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1.
One hundred nineteen hepatic tissue samples from 117 Bedlington Terriers were divided into 6 groups depending on the severity of histopathologic hepatic changes. Group 0 comprised dogs with microscopically normal livers. Group I dogs had copper-positive, lipofuscin-containing lysosomes present in centrilobular hepatocytes. Microfoci of hepatic necrosis, in addition to the increased numbers of the copper-positive, lipofuscin-containing lysosomes in centrilobular and periportal hepatocytes, were present in group II dogs. Group III dogs had more copper-positive, lipofuscin-containing lysosomes present translobularly and morphologic changes consistent with chronic active hepatitis. Mixed micro- or macronodular cirrhosis and translobular presence of copper-positive, lipofuscin-containing lysosomes characterized group IV dogs. Dogs in group V had massive hepatic necrosis and morphologic changes that were consistent with the changes in group III and IV dogs. Histochemical staining for copper was useful in making the microscopic diagnosis of this disease and was shown to be necessary in early diagnosis (group I) when other clinical and pathologic values associated with this syndrome were not consistently abnormal. Copper histochemical stains varied in sensitivity. Timm's silver sulfide was more sensitive for copper than was rubeanic acid, which was more sensitive than rhodanine staining. The brown pigment associated with the copper in the lysosomes was shown to be lipofuscin pigment with the aid of histochemical staining with orcein, Prussian blue, periodic acid-Schiff, and acid-fast stains together with fluorescent microscopy (excitation maxima: 365 nm; emissions: 420 + nm). Since these were positive only in later stages of the hepatic disease, they were not especially useful in its early diagnosis. The severity of the histopathologic hepatic changes was shown to increase with age and was associated with increasing hepatic copper concentration. These observations illustrate that this inherited, chronic hepatic degeneration in the Bedlington Terrier is progressive. Clinical chemical tests were diagnostically useful only in later stages of the disease. Alanine transaminase activity was of most value, but was not always abnormal, even when severe hepatic damage was present. Clinical signs of hepatic disease were seen in dogs in groups III, IV, and V. Death due to hepatic failure occurred only in dogs in groups III, IV, and V. Hemosiderin was present in increased amounts in the liver, bone marrow, spleen, and lymph nodes of affected Bedlington Terriers, indicating that a possible defect in iron metabolism and/or an increase in RBC turnover existed.(ABSTRACT TRUNCATED AT 400 WORDS)  相似文献   

2.
The objectives of this study were to determine the time course of copper (Cu) absorption in the Bedlington Terrier (BT) dog after duodenal infusion of Cu and to determine the onset of Cu accumulation in BT puppies. At 80 minutes after infusion, Cu was present in the bile and liver at 26.1 and 2675 microg/g dry weight (dw), as compared with 598 and 224 microg/g dw, respectively, in the control. In the puppies, the mean liver Cu concentrations were 443 +/- 216 microng/g dw as compared with 54 +/- 34 microg/g dw in their controls. The BT puppies had large numbers of Cu granules in their hepatic lysosomes, with very few in the bile canaliculi. In contrast, the controls had few granules in their lysosomes and large numbers in their canaliculi. These results suggest that hepatic Cu accumulation occurs rapidly and in utero in the BT.  相似文献   

3.
Concentrations of iron, copper, and zinc were measured in livers of 95 dogs that were suspected of having liver disease. Iron concentrations ranged from 177 to 7,680 ppm (dry weight basis); 54 dogs had iron concentrations greater than the normal concentration of 1,200 ppm. Iron stores were present in Kupffer cells and macrophages but not hepatocytes. The dogs did not have lesions of hemochromatosis. Dogs with high liver iron tended to have high liver copper and inflammatory lesions. High liver copper concentrations usually were associated with hepatocellular necrosis and fibrosis. High liver zinc was found in only 5 animals and was accompanied by histologic inflammatory lesions in one. In humans, increased iron concentration in the liver exacerbates liver damage caused by a variety of insults, and the same may be true for dogs.  相似文献   

