bluuebunny/crossref_metadata_2025_split huggingface dataset:
Ultra-Performance Liquid Chromatography Mass Spectrometry and Sensitive Bioassay Methods for Quantification of Posaconazole Plasma Concentrations after Oral Dosing
Authors: Rochat Bertrand , Pascual Andres , Pesse Benoît , Lamoth Frédéric , Sanglard Dominique , Decosterd Laurent A. , Bille Jacques , Marchetti Oscar 
Published: October 2010

ABSTRACT

Posaconazole (POS) is a new antifungal agent for prevention and therapy of mycoses in immunocompromised patients. Variable POS pharmacokinetics after oral dosing may influence efficacy: a trough threshold of 0.5 μg/ml has been recently proposed. Measurement of POS plasma concentrations by complex chromatographic techniques may thus contribute to optimize prevention and management of life-threatening infections. No microbiological analytical method is available. The objective of this study was to develop and validate a new simplified ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) method and a sensitive bioassay for quantification of POS over the clinical plasma concentration range. The UPLC-MS/MS equipment consisted of a triple quadrupole mass spectrometer, an electrospray ionization (ESI) source, and a C
18
analytical column. The
Candida albicans
POS-hypersusceptible mutant (MIC of 0.002 μg/ml) Δ
cdr1
Δ
cdr2
Δ
flu
Δ
mdr1
Δ
can
constructed by targeted deletion of multidrug efflux transporters and calcineurin genes was used for the bioassay. POS was extracted from plasma by protein precipitation with acetonitrile-methanol (75%/25%, vol/vol). Reproducible standard curves were obtained over the range 0.014 to 12 (UPLC-MS/MS) and 0.028 to 12 μg/ml (bioassay). Intra- and interrun accuracy levels were 106% ± 2% and 103% ± 4% for UPLC-MS/MS and 102% ± 8% and 104% ± 1% for bioassay, respectively. The intra- and interrun coefficients of variation were 7% ± 4% and 7% ± 3% for UPLC-MS/MS and 5% ± 3% and 4% ± 2% for bioassay, respectively. An excellent correlation between POS plasma concentrations measured by UPLC-MS/MS and bioassay was found (concordance, 0.96). In 26 hemato-oncological patients receiving oral POS, 27/69 (39%) trough plasma concentrations were lower than 0.5 μg/ml. The UPLC-MS/MS method and sensitive bioassay offer alternative tools for accurate and precise quantification of the plasma concentrations in patients receiving oral posaconazole.
Novel Daptomycin Combinations against Daptomycin-Nonsusceptible Methicillin-Resistant
Staphylococcus aureus
in an
In Vitro
Model of Simulated Endocardial Vegetations
Authors: Steed Molly E. , Vidaillac Celine , Rybak Michael J. 
Published: October 2010

ABSTRACT

Reduced susceptibility to daptomycin has been reported in patients with infections due to methicillin-resistant
Staphylococcus aureus
(MRSA). Although infections with daptomycin-nonsusceptible (DNS) MRSA are infrequent, optimal therapy of these strains has not been determined. We investigated the killing effects of novel antibiotic combinations with daptomycin (DAP) against two clinical DNS MRSA isolates (SA-684 and R6003) in a 72-h
in vitro
pharmacokinetic/pharmacodynamic (PK/PD) model with simulated endocardial vegetations (SEV). Simulated regimens included DAP at 6 mg/kg every 24 h (q24h) alone or in combination with trimethoprim-sulfamethoxazole (TMP/SMX) at 160/800 mg q12h, linezolid (LIN) at 600 mg q12h, cefepime (CEF) at 2 g q12h, and nafcillin (NAF) at 4 g q4h. Bactericidal activity was defined as a ≥3-log
10
CFU/g kill. Differences in CFU/g were evaluated between 4 and 72 h by analysis of variance with the Bonferroni post hoc test. DAP MICs were 4 and 2 mg/liter for SA-684 and R6003, respectively. In the PK/PD model, DAP alone was slowly bactericidal, achieving a 3-log
10
kill at 24 and 50 h for SA-684 and R6003, respectively. Against SA-684, DAP plus TMP/SMX, CEF, LIN, or NAF was bactericidal at 4, 4, 8, and 8 h, respectively, and maintained this activity for the 72-h study duration. DAP plus TMP/SMX or CEF exhibited superior killing than DAP alone against SA-684 between 4 and 72 h, and overall this was significant (
P
< 0.05). Against R6003, DAP plus TMP/SMX was bactericidal (8 h) and superior to DAP alone between 8 and 72 h (
P
< 0.001). The unique combination of DAP plus TMP/SMX was the most effective and rapidly bactericidal regimen against the two isolates tested and may provide a clinical option to treat DNS
S. aureus
infections.
Testing Nucleoside Analogues as Inhibitors of
Bacillus anthracis
Spore Germination
In Vitro
and in Macrophage Cell Culture
Authors: Alvarez Zadkiel , Lee Kyungae , Abel-Santos Ernesto 
Published: October 2010

