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1.
Metabolic disturbances following intravenous and intramammary administration of endotoxins in ruminants are described. In contrast to the similarity in response of blood biochemical parameters after intravenous and intramammary administrations of endotoxins, responses in plasma concentrations of enzyme activities, the thyroid hormones, cortisol, and somatotropin differ markedly. Biochemical changes in blood after endotoxin administration are predominantly dose-dependent; thus some of the biochemical parameters - especially plasma concentrations of Fe and Zn - serve also to evaluate the effects of certain drugs in endotoxin models. Changes in milk composition have been documented only after intramammary infusion of endotoxins and can partly be explained by the increased permeability of the blood/milk barrier. Appearance and production of milk returns to normal within a week after intramammary endotoxin treatment, indicating that the mammary gland is only temporarily damaged by endotoxin-induced mastitis.  相似文献   

2.
Summary

Metabolic disturbances following intravenous and intramammary administration of endotoxins in ruminants are described. In contrast to the similarity in response of blood biochemical parameters after intravenous and intramammary administrations of endotoxins, responses in plasma concentrations of enzyme activities, the thyroid hormones, cortisol, and somatotropin differ markedly. Biochemical changes in blood after endotoxin administration are predominantly dose‐dependent; thus some of the biochemical parameters ‐ especially plasma concentrations of Fe and Zn ‐ serve also to evaluate the effects of certain drugs in endotoxin models.

Changes in milk composition have been documented only after intramammary infusion of endotoxins and can partly be explained by the increased permeability of the blood/milk barrier. Appearance and production of milk returns to normal within a week after intramammary endotoxin treatment, indicating that the mammary gland is only temporarily damaged by endotoxin‐induced mastitis.  相似文献   

3.
The role of endotoxin in the pathogenesis of coliform mastitis in sows   总被引:1,自引:0,他引:1  
Sows were made tolerant to Escherichia coli endotoxin by daily intravenous (IV) injection of the pyrogen. A refractory state was induced, characterised by a markedly decreased fever. In contrast, intramammary (IMM) infusion of only a quarter of the endotoxin dose to which the animals were made tolerant by IV injection produced a markedly increased fever. This finding suggests that inflammatory endogenous mediators were released in the mammary glands and that their subsequent absorption into the blood circulation, and not the absorption of endotoxin caused fever.  相似文献   

4.
Summary

Sows were made tolerant to Escherichia coli endotoxin by daily intravenous (IV) injection of the pyrogen. A refractory state was induced, characterised by a markedly decreased fever. In contrast, intramammary (IMM) infusion of only a quarter of the endotoxin dose to which the animals were made tolerant by IV injection produced a markedly increased fever. This finding suggests that inflammatory endogenous mediators were released in the mammary glands and that their subsequent absorption into the blood circulation, and not the absorption of endotoxin caused fever.  相似文献   

5.
It is a common theory that the systemic signs in cows suffering from coliform mastitis would be caused by absorption of endotoxin from the udder into the circulation. However, definite proof to validate this hypothesis is as yet not available. Therefore, the effects on some clinical and clinical-chemical parameters of administering either intravenously or intramammarilyE. coli endotoxin to normal and endotoxin-tolerant ruminants were comparatively examined. The absence of marked effects on rumen motility following the intramammary administration of endotoxin was striking. Moreover, in cows the intramammary administration of one fifth of the dose of endotoxin to which the animals were made tolerant produced a maximum effect on body temperature and plasma zinc concentrations. These observations suggest the release of inflammatory endogenous mediators in the udder and their subsequent absorption into the circulation rather than the absorption of endotoxin. However, attempts to validate this hypothesis failed. Further research for detection methods more sensitive than the bioassay used in this study is recommended.  相似文献   