4.
Copper toxicosis in veal calves   总被引:1,自引:0,他引:1  
Copper toxicosis was diagnosed in 7 veal calves, 10-16 weeks old, from 5 separate farms. All calves died without specific clinical signs, although 4 of the calves were icteric. The calves' dietary rations had been supplemented with various copper-containing hematinics. Peritoneal hemorrhage was reported at post-mortem in 2 calves. Microscopic evidence of hepatopathy consisted of hepatocellular degeneration and necrosis, hemorrhage, and fibrosis. Concentrations of copper in livers from intoxicated calves ranged from 277 to 684 ppm and in kidneys from 1.1 to 82.0 ppm. The extent and severity of lesions in livers appeared to correlate with concentrations of copper. Nephrosis was minimal, without evidence of hemoglobinuria.  相似文献   

5.
Hereditary copper toxicosis in West Highland white terriers   总被引:1,自引:0,他引:1  
Histologic, histochemical and atomic absorption studies on liver tissue from 71 West Highland white terriers are reported. Twenty-seven dogs had histologically normal liver and copper concentration comparable to mongrel control dogs. Forty-four dogs had hepatic copper concentrations up to 22 times the mean copper concentration found in clinically normal mongrel dogs. Hepatitis, hepatic necrosis and cirrhosis were associated with the increased copper concentration in some dogs. Matings between dogs with high liver copper concentration produced pups with high liver concentration. The copper storage defect is inherited.  相似文献   

6.
Six Merino sheep were dosed orally with a 0.2 per cent solution of copper sulphate, six others were undosed controls. Liver biopsies were obtained and stained for copper by the p-dimethylaminobenzylidene rhodanine (DMABR), rubeanic acid (RA) and ferricyanide (FCN) methods for examination by light microscopy. The initial and most marked accumulations of copper were found within the hepatocytes of the centrilobular zones. Increased copper loading resulted in copper deposition extending through the midlobular to the periportal zones. The deposition of copper was unequal between hepatocytes and with increasing copper loading isolated hepatocytes became packed with copper containing granules. Copper appeared within Kupffer cells and macrophages of portal triads. The first Kupffer cells to be positively stained and the greatest number of such cells were adjacent to the central veins. Accumulation of copper was demonstrated with hepatocytes at copper concentrations equivalent to 44.3 micrograms copper g-1 liver wet weight. The FCN method provided a more satisfactory demonstration of intracellular copper than the RA technique and the latter was better than the DMABR method. However, the DMABR technique provided the clearest morphological details.  相似文献   

7.
The effects of intravenously administered thiomolybdate on the liver and kidney of copper loaded sheep were studied using 16 ewes in three groups. Copper, iron and molybdenum concentrations were determined by spectrophotometry and the distribution of copper in the liver and kidney was studied histochemically. Following thiomolybdate administration, the concentration of copper in the liver was reduced, that of molybdenum increased and the concentration of copper and molybdenum in the kidney increased. The reduction of copper concentration in the liver was associated with reductions in the number and size of granules in hepatocytes which stained positively for copper and in the number of Kupffer cells containing positively staining granules. The decrease in the amount of copper in hepatocytes appeared to be greater than that in Kupffer cells. This effect was greatest in the centrilobular zones and least in the periportal zones. The increased concentration of copper and molybdenum in kidney was associated with an increase in the number and size of granules staining positively for copper in the epithelial cells of the proximal convoluted tubules which suggested an uptake of copper-molybdenum complexes by the lysosomes of these cells.  相似文献   