ABSTRACT

Bacillus anthracis
, the etiological agent of anthrax, has a dormant stage in its life cycle known as the endospore. When conditions become favorable, spores germinate and transform into vegetative bacteria. In inhalational anthrax, the most fatal manifestation of the disease, spores enter the organism through the respiratory tract and germinate in phagosomes of alveolar macrophages. Germinated cells can then produce toxins and establish infection. Thus, germination is a crucial step for the initiation of pathogenesis.
B. anthracis
spore germination is activated by a wide variety of amino acids and purine nucleosides. Inosine and
l
-alanine are the two most potent nutrient germinants
in vitro
. Recent studies have shown that germination can be hindered by isomers or structural analogues of germinants. 6-Thioguanosine (6-TG), a guanosine analogue, is able to inhibit germination and prevent
B. anthracis
toxin-mediated necrosis in murine macrophages. In this study, we screened 46 different nucleoside analogues as activators or inhibitors of
B. anthracis
spore germination
in vitro
. These compounds were also tested for their ability to protect the macrophage cell line J774a.1 from
B. anthracis
cytotoxicity. Structure-activity relationship analysis of activators and inhibitors clarified the binding mechanisms of nucleosides to
B. anthracis
spores. In contrast, no structure-activity relationships were apparent for compounds that protected macrophages from
B. anthracis
-mediated killing. However, multiple inhibitors additively protected macrophages from
B. anthracis
.
Efficacy of a Doxycycline Treatment Regimen Initiated during Three Different Phases of Experimental Ehrlichiosis
Authors: McClure Jennifer C. , Crothers Michelle L. , Schaefer John J. , Stanley Patrick D. , Needham Glen R. , Ewing S. A. , Stich Roger W. 
Published: October 2010

ABSTRACTDoxycycline is the treatment of choice for canine monocytic ehrlichiosis (CME), a well-characterized disease and valuable model for tick-borne zoonoses. Conflicting reports of clearance ofEhrlichia canisafter treatment with doxycycline suggested that the disease phase during which treatment is initiated influences outcomes of these treatments. The purpose of this study was to evaluate the efficacy of a 28-day doxycycline regimen for clearance of experimentalE. canisinfections from dogs treated during three phases of the disease. Ten dogs were inoculated with blood fromE. caniscarriers and treated with doxycycline during acute, subclinical, or chronic phases of CME. Daily rectal temperatures and semiweekly blood samples were monitored from each dog, andRhipicephalus sanguineusticks were acquisition fed on each dog for xenodiagnosis. Blood collected from dogs treated during acute or subclinical CME became PCR negative forE. canisas clinical parameters improved, but blood samples collected from dogs treated during chronic CME remained intermittently PCR positive.R. sanguineusticks fed on dogs after doxycycline treatments became PCR positive forE. canis, regardless of when treatment was initiated. However, fewer ticks became PCR positive after feeding on two persistently infected dogs treated with doxycycline followed by rifampin, suggesting that antibiotic therapy can reduce tick acquisition ofE. canis.
CD46 Engagement on Human CD4+T Cells Produces T Regulatory Type 1-Like Regulation of Antimycobacterial T Cell Responses
Authors: Truscott Steven M. , Abate Getahun , Price Jeffrey D. , Kemper Claudia , Atkinson John P. , Hoft Daniel F. 
Published: October 2010

