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BACKGROUND: Symmetric dimethylarginine (SDMA), a sensitive biomarker for detecting renal injury, has not been characterized in goats. Obstructive urolithiasis (OU) is the most common urinary tract disease in male small ruminants. HYPOTHESIS/OBJECTIVE: Establish an SDMA reference interval (RI) in healthy adult goats and describe SDMA concentrations in goats with OU. We hypothesize that the SDMA RI in healthy adult goats will be similar to that of other adult veterinary species and that SDMA can be utilized to assess the renal function of goats experiencing OU. ANIMALS: Fifty-five healthy adult male and female goats from a university herd were enrolled for SDMA RI development. Twenty male and female goats from a university herd were enrolled for validation of the SDMA RI established. Thirteen male goats diagnosed with OU were enrolled. METHODS: Clinical trial. Serum samples for all animals enrolled were collected and analyzed for SDMA using an immunoassay (IDEXX Laboratories, Inc); goats with OU had additional blood work analyzed (PCV, total solids, and serum biochemistry). Symmetric dimethylarginine and other values in goats with OU were analyzed and compared at specific time points. RESULTS: The SDMA RI for healthy, adult goats is 8.03 µg/dL (90% CI 4.81-11.04) to 25.93 µg/dL (90% CI 22.88-28.97). There was no correlation identified between serum creatinine and SDMA in goats with OU. CONCLUSIONS AND CLINICAL IMPORTANCE: The SDMA RI for adult goats is higher than in other adult large animal species. Use of SDMA in goats with OU is not useful in assessing their renal function.
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BACKGROUND: Pharmacological activity of intramammary drugs depends on adequate drug concentrations within the cistern, but sampling is often limited. Insight into the active drug concentration within the mammary cistern may assist in determining effective and appropriate therapeutic decisions for cows being treated for mastitis. OBJECTIVE: Evaluate the disposition of ceftiofur hydrochloride administered intramammary in diseased and nondiseased quarters. Whole milk and ultrafiltrate sampling techniques were compared. ANIMALS: Ten mature, late lactation Holstein (n = 9) and Jersey (n = 1) dairy cows (422-670 kg) with naturally occurring clinical mastitis, producing between 1.4 and 15.9 kg/day of milk. METHODS: Ultrafiltration probes were placed in both mastitic and healthy quarters. Each quarter was treated with 2 doses of 125 mg ceftiofur hydrochloride suspension, and whole milk and milk ultrafiltrate samples were collected. Ceftiofur concentrations in composite whole milk and milk ultrafiltrate were analyzed. RESULTS: The maximum concentration of ceftiofur was higher in ultrafiltrate samples, but no differences were identified in healthy or mastitic quarters. The use of ultrafiltration probes provides a novel technique for free drug concentrations within the mastitic and healthy bovine mammary gland. CONCLUSIONS AND CLINICAL IMPORTANCE: Significant inter- and intracow variability and lower daily milk weights may overestimate ceftiofur concentrations available within the cistern. The pharmacokinetic (PK) parameters reported in milk ultrafiltrate will help establish a link between the PK and the corresponding drug effect, potentially providing a meaningful rationale for the selection of a safe and effective dose in cows with mastitis.
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In order to mitigate the food animal sector's role in the growing threat of antimicrobial resistance (AMR), the World Health Organization (WHO) suggests the use of lower tier antimicrobials, such as florfenicol. Florfenicol has two dosing schemes used to treat primarily bovine respiratory disease. In this study, the objective was to characterize the plasma and gastrointestinal pharmacokinetics of each dosing regimen and assess the effect of these dosing regimens on the prevalence of resistant indicator bacteria over time. Twelve steers underwent abdominal surgery to facilitate the placement of ultrafiltration probes within the lumen of the ileum and colon, as well as placement of an interstitial probe. Following surgery, cattle were dosed with either 20 mg/kg IM every 48 h of florfenicol given twice (n = 6) or a single, subcutaneous dose (40 mg/kg, n = 6). Plasma, interstitial fluid, gastrointestinal ultrafiltrate, and feces were collected. Pharmacokinetic analysis demonstrated high penetration of florfenicol within the gastrointestinal tract for both the high and low dose group (300%, 97%, respectively). There was no significant difference noted between dosing groups in proportion or persistence of phenotypically resistant bacterial isolates; however, the percent of resistant isolates was high throughout the study period. The recommendation for the use of a lower tier antimicrobial, such as florfenicol, may allow for the persistence of co-resistance for antibiotics of high regulatory concern.
