bluuebunny/crossref_metadata_2025_split huggingface dataset:
Influence of oxytetracycline on carprofen pharmacodynamics and pharmacokinetics in calves
Authors: Brentnall C. , Cheng Z. , Mckellar Q. A. , Lees P. 
Published: August 2012

A tissue cage model of inflammation in calves was used to determine the pharmacokinetic and pharmacodynamic properties of individual carