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1.
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   

2.
Data from the literature on the clinical effects of bacterial endotoxins in ruminants are reviewed. Special attention is paid to the effects on body temperature and reticulo-rumen motility. Furthermore, the effects of repeated intravenous injection of endotoxin are summarised. Pathophysiological disturbances after intramammary infusion of endotoxins proved to be identical to those found after intravenous injection of non-lethal doses. Strikingly, however, no marked inhibitory effect on rumen motility nor abortion was observed after intramammary infusion of endotoxins. Moreover, in cows that were made tolerant to endotoxin by daily intravenous injections, intramammary infusion of one-fifth of this daily dose produced a maximum effect on body temperature and plasma Zn concentrations. This suggests that inflammatory endogenous mediators were released in the udder and then absorbed into the blood circulation, rather than the absorption of endotoxin.  相似文献   

3.
Concentrations of tumor necrosis factor-alpha (TNF-alpha) and of NO(x) (sum of nitrite and nitrate as indicators of endogenous nitric oxide production) in milk and blood plasma were measured in three mastitis models in dairy cows in early lactation. Escherichia coli P4:O37 bacteria or endotoxin O111:B4 were administered into both left quarters of 12 and 6 cows, respectively. Six of the E. coli-infected cows were treated with a bactericidal antibiotic (Enrofloxacin; Bayer AG, Leverkusen, Germany) i.v. at 10 hr and subcutaneously (sc) at 30 hr after infection. NO(x) concentrations transiently increased maximally 10- to 11-fold in milk of E. coli-infected quarters with or without antibiotic treatment at 24 hr and after endotoxin administration. NO(x) concentrations did not change in milk of unchallenged quarters and in blood plasma. Increases of NO(x) were proceeded by a transient (96- to 149-fold) rise of milk TNF-alpha concentrations, which in endotoxin-administered quarters was maximal at 6 hr and in infected quarters without or with Enrofloxacin treatment at 10 and 14 hr. In blood plasma TNF-alpha concentrations only moderately increased to peaks in endotoxin-administered cows at 6 hr and in E. coli-infected cows at 14 hr postchallenge. In one severely sick, nontreated E. coli-infected cow milk, TNF-alpha response at 14 hr was excessive and followed by a spectacular rise of NO(x) concentration in milk between 48 and 72 hr. In conclusion, a possible clinical relevance of nitric oxide production associated with a rise of intramammary and systemic TNF-alpha during acute mastitis by E. coli infection and endotoxin in lactating dairy cows is indicated, but could not be inhibited by antibiotic treatment.  相似文献   

4.
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   

5.
Pharmacokinetics of florfenicol 30% injectable solution was determined in lactating cows after intravenous, intramammary and intramuscular administration. Serum concentration-time data generated in the present study were analysed by non-compartmental methods based on statistical moment theory. Florfenicol half-life was 176 min, mean residence time 129 min, volume of distribution at steady-state 0.35 L/kg, and total body clearance 2.7 mL/min·kg after intravenous administration at 20 mg/kg. The absorption after intramuscular administration appeared slow and the kinetic parameters and the serum concentration vs. time curve were characteristic of absorption rate-dependent elimination. The absorption after intramammary administration of florfenicol at 20 mg/kg was good (53.9%) and resulted in serum concentrations with apparent clinical significance. The intramammary administration resulted in serum florfenicol concentrations that were significantly higher than the respective serum concentrations following Intravenous administration 4 h after administration and thereafter. Florfenicol absorption was faster from the mammary gland than from the muscle. The maximum serum concentrations ( C max) were 6.9 μg/mL at 360 min after intramammary administration and 2.3 μg/mL at 180 min after intramuscular administration. The bioavailability of florfenicol was 54% and 38% after intramammary and intramuscular administration, respectively. The C max in milk was 5.4 μg/mL at 180 min after intravenous and 1.6 μg/mL at 600 min after intramuscular administration.  相似文献   

6.
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   

7.
The disposition of chloramphenicol after intramammary and intravenous administration was followed through determinations of chloramphenicol in blood and milk by means of high-performance differential pulse polarography. The concentration-time curves obtained reflected the different modes of administration, and allowed calculation of some pharmacokinetic parameters. The results of the polarographic determination in blood agreed fairly well with those of the microbiological assay in serum. Several body fluids and tissues of the cows were examined for residues of chloramphenicol and degradation products, both by the microbiological method and by high-performance liquid chromatography with ultraviolet detection. In urine, chloramphenicol and chloramphenicol glucuronide were found; in the other fluids and tissues only now and then a trace of chloramphenicol or a degradation product was detected. From these results it appears that chloramphenicol and degradation products are eliminated rapidly and completely after intravenous or intrammary application. No accumulation of degradation products occurred.  相似文献   

8.
The response of the pony to increasing doses of Escherichia coli endotoxin was evaluated using intravenous and intraperitoneal administration models. Marked changes were seen in all parameters measured following endotoxin administration. Leukopenia (neutropenia, lymphopenia) and thrombocytopenia were not dose-dependent. Similarly, elevated plasma fibrinogen and altered glucose concentrations (hyperglycemia and hypoglycemia), pyrexia and increased lactate/pyruvate ratios were apparent at all endotoxin doses but were not dose related. The widely used packed cell volume and capillary refill time, we well as blood lactate and possibly serum beta-glucuronidase, were increased in a dose-related manner.  相似文献   

