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1.
The effect of tetrathiomolybdate (TM), disodium calcium ethylenediamine tetraacetate (EDTA), D-penicillamine (PEN), 2-3 dimercapto-1-propanol (BAL) and dimethyl dithiocarbamate (DDC) administration on biliary and urinary excretion of copper (Cu), zinc (Zn) and iron (Fe) was investigated in sheep on a low Cu diet (Group A) and a high Cu diet (Group B). Only biliary Cu excretion increased significantly (P<0.01) with TM treatment. Urinary Cu excretion increased (P<0.01) following PEN treatment. TM, EDTA, PEN, BAL and DDC adminstration increased Cu excretion via bile and urine by 254, 11, 266, 46 and 16%, respectively in Group A sheep, and by 354, 13, 196, 20 and (-) 31% in Group B sheep. Urinary Zn excretion increased (P<0.01) following EDTA and PEN treatments. Only urinary Fe excretion increased (P<0.01) with EDTA treatment. The results show that TM and PEN are the most efficient decoppering agents, but PEN unlike TM also removes Zn. The major routes of excretion of Cu chelates by TM and PEN are different. TM increases Cu excretion significantly (P<0.05 in Group A and P<0.01 in Group B) in bile with only a slight increase in urinary Cu whereas PEN increases Cu excretion significantly (P<0.01) in urine. Therefore from a therapeutic view, a combination therapy of TM and PEN would be useful to maximize Cu removal from the body.  相似文献   

2.
During an outbreak of chronic copper poisoning, fecal and urinary copper excretion were measured following treatment with molybdenum and sulfur supplementation of the feed (0.1 g ammonium molybdate plus 1 g sodium sulfate/sheep/day) or oral penicillamine (50 mg/kg bodyweight/day) using rams in metabolism cages. Serum glutamic-oxaloacetic transaminase activities and liver levels of molybdenum and copper in sheep that died were also monitored. Within four days of starting molybdenum and sulfur supplementation a highly significant increase in fecal copper excretion was evident and the increase persisted throughout the monitoring period (five weeks — general treatment of the flock continued for another three weeks). There was no effect of the molybdenum and sulfur supplementation on urinary excretion of copper. The molybdenum and sulfur supplementation was very effective, resulting in a rapid marked decrease in mortality. Oral penicillamine treatment induced cupruresis but did not affect fecal copper excretion. The results indicated that, while the cost of penicillamine may be a limiting factor for general treatment of a flock, it may be the drug of choice for the therapy of valuable breeding animals because cupruresis may be accurately and individually controlled. Serum glutamicoxaloacetic transaminase activities were a valuable aid in diagnosing chronic copper toxicosis as well as for monitoring recovery. High initial liver copper levels were gradually reduced following molybdenum and sulfur treatment. However, at the end of the study the liver copper levels of dead sheep varied within wide limits and there were still some sheep with high liver copper levels.  相似文献   

3.
Urinary excretion of nietals during treatment with 2-rnercaptopropioiiylglycine (2-MPG) was studied in 11 normal and 20 cystinuric male dogs. 'Ihe results
were compared with those obtained during D-penicillamine treatment.
Twenty-four-h urine and morning samples of urine were taken for determina-
tion of 13 metals before and during treatment. After single intravenous and oral
D-penicillamine treatment of the normal dogs, significant increases were found
in the 24-11 urinary excretion of Ca, Cu and Zn. Oral intake of D-penicillamine
increased the excretion of Ch, Cr, Fe and Mg as well. No effect on renal metal
excretion was observed after single intravenous and up to 2 months of daily oral
treatment with 2-MPG.
In 14 cystinuric dogs no effect was found after single intravenous and oral
administrations of 2-MPG. However, after oral treatment of six cystinuric dogs
with 2-MPG for 2–4 months, significantly increased excretions of Ca and Mg
were found. Fourteen of the cystinuric dogs were also investigated after 2–6
years of continuous 2-MPG treatment, and after this period no significant
elevation in the urinary excretion of metals was found. The present study shows
that in contrast to D-penicillamine, 2-MPG does not increase the urinary
excretion of metals to any appreciable extent. Observed increases in the
excretion of Ca and Mg seemed to be a temporary effect only.  相似文献   

4.
The efficacy of a molybdate formulation and a zinc oxide bolus as prophylactic agents for enzootic icterus was evaluated in sheep. Before copper loading, liver biopsies were performed on 12 male, 6-month-old, Mutton Merino sheep to determine hepatic copper (Cu) and zinc (Zn) concentrations. The animals were restrictively randomised according to liver copper concentrations to 3 treatment groups (n = 4) to achieve similar mean liver copper concentrations per group. All sheep received 4 ml/kg of a 0.5 % aqueous solution of CuSO4 5H2O intraruminally 7 days per week for 10 weeks. On Day 0 the sheep in the Mo-group were injected subcutaneously with 42 mg molybdenum (Mo) contained in a commercial molybdate formulation. The animals in the Zn-group each received a zinc oxide bolus, containing 43 g zinc oxide, via a rumen cannula. Treatment was repeated on Day 42. Four animals served as untreated controls. Urinary copper excretion, plasma copper concentration, haematocrit and glutamate dehydrogenase (GLDH) activity were determined throughout the trial. The animals were sacrificed after 10 weeks and liver samples were submitted for histopathological examination. Liver and kidney copper and zinc concentrations were determined. Neither the molybdate treatment nor the zinc oxide boluses prevented hepatic copper accumulation. The urinary copper excretion, plasma copper concentration, haematocrit and GLDH activity were not significantly different (P > 0.05) from the controls.  相似文献   

5.
To determine whether copper removed from the liver by tetrathiomolybdate (TTM) but not excreted in bile, is excreted in saliva or urine, the effect of an intravenous injection of 100 mg of TTM, as ammonium tetrathiomolybdate, on copper excretion by these routes was measured in conscious sheep and sheep maintained under general anaesthesia. During 4.5 hours the total amount of copper excreted in bile in the untreated, conscious animal was 0.52 +/- 0.04 mumols (mean +/- SE). A dose of 100 mg TTM increased excretion by an average of 11.7-fold to 6.06 +/- 0.29 mumols. Under halothane or barbiturate general anaesthesia copper excretion was increased 3.4-fold to 1.78 +/- 0.30 mumols. In anaesthetised sheep 100 mg TTM produced a 40.7-fold increase to 21.18 +/- 0.95 mumols. Neither anaesthesia nor TTM caused any increase in copper excretion in saliva or urine.  相似文献   

6.
The copper (Cu), zinc (Zn), and iron (Fe) excreted daily in the bile of three sheep were estimated at 0.20, 0.10 and 0.36 mg respectively. Intravenous administration of tetrathiomolybdate (TM) increased bile Cu excretion and reduced liver Cu concentration. Tetrathiomolybdate had no significant effect on the excretion of Zn and Fe. These findings indicate that at least one of the mechanisms by which TM induces hypocuprosis is by increasing biliary Cu excretion. Hence it has a possible use in the treatment of Cu storage diseases in man and animals.  相似文献   

7.
Four weeks after the introduction of a new ration, a herd of sheep in the Swiss midland area was affected by depression, anorexia, decreased milk production, anemia, hemoglobinuria and frequent recumbency. Seventeen ewes died within a few days. A diagnosis of chronic copper poisoning was based on the results of feed analysis, histopathological findings and the toxicological examination of liver tissue. The remaining sheep were treated with oral ammonium molybdate and sodium sulfate, which together provide an inexpensive alternative to the chelator D-penicillamine.This combination not only prevents further copper intake, but also supports its elimination from the hepatocellular storage compartments. Serum copper levels have been determined to monitor the mobilization of copper following this antidote therapy.  相似文献   

8.
The effects of interrupting the enterohepatic circulation (EHC) of bile salts for seven hours and of feeding copper and heliotrope alone and combined for 13 weeks, on bile flow and excretion of copper, zinc, iron and alpha-mannosidase were studied in sheep. Interruption of EHC reduced bile flow rate and increased the concentration of copper, zinc, iron and bile acids while alpha-mannosidase's activity remained stable. Changes in concentration were related to changes in bile volume for copper and zinc only. Total output per hour was not changed. Biliary concentration of copper correlated with alpha-mannosidase's activity in control sheep and those given copper or heliotrope, supporting the hypothesis that lysosomes are involved in biliary secretion of copper in sheep. Increasing the intake of copper increased the rate of excretion of copper in bile. Copper output was lower when heliotrope was fed alone.  相似文献   

