@article{mason_mullen_washburn_anderson_baynes_2018, title={Comparison of the pharmacokinetics of plant-based treatments in milk and plasma of USDA organic dairy cattle with and without mastitis}, volume={35}, ISSN={["1944-0057"]}, DOI={10.1080/19440049.2018.1502475}, abstractNote={ABSTRACT Organic dairy products are the second largest sector of the organic food market. Organic dairy products come from United States Department of Agriculture (USDA) certified organic dairy cattle that meet USDA organic standards. Organic dairy cattle in the US cannot be treated with antibiotics for mastitis, one of the costliest diseases of dairy cattle, and thus effective alternatives are needed. When any compound (medication or other non-food product) is used in a food producing animal, a withhold time for that compound that meets US Food and Drug Administration (FDA) standards for food safety must be applied to the animal and its products (like milk). However, there are no US FDA products approved for mastitis that maintain USDA certified organic dairy cattle’s organic status. Thus, we studied the pharmacokinetics of 3 compounds (garlic, thymol and carvacrol) used on organic both healthy and mastitic organic dairy cattle. We also used this information to estimate a milk withhold time using methods consistent with US FDA requirements. For thymol intra-mammary and carvacrol intra-mammary or topical administration, all compounds were partially absorbed into the body from the milk or skin. Thymol and carvacrol are measurable in plasma (at 0.0183 and 0.0202 µg/mL, respectively) after intramammary administration with similar elimination half lives of 1.7 h. Milk concentrations of thymol and carvacrol are much higher at 2.958 and 4.487 µg/mL in healthy cattle, respectively. Concentrations are not significantly different in cows with mastitis as compared to those in healthy cows. Despite these compounds being natural products, they should have a withhold time for milk of at least 24 h after administration. For garlic, levels remained below the limit of detection in milk and plasma and thus no withdrawal time appears to be needed for milk.}, number={9}, journal={FOOD ADDITIVES AND CONTAMINANTS PART A-CHEMISTRY ANALYSIS CONTROL EXPOSURE & RISK ASSESSMENT}, author={Mason, Sharon E. and Mullen, Keena A. E. and Washburn, Steven P. and Anderson, Kevin L. and Baynes, Ronald E.}, year={2018}, pages={1716–1727} }
 @article{mullen_lyman_washburn_baynes_anderson_2018, title={Effect of 3 phytoceutical products on elimination of bacteria in experimentally induced Streptococcus uberis clinical mastitis}, volume={101}, ISSN={["1525-3198"]}, DOI={10.3168/jds.2017-14279}, abstractNote={Our objective was to assess the ability of 3 herbal products to eliminate experimentally induced Streptococcus uberis mastitis. These herbal products, also known as phytoceuticals, are used in organically managed dairy cattle to maintain or promote udder health. The products tested were an intramammary product, a topical product, and a product applied to the vulvar area. These products are not approved by the US Food and Drug Administration for treatment of mastitis but they are sold to enhance milk quality or for maintenance or improvement of udder health. Each of the products contains at least one component shown to have antibacterial activity. In this study, we successfully challenge-inoculated 25 lactating dairy cows maintained under organic conditions with an isolate of S. uberis. All challenged cows were positive for S. uberis by milk culture after challenge. When cows met predefined criteria indicating the presence of clinical mastitis, treatment with 1 of the 3 products was initiated based upon a predetermined random allocation. Culture of aseptically collected quarter milk samples was performed before, during, and following challenge with S. uberis. Eight, 8, and 9 cows received the intravulvar, intramammary, and topical treatments, respectively. Milk from all cows that were treated with phytoceuticals were culture-positive for S. uberis at every time point following treatment through 168 h following the last phytoceutical treatment. Based upon the presence of clinical signs and for humane reasons, 2 intravulvar-treated cows, 1 topical-treated, and 4 intramammary-treated cows received intramammary antibiotic therapy. We concluded that the phytoceuticals tested, as dosed and used in this trial, did not produce bacterial cures in S. uberis-induced mastitis.}, number={11}, journal={JOURNAL OF DAIRY SCIENCE}, author={Mullen, K. A. E. and Lyman, R. L. and Washburn, S. P. and Baynes, R. E. and Anderson, K. L.}, year={2018}, month={Nov}, pages={10409–10413} }
