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1.
Toxin produced by Pasteurella multocida type D was investigated for its effect on serum complement and serum biochemistry in rats. Rats were given a sublethal single subcutaneous injection of D toxin equivalent to 0.2 microgram/kg of body weight. Serum obtained 1, 3, 5 and 7 days post-treatment was tested for complement activity, total bilirubin, aspartate aminotransferase (AST), alanine aminotransferase (ALT) and alkaline phosphatase (ALP). Serum complement titers were significantly elevated (P less than 0.05) at all times after injection of toxin compared to rats injected with diluent and tested at the same intervals. Bilirubin was decreased but both control and D toxin-treated rats had low concentrations of bilirubin in their sera. The other biochemical constituents measured had no consistent pattern that would indicate liver damage in the rats.  相似文献   

2.
Lysis of bovine platelets by Pasteurella haemolytica leukotoxin   总被引：3，自引：0，他引：3  
Pasteurella haemolytica A1 culture supernatants caused rapid cytolysis (less than 5 minutes) of isolated bovine platelets as measured by leakage of the cytoplasmic enzyme lactate dehydrogenase (LD). The platelet lytic factor had several features similar to P haemolytica leukotoxin. Like P haemolytica leukotoxin, the platelet lytic factor was produced by P haemolytica during logarithmic growth phase, was heat-labile, and was active against target cells (platelets) from ruminant species (cattle and sheep), but not from non-ruminant species (horses, pigs, and human beings). Additionally, the platelet lytic factor was neutralized with antileukotoxin rabbit serum. The amount of LD leaked by a fixed concentration of bovine platelets was proportional to the amount of toxin added at low toxic doses and became maximal at 88 +/- 11% of the total platelet LD activity for high doses of toxin. When a fixed dose of toxin was used and the platelet concentration was varied, LD leakage was initially proportional to the platelet concentration, but plateaued at higher platelet concentrations. The platelet lytic factor required Ca2+ and was inhibited by addition of the Ca2+ chelator ethylene glycol-bis(beta-aminoethyl ether)N,N,N',N'-tetraacetic acid. Toxin-mediated platelet damage may be important in thrombi formation and fibrin exudation typically associated with P haemolytica pleuropneumonia of cattle.  相似文献   

3.
One hundred seventy-nine tumor-bearing dogs were treated with 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea (CCNU) between 1995 and 2001. CCNU was given as a single dose of 50-110 mg/m2 body surface area PO. Treatment interval varied, but the minimal interval between CCNU doses was 3 weeks. After treatment, 11 dogs (6.1%) developed hepatic toxicity. The median number of CCNU doses and the median total cumulative CCNU dose were significantly higher in dogs that developed hepatic toxicity (4 doses; 350 mg/m2) than in dogs without hepatic damage (3 doses; 230 mg/m2). Median duration to detection of hepatic toxicity from the last dose of CCNU was 11 weeks (range 2-49 weeks). Common biochemical abnormalities were abnormally high serum liver enzyme activities and hypoalbuminemia. Six dogs with CCNU-associated hepatic toxicity had ascites, and 3 dogs had concurrent pleural effusion. Serum concentrations of bile acids were abnormally high in 4 of 5 dogs tested. Percutaneous ultrasound-guided liver biopsies were performed in 10 dogs, and findings were nonspecific and chronic in nature. Seven dogs were euthanized because of progressive liver failure, and their median survival from diagnosis of liver disease was 9 weeks. Three dogs died of other causes and 1 dog of unknown cause. Although clinical signs resolved in 3 dogs, biochemical abnormalities and histopathologic lesions persisted 4 to 38 months from the time of diagnosis of liver disease. Our findings suggest that CCNU can cause delayed, cumulative dose-related, chronic hepatotoxicity that is irreversible and can be fatal.  相似文献   

