dairy herd was investigated. Eight fatal cases of CCP were identified over a 17-month period, from December 1999 to May 2001, involving seven Jersey cows and one Holstein-Friesian; seven cows were dry when CCP occurred. Case diagnostic criteria were necrotising hepatopathy associated with abnormally high liver and kidney Cu concentrations. Analysis of the ration for the high-yielding Jersey cow group revealed about 50 mg Cu/kg dry matter intake (DMI). Risk factors predisposing to fatal CCP were Jersey breed, previous high yield, first two weeks of the dry period and moderately high dietary Cu (greater than 40 mg Cu/kg DMI).     

Use of zinc acetate to treat copper toxicosis in dogs.

Zinc acetate was used for the treatment and prophylaxis of hepatic copper toxicosis in 3 Bedlington Terriers and 3 West Highland White Terriers. Two dogs of each breed were treated for 2 years, and 1 of each breed for 1 year. A dosage of 200 mg of elemental zinc per day was required to achieve therapeutic objectives related to copper, which included a doubling of plasma zinc concentration to 200 micrograms/dl and a suppression of oral 64 copper absorption. The dosage was later reduced to 50 to 100 mg/day to avoid an excessive increase in plasma zinc concentration. The preliminary clinical results were good. Three dogs had mild to moderate active liver disease and high liver copper concentrations at the time of initiation of zinc administration. Biopsy of the liver 2 years later revealed a reduction in hepatitis and copper concentrations. One other dog without active hepatitis also had a reduction in hepatic copper concentrations over a 2-year period. All 6 dogs have done well clinically. On the basis of these findings, we believe zinc acetate to be an effective and nontoxic treatment for copper toxicosis in dogs.     

Impact of molybdenum on the copper status of red deer (Cervus elaphus)

AIM: To determine the effect of increasing molybdenum (Mo) intakes on serum and liver copper (Cu) concentrations and growth rates of grazing red deer (Cervus elaphus). METHODS: Molybdenum- and Cu-amended fertilisers were applied to six 1.1-ha paddocks in a 3 x 2 design. Three levels of Mo were applied on two paddocks at each level in mid April (designated Day 1); levels were: none (control), 0.5 (medium) and 1.0 (high) kg Mo/ha as sodium molybdate. In late May (Day 39), two levels of Cu (none and 3.0 kg Cu/ha, as copper sulphate) were applied to each of the three levels of Mo-treated paddocks. Pasture Mo, Cu and sulphur (S) concentrations were measured at about fortnightly intervals. In late June (Day 74), ten 6-month-old red deer hinds were placed on the six experimental pastures, and serum and liver Cu concentrations were monitored at about monthly intervals for 102 days. The hinds were weighed on four occasions during the trial. RESULTS: Mean pasture Mo concentrations on Day 56 were 2, 4.6 and 11.3 mg/kg dry matter (DM) for the untreated control, medium and high Mo-treated pastures, respectively. Pasture Cu concentration was 95 mg/kg DM on Day 59, 53 mg/kg DM on Day 90, and 9 mg/kg DM by Day 153. Mean S concentration in pasture was 3.3 (range 3.03-3.45) g/kg DM. Copper application to pasture had no significant effect on serum and liver Cu concentrations in deer so data were pooled within Mo treatment. Mean initial (Day 74) serum Cu concentration was 9.2 micromol/L. In the deer grazing the control Mo pasture, this increased to 10.3 micromol/L on Day 112, before decreasing to 6.4 micromol/L on Day 176. In deer grazing the medium and high Mo-treated pastures, mean serum Cu concentrations were 3.8 and 3.9 micromol/L, respectively, on Day 112, and 2.5 and 3.3 micromol/L, respectively, on Day 176. Mean initial (Day 74) liver Cu concentration was 131 micromol/kg fresh tissue. In the deer grazing the control Mo pasture, this declined to 120 and 52 micromol/kg on Days 112 and Day 176, respectively. In deer grazing the medium and high Mo-treated pastures, liver Cu concentrations decreased to 55 and 52 micromol/kg fresh tissue, respectively, on Day 112, and 21 and 20 micromol/kg fresh tissue, respectively, on Day 176. Mean serum and liver Cu concentrations were not significantly different between deer grazing the medium and high Mo-treated pastures, and were lower (serum p=0.003, liver p<0.001) in those groups than in deer grazing the untreated control pastures. No clinical signs of Cu deficiency associated with lameness were observed. Deer grazing pastures that had Mo concentrations >10 mg/kg DM had lower (p=0.002) growth rates (100 vs 130 g/day) than those on pastures containing <2.4 mg Mo/kg DM. CONCLUSION: Increasing pasture Mo concentrations from 2 mg/kg DM to > or =4.6 mg/kg DM significantly reduced serum and liver Cu concentrations in grazing deer. Reduced growth rate was observed at pasture Mo concentrations >10 mg/kg DM.     