 @article{mzyk_bublitz_sylvester_mullen_hobgood_baynes_foster_2018, title={Short communication: Use of an ultrafiltration device in gland cistern for continuous sampling of healthy and mastitic quarters of lactating cattle for pharmacokinetic modeling.}, volume={101}, url={https://doi.org/10.3168/jds.2018-14849}, DOI={10.3168/jds.2018-14849}, abstractNote={Pharmacokinetic studies of the drugs in the milk are often limited due to infrequent sampling associated with milking. Alternatively, frequent sample collection with repeated milking may increase drug elimination. The objective of this study was to determine the feasibility of continuously sampling the udder using ultrafiltration. An ultrafiltration probe was placed into the gland cisterns through mammary parenchyma of normal and mastitic quarters of 6 mature mid-lactation Jersey cows with naturally occurring subclinical mastitis. An ultrafiltration probe was secured to the caudal or lateral aspect of the udder depending on the quarter being sampled. The timed interval samples were collected at 0, 2, 4, 6, 8, 12, 18, 24, 28, 32, 36, 48, 60, 72, 84, and 96 h after drug administration. Plasma samples were collected at the same time points. Each cow received 2.2 mg/kg of flunixin intravenously before milking at time 0. All cows were routinely milked by machine every 12 h. Flunixin concentrations in plasma, whole milk, and milk ultrafiltrates were analyzed by use of ultra-high-performance liquid chromatography with mass spectrometric detection. We found no significant effects on the appearance of the milk or the ability to milk the cows after implantation of the ultrafiltration probes. The concentration of flunixin collected from the ultrafiltration probes in the mastitic quarters tended to be greater than that of the healthy quarters. We concluded that collection of ultrafiltration samples from the mammary gland of cows provides a viable means to continuously assess drug concentrations in the milk while continuing to milk the cow normally. This study demonstrates the utility of continuous sampling of milk via ultrafiltration for future pharmacokinetic studies in cattle.}, number={11}, journal={Journal of dairy science}, author={Mzyk, D. A. and Bublitz, C. M. and Sylvester, H. and Mullen, K. A. E. and Hobgood, G. D. and Baynes, R. E. and Foster, Derek}, year={2018}, month={Sep}, pages={10414–10420} }
 @article{mason_mullen_anderson_washburn_yeatts_baynes_2017, title={Pharmacokinetic analysis of thymol, carvacrol and diallyl disulfide after intramammary and topical applications in healthy organic dairy cattle}, volume={34}, ISSN={1944-0049 1944-0057}, url={http://dx.doi.org/10.1080/19440049.2017.1285056}, DOI={10.1080/19440049.2017.1285056}, abstractNote={ABSTRACT Mastitis is among the most costly concerns for dairy producers whether cattle are managed conventionally or organically. Unfortunately, there are no USFDA-approved mastitis treatments that allow dairy cows in the United States to maintain organic dairy status. We investigated the plasma pharmacokinetics of three organic mastitis products currently used by organic producers and organic dairy veterinarians. Those products include intramammary, topical and intravaginal preparations, each dosed at two levels. Additionally, tissue data were collected for kidney, liver and fat in order to estimate a withholding time for each of the products. The lower limit of quantification (LOQ) and lower limit of detection (LOD) were 0.001 and 0.0005 µg ml–1, respectively, in plasma and all tissues except fat for both thymol and carvacrol. Fat had an LOQ of 0.01 µg ml–1 and an LOD of 0.005 µg ml–1 for thymol and carvacrol. Diallyl disulfide had an LOQ of 0.005 µg ml–1 and LOD of 0.001 µg ml–1 in all tissues. For diallyl disulfide (garlic), no levels above 0.001 µg ml–1 were measurable in plasma or tissues. For topical and intramammary products, levels were measurable in the plasma, liver, kidney and fat up to 72 h after the last dose. The plasma half-lives were short for thymol (approximately 1.6 h) and carvacrol (approximately 1.5 h), whereas the estimated half-lives for these substances in tissues ranged from 13.9 to 31.5 h for thymol and from 16.9 to 25 h for carvacrol. The predicted amount of time that the molecules would be found in the body based on the slowest depletion time of liver tissue was 13 days for thymol and 10 days for carvacrol. The apparent half-life of topically applied carvacrol was approximately 4.5 h in plasma, with an estimated withhold time of 10 days. These times were calculated using the USFDA’s tolerance limit method for meat withdrawal times.