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1.
The degree to which the selectin inhibitor TBC1269 reduces neutrophil infiltration in specific microscopic locations of the lung during acute pneumonia of neonates was determined. Neonatal calves were inoculated intrabronchially with Mannheimia (Pasteurella) haemolytica or saline, and lung tissue was collected at 2 and 6 hours postinoculation (PI). One 6-hour group inoculated with M. haemolytica received TBC1269 intravenously before and after inoculation with M. haemolytica. Infiltrates of neutrophils were significantly higher in the alveolar lumen and septae but lower in the bronchial lumen and epithelium at 6 hours PI than at 2 hours PI. Significantly fewer neutrophils (P < 0.05) were present in the alveolar lumen and septae, and the bronchiolar lumen and lamina propria in the lungs of TBC1269-treated calves compared with untreated calves at 6 hours PI. TBC1269 did not alter the infiltration into bronchi and blood vessels or the expression of the selectin-independent adhesion molecule, ICAM-1. This work suggests that during acute pneumonia of neonates 1) neutrophil infiltrates progressively increase in the alveolar lumens and septae but decrease in the bronchial lumen and epithelium with time, 2) TBC1269 reduces neutrophil infiltration into specific regions of alveoli and bronchioles rather than uniformly throughout the lung, and 3) selectin inhibition does not affect the location and intensity of ICAM-1 expression.  相似文献   

2.
OBJECTIVE: To determine effects of the selectin inhibitor TBC1269 on neutrophil-mediated pulmonary damage during acute Mannheimia haemolytica-induced pneumonia in newborn calves. ANIMALS: Eighteen 1- to 3-day-old colostrum-deprived calves. PROCEDURE: Mannheimia haemolytica or saline (0.9% NaCl) solution was inoculated in both cranial lung lobes of 12 and 6 calves, respectively. Calves were euthanatized 2 (saline, n = 3; M haemolytica, n = 4) or 6 hours (saline, n = 3; M haemolytica, n = 8) after inoculation. Four M haemolytica-inoculated calves euthanatized at 6 hours also received TBC1269 (25 mg/kg, IV) 30 minutes before and 2 hours after inoculation. Conjugated diene (CD) concentrations, inducible nitric oxide synthase (iNOS) expression, and apoptotic cell counts were determined in lung specimens collected during necropsy. RESULTS: Conjugated diene concentrations were significantly increased in all M haemolytica-inoculated groups, compared with saline-inoculated groups. Calves treated with TBC1269 had decreased concentrations of CD, compared with untreated calves, although the difference was not significant. Number of apoptotic neutrophils and macrophages increased significantly inTBC1269-treated calves, compared with untreated calves. Inducible nitric oxide synthase was expressed by epithelial cells and leukocytes. However, iNOS was less abundant in airway epithelial cells associated with inflammatory exudates. Degree of iNOS expression was similar between TBC1269-treated and untreated calves. CONCLUSIONS: Mannheimia haemolytica infection in neonatal calves resulted in pulmonary tissue damage and decreased epithelial cell iNOS expression. The selectin inhibitor TCB1269 altered, but did not completely inhibit, neutrophil-mediated pulmonary damage.  相似文献   

3.
OBJECTIVE: To examine effects of danofloxacin and tilmicosin on continuously recorded body temperature in beef calves with pneumonia experimentally induced by inoculation of Mannheimia haemolytica. ANIMALS: 41 Angus-cross heifers (body weight, 160 to 220 kg) without a recent history of respiratory tract disease or antimicrobial treatment, all from a single ranch. PROCEDURE: Radiotransmitters were implanted intravaginally in each calf. Pneumonia was induced intrabronchially by use of logarithmic-phase cultures of M. haemolytica. At 21 hours after inoculation, calves were treated with saline (0.9% NaCl) solution, danofloxacin, or tilmicosin. Body temperature was monitored from 66 hours before inoculation until 72 hours after treatment. Area under the curve (AUC) of the temperature-time plot and mean temperature were calculated for 3-hour intervals and compared among treatment groups. RESULTS: The AUCs for 3-hour intervals did not differ significantly among treatment groups for any of the time periods. Analysis of the mean temperature for 3-hour intervals revealed significantly higher temperatures at most time periods for saline-treated calves, compared with temperatures for antimicrobial-treated calves; however, we did not detect significant differences between the danofloxacin- and tilmicosin-treated calves. The circadian rhythm of temperatures before exposure was detected again approximately 48 hours after bacterial inoculation. CONCLUSIONS AND CLINICAL RELEVANCE: Danofloxacin and tilmicosin did not differ in their effect on mean body temperature for 3-hour intervals but significantly decreased body temperature, compared with body temperature in saline-treated calves. Normal daily variation in body temperature must be considered in the face of respiratory tract disease during clinical evaluation of feedlot cattle.  相似文献   