9.
Five female Doberman Pinschers with increased hepatic copper concentrations and persistent (3-4 years) subclinical hepatitis were treated with D-penicillamine for 4 months. Before and after treatment, the dogs underwent clinical, hematologic (red blood cell, white blood cell, and differential and thrombocyte counts), and clinical chemistry (creatinine, alkaline phosphatase, alanine aminotransferase, and total bile acid concentrations) examinations, and liver biopsies were examined histologically and their copper content measured quantitatively. No adverse effects were observed during treatment, and CBC and serum chemistry test results did not change. The mean liver copper concentration was 1,036 mg/kg dry matter before treatment and decreased to 407 mg/kg after treatment (P = .03). The copper concentrations had decreased (by between 134 and 1,135 mg/kg dry matter) in all of the dogs. The histopathologic appearance had improved or returned to normal in all 5 dogs. We conclude that D-penicillamine effectively reduced copper retention in these dogs and improved the histopathologic appearance of the lesions. However, because D-penicillamine has both copper-chelating and anti-inflammatory properties, it is not possible to draw conclusions on the etiology of this disease.  相似文献   

10.
AIM: To study the urinary disposition of orally administered sporidesmins A and D in sheep and identify factors influencing their kinetics, particularly the influence of breeding for resistance and susceptibility to sporidesmin, the mycotoxin responsible for the hepatogenous photosensitisation, facial eczema. METHODS: A competitive ELISA was used to monitor urinary output of immunoreactive metabolites after the intraruminal administration, to female Romney sheep, of either sporidesmin A or sporidesmin D, the nontoxic analogue. Preliminary characterisation of metabolites was carried out using HPLC with fractions monitored by ELISA. RESULTS: Maximum urinary excretion rates of immunoreactive metabolites occurred 2-8 h after dosing with sporidesmin D and 15-30 h after dosing with sporidesmin A. Sporidesmin D caused no liver injury, as detected by changes in serum enzyme activity, while the liver injury caused by sporidesmin A was greatest for the sheep with the highest cumulative output of metabolite. When sporidesmin D was administered in two separate doses to sheep bred for either resistance or susceptibility to facial eczema, the variability of metabolic output between sheep within groups was much less after the second dose. The mean urinary metabolite excretion was greater for the susceptible than the resistant sheep but the difference was not significant. Potentiation (caused by pre-administration of small doses of sporidesmin A) resulted in a more severe reaction to the dosed sporidesmin A. Urinary output of metabolite was less in the potentiated than in the unpotentiated sheep. When resistant and susceptible sheep were dosed with sporidesmin A after potentiation there was no difference between them in their cumulative totals or excretion rates of immunoreactive metabolites. However, the volume of urine produced by the susceptible sheep was lower and less variable than the resistant sheep and consequently the concentration of their urinary metabolites was higher. Preliminary ELISA examination of HPLC-fractionated urine from a sheep dosed with sporidesmin A indicated the presence of several metabolites of sporidesmin. CONCLUSION: Sporidesmin A and metabolites are rapidly excreted in urine but not as rapidly as sporidesmin D and its metabolites. Only minor differences between sheep bred for resistance and susceptibility were seen. Potentiation caused a more severe reaction to sporidesmin A and less urinary excretion of the sporidesmin and its metabolites. CLINICAL RELEVANCE: This work is part of a programme with the aim of identifying FE-resistant animals without the need for sporidesmin dosing.  相似文献   