8.
Abnormal hepatic copper storage in a teleost fish (Morone americana)   总被引:1,自引:0,他引:1  
Excessive copper storage in livers of feral white perch (Morone americana) from the Chesapeake Bay is described. Age-related, progressive accumulation of hepatic copper in levels often exceeding 1,000 micrograms/g wet weight was associated with peribiliary fibrosis and inflammation, bile duct hyperplasia, prominent, enlarged melanomacrophage centers, and disruption of hepatic architecture in older fish. Levels of zinc were mildly elevated compared to striped bass (Morone saxitilis) and adult rats. Cholangiomas were found in two perch. Rubeanic acid-stained liver had abundant copper-positive cytoplasmic granules in hepatocytes and cells of melanomacrophage centers. Subcellular fractionation showed that 90% of hepatocellular copper was in nuclei/cell debris fractions (which also contain tertiary lysosomes). Using electron probe microanalysis, high copper levels were localized in hepatocellular cytoplasmic bodies. Resolution of hepatic cytosol by gel permeation chromatography indicated that approximately 50% of the cytosolic copper in the white perch was bound to non-specific high molecular weight proteins, with the remaining 50% eluting at a peak where rat metallothionein is located. Ultrastructural examination revealed abundant lysosomes, increased size and number of peroxisomes, and increased density and numbers of mitochondrial matrix granules. This study indicates that white perch may be a model for studying effects of excessive copper accumulation and cellular mechanisms which control copper kinetics.  相似文献   

9.
Eight of 9 Mute swans (Cygnus olor) untied in the river acrossing the central part of Tottori-city died within the period of 40 days of summer in 1989. Seven of 8 Mute swans were pathologically examined. In all swans many yellowish-brown to greenish-brown granules were found in the cytoplasm of hepatocytes. The granules were intensely stained with rhodanine copper stain, schmorl method, and Berlin blue stain. Ultrastructurally, many lysosomes increased in size and density in the cytoplasm of hepatocytes. Other three swans, that died at other places, were served as controls. In control swans, many brown granules intensely stained with schmorl method and Berlin blue stain were also found in hepatocytes, but the number of rhodanine-positive granules were fewer than those of the affected cases. X-ray qualitative analysis showed three peaks corresponding to copper, zinc and sodium in the liver of the affected and control swans. Quantitative analysis demonstrated that mean hepatic copper concentration of the affected group was significantly higher than that of control group (P less than 0.01). From these findings, we concluded that all of 7 Mute swans died of copper poisoning.  相似文献   

10.
Three different histochemical methods for copper detection were compared. Atomic absorption analysis was used to substantiate the tissue stains. There was good correlation between rhodanine staining and rubeanic acid-stained tissue sections. The orcein reaction for copper-associated protein did not consistently correlate with the methods demonstrating copper. Prolonged staining (72 hours) with rubeanic acid more consistently and clearly detected increased copper in canine livers than did staining with rhodanine. Seventy-two hour staining with rubeanic acid is the method of choice for histochemical detection of copper in canine liver.  相似文献   

11.
Copper absorption, liver accumulation and development of copper toxicosis in sheep are influenced by a variety of other elements, in particular molybdenum, sulphur and zinc (Underwood 1977). In a previous study on liver concentrations of copper, molybdenum and zinc in normal and copper-poisoned sheep, no direct correlation was found between the concentrations of the three metals, but molybdenum was significantly lower in the livers from sheep dead from chronic copper poisoning than in normal animals (Frøslie & Norheim 1976).  相似文献   

12.
A 1‐year‐old female Boer goat was presented with a 1‐day history of pigmenturia, anorexia, and shivering. Anemia was not present initially, but progressive hemolytic anemia developed subsequently and was characterized by the finding of Heinz bodies in both intact RBCs and in ghost cells and the presence of atypical fusiform RBCs. Plasma biochemical analysis revealed increased activities of aspartate aminotransferase and gamma‐glutamyltransferase, hyperbilirubinemia, and azotemia. Histopathologic examination of a liver biopsy revealed necrosis of individual hepatocytes and intracytoplasmic rhodamine‐positive granules, consistent with copper. Copper concentration in ante‐mortem hepatic tissue was increased, and a diagnosis of copper toxicosis was made. Despite supportive therapy, the goat continued to decline and was euthanized. Necropsy findings included hepatic necrosis and hemoglobinuric nephrosis. Freshly collected specimens of liver and kidney had markedly increased copper concentrations. The mineral composition of the water, grass hay, and goat chow was evaluated, and toxins and significant mineral imbalances were not found. The underlying cause of the hepatic accumulation and subsequent release of copper remains unclear in this goat. Recently, Boer goats have been recognized as being prone to copper toxicosis and may be more susceptible than other breeds; similar to sheep, Boer goats may experience a hemolytic crisis secondary to copper toxicosis.  相似文献   