Effects of copper supplementation on the copper status of peripartum beef cows and their calves

The effects of copper supplementation on the copper status of 40 late-pregnant Aubrac beef cows grazing a copper-deficient pasture and later fed a marginally deficient diet were studied for five months. They were divided into four equal groups; the control group received no copper supplement, groups 1 and 2 received copper as copper sulphate at 10 and 30 mg/kg of diet dry matter (DM), respectively, for five months, and group 3 received 120 mg/kg of diet dry matter for 10 days. Plasma copper concentration and the activity of erythrocyte superoxide dismutase (eSOD) were measured at the beginning of the experiment, in the cows and calves during weeks 1 and 3 after calving, and in the calves before they were turned out to pasture at a mean (sd) age of 51 (26) days. In spite of the low dietary copper content (4.2 mg/kg of DM), the plasma copper concentration of the control cows increased during the winter. All the copper supplements resulted in normal and similar plasma copper concentrations in the cows after calving, but the concentration decreased slightly between weeks 1 and 3 after calving in the group supplemented for 10 days. The treatments did not affect the eSOD of the cows. The calves born to the four groups showed the same patterns of plasma copper and eSOD. Compared with the cows, the calves had low plasma copper concentrations at week 1 and values in the normal range at week 3; their eSOD was high at weeks 1 and 3 but decreased after week 3.     

The effect of copper-amended fertiliser and copper oxide wire particles on the copper status of farmed red deer (Cervus elaphus) and their progeny

AIM: To determine changes in serum and liver copper concentrations in postnatal, weaner, yearling, and mature deer after grazing pasture topdressed with copper (Cu) at two rates of application of copper sulphate (CuSO4(.)5H2O), and following oral administration of copper oxide (CuO) wire particles to some of the deer. METHODS: In mid-March 2000 (Year 1), 1.1-ha paddocks (two/treatment) of ryegrass/white clover pasture received either 0 (Control), 6 (Low) or 12 (High) kg CuSO4(.)5H2O /ha applied with 250 kg potash superphosphate/ha. They were grazed by 4-month-old red deer hinds (n=11/treatment) from mid-April 2000 until early March 2001. In mid-March 2001 (Year 2), the pastures were topdressed again as for Year 1, and the original hinds, now yearlings which had grazed as a single group between studies, were returned to their respective treatments in mid-April 2001 and remained on the trial until mid-March 2002. They were mated during April/May. The pastures were also grazed by pregnant mature hinds (n=8/treatment) from mid-May 2001. As the Cu status (i.e. liver Cu concentration) of the yearling hinds on the pasture treated with 6 kg CuSO4(.)5H2O/ha was not significantly different from the untreated animals, in late July 2001 the yearling and mature deer on this treatment were treated orally with 10 g CuO wire particles. The mature hinds calved in November and the yearling hinds in December. Pasture samples were collected at about monthly intervals to determine concentrations of Cu and other minerals. In Year 1, liver biopsies and blood samples were collected at 4-6-weekly intervals for determination of Cu concentrations. In Year 2, samples were collected similarly at 6-12-weekly intervals. Liver biopsies and blood were also collected from progeny, along with milk from their dams. Liveweights were determined at 3-7-monthly intervals, as well as data on calving/mortality rates. RESULTS: Pasture Cu concentrations before the application of CuSO4(.)5H2O were 6-9 mg Cu/kg dry matter (DM) and remained at this level in the untreated Control paddocks throughout the study. In Year 1, 28 days after treatment, pasture Cu concentration was 25 and 35 mg Cu/kg DM for the Low and High treatments, respectively; while at the same time for the same treatments in Year 2 it was 20 and 60 mg/kg DM, respectively. A second 60 mg Cu/kg DM peak also occurred on Day 85 in Year 2 with the High treatment. The pasture Cu concentration returned to 6-9 mg/kg DM, and there were no differences between treatments at Days 80 and 150 in Years 1 and 2, respectively. In Years 1 and 2, the Low treatment had no significant effect on the Cu status of the weaner and yearling hinds, respectively, when compared with that of animals grazing the untreated Control pastures. Weaner (Year 1) and yearling (Year 2) deer on the High treatment had significantly higher mean serum and liver Cu concentrations in the late winter and spring period when compared with those on untreated Control pastures. CuO wire particles increased the mean serum Cu concentration at Days 60 and 180, and liver Cu concentration at Day 60, in yearling hinds. A similar effect was observed in mature hinds. Regardless of Cu treatment, the liver Cu concentration of the 1-4-week-old progeny was markedly greater (p<0.001) than that of their dams, and then decreased significantly until weaning in March. In progeny of treated yearling hinds, but not mature hinds, serum and liver Cu concentrations were significantly higher (p=0.013) than progeny of untreated dams. CONCLUSION: Topdressing pastures with CuSO4(.)5H2O at a rate of 12 kg/ha, but not 6 kg/ha, in mid-March was effective in increasing the Cu status of weanling hinds; while pastures topdressed with 12 kg CuSO4(.)5H2O /ha in mid-March and dosing hinds with 10 g CuO in late July were effective in increasing the Cu status of pregnant hinds, and in the case of the yearling hinds, significantly improved the Cu status of their progeny from birth to weaning.     

Copper-associated liver disease in Dalmatians: a review of 10 dogs (1998-2001)

This retrospective study summarizes 10 Dalmatians suspected of having hepatic copper toxicosis. Hepatic copper toxicosis can result from either a primary metabolic defect in hepatic copper metabolism or from altered hepatic biliary excretion of copper. An inherited copper-associated hepatopathy has been documented in Bedlington Terriers, and there is evidence for familial copper-associated liver disease in West Highland White (WHW) Terriers and Skye Terriers. Nine of the 10 Dalmatians in this study presented for gastrointestinal clinical signs, including anorexia and vomiting. All animals had increased alanine aminotransferase (ALT) enzyme activity, and 9 of 10 had increased alkaline phosphatase (ALP) enzyme activity. The relative increase in ALT activity was much greater than the relative increase in ALP activity, suggesting a predominantly hepatocellular rather than cholestatic liver disease. The mean hepatic copper concentration for 9 Dalmatians was 3,197 microg/g dry weight liver (dwl) (normal, <450 microg/g). In 5 of these 9 dogs, hepatic copper concentrations exceeded 2,000 microg/g dwl. Necroinflammatory alterations associated with copper-laden parenchymal cells were the notable histopathologic finding. The inflammatory infiltrate was either primarily lymphocytic or neutrophilic. Morphologic features of cholestasis generally were not prominent except in those dogs with severe pathology. These findings lend support to the hypothesis that a primary metabolic defect in hepatic copper metabolism occurs in the Dalmatian breed. The mechanism and genetic basis of this condition require further study.     

Microemulsified cyclosporine-based immunosuppression for the prevention of acute renal allograft rejection in unrelated dogs: preliminary experimental study

OBJECTIVES: To determine whether the microemulsified formulation of cyclosporine (MCsA; Neoral; Novartis A.G.), combined with azathioprine (Imuran; Glaxo Wellcome), and prednisolone (Delta-Cortef; Upjohn), would be effective in preventing acute renal allograft rejection in unrelated mongrel dogs. To document any toxic effects associated with this drug combination. STUDY DESIGN: rospective, pilot study. ANIMALS: Four healthy, adult, mongrel, canine renal allograft recipients. METHODS: Heterotopic renal transplantation, with bilateral nephrectomy, was performed in 4 dogs. Allografts were harvested from 2 unrelated dogs that were to be euthanatized for reasons unrelated to this study. The dogs were treated for 100 days or until signs of illness or allograft rejection required euthanasia. Microemulsified cyclosporine (20 mg/kg/day), azathioprine (5 mg/kg every other day), and prednisolone (1 mg/kg/day) were administered for the prevention of acute rejection. Body weight, serum biochemistry profiles, complete blood counts, and trough whole-blood cyclosporine concentrations were measured throughout the study. Cyclosporine dose was adjusted to maintain a trough concentration of 400-500 ng/mL. Azathioprine dose was decreased if evidence of hepatotoxicity developed or if the total blood white cell count was <4,000 cells/micro L. The prednisolone was tapered by 0.25 mg/kg increments every 3 weeks and discontinued 14 days before the end of the study in the surviving dogs. Complications were recorded. A complete necropsy and histopathologic examination were performed in each recipient. RESULTS: Two of the 4 dogs survived the 100-day period. One dog was euthanatized at 8 days because of an intestinal intussusception. One dog was euthanatized at 64 days because of a severe upper respiratory infection. At the time of death, these 2 dogs had plasma creatinine concentrations of 1.5 and 2.6 mg/dL, respectively, with no histopathologic evidence of allograft rejection. All dogs had transient weight loss (range, 4.6%-17.7% of preoperative body weight) between days 7 and 14. Two dogs had evidence of hepatotoxicity. The 2 dogs surviving to 100 days had normal serum creatinine concentrations and no clinical signs of rejection. One of these dogs had evidence of a grade IIa acute/active rejection based on the modified BANFF 97 histopathologic classification. The second dog had no evidence of rejection or inflammation within the allograft. CONCLUSIONS: This preliminary experimental study shows that immunosuppression using MCsA, combined with azathioprine and prednisolone, may be effective in preventing acute renal allograft rejection in unrelated mongrel dogs for 100 days. Complications included ileocolic intussusception, upper respiratory infection, weight loss, and transient hepatotoxicity. CLINICAL RELEVANCE: Immunosuppression using MCsA, azathioprine, and prednisolone may be effective in preventing acute renal allograft rejection in unrelated, mongrel dogs. This triple drug protocol is cost-effective and was easy to administer. Further investigation is warranted to minimize toxic effects and to determine the efficacy of prophylactic renal biopsies to detect and treat subclinical acute/active rejection.     

Copper oxide needles for cattle: a comparison with parenteral treatment

Two trials of oral copper oxide needles for cattle are described. In one, a dose of 13.0 g copper oxide/100 kg liveweight in yearling bullocks was compared with parenteral copper at a total dose rate of 400 mg copper. In the second, three oral dose rates (3.5, 7.0 and 10.5 g copper oxide/100 kg liveweight) in calves were compared over two years with a total dose of 500 mg parenteral copper. In both trials liver copper values reached a peak at about six weeks after oral dosing and in the second trial the peak was dose related. Thereafter liver levels declined in all the oral treatment groups; normal levels of more than 30 mg/kg liver dry matter were maintained for 30 weeks in the first trial and for 40 to 47 weeks, depending on dose rate, in the second. In both trials repeated parenteral treatments were required to maintain liver levels within the normal range. The results support earlier findings that an adequate dose of copper oxide needles can maintain the copper status of cattle for periods of at least six months.     

蛋氨酸铜对西门塔尔牛发情周期生殖激素分泌的影响

选用16头18月龄,体况良好,体重380±26 kg的西门塔尔牛育成母牛,采用完全随机区组设计分为4组,以蛋氨酸铜为铜源,研究日粮加铜(0、8、16和24 mg/kg)对发情周期生殖激素分泌规律的影响。结果表明:8 mg/kg组和16 mg/kg组显著提高了发情周期LH、FSH、P4和E2水平(P<0.05);24 mg/kg组有所提高,但不显著(P>0.05)。说明添加蛋氨酸铜8~16 mg/kg对发情周期生殖激素分泌有显著促进作用。考虑基础日粮的含铜量,建议日粮铜水平为:13.87~21.87 mg/kg。     

Diagnosis of copper deficiency and effects of supplementation in beef cows.

