Depletion of intramuscularly injected ceftiofur from the milk of dairy cattle.

Ceftiofur sodium, a new broad-spectrum cephalosporin, has been approved in the US, Canada, and several other countries throughout the world to treat bovine respiratory disease in cattle and dairy cows. In Experiment 1, 6 lactating cows were intramuscularly treated with 2.29 mg of [14C]ceftiofur/kg of BW daily for 5 d. In Experiment 2, 30 additional cows at three locations were similarly treated with 2.2 mg of ceftiofur (unlabeled)/kg of BW. Milk was collected every 12 and 24 h after each dose and every 12 h up to 5 d after the last dose. The majority of milk samples, both during treatment (12 and 24 h after each dose) and after the last dose (up to 5 d following ceftiofur treatment), were negative by screening procedures based on microbial inhibition (Delvotest-P, Bacillus stearothermophilus disk assay, and cylinder plate assays). The receptor-binding Charm Test II assay, which has a limit of detection of .005 ppm of ceftiofur, gave positive tests for milk samples up to 48 h following treatment. When the Charm Test II assay is used with .008 IU/ml of penicillin as a positive control, 44% of the samples from individual cows were negative at 12 h posttreatment. Ninety percent of the samples from individual cows were negative at 24 h after the last treatment. The use of ceftiofur in dairy cattle in accordance with the label directions does not result in total residues in milk higher than the FDA-calculated safe concentration of 1-ppm ceftiofur equivalents. The milk from individual cows did not test positive by the commercial screening assays examined in this study, except for the Charm Test II. The Charm Test II was 90% negative using the Charm Sciences criteria at 24 h after the last treatment.     

Ivermectin residues in the edible tissues of swine and cattle: effect of cooking and toxicological evaluation

Young male pigs (25-40 kg bw) were treated experimentally with a single 0.4 mg/kg bw, s.c. dose of ivermectin (Ivomec vet. inj., MSD). The disappearance of the drug from the edible tissues 7-21 days after treatment was studied using a sensitive high-performance liquid chromatographic method. The highest residue levels were found at the injection site (up to 59 and 2.6 mg/kg 7 and 14 days post-injection, respectively). Among the other tissues studied, the residue levels 7 days post-injection showed the following order: liver (less than or equal to 50 micrograms/kg) greater than kidney (less than or equal to 25 micrograms/kg) greater than muscle (less than or equal to 20 micrograms/kg). After 21 days only traces of ivermectin (less than or equal to 2 micrograms/kg) could be detected in the muscle and other edible tissues, including the injection site. Similar residue concentrations were found in slaughterhouse material from sows therapeutically treated with ivermectin for parasite infestation. An ordinary culinary preparation of the minced beef muscle from a bull treated with ivermectin resulted in a 45% (boiling) or 50% (frying) decrease in the drug residue. Based on the known toxic effects of the drug and the results of the present and other residue studies, the suggested withdrawal time for Ivomec in edible tissues of swine and cattle is 21 and 28 days, respectively.     

A survey of gross pathologic conditions in cull cows at slaughter in the Great Lakes region of the United States

The prevalence and severity of multiple gross pathologic lesions and abnormalities in cull dairy and beef cows was evaluated at a commercial abattoir in the Great Lakes region of the United States; 1,461 cattle were examined at slaughter over the course of 3 production days and evaluated for the occurrence and severity of lung, liver, rumen, and carcass abnormalities and pathologies. Of the 1,461 cattle examined at slaughter, 87% were classified as Holstein cows and 13% were classified as other cows. Liver abscesses were observed in 32% of the population and over half were classified as severe (18.5% population prevalence). The frequency distribution of cattle observed with a liver abscess was not different among production days. Severe ruminal lesions and rumenitis scars were observed in 10.0% of the population, and 25.1% of cattle were observed to have short or denuded papillae. Severe bovine respiratory disease complex lesions were observed in 10.3% of cattle. The most common reason for USDA postmortem carcass condemnation was malignant lymphoma (9 of 41). Only 45.9% of carcasses were free from bruising. Results indicate that ruminal acidosis and bovine respiratory disease complex occur at a relatively high frequency in this population. Although cows are routinely culled for reproductive failure or low milk production, the underlying reason may be causally related to these relatively prevalent conditions. Further investigation is warranted to assess this relationship and to examine the use of specific health intervention strategies within this demographic of cattle.     