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Antimicrobial drugs administered systemically may cause the emergence and dissemination of antimicrobial resistance among enteric bacteria. To develop logical, research-based recommendations for food animal veterinarians, we must understand how to maximize antimicrobial drug efficacy while minimizing risk of antimicrobial resistance. Our objective is to evaluate the effect of two approved dosing regimens of enrofloxacin (a single high dose or three low doses) on Escherichia coli in cattle. We look specifically at bacteria above and below the epidemiological cutoff (ECOFF), above which the bacteria are likely to have an acquired or mutational resistance to enrofloxacin. We developed a differential equation model for the antimicrobial drug concentrations in plasma and colon, and bacteria populations in the feces. The model was fit to animal data of drug concentrations in the plasma and colon obtained using ultrafiltration probes. Fecal E. coli counts and minimum inhibitory concentrations were measured for the week after receiving the antimicrobial drug. We predict that the antimicrobial susceptibility of the bacteria above the ECOFF pre-treatment strongly affects the composition of the bacteria following treatment. Faster removal of the antimicrobial drugs from the colon throughout the study leads to improved clearance of bacteria above the ECOFF in the low dose regimen. If we assume a fitness cost is associated with bacteria above the ECOFF, the increased fitness costs leads to reduction of bacteria above the ECOFF in the low dose study. These results suggest the initial E. coli susceptibility is a strong indicator of how steers respond to antimicrobial drug treatment.
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Antibacterianos/farmacologia , Enrofloxacina/farmacologia , Escherichia coli/efeitos dos fármacos , Modelos Estatísticos , Relação Dose-Resposta a DrogaRESUMO
Antimicrobial drug concentrations in the gastrointestinal tract likely drive antimicrobial resistance in enteric bacteria. Our objective was to determine the concentration of ceftiofur and its metabolites in the gastrointestinal tract of steers treated with ceftiofur crystalline-free acid (CCFA) or ceftiofur hydrochloride (CHCL), determine the effect of these drugs on the minimum inhibitory concentration (MIC) of fecal Escherichia coli, and evaluate shifts in the microbiome. Steers were administered either a single dose (6.6 mg/kg) of CCFA or 2.2 mg/kg of CHCL every 24 hours for 3 days. Ceftiofur and its metabolites were measured in the plasma, interstitium, ileum and colon. The concentration and MIC of fecal E. coli and the fecal microbiota composition were assessed after treatment. The maximum concentration of ceftiofur was higher in all sampled locations of steers treated with CHCL. Measurable drug persisted longer in the intestine of CCFA-treated steers. There was a significant decrease in E. coli concentration (P = 0.002) within 24 hours that persisted for 2 weeks after CCFA treatment. In CHCL-treated steers, the mean MIC of ceftiofur in E. coli peaked at 48 hours (mean MIC = 20.45 ug/ml, 95% CI = 10.29-40.63 ug/ml), and in CCFA-treated steers, mean MIC peaked at 96 hours (mean MIC = 10.68 ug/ml, 95% CI = 5.47-20.85 ug/ml). Shifts in the microbiome of steers in both groups were due to reductions in Firmicutes and increases in Bacteroidetes. CCFA leads to prolonged, low intestinal drug concentrations, and is associated with decreased E. coli concentration, an increased MIC of ceftiofur in E. coli at specific time points, and shifts in the fecal microbiota. CHCL led to higher intestinal drug concentrations over a shorter duration. Effects on E. coli concentration and the microbiome were smaller in this group, but the increase in the MIC of ceftiofur in fecal E. coli was similar.