4.
Intraperitoneal exposure of turkey poults to various concentrations of Bordetella avium sonicate containing heat-labile toxin indicated a high degree of toxicity: poults died after exposure to sonicate containing as little as 6.32 micrograms of protein. The toxic effects were dose-related: poults that received sonicate containing 158 micrograms of protein died in 4 to 6 1/2 hours, those that received 31.6 and 6.32 micrograms of protein died in 25 to 30 hours, and those that received 1.2 micrograms survived the 6-day course of the study and were apparently unaffected. Histologic examination of poults that received lethal doses of the toxin revealed degeneration and necrosis of parenchymal cells of the liver and pancreas as well as hyperemia, hemorrhage, and necrosis of the mucosa of the small intestine. No lesions were observed in poults that received the sublethal dose of toxin or in unexposed poults. Repeated intranasal exposure of poults to the sonicate did not produce clinical signs of disease or gross lesions.  相似文献   

5.
Male Fischer rats, 6 weeks old, were injected once with one of five doses of azoxymethane. There was a dose response to the carcinogen as determined by weight gain and tumor induction. Rats given the three highest doses developed tumors of the gastrointestinal tract, auditory sebaceous glands, kidney, liver, and preputial gland, whereas rats receiving the lowest doses had tumors mainly of the intestine. Chronic liver lesions in high-dose rats were cirrhosis with megalocytosis, mild fibrosis, nodular hepatocellular hyperplasia, and hyperplasia of bile ductules.  相似文献   

6.
1,3,5-Trinitrobenzene (TNB) is a soil and water contaminant at certain military installations. Encephalopathy in rats given 10 daily oral doses of TNB has been reported. The lesion was bilaterally symmetric vacuolation and microcavitation in the cerebellar roof nuclei, vestibular nuclei, olivary nuclei, and inferior colliculi. The contribution of the blood-brain barrier (BBB) in the genesis of these lesions remains uncertain. One of the main goals of the present work was to evaluate the functional state of the BBB. Male Fischer 344 rats (five rats/group) were euthanatized after four, five, six, seven, eight, or 10 daily doses of TNB (71 mg/kg). A different set of rats (five rats/group) was allowed to recover for 10 or 30 days after receiving 10 doses of TNB. Integrity of the BBB was assessed by immunohistochemical staining for extravasated plasma albumin on paraffin-embedded sections. Rats euthanatized after four to eight doses had no lesions, and albumin extravasation in the susceptible regions of the brain was minimal. Rats receiving 10 daily doses of TNB had bilaterally symmetric vacuolation and microcavitation in the cerebellar nuclei, vestibular nuclei, and inferior colliculi in association with multifocal, often confluent foci of extravasated albumin in susceptible nuclei. Albumin was present in vascular walls, extracellular space, and neurons. Immunoreactivity in neurons was of two types: cytoplasmic staining representing pinocytic uptake and homogeneous staining of the entire neuron (nucleus and cytoplasm) due to uncontrolled albumin leakage through the damaged cell membrane. In rats allowed to recover for 10 days, the microcavitated foci were infiltrated by glial and gitter cells. Albumin immunoreactivity was present as extracellular granular debris, and neuronal staining (for albumin) was mild. In rats allowed to recover for 30 days, immunoreactivity to albumin was not seen. This study demonstrates that TNB-mediated tissue damage is accompanied by breakdown of the BBB. The presence of vacuolation and associated extravasated serum proteins in TNB-treated rats is an indication of vasogenic brain edema, which appears to be a critical event in TNB toxicity. Additional studies are needed to determine the reason for selective regional vulnerability and brain microvascular susceptibility to TNB.  相似文献   