4.
OBJECTIVES: To determine the structural and functional alterations in circulating neutrophils that may lead to sequestration in lung microvasculature and endothelial injury in calves with experimentally induced pneumonic pasteurellosis. ANIMALS: 10 healthy, 2- to 4-week-old male Holstein calves. PROCEDURES: Holstein calves were anesthetized and inoculated intrabronchially with Dulbecco phosphate buffered saline (0.9% NaCl) solution (DPBSS; 5 control calves) or 1 x 10(9) Pasteurella haemolytica organisms (5 infected calves). Blood samples were collected before and 1, 2, 4, and 6 hours after inoculation. Total and differential WBC count, dilute whole blood leukocyte deformability, neutrophil size distribution, and neutrophil surface CD11b expression were measured in blood samples. RESULTS: A progressive decrease in leukocyte deformability and increase in neutrophil size was detected 1, 2, 4, and 6 hours after inoculation of P haemolytica. Neutrophil surface CD11b expression was greater than baseline values at 6 hours after inoculation of P haemolytica. Two populations of neutrophils with an increase in size were detected in P haemolytica-infected calves. Both subpopulations had increased CD11b expression, compared with neutrophils that were typical in size. CONCLUSIONS AND CLINICAL RELEVANCE: Neutrophils circulate in an activated and nondeformable state in calves with experimentally induced pneumonic pasteurellosis. A decrease in neutrophil deformability and neutrophil aggregation may contribute to neutrophil trapping in the lung microvasculature during pneumonic pasteurellosis in calves.  相似文献   

5.
Acute lung injury was induced in 24 calves by intratracheal inoculation with Pasteurella haemolytica. Calves in groups 1 and 2 were neutrophil depleted, using hydroxyurea given IV. Group 1 calves (n = 7) were inoculated intratracheally with saline solution, and group 2 calves (n = 7) were inoculated with P haemolytica. Group 3 calves (n = 7) had normal numbers of neutrophils and were inoculated with P haemolytica. Group 4 calves (n = 3) were treated acutely with hydroxyurea IV, had normal numbers of neutrophils, and were inoculated with P haemolytica. After inoculation, calves with normal numbers of neutrophils (groups 3 and 4) became hypoxemic 2 hours after inoculation, and hypoxemia persisted until necropsy (6 hours after inoculation). These calves also developed tachypnea, bradycardia, neutropenia, and lymphopenia. Lung lesions consisted of necrosis of the alveolar walls, intra-alveolar hemorrhage, and a severe exudative and necrotizing bronchopneumonia, with accumulation of proteinaceous fluid in alveoli and lymphatics. In neutrophil-depleted calves (groups 1 and 2), blood gas values, heart and respiratory rates, and numbers of circulating leukocytes did not change after inoculation with saline solution or with P haemolytica. At necropsy, the lungs of neutrophil-depleted calves were grossly normal. Therefore, neutrophils were required for the acute lung injury induced by P haemolytica. The protective effect of neutrophil depletion was a specific effect of hydroxyurea because calves with high circulating concentrations of hydroxyurea and calves with normal numbers of neutrophils (group 4) developed lung injury.  相似文献   