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Antibacterianos/química , Antibacterianos/farmacocinética , Doenças dos Bovinos/microbiologia , Cefalosporinas/química , Cefalosporinas/farmacocinética , Farmacorresistência Bacteriana , Escherichia coli/efeitos dos fármacos , Animais , Antibacterianos/administração & dosagem , Bovinos , Doenças dos Bovinos/tratamento farmacológico , Cefalosporinas/administração & dosagem , Escherichia coli/classificação , Escherichia coli/genética , Fezes/microbiologia , Testes de Sensibilidade Microbiana , Microbiota , RNA Ribossômico 16S/genéticaRESUMO
BACKGROUND & AIMS: The epithelial response is critical for intestinal defense against Cryptosporidium, but is poorly understood. To uncover the host strategy for defense against Cryptosporidium, we examined the transcriptional response of intestinal epithelial cells (IECs) to C parvum in experimentally infected piglets by microarray. Up-regulated genes were dominated by targets of interferon (IFN) and IFN-λ3 was up-regulated significantly in infected piglet mucosa. Although IFN-λ has been described as a mediator of epithelial defense against viral pathogens, there is limited knowledge of any role against nonviral pathogens. Accordingly, the aim of the study was to determine the significance of IFN-λ3 to epithelial defense and barrier function during C parvum infection. METHODS: The significance of C parvum-induced IFN-λ3 expression was determined using an immunoneutralization approach in neonatal C57BL/6 mice. The ability of the intestinal epithelium to up-regulate IFN-λ2/3 expression in response to C parvum infection and the influence of IFN-λ2/3 on epithelial defense against C parvum invasion, intracellular development, and loss of barrier function was examined using polarized monolayers of a nontransformed porcine-derived small intestinal epithelial cell line (IPEC-J2). Specifically, changes in barrier function were quantified by measurement of transepithelial electrical resistance and transepithelial flux studies. RESULTS: Immunoneutralization of IFN-λ2/3 in C parvum-infected neonatal mice resulted in a significantly increased parasite burden, fecal shedding, and villus blunting with crypt hyperplasia during peak infection. In vitro, C parvum was sufficient to induce autonomous IFN-λ3 and interferon-stimulated gene 15 expression by IECs. Priming of IECs with recombinant human IFN-λ3 promoted cellular defense against C parvum infection and abrogated C parvum-induced loss of barrier function by decreasing paracellular permeability to sodium. CONCLUSIONS: These studies identify IFN-λ3 as a key epithelial defense mechanism against C parvum infection.
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Criptosporidiose/imunologia , Cryptosporidium parvum/fisiologia , Citocinas/genética , Mucosa Intestinal/imunologia , Regulação para Cima , Animais , Linhagem Celular , Criptosporidiose/genética , Criptosporidiose/parasitologia , Citocinas/metabolismo , Modelos Animais de Doenças , Perfilação da Expressão Gênica , Camundongos , Camundongos Endogâmicos C57BL , Análise de Sequência com Séries de Oligonucleotídeos , SuínosRESUMO
Objective: The intestinal concentrations of antimicrobial drugs that select for resistance in fecal bacteria of cattle are poorly understood. Our objective was to associate active drug concentrations in the intestine of steers with changes in the resistance profile and composition of the fecal microbiome. Methods: Steers were administered either a single dose (12.5 mg/kg) or 3 multiple doses (5 mg/kg) of enrofloxacin subcutaneously every 24 h. Enrofloxacin and ciprofloxacin concentrations in intestinal fluid were measured over 96 h, and the abundance and MIC of E. coli in culture and the composition of the fecal microbiota by 16S rRNA gene sequencing were assessed over 192 h after initial treatment. Results: Active drug concentrations in the ileum and colon exceeded plasma and interstitial fluid concentrations, but were largely eliminated by 48 h after the last dose. The concentration of E. coli in the feces significantly decreased during peak drug concentrations, but returned to baseline by 96 h in both groups. The median MIC of E. coli isolates increased for 24 h in the single dose group, and for 48 h in the multiple dose group. The median MIC was higher in the multiple dose group when compared to the single dose group starting 12 h after the initial dose. The diversity of the fecal microbiota did not change in either treatment group, and taxa-specific changes were primarily seen in phyla commonly associated with the rumen. Conclusions: Both dosing regimens of enrofloxacin achieve high concentrations in the intestinal lumen, and the rapid elimination mitigates long-term impacts on fecal E. coli resistance and the microbiota.