}, number={5}, journal={Food Additives & Contaminants: Part A}, publisher={Informa UK Limited}, author={Mason, Sharon E. and Mullen, Keena A. E. and Anderson, Kevin L. and Washburn, Steven P. and Yeatts, James L. and Baynes, Ronald E.}, year={2017}, month={Feb}, pages={1–10} }
 @article{armorini_yeatts_mullen_mason_mehmeti_anderson_washburn_baynes_2016, title={Development of a HS-SPME-GC-MS/MS Method for the Quantitation of Thymol and Carvacrol in Bovine Matrices and To Determine Residue Depletion in Milk and. Tissues}, volume={64}, ISSN={["1520-5118"]}, DOI={10.1021/acs.jafc.6b02899}, abstractNote={Thymol and carvacrol may be present in several phytoceutical products but there are no well-defined methods to measure these compounds in meat and milk from treated animals. U.S. regulatory authorities deem their presence as an adulteration of food. A rapid and sensitive HS-SPME-GC-MS/MS method was developed for the detection of thymol and carvacrol in bovine milk, plasma, liver, kidney, and fat. Inter- and intraday precision values were all less than 15.7 and 20.2% for thymol and carvacrol, respectively. The accuracy was in ranges of 69.9-111.8% for thymol and 74.0-119.2% for carvacrol. With the exception of fat tissue, stability studies showed that both compounds are stable over a 2 month period. A pilot pharmacokinetic study was conducted to evaluate the developed analytical method and to provide initial estimates of thymol and carvacrol depletion in plasma, milk, and several tissues. Treatment of lactating dairy cattle with phytoceutical products containing these substances resulted in low but measurable residue levels at 96 h for liver and 36 h for milk with very short apparent plasma and milk half-lives (<3.0 h).}, number={41}, journal={JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY}, author={Armorini, Sara and Yeatts, James E. and Mullen, Keena A. E. and Mason, Sharon E. and Mehmeti, Elmira and Anderson, Kevin L. and Washburn, Steve P. and Baynes, Ronald E.}, year={2016}, month={Oct}, pages={7856–7865} }
 @article{mullen_anderson_washburn_2014, title={Effect of 2 herbal intramammary products on milk quantity and quality compared with conventional and no dry cow therapy}, volume={97}, ISSN={["1525-3198"]}, DOI={10.3168/jds.2013-7460}, abstractNote={Dry cow therapy, administered at the end of lactation, is aimed at eliminating current and preventing future intramammary (IMM) bacterial infections and typically involves intramammary administration of antibiotics. Certified organic dairies in the United States are restricted from using antibiotics and must consider an alternative therapy or no dry cow therapy. The current study compared 2 herbal products to conventional dry cow therapy and no treatment for a total of 5 treatments over 2 trials. Trial 1 was conducted over 3 yr on 1 research farm and trial 2 included 4 commercial farms plus the research herd over 2 yr. Treatments included (1) a conventional IMM antibiotic and internal teat sealant (penicillin-dihydrostreptomycin and bismuth subnitrate; CON); (2) an herbal IMM product purported to act as a teat sealant (Cinnatube, New AgriTech Enterprises, Locke, NY; CIN); (3) an herbal IMM product (Phyto-Mast, Bovinity Health LLC, Narvon, PA; P-M); (4) Phyto-Mast and Cinnatube (PC); or (5) no dry cow therapy (NT). Each treatment group was balanced by breed, lactation number, due date, herd, and year. However, the CON treatment was used only in the research herd because of the intent to avoid antibiotic usage on the other 4 farms. Comparisons among treatments included the difference between pre- and posttreatment 305-d mature equivalent milk production (trial 1), somatic cell score change from dry-off to freshening at the cow and quarter