6.
OBJECTIVE: To determine whether platelet-activating factor (PAF) is involved in acute lung microvascular injury associated with pneumonic pasteurellosis in calves. ANIMALS: 15 healthy 2- to 4-week-old male Holstein calves. PROCEDURE: Calves were anesthetized and inoculated intrabronchially with saline (0.9% NaCl) solution (n = 5) or 1x10(9) Pasteurella haemolytica organisms (n = 10). Of the 10 calves inoculated with P haemolytica, 5 also were treated with WEB 2086, a potent inhibitor of PAF, and 5 were treated with vehicle. Blood and bronchoalveolar lavage samples were collected before and 1, 2, 4, and 6 hours after inoculation of P. haemolytica. Blood samples were analyzed to evaluate total number and differential counts of leukocytes, dilute whole-blood leukocyte deformability, size of neutrophils, and neutrophil CD11b expression. Bronchoalveolar lavage samples were analyzed for total number and differential counts of nucleated cells, total protein concentration, and hemoglobin concentration. Size and gross and histologic appearance of lung lesions also was determined. RESULTS: Treatment of calves with WEB 2086 reduced size of lung lesions, attenuated the increase in microvascular permeability, and reduced neutrophil infiltration in the first 4 hours after inoculation. Treatment with WEB 2086 also attenuated a decrease in leukocyte deformability, increase in size of neutrophils, and CD11b expression by circulating neutrophils. CONCLUSIONS AND CLINICAL RELEVANCE: It appears that PAF is a major mediator for altered lung microvascular permeability and activation of circulating neutrophils in the first 4 hours after onset of pneumonic pasteurellosis in calves.  相似文献   

7.
Systemic and pulmonary antibody responses of calves to Pasteurella haemolytica were evaluated by measuring immunoglobulin production in blood for 9 days and in pulmonary lavage fluid for 7 days after intrapulmonary inoculation. Clinical signs, pulmonary lesions, pulmonary and systemic inflammatory response, and amount of antigen in lavage fluid were used to evaluate the response of calves to challenge with P haemolytica. The pulmonary response consisted of production of IgG, IgE, and IgM antibodies to P haemolytica antigens and a 17- to 68-fold increase of cells in lavage fluid 8 hours after inoculation, with a gradual decrease toward normal. Antibodies of the IgM isotype to P haemolytica were demonstrated as early as 8 hours through 7 days after inoculation in 3 of 3 calves. Of the anti-P haemolytica isotypes, IgM was found in the highest concentration. In all of the inoculated calves, IgE was found 1 to 2 days after inoculation, and IgG was found in 2 of 3 inoculated calves from day 1 through 7 after inoculation. Detection of IgG correlated with smaller pulmonary lesions. Immunoglobulin A was not detected in lavage fluid. Serum was evaluated for IgG and IgM antibody response to P haemolytica. Specific IgM was detectable 5 days after inoculation, and IgG was detectable 7 days after inoculation. Pasteurella haemolytica antigens were not detected in serum or plasma. A transient increase in neutrophil count was found 8 hours after inoculation, with return to baseline values by 24 hours after inoculation.(ABSTRACT TRUNCATED AT 250 WORDS)  相似文献   

8.
Anionic peptides (APs) are small antimicrobial peptides present in human and ovine lung. In this study APs were also detected in bovine lung, and production of APs in lungs with acute inflammation induced by various stimuli was determined. The distribution and intensity of APs were determined by immunohistochemistry in lungs of 1) neonatal calves (1-3 days of age) inoculated with Mannheimia (Pasteurella) haemolytica, a known inducer of the bovine beta-defensin lingual antimicrobial peptide (LAP) or pyrogen-free saline (PFS), and 2) growing calves (3 months of age) similarly inoculated with M. haemolytica, a lipopolysaccharide (LPS) from M. haemolytica, an LPS-associated protein from M. haemolytica, or PFS. APs were also detected by western blots with the same antibody in lungs of the calves above, as well as in calves inoculated with Pseudomonas aeruginosa, and an adult cow. Anionic peptide (AP) immunoreactivity was detected in bands (approximate weights) in the western blots of lung at 28-30 (strongest signal), 31, 45, and 52-60 kd regardless of inoculum. The adult cow lacked bands at 45 kd, but it had additional bands at 64 (inconsistently) and 35-38 kd. All these band sizes are consistent with those of the western blots of human and ovine lung. The cellular distribution of APs in lung of neonatal and growing cattle was similar to that in lung of human and sheep. In lungs with acute inflammation induced by live bacteria, LPS, or protein, AP distribution and intensity were similar to those in control (PFS-inoculated) lungs and slightly decreased in bronchioles. This work demonstrates that AP is present in lung of cattle and is thereby conserved among two ruminant species and man. Distribution and intensity of AP production are not enhanced by infection or acute inflammation and are decreased in bronchioles, which suggests that AP is not induced like beta-defensins such as LAP, but, instead, is produced constitutively.  相似文献   