9.
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   

10.
Methscopolamine was used to induce ruminal stasis in calves. Clinical and blood biochemical parameters were studied to judge the possible role of gastro-intestinal endotoxins from Gram-negative bacteria. Two trials were carried out where one injection of 100 mg and 3 consecutive injections of 70 mg of methscopolamine were administered. The animals showed signs of ruminal stasis. General clinical signs and changes in blood biochemical parameters were similar to what is found in endotoxaemia or in induced ruminal acidosis. Relevant parameters such as prostaglandin F2 alpha metabolite, endotoxin, iron, zinc, calcium and glutamate dehydrogenase changed significantly indicating exposure of endotoxins.  相似文献   

11.
在奶牛乳房内灌注头孢噻呋钠后,采用超高效液相色谱一串联质谱法测定牛乳中头孢噻呋的浓度,对其消除动力学进行了研究。3头实验奶牛按每个乳房0．3g头孢噻呋灌注,牛乳中药物达到的最高浓度Cmax=107．89μg／mL,达峰时间Tmax=8h,药物半衰期T1/2=13．97h。在乳房内用药后的最初56h内,头孢噻呋浓度快速下降;最后一次给药88h后,所有乳腺中头孢噻呋的浓度都低于允许限量（0．1μg／mL）。故建议头孢噻呋在牛奶中的休药期为4d。  相似文献   

12.
Arachidonic acid metabolites (AAM) were measured in milk and plasma during the course of acute endotoxin-induced mastitis in 12 lactating cows. Mastitis was induced by intramammary challenge exposure with 10 micrograms of Escherichia coli (026:B6) endotoxin. Endotoxin was injected into the teat cistern via the teat canal of a single randomly selected rear quarter of each cow. Concentrations of prostaglandin (PG) F2 alpha and thromboxane (Tx) B2 in fat-free unextracted milk and of 15-keto-13,14-dihydro-PGF2 alpha in plasma were measured by radioimmunoassay. Total production of AAM in milk was determined by measuring quarter milk production. The AAM were compared in 6 cows administered flunixin meglumine (1.1 mg/kg of body weight) and in 6 cows administered saline solution. Concentrations of TxB2 in milk were significantly (P less than 0.001) increased during the early course of acute mastitis in endotoxin-treated quarters of cows not administered flunixin meglumine. Peak concentrations of TxB2 in milk occurred at 8 hours after endotoxin inoculation. Flunixin meglumine treatment produced significant (P less than 0.05) reductions in milk TxB2 and plasma 15-keto-13,14-dihydro-PGF2 alpha concentrations. Concentrations of PGF2 alpha in milk and total PGF2 alpha and TxB2 production per quarter per milking were not significantly influenced by endotoxin challenge or by flunixin meglumine treatment.  相似文献   

13.
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   

14.
Polymorphonuclear leukocytes (PMN) isolated from the blood of bovines which do not react with an influx of cells into the milk upon intramammary administration of low doses of endotoxin (Group II), show a diminished chemotactic activity in vitro as compared to PMN of bovines which do respond to intramammary endotoxin administration (Group I; 8). The purpose of the present study was to determine whether other immune cells affected the chemotactic activity of PMN of Group I and II bovines. Mononuclear leukocyte suspensions of Group I animals had no effect on the migration of PMN of Group I animals. In contrast, the distance migrated by Group II PMN was diminished in the presence of Group II mononuclear leukocytes. As a consequence, this phenomenon resulted in a much larger difference in chemotactic activity of PMN in vitro between Group I and Group II bovines. It can be concluded that the chemotactic activity of PMN of animals which are more susceptible for mastitis as indicated by non-responsiveness to intramammary endotoxin-infusions, was further down-regulated by mononuclear leukocytes.  相似文献   

15.
Endotoxin-induced synthesis of thromboxane A2 (TXA2), prostacyclin (PGI2) and prostaglandin E2 (PGE2) was studied in 3 cows after intravenous E. coli endotoxin (055:B5-0.025 mg/kg b.w.) administration. Blood sampling and monitoring of clinical signs were performed from 2 h prior to until 6 h after endotoxin challenge. Blood samples were analyzed for stable hydrolysis products of TXA2 (TXB2), PGI2 (6-keto PGF) and PGE2 (bicyclic PGE2), biochemical and haematological parameters. In a similar experimental design the efficacy of the non-steroidal anti-inflammatory drugs (NSAID) flunixin meglumine (FM) and phenylbutazone (PB) in suppressing eicosanoid synthesis and clinical signs in response to endotoxin challenge was investigated. Two groups of cows, each comprising 2 animals, were treated with FM and PB prior to endotoxin challenge. It was observed that plasma concentrations of TXB2, 6-keto PGF and bicyclic PGE2 increased rapidly after endotoxin challenge. Concentrations were significantly elevated for hours and were correlated to the severity of clinical signs of endotoxicosis. Pretreatment with NSAID suppressed mediator production and alleviated clinical signs. The experiments suggest a certain pathophysiological role of TXA2, PGI2 and PGE2 for the early systemic ill-effects of bovine endotoxicosis.  相似文献   