The effects of feeding supplementary dietary copper to a herd of 400 beef cows, were studied over a two year period. In the first year of the trial, the calves showed clinical signs of copper deficiency. There was improved growth following subcutaneous injection of copper ethylenediamine tetraacetate, and the treated calves had a 2.8% increase in adjusted weaning weights. In the second year of the trial pregnant cows were fed a basal ration of bromegrass silage, barley and minerals over the winter feeding period. The feed was supplemented with copper so that half received 5.5 mg/kg of copper on a dry matter basis and half 40 mg/kg. Calving occurred in the spring and half the calves were treated with injectable copper at birth and again at 12 weeks of age. There was no evidence of copper deficiency in the calves and there was no effect of high level copper supplementation on calf birth weight, or neutrophil candidacidal activity. Susceptibility to diarrhea varied in a complex fashion; morbidity was lowest in calves born to dams fed supplementary copper and highest in calves born to supplemented dams and injected with copper at birth. The cows and calves grazed the same copper deficient pasture over the summer. The average daily gain for calves born to supplemented cows was 0.999 +/- 0.010 kg/day (x +/- SEM) which was significantly greater than the 0.972 +/- 0.009 kg/day for calves from nonsupplemented dams (p = 0.044). The benefit of copper supplementation on 200 day weaning weight was estimated at 4.8 kg. Evidence of copper deficiency was seen when a herd test showed mean serum levels below 9 mumol/L and liver values below 0.09 mmol/kg wet matter.     

The safety of dirlotapide in dogs

The safety of dirlotapide in dogs was evaluated in two studies with parallel designs. In an acute tolerance study, 24 beagles (six dogs per treatment) were treated orally once daily for 14 days with placebo or dirlotapide at 2.5, 5.0, or 10.0 mg/kg/day. In a margin-of-safety study, 38 overweight, neutered beagles were treated orally once daily for 3 months with dirlotapide at doses up to 0.5 mg/kg/day (six dogs), 1.5 mg/kg/day (12 dogs) and 2.5 mg/kg/day (six dogs). Control dogs received placebo at 0.3 mL/kg/day (10 dogs) and 0.5 mL/kg/day (four dogs). Results were similar for both studies, and no serious adverse events were observed. Dirlotapide was clinically well-tolerated in dogs at dosages up to 10 mg/kg/day for 14 days and 2.5 mg/kg/day for 3 months. Dirlotapide produced the expected decrease in food intake and body weight (up to 20–40%) without ill effects. Clinical, pathologic, and histopathologic findings were reversible and consistent with suppression of food intake and rapid weight loss produced by elevated dirlotapide dosages. In both studies, sporadic emesis and loose stools were observed in both placebo and dirlotapide-treated dogs. Incidence of emesis generally increased with dose and decreased with treatment time. Elevations in hepatic transaminase activity were seen in dogs treated with more than 1.5 mg/kg dirlotapide daily, but were not associated with clinical signs or microscopic evidence of hepatic degeneration or necrosis.     

饲料镉对必需微量元素在猪组织中分布的影响

将96头体重27kg左右杜长大生长猪,随机分为2组,每组设3个重复(公、母各半),分别饲喂添加0、10.0mg/kg镉的饲粮,进行了83d的饲养试验,期间每隔两周固定从每个重复中选2头猪(公、母各半)前腔静脉采血。饲养试验结束后,从每组中各选取12头试验猪(公母各半)屠宰,并采集血清、内脏器官样品测定铁、铜、锌的含量。结果表明:添加10.0mg/kg镉显著影响猪的生长性能,其日增重降低18.6%(P<0.05),饲料转化率降低15.1%(P<0.05);10.0mg/kg镉引起了一些组织中铁含量的显著降低(P<0.05)及铜含量的显著升高(P<0.05),肾锌水平显著提高(P<0.05),而心脏、胰脏中锌含量显著降低(P<0.05);添加镉对淋巴结和心脏铁含量、淋巴结和胰脏铜含量及肝脏和脾脏锌含量无显著(P>0.05)影响。     

Impact of molybdenum on the copper status of red deer (Cervus elaphus)

AIM: To determine the effect of increasing molybdenum (Mo) intakes on serum and liver copper (Cu) concentrations and growth rates of grazing red deer (Cervus elaphus).