11.
Twenty mature Holstein cows were randomized into 5 treatment groups. Cows of groups 2 to 5 were given 2 mg of elemental Pb/kg of body weight for 28 days. Clinical signs of plumbism were scored, and blood for Pb, progesterone, and hematologic analyses was collected weekly. Cows also were examined weekly for anomalous ovarian cycles. Starting on study day 28, cows in group 3 were treated once daily with 2 mg of thiamine HCl/kg (IM) for 13 days, cows in group 4 were treated twice daily with 62 mg of Na2,Ca-EDTA/kg (IV) for 4 days, and cows in group 5 were given thiamine (dosage regimen the same as for group 3) plus Na2,Ca-EDTA (dosage regimen the same as for group 4). On study days 96 through 139, cows were slaughtered in a commercial abattoir and samples of blood, skeletal muscles, bones, liver, and kidneys were collected and assayed for Pb concentration. Thiamine was not effective in reducing blood Pb concentration, and treatment with Na2,Ca-EDTA and thiamine plus Na2,Ca-EDTA was effective in reducing the concentration of Pb in blood. However, treatment with thiamine was more effective than treatment with Na2,Ca-EDTA or thiamine plus Na2,Ca-EDTA in inducing remission of clinical signs of plumbism. The concentration of Pb in blood was significantly (P less than 0.05) correlated to the concentration of Pb in liver, kidneys, skeletal muscles, and bones. Significant (P less than 0.05) relationship existed between number of days from Pb exposure to slaughter and concentration of Pb in blood, liver, and skeletal muscles. Exposure to Pb did not significantly alter CBC values.(ABSTRACT TRUNCATED AT 250 WORDS)  相似文献   

12.
本试验旨在研究肉羊在不同日粮精粗比条件下氮沉积和尿嘌呤衍生物的排出规律。选择12只体况健康的9月龄、体重(47.21±3.35)kg杜×寒杂交绵羊公羊,试验日粮为12种不同精粗比的全混合颗粒饲料,采用12×4不完全拉丁方设计,进行4期消化代谢试验,试验每期19 d,其中预试期14 d,正试期5 d,采用全收粪、尿法。结果表明:随日粮精粗比的提高,尿氮排出量和氮沉积量均显著提高(P<0.05),日粮精粗比对粪氮排出量的影响不显著(P>0.05),氮沉积量与氮采食量之间存在线性相关(R2=0.72,P<0.05);尿中尿囊素排出量和总尿嘌呤衍生物排出量均随日粮精粗比升高而显著升高(P<0.05),尿囊素、尿酸、黄嘌呤和次黄嘌呤排出量占总尿嘌呤衍生物排出量的比例变化范围分别为69.92%~84.76%、2.89%~7.58%和9.39%~25.04%。日粮精粗比对粪氮与尿氮有不同的影响,对尿嘌呤衍生物排出量影响显著;尿嘌呤衍生物排出量与尿氮排出量存在着线性相关,相关方程为Y=0.429X+0.324(R2=0.85)。  相似文献   

13.
The effects of the antidiuretic hormone (ADH) on the renal excretion of urea and electrolytes were studied in sheep, subjected to water stress, before and after 36-hour fasting. The intravenous administration of synthetic lysine-vasopressin (L-VP) at the dose of 100 microgram per kg induced only a temporary, statistically insignificant, drop of the urinary urea outputs by the fed as well as fasting sheep. L-VP did not influence the excretion of sodium and potassium electrolytes either. It follows from the results that there are no differences in the renal response to ADH between the fed sheep and sheep that have fasted for 36 hours.  相似文献   

14.
This study investigated the effects of intravenous (IV) administration of tetrathiomolybdate (TTM), and α(2)-adrenergic agonist clonidine (CLO) and α(2)-antagonist idazoxan (IDA), alone or in combination with TTM, on sheep fed low (LCu) and high (HCu) copper diets. Effects on bile flow, biliary Cu concentration and excretion, plasma Cu concentration, and lysosomal enzyme β-glucuronidase (β-GLU) activity in bile and plasma were determined. Tetrathiomolybdate alone or with CLO or IDA significantly enhanced biliary Cu excretion most likely by removing Cu from hepatocyte lysosomes as evidenced by a significant increase in β-GLU enzyme activity in bile. A significant increase in plasma β-GLU concentration occurred only in sheep treated with CLO in combination with TTM. Because of the lytic nature of the lysosomal enzymes, caution is advocated in use of drugs, especially α(2)-adrenergic agonists, to further enhance TTM-induced biliary Cu excretion in the treatment of chronic Cu poisoning in sheep.  相似文献   

