bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pharmacokinetics and tissue depletion of florfenicol in Leghorn and Taiwan Native chickens
Authors: CHANG S. K. , DAVIS J. L. , CHENG C. N. , SHIEN R. H. , HSIEH M. K. , KOH B. W. , CHOU C. C. 
Published: June 2010

Chang, S. K., Davis, J. L., Cheng, C. N., Shien, R. H., Hsieh, M. K., Koh, B. W., Chou, C. C. Pharmacokinetics and tissue depletion of florfenicol in Leghorn and Taiwan Native chickens.J. vet. Pharmacol. Therap.33, 471–479.Florfenicol (Ff) is a synthetic antibiotic with a broad antibacterial spectrum and high therapeutic effectiveness that was specifically developed for veterinary use. In the present study, tissue residual levels and the pharmacokinetics of Ff after oral administration of 30 mg/kg to Leghorn and Taiwan Native chicken were studied. Furthermore, differential pharmacokinetics between leg and breast muscles were compared using samples collected from an optimized microdialysis model designed for avian species. Significant differences inCmaxwere detected between the plasma and muscle microdialysates, and between the breast and leg microdialysates of the Leghorn chickens by noncompartmental pharmacokinetic analysis. After a single oral dose of Ff at 30 mg/kg, the drug was quickly absorbed and widely distributed with tissue penetration factors significantly different between leg and breast muscles. The serum protein binding of Ff was estimated to be 16.8 ± 1.2%. Significant breed differences in tissue depletion were noted and characterized by higher Ff concentration in the brain, lung, kidney and at least 12 h longer resident times in kidney, heart and spleen for Taiwan Native chicken. Results from this investigation demonstrate the practicality of usingin vivomicrodialysis in chickens for pharmacokinetic studies and reveal significant time‐dependent differences in the free concentrations of Ff in leg and breast muscles. The tissue depletion study signified breed differences in tissue residue concentration and detection times between Leghorn and Taiwan Native chickens. Therefore, currently used withdrawal times for Ff in chickens can not be assumed safe for Taiwan Native chickens.
Excretion mass balance evaluation, metabolite profile analysis and metabolite identification in plasma and excreta after oral administration of [14C]‐meloxicam to the male cat: preliminary study
Authors: GRUDE P. , GUITTARD J. , GARCIA C. , DAOULAS I. , THOULON F. , EBNER T. 
Published: June 2010

Grudé, P., Guittard, J., Garcia, C., Daoulas, I., Thoulon, F., Ebner, T. Excretion mass balance evaluation, metabolite profile analysis and metabolite identification in plasma and excreta after oral administration of [14C]‐meloxicam to the male cat: preliminary study.J. vet. Pharmacol. Therap.doi: 10.1111/j.1365‐2885.2010.01157.x.The objective of this study was to investigate the metabolic pathways and routes of excretion of oral meloxicam in the cat. [14C]‐meloxicam was administered orally to three fasted male cats. Urine, faeces, vomit and cage washes were collected over the following 144 h period. Blood was collected predosing and at 3 and 12 h postdosing. Metabolites were identified by HPLC/MS/MS. When possible a metabolic structure was proposed for each metabolite detected. Only unchanged meloxicam was identified in plasma. Five major metabolites were detected in urine and four in faeces, which were identified by HPLC/MS/MS as products of oxidative metabolism. No conjugated metabolites were detected. Elimination occurred early (61% during the first 48 h). A total of 21% of the recovered dose was eliminated in urine (2% as unchanged meloxicam, 19% as metabolites) and 79% in the faeces (49% as unchanged meloxicam, 30% as metabolites). The results indicate that after oral administration the major route of excretion of meloxicam in the cat is faecal and that the main pathway of biotransformation of meloxicam in the cat is oxidation.
Pharmacokinetics of ketamine in plasma and milk of mature Holstein cows
Authors: SELLERS G. , LIN H. C. , RIDDELL M. G. , RAVIS W. R. , LIN Y. J. , DURAN S. H. , GIVENS M. D. 
Published: June 2010