9.
Three, 5, or 7 days after inoculation with bovine viral diarrhea (BVD) virus (n = 12) or Mycoplasma bovis (n = 12), groups of calves were exposed to aerosols of Pasteurella haemolytica and were euthanatized 4 hours later. Histologic lesions in the lungs and the ratios of neutrophils to alveolar macrophages, collected by bronchoalveolar lavage, were compared with those of clinically healthy calves (n = 8) and calves inoculated with BVD virus only (n = 4), M bovis only (n = 4), or P haemolytica only (n = 2). Inoculation with BVD virus or M bovis did not have a significant (P greater than 0.05) effect on the neutrophil/macrophage ratio in the bronchoalveolar lavage. Aerosol exposure to P haemolytica induced a marked and significant (P less than 0.01) change in the neutrophil/macrophage ratio (from less than 1:9 to greater than 9:1). The reversed neutrophil/macrophage ratio in calves exposed to P haemolytica correlated well with the histologic changes in which small bronchi and bronchioles were plugged with purulent exudate. Inoculation with BVD virus did not induce gross or microscopic lesions in the lungs. Inoculation with M bovis resulted in a severe peribronchial lymphoid hyperplasia with mild exudation of neutrophils and macrophages into the cranioventral parts of the lungs.  相似文献   

10.
Lecithin:cholesterol acyltransferase (LCAT), the enzyme responsible for esterification of cholesterol in plasma, is reported to be implicated in the regulation of inflammation in laboratory animals. The purpose of the present study was to elucidate the possible relevance of LCAT in the pathogenesis of calf pneumonia induced by inoculations of Pasteurella haemolytica and bovine herpes virus-1 into the calf lung. Serum LCAT activity was significantly (P < 0.01) reduced in calves inoculated with Pasteurella haemolytica. The concentration of cholesteryl esters (CE), the product of the LCAT reaction, was also decreased in the inoculated group. Decreases in LCAT activity and the CE concentration were similarly observed in calves in which bovine herpes virus-1 was inoculated. In both bacteria- and virus-inoculated calves, CE concentrations in the high-density lipoprotein fractions were distinctly decreased, whereas those in the low-density lipoprotein fractions were practically unaltered. The acute-phase proteins haptoglobin and serum amyloid A were detected in sera from the bacteria- and virus-inoculated calves; however, the two acute-phase proteins were also found in sera from the control calves. These results suggest that decreases in LCAT activity and the CE concentration are involved in the pathogenesis of pneumonia induced by inoculation of calves with Pasteurella haemolytica and bovine herpes virus-1, and also that the change in the LCAT system is more intimately related to the occurrence of calf pneumonia than the induction of acute-phase proteins such as haptoglobin.  相似文献   

11.
Iron plays a central role in bacterial infections, influencing both bacterial virulence and host cellular defense mechanisms. We investigated whether iron chelation might be of benefit in the treatment of pneumonic pasteurellosis of calves. Neutrophils obtained from calves previously treated with the iron chelator, deferoxamine, were studied for their responses to latex and opsonized zymosan by luminol-enhanced chemiluminescence and to phorbol myristate acetate and opsonized zymosan by superoxide generation. Treatment with deferoxamine in vivo failed to influence these in vitro measures of neutrophil oxidative metabolism. Furthermore, iron depletion with deferoxamine failed to modify the pathophysiological derangements that occurred in calves following experimental induction of pneumonia by intratracheal inoculation with Pasteurella haemolytica. These data indicate that iron chelation using deferoxamine cannot be recommended as an adjunct to conventional therapy in the treatment of pneumonic pasteurellosis of cattle.  相似文献   