15.
The relationship between blood plasma level and urinary excretion of allantoin (AN) was examined in sheep and goats during fasting to investigate the possible use of purine derivatives (PD) in urine and/or plasma for estimating the microbial protein production in the rumen, and the further digestion in the lower guts of ruminants. Urinary AN excretion decreased markedly during fasting (0.13 mmol/kgW0.75 per day), although urinary levels of other PD, hypoxanthine + xanthine and uric acid did not differ irrespective of the feeding condition, that is, feeding, fasting and refeeding in both species. The AN concentration in blood plasma also decreased drastically in the starvation period, and was suddenly increased on refeeding in sheep and goats, and these phenomena were very similar to those of urinary AN excretion. Therefore, there was a high positive correlation between plasma AN level and urinary AN excretion, and the coefficient of correlation was statistically significant (P < 0.01). These results clearly indicate that changes in urinary AN reflect change in plasma AN, which is induced by the catabolism of purine base in the body.  相似文献   

16.
The renal excretion of selenium was investigated in ewes with an excretion of hypotonic urine (control group) and in ewes with a formation of highly concentrated urine. Chronic stimulation of the urinary concentrating activity of sheep kidneys was induced by a long-term treatment with 1-desamino-8-D-arginine vasopressin (dDAVP), a synthetic analogue of vasopressin with prolonged effects. Young animals with 22 to 25 kg b.w. were fed a normal protein diet providing a daily intake of 129.25 g of crude protein, 12.03 MJ of digestible energy and 0.18 mg of selenium for 3 weeks. The vasopressin treated sheep (n = 11) were given subcutaneous injections of 12.5 micrograms of dDAVP in glycerol twice daily for one week before the clearance measurement of renal functions. The control group (n = 11) was treated with glycerol only. The administration of dDAVP resulted in a highly significant decrease of the urinary flow rate (from 3.19 +/- 0.50 in control group to 0.33 +/- 0.03 mL.min-1 in dDAVP animals, P < 0.001) without changes in the glomerular filtration rate (80.18 +/- 6.36 in controls vs. 77.86 +/- 6.26 mL.min-1, NS). No effects on plasma selenium level were observed (0.17 +/- 0.03 in controls vs. 0.20 +/- 0.03 mumol.L-1, NS) but the amounts of selenium excreted were found to be highly significantly reduced (from 0.29 +/- 0.05 in controls to 0.03 +/- 0.01 nmol.min-1, P < 0.001) in dDAVP treated sheep. Despite a large reduction in urinary flow rate, the selenium concentration in urine was actually the same in both groups (0.09 +/- 0.01 mumol.L-1) resulting in a sharp fall in the renal clearance of selenium (2.20 +/- 0.54 in controls vs. 0.18 +/- 0.03 mL.min-1, P < 0.01) due to dDAVP. This seems to be a consequence of the large increase in the selenium solvent drag induced by a vasopressin treatment. The results presented suggest that vasopressin may contribute to maintenance of the selenium balance in sheep via its effects on renal function.  相似文献   

17.
In this study, we investigated parthenogenetic induction of canine oocytes by electrical stimulation following Ca-EDTA treatment. Oocyte maturation, parthenogenetic development, and cleavage rate in canine after various electrical stimulations (1.5, 1.8, 2.1 kV/cm) for 50 μs with single DC pulse following 1 mM Ca-EDTA treatment were investigated. In oocyte activated electrically at the voltage of 1.5 kV/cm after 1 mM Ca-EDTA treatment, the rate of pronucleus and two-cell was 4.1% and 2.7%, respectively. Although electrical stimulation could parthenogenetically induce immature oocyte to cleavage stage, degeneration rate in all experimental groups was more than 60%. This means that electrical stimulation after Ca-EDTA treatment could cause canine oocytes to be degenerated. However, two-cell in canine oocyte by parthenogenesis was for the first time induced. Therefore, we suggested that electrical stimulation for canine oocytes could induce parthenogenetically early embryonic cleavage. This result can be used as a basic data for parthenogenesis study in canine. Also, to perform more developed embryonic development, further study to parthenogenesis in canine need to be developed.  相似文献   