Sellers, G., Lin, H. C., G. Riddell, M. G., Ravis, W. R., Lin, Y. J., Duran, S. H., Givens, M.D. Pharmacokinetics of ketamine in plasma and milk of mature Holstein cows.J. vet. Pharmacol. Therap.33, 480–484.The purpose of this study was to evaluate the pharmacokinetics of ketamine in mature Holstein cows following administration of a single intravenous (i.v.) dose. Plasma and milk concentrations were determined using a high‐performance liquid chromatography assay. Pharmacokinetic parameters were estimated using a noncompartmental method. Following i.v. administration, plasmaTmaxwas 0.083 h and plasmaCmaxwas 18 135 ± 22 720 ng/mL. PlasmaAUCwas 4484 ± 1,398 ng·h/mL. Plasmat½βwas 1.80 ± 0.50 h and mean residence time was 0.794 ± 0.318 h with total body clearance of 1.29 ± 0.70 L/h/kg. The mean plasma steady‐state volume of distribution was calculated as 0.990 ± 0.530 L/kg and volume of distribution based on area was calculated as 3.23 ± 1.51 L/kg. The last measurable time for ketamine detection in plasma was 8.0 h with a mean concentration of 24.9 ± 11.8 ng/mL. MilkTmaxwas detected at 0.67 ± 0.26 h withCmaxof 2495 ± 904 ng/mL. MilkAUCtill the last time was 6593 ± 2617 ng·h/mL with meanAUCmilk toAUCplasma ratio of 1.99 ± 2.15. The last measurable time that ketamine was detected in milk was 44 ± 10.0 h with a mean concentration of 16.0 ± 9.0 ng/mL.
Insect nicotinic acetylcholine receptor agonists as flea adulticides in small animals
Authors: VO D. T. , HSU W H. , ABU‐BASHA E. A. , MARTIN R. J. 
Published: June 2010

Vo, D. T., Hsu, W. H., Abu‐Basha, E. A., Martin, R. J. Insect nicotinic acetylcholine receptor agonists as flea adulticides in small animals.J. vet. Pharmacol. Therap.doi: 10.1111/j.1365‐2885.2010.01160.x.Fleas are significant ectoparasites of small animals. They can be a severe irritant to animals and serve as a vector for a number of infectious diseases. In this article, we discuss the pharmacological characteristics of four insect nicotinic acetylcholine receptor (nAChR) agonists used as flea adulticides in dogs and cats, which include three neonicotinoids (imidacloprid, nitenpyram, and dinotefuran) and a macrocyclic lactone (spinosad). Insect nAChR agonists are one of the most important classes of insecticides, which are used to control sucking insects on both plants and animals. These novel compounds provide a new approach for practitioners to safely and effectively eliminate adult fleas.
Pharmacokinetic profile and behavioral effects of gabapentin in the horse
Authors: TERRY R. L. , McDONNELL S. M. , Van EPS A. W. , SOMA L. R. , LIU Y. , UBOH C. E. , MOATE P. J. , DRIESSEN B. 
Published: June 2010

