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1.
A study was designed to determine the effect of Pasteurella haemolytica infection on the rate and extent of penetration of sulfadiazine and trimethoprim into tissue chambers implanted SC in cattle. Thermoplastic tissue chambers were implanted SC in 6 calves. At 35 days after implantation, sulfadiazine (25 mg/kg of body weight) and trimethoprim (5 mg/kg) were administered IV to 5 of the calves. Chamber fluid and blood samples were collected from each animal at various time intervals for 24 hours after administration. Ten days later, all chambers were inoculated with P haemolytica serotype 1. At 36 hours after inoculation, a second pharmacokinetic study was conducted, using sulfadiazine and trimethoprim. Drug doses and sampling schedules were identical to those used prior to inoculation. A histologic study of infected chamber tissue was conducted, using the calf not included in the pharmacokinetic studies. Disposition curves of antimicrobials in serum and chamber fluid were well described by 2-compartment and 1-compartment pharmacokinetic models, respectively. Inoculation of P haemolytica into tissue chambers was accompanied by marked changes in the composition of chamber fluid. Increased total protein and albumin concentrations, decreased pH, and disruption of chamber tissue vasculature were associated with a significant increase in the penetration of sulfadiazine and trimethoprim into infected tissue chambers, compared with that in noninfected chambers. This increased penetration was accompanied by increases in the apparent volume of distribution for sulfadiazine and trimethoprim.  相似文献   

2.
A subcutaneous soft tissue infection model in calves was used to study the in vivo response of Pasteurella haemolytica to erythromycin and dexamethasone. Two tissue chambers were implanted SC in each of 12 calves. At 45 days after implantation, all tissue chambers were inoculated with an erythromycin-sensitive strain of P haemolytica. Starting 24 hours after inoculation, calves were allotted to 4 groups of equal size and a 2 x 2-factorial arrangement of treatments was applied: 3 calves were given erythromycin (30 mg/kg of body weight, IM, for 5 days), 3 calves were given dexamethasone (0.05 mg/kg, IM, for 2 days), 3 calves were given erythromycin and dexamethasone, and the remaining calves served as nontreated controls. Chamber fluids were tested daily, and the response to treatment was measured. Neither erythromycin nor dexamethasone affected viability or growth of bacteria within tissue chambers. Dexamethasone had no effect on the influx of neutrophils into infected chambers. Despite repeated administration of a high dose of erythromycin and attainment of adequate concentration in serum, erythromycin concentration in chamber fluids did not exceed the minimal inhibitory concentration established in vitro. These results indicate that the clinical efficacy of erythromycin against P haemolytica sequestered in consolidated pneumonic lesions may not be well correlated with predictions based on serum pharmacokinetic and in vitro susceptibility data.  相似文献   

3.
Subcutaneously implanted tissue chambers: a pathophysiological study   总被引：3，自引：0，他引：3  
Tissue and fluid changes occurring within tissue chambers were characterised as a function of time after subcutaneous implantation in cattle. Cytological and chemical investigation revealed that the composition of fluid within chambers approached the theoretical composition of true interstitial fluid as time after implantation progressed. Erythrocyte and leucocyte numbers decreased sharply immediately after implantation and had reached stable numbers by 40 days after implantation. At this stage, chamber fluid samples had lower total protein and albumin concentrations, higher K+ and Cl- concentrations and lower pH than corresponding blood samples. Despite an ongoing low-grade chronic inflammatory reaction resulting in fibrous encapsulation of chambers, the vascularity of chamber tissue did not diminish with time after implantation. By 40 days after implantation, the cellular and chemical constituents had stabilised enough to allow use of the model to study drug distribution.  相似文献   

4.
Distribution of erythromycin into subcutaneous tissue chambers was characterised pharmacokinetically and the effect of Pasteurella haemolytica infection on the extent of penetration was studied. Thermoplastic tissue chambers were implanted subcutaneously in the paralumbar fossae of six calves. Thirty-five days after implantation, the tissue chamber distribution of intramuscularly administered erythromycin (30 mg kg−1) was studied. Chambers were then inoculated with P haemolytica and the tissue chamber pharmacokinetics of erythromycin were again studied. Diffusion of erythromycin into tissue chambers was best described using a two-compartment model with tissue chambers representing a relatively inaccessible compartment. Despite changes in chamber fluid pH, the extent of erythromycin penetration into chambers was not affected by P haemolytica inoculation. Comparison of computer simulated concentration-time curves resulting from different routes of administration revealed that penetration of erythromycin into less accessible sites was more likely to be higher after intravenous administration than after intramuscular administration.  相似文献   

5.
OBJECTIVES: To determine systemic and local platinum concentrations released from subcutaneously implanted cis-diamminedichloroplatinum (cisplatin) -impregnated polymethylmethacrylate (PMMA) and to evaluate systemic or local adverse reactions. ANIMALS: 6 healthy dogs. PROCEDURE: Cisplatin (20 mg) was inserted into PMMA that was fashioned into cylinders and placed into subcutaneous tissue chambers overlying the thorax (treated site). An empty tissue chamber was placed over the opposite side (control site). Plasma samples were obtained for platinum determination before implantation, at 3, 6, and 12 hours after implantation on day 0, and once daily on days 1, 2, 3, 7, 14, 21, and 29. At similar times on similar days, tissue chamber fluid samples also were obtained for platinum determination. Complete blood count, serum urea nitrogen and creatinine concentration determinations, and urinalyses were performed on days 1, 2, 3, 7, 14, 21, and 29. Complete necropsy was performed at conclusion of the study. RESULTS: Tissue chamber platinum concentrations at the treated site were significantly greater than plasma and control site tissue chamber concentrations on days 2, 3, 7, 10. Mean plasma platinum concentration at 3 (0.735 microg/ml), 6 (0.691 microg/ml), 12 (0.534 microg/ml), 24 (0.131 microg/ml), 48 (0.2 microg/ml), 72 (0.1 microg/ml), and 158 (0.014 microg/ml) hours was significantly greater than pretreatment values (0.0 microg/ml). Plasma platinum concentration 10 days after treatment (0.011 microg/ml) did not significantly differ from pretreatment values. Local or systemic adverse reactions were not apparent. CONCLUSIONS: The route of cisplatin administration was safe. Greater concentration of platinum was released locally relative to plasma concentration for an extended period.  相似文献   

6.
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   

7.
The effect of Mannheimia haemolytica infection on the penetration of ceftiofur and desfuroylceftiofur metabolites into tissue chambers was studied in cattle after subcutaneous administration of ceftiofur crystalline free acid sterile suspension (CCFA-SS). Four tissue chambers were implanted subcutaneously in each of 12 calves. Approximately 45 days after implantation, two chambers were inoculated with M. haemolytica (10(6) colony-forming units per chamber) while the remaining two chambers were inoculated with sterile phosphate-buffered saline. Twenty-four hours after inoculation, CCFA-SS was administered subcutaneously in the middle third of the caudal ear pinna of each calf. Chamber fluid and blood samples were collected at predetermined times for 10 days following dosing and analyzed for ceftiofur and desfuroylceftiofur metabolites by high-performance liquid chromatography. Concentrations of ceftiofur and desfuroylceftiofur metabolites in plasma and tissue chamber fluid remained above a threshold of 0.2 microg/mL for at least 8 days. Infected tissue chamber fluid concentrations of ceftiofur and desfuroylceftiofur metabolites were significantly higher than those in non-infected tissue chamber fluid, which correlated with significantly higher total protein concentration in infected tissue chambers. These results indicate that single subcutaneous administration of CCFA-SS at 6.6 mg/kg can be expected to provide effective therapy of susceptible bacterial infections for a period of at least 1 week.  相似文献   

8.
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   

9.
The results showed that co-administration of either vitamin K or levamisole along with phenylbutazone abolished the latter's anti-inflammatory and antipyretic activities and reduced its analgesic effect. Prolonged administration of phenylbutazone alone to rats for 21 days increased significantly serum glutamate oxalacetate transaminase (SGOT) activity, urea and creatinine concentrations, while it decreased with significance uric acid concentration in the serum. Vitamin K, when administered together with phenylbutazone, reduced its effect on SGOT activity and creatinine concentration. Levamisole antagonised the uricosuric effect of phenylbutazone, when both were concomitantly given. Histopathological examination of the liver of rats, given phenylbutazone alone, showed mild degenerative changes, whereas in combination with levamisole these changes were exacerbated. Kidney showed oedema, degeneration, congestion, and haemorrhage. These changes were severe in rats, given phenylbutazone alone, moderate in levamisole-treated animals, and mild in those given both drugs. Combination of levamisole with phenylbutazone not only decreased the congestion of gastric mucosa but also activated the gastric glands.  相似文献   

