Mesh-like vascular changes in copper deficiency-induced rat cardiomyopathy

The pathological effects of copper deficiency (COD) are well known. However, the pathogenesis of cardiomyopathy resulting from COD remains unclear. In this study, aimed to elucidate the pathogenesis of COD-induced cardiomyopathy by examining the morphology of the cardiovascular system in copper-deficient rats using histopathology, immunohistochemistry, and scanning and transmission electron microscopy. Changes detected in the myocardium and interstitium were consistent with those reported for COD. Morphological changes included mesh-like changes in the capillary endothelial cells that appear to be a novel finding in COD-induced cardiomyopathy. These changes are hypothesized to result from abnormal vascular remodeling following damage to the basement membrane and due to the mechanical effects of myocardial contractions. Although cardiomyopathy may be associated with microcirculatory disorders arising from these lesions, further investigations are necessary to demonstrate a causal relationship between the pathogenesis of cardiomyopathy and the contribution of these lesions to disease progression.     

Anaemia and changes in erythrocyte morphology associated with copper and selenium deficiencies and dietary restriction in rats

Both selenium and copper deficiencies in rats caused morphological changes in erythrocytes but only copper deficiency resulted in anaemia. Similar but less severe morphological changes occurred when rats consuming selenium- and copper-adequate diets had their food intake restricted to that of the copper-deficient animals. Since selenium deficiency did not affect the severity of changes due to copper deficiency this suggests that alterations of erythrocyte morphology may not be entirely due to impaired functions of selenium and copper in cell antioxidant systems. Thus, erythrocyte structure was sensitive to several dietary changes and such alterations are probably independent of the anaemia induced by copper deficiency. This possibility should be considered when changes in erythrocyte morphology are attributed to copper or selenium deficiency in animals which also have a restricted food intake.     

Osteochondrosis and epiphyseal bone abnormalities associated with copper deficiency in bison calves

Two bison calves were submitted to the Western College of Veterinary Medicine to confirm suspected copper deficiency. In addition to clinical signs, there were pathologic changes in the cartilage and subchondral bone of several joints. Water analysis indicated high levels of sulfate in the drinking water, contributing to a secondary copper deficiency.     

Changes in enterocyte mitochondria associated with deficiency of copper in cattle.

Comparisons were made between specimens of intestinal mucosa from three young Friesian steers, killed when showing clinical signs associated with copper deficiency, and three controls that had received supplementary copper. Copper deficiency was associated with marked depletion of cytochrome oxidase in the epithelium of the duodenum, jejunum and ileum, and with partial villus atrophy in the duodenum and jejunum. Enterocytes from the duodenum, jejunum and ileum showed mitochondrial abnormalities ranging from slight swelling to marked localised dilation. Many of the mitochondria not affected by swelling had a distinctly condensed appearance. These changes are discussed in relation to the copper-responsive diarrhoea that affects a proportion of cattle suffering from copper deficiency.     

铜缺乏奶牛神经递质酶的组化特征

为探讨铜缺乏对奶牛大脑、小脑及脊髓乙酰胆碱酯酶（ACHEase)组化特征（分布特点及活性）的影响，本实验选择铜缺乏症高发区自然发病的奶犊牛6头，剖杀后采集大脑、小脑、脊髓作冰冻切片及酶组化染色，以6头同年生健康奶犊牛为对照。实验结果表明，发病奶牛大脑、小脑及脊髓中ACHEase计数值均显著低于对照组奶牛（P＜0．05）；除大脑外，铜缺额奶牛脊髓上小脑中ACHEase的扫描值也显著低于对照组（P＜0．05）；发病奶牛脊髓小脑中ACHEase的扫描值也低于对照组（P＜0．05）；发病奶牛组织中ACHEase酶颗粒的分布也发生特征性的变化。结论：神经递质酶活性的改变是导致奶牛铜缺乏症病理过程的重要原因。     

铜缺乏奶牛琥珀酸脱氢酶的组化特征

为探讨铜缺乏对奶牛心脏、肝脏、肾脏琥珀酸脱氢酶 (SDHase)组化特征 (分布特点及活性 )的影响 ,本实验选择铜缺乏症高发区自然发病的奶犊牛 6头 ,剖杀后采集心、肝、肾作冰冻切片及酶组化染色 ,以 6头同年生健康奶犊牛为对照。实验结果表明 ,发病组奶牛心脏中 SDHase计数值显著高于对照组 (P<0 .0 5 ) ,而肝脏、肾脏中SDHase计数值显著低于对照组 (P<0 .0 5 ) ;健康组奶牛心脏、肝脏、肾脏中 SDH活性扫描值均显著大于发病组(P<0 .0 5 )。发病奶牛组组织中 SDHase酶颗粒的分布也发生特征性的变化。结论 :氧化呼吸链关键酶活性的改变是导致奶牛铜缺乏症病理过程的重要原因     