Terry, R. L., McDonnell, S. M., van Eps, A. W., Soma, L. R., Liu, Y., Uboh, C. E., Moate, P. J., Driessen, B. Pharmacokinetic profile and behavioral effects of gabapentin in the horse.J. vet. Pharmacol. Therap.33, 485–494.Gabapentin is being used in horses although its pharmacokinetic (PK) profile, pharmacodynamic (PD) effects and safety in the equine are not fully investigated. Therefore, we characterized PKs and cardiovascular and behavioral effects of gabapentin in horses. Gabapentin (20 mg/kg) was administered i.v. or p.o. to six horses using a randomized crossover design. Plasma gabapentin concentrations were measured in samples collected 0–48 h postadministration employing liquid chromatography‐tandem mass spectrometry. Blood pressures, ECG, and sedation scores were recorded before and for 12 h after gabapentin dosage. Nineteen quantitative measures of behaviors were evaluated. After i.v. gabapentin, the decline in plasma drug concentration over time was best described by a 3‐compartment mammillary model. Terminal elimination half‐life (t1/2γ) was 8.5 (7.1–13.3) h. After p.o. gabapentin terminal elimination half‐life () was 7.7 (6.7–11.9) h. The mean oral bioavailability of gabapentin (±SD) was 16.2 ± 2.8% indicating relatively poor absorption of gabapentin following oral administration in horses. Gabapentin caused a significant increase in sedation scores for 1 h after i.v. dose only (P < 0.05). Among behaviors, drinking frequency was greater and standing rest duration was lower with i.v. gabapentin (P < 0.05). Horses tolerated both i.v. and p.o. gabapentin doses well. There were no significant differences inand. Oral administration yielded much lower plasma concentrations because of low bioavailability.
In vitroandex vivoinhibition of COX isoforms by robenacoxib in the cat: a comparative study
Authors: SCHMID V.B. , SEEWALD W. , LEES P. , KING J.N. 
Published: June 2010

Schmid, V.B., Seewald, W., Lees, P., King, J.N.In vitroandex vivoinhibition of COX isoforms by robenacoxib in the cat: a comparative study.J. vet. Pharmacol. Therap.33, 444–452.Robenacoxib is a novel nonsteroidal anti‐inflammatory drug (NSAID) developed for use in companion animals. Whole blood assays were used to characterize in the cat the pharmacodynamics of robenacoxib for inhibition of the cyclooxygenase (COX) isoforms, COX‐1 and COX‐2, in comparison with other NSAIDs. Based onin vitroIC50COX‐1:IC50COX‐2 ratios, robenacoxib was COX‐2 selective (ratio = 32.2), diclofenac (ratio = 3.9) and meloxicam (ratio = 2.7) were only weakly COX‐2 preferential, and ketoprofen (ratio = 0.049) was COX‐1 selective. In anin vivopharmacokineticex vivopharmacodynamic study, after both p.o. (1–2 mg/kg) and subcutaneous (2 mg/kg) dosing, robenacoxib achieved peak blood concentrations rapidly (Tmax = 1 h for both administration routes) and was cleared from blood relatively rapidly (mean residence time was 1.70 h after p.o. and 1.79 h after subcutaneous dosing). Inex vivoCOX isoform inhibition assays, orally (1–2 mg/kg) or subcutaneously (2 mg/kg) administered robenacoxib significantly inhibited COX‐2, with a relatively short duration of action in the central compartment, and had no effect on COX‐1. Therefore robenacoxib was COX‐2 selective and spared COX‐1in vivo. In contrast, meloxicam (0.3 mg/kg via subcutaneous injection) inhibited both COX‐1 and COX‐2 isoforms significantly for at least 24 h, indicating nonselectivityin vivo.
Mycobacterium tuberculosis CYP125A1, a steroid C27 monooxygenase that detoxifies intracellularly generated cholest‐4‐en‐3‐one
Authors: Ouellet Hugues , Guan Shenheng , Johnston Jonathan B. , Chow Eric D. , Kells Petrea M. , Burlingame Alma L. , Cox Jeffery S. , Podust Larissa M. , De Montellano Paul R. Ortiz 
Published: June 2010