18.
Summary

The disposition and urinary excretion of ciprofloxacin (CIP) following intravenous (IV) or intramuscular (IM) administration of 7.5 mg/kg body weight in sheep (n = 5) was studied. The intravenous plasma concentration curve was best described pharmacokinetically by a two‐compartment open model, while the intramuscular administration data fitted better to a one‐compartment open model. Mean elimination half‐lives after IV and IM administration were 72 and 184 minutes, respectively. The absorption of intramuscularly administered CIP in sheep was fast: maximal plasma concentration (Cmax) was reached quickly (tmax 31.93 min) and attained values of 0.69 ± 0.27 mg/l. The bioavailability was 49%. The urinary data showed a significant decrease in the elimination rate constant of CIP when CIP was administered intramuscularly. The other parameters calculated did not display differences between the two routes of administration. The results obtained suggest that when CIP was administered by the IM route in the assayed dose, it was able to maintain serum concentrations above the MIC of most common pathogens over an 8‐hour period.  相似文献   

19.
Two in vivo digestibility trials with sheep were conducted to identify the minimum period length of feeding a new diet to obtain reproducible values of nutritional variables onward and the minimum length of collection period as to obtain maximal precision for each variable. Trial 1 was conducted with ten Polwarth male sheep (34 ± 5 kg body weight (BW)) throughout three 21‐day periods, in a completely randomized two‐way crossover design. The animals were divided into two groups (Group A and B, n = 5 per group) which were fed ad libitum with a sequence of the following diets throughout the periods: Group A: hay – hay plus concentrate – hay; Group B: hay plus concentrate – hay – hay plus concentrate. The concentrate was included in a proportion of 0.33 of the total diet. The intake, and the faecal and urinary excretion were measured daily throughout the experiment. For evaluating rumen fermentation variables, in Trial 2 four Santa Inês male sheep (65 ± 5 kg BW) fitted with ruminal cannula were used. The animals were randomly divided into two groups (n = 2 per group), and the trial was conducted through four 21 days experimental period, in a three‐way crossover design, using experimental diets and feeding management similar to Trial 1. The results indicated that, even though no clear or consistent steady‐state condition was identified for rumen fermentation or urinary excretion variables, the adaptation period for measuring OM digestibility in in vivo trials with sheep fed ad libitum where the diet shifts from one of only hay to another containing concentrate, or vice‐versa, should be at least 12 days long. Moreover, although no precision improvement was obtained by increasing the collection period above 1 day for measuring OM digestibility, the minimal length of collection period should be 4 days for measuring faecal excretion variables and 7 days for measuring urinary excretion variables.  相似文献   

20.
日粮中添加丙烯酸对绵羊消化代谢的影响   总被引:2,自引:1,他引:1  
选取25只身体健康,体重32kg左右的8月龄中国美利奴(新疆型)细毛公羊,日粮精粗比为25∶75,采用分组试验设计,分别是对照组、添喂丙酸8,12mmol/(d·只)组和添喂丙烯酸8,12mmol/(d·只)组,研究丙烯酸对绵羊消化代谢和体增重的影响。结果表明,与对照组和添喂丙酸组相比,添喂丙烯酸组绵羊干物质采食量没有显著差异(P>0.05);添喂丙烯酸组与对照组相比,半纤维素消化率提高5.15%~9.70%,纤维素消化率提高3.64%~5.73%,但差异不显著(P>0.05);8mmol丙烯酸组钙、磷的消化率分别高于8mmol丙酸组2.86%和8.39%,但差异不显著(P>0.05);添喂8,12mmol/(d·只)丙烯酸组绵羊的尿氮排出量(g/d)分别低于对照组12%和18%,而N保留率与对照组相比分别提高5.35%和3.91%,但均没有显著差异(P>0.05)。添喂丙烯酸组绵羊的体增重和饲料利用率与对照组和丙酸组相比没有显著差异(P>0.05)。本研究表明,添喂丙烯酸对绵羊的采食量、干物质、有机物、粗蛋白、纤维素、半纤维素的消化量(率)均无显著影响(P>0.05),对绵羊氮、钙、磷的代谢无显著影响(P>0.05)。  相似文献   

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