13.
Cobalt and copper concentrations were measured in 599 lamb livers collected at slaughter from 58 sheep flocks in 6 different parts of Norway in 1993. Information about pasture, additional feeding and mineral supplements in the flocks was obtained through a questionnaire. Average hepatic levels of cobalt in the lamb flocks varied from < 0.003 to 0.22 microg/g ww, and of copper from 5 to 240 microg/g ww. Flocks with deficient or marginal cobalt status were found in all parts of southern Norway, but primarily in the west and south-west. Some flocks with marginal copper status were found in the south-west, while flocks with signs of excessive hepatic copper concentrations were found mainly in inner parts of central and northern Norway. Hepatic copper concentrations were significantly higher in lambs that had grazed mountain pastures than in those that had grazed lowland pastures in the summer.  相似文献   

14.
Three goats were dosed orally with a 0.2 % aqueous copper sulphate solution. The dosing was 20 mg copper sulphate/kg body weight twice a day for 56 to 113 days. One of the goats accumulated substantial amounts of copper in the liver and developed two haemolytic crises. The two other goats showed only increased liver copper concentrations before they were killed. The results indicate that the goats were susceptible in varying degrees to repeated oral copper dosing, and that two of the goats were significantly less susceptible to copper than sheep. The goat that turned into a haemolytic crisis showed changes similar to those seen in sheep as far as blood and plasma parameters are concerned. The gross and histological lesions were also mainly of the same type as described in sheep. The hepatic lesions found in the goat differed to some degree from those found in sheep as the necroses were more distinctly located to the centrilobular area, and as the iron pigments were mainly located in phagocytes in the hepatic sinusóides.  相似文献   

15.
Young male rats were fed a diet containing 0, 1, 10, 100, or 500 ppm of a commercial mixture of polybrominated biphenyls (PBB) that had been accidentally incorporated into a mineral mixture and fed to Michigan livestock and poultry. After 30 days, 9 of the 12 rats in each group were killed and tissues were examined. Liver weight to body weight ratios were significantly increased at all feeding levels; at 500 ppm, liver weight had more than doubled. Kidney weight was not affected. Microscopic lesions were mostly confined to the liver and consisted of extensive swelling and vacuolation of hepatocytes in rats fed diets containing 100 and 500 ppm of PBB. Slight swelling and vacuolation were seen in rats fed the diet containing 10 ppm, and lesions were not found at 0 or 1 ppm. There was a significant increase in hepatic mitochondrial size at 1 ppm, and smooth endoplasmic reticulum was markedly increased at 100 and 500 ppm. Myelin bodies were present at 100 and 500 ppm, and vacuoles were numerous. Rats killed at 60 days had similar lesions. The activity of hepatic microsomal enzymes increased at all levels of feeding of PBB. Rat pups nursing dams fed a diet containing 10 ppm of PBB had microscopic and ultrastructural hepatic lesions. When guinea pigs were fed PBB at the same amounts as were rats, the results were strikingly different. Guinea pigs fed a diet containing 500 ppm of PBB died within 15 days; at 100 ppm, only 2 of 6 survived for 30 days. Effects on liver weight were inconsistent, but 2 of 6 fed a diet containing 10 ppm had enlarged livers.  相似文献   