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OBJECTIVE To identify factors associated with strongyle infection and parasite reduction strategies associated with low strongyle fecal egg counts (FECs) in goats on farms in North Carolina. DESIGN Cross-sectional study. ANIMALS 631 adult goats on 52 farms in North Carolina. PROCEDURES Participating farms were visited to collect fecal samples from goats and administer a survey regarding goat, environmental, and management factors. The McMaster technique was used to determine strongyle FEC for each sample. Univariate followed by multivariate modeling was performed to identify factors associated with FEC at the farm and individual goat level. RESULTS Multivariate analysis controlling for several other factors and multiple comparisons revealed that farms on which no anthelmintic drugs had ever been used had the lowest mean FECs, compared with farms on which specific strategies for parasite control were used; no other variables were significant. For individual goat FEC, significant variables included goat breed, breed type, owner-defined purpose, daily dietary protein intake, and fecal coccidia score. In particular, companion goats (vs meat or dairy goats) had the lowest FECs. Higher dietary protein intake and coccidia scores were associated with higher FECs. Among females, goats that had kidded in the last 6 weeks had the highest FECs. CONCLUSIONS AND CLINICAL RELEVANCE Various factors were identified that appeared to influence the likelihood of strongyle infection in goats. The finding that farms with no history of anthelmintic use had the lowest mean FECs suggested that a focus on preventative measures could reduce the need for anthelmintic drugs and, by extension, lessen the opportunity for the development of anthelmintic resistance.
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Doenças das Cabras/epidemiologia , Infecções por Strongylida/veterinária , Strongyloides/isolamento & purificação , Animais , Estudos Transversais , Feminino , Doenças das Cabras/parasitologia , Cabras , Masculino , North Carolina/epidemiologia , Contagem de Ovos de Parasitas/veterinária , Prevalência , Infecções por Strongylida/epidemiologiaRESUMO
The Bovine Educational Symposium (BES) is a unique opportunity for North Carolina State University (NCSU) veterinary students to visit dairy farms, feedlots, cow-calf operations, and processing facilities, and to meet local bovine veterinarians. We hypothesized that this active learning opportunity would increase knowledge, change perceptions of animal agriculture and food-animal medicine, and provide skills that persist beyond graduation. Pre- and post-trip surveys were administered to 124 first-, second-, and third-year veterinary students attending BES over 3 years. The surveys assessed students' perceived competence with regard to 12 key areas of bovine practice, attitudes toward segments of the cattle industry, attitudes to veterinarians' role in these segments, and interest in a career in bovine practice. Content knowledge was assessed using a multiple-choice test for comparison to self-assessments. A control group of 10 fourth-year students was administered the same tests before and after a 2-week food-animal clinical rotation. A convenience sample of nine BES alumni were interviewed to assess their opinion on the educational impact of BES. BES participants exhibited significant gains in perceived competence and actual knowledge in all 12 areas, and they also had improved perceptions of animal agriculture and increased interest in food-animal careers. Benefits noted by alumni ranged from improved knowledge of basic concepts of biosecurity and population medicine to greater appreciation for professional skills, including client communication. Immersing pre-clinical veterinary students in an active learning environment can have a significant impact on their knowledge and perception of food-animal medicine, irrespective of students' ultimate career goals.