16.
The clinical effect of flunixin meglumine administration was determined in cows with acute mastitis induced by intramammary administration of endotoxin. In 12 lactating cows, 10 micrograms of Escherichia coli 026:B6 endotoxin were administered via a teat cannula into the teat cistern of single randomly selected rear quarters. Cows were challenge exposed as pairs. One cow in each pair was administered parenteral flunixin meglumine (6 cows) and 1 cow per pair was administered saline solution (6 cows). Multiple doses (7) of 1.1 mg of flunixin meglumine/kg of body weight or saline solution were administered at 8-hour intervals beginning 2 hours after endotoxin. Cow and quarter clinical signs as well as milk somatic cell concentrations, bovine serum albumin, electrical conductivity, and milk production were determined before and for 14 days after endotoxin inoculation. Intramammary endotoxin produced signs characteristic of acute coliform mastitis. Quarter and systemic abnormalities occurred and milk production was reduced by approximately 50% at 12 hours after endotoxin. Flunixin meglumine therapy significantly (P less than or equal to 0.05) reduced rectal temperatures and quarter signs of inflammation and improved clinically graded depression when compared with these signs in saline solution-treated controls. Milk production and laboratory indicators of inflammation in milk were not significantly (P greater than 0.05) different for flunixin meglumine vs saline solution controls. The clinical response observed was consistent with the antipyretic, analgesic, and anti-inflammatory properties of flunixin meglumine.  相似文献   

17.
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   

18.
OBJECTIVE: To determine the elimination kinetics of ceftiofur hydrochloride in milk after intramammary administration in lactating dairy cows. DESIGN: Prospective study. ANIMALS: 5 lactating dairy cows. PROCEDURE: After collection of baseline milk samples, 300 mg (6 mL) of ceftiofur was infused into the left front and right rear mammary gland quarters of each cow. Approximately 12 hours later, an additional 300 mg of ceftiofur was administered into the same mammary gland quarters after milking. Milk samples were collected from each mammary gland quarter every 12 hours for 10 days. Concentrations of ceftiofur and its metabolites in each milk sample were determined to assess the rate of ceftiofur elimination. RESULTS: Although there were considerable variations among mammary gland quarters and individual cows, ceftiofur concentrations in milk from all treated mammary gland quarters were less than the tolerance (0.1 microg/mL) set by the FDA by 168 hours (7 days) after the last intramammary administration of ceftiofur. No drug concentrations were detected in milk samples beyond this period. Ceftiofur was not detected in any milk samples from nontreated mammary gland quarters throughout the study. CONCLUSIONS AND CLINICAL RELEVANCE: Ceftiofur administered by the intramammary route as an extra-label treatment for mastitis in dairy cows reaches concentrations in milk greater than the tolerance set by the FDA. Results indicated that milk from treated mammary gland quarters should be discarded for a minimum of 7 days after intramammary administration of ceftiofur. Elimination of ceftiofur may be correlated with milk production, and cows producing smaller volumes of milk may have prolonged withdrawal times.  相似文献   

19.
The effects of intravenous administration of Escherichia coli endotoxin were studied in eight mature lactating cows. Three cows were studied following intrammary infection with E. coli. Significant clinical findings are presented. Significant clinico-pathological findings include leukopenia, decreased blood serum calcium concentrations and increased levels of serum glutamic-oxaloacetic transaminase and serum ornithine-carbamyl transferase. Significant elevations of plasma corticosteroids were also noted.  相似文献   

20.
Spiramycin is a macrolide antibiotic that is active against most of the microorganisms isolated from the milk of mastitic cows. This work investigated the disposition of spiramycin in plasma and milk after intravenous, intramuscular and subcutaneous administration. Twelve healthy cows were given a single injection of spiramycin at a dose of 30,000 IU/kg by each route. Plasma and milk were collected post injection. Spiramycin concentration in the plasma was determined by a high performance liquid chromatography method, and in the milk by a microbiological method. The mean residence time after intravenous administration was significantly longer (P less than 0.01) in the milk (20.7 +/- 2.7 h) than in plasma (4.0 +/- 1.6 h). An average milk-to-plasma ratio of 36.5 +/- 15 was calculated from the area concentration-time curves. Several pharmacokinetic parameters were examined to determine the bioequivalence of the two extravascular routes. The dose fraction adsorbed after intramuscular or subcutaneous administration was almost 100% and was bioequivalent for the extravascular routes, but the rates of absorption, the maximal concentrations and the time to obtain them differed significantly between the two routes. Spiramycin quantities excreted in milk did not differ between the two extravascular routes but the latter were not bioequivalent for maximal concentration in the milk. However, the two routes were bio-equivalent for the duration of time the milk concentration exceeded the minimal inhibitory concentration (MIC) of various pathogens causing infections in the mammary gland.(ABSTRACT TRUNCATED AT 250 WORDS)  相似文献   

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