12.
This investigation was conducted to determine if Pasteurella haemolytica within feedlot cattle affected by pneumonic pasteurellosis express fimbriae (pili) and bacterial glycocalyx. Bacteriological culture of pulmonary tissue from three calves with fibrinous pneumonia resulted in heavy growth of P. haemolytica. Transmission electron microscopy of the lungs showed numerous microcolonies of gram-negative bacteria with morphology typical of Pasteurella haemolytica. The cells within these microcolonies possessed bacterial glycocalyces which stained with ruthenium red. Glycocalyx-encased microcolonies were also present in specimens examined by scanning electron microscopy. Typical P. haemolytica cells were evident in a tracheal specimen and these bacteria had radial glycocalyces consistent with polysaccharide and proteinaceous material condensed on linear structures suggestive of fimbriae. The pathogenetic importance of the bacterial glycocalyx and fimbriae in shipping fever pneumonia has yet to be established but their presence in clinical cases of Pasteurella pneumonia in feedlot cattle further supports a possible role in the initiation and progression of this disease as well as bacterial resistance to antimicrobial agents.  相似文献   

13.
Five calves were inoculated intravenously with 10(8) colony forming units (cfu) of Pasteurella haemolytica A1; the mean score for pneumonic consolidation 3 days post-inoculation was 28%, and the mean clinical score was 7.8. Five calves inoculated intratracheally with 10(9) cfu of the same strain of P. haemolytica had comparable scores (34% and 8.8). Histological lesions of fibrinous pneumonia were similar in all calves. P. haemolytica was recovered from all but one of the affected lungs. From one calf killed in extremis 3 hours after intravenous inoculation, numbers of bacteria recovered from lung were 1,000-fold greater than from liver and spleen. A similar difference in bacterial numbers was also obtained from a gnotobiotic calf killed in extremis, 12 hours after intravenous inoculation of 10(8) cfu P. haemolytica. Evidence from these experiments supports the hypothesis that the blood-borne route is important in the pathogenesis of bovine pneumonic pasteurellosis.  相似文献   

14.
OBJECTIVE: To compare concentrations of danofloxacin, enrofloxacin, and ciprofloxacin in plasma and respiratory tissues of calves treated after challenge with Mannheimia haemolytica. ANIMALS: 75 calves. PROCEDURE: 24 hours after challenge with M. haemolytica, 72 calves with clinical signs of respiratory tract disease were randomly assigned to 1 of 12 equal treatment groups.Three nonchallenged, nontreated calves formed a control group. Challenged calves were treated with danofloxacin (6 and 8 mg/kg, SC) and enrofloxacin (8 mg/kg, SC) once. At 1, 2, 6, and 12 hours after treatment, 6 calves from each treatment group were euthanatized. Antimicrobial drug concentrations were assayed in various specimens. Peak plasma concentration (Cmax)-to-minimum inhibitory concentration (MIC; Cmax-to-MIC) ratios and the area under the concentration versus time curve over a 12-hour period-to-MIC ratios (AUC(12h)-to-MIC) were calculat-ed. RESULTS: Danofloxacin and enrofloxacin had MICs of 0.03 microg/mL for the M. haemolytica challenge isolate. Danofloxacin administered at doses of 6 and 8 mg/kg resulted in numerically higher geometric mean concentrations of danofloxacin in plasma and all respiratory tissues than geometric mean concentrations of enrofloxacin after treatment with enrofloxacin. Geometric mean concentrations of enrofloxacin were numerically higher than geometric mean concentrations of ciprofloxacin metabolite in plasma and almost all respiratory tissues. Danofloxacin and enrofloxacin achieved Cmax-to-MIC ratios >10 and AUC(12h)-to-MIC ratios >125 hours. CONCLUSIONS AND CLINICAL RELEVANCE: When used to treat pneumonic pasteurellosis in calves, danofloxacin and enrofloxacin can be expected to deliver concentration-dependent bactericidal activity against M. haemolytica, the bacteria most commonly associated with bovine respiratory tract disease.  相似文献   