Oxytocin precursor gene expression in bovine skeletal muscle is regulated by 17β-oestradiol and dexamethasone

Growth promoter administration, in livestock, potentially poses a major threat to public health, due to the potential endocrine and carcinogenic activity of residues, accumulating in edible tissues, such as skeletal muscle. Therefore, development of new screening tests and methods for the detection of illicit treatments of food animals would be useful. In this study the serum concentrations of oxytocin peptide were measured in beef cattle receiving 17β oestradiol, dexamethasone or placebo over a period of 40 days. Changes in gene expression of oxytocin precursor in skeletal muscle were also examined in these animals. Serum analysis using an oxytocin EIA kit indicated a significant up-regulation of the biosynthesis of this nonapeptide only in cattle after 17β oestradiol, but not after dexamethasone or placebo treatment. Quantitative PCR (qPCR) analysis showed a significant overexpression of the oxytocin precursor gene by 33.5 and 13.3-fold in cattle treated with 17β oestradiol and dexamethasone, respectively, in comparison to placebo treated animals. Regulation of gene expression by some myogenic regulatory factors in skeletal muscle was also evaluated in these animal groups, confirming the activity of both growth promoters on this gene. To investigate the use of the oxytocin precursor gene as biomarker for 17β oestradiol and dexamethasone treatment in beef cattle, an absolute quantification of this gene by qPCR was developed. A standard curve was generated and developed with TaqMan® technology and optimal criterion value, sensitivity and specificity of this screening method were established through ROC analysis. This analysis suggested that the up-regulation of oxytocin precursor gene expression in skeletal muscle tissue is a valid marker for detection of illicit 17β oestradiol and/or dexamethasone use in beef cattle. This method may serve as a novel diagnostic tool in the screening phase, and, if introduced in routine testing, may significantly improve overall efficacy and success of the food screening process ordered by state authorities.     

Development of a physiologically based pharmacokinetic model for flunixin in cattle (Bos taurus)

Frequent violation of flunixin residues in tissues from cattle has been attributed to non-compliance with the USFDA-approved route of administration and withdrawal time. However, the effect of administration route and physiological differences among animals on tissue depletion has not been determined. The objective of this work was to develop a physiologically based pharmacokinetic (PBPK) model to predict plasma, liver and milk concentrations of flunixin in cattle following intravenous (i.v.), intramuscular (i.m.) or subcutaneous (s.c.) administration for use as a tool to determine factors that may affect the withdrawal time. The PBPK model included blood flow-limited distribution in all tissues and elimination in the liver, kidney and milk. Regeneration of parent flunixin due to enterohepatic recirculation and hydrolysis of conjugated metabolites was incorporated in the liver compartment. Values for physiological parameters were obtained from the literature, and partition coefficients for all tissues but liver and kidney were derived empirically. Liver and kidney partition coefficients and elimination parameters were estimated for 14 pharmacokinetic studies (including five crossover studies) from the literature or government sources in which flunixin was administered i.v., i.m. or s.c. Model simulations compared well with data for the matrices following all routes of administration. Influential model parameters included those that may be age or disease-dependent, such as clearance and rate of milk production. Based on the model, route of administration would not affect the estimated days to reach the tolerance concentration (0.125 mg kg^?1) in the liver of treated cattle. The majority of USDA-reported violative residues in liver were below the upper uncertainty predictions based on estimated parameters, which suggests the need to consider variability due to disease and age in establishing withdrawal intervals for drugs used in food animals. The model predicted that extravascular routes of administration prolonged flunixin concentrations in milk, which could result in violative milk residues in treated cattle.     

