Short communication: Use of an ultrafiltration device in gland cistern for continuous sampling of healthy and mastitic quarters of lactating cattle for pharmacokinetic modeling.

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.

Short communication: Effect of 3 phytoceutical products on elimination of bacteria in experimentally induced Streptococcus uberis clinical mastitis.

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.

The effectiveness of eHealth interventions on physical activity and measures of obesity among working-age women: a systematic review and meta-analysis.

Physical inactivity and obesity are modifiable risk factors for cardiovascular disease, particularly in women. eHealth interventions may increase physical activity and improve obesity-related outcomes among women. The objective of this study was to review the evidence of the effectiveness of eHealth interventions to increase moderate-to-vigorous physical activity among working-age women. The secondary objective was to examine their effectiveness on improving obesity-related outcomes. A comprehensive search strategy was developed for eight electronic databases; through July 2016. All studies consisting of >80% women of working-age (18-65 years) in high income countries were included. Multiple unblinded reviewers determined study eligibility and extracted data. Risk of bias was evaluated using the Cochrane Risk of Bias Tool and data quality using the Grading of Recommendations Assessment, Development and Evaluation approach. Data were pooled using a random-effects model. Sixty studies were included in the review of which 20 were in the meta-analysis. The meta-analysis demonstrated eHealth interventions improved moderate-to-vigorous physical activity (standard mean difference = 1.13, 95% confidence interval: 0.58, 1.68, P < 0.0001); an increase of ~25 min week-1 . No changes were observed in obesity-related outcomes; waist circumference (P = 0.06), body mass (P = 0.05) and body mass index (P = 0.35). eHealth interventions are effective at increasing min week-1 of moderate-to-vigorous physical activity among working-age women from high income countries.

Why are adult women physically active? A systematic review of prospective cohort studies to identify intrapersonal, social environmental and physical environmental determinants.

OBJECTIVE: This study aims to systematically review available evidence from prospective cohort studies to identify intrapersonal, social environmental and physical environmental determinants of moderate-to-vigorous intensity physical activity (MVPA) among working-age women. METHODS: Six databases were searched to identify all prospective cohort studies that reported on intrapersonal (e.g. self-efficacy and socioeconomic status [SES]), social (e.g. crime, area SES and social support) and/or physical (e.g. weather, work and recreation) environmental determinants of MVPA in working-age (mean 18-65 years) women. A qualitative synthesis including harvest plots was completed. PROSPERO: CRD42014009750 RESULTS: Searching identified 17,387 potential articles; 97 were used in the analysis. The majority (n = 87 studies) reported on ≥1 intrapersonal determinant. Very few (n = 34) examined factors in the social or physical environments, and none looked at social policy. Positive and consistent influencers included higher self-efficacy (n = 18/23), self-rated health (n = 8/13) and intentions (n = 10/11) and perceived behavioural control (n = 5/7) to be physically active. Having children in the household was negatively related to MVPA (n = 9/15). CONCLUSIONS: Physical activity intervention studies should consider a woman's level of self-efficacy and perceived behavioural control to be physically active. Additional studies are needed on the impact of children in the household, having a spouse/partner and using group goal setting. More evidence is needed to evaluate the impact of environmental factors.

Invited review: Genetic considerations for various pasture-based dairy systems.

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.

Short communication: an in vitro assessment of the antibacterial activity of plant-derived oils.

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.

Effect of 2 herbal intramammary products on milk quantity and quality compared with conventional and no dry cow therapy.

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.

Comparisons of milk quality on North Carolina organic and conventional dairies.

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.

Abnormal desmopressin-induced forearm vasodilatation in patients with heart failure: dependence on nitric oxide synthase activity.

BACKGROUND: Peripheral vasodilatation in response to muscarinic agonists has been shown to be subnormal during heart failure. However, a more recent study suggested that the abnormal muscarinic-induced vasodilatation was not due to abnormal nitric oxide synthase activity. This study was designed to show that nitric oxide synthase contributes to desmopressin-induced forearm vasodilatation and to determine whether vasodilatation mediated by nitric oxide synthase is abnormal during heart failure. METHODS: Desmopressin (10, 50, and 100 ng/min) was infused into the brachial artery of 10 healthy subjects and eight patients with heart failure, and forearm blood flow was measured by venous occlusion plethsymography. Desmopressin responses were then recorded during inhibition of nitric oxide synthase with L-monomethylarginine or after aspirin. RESULTS: In healthy subjects, desmopressin caused a significant (p < 0.001) dose-dependent increase in forearm blood flow of 0.9 +/- 0.6, 4.0 +/- 2.6, and 7.9 +/- 2.6 ml/min/dl, respectively. Desmopressin responses in heart failure of 0.8 +/- 0.6, 1.7 +/- 1.4, and 3.1 +/- 1.0 ml/min/dl were significantly less (p < 0.001) than normal. L-Monomethylarginine reduced desmopressin responses in normal subjects (p < 0.01), and this inhibitory effect was significantly (p < 0.01) greater than in patients with heart failure. Aspirin did not affect desmopressin-induced vasodilatation. CONCLUSION: Nitric oxide synthase contributes to desmopressin-induced forearm vasodilatation. In response to desmopressin, patients with heart failure have subnormal vasodilatation mediated through nitric oxide synthase.

Randomized, double-blind, placebo-controlled study of supplemental oral L-arginine in patients with heart failure.

BACKGROUND: Patients with heart failure have reduced peripheral blood flow at rest, during exercise, and in response to endothelium-dependent vasodilators. Nitric oxide formed from L-arginine metabolism in endothelial cells contributes to regulation of blood flow under these conditions. A randomized, double-blind crossover study design was used to determine whether supplemental oral L-arginine can augment peripheral blood flow and improve functional status in patients with moderate to severe heart failure. METHODS AND RESULTS: Fifteen subjects were given 6 weeks of oral L-arginine hydrochloride (5.6 to 12.6 g/d) and 6 weeks of matched placebo capsules in random sequence. Compared with placebo, supplemental oral L-arginine significantly increased forearm blood flow during forearm exercise, on average from 5.1 +/- 2.8 to 6.6 +/- 3.4 mL. min-1. dL-1 (P < .05). Furthermore, functional status was significantly better on L-arginine compared with placebo, as indicated by increased distances during a 6-minute walk test (390 +/- 91 versus 422 +/- 86 m, P < .05) and lower scores on the Living With Heart Failure questionnaire (55 +/- 28 versus 42 +/- 26, P < .05). Oral L-arginine also improved arterial compliance from 1.99 +/- 0.38 to 2.36 +/- 0.30 mL/mm Hg (P < .001) and reduced circulating levels of endothelin from 1.9 +/- 1.1 to 1.5 +/- 1.1 pmol/L (P < .05). CONCLUSIONS: Supplemental oral L-arginine had beneficial effects in patients with heart failure. Further studies are needed to confirm the therapeutic potential of supplemental oral L-arginine and to identify mechanisms of action in patients with heart failure.