ABSTRACTUnderstanding the regulation of human immune responses is critical for vaccine development and treating infectious diseases. We have previously shown that simultaneous engagement of the T cell receptor (TCR) and complement regulator CD46 on human CD4+T cells in the presence of interleukin-2 (IL-2) induces potent secretion of the immunomodulatory cytokine IL-10. These T cells mediate IL-10-dependent suppression of bystander CD4+T cells activatedin vitrowith anti-CD3 and anti-CD28 costimulation, reflecting a T regulatory type 1 (Tr1)-like phenotype. However, CD46-mediated negative regulation of pathogen-specific T cells has not been described. Therefore, we studied the ability of CD46-activated human CD4+T cells to suppress T cell responses toMycobacterium bovisBCG, the live vaccine that provides infants protection against the major human pathogenMycobacterium tuberculosis. Our results demonstrate that soluble factors secreted by CD46-activated human CD4+T cells suppress mycobacterium-specific CD4+, CD8+, and γ9δ2TCR+T cells. Dendritic cell functions were not downregulated in our experiments, indicating that CD46-triggered factors directly suppress pathogen-specific T cells. Interestingly, IL-10 appeared to play a less pronounced role in our system, especially in the suppression of γ9δ2TCR+T cells, suggesting the presence of additional undiscovered soluble immunoregulatory factors. Blocking endogenous CD46 signaling 3 days after mycobacterial infection enhanced BCG-specific T cell responses in a subset of volunteers. Taken together, these results indicate that CD46-dependent negative regulatory mechanisms can impair T cell responses vital for immune defense against mycobacteria. Therefore, modulating CD46-induced immune regulation could be integral to the development of improved tuberculosis therapeutics or vaccines.
Procedures to eliminate H3N2 swine influenza virus from a pig herd
Authors: Torremorell M. , Juarez A. , Chavez E. , Yescas J. , Doporto J. M. , Gramer M. 
Published: October 2010

A three‐site pig herd infected with a H3N2 swine influenza virus (SIV) underwent a herd SIV elimination programme using herd closure and partial depopulation. The herd consisted of sow, nursery and finishing units, 1 to 2 km apart. Disease was noted in the sow unit and then the nursery unit. The herd temporarily stopped introduction of replacement animals, and replacement gilt introductions in the breeding herd was changed from monthly to quarterly. Gilts from a serologically negative source were also introduced and monitored. Virus elimination from growing pigs was attempted by totally depopulating the nursery and finishing sites once there was evidence that shedding in site 1 had stopped. Sentinel gilts remained serologically negative by haemagglutination inhibition (HI) test (0 of 69 animals negative) for at least 20 months after the initial disease. After restoring the pig flow in site 2, pigs did not experience flu‐like clinical signs and HI serology results remained negative (0 of 30 animals tested) for the six months following repopulation of sites 2 and 3. In addition, nursery mortality was improved by 2·2 per cent, the growth rate was improved by 0·123 kg/day and feed efficiency was improved 0·26 points. Based on these results, SIV elimination was considered successful.
Recent bruising in cattle at abattoirs
Authors: McNally P. W. , Warriss P. D. 
Published: October 2010

In two surveys of a total of over 16,000 cattle carcases, animals from live auctions had more bruising and more meat rejected for bruising than animals from dealers and farms. The proportion of carcases with stick‐markings was higher in market cattle (2.5 per cent) than in cattle from farms (0.9 per cent). The amount of bruising was much higher in animals which were stick‐marked (35 per cent) than in the whole population surveyed (6.5 per cent). Young bulls had the lowest percentage of bruising and the least amount of meat rejected of all the categories of animals surveyed. There was less ‘important’ bruising in animals travelling less than 50 miles from markets, but over 50 miles the amount of ‘important’ bruising did not increase. However, the incidence of all bruising increased with the distance travelled and with the time the animal spent in the lairage. More than half the carcases surveyed (59 per cent) had some degree of bruising caused by preslaughter handling. The areas most frequently bruised were the butt and hip, loin, shoulder/foreleg and neck, hind leg and flank/brisket. The number of carcases with an ultimate pH (pHu) of over 5.8 and the average pHu of the muscle increased with the amount of carcase bruising.
Babesiosis in a six‐day‐old calf
Authors: Egeli A. K. 
Published: October 2010

Babesiosis was diagnosed in a six‐day‐old calf born indoors to a heifer which had been on a tick‐infested pasture until 14 days before calving. The calf had typical symptoms of haemolytic anaemia and died after three days despite a blood transfusion. The erythrocytes in a blood smear made on the day it became ill were heavily infected with Babesia divergens and the lesions observed post mortem were similar to those described in babesiosis in adult cattle.
Treatment and control of psoroptic mange (sheep scab) with moxidectin
Authors: O'Brien D. , Parker L. D. , Menton C. , Keaveny C. , McCollum E. , O'Laoide S. 
Published: October 2010