Short communication: Determination of the milk pharmacokinetics and depletion of milk residues of flunixin following transdermal administration to lactating Holstein cows

Flunixin is a nonsteroidal anti-inflammatory drug and the most commonly prescribed analgesic in cattle in the United States. Recently, the US Food and Drug Administration (FDA) approved a transdermal formulation of flunixin for control of pyrexia associated with bovine respiratory disease and the control of pain associated with foot rot. The transdermal formulation is not currently approved for use in lactating dairy cattle in the United States, but extra-label use in dairy cattle is permissible under US regulations. The objectives of this study were to determine the pharmacokinetics in milk of dairy cows treated with transdermal flunixin and determine an appropriate withdrawal time for milk. Ten lactating Holstein cows were enrolled into the study in mid lactation. Following treatment, cows were milked 3 times per day through 144 h. Milk samples were collected for drug analysis using ultra-high-pressure liquid chromatography coupled with a triple quadrupole mass spectrometer. The geometric mean maximum concentration for flunixin in milk was 0.010 μg/mL and was 0.061 μg/mL for the active metabolite, 5-hydroxyflunixin. The geometric mean terminal half-life was 20.71 h for flunixin and 22.62 h for 5-hydroxyflunixin. Calculations to approximate a withdrawal time in milk following transdermal flunixin administration were accomplished using a statistical tolerance limit procedure. This analysis indicated that it would be prudent to observe a withdrawal period of 96 h following the last treatment. This is more than twice as long as the labeled withdrawal period of 36 h following use of the injectable formulation. The withdrawal period suggested by this work should be applied carefully, as this study was not conducted under the full quality control practices required by the US FDA for a full drug approval study. Caution should be taken when applying this withdrawal time to diseased animals, animals that are milked with different milking frequencies, and those in different stages of production as these have all been shown to affect drug depletion from milk.     

Effect of chemical dehairing on the prevalence of Escherichia coli O157:H7 and the levels of aerobic bacteria and enterobacteriaceae on carcasses in a commercial beef processing plant

The objective of this experiment was to test the hypothesis that cleaning cattle hides by removing hair and extraneous matter before hide removal would result in improved microbiological quality of carcasses in commercial beef processing plants. To test this hypothesis, we examined the effect of chemical dehairing of cattle hides on the prevalence of Escherichia coli O157:H7 and the levels of aerobic bacteria and Enterobacteriaceae on carcasses. Samples from 240 control (conventionally processed) and 240 treated (chemically dehaired before hide removal) hides (immediately after stunning but before treatment) and preevisceration carcasses (immediately after hide removal) were obtained from four visits to a commercial beef processing plant. Total aerobic plate counts (APC) and Enterobacteriaceae counts (EBC) were not (P > 0.05) different between cattle designated for chemical dehairing (8.1 and 5.9 log CFU/100 cm2 for APC and EBC, respectively) and cattle designated for conventional processing (8.0 and 5.7 log CFU/100 cm2 for APC and EBC, respectively). However, E. coli O157:H7 hide prevalence was higher (P < 0.05) for the control group than for the treated group (67% versus 88%). In contrast to hides, the bacterial levels were lower (P < 0.05) on the treated (3.5 and 1.4 log CFU/100 cm2 for APC and EBC) than the control (5.5 and 3.2 log CFU/100 cm2 for APC and EBC) preevisceration carcasses. Prevalence of E. coli O157:H7 was lower (P > 0.05) on treated than on control preevisceration carcasses (1% versus 50%). These data indicate that chemical dehairing of cattle hides is an effective intervention to reduce the incidence of hide-to-carcass contamination with pathogens. The data also imply that any effective hide intervention process incorporated into beef processing procedures would significantly reduce carcass contamination by E. coli O157:H7.     

Investigations on the occurrence of non-extractable residues of trienbolone acetate in cattle tissues in respect to their bioavailability and immunological reactivity

3H-trienbolone acetate (TBA) was injected/implanted in cattle and the distribution of radioactivity in liver and muscular tissue was determined, applying rigorously standardized organic or aqueous extraction procedures, either directly or following enzymatic hydrolysis and proteolytic procedures. These steps yielded almost 100% recovery of the radioactivity and indicated that only between 5% and 15% of the total residues present was extractable with organic solvents. The remaining radioactivity was either soluble in aqueous media or stayed bound to tissue structures. Similarly processed liver tissue from a calf treated with 3500 mg TBA 68 days prior to slaughter was examined by applying radioimmunoassay for the determination of TBA/trienbolone (TBOH). Indications of the presence of trienic-steroid type residues were only obtained for fractions containing residues extractable with organic solvents.     