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Escolha da Profissão , Currículo , Educação em Veterinária , Carne , Médicos Veterinários , Agricultura , Animais , Bovinos , Humanos , Autoavaliação (Psicologia) , Inquéritos e QuestionáriosRESUMO
Adequate absorption of bovine colostrum correlates with improved neonatal health. The apparent efficiency of absorption (AEA) of immunoglobulins can be measured using a mathematical equation based on serum and colostral IgG concentration levels, as well as calf body weight and the volume of colostrum being fed. Although commonly measured in research projects, little information is available on the normal AEA across a large group of healthy calves on multiple farms. The purpose of this study was to observe how contributing factors (volume of feeding, birth weight, and time of feeding) can alter AEA and establish a reference range for AEA in healthy calves. Study subjects were 100 Holstein heifer calves from 5 different dairies in North Carolina and Colorado. After a normal calving, the heifer received either 4 or 5.6 L of colostrum within 4 h of birth, an aliquot of the fed colostrum was saved, and a blood sample was collected between 24 and 36 h after birth. Birth weights were measured using the same weight tape on each farm. Radial immunodiffusion assay was performed to obtain IgG concentrations in the colostrum and serum samples. From this data, the AEA was calculated. The AEA ranged from 7.7 to 59.9% with mean of 28.1 ± 9.5% and median of 27.5%. The AEA of 69% of the calves fell between 21 and 40%. The AEA varied widely between calves, even when feeding was standardized. Results suggest that serum IgG concentration may potentially be increased by feeding increased volumes of colostrum or genetic selection, given the wide range of AEA values obtained.
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Animais Recém-Nascidos , Colostro/metabolismo , Imunoglobulina G/sangue , Animais , Peso ao Nascer , Bovinos , Feminino , ImunodifusãoRESUMO
Small ruminants have been implicated in outbreaks of Escherichia coli O157:H7 at livestock exhibitions throughout the United States. Additionally, goat meat or milk may serve as a reservoir for foodborne transmission of the organism. These associations highlight the public health importance of an effective strategy to reduce E. coli O157:H7 shedding in goats. We examined the efficacy of the SRP® vaccine in goats orally challenged with E. coli O157:H7. Mixed-breed goats (n = 14) were randomly allocated into vaccinated and unvaccinated treatments (n = 7 per treatment). Goats were housed with a vaccinated and unvaccinated animal in each pen. Feces were collected for 3 weeks, then at necropsy, gastrointestinal contents were collected to determine the concentration of E. coli O157:H7. Three isolates per positive sample were saved and evaluated by pulsed-field gel electrophoresis (PFGE) to assess strain persistence over time. The mean concentration of E. coli O157:H7 in the feces of goats was numerically reduced in the vaccinated treatment; however, it was not statistically significant. In addition, the total number of days goats were fecal positive for E. coli O157:H7 were not different between vaccinated and unvaccinated treatments. Pulsotypes of isolates revealed that goats initially shed two of the four challenge strains of E. coli O157:H7, after which there was a distinct shift to two different strains. Further work is needed to evaluate cost-effective intervention strategies that reliably reduce E. coli O157:H7 shedding in goats, particularly those that may reduce the risk of transmission at public events, including petting zoos and fairs.
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Infecções por Escherichia coli/prevenção & controle , Vacinas contra Escherichia coli/imunologia , Doenças das Cabras/prevenção & controle , Cabras/imunologia , Administração Oral , Animais , Proteínas da Membrana Bacteriana Externa/imunologia , Eletroforese em Gel de Campo Pulsado , Infecções por Escherichia coli/veterinária , Escherichia coli O157/imunologia , Proteínas de Escherichia coli/genética , Proteínas de Escherichia coli/imunologia , Fezes/microbiologia , Contaminação de Alimentos/prevenção & controle , Microbiologia de Alimentos , Doenças das Cabras/microbiologia , Cabras/microbiologia , Masculino , Leite/microbiologia , Porinas/imunologia , Receptores de Superfície Celular/imunologia , Carne Vermelha/microbiologia , Vacinação/veterináriaRESUMO