levels (trials 1 and 2), and milk microbiology change over the dry period (trial 2). We detected no significant differences among treatments for milk yield differences between the lactation following treatment and the lactation preceding treatment. Changes in somatic cell score from one lactation to the next also did not differ significantly among treatments in either trial. Cure rates were not significantly different among treatments; only 19.6% of all quarters were infected at dry off. The proportion of quarters with new infections at 3 to 5d postcalving did not significantly differ among treatments, except between CIN and NT. Percentages (least squares means ± standard error) of quarters with new infections were 24 ± 21% for CON, 15 ± 7% for CIN, 30 ± 10% for P-M, 32 ± 11% for PC, and 35 ± 11% for NT. The efficacy of the herbal products was similar to that of conventional therapy, and the herbal products had no apparent adverse effects.}, number={6}, journal={JOURNAL OF DAIRY SCIENCE}, author={Mullen, K. A. E. and Anderson, K. L. and Washburn, S. P.}, year={2014}, month={Jun}, pages={3509–3522} }
 @article{washburn_mullen_2014, title={Invited review: Genetic considerations for various pasture-based dairy systems}, volume={97}, ISSN={["1525-3198"]}, DOI={10.3168/jds.2014-7925}, abstractNote={Pasture-based dairy systems use grazing to supply significant percentages of the dry matter intake of cows and heifers. Such systems vary from those for which pasture is used only as a supplemental feed for cows primarily fed a total mixed ration to those for which pasture is the primary source of dry matter for the herd. Cows that are optimal in a pasture system share many general characteristics with cows that are appropriate for a nonpasture system, including feed efficiency, maintenance of body condition, reproductive fitness, udder health, longevity, and the ability to adapt to various management systems. However, in such divergent feeding systems, the relative importance of various traits can differ. In pasture systems where cow nutrient demand intentionally coincides with seasonal forage availability, the focus of selection has emphasized fertility and other fitness traits, as well as yields of milk or milk components. Breeds or strains with higher yields of protein and fat typically have advantages in grazing systems that supply milk to solids-based or cheese markets. Holstein cows with high percentages of North American ancestry can work well in grazing systems that include supplemental concentrates or partial mixed rations, particularly if calving intervals are less restrictive. Crossbred cows can be selected for use in specific grazing systems as well as for specific milk markets, with the added advantage of heterosis. Breeds and crosses with high fertility are important for seasonal breeding and calving. The ability of cattle to both milk and maintain sufficient body condition for reproduction is important for any dairy production system but is critical in a seasonal system. Dairy farms that depend on pasture for most of dry matter for cows typically have lower production per cow than nongrazing dairies but have the potential to be economically competitive because of lower operating and overhead costs. Although the principles of selection are similar across a variety of pasture-based and nonpasture systems, we document from studies and observations covered herein that optimal breeds, breed strains, and selection strategies can differ based on varying management constraints and objectives.}, number={10}, journal={JOURNAL OF DAIRY SCIENCE}, author={Washburn, S. P. and Mullen, K. A. E.}, year={2014}, month={Oct}, pages={5923–5938} }
 @article{mullen_lee_lyman_mason_washburn_anderson_2014, title={Short communication: An in vitro assessment of the antibacterial activity of plant-derived oils}, volume={97}, ISSN={["1525-3198"]}, DOI={10.3168/jds.2013-7806}, abstractNote={Nonantibiotic treatments for mastitis are needed in organic dairy herds. Plant-derived oils may be useful but efficacy and potential mechanisms of action of such oils in mastitis therapy have not been well documented. The objective of the current study was to evaluate the antibacterial activity of the plant-derived oil components of Phyto-Mast (Bovinity Health LLC, Narvon, PA), an herbal intramammary product, against 3 