7.
Dose response of sheep poisoned with locoweed (Oxytropis sericea).   总被引：1，自引：0，他引：1  
Locoweed poisoning occurs when livestock consume swainsonine-containing Astragalus and Oxytropis species over several weeks. Although the clinical and histologic changes of poisoning have been described, the dose or duration of swainsonine ingestion that results in significant or irreversible damage is not known. The purpose of this research was to document the swainsonine doses that produce clinical intoxication and histologic lesions. Twenty-one mixed-breed wethers were dosed by gavage with ground Oxytropis sericea to obtain swainsonine doses of 0.0, 0.05, 0.1, 0.2, 0.4, 0.8, and 1.0 mg/kg/day for 30 days. Sheep receiving > or = 0.2 mg/kg gained less weight than controls. After 16 days, animals receiving > or = 0.4 mg/kg were depressed, reluctant to move, and did not eat their feed rations. All treatment groups had serum biochemical changes, including depressed alpha-mannosidase, increased aspartate aminotransferase and alkaline phosphatase, as well as sporadic changes in lactate dehydrogenase, sodium, chloride, magnesium, albumin, and osmolarity. Typical locoweed-induced cellular vacuolation was seen in the following tissues and swainsonine doses: exocrine pancreas at > or = 0.05 mg/kg; proximal convoluted renal and thyroid follicular epithelium at > or = 0.1 mg/kg; Purkinje's cells, Kupffer's cells, splenic and lymph node macrophages, and transitional epithelium of the urinary bladder at > or = 0.2 mg/kg; neurons of the basal ganglia, mesencephalon, and metencephalon at > or = 0.4 mg/kg; and cerebellar neurons and glia at > or = 0.8 mg/kg. Histologic lesions were generally found when tissue swainsonine concentrations were approximately 150 ng/g. Both the clinical and histologic lesions, especially cerebellar lesions are suggestive of neurologic dysfunction even at low daily swainsonine doses of 0.2 mg/kg, suggesting that prolonged locoweed exposure, even at low doses, results in significant production losses as well as histologic and functional damage.  相似文献   

8.
Rats (Sprague-Dawley) and mice (Balb/c) were given microcystin LR intraperitoneally and were killed at intervals up to 24 hr (rats) or 90 min (mice) and necropsied. The lowest consistently lethal dose was 160 micrograms/kg in rats and 100 micrograms/kg in mice. Rats that were clinically unaffected had no lesion. All clinically affected rats in all dose groups died (from 20 to 32 hr after toxin) and had similar hepatic lesions. Livers were enlarged and dark red beginning 40 to 60 min after toxin. Mild disassociation and rounding of centrilobular hepatocytes developed within 20 min. By 60 min after toxin, degeneration and necrosis of hepatocytes involved most of the lobules except for small periportal zones. Weights of livers and kidneys were significantly increased. Eosinophilic fibrillar material filled renal glomerular capillaries as early as 9 hr after toxin. At 18 to 24 hr there was moderate vacuolation of proximal tubular epithelium with mild tubular dilatation. Beginning at 1 hr, intact hepatocytes and hepatic debris were present in pulmonary vessels. Analysis of serum revealed an increase in alanine aminotransferase 40 min after toxin; at 6 to 12 hr there were significant increases in alkaline phosphatase, total bilirubin, blood urea nitrogen, and creatinine. Mice survived only 60 to 90 min after toxin. Hepatic lesions were similar to those in rats, but renal and pulmonary lesions were not seen.  相似文献   

9.
Plasma concentrations of porcine growth hormone (PGH) were similar in healthy pigs and those with atrophic rhinitis (AR), therefore, observed reduced growth rates and feed efficiency in naturally infected pigs with AR were not attributed to low concentrations of plasma PGH. Also, pituitary glands in both groups of pigs were responsive to growth hormone-releasing hormone (GHRH) challenge by increasing PGH secretion. Administration of clonidine hydrochloride to pigs naturally infected with AR failed to elicit any significant change (5.3 +/- 1.4 ng/ml) in the plasma concentration of PGH within a 45-minute bleeding interval. The pretreatment concentrations of PGH were similar in specific-pathogen-free toxin-treated and specific-pathogen-free control groups, but they increased significantly in toxin-treated pigs (20.7 +/- 8.2 ng/ml) within 15 minutes after GHRH injection. Porcine growth hormone release in toxin-treated pigs was variable; however, all pigs did not respond to GHRH administration: 3 responded with an increase in PGH release (35.6 +/- 10.6 ng/ml), 2 did not respond (6.7 +/- 0.5 ng/ml), and 1 had a decrease in PGH release (3.9 ng/ml). Therefore, the observed reduced growth rates reported in the literature may be attributed to factors at the target level of PGH action, such as insufficient or down-regulation of PGH receptors, changes or impaired ability in the PGH receptor-binding characteristics, and inability of PGH receptor complex to transduce signal. Toxins are known to modulate signal transduction pathways. It has been speculated that serotype-D Pasteurella multocida toxin may influence growth by its effect on signal transduction from PGH receptor complex on the cell membrane to the interior of the cell.(ABSTRACT TRUNCATED AT 250 WORDS)  相似文献   