In an investigation into alternative methods for the treatment and control of sheep scab, the efficacy of moxidectin, a second generation milbemycin, was evaluated in a series of laboratory and field studies in Ireland. Initial laboratory trials demonstrated that moxidectin, given as a subcutaneous injection at 200 μg/kg bodyweight was effective in the treatment of clinical psoroptic mange. Subsequent work showed that a single injection of clean sheep with moxidectin at the same dose rate provided protection against natural and experimental sheep scab infection for up to 35 days. This residual protective efficacy was tested in a large scale field trial in County Offaly, Ireland, in which more than 6500 sheep on 50 farms received a single prophylactic injection with moxidectin in the autumn and remained free from scab throughout the winter. This was comparable to the preventive effect of the annual compulsory dipping programme applied at that time. In a parallel series of field trials conducted across several counties in Ireland, two injections, 10 days apart, were effective in the treatment of outbreaks of scab. It is concluded that moxidectin is suitable for the treatment and control of sheep scab and has advantages over some existing methods because of its ease of use, safety for the user, the sheep and the environment, and because it also provides worm control owing to its efficacy against the major nematodes of sheep.
Incidence of production diseases and other health problems in a group of dairy herds in England
Authors: Esslemont R. J. , Kossaibati M. A. 
Published: October 2010

The incidence of major production diseases and other health problems was investigated in 90 Friesian/Holstein dairy herds in England (average size 152 cows) for cows calving during 12 months in 1992–1993. The mean incidence of mastitis was 33.2 cases per 100 cows, and it affected 20.6 per cent of the herd with 1.6 cases for each affected cow. On average, 17.4 per cent of the cows suffered from lameness, with 14 cases per affected cow and a total of 24.0 cases per 100 cows. Cows treated for oestrus‐not‐observed totalled 33.6 per cent, with 46‐4 treatments per 100 cows. The incidence of milk fever was 7.7 cases per 100 cows. Retained fetal membranes affected 3‐6 per cent of cows. Vulval discharge affected 15 per cent of the average herd with 1.4 treatments per affected cow and a total of 21.2 treatments per 100 cows. The mean incidence of twinning was 4.1 per cent. Calf mortality claimed 7.8 calves per 100 calves born. The average number of cows given aid at calving was 8.7 per 100 cows calving.
Epidemiology of lameness in dairy cattle: the influence of cubicles and indoor and outdoor walking surfaces
Authors: Faull W. B. , Hughes J. W. , Clarkson M. J. , Downham D. Y. , Manson F. J. , Merritt J. B. , Murray R. D. , Russell W. B. , Sutherst J. E. , Ward W. R. 
Published: October 2010

A survey of cubicles and indoor and outdoor walking surfaces on 37 farms served by four veterinary practices in Somerset, Cheshire, Wirral and west Wales was carried out in 1989 to 1991. A study of the space requirements of Friesian/Holstein cows at pasture showed that they required approximately 240 cm × 120 cm lying space and a further 60 cm lunging space for rising. By these standards, 87 per cent of the cubicles were too short and 50 per cent were too wide or too narrow. Over 1500 observations on cows lying down, rising and standing indicated that only 12 per cent of the cubicles permitted real freedom of movement; 91 per cent of top partition rails were judged to be too low and 70 per cent of bottom rails too low or too high. In addition, the kerb was very high in 76 per cent of the cubicles. As a result, 10 per cent of cows appeared moderately or severely restricted when lying down, 33 per cent when rising and 55 per cent when standing. Over 2000 cubicle beds were also studied; 75 per cent had a concrete base and of those, 63 per cent were judged to have too little bedding and 11 per cent next to none. Higher incidences and prevalences of lameness were associated with limited borrowing space (P<0.01) low bottom rails (P<0.05), high kerbs (P<0.05) and inadequate bedding (P<0.01). Of 3190 walking surfaces, only 25 per cent were classified as satisfactory in the first winter and 34 per cent in the second. In general, surfaces in silage bays were too rough and those in other sites were too smooth. The farms with the smoothest indoor walking surfaces had a significantly higher incidence of lameness (P<0.01). Of 3335 outdoor walking surfaces only 25 per cent were classified as satisfactory, and 70 per cent were too rough. The incidence of lameness was not significantly related to these findings.
Effect of forage supplements on the incidence of bloat in dairy cows grazing high clover pastures
Authors: Phillips C. J. C. , James N. L. , Murray‐Evans J. P. 
Published: October 2010