Use of erythrocyte copper:zinc superoxide dismutase activity and hair or fleece copper concentrations in the diagnosis of hypocuprosis in ruminants

Changes in the activity of superoxide dismutase, a copper-containing enzyme in erythrocytes (ESOD), and changes in copper in hair or fleece were compared with the changes in plasma copper during copper depletion and repletion in steers, lambs and ewes. During depletion the decline in ESOD began later than the decline in plasma copper: the lag varied from 0 to 80 days in individual steers and it was least evident when young rapidly growing lambs were subjected to severe depletion. ESOD activity eventually declined at only one-third to one-seventh of the rate shown by plasma copper, the difference being particularly marked in severely depleted lambs. Repletion of ESOD began after repletion in plasma copper and continued more slowly particularly in growing animals. Hair and fleece copper also responded relatively slowly to depletion and repletion. Low values of ESOD and hair or fleece copper may have diagnostic significance, indicating a more prolonged or intense deficiency of copper and a higher probability of clinical and production responses to copper therapy than low plasma or liver copper values.     

Plasma and liver copper values in horses with equine degenerative myeloencephalopathy.

Equine degenerative myeloencephalopathy (EDM) is a common spinal cord disease in the horse. The etiology of EDM currently is unknown. In other species, there are similarities in the clinical signs and neuropathological changes observed in EDM and in copper deficiency. The objective of this study was to determine if horses affected with EDM had low levels of plasma or liver copper. Plasma copper values were determined in 25 EDM affected horses and 35 normal horses. Liver copper levels were determined on 13 EDM affected horses and 22 normal horses. Plasma and liver copper values were not significantly lower in EDM affected horses than in control horses.     

The effect of copper deficiency on the peripheral blood cells of cattle

Six female cattle were given molybdenum (30 ppm) and sulphate (225 ppm) to induce experimental secondary copper deficiency. The total and differential leukocyte numbers and lymphocyte subpopulations were counted and the neutrophil activity was assessed by means of nitroblue tetrazolium reduction and phagocytosis of sheep erythrocytes. The serum caeruloplasmin activity and concentration were also determined. Copper deficiency was confirmed from decreased serum copper levels, the animals with values less than 5.9 µmol/L being considered deficient. Total leukocyte numbers were not affected by the copper deficiency. However, differential counts showed a marked increase in monocyte subpopulations, a significant decrease in B lymphocytes and reduced neutrophil activity. The serum caeruloplasmin activity was decreased about 50%, but the total serum protein concentration was less altered. We concluded that the effect of these changes on the animals' immune competence may contribute to a greater incidence of infectious diseases in copper-deficient cattle.     

Effects of molybdenum or iron induced copper deficiency on the viability and function of neutrophils from cattle

Neutrophils from cattle with copper deficiency induced by molybdenum (0.052 mmol molybdenum kg-1 diet) or iron (8.95 mmol iron kg-1 diet) had an impaired ability to kill ingested Candida albicans and were less viable than those from copper-supplemented cattle in in vitro tests of function. Restricted intake (80 per cent of ad libitum) of a copper-adequate diet by cattle also decreased neutrophil candidacidal activity and viability. Additionally, the ingestion of C albicans by neutrophils was impaired by the molybdenum or iron treatments but not by restricted food intake. The changes in neutrophil function and the severity of copper deficiency, in biochemical terms, induced by the molybdenum or iron treatments were greater than those induced by diets of low copper content.     

铜缺乏对奶牛肝脏金属硫蛋白代谢的影响

为阐明金属硫蛋白在铜缺乏奶牛肝脏中的代谢特征 ,选择铜缺乏区有明显临床症状的奶牛 6头 ,采集肝脏样品后用差速离心法分离肝脏金属硫蛋白 ,以Sephadex G75进行层析纯化 ,测定各部分洗脱液中金属元素铜、锌、铁、镁的含量。将 6头健康奶牛的肝脏样品作为对照。试验结果表明 ,发病奶牛肝细胞浆Sephadex G75柱层析洗脱液中铜、铁含量峰值显著高于健康奶牛 ,且在后面部分层析液中出现小峰 ;发病奶牛肝细胞浆金属硫蛋白 (MT)层析液锌、镁含量曲线峰值宽阔且高于对照组 ,第 2峰形宽大且有前移现象。结论 :铜缺乏能够改变奶牛肝脏中金属硫蛋白的代谢     

Use of copper oxide wire particles (Copinox) for the prevention of congenital copper deficiency in a herd of German Improved Fawn breed of goat