SummaryThe infectivity and persistence of Mycobacterium tuberculosis requires the utilization of host cell cholesterol. We have examined the specific role of cytochrome P450 CYP125A1 in the cholesterol degradation pathway using genetic, biochemical and high‐resolution mass spectrometric approaches. The analysis of lipid profiles from cells grown on cholesterol revealed that CYP125A1 is required to incorporate the cholesterol side‐chain carbon atoms into cellular lipids, as evidenced by an increase in the mass of the methyl‐branched phthiocerol dimycocerosates. We observed that cholesterol‐exposed cells lacking CYP125A1 accumulate cholest‐4‐en‐3‐one, suggesting that this is a physiological substrate for this enzyme. Reconstitution of enzymatic activity with spinach ferredoxin and ferredoxin reductase revealed that recombinant CYP125A1 indeed binds both cholest‐4‐en‐3‐one and cholesterol, efficiently hydroxylates both of them at C‐27, and then further oxidizes 27‐hydroxycholest‐4‐en‐3‐one to cholest‐4‐en‐3‐one‐27‐oic acid. We determined the X‐ray structure of cholest‐4‐en‐3‐one‐bound CYP125A1 at a resolution of 1.58 Å. CYP125A1 is essential for growth of CDC1551 in media containing cholesterol or cholest‐4‐en‐3‐one. In its absence, the latter compound is toxic for both CDC1551 and H37Rv when added with glycerol as a second carbon source. CYP125A1 is a key enzyme in cholesterol metabolism and plays a crucial role in circumventing the deleterious effect of cholest‐4‐en‐3‐one.
LapF, the second largest Pseudomonas putida protein, contributes to plant root colonization and determines biofilm architecture
Authors: Martínez‐Gil Marta , Yousef‐Coronado Fátima , Espinosa‐Urgel Manuel 
Published: June 2010

SummaryWe have investigated the role of LapF, one of the two largest proteins encoded in the genome of Pseudomonas putida KT2440, in bacterial colonization of solid surfaces. LapF is 6310 amino acids long, and is localized on the cell surface. The C‐terminal region of the protein is essential for its secretion, which presumably requires the ABC transporter encoded by an operon (lapHIJ) adjacent to the lapF gene. Although the initial attachment stages are not different between the wild type and a lapF mutant, microcolony formation and subsequent development of a mature biofilm is impaired in the mutant. This is consistent with the expression pattern of lapF; activation of its promoter takes place at late stages of growth and is regulated by the alternative sigma factor RpoS. A lapF mutant is also affected in individual and competitive plant root colonization. In these assays, mixed microcolonies formed by cells of both the wild‐type and the mutant strains could be observed but microcolonies of the mutant alone were not found. These data and the localization of the protein at discrete spots in areas of contact between cells in biofilms suggest that LapF determines the establishment of cell–cell interactions during sessile growth.
A cyanobacterial serine protease of Plasmodium falciparum is targeted to the apicoplast and plays an important role in its growth and development
Authors: Rathore Sumit , Sinha Dipto , Asad Mohd , Böttcher Thomas , Afrin Farhat , Chauhan Virander S. , Gupta Dinesh , Sieber Stephan A. , Mohmmed Asif 
Published: June 2010

SummaryThe prokaryotic ATP‐dependent protease machineries such as ClpQY and ClpAP in the malaria parasite may represent potential drug targets. In the present study, we show that the orthologue of cyanobacterial ClpP protease in Plasmodium falciparum (PfClpP) is expressed in the asexual blood stages and possesses serine protease activity. The PfClpP was localized in the apicoplast using a GFP‐targeting approach, immunoelectron microscopy and by immunofluorescence assays. A set of cell permeable β‐lactones, which specifically bind with the active site of prokaryotic ClpP, were screened using an in vitro protease assay of PfClpP. A PfClpP‐specific protease inhibitor was identified in the screen, labelled as U1‐lactone. In vitro growth of the asexual stage parasites was significantly inhibited by U1‐lactone treatment. The U1‐treated parasites showed developmental arrest at the late‐schizont stage. We further show that the U1‐lactone treatment resulted in formation of abnormal apicoplasts which were not able to grow and segregate in the parasite progeny; these effects were also evident by blockage in the replication of the apicoplast genome. Overall, our data show that the PfClpP protease has confirmed localization in the apicoplast and it plays important role in development of functional apicoplasts.
MUTYH‐associated polyposis – variability of the clinical phenotype in patients with biallelic and monoallelic MUTYH mutations and report on novel mutations
Authors: Morak M , Laner A , Bacher U , Keiling C , Holinski‐Feder E 
Published: June 2010