6.
Flurbiprofen, a potent non-steroidal anti-inflammatory and antipyretic agent, was given as an intravenous infusion (2 mg/kg) followed by a bolus injection of 1 mg/kg six hours later. After drug administration body temperature and rumen contractions were slightly depressed, whereas urea values gradually increased; serum sorbitol dehydrogenase (SDH) activity, plasma iron concentration and the number of circulating lymphocytes were significantly lower. Intravenous injection of endotoxin from Escherichia coli O111B4 (0.1 microgram/kg) caused shivering, fever, inhibition of rumen contractions, changes in heart rate, lymphopenia, neutropenia followed by neutrophylic leucocytosis, changes in urea values, hypoferraemia, hypozincaemia and a decline in serum alkaline phosphatase (ALP) activity, whereas gamma-glutamyltranspeptidase, glutamic oxalacetic transaminase, lactic dehydrogenase and SDH values were not significantly altered. Pretreatment with flurbiprofen completely abolished the febrile reactions to endotoxin. The endotoxin-induced inhibition of rumen contractions was only delayed. The drug blocked the initial tachycardia to endotoxin but did not prevent the secondary biphasic increase in heart rate. Flurbiprofen failed to modify the endotoxin-induced decrease in both plasma zinc and serum ALP activity whereas the decline in plasma iron concentration was delayed. After drug pretreatment the changes in circulating white blood cells were more pronounced. These data demonstrate that most of the haematological, blood biochemical and clinical effects of endotoxin cannot be blocked by flurbiprofen, and that these effects are not due to the increase in body temperature alone. Tolerance induced by repetitive daily intravenous administration of endotoxin resulted in an almost complete abolition of all the effects. However, the plasma iron values from tolerant goats were significantly lower than those from non-tolerant animals, which demonstrates that the development of a refractory state can result in modification of this biochemical parameter.  相似文献   

7.
利福昔明乳房注入剂(干乳期)对奶牛的安全性研究   总被引:1,自引:0,他引:1  
研究利福昔明乳房注入剂(干乳期)对健康奶牛的正常体温、日产奶量、奶中体细胞数和乳房内菌群的影响。选择健康泌乳期奶牛12头,给药前1 d和给药前0 d,统计记录各试验奶牛的直肠温度、日产奶量,检测每个乳区采集奶样的体细胞数,并对给药前0 d的奶样进行病原菌分离检测。每头入选奶牛的四个乳区分别单次灌注利福昔明乳房注入剂,在给药后的第1、3、5、7、10天分别记录每头奶牛的日产奶量;在给药后的第12小时、3、5、7、10天分别采集奶样进行体细胞检测,同时检查直肠温度;在给药后的第10天对采集的奶样进行病原菌检测。比较奶牛用药前后直肠温度、日产奶量、奶中体细胞数和病原菌的变化。试验期间对给药奶牛进行连续观察,记录奶牛是否出现红、肿、热、痛等临床症状。结果表明。给药前1 d、给药当天和最后一次给药后的第1、3、5、7、10天,试验奶牛的日产奶量平均值分别为30.5、30.3、29.8、30.3、30.0、30.9和31.0 kg,相互之间无显著性差异(P>0.05);给药前后各时间点采集的奶中体细胞数大都维持在30~50万/mL;给药前后各时间点测得的奶牛直肠温度无显著性差异(P>0.05);病原菌检测结果显示,在给药前0 d分离到7株大肠杆菌、6株链球菌和9株葡萄球菌,给药后第10天采集的奶样中未检测到大肠杆菌和葡萄球菌,仅检测到1株链球菌。与给药前相比,奶中的病原菌数量有所减少,无新增感染。利福昔明乳房注入剂(干乳期)对奶牛正常体温、产奶量、奶中体细胞数无不良影响,该制剂对于奶牛是安全的。  相似文献   

8.
1. The effect of bacterial endotoxin injection was studied in growing pullets of different ages. Commercial chicks were divided into 5 groups according to age. Bacterial endotoxins (E. coli and S. typhimurium) were injected intravenously and rectal temperature was measured over a period of 300 min. 2. The results showed no significant effect of age on the febrile response induced by bacterial endotoxins, but a slight tendency towards a reduced fever peak was observed with increasing age. The response latency also increased with age.  相似文献   