In a herd of German Improved Fawn breed of goat in the year 2000 neonatal kid losses due to congenital copper deficiencies were observed. To clarify the problems and to prevent losses in the next breeding season serum copper levels of 10 dams and four control Boer goats were investigated at four time points during one year. Additionally ten kids of the following year were sampled and the serum copper levels were studied. Immediatly after parturition and 8 weeks later the dams showed low serum copper levels (10.4 +/- 11.1 micromol/l, 5.7 +/- 2.9 micromol/l resp.). At the end of the pasture season an increase of serum copper could be measured (19.3 +/- 16.0 micromol/l). To prevent enzootic ataxia due to congenital copper deficiency, the dams were treated with copper oxide wire particles in the next late gestation. At this time point serum copper concentrations started to decrease (18.5 +/- 8.4 micromol/l). The re-examination 3 month later demonstrated an increase of the serum mean copper concentrations up to 23.4 micromol/l in the dams and to 16.2 micromol/l in the kids. The serum copper levels were significantly higher compared to the levels the year before. Big variation of the serum copper levels in the control Boer goats occurred during the year, but no clinical symptoms of copper deficiency could be observed. The copper levels in the grass and soil samples were 6.8 mg/kg and 0.2 mg/kg dry substance, respectively. A secondary copper deficiency based on cadmium could be excluded through the low levels of soil samples. The contents of sulphur and molybdenum were not determined. The results indicate that the German Improved Fawn breed of goats suffered from a primary copper deficiency due to the inefficient mineral supplementation. The administration of Copinox in the last third of the gestation leads to a continious raising of the copper concentrations in the serum and is suited to prevent ataxia due to congential copper deficiency in neonatal kids.     

Effects of concurrent copper deficiency and gastro-intestinal nematodiasis on circulating copper and protein levels, liver copper and bodyweight in sheep

Sheep were rendered hypocupraemic using parenteral ammonium tetrathiomolybdate (ATM). Fifteen thousand third stage larvae of Trichostrongylus axei and T. colubriformis in the ratio 1:1 were administered three times per week for six weeks, starting four weeks after cessation of ATM treatment. The changes in liver and plasma copper (Cu), caeruloplasmin activity, serum proteins, faecal nematode egg counts and total nematode counts were measured in the sheep for 10 weeks after infection. Decreases in liver Cu, plasma Cu and caeruloplasmin activities were detected soon after infection. There was a significant (P less than 0.05) interaction of the effects of Cu deficiency and nematode infection on these changes. Hypoproteinaemia, attributed to serum albumin loss, was demonstrated seven weeks after infection, but this was not associated with the interaction of Cu deficiency and nematode infection. No changes in serum globulins were detected. Although the results support the contention that gastro-intestinal nematodiasis can significantly exacerbate an existing Cu deficiency in sheep, there was no evidence that hypocuprosis would predispose sheep to higher nematode burdens.     

Serum copper concentrations in beef cows and heifers

OBJECTIVE: To characterize serum copper status of cows and heifers in beef cow-calf herds throughout the United States and to evaluate use of copper supplements in those herds. DESIGN: Cross-sectional survey. ANIMALS: 2,007 cows and heifers from 256 herds in 18 states. PROCEDURES: Producers participating in a health and management survey conducted as part of the National Animal Health Monitoring System voluntarily allowed serum samples to be obtained from cows and heifers for determination of copper concentration. Results were categorized as deficient, marginally deficient, or adequate. The proportion of cattle and herds (on the basis of mean value of the tested cattle) in each category was determined. Copper concentrations were compared between herds that reportedly used copper supplements and those that did not. RESULTS: Overall, 34 of 2,007 (1.7%) cows and heifers were deficient in copper, and 781 (38.9%) were marginally deficient. In each region, at least a third of the cattle were deficient or marginally deficient. For herds, 92 of 256 (35.9%) were marginally deficient, and 22 (0.8%) were deficient. Approximately half of the producers reported use of copper supplements, but a sizeable proportion of those producers' cattle and herds were classified as marginally deficient or deficient. CONCLUSIONS AND CLINICAL RELEVANCE: Copper deficiency is not restricted to a single geographic region of the United States. Copper deficiency can persist despite reported use of supplements by producers. Veterinarians dealing with beef cow-calf herds that have problems consistent with copper deficiency should not rule out copper deficiency solely on the basis of geographic region or reported use of copper supplements for the herd.     