The effect of offering forage supplements of different compositions was examined in two experiments with cows grazing high clover swards. In the first experiment strawmix supplements of high or low energy content (11 and 9 MJ metabolisable energy/kg dry matter [DM]) and high or low crude protein content (17 and 4 g/kg DM) were offered for periods of three weeks. The energy and protein contents were varied by the content of molasses and soyabean meal, respectively. The high energy, high protein supplement increased the incidence of bloat, and the low energy, high protein supplement reduced it, compared with grazing alone. Bloat was most evident in the first two weeks of each feeding period, suggesting that the cows partially adapted to the diets within three weeks. In the second experiment silage supplements reduced the incidence of bloat among cows grazing both tall and short swards. The most suitable forages to feed when there is a risk of bloat are those that are slowly fermented in the rumen but are eaten in sufficient quantity to reduce periods of rapid herbage intake.
Evaluation of the effects of nursery depopulation on the persistence of porcine reproductive and respiratory syndrome virus and the productivity of 34 farms
Authors: Dee S. A. , Joo H. S. , Polson D. D. , Park B. K. , Pijoan C. , Molitor T. W. , Collins J. E. , King V. 
Published: October 2010

Nursery depopulation has been described as an effective strategy for improving the performance of weaned pigs. In order to assess whether the strategy was effective under a wide range of conditions, a study was carried out on 34 farms in the USA. Four groups with different depopulation protocols were designed on the basis of the location of the depopulated facility (on site vs off site) and the period for which the nursery remained empty (seven days vs 14 days). The changes in average daily liveweight gain, percentage mortality, feed efficiency and treatment cost per pig produced were assessed 12 months before and after nursery depopulation. The ability to eliminate porcine reproductive and respiratory syndrome (PRRs) virus was examined by indirect fluorescent antibody testing of the nursery pigs. Significant improvements (P<0.0001) were detected in both average daily gain and percentage mortality after depopulation when the differences within an individual group were analysed, but no significant differences (P>O.14) were observed between the study groups. Serological testing indicated that antibodies to PRRS virus were still present in 14 of the 34 farms after depopulation.
Corynebacterium pseudotuberculosisinfection in Israeli cattle: clinical and epidemiological studies
Authors: Yeruham I. , Elad D. , Van‐Ham M. , Shpigel N. Y. , Perl S. 
Published: October 2010

Morbidity due toCorynebacterium pseudotuberculosisinfection occurred in 29 dairy herds in Israel during 1989 to 1995. The disease occurred sporadically in 17 of the herds with a morbidity of up to 5 per cent, and was epidemic in 12, with a morbidity of 5 to 35 per cent. Cutaneous abscesses were diagnosed in 609 animals. Young cattle appeared to be less susceptible to the disease than older cows. Beef cattle herds were not affected. The disease appeared in the cutaneous form in 92.5 per cent of cases, the cutaneous and mastitic form in 5.9 per cent and the cutaneous and visceral form in 1.6 per cent. The cutaneous form appeared as deep subcutaneous abscesses on various parts of the body, with granulating ulcers exuding pus and blood. In 10 of the herds,C pseudotuberculosiswas isolated from 33 mastitic cows which also had cutaneous lesions. The visceral form of the disease was detected when severely affected animals were slaughtered. In 23 of the herds, the disease occurred during the spring and summer dry season, from March to October; the highest prevalence was in the semi‐arid Negev region. In 25 herds, the infection lasted for up to five months. The skin lesions on individual cows healed on average in 23.4 days, after either local or parenteral treatment. No significant difference was observed between the effect of systemic antibiotic treatment and local antiseptic treatment. One hundred and two (16.7 per cent) severely affected animals were culled. There was a decrease in milk production and large increases in somatic cell counts in the 12 herds in which the disease was epidemic. None of the strains of isolatedC pseudotuberculosisreduced nitrate.
Novel cypermethrin formulation for the control of sea lice on salmon (Salmo salar)
Authors: Hart J. L. , Thacker J. R. M. , Braidwood J. C. , Fraser N. R. , Matthews J. E. 
Published: October 2010

A novel formulation of cypermethrin was applied as a bath treatment to Atlantic salmon infested with sea lice on a commercial fish farm on the Isle of Skye, Scotland. Twenty 15 m × 15 m cages were treated with cypermethrin at a concentration of 5 μg/litre sea water. The numbers of sea lice of all stages were recorded on five fish per cage before the treatment and one, seven and 16 days after treatment. Statistically significant reductions in the numbers of chalimus III and IV pre‐adults and adults were recorded over the whole period; the average percentage reductions at one and 16 days after treatment were 59 per cent and 90 per cent (chalimus III and IV), 98 per cent and 95 per cent (pre‐adults), and 99 per cent (adults), respectively.