Haemonchus contortus parasitism is a major disease of sheep, with these parasites frequently demonstrating multi-drug class anthelmintic resistance. Copper oxide wire particles (COWP) have shown potential as adjuncts or alternatives to anthelmintics in resistant flocks. The purpose of this study was to compare the efficacy of two different COWP treatment regimens or placebo in the control of H. contortus in weaned lambs within a flock historically shown to have multi-drug resistant H. contortus using the DrenchRite® assay. Data from 43 lambs within 3 treatment groups in a double blind study were included in the experiment. Treatments were administered as a total of 2 boluses, each given on separate occasions (day 0 and day 42), so that each lamb received either 2 placebos, a single dose of 2g COWP followed by placebo, or two doses of 1g COWP. Strongyle-type fecal egg counts (FEC) were performed at initial treatment (day 0), on day 10, at second treatment (day 42), on day 52, and at study end (day 84). At the start of the trial, mean±standard deviation FEC were 1634.4±825.2, 2241.7±1496.8, and 2013.3±1194.2epg for the 2g, 1g×2, and control groups, respectively. At the end of the trial, FEC were 757.1±825.3, 483.4±557.2, and 1660.0±1345.3epg for the 2g, 1g×2, and control groups, respectively. Lambs given a 2g single dose of COWP or a 1g dose of COWP twice had reductions in strongyle-type FEC (p≤0.01) from trial start to trial end, whereas lambs given placebo did not. Average daily gains did not differ significantly among groups. Although copper is potentially toxic to sheep, no signs of toxicity were observed during this trial, which was consistent with similar studies at this treatment dose. The study indicated that administering COWP to lambs at weaning reduced FEC.
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Anti-Helmínticos/farmacologia , Cobre/uso terapêutico , Resistência a Medicamentos , Hemoncose/veterinária , Doenças dos Ovinos/terapia , Animais , Cobre/administração & dosagem , Relação Dose-Resposta a Droga , Feminino , Hemoncose/parasitologia , Hemoncose/terapia , Masculino , OvinosRESUMO
This study aimed to determine the effects of high-pressure processing on the immunoglobulin concentration, microbial load, viscosity, and transfer of passive immunity to calves when applied to bovine colostrum as an alternative to thermal pasteurization. A pilot study using Staphylococcus aureus was conducted to determine which pressure-time treatments are most appropriate for use with bovine colostrum, with the goals of maximizing bacterial inactivation while minimizing IgG content and viscosity changes. Following the pilot study, an inoculation study was conducted in which first-milking colostrum samples from Holstein-Friesian cows were inoculated with known concentrations of various bacteria or viruses and pressure processed at either 300 MPa for up to 60min or at 400MPa for up to 30min. The recovery of total native aerobic bacteria, Escherichia coli, Salmonella enterica ssp. enterica serovar Dublin, Mycobacterium avium ssp. paratuberculosis, bovine herpesvirus type 1, and feline calicivirus were determined after processing. Colostrum IgG content was measured before and after pressure processing. Shear stress and viscosity for each treatment was determined over shear rates encompassing those found during calf feeding and at normal bovine body temperature (37.8°C). Following a calf trial, serum IgG concentration was measured in 14 calves fed 4 L of colostrum pressure processed at 400MPa for 15min. In the pilot study, S. aureus was effectively reduced with pressure treatment at 300 and 400MPa (0, 5, 10, 15, 30, and 45min), with 2 treatments at 400MPa (30, 45min) determined to be inappropriate for use with bovine colostrum due to viscosity and IgG changes. High-pressure processing at 300MPa (30, 45, and 60min) and 400MPa (10, 15, and 20min) was shown to effectively reduce total native aerobic bacteria, E. coli, Salmonella Dublin, bovine herpesvirus type 1, and feline calicivirus populations in bovine colostrum, but no decrease occurred in Mycobacterium avium ssp. paratuberculosis. All inoculation study pressure treatments insignificantly decreased IgG content of colostrum. Treatment of colostrum at 400MPa for 15min during the calf trial decreased IgG content of colostrum. Treatment at 400MPa for 15min increased colostrum viscosity, with 2 of 14 samples requiring dilution with water for calf feeding. Calves fed pressure-processed colostrum had similar serum IgG but lower efficiency of absorption than calves fed heat-treated colostrum. The results of this study suggest that high-pressure processing of bovine colostrum maintains an acceptable IgG level while decreasing bacterial and viral counts. Changes in viscosity sometimes made calf feeding more difficult, but still feasible. Additional research to optimize this technology for on-farm use is necessary.