Morak M, Laner A, Bacher U, Keiling C, Holinski‐Feder E. MUTYH‐associated polyposis – variability of the clinical phenotype in patients with biallelic and monoallelic MUTYH mutations and report on novel mutations.To further characterize 215 APC mutation‐negative patients with colorectal neoplasias classified in classical, attenuated, or atypical familial adenomatous polyposis (FAP) coli we performed mutation screening in the Mut Y homologue (MUTYH) gene.The incidence was 15% for biallelic and 3.7% for monoallelic MUTYH mutations. We describe six novel MUTYH mutations in biallelic constellation and two novel monoallelic missense mutations.Of 33 MUTYH‐associated polyposis coli (MAP) patients 57% were attenuated familial adenomatous polyposis (AFAP) patients, 10% display early‐onset classical FAP and 18% had only few adenomas at higher age. Biallelic cases had a high incidence of extracolonic polyposis in 32% and colorectal cancer (CRC) in 33% of the cases.The clinical picture of MAP ranged from classical FAP or synchronous CRC at age 30 years to few adenomas at age 54 years without evidence of CRC, initially suspected for hereditary non‐polyposis colorectal cancer (HNPCC). The mean age of onset was 43 years, with 11 (33%) patients being younger than 40 years of age, indicating that the clinical manifestation can be earlier than so far reported. Monoallelic MUTYH mutation carriers had a positive family history in seven of eight cases allowing the hypothesis of a disease‐causing synergism of MUTYH mutations with other genes.
Reproductive decision‐making: a qualitative study among couples at increased risk of having a child with retinoblastoma
Authors: Dommering CJ , Van Den Heuvel MR , Moll AC , Imhof SM , Meijers‐Heijboer H , Henneman L 
Published: June 2010

Dommering CJ, van den Heuvel MR, Moll AC, Imhof SM, Meijers‐Heijboer H, Henneman L. Reproductive decision‐making: a qualitative study among couples at increased risk of having a child with retinoblastoma.Little is known about the reproductive decision‐making process of couples with an increased risk of having a child with retinoblastoma (Rb). A qualitative study was conducted to explore the impact of prospective risk on reproductive decisions, factors influencing these decisions, and the needs of couples with regard to reproductive counselling. Fourteen couples of childbearing age who received genetic counselling between 2002 and 2006 participated in semi‐structured interviews in 2008. The risk of having a child with Rb ranged from less than 1% to 50%. In most cases, the diagnosis of Rb influenced subsequent family planning. Prenatal diagnosis was used by two couples, while others refrained from having more children. Reproductive decisions were influenced by the burden of the disease for the patient and family members, the impact of ophthalmological screening under anaesthesia, and couples' perceived risk, which did not always relate to their actual risk. Reproductive choices with regard to the number of children wanted changed over time. Our findings indicate topics to be discussed during genetic counselling of couples at increased risk for a child with Rb. We suggest continued access to genetic counselling also after the initial diagnosis and treatment.
Spinal arteriovenous malformation presenting as spastic monoplegic cerebral palsy in a child
Authors: Flett Peter John , Baulderstone David , Russo Remo , Davies Roger Philip 
Published: June 2010