15.
Lipoprotein lipid and apoprotein concentrations are known to be altered during the acute-phase response. We have previously shown that the serum activity of lecithin:cholesterol acyltransferase (LCAT) and concentration of cholesteryl esters, both constituents of the high-density lipoprotein (HDL) fraction, are reduced in calves inoculated with Pasteurella haemolytica and bovine herpes virus-1, the two major pathogens for calf pneumonia. The concentration of apolipoprotein C-III (apoC-III), a low molecular mass protein component distributed mainly in the HDL fraction, was therefore examined in bacteria- and virus-inoculated calves. An enzyme-linked immunosorbent assay demonstrated that it was decreased by inoculations of Pasteurella haemolytica and bovine herpes virus-1. The decrease was detected as early as 1 day after inoculation in both groups. A decreased serum apoC-III concentration was also observed by immunoblot analysis. It was detected in the HDL fractions from the bacteria- and virus-inoculated calves, and HDL apoC-III concentrations in the inoculated calves were decreased compared with controls. These results, coupled with the previous findings on LCAT activity and the cholesteryl ester concentration, indicate that a decreased HDL concentration is one of the early events occurring during the acute-phase response evoked by infections with Pasteurella haemolytica and bovine herpes virus-1.  相似文献   

16.
Pasteurella haemolytica pneumonia of the right caudal lung lobe was experimentally induced in 2-week-old Holstein calves (n = 11) by endobronchial inoculation of 7.9 x 10(10) colony-forming units of 6-hour log-phase bacteria. Calves were studied for 72 hours after inoculation. The challenge procedure consistently induced a lesion in the right caudal lung lobe, which was consistent radiographically with results of pathologic examination and a similar volume of bronchography contrast medium. Clinically, the calves developed a significant increase in rectal temperature within 24 hours after inoculation. Seventy-two hours after inoculation, the total WBC counts, absolute band neutrophil counts, monocyte counts, and blood fibrinogen concentrations were significantly higher than normal and albumin concentration was significantly decreased. Necropsy revealed a circular to oblong lesion that was congested, edematous, and firm and occupied 20 to 40% of the right caudal lung lobe. Histologic examination revealed a severe acute inflammatory reaction characterized by cellular exudate and proteinaceous fluid in the alveoli, interlobular septa, and pleura.  相似文献   

17.
A study was designed to develop and define a sc tissue chamber as a suitable device for establishing a soft-tissue infection model in cattle and to use this model to study the interaction between Pasteurella haemolytica, sulfadiazine/trimethoprim, and bovine viral diarrhea virus (BVDV). Thermoplastic tissue chambers were implanted in the paralumbar fossae of 20 calves. At 35 days after implantation, calves were allotted to 4 groups of equal size and the calves in 2 groups were inoculated intratracheally with a New York-1 strain of BVDV. At 45 days after implantation, all chambers were inoculated with a 6-hour culture of P haemolytica serotype 1. Starting 36 hours after bacterial inoculation, sulfadiazine/trimethoprim was administered IV once a day to half of the virus-inoculated calves and to half of those calves that had not been exposed to virus. Inoculation of P haemolytica into tissue chambers resulted in the establishment of a localized soft-tissue infection, characteristic of pneumonic pasteurellosis. Despite the maintenance of chamber antimicrobial concentrations that exceeded minimal bactericidal concentrations established in vitro, the infections were not sterilized. This lack of efficacy was associated with decreased pH and increased protein concentrations in chamber fluids after inoculation. Infection with BVDV, which is thought to depress host defenses, had no effect on the response of P haemolytica to sulfadiazine/trimethoprim administration. Observation of responsive antibody titers, bacterial phagocytosis, and high leukocyte viability within P haemolytica-infected chambers documented functional host defenses within tissue chambers.  相似文献   