10.
Calves from the dairy herd of the institute reared in groups with changing (Gw, N 16, m 9, w 7) and constant composition (Gk, N 16, m 9, w 7) since the first day of life and single box reared calves (E, N 11, m 7, w 4) were tested at 15, 30, 60 and 90 days of age. Venous blood samples were analysed for total protein, albumin, creatinine, blood urea, glucose, Ca, Mg, P and iron. At 15 days between group differences of mean values existed for total protein, albumin, blood urea, creatinine and at 30 days for rectal temperature, albumin, blood urea, Ca, P and Fe, at 60 days for blood urea, glucose, Ca, Mg, P and at 90 days for total protein, albumin, creatinine, glucose, Mg and P. Interactions between group and gender could not be demonstrated. Significant changes of variables with age were most frequent in calves of group Gk, and more frequent with creatinine, blood urea, Fe and glucose. Creatinine concentration diminished permanently with age of the animals, that one of total protein and albumin increased moderately. Blood urea was higher at 90 days, and serum iron at 60 and 90 days than before. Blood glucose concentration at 90 days was lower in calves of group Gw and Gk comparing group E. Significant group differences appeared at 15 days (total protein, albumin, blood urea, creatinine) and remained till 60 days (blood urea) and 90 days (total protein, albumin) or became stronger at 90 days (creatinine). Total protein, albumin and blood urea were higher in group E than in group Gk and Gw calves. Group Gw calves had smallest glucose concentrations at 60 and 90 days. Significant between groups differences for Ca, Mg, P existed for all sampling points, those for serum iron at 30 days only. Greater Ca and Mg values were found in group Gk and group E calves, greater P concentrations up to 60 days of age in group E calves. P concentrations changed differently in group Gk and group Gw calves with age. Creatinine showed moderately high between sampling point correlations. Changes of variables in calves between age points in relation to the starting situation at 15 days of age showed significant correlations in many cases meaning that there were directed individual and time specific adaptation processes.  相似文献   

11.
A soft-tissue infection model was created in eight horses by infecting subcutaneous tissue chambers with Streptococcus zooepidemicus organisms. Responses of the horses to the infections were determined by monitoring changes in the complete blood count and body temperature and by following changes in the cytology and protein content of the tissue chambers. Systemic reactions to the infections included a mild neutrophilia, mild pyrexia and mild anemia. There was a marked influx of neutrophils and protein into the chambers after they were seeded with bacteria and chamber neutrophil viability decreased markedly at the height of the infection. Subsequent to establishing tissue chamber infections four of the horses were treated with intravenous cephapirin t.d. at a dosage of 20 mg/kg for 5 days. Quantitative culturing of tissue chamber fluid was performed to analyze the efficacy of cephapirin therapy. Cephapirin therapy was accompanied by decreases in the systemic neutrophilia, pyrexia, anemia, and chamber bacterial counts. However, cephapirin did not eliminate the infection in any of the chambers. Chamber neutrophil viability was markedly increased during the cephapirin therapy period.  相似文献   

12.
Simultaneous administration of a nonselective COX inhibitor and a COX‐2 specific NSAID has not been previously reported in horses. The goal of this study was to determine the safety of a 10‐day dosage regimen of phenylbutazone and firocoxib, both at their standard dosages, in horses. Six horses were administered 2.2 mg/kg of phenylbutazone and 0.1 mg/kg of firocoxib by mouth, daily for 10 days. Horses were assessed daily for changes in behavior, appetite, fecal consistency, signs of abdominal pain, and oral mucous membrane ulceration. Horses were assessed prior to and on the last day of treatment for changes in serum creatinine, albumin, total protein, and urine‐specific gravity. Horses underwent endoscopic examination of the esophagus, stomach, and pylorus prior to and 24 hours after the last treatment. A significant change in serum creatinine and total protein was observed on day 10 of treatment. No other significant findings were noted during the experiment. Results indicated that co‐administration of phenylbutazone and firocoxib may cause renal disease.  相似文献   