METHODS: Molybdenum- and Cu-amended fertilisers were applied to six 1.1-ha paddocks in a 3 × 2 design. Three levels of Mo were applied on two paddocks at each level in mid April (designated Day 1); levels were: none (control), 0.5 (medium) and 1.0 (high) kg Mo/ha as sodium molybdate. In late May (Day 39), two levels of Cu (none and 3.0 kg Cu/ha, as copper sulphate) were applied to each of the three levels of Mo-treated paddocks. Pasture Mo, Cu and sulphur (S) concentrations were measured at about fortnightly intervals. In late June (Day 74), ten 6-month-old red deer hinds were placed on the six experimental pastures, and serum and liver Cu concentrations were monitored at about monthly intervals for 102 days. The hinds were weighed on four occasions during the trial.

RESULTS: Mean pasture Mo concentrations on Day 56 were 2, 4.6 and 11.3 mg/kg dry matter (DM) for the untreated control, medium and high Mo-treated pastures, respectively. Pasture Cu concentration was 95 mg/kg DM on Day 59, 53 mg/kg DM on Day 90, and 9 mg/kg DM by Day 153. Mean S concentration in pasture was 3.3 (range 3.03–3.45) g/kg DM. Copper application to pasture had no significant effect on serum and liver Cu concentrations in deer so data were pooled within Mo treatment. Mean initial (Day 74) serum Cu concentration was 9.2 µmol/L. In the deer grazing the control Mo pasture, this increased to 10.3 µmol/L on Day 112, before decreasing to 6.4 µmol/L on Day 176. In deer grazing the medium and high Mo-treated pastures, mean serum Cu concentrations were 3.8 and 3.9 µmol/L, respectively, on Day 112, and 2.5 and 3.3 µmol/L, respectively, on Day 176. Mean initial (Day 74) liver Cu concentration was 131 µmol/kg fresh tissue. In the deer grazing the control Mo pasture, this declined to 120 and 52 µmol/kg on Days 112 and Day 176, respectively. In deer grazing the medium and high Motreated pastures, liver Cu concentrations decreased to 55 and 52 µmol/kg fresh tissue, respectively, on Day 112, and 21 and 20 µmol/kg fresh tissue, respectively, on Day 176. Mean serum and liver Cu concentrations were not significantly different between deer grazing the medium and high Mo-treated pastures, and were lower (serum p=0.003, liver p<0.001) in those groups than in deer grazing the untreated control pastures. No clinical signs of Cu deficiency associated with lameness were observed. Deer grazing pastures that had Mo concentrations >10 mg/kg DM had lower (p=0.002) growth rates (100 vs 130 g/day) than those on pastures containing <2.4 mg Mo/kg DM.

CONCLUSION: Increasing pasture Mo concentrations from 2 mg/kg DM to ≥4.6 mg/kg DM significantly reduced serum and liver Cu concentrations in grazing deer. Reduced growth rate was observed at pasture Mo concentrations >10 mg/kg DM.     

Tetramine cupruretic agents: a comparison in dogs

The cupruretic effects of 2 tetramine (N,N'-bis (2-aminoethyl) alkane diamine) chelators were examined in healthy dogs fed a commercial dog food containing 12.2 micrograms of copper/g of dry diet. Two groups of 3 dogs each were given either 300 mg of 2,2,2-tetramine tetrahydrochloride or 2,3,2-tetramine tetrahydrochloride for 23 consecutive days. Serum and 24-hour urine samples obtained before drug administration and during therapy were analyzed for copper, zinc, and iron concentrations. Both tetramines produced a significant cupruresis without significant changes in serum copper or in serum or urine zinc and iron concentrations. The 2,3,2-tetramine tetrahydrochloride produced a 4- to 9-fold greater cupruresis than did 2,2,2-tetramine tetrahydrochloride and resulted in a daily loss of more than 2 mg of copper in the urine. The dogs had no laboratory or clinical evidence of toxic side effects to either cupruretic agent during the treatment period. The results of the present study indicate that 2,3,2-tetramine should be an effective decoppering drug for use in dogs.