9.
Four clinically normal stallions were infused intravenously with endotoxin (LPS) from Escherichia coli 055:B5 at a dose of 0.3 microg/kg b.w. and four stallions were treated with flunixin meglumine (FM) as a single intravenous injection at a dose of 1.1 mg/kg b.w., 5 min after the infusion of LPS. In response to endotoxin infusion, stallions' reaction was fever (increased rectal and scrotal skin temperature), increased heart rate (HR) and leucopenia. Administration of endotoxin also influenced the level of testosterone (decrease at 3-24 h and increase at 48-72 h after LPS administration) in the blood serum. FM treatment prevented an endotoxin-induced increase in rectal and scrotal skin temperature, HR, with no influence on the decrease of leucocytes. Administration of FM only had a significant effect on the latter changes (at 24-72 h) of serum testosterone concentration after addition of endotoxin.  相似文献   

10.
Plasma disposition of aditoprim, a new dihydrofolate reductase inhibitor, was studied in healthy cows and cows with endotoxin-induced mastitis. A single dose of 5 mg of aditoprim/kg of body weight was administered IV to 5 healthy cows and to the same cows 3 weeks later at 2 hours after intramammary infusion of 0.1 mg of endotoxin into the rear quarters. Mastitis developed in all endotoxin-infused quarters and cows had systemic signs of disease (fever, tachycardia, depression) from 2 to 10 hours after infusion of endotoxin. Pharmacokinetic characteristics of aditoprim in healthy cows were a large volume of distribution (6.28 L/kg), a systemic clearance of 0.82 L/h/kg, and an elimination half-life of 7.26 hours. In cows with mastitis, plasma concentrations of aditoprim were lower between 5 and 26 hours after injection. The systemic clearance (1.00 L/h/kg) and the volume of distribution (12.25 L/kg) were significantly higher in cows with mastitis, but elimination half-life was not significantly different. The lower plasma concentrations of aditoprim between 5 and 26 hours after injection in cows with mastitis are explained by fluid compartment shifts and/or blood flow changes induced by mastitis, although increased elimination of aditoprim in cows with mastitis cannot completely be ruled out. The antibacterial activity of aditoprim is nearly the same as that of trimethoprim. The longer elimination half-life time of aditoprim, however, indicates that it may have a practical pharmacotherapeutic advantage over trimethoprim.  相似文献   

11.
Low doses of 10(-7) mg Escherichia coli endotoxin applied as intramammary infusion into single bovine quarters induced a rise in milk cell count without other inflammatory signs. Significantly fewer quarters responded in early lactation than in mid lactation. Maximum cell count was also somewhat later and less pronounced in early lactation. The rise in milk cell count after infusion of E. coli endotoxin was related to in vitro chemotactic activity of blood polymorphonuclear leucocytes (PMN). PMN isolated from cows which did not respond with a rise in milk cell count upon endotoxin infusion showed a diminished chemotactic activity in vitro as compared to PMN isolated from animals which did respond to an intramammary endotoxin infusion with a rise in milk cell count. No differences in phagocytic and metabolic activity were observed in vitro between the PMN isolated from the two groups of animals.  相似文献   

12.
The influence of giving 1 dose of polymyxin B (1.6 X 10(6) U/quarter) by the intramammary route to dairy cows to modify the clinicopathologic course of mastitis induced by intramammary infusion of Escherichia coli endotoxin (1 mg/quarter) was examined. Pretreatment with polymyxin B or its simultaneous administration reduced and delayed the typical febrile and leukopenic responses to endotoxin infusion, prevented an increase in plasma lactate dehydrogenase activity and a reduction in plasma zinc concentration, but only marginally influenced the degree of udder inflammation and had no effect on leukocytosis in the milk. Intramammary infusion of polymyxin B at 30 or 60 minutes after endotoxin was infused prevented the increase in plasma lactate dehydrogenase activity and moderated the decrease in plasma zinc concentration, but otherwise failed to alter the clinicopathologic course of endotoxin-induced acute mastitis.  相似文献   

13.
内毒素对山羊肝脏的病理损伤和654-2的保护效应   总被引:1,自引:1,他引:0  
通过给山羊静注大肠杆菌内毒素(ET)诱导ET休克,探讨ET休克时山羊肝脏的病理损伤,并观察山莨菪碱(654-2)对其影响。结果表明,ET自理组在注射后5h,肝脏表现出明显的病理变化,特征为实质细胞退行性变化,微血管淤血、有透明血栓形成,血管内有淋巴细胞和中性粒细胞粘聚,且肝脏有明显的超微结构变化。654-2能有效地缓解或减轻ET引起的毒性损伤。  相似文献   