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Colostro/imunologia , Imunoglobulina G/sangue , Animais , Animais Recém-Nascidos , Bovinos , Escherichia coli/imunologia , Feminino , Projetos Piloto , Staphylococcus aureus/imunologia , ViscosidadeRESUMO
[This corrects the article DOI: 10.1371/journal.pone.0149100.].
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Bacterial pneumonia is the most common reason for parenteral antimicrobial administration to beef cattle in the United States. Yet there is little information describing the antimicrobial concentrations at the site of action. The objective of this study was to compare the active drug concentrations in the pulmonary epithelial lining fluid and interstitial fluid of four antimicrobials commonly used in cattle. After injection, plasma, interstitial fluid, and pulmonary epithelial lining fluid concentrations and protein binding were measured to determine the plasma pharmacokinetics of each drug. A cross-over design with six calves per drug was used. Following sample collection and drug analysis, pharmacokinetic calculations were performed. For enrofloxacin and metabolite ciprofloxacin, the interstitial fluid concentration was 52% and 78% of the plasma concentration, while pulmonary fluid concentrations was 24% and 40% of the plasma concentration, respectively. The pulmonary concentrations (enrofloxacin + ciprofloxacin combined) exceeded the MIC90 of 0.06 µg/mL at 48 hours after administration. For florfenicol, the interstitial fluid concentration was almost 98% of the plasma concentration, and the pulmonary concentrations were over 200% of the plasma concentrations, exceeding the breakpoint (≤ 2 µg/mL), and the MIC90 for Mannheimia haemolytica (1.0 µg/mL) for the duration of the study. For ceftiofur, penetration to the interstitial fluid was only 5% of the plasma concentration. Pulmonary epithelial lining fluid concentration represented 40% of the plasma concentration. Airway concentrations exceeded the MIC breakpoint for susceptible respiratory pathogens (≤ 2 µg/mL) for a short time at 48 hours after administration. The plasma and interstitial fluid concentrations of tulathromcyin were lower than the concentrations in pulmonary fluid throughout the study. The bronchial concentrations were higher than the plasma or interstitial concentrations, with over 900% penetration to the airways. Despite high diffusion into the bronchi, the tulathromycin concentrations achieved were lower than the MIC of susceptible bacteria at most time points.
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Antibacterianos/farmacocinética , Células Epiteliais/metabolismo , Líquido Extracelular/metabolismo , Mucosa Respiratória/metabolismo , Animais , Antibacterianos/sangue , Disponibilidade Biológica , Bovinos , Cefalosporinas/sangue , Cefalosporinas/farmacocinética , Estudos Cross-Over , Dissacarídeos/sangue , Dissacarídeos/farmacocinética , Enrofloxacina , Líquido Extracelular/química , Fluoroquinolonas/sangue , Fluoroquinolonas/farmacocinética , Compostos Heterocíclicos/sangue , Compostos Heterocíclicos/farmacocinética , Pulmão/metabolismo , Masculino , Mannheimia haemolytica/efeitos dos fármacos , Mannheimia haemolytica/crescimento & desenvolvimento , Testes de Sensibilidade Microbiana , Tianfenicol/análogos & derivados , Tianfenicol/sangue , Tianfenicol/farmacocinética , Drogas Veterinárias/sangue , Drogas Veterinárias/farmacocinéticaRESUMO
Diarrhea due to Salmonella infection is an important cause of neonatal calf diarrhea. The acquisition of passive immunity in the calf by vaccinating the dam has shown some success in previous studies; however, no data exists on the use of currently licensed vaccines in the United States. Therefore, the purpose of this study was to determine whether vaccinating cows in late gestation with a commercially available Salmonella Dublin vaccine would stimulate Salmonella-specific antibodies in the colostrum of cows at calving and whether these antibodies would be transferred to the calf. Thirty Holstein cows were vaccinated 3 wk before the end of lactation with a Salmonella enterica serovar Dublin vaccine, with a second dose given at dry-off. An additional 30 cows received only saline. Calves had a blood sample collected immediately after birth and were then fed fresh colostrum from their dam within 2 h of calving. A postcolostrum blood sample was collected 24 to 48 h later. Salmonella Dublin antibodies in colostrum as well as serum from the cows and calves were measured using an ELISA technique. Results of this study showed that vaccinated cattle had elevated Salmonella Dublin antibody titers at the time of calving (40.3 ± 9.1) as compared with control cows (-9.4 ± 1.1). Calves that received colostrum from vaccinated cattle also had a significant increase in Salmonella Dublin antibodies (88.5 ± 8.9) as compared with calves born to unvaccinated cows (-3.2 ± 1.2). This study demonstrated that the use of a commercially available Salmonella Dublin vaccine can stimulate antibodies that are passed on to the calf via colostral transfer. Further studies need to be done to determine whether these antibodies will offer protection against Salmonella challenge.