13.
This paper describes the use of subcutaneously-placed tissue chambers as a sterile soft-tissue inflammation model in Thoroughbred horses. Acute, nonimmune inflammation was initiated by injecting a sterile lambda carrageenan solution into a tissue chamber. This model was used to study the temporal changes in oxygen and carbon dioxide tensions, pH, bicarbonate, protein, albumin, prostaglandin E2 (PGE2) and leukotriene B4 (LTB4) concentrations, cell counts and differential counts in tissue fluid from inflamed tissue chambers and control chambers. Skin temperatures over control and inflamed chambers were also compared. Carrageenan-induced inflammation resulted in significant increases in tissue-fluid carbon dioxide tension, leucocyte count, albumin, and PGE2 and LTB4 concentrations. It also resulted in a significant decrease in tissue fluid pH and HCO3- concentration. Inflammation did not result in significant changes in tissue-fluid protein concentration, differential cell counts or skin temperature over the chambers. The use of this type of tissue chamber is wellsuited for studying the pathophysiology of a self-contained, non-immune inflammatory process. The model described in this paper could prove to be very useful in studies of the distribution of anti-inflammatory drugs and the effects of such drugs on various aspects of the inflammatory process.  相似文献   

14.
Two mature horses were examined for changes in laboratory and physical findings after experimentally induced bladder rupture. The postrupture laboratory diagnostic changes, which provide valuable information for a correct diagnosis are described. Hematology, serum and peritoneal fluid sodium, potassium, calcium, phosphorous, creatinine, urea nitrogen, albumin and peritoneal fluid components were measured and evaluated versus time. Hyponatremia and hyperkalemia occurred, as well as increased concentrations of peritoneal fluid potassium and inorganic phosphorus. In addition, peritoneal fluid creatinine:serum creatinine and peritoneal fluid urea nitrogen:serum urea nitrogen ratios were followed with time. Hematology and cytology of the peritoneal fluid showed an inflammatory response to urine contamination of the abdominal cavity. Physical findings of tachypnea and tachycardia as well as a mild colic were absent until nearly 50 hours postrupture. Based on these findings, it was concluded that the peritoneal fluid creatinine:serum creatinine ratio was the most useful antemortem laboratory diagnostic aid.  相似文献   

15.
The study describes a technique of ultrasonographically guided transcutaneous catheter implantation into the abdominal aorta of 29 6- to 8-week-old German Holstein calves. Catheters were implanted between the left transverse processes of L3 and L4, left in place for 2 days and used for serial blood sampling and continuous measurement of blood pressure. Complete cell counts and clinical examination were performed before, as well as 1 and 5 days after implantation. Catheterization was successful in all calves. The catheter was patent for blood sampling and pressure recordings at all times. A significant decrease in red blood cells was found in all animals after catheterization, which remained reduced for 5 days. Clinical signs of anaemia were absent. In conclusion, ultrasonographically guided catheterization of the abdominal aorta provides a continuous arterial access in calves, whereby the minimal invasive technique and the ultrasonographical guidance reduces accidental tissue trauma and pain for the animal.  相似文献   

16.
Pharmacokinetic variables of amikacin in cows were determined after administration of amikacin sulphate either intravenously (IV) or intramuscularly (IM) at a dose of 25 mg/kg per day for three days. Amikacin concentrations at time zero and maximum serum concentrations were 240.8 microg/mL and 122.53 microg/mL, respectively. The elimination half-life remained unchanged during the three days of administration (T1/2beta = 1.33 +/- 0.029 h for the IV route and T1/2beta = 2.75 +/- 0.38 h for the IM route). Apparent volumes of distribution suggest limited distribution out of the central compartment (VdAUC = 0.154 +/- 0.005 L/kg; Vdc = 36.50 +/- 2.35 L; Vdss = 0.092 +/- 0.004 L/kg). Bioavailability after IM administration was 95%. Serum profiles of urea, creatinine, albumin, electrolytes and pH after 5-day treatment with amikacin at a dose of 25 mg/kg per day IM revealed no changes. Assessment of diffusion of amikacin to milk by a commercially available screening method to detect antibiotic residues revealed that amikacin could not be detected by the fifth milking period after the last treatment. These results suggest that it would be rational to use a large single-daily dose of amikacin for future clinical trials in cows.  相似文献   