AbstractA case of spinal arterio‐venous malformation (AVM) initially diagnosed as unilateral cerebral palsy (CP) is reported. The presentation was of a long‐standing spastic monoparesis of the left leg, with initial response to Botulinum toxin injections to the calf and tibialis posterior muscles. This was followed by progressive deterioration occurring over a 3‐month period before further investigation and definitive diagnosis at 7 years. Imaging demonstrated a large extra‐medullary spinal AVM compressing the mid‐thoracic cord. This was successfully managed by embolisation with a non‐adhesive polymer: ethylene‐vinyl alcohol copolymer injected into the dominant feeding vessel. This case highlights the need to consider alternative diagnoses when a child with a diagnosis of CP presents with atypical clinical features such as monoparesis and has worsening or altered clinical signs. Moreover, a normal magnetic resonance imaging brain scan and the absence of ipsilateral upper limb neurological signs or functional impairment should raise suspicion even in the context of static lower limb signs. A literature review was performed on the management of spinal AVM in children and this will be is discussed.
Predator control promotes invasive dominated ecological states
Authors: Wallach Arian D. , Johnson Christopher N. , Ritchie Euan G. , O’Neill Adam J. 
Published: June 2010

Ecology Letters (2010) 13: 1008–1018AbstractInvasive species are regarded as one of the top five drivers of the global extinction crisis. In response, extreme measures have been applied in an attempt to control or eradicate invasives, with little success overall. We tested the idea that state shifts to invasive dominance are symptomatic of losses in ecosystem resilience, due to the suppression of apex predators. This concept was investigated in Australia where the high rate of mammalian extinctions is largely attributed to the destructive influence of invasive species. Intensive pest control is widely applied across the continent, simultaneously eliminating Australia’s apex predator, the dingo (Canis lupus dingo). We show that predator management accounts for shifts between two main ecosystem states. Lethal control fractures dingo social structure and leads to bottom‐up driven increases in invasive mesopredators and herbivores. Where control is relaxed, dingoes re‐establish top–down regulation of ecosystems, allowing for the recovery of biodiversity and productivity.
Spatial mismatch and congruence between taxonomic, phylogenetic and functional diversity: the need for integrative conservation strategies in a changing world
Authors: Devictor Vincent , Mouillot David , Meynard Christine , Jiguet Frédéric , Thuiller Wilfried , Mouquet Nicolas 
Published: June 2010

Ecology Letters (2010) 13: 1030–1040AbstractFunctional and phylogenetic diversity are increasingly quantified in various fields of ecology and conservation biology. The need to maintain diversity turnover among sites, so‐called beta‐diversity, has also been raised in theoretical and applied ecology. In this study, we propose the first comprehensive framework for the large‐scale mapping of taxonomic, phylogenetic and functional diversity and of their respective turnover. Using high‐resolution data on the spatial distribution and abundance of birds at a country scale, we disentangled areas of mismatches and congruencies between biodiversity components. We further revealed unequal representation of each component in protected areas: functional diversity was significantly under‐represented whereas taxonomic diversity was significantly over‐represented in protected areas. Our results challenge the use of any one diversity component as a surrogate for other components and stress the need to adopt an integrative approach to biodiversity conservation.
Nitrogen availability is a primary determinant of conifer mycorrhizas across complex environmental gradients
Authors: Cox Filipa , Barsoum Nadia , Lilleskov Erik A. , Bidartondo Martin I. 
Published: June 2010

Ecology Letters (2010) 13: 1103–1113AbstractGlobal environmental change has serious implications for functional biodiversity in temperate and boreal forests. Trees depend on mycorrhizal fungi for nutrient uptake, but predicted increases in nitrogen availability may alter fungal communities. To address a knowledge gap regarding the effects of nitrogen availability on mycorrhizal communities at large scales, we examine the relationship between nitrogen and ectomycorrhizas in part of a European biomonitoring network of pine forest plots. Our analyses show that increased nitrogen reduces fungal diversity and causes shifts in mycorrhizal community composition across plots, but we do not find strong evidence that within‐plot differences in nitrogen availability affect ectomycorrhizal communities. We also carry out exploratory analyses to determine the relative importance of other environmental variables in structuring mycorrhizal communities, and discuss the potential use of indicator species to predict nitrogen‐induced shifts in fungal communities.