mastitis-causing pathogens: Staphylococcus aureus, Staphylococcus chromogenes, and Streptococcus uberis. Plant-derived oils evaluated were Thymus vulgaris (thyme), Gaultheria procumbens (wintergreen), Glycyrrhiza uralensis (Chinese licorice), Angelica sinensis, and Angelica dahurica. Broth dilution testing according to standard protocol was performed using ultrapasteurized whole milk instead of broth. Controls included milk only (negative control), milk + bacteria (positive control), and milk + bacteria + penicillin-streptomycin (antibiotic control, at 1 and 5% concentrations). Essential oil of thyme was tested by itself and not in combination with other oils because of its known antibacterial activity. The other plant-derived oils were tested alone and in combination for a total of 15 treatments, each replicated 3 times and tested at 0.5, 1, 2, and 4% to simulate concentrations potentially achievable in the milk within the pre-dry-off udder quarter. Thyme oil at concentrations ≥2% completely inhibited bacterial growth in all replications. Other plant-derived oils tested alone or in various combinations were not consistently antibacterial and did not show typical dose-response effects. Only thyme essential oil had consistent antibacterial activity against the 3 mastitis-causing organisms tested in vitro. Further evaluation of physiological effects of thyme oil in various preparations on mammary tissue is recommended to determine potential suitability for mastitis therapy.}, number={9}, journal={JOURNAL OF DAIRY SCIENCE}, author={Mullen, K. A. E. and Lee, A. R. and Lyman, R. L. and Mason, S. E. and Washburn, S. P. and Anderson, K. L.}, year={2014}, month={Sep}, pages={5587–5591} }
 @article{mullen_sparks_lyman_washburn_anderson_2013, title={Comparisons of milk quality on North Carolina organic and conventional dairies}, volume={96}, ISSN={0022-0302}, url={http://dx.doi.org/10.3168/jds.2012-6519}, DOI={10.3168/jds.2012-6519}, abstractNote={The organic dairy industry is growing rapidly across the United States and has recently expanded into the southeastern states. To date, no published comparisons of milk quality exist between organic and conventional dairies in the Southeastern United States. Maintaining high milk quality is challenging in this region due to the longer periods of high heat and humidity. The objective of this observational study was to compare milk quality on organic and conventional dairies in North Carolina during the warm summer months of the year. Data were compared from 7 organically and 7 conventionally managed herds in North Carolina. To assess milk quality, milk samples were aseptically collected from each functional quarter of each cow in the milking herds at the time of sampling and linear somatic cell scores (SCS) were obtained for individual cows. A total of 4,793 quarter milk samples (2,526 conventional and 2,267 organic) were collected from 1,247 cows (652 conventional and 595 organic). Milk samples were cultured and bacterial growth was identified using protocols consistent with those of the National Mastitis Council (Verona, WI). Subclinical mastitis was defined as the presence of SCS ≥ 4 and also a microbiological infection in at least 1 quarter. The proportion of cows with subclinical mastitis did not differ between conventional (20.8%) and organic (23.3%) herds. No significant difference was observed between herd management types in the proportion of cows without microbiological growth in milk samples. Also, no significant differences were observed between organic and conventional herds for cow-level prevalence of Staphylococcus aureus, coagulase-negative Staphylococcus spp., Streptococcus spp., or Corynebacterium spp. Two of the organic herds had a notably higher prevalence of Corynebacterium spp. and higher SCS. Coliforms were found in 5 of 7 conventional herds and in only 1 of 7 organic herds. Mean SCS did not differ between conventional (3.3±0.2) and organic (3.5±0.2) herds. Despite differences in herd management, milk quality was remarkably similar between the organic and conventional dairies compared for this study.}, number={10}, journal={Journal of Dairy Science}, publisher={American Dairy Science Association}, author={Mullen, K.A.E. and Sparks, L.G. and Lyman, R.L. and Washburn, S.P. and Anderson, K.L.}, year={2013}, month={Oct}, pages={6753–6762} }