17.
A radioimmunoassay for zeranol has been validated and used to measure the concentration of zeranol in the urine of sheep and cattle treated with zeranol (Ralgro). The assay uses an antibody raised against zeranol-16-carboxy-propyl ether conjugated to human serum albumin. In sheep and cattle urine the limits of detection were approximately 2 ng/ml and 2.5 ng/ml, respectively. In two trials 13 sheep were implanted with 12 mg zeranol at the base of the ear. The mean maximum concentrations of zeranol observed in urine were 45 ng/ml (Trial I) on day 35 and 90 ng/ml (Trial II) on day 56, and had declined to 26 ng/ml 42 days after implantation (Trial I) and 11.7 ng/ml 70 days after implantation (Trial II). In four cattle implanted with 36 mg zeranol the concentrations of zeranol in urine reached a mean maximum concentration of 13.5 ng/ml 22 days after implantation and had declined to 2.9 ng/ml 69 days after implantation.  相似文献   

18.
The disposition kinetics and systemic availability of phenylbutazone were studied in healthy dairy cows. The same dose (6mg/kg) of phenylbutazone was administered by the i.v., i.m. and oral routes. The elimination half time after intravenous administration ranged from 32.4 to 60.8h. The result suggested that the distribution of phenylbutazone in cows can be described by a two-compartment open model. Total body clearance of the drug had a mean value of 0.0016 ml/kg-h. The overall tissue to plasma level ratio (k12/k21-β), after distribution equilibrium had been attained was 0.64. Phenylbutazone was shown, by an equilibrium dialysis method, to be highly bound to plasma proteins (93%) at serum levels of 100 μ/ml. The systemic availability of phenylbutazone was 69% and 89% when administered orally and intramuscularly respectively. Animals receiving half the dose of phenylbutazone (3 mg/kg) intravenously did not differ from cows receiving 6 mg/kg in elimination half-life and other distribution and elimination kinetic parameters. Based on the experimental data obtained, a dosage regimen is proposed, consisting of a priming oral dose of 9 mg/kg and maintenance doses of 4.5 mg/kg of phenylbutazone orally administered at 48 h intervals. The relatively long half-life in cattle, however, complicates the use of phenylbutazone because of the drug residue problem.  相似文献   

19.
Plasma elimination rates of sulfamethazine (100 mg/kg of body weight, IV), trimethoprim (20 mg/kg, IV), and antipyrine (35 mg/kg, IV) were studied in adult female dwarf goats (n = 5) before and after implantation with trenbolone acetate (5 mg/kg). Pretreatment with trenbolone caused a significant decrease in the elimination rate of the drugs tested: for sulfamethazine, 5 times; for antipyrine, 3 times; and for trimethoprim, 2 times. After treatment with testosterone (1 mg/kg, SC, twice weekly for 2.5 weeks), female goats (n = 5) had a similar decrease in the elimination rate of sulfamethazine. Other induced effects included a change in social behavior, a lower voice, and the development of a typical billy goat-like odor. Plasma creatinine concentrations after androgen administration were significantly higher than those before androgen administration; changes were not observed in plasma urea values. Because of the differences observed, we believe that more attention should be paid to the effects of androgenic agents on drug kinetic properties, with particular reference to studies on clinical efficacy, side effects, and drug residues in food products.  相似文献   

20.
Xenotransplantation of porcine pancreatic endocrine (PE) cells in a diffusion chamber, a bioartificial endocrine pancreas (Bio-AEP), was conducted to total pancreatectomized dogs. Six pancreatectomized dogs were divided into two groups of 3 dogs each. In three dogs of the control group, exogenous insulin was administered twice a day for 30 weeks to maintain fasting blood glucose (FBG) levels within the normal range. The remaining three dogs were implanted with Bio-AEPs (implantation group), in addition to daily insulin administration. In the implantation group, Bio-AEPs containing 1.3 to 1.8 x 10(7) cells per kg of body weight of the recipient were implanted without fixation into the abdominal cavity. In the control group, exogenous insulin requirements did not decrease during the experimental period, whereas it significantly decreased for a certain period (3, 11, 17 weeks) after implantation in all implanted dogs. In the implantation group, laparotomy was performed after FBG and the exogenous insulin requirement increased again and Bio-AEPs were removed. Two Bio-AEPs were completely destroyed, and the remaining one was encapsulated by thin fibrous tissue. In this dog, effusion was present within the capsule, but the Bio-AEP was not destroyed. Histopathologically, the necrosis, presumably caused by hypoxia, of the PE-cells was observed on transmission electron microscopy. In conclusion, Bio-AEP could function for a certain period after implantation in this study. However, more preclinical researches should be needed to apply this technique for the treatment of diabetic dogs.  相似文献   

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