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Anticorpos Antibacterianos/imunologia , Doenças dos Bovinos/prevenção & controle , Colostro/imunologia , Complicações na Gravidez/imunologia , Salmonella enterica/imunologia , Vacinação/veterinária , Animais , Bovinos/imunologia , Doenças dos Bovinos/imunologia , Diarreia/veterinária , Ensaio de Imunoadsorção Enzimática/veterinária , Feminino , Lactação , Gravidez , Vacinas contra SalmonellaRESUMO
Collection of fluid from the lumen of the gastrointestinal tract is commonly necessary for research projects, but presents challenges including intestinal motility and potential for leakage of intestinal contents. In this study, ultrafiltration collection devices were surgically implanted in the ileum and spiral colon of 12 steers for repeated collection of intestinal fluid over 48 hours. There were no significant complications associated with surgery or during the post-operative period, nor were there any significant pathologic changes found at necropsy 3 or 4 days post-surgery. Over 48 hours, we obtained 88% of the desired 212 samples. Only two devices failed to routinely collect samples. Use of ultrafiltration probes is a novel, consistent and humane method to repeatedly sample the gastrointestinal contents.
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Líquidos Corporais , Colo/cirurgia , Íleo/cirurgia , Secreções Intestinais , Manejo de Espécimes/veterinária , Ultrafiltração/instrumentação , Animais , Bovinos , Manejo de Espécimes/métodosRESUMO
BACKGROUND & AIMS: Although we are beginning to understand where, when, and how intestinal epithelial cells are shed, physiologically, less is understood about alterations in cell fate during minimally invasive epithelial infections. We used a piglet model of Cryptosporidium parvum infection to determine how elimination of infected enterocytes is balanced with the need to maintain barrier function. METHODS: We studied the effects of enterocyte shedding by C parvum-infected ileum on barrier function ex vivo with Ussing chambers. The locations and activities of caspase-3, nuclear factor κB (NF-κB), and inhibitor of apoptosis proteins (IAP) were assayed by enzyme-linked immunosorbent assay, immunoblot, and tissue immunoreactivity analyses and using specific pharmacologic inhibitors. The location, specificity, and magnitude of enterocyte shedding were quantified using special stains and light microscopy. RESULTS: Infection with C parvum activated apoptotic signaling pathways in enterocytes that resulted in cleavage of caspase-3. Despite caspase-3 cleavage, enterocyte shedding was confined to villus tips, coincident with apoptosis, and observed more frequently in infected cells. Epithelial expression of X-linked inhibitor of apoptosis protein (XIAP), activation of NF-κB, and proteasome activity were required for control of cell shedding and barrier function. The proteasome blocked activity of caspase-3; this process was mediated by expression of XIAP, which bound to cleaved caspase-3. CONCLUSIONS: We have identified a pathway by which villus epithelial cells are maintained during C parvum infection. Loss of barrier function is reduced by active retention of infected enterocytes until they reach the villus tip. These findings might be used to promote clearance of minimally invasive enteropathogens, such as by increasing the rate of migration of epithelial cells from the crypt to the villus tip.