14.
Permeability of the blood-milk barrier to methylene blue in cows and goats   总被引:1,自引:0,他引:1  
A 2% aqueous solution of methylene blue was administered as a single intravenous (i.v.) bolus injection (10 mg/kg) to six lactating cows and seven lactating goats and as a continuous i.v. drip to five lactating goats. The same dose was administered as a 10% solution by intramammary infusion to five lactating goats. Blood and milk samples collected at various times after these treatments were assayed for the drug by a colorimetric method. Methylene blue, a highly charged molecule (pKa<1), passed readily from blood into milk; drug concentrations in milk 4-36 h after the single i.v. bolus injection were higher than those in blood. When examined at constant methylene blue levels in blood, a milk-blood ratio of 5: 1 was observed. After intramammary infusion, the drug passed quickly into systemic circulation, peaked at 3 h and was still detectable in blood 12 h after infusion. The drug appeared in the urine within 1 5 min after intramammary infusion. The rapid movement of the drug across the blood-milk barrier cannot be explained on the basis of its known physicochemical properties or according to the pH-pKa passive diffusion concept.  相似文献   

15.
OBJECTIVE: To determine the effects of 2 anti-inflammatory drugs in lactating Holstein cows with endotoxin-induced mastitis. ANIMALS: 30 multiparous Holstein cows that had been lactating for 30 to 60 days. PROCEDURE: Bacterial culture of milk samples and physical examinations established that study cows were in good health and free of mastitis. Mastitis was induced in 1 front mammary gland by intramammary administration of purified bacterial endotoxin. Cows were allocated into 1 of 3 treatment groups: untreated endotoxic mastitis (n = 9), endotoxic mastitis plus flunixin meglumine (9), and endotoxic mastitis plus isoflupredone acetate (10). Heart rate, rectal temperature, mammary surface area, and rumen motility were recorded hourly for 14 hours following endotoxin administration. Flunixin meglumine or isoflupredone acetate was administered after mammary swelling and rectal temperature > or = 40 degrees C had developed. Milk production was evaluated from 5 days before to 10 days after induction of mastitis. RESULTS: Neither drug ameliorated loss of milk production or swelling of the affected mammary gland. Both drugs reduced mean heart rate during the 14 hours following endotoxin administration, compared with untreated control cows. Cows treated with flunixin meglumine had increased rumen motility and decreased rectal temperature during the same period, compared with all other cows. CONCLUSIONS AND CLINICAL RELEVANCE: Neither drug enhanced recovery of milk production following endotoxin-induced mastitis. Flunixin meglumine decreased rectal temperature, whereas isoflupredone did not; however, it has not been established that reduction of fever is beneficial to cows with naturally occurring mastitis.  相似文献   

16.
The antipyretic efficacy of meloxicam was evaluated in a feline endotoxin model using a replicated change-over design. Twelve adult cats of both sexes were allocated at random to three experimental groups. At 30 min prior to the intravenous (i.v.) endotoxin challenge (0.5 µg/kg body weight(b.w.)), 2 animals in each group received an i.v. injection of 0.1, 0.3 or 0.5 mg meloxicam/kg b.w. and the two remaining animals in each group received physiological saline. In a second phase, 21 days later, the meloxicam/placebo treatment was exchanged within each group. The rectal temperature and scores for general demeanour were determined at 30-min intervals from before dosing to 300 min after the endotoxin challenge. Haematological parameters were analysed before and 60 min after administration of endotoxin. The results indicated a significant dose-dependent antipyretic response to meloxicam after endotoxin challenge. The antipyretic response in the medium- and high-dose meloxicam groups did not differ significantly, but both were significantly different from the low-dosage group. The individual effects of endotoxin on general demeanour were rather variable but meloxicam tended to have a beneficial effect. Endotoxin induced a reduction in the white blood cell count but this was not influenced by meloxicam. It was concluded that the pyretic endotoxin model is very suitable for studying new NSAIDs in cats and that the optimum single dose of meloxicam in this model was 0.3 mg/kg b.w.Abbreviations AUC area under the curve - b.w. body weight - i.v. intravenous - LPS lipopolysaccharide - MCV mean corpuscular volume - NSAID non-steroidal anti-inflammatory drug - WBC white blood cell count  相似文献   