10.
The purpose of this in vitro study was to determine whether Pasteurella haemolytica capsular extract (CE) damages bovine pulmonary endothelial cells (EC) directly or through neutrophil-mediated mechanisms. Chromium 51-labeled EC were treated with the following variables: CE (1, 10, and 100 ng of protein/ml), CE and bovine neutrophils (10(6) cells/well), and CE and polymyxin B (500 U/ml). Although only minimal damage to EC occurred by 5 hours after treatment, by 22 hours after treatment, the 10-ng and 100-ng CE dose produced severe damage to EC, as indicated by 51Cr release, cellular detachment, and loss of monolayer confluency. The component in the CE that was toxic to the EC was lipopolysaccharide, evidenced by effective neutralization of the toxic effect with polymyxin B. Neutrophils inhibited the CE-mediated EC toxicity and were activated, as indicated by shape change and adhesion to EC monolayers. We concluded that the lipopolysaccharide component of CE causes direct damage to EC, which can be attenuated by neutrophils and polymyxin B.  相似文献   

11.
Pasteurella multocida toxin was purified by affinity chromatography and inactivated by treatment with formaldehyde before use as a single component vaccine against progressive atrophic rhinitis in pigs. Twenty pregnant gilts which were vaccinated twice before farrowing with either low or high doses of the purified toxoid, developed dose-dependent positive serum and colostrum titres to the toxin and, unlike the progeny of 10 untreated control gilts, the offspring of the vaccinated gilts also had serum titres. These titres could be measured in blood samples taken for more than eight weeks from birth for most pigs born to gilts vaccinated with low doses and more than 12 weeks for pigs born to gilts vaccinated with high doses of the vaccine. All the piglets were inoculated intranasally with Bordetella bronchiseptica and toxigenic P multocida. The clinical and post mortem examinations of snouts revealed a significant reduction in the frequency and degree of conchal atrophy in the two groups of pigs from the vaccinated gilts compared with the pigs from control gilts. Clinically 90 per cent of the snouts of pigs born to vaccinated gilts appeared normal whereas only 28 per cent of the snouts of control pigs were not shortened or deviated at eight weeks of age. At slaughter 11 per cent of the pigs born to vaccinated gilts and 81 per cent of the control pigs had severe turbinate atrophy.(ABSTRACT TRUNCATED AT 250 WORDS)  相似文献   

12.
Rats were vaccinated with a toxoid (D-toxoid) prepared from purified heat-labile toxin (D-toxin) produced by Pasteurella multocida serogroup D. Vaccination of rats with D-toxoid prevented death and other effects of D-toxin (hepatic necrosis, development of elevated leukocyte counts, lymphopenia, neutrophilia, and elevated complement titers) that occurred in phosphate buffered saline (PBS)-vaccinated control rats.  相似文献   