Sensitivity and specificity of serum copper determination for detection of copper deficiency in feeder calves

OBJECTIVE: To determine the relationship between serum and liver copper concentrations and evaluate serum copper determination for diagnosis of copper deficiency in juvenile beef calves. DESIGN: Cross-sectional study. ANIMALS: 105 juvenile beef calves. PROCEDURE: Copper concentrations were measured in paired liver and serum samples from 6- to 9-month-old beef calves. Regression models that predicted liver copper concentration as a function of serum copper concentration were developed. Sensitivity and specificity of serum copper concentration for detection of low liver copper concentration were determined, using a range of serum copper concentrations as test endpoints. Positive and negative predictive values were calculated. RESULTS: The association between serum and liver copper concentrations was significant; however, regression models accounted for only a small portion of the variation in liver copper concentrations. For a serum copper concentration endpoint of 0.45 microg/g, sensitivity and specificity for detection of low liver copper concentration were 0.53 and 0.89, respectively. Positive and negative predictive values of serum copper concentration for detection of low liver copper concentration ranged from 0.37 to 0.85 and 0.63 to 0.94, respectively. CONCLUSIONS AND CLINICAL RELEVANCE: Regression models are inappropriate for predicting copper status as a function of serum copper concentration. Serum copper concentration is fairly specific for detection of low liver copper concentration but only marginally sensitive when serum copper concentration of 0.45 microg/g is used as a test endpoint. The value of serum copper concentration as a diagnostic indicator depends on prevalence of copper deficiency.     

摇摆病奶牛体内铜状态及其与NO水平的关系

为探明枘本中反映铜状态的几个重要标识与奶牛摇摆病之间的关系，并阐述奶牛体内NO水平及自由基的含量在该病发生中的作用，实验抽样测试了病区及非病区同年生奶犊牛血清铜、全血铜含量及血浆铜氧化酶（CP）、血清超氧化物歧化酶（CuZn-SOD）的活性；同时也检测了全血总自由基相对含量及血清NO含量。实验结果表明：病区奶牛化物歧化酶CuZn-SOD活性极显著地高于非病区奶牛（P＜0.01），并且病区发病奶牛与临床健康奶牛相比，该酶活性差异显著（P＜0.05）；病区奶牛CP活性显著低于非病区，同时病区临床健康牛与病牛间该酶活性差异显著（P＜0.05）；发病牛与病区临床健康牛的血清铜及全血铜之间的差异不显著（P＞0.05）；病区奶牛NO含量显著低于非病区而自由基含量显著高于非病区。结论 CuZn－SOD及CP更能反映机体内缺铜的程度；铜缺乏导致的机体自由基堆积和NO水平的改变也是该病发生的重要因素。     

Presumptive copper deficiency in hand-reared captive pronghorn (Antilocapra americana) fawns.

Presumptive copper deficiency was diagnosed in hand-reared captive pronghorn (Antilocapra americana) at the Los Angeles Zoo. Clinical signs, which were manifested in growing fawns, included anemia, anorexia, diarrhea, progressive paresis/recumbency, and aortic rupture. The range of serum copper concentrations in fawns born during the 1989 season (0.08-0.67 ppm) was below levels considered normal for domestic sheep and goats (0.7-2.0 ppm) and below concentrations measured in adult pronghorn (0.4-1.43 ppm). Copper sulfate supplementation of the hand-rearing formula, which was initiated in 1989, resulted in a significant increase in mean (+/- SD) serum copper levels from 0.45 +/- 0.18 ppm before supplementation to 0.68 +/- 0.05 ppm after supplementation (P < 0.05). Fawns born in subsequent seasons (April 1990-August 1993) continued to be supplemented with copper in the hand-rearing formula. Mean serum copper concentration from these fawns (0.68 +/- 0.22 ppm) was similar to the mean values from supplemented 1989 fawns and adult pronghorn in this herd (0.85 +/- 0.34 ppm; P > 0.05). No clinical signs of copper deficiency were detected in any fawns after supplementation was started. Analyses of the herd's diet revealed marginal dietary copper levels. Suspected dietary deficiency was confirmed by marginal tissue and serum copper concentrations in some of the herd's adult animals. Dietary copper levels were corrected to prevent future cases of clinical copper deficiency.     

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.     

毛皮动物铜锌的营养需要及缺乏症

在铜锌生物学作用基础上,阐述了毛皮动物对铜锌的营养需要,并根据国外的标准给出了适宜的推荐量：同时,针对毛皮动物铜锌缺乏的症状,分析其缺乏的可能原因及评价铜锌营养状况的方法;最后,结合铜锌比、铜锌超氧化物歧化酶说明铜锌两种微量元素在毛皮动物营养中的相互关系。     

引起羔羊摇摆病病因的诊断与分析

通过对青海省湟中县某羔羊群中发生摇摆病的发病情况、临床症状、病理变化、分离培养、重金属盐及微量元素的检测和治疗性诊断的初步分析,初步认为引起湟中县某羔羊群中发生摇摆病的病因为铜缺乏症。