18.
Four control calves were aerosolized with parainfluenza-3 and one week later with Pasteurella haemolytica. Three calves were given Corynebacterium parvum at a dose of 15 mg/m2 body surface area, infected with parainfluenza-3 virus one week later, and aerosolized with P. haemolytica two weeks after C. parvum injection. All calves were killed four hours after P. haemolytica exposure and the bacterial retention in the lung was determined. Parainfluenza-3 viral infection did not exert any suppressive effect on pulmonary clearance of P. haemolytica in six out of seven calves used. However, the bacterial colony counts in the lungs of control calves were higher (P less than 0.05) than those in calves given C. parvum. Hence, C. parvum appeared to enhance bacterial clearance. Despite the marked influx of neutrophils into the lungs after the bacterial inoculation, the neutrophil:macrophage ratio in lavage samples was less in calves given C. parvum than in the control calves. The alveolar macrophages in C. parvum treated calves were generally larger but did not differ significantly (P less than 0.05) from those in the controls. There was no significant (P less than 0.05) correlation between the percentages of alveolar macrophages and the bacterial clearance. In calves given C. parvum, bacterial clearance was enhanced in those calves which had larger macrophages.  相似文献   

19.
The effect of bacterial infection on antibiotic activity and penetration of parenterally administered ceftiofur into implanted tissue chambers was studied in cattle. Tissue chambers were implanted subcutaneously in the paralumbar fossae of eight calves (256-290 kg body weight). Approximately 80 days after implantation, the two chambers on one side of each animal were inoculated with Pasteurella haemolytica (106 CFU/chamber). Eighteen hours after inoculation, ceftiofur sodium was administered intravenously (5 mg/kg) to each of the calves. Non-infected chamber fluid, infected chamber fluid and heparinized blood samples were collected immediately before and at 1, 3, 6, 12 and 24 h after drug administration. Concentrations of ceftiofur and desfuroylceftiofur metabolites and ceftiofur-equivalent microbiological activity were measured by high-pressure liquid chromatography and microbiological assay respectively. Concentrations of ceftiofur and desfuroylceftiofur metabolites and antimicrobial activity in P. haemolytica -infected tissue chambers were significantly higher than those in non-infected tissue chambers at all sampling times, indicating that ceftiofur, regardless of the method used for analysis, localizes at higher concentrations at tissue sites infected with P. haemolytica . Antibiotic activity-concentration ratios were lower in plasma and infected chamber fluid compared with non-infected chamber fluid, suggesting that antibiotic was bound to proteins. However, higher antimicrobial activity in the infected chamber fluid compared with the non-infected chamber fluid suggests that active drug is reversibly bound to proteins. Protein-bound desfuroylceftiofur may represent a reservoir for release of active drug at the site of infection in the animal.  相似文献   

20.
Mannheimia haemolytica and bovine respiratory disease   总被引：1，自引：0，他引：1  
Mannheimia haemolytica is the principal bacterium isolated from respiratory disease in feedlot cattle and is a significant component of enzootic pneumonia in all neonatal calves. A commensal of the nasopharynx, M. haemolytica is an opportunist, gaining access to the lungs when host defenses are compromised by stress or infection with respiratory viruses or mycoplasma. Although several serotypes act as commensals, A1 and A6 are the most frequent isolates from pneumonic lungs. Potential virulence factors include adhesin, capsular polysaccharide, fimbriae, iron-regulated outer membrane proteins, leukotoxin (Lkt), lipopolysaccharide (LPS), lipoproteins, neuraminidase, sialoglycoprotease and transferrin-binding proteins. Of these, Lkt is pivotal in induction of pneumonia. Lkt-mediated infiltration and destruction of neutrophils and other leukocytes impairs bacterial clearance and contributes to development of fibrinous pneumonia. LPS may act synergistically with Lkt, enhancing its effects and contributing endotoxic activity. Antibiotics are employed extensively in the feedlot industry, both prophylactically and therapeutically, but their efficacy varies because of inconsistencies in diagnosis and treatment regimes and development of antibiotic resistance. Vaccines have been used for many decades, even though traditional bacterins failed to demonstrate protection and their use often enhanced disease in vaccinated animals. Modern vaccines use culture supernatants containing Lkt and other soluble antigens, or bacterial extracts, alone or combined with bacterins. These vaccines have 50-70% efficacy in prevention of M. haemolytica pneumonia. Effective control of M. haemolytica pneumonia is likely to require a combination of more definitive diagnosis, efficacious vaccines, therapeutic intervention and improved management practices.  相似文献   

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