13.
The aim of the experiment was to observe the acute toxicity and the long-term toxicity of Chansu pellets in mice, and to evaluate its safety and provide the theoretical basis for clinical use. Kunming mice were selected for acute toxicity test. The acute toxicity of Chansu pellets was determined by oral administration to mice twice. In the sub-chronic toxicity test, 120 SD rats were divided into low, middle and high dose groups and the control group (the same volume of distilled water) intragastric administration. Respectively, after 28 d of continuous administration and 2 weeks after drug withdrawal, the rats were weighed, and 20 rats (10 mice remaining after cessation of administration) in each group were sacrificed at random. The hematological and biochemical parameters were measured and the histopathological examination was performed. In the acute toxicity, time of death concentrated in 1 to 4 h. LD50 was 13.21 g/kg. In the sub-chronic, after 28 d of continuous dosing, the body weights of male rats of high dose group and the control group were extremely significantly different (P <0.01). Aspartate aminotransferase and alkaline phosphatase of high dose group were extremely significantly different (P <0.01) compared with control group. Kidneys coefficients of high and middle dose groups compared with control group were extremely significantly different (P <0.01). After two weeks the withdrawal recovery, biochemical indicators of high dose group's recovery was not good. Middle and low dose groups had good recovery. Pathological examination showed that high and middle dose groups' rat liver and kidney swelling congestion. High dose rat liver surface were blister-like lesions. The results showed that Chansu pellets were less acute toxicity. Long-term use of large doses could cause liver and kidney damage. Therefore, we should pay attention to dose and duration of treatment in clinical application.  相似文献   

14.
The effects of purified Pasteurella multocida toxin (PMT) on osteoclast formation from hemopoietic progenitor cells were studied using an in vitro system. Mononuclear adherent mouse bone marrow cells were cultured for 7 or 14 days in the presence of PMT, or 1,25-dihydroxy-vitamin D3, or both. Mononuclear osteoclast-like cells, which are postmitotic osteoclast precursor cells, were identified as tartrate-resistant acid phosphatase (TRAP)-positive mononuclear cells possessing calcitonin receptors. Multinucleated osteoclast-like cells were TRAP-positive multinuclear cells with calcitonin receptors. The results demonstrate that, as does 1,25(OH)2D3, Pasteurella multocida toxin stimulates proliferation of adherent bone marrow mononuclear cells (progenitor cells), and their differentiation into postmitotic mononuclear osteoclast precursor cells. It also causes fusion of the latter into multinuclear osteoclasts; however, the number of osteoclasts obtained with PMT is smaller than with 1,25-dihydroxy-vitamin D3.  相似文献   

15.
Acute, subacute and chronic toxicity of TURISYNCHRON and its zinc complex (SUISYNCHRON) was tested in mice, rats and dogs. The acute toxicity of SUISYNCHRON was lower than that of TURISYNCHRON in mice and rats. Ulcerative lesions in the duodenum produced by high doses of SUISYNCHRON were quantitatively less pronounced than those produced by similar doses of TURISYNCHRON. Subacute toxicity testing in rats showed that neither preparation had any toxic effect on haematological, clinical chemical or histological criteria in the dosages selected. Chronic toxicity testing of TURISYNCHRON in dogs did not reveal any evidence of toxic damage.  相似文献   

16.
A highly pure heat-labile dermonecrotic toxin (DNT) of Pasteurella multocida was isolated from bacterium-free broth culture fluid. The protocol for the isolation included the following steps: ammonium sulphate precipitation, gel filtration, ion exchange chromatography and preparative polyacrylamide gel electrophoresis (PAGE). About 1 mg of purified DNT was recovered from 3 l of broth culture fluid. The final product was toxic for embryonic bovine lung (EBL) cells, lethal for mice, dermonecrotic in the guinea pig skin test and inactivated by heating at 56 degrees c. The recovery of biological activity was about 5% that of the original culture fluid and the specific activity had increased about 4000 times. After sodium dodecyl sulphate (SDS)-PAGE and silver staining a single band appeared, indicating that the purified DNT was free from contaminating proteins. The molecular weight of the toxin was approximately 125,000 daltons. The minimal toxic dose of DNT protein for embryonic bovine lung cells was about 2 ng, the minimal dermonecrotic dose in the guinea pig skin test was about 80 ng and the 50% lethal dose for mice about 300 ng.  相似文献   