17.
Midlactation cows were infused with 10 micrograms endotoxin in the same two homolateral quarters after each of several consecutive milkings to study the effect of prolonged, endotoxin-induced mastitis on lactational performance. The initial infusion induced an acute response with systemic involvement. Inflammation developed in infused quarters, and milk production declined and milk composition was altered in all quarters. Subsequent infusions failed to induce systemic responses. Furthermore, milk yield and composition in uninfused quarters returned to pre-treatment levels despite further infusions. In infused quarters, milk yield, protein percentage and serum albumin concentration showed partial recovery during the endotoxin infusion period. In contrast, decreased lactose concentration, and increased cell count, N-acetyl-beta-D-glucosaminidase and lactoferrin levels persisted throughout the infusion period. After infusions were stopped, all measurements returned to near pretreatment levels. These data demonstrate that systemic, but not local, responses become refractory to multiple intramammary endotoxin infusions, and that multiple infusions have continued but little progressive or permanent, inhibitory effects on lactational performance despite a persistent mammary leucocytosis.  相似文献   

18.
The purpose of this study was to assess whether pentoxifylline, a drug that can inhibit the production and action of pro-inflammatory cytokines, had beneficial effects on the acute-phase response toE. coli endotoxin in the dwarf goat. First, the effects of 0.5 mg/kg per min pentoxifylline given intravenously over 15 min were examined in five goats. One week later, the clinical changes caused by i.v. injection ofE. coli endotoxin (LPS: 0.1 µg/kg) were determined. This endotoxin induced fever, tachycardia, inhibition of rumen motility, and decreases in plasma zinc and iron concentrations. Three weeks later, the effects ofE. coli LPS were again determined immediately after pentoxifylline infusion in the same group of animals. It was concluded that a pharmacological dose of pentoxifylline has no protective effects on the acute-phase response reactions induced by a pyrogenic dose ofE. coli LPS Abbreviations AMP adenosine phosphate - APR acute-phase response - GMP guanosine phosphate - IL interleukin - i.v. intravenous - LPS lipopolysaccharides - NO nitric oxide - POF pentoxifylline - r recombinant - SEM standard error of mean - TNF tumour necrosis factor  相似文献   

19.
The intravenous injection of chickens aged six to 11 weeks with Escherichia coli endotoxins (serogroups O111 and O78) produced a large increase in the plasma corticosterone concentration which was maximal (five to 10-fold) after 1 h and still evident after 8 h. It did not vary with the dose over the range 0.1 to 2 mg/kg and was smaller than that produced by adrenocorticotrophic hormone (ACTH) (20 iu/kg). A decrease in growth hormone concentration was detected between 1 and 2 h after endotoxin administration in six- to seven-week-old birds, this change being opposite to that which occurs in man.  相似文献   

20.
This study examined the safety of intravenous hypertonic saline in cattle with experimental gram-negative endotoxemia. Cerebrospinal fluid (CSF) composition was examined in five control cows and eight treated cows 24 hours after the intramammary infusion of 1 mg of endotoxin. Four of the endotoxin challenged cows were treated intravenously with isotonic (0.9%) sodium chloride and four cows were treated intravenously with hypertonic (7.5%)sodium chloride. Decreased CSF osmolality, and sodium and alpha globulin concentrations and increased CSF concentrations of beta globulin were observed in both endotoxin-challenged saline-treated groups. No CSF compositional differences were observed between endotoxin-challenged cows receiving isotonic or hypertonic saline. Although no cytologic or biochemical evidence of salt poisoning was observed in cows receiving hypertonic saline, significant changes were observed in the CSF composition of both endotoxin-infused saline-treated groups.  相似文献   

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