16.
Copper poisoning in four llamas   总被引:1,自引:0,他引:1  
Copper poisoning developed in 1 adult and 3 juvenile llamas after excessive dietary intake of copper resulted in an incorrect copper:molybdenum ratio. Total dietary copper was determined to be 36 mg/kg of feed, with a copper:molybdenum ratio of 16.6:1. Clinical signs associated with the toxicosis included acute onset of anorexia and lethargy. Liver enzyme activities (aspartate amino transaminase, lactate dehydrogenase, gamma-glutamyl transferase) and serum copper concentration were high in specimens obtained within 48 hours before death. Gross necropsy findings were limited to mild hepatomegaly. Histologically, hepatic lesions included acute massive necrosis of hepatocytes with and without bile duct proliferation, double hepatic plates with loss of orientation, anisocytosis, anisokaryosis, and an intralobular mosaic pattern of necrosis involving half of the hepatocytes. Analysis of hepatic copper concentrations suggested that juvenile llamas develop signs of poisoning at lower hepatic copper concentrations, compared with adults.  相似文献   

17.
Copper toxicosis in Bedlington Terriers in the United Kingdom   总被引:1,自引:0,他引:1  
This paper summarizes the clinical and laboratory data on two adult Bedlington Terriers with liver disease associated with copper toxicosis. The younger dog, at 3 years, had elevated serum levels of alanine aminotransferase and alkaline phosphatase with active parenchymal cell degeneration and hepatitis. The second dog developed chronic hepatic failure at 5 years with advanced cirrhosis. Both dogs had stainable copper granules in the liver and chemical analysis of their livers revealed elevated copper contents (1,027 and 10,728 μg/g dry weight; normal less than 300 μg/g). These are the first published cases of this inherited abnormality of copper metabolism in this breed in this country.  相似文献   

18.
对采集于广州市白云区蚌湖镇的疑似坦布苏病毒感染的蛋鸭病例进行剖解,观察大体器官病变。取肝脏组织首先进行该病毒的RT-PCR鉴定,确认自然感染该病毒后,对其肝脏进行光学和透射电镜观察。结果显示:坦布苏病毒自然感染的严重病例,剖解见肝脏肿大,色泽偏土黄,有暗红色出血斑,边缘增厚,质地变脆。光镜观察,见肝细胞索受损严重,细胞排列紊乱,胞内结构破坏,着色性下降,异嗜性白细胞浸润,在变性坏死的肝细胞周围聚集多量含铁血黄素颗粒。电镜观察发现,肝细胞严重损伤,大量肝细胞肿胀坏死,原生质外流,细胞质充满肿胀的囊泡,糖原外泄,线粒体肿胀变性;细胞核严重空泡化,核膜破裂,核质外流,出现大片的核内空白区。肝内见多量异嗜性白细胞,亦可见多量巨噬细胞和少量上皮样细胞,后二者都具有旺盛的吞噬或吞饮活动。  相似文献   

19.
A 2-year-old, castrated, male European Shorthair cat was presented with inappetence, vomiting, and fever. Ascites and an irregularly nodular liver were observed on laparotomy; in view of the poor prognosis, the animal was euthanatized. Histopathologic examination of the liver showed a chronic hepatitis with cirrhosis associated with massive accumulation of copper in hepatocytes and macrophages, particularly in the fibrotic areas between the regenerative nodules. Electron microscopy and energy-dispersive X-ray analysis revealed lysosomal accumulation of copper in the hepatocytes. Analytical determination showed very high copper concentrations in the liver. No evidence for increased dietary or environmental copper could be found. This and the pattern of hepatic copper storage, the associated inflammation and fibrosis, strongly suggest a primary copper storage disorder.  相似文献   

20.
Chronic copper toxicity in a dairy cow   总被引:2,自引:2,他引:0       下载免费PDF全文
A three year old Holstein dairy cow fed a ration containing a copper supplement died of chronic copper poisoning. The concentration of copper in the liver was 331 ppm (wet weight). The typical lesions of chronic copper toxicity including icterus, hepatic fibrosis and hemoglobinemic nephrosis were found at necropsy. The chronic copper toxicity was not considered to be a herd problem since the liver copper concentration in a slaughtered cull animal and blood samples taken from five animals in the same herd were within normal limits.  相似文献   

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