17.
Intravenous administration of ammonium tetrathiomolybdate (three doses on alternate days) appeared to be an effective means of containing the acute phase of copper toxicity in sheep, whether this arose from continuous ingestion of high copper feeds or by injudicious use of copper preparations for the control of copper deficiency. No adverse effects were recorded on lamb numbers, birth weight or survival of lambs born to ewes of normal to low copper status when the treatment was applied at sensitive periods of the reproductive cycle. Decreases in 'available' plasma copper and in liver damage occurred rapidly in response to intravenous tetrathiomolybdate and it is suggested that all animals at risk be treated.  相似文献   

18.
玉米赤霉烯酮的生殖毒性研究进展   总被引：2，自引：0，他引：2  
玉米赤霉烯酮是一种特殊毒性的生物毒素,它的强雌激素样作用对动物机体的伤害很大,不仅引起动物流产、死胎、低产仔率等生殖机能异常,还可以导致繁殖功能下降、不育、畸形等.已有研究表明,ZEA对肝脏、肾脏、生殖系统和免疫系统产生明显的损伤,对细胞和遗传性也有毒性作用.目前,虽然国内外学者做了大量的研究,来揭示玉米赤霉烯酮损害机体生殖功能的机制,但关于它影响机体的生殖性能更详尽的机制还亟待进一步的研究.文章主要针对玉米赤霉烯酮的生殖毒性进行了综述,总结出ZEA对生殖系统的毒性机制,从而为临床预防及治疗繁殖疾病提供理论依据.  相似文献   

19.
Role of bentonite in prevention of T-2 toxicosis in rats   总被引：8，自引：0，他引：8  
Experiments were conducted to determine the effect of bentonite and nonnutritive dietary polymers on toxicity and metabolism of T-2 toxin in rats. Male weanling rats were fed diets containing 5% bentonite, anion exchange resin, cation exchange resin or vermiculite-hydrobiotite. Each diet was fed with and without 3 micrograms T-2 toxin/g of feed for 2 wk. Bentonite and anion exchange resin were the treatments most successful at overcoming growth depression and feed refusal caused by T-2 toxin. Subsequent experiments tested bentonite and anion exchange resin at 0, 2.5, 5.0, 7.5 and 10% of the diet. Bentonite fed at 10% was the most effective treatment at overcoming feed refusal and growth depression. Rats were fed 0, 5, 7.5 or 10% bentonite for 2 wk and then dosed with [3H] T-2 toxin. Urine and feces were collected for 21 h after dosing and tissues were excised for determination of residual 3H. Feeding bentonite had little effect on the fraction of the dose excreted in the urine. Significant increases in fecal excretion of 3H were shown, when the feeding of 5, 7.5 or 10% bentonite was compared with the casein-based, semi-purified control diet. Dietary bentonite had no effect on residual 3H in liver or kidney, but all concentrations of bentonite tested reduced residual 3H in muscle. More 3H was found in the digesta in the small intestine and in the wall of the intestinal tissue when rats fed 5% bentonite were compared with the controls. Intestinal transit time for rats fed bentonite diets was reduced compared with that of the controls as indicated by chromic oxide marker studies.(ABSTRACT TRUNCATED AT 250 WORDS)  相似文献   

20.
Sixteen 8- to 9-week-old Pasteurella multocida-free New Zealand White rabbits were divided into two equal groups. The first group was inoculated intranasally with P multocida serotype D:1 strain and the second group that was inoculated with phosphate-buffered saline (PBS) only was used as a control group. Pasteurella multocida was isolated from the nasal cavity of all infected rabbits in group 1 and from tracheal swabs of seven rabbits in this group. Four rabbits in group 1 died with clinical signs of septicaemia, two rabbits had mucopurulent nasal discharge and pneumonic lesions and the other two did not show any clinical signs or gross lesions. The ultrastructural changes detected were deciliation or clumping of cilia of ciliated epithelium, cellular swelling, vacuolation and sloughing. The subepithelial capillaries showed congestion, intravascular fibrin deposition, platelets aggregation and endothelial injury. Pasteurella multocida was observed attached to the injured endothelial cells. Heterophils, mast cells, vacuolated monocytes and macrophages infiltrated the lamina propria and between the degenerated epithelial cells.  相似文献   

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