Blood in the respiratory tract during slaughter with and without stunning in cattle

Bovine respiratory tracts were examined for blood following shechita without stunning, halal slaughter without stunning, and captive bolt stunning with sticking. In all three methods the cattle were in the upright (standing) position at the start of bleeding. Those that had not been stunned continued to breathe during the early part of bleeding whilst those that were stunned were not breathing. Nineteen percent of the shechita, 58% of the halal and 21% of the stunned plus stuck cattle had blood lining the inner aspect of the trachea. Thirty six percent, 69% and 31% had blood in the upper bronchi, respectively. Ten percent, 19% and 0% had fine bright red blood-tinged foam in the trachea, respectively. It was concluded that concerns about suffering from airway irritation by blood could apply in animals that are either not stunned before slaughter or do not lose consciousness rapidly whilst blood is present in the respiratory tract.     

Effect of vitamin E supplementation on α-tocopherol and β-carotene concentrations in tissues from pasture- and grain-fed cattle

The effects of dietary vitamin E supplementation of grain-fed cattle on lipid oxidation and meat colour have been extensively investigated, but little attention has been given to pasture-fed cattle where meat is likely to contain naturally high amounts of α-tocopherol and carotenoids. In the work described, we evaluated the effects of pasture-feeding alone and with vitamin E supplementation on tissue levels of anti-oxidants and compared the findings with those obtained for grain-fed cattle with and without supplementation. Sorghum was the major component of the grained-based ration. α-Tocopherol concentrations in plasma, muscle and fat tissues of pasture-fed cattle were not affected by vitamin E supplementation (2500 IU/head/day for 132 days prior to slaughter) while those of grain-fed cattle increased significantly. The α-tocopherol concentrations in the supplemented grain-fed cattle were similar in muscle and liver to pasture-fed animals but were lower in their fat (P<0.05). The major carotenoid present in all tissues studied from pasture-fed was β-carotene and its contents in plasma, liver, fat and muscles were decreased (P<0.05) by supplementation with vitamin E. Carotenoids were essentially absent in grain-fed cattle except for small amounts in liver. The implication of this study for the meat industry is that cattle grazed on good pasture can achieve concentrations of α-tocopherol in muscles and other tissues at least as high as those obtained by supra-nutritional supplementation of grain-fed cattle with vitamin E. However, α-tocopherol supplementation of pasture-fed cattle reduced tissue concentrations of β-carotene, which would reduce carcase fat yellowness and make pasture-fed cattle more acceptable to some Asian markets.     

The effect of production system and age on levels of iron, taurine, carnosine, coenzyme Q(10), and creatine in beef muscles and liver

Samples of longissimus (LL) and triceps brachii (TB) muscles from Angus-cross heifers finished either on a high-concentrate ration in Washington, USA, (US cattle, n = 15) or on pasture in New Zealand (NZ cattle, n = 16) were assessed for composition characteristics. Half of the NZ cattle were of a similar age to the US cattle (NZAge) and half were of a similar weight (NZWt). Iron concentration was higher in TB (20.9 vs. 17.5 μg g⁻¹; P < 0.001) and was higher for the NZWt group than the NZAge group or the US cattle. The proportion of iron as haem iron was highest for the NZWt group (87.3%; P < 0.01), but the proportion as soluble haem iron was highest for the US cattle. For a sub-group of 10 pasture-finished cattle, iron levels in cheek muscle were higher than for LL or TB, and liver levels were 66% higher than cheek muscle. The proportion of haem iron, however, was lowest in liver (55.3%) and was lower in cheek muscle (78.4%) than LL or TB. Relative to LL, TB had higher levels of taurine and coenzyme Q₁₀, but lower levels of carnosine, creatine and creatinine, as expected for a muscle with a more aerobic metabolism. These differences were magnified for the even more aerobic cheek muscle. Differences between the two NZ groups were small, but muscles from the US cattle contained less taurine, carnosine, coenzyme Q₁₀, and creatinine. Reasons for these differences in various meat components for similar cattle from different production systems are not clear.     

The lead, cadmium and mercury concentrations in muscle, liver and kidney from Finnish pigs and cattle during 1987-1988

The lead, cadmium and mercury concentrations in muscle, liver and kidney from Finnish pigs and cattle were determined. The average wet weight lead concentrations in pig muscle, liver and kidney were 15 micrograms/kg, 38 micrograms/kg and 40 micrograms/kg, respectively. The corresponding concentrations for cattle were 13 micrograms/kg, 57 micrograms/kg and 110 micrograms/kg. The average wet weight cadmium concentrations were 1.5 micrograms/kg, 28 micrograms/kg and 170 micrograms/kg (pigs) and 1.3 micrograms/kg, 61 micrograms/kg and 350 micrograms/kg (cattle). The corresponding mercury concentrations were 11 micrograms/kg, 12 micrograms/kg and 14 micrograms/kg (pigs) and 11 micrograms/kg, 12 micrograms/kg and 15 micrograms/kg (cattle). The average concentrations were at or above the detection limit of the metal in question. According to the results obtained by the National Veterinary Institute, the cadmium concentration in pigs and cattle has decreased during the period 1973-1988. The provisional tolerable daily intake of lead/person (60 kg), recommended by GEMS/Food, is 0.43 mg. According to the results for lead levels in these products in Finland, a daily intake of 29 kg pig muscle, 33 kg cattle muscle, 11 kg pig liver, 8 kg cattle liver, 11 kg pig kidney or 4 kg cattle kidney would be required to reach this norm. The corresponding provisional tolerable daily intake of cadmium/person (60 kg) is 0.06 mg and is equivalent to 40 kg pig muscle, 46 kg cattle muscle, 2 kg pig liver, 1 kg cattle liver, 0.4 kg pig kidney and 0.2 kg cattle kidney. The validity of the methods was tested four times a year using spiked check samples.     

Depletion of protein-bound furazolidone metabolites containing the 3-amino-2-oxazolidinone side-chain from liver, kidney and muscle tissues from pigs.

Ten 3-month-old pigs were treated with feed containing 300 mg furazolidone per kg for a period of 7 days, followed by withdrawal periods of 0, 1, 2, 3 or 4 weeks (two per group). The treatment resulted in the formation of protein-bound metabolites containing an intact 3-amino-2-oxazolidinone (AOZ) side-chain that could be chemically released and then detected in liver, kidney and rump muscle tissues even 4 weeks after dosing. In tissues from animals killed at the end of the medication period, 993, 600 and 124 ng of AOZ were released from 1 g of liver, kidney and muscle respectively. In the tissues of the animals killed after a further 4 weeks the corresponding levels were 41, 7 and 10 ng/g respectively. It may be concluded that long withdrawal periods prior to slaughter for human consumption are required for pigs treated with furazolidone, because of the long residence time of protein-bound AOZ and the possibility that it might be released from its protein-bound form in the stomach and subsequently be transformed into a hydrazine.     

Identification of the species of origin of fresh,cooked and canned meat and meat products using antisera to thermostable muscle antigens by ouchterlony's double diffusion test

Antisera to thermostable muscle antigens (TMA) from 14 species of bovidae were raised in goats and/or sheep. To achieve species specificity the antisera were absorbed with serum from the other species. While the absorbed antisera to TMA of buffalo, impala, eland, waterbuck, wildebeest and oryx were rendered specific, the antiserum to cattle TMA cross-reacted with buffalo fresh meat antigens (FMA) and cooked meat antigens (CMA) but not with buffalo thermostable muscle antigens. Fresh and cooked muscle antigens from these two species could be differentiated by the antiserum to buffalo TMA. A similar approach was used to differentiate the FMA, CMA, and TMA of kongoni, topi and wildebeest. Antiserum to cattle TMA proved useful in detecting the presence of beef meat in meat products that had undergone commercial sterilisation.     

Contribution of cattle products to dietary intake of trace and toxic elements in Galicia, Spain

In Galicia, Spain, liver copper concentrations, muscle zinc concentrations and kidney cadmium concentrations (in adult cattle) can exceed acceptable maximum concentrations which have been adopted by some countries. The aim was to calculate the contribution of cattle products to the daily intake of trace and toxic metals by humans in Galicia and to evaluate whether there was any health risk to consumers. This was done by comparing calculated intakes with published acceptable daily intake rates for toxic elements and with the accepted safe ranges for population mean intakes of the essential metals. Typically, the contribution of cattle meat and offal to the daily cadmium, lead and arsenic intake of people in Galicia was minimal because offal is rarely eaten. However, liver from older cattle, especially animals from relatively contaminated areas, could pose a health risk if offal was consumed in substantial quantities. Muscle and liver from Galician cattle that exceeded acceptable maximum concentrations for copper and zinc did not pose a risk to human health.     

Rapid depletion of marbofloxacin residues in rabbit after therapeutic treatment

Although rabbit meat production represents a very small percentage of the world meat market, this percentage has been growing continuously during the last 30 years. Rabbit is considered a minor food species, and therefore no drugs are specifically registered for this animal. This situation encourages rabbit farmers to make off-label use of antibacterial drugs authorized for food-producing animal species other than rabbits. In the present study, the distribution and elimination of the fluoroquinolone antibacterial agent marbofloxacin in rabbit muscle, liver, and kidney was investigated. Marbofloxacin was chosen as a representative of a new generation of antibacterial drugs active against most gram-positive and gram-negative bacteria and mycoplasms; it is well tolerated and has short elimination times in bovine and swine species. Rabbits were treated with marbofloxacin at 2 mg kg of body weight(-1) for 5 days. Residual concentrations in liver, kidney, and muscle tissues were determined posttreatment with high-performance liquid chromatography and fluorescence detection. Marbofloxacin was rapidly distributed and eliminated from rabbit tissues. Concentrations were higher in the liver and kidney than in muscle. However, 48 h after the end of treatment, marbofloxacin concentrations dropped below the maximum residue level fixed for this antibacterial drug in cattle and pigs. Considering the efficacy of marbofloxacin for the treatment of the most common rabbit diseases, its tolerability, and its short elimination time as verified in the present study, use of this antibacterial drug could be extended to therapeutic treatment of rabbits.     

微囊藻毒素-LR对小鼠毒性机制的研究

目的：探讨微囊藻毒素-LR(MC-LR)引起小鼠机体损伤可能的作用机制。方法：通过腹腔注射单次给予小鼠30μg/kg bw 剂量的MC-LR,测定其在给药后1、4、8h 的脏器系数和一些血液生化指标。结果：短时间内(给药后4h)肝脏系数显著增加,肾脏系数变化不明显;血液CAT 含量显著上升,BUN 先显著上升再显著下降;CAT 活力显著上升;SOD 变化不明显。结论：MC-LR 首先攻击肝细胞,产生大量的自由基,破坏细胞膜,进而损伤了肝细胞,影响氨基酸的代谢,使肝脏充血、肿胀;接着又引发肾功能不全,使肾小管过滤能力降低;最后,随着时间的推移,对机体造成了潜在的永久伤害,但机体的修复功能使这种伤害表观上不可见,即MCLR对机体造成的损害在一定程度上是可逆的。     

Chlorinated compounds in tissues of chickens raised on pentachlorophenol-contaminated litter

Broiler chickens were raised on commercial wood shavings containing 134 p.p.m. pentachlorophenol and on control litter consisting of corn-cob chips. Initial analysis of the wood-shaving litter showed the presence of hepta-, octa- and nonachlorinated diphenyl ethers, octa- and nonachlorinated 2-phenoxyphenols, and hepta- and octachlorinated dibenzodioxins. Analysis of liver, fat, and muscle tissue after nine weeks indicated the assimilation of these compounds with pentachlorophenol being present in the highest concentration. Chlorinated diphenyl ethers were detectable only in fat, while octa- and nonachlorinated 2-phenoxyphenols were found in all three tissues examined. While liver and fat contained hepta- and octachlorinated dibenzodioxins, no hexachlorinated congener was detected nor were significant amounts of dioxin found in muscle tissue. Although gross pathological examination of the birds did not indicate abnormalities, a mixed type of hepatic enzyme induction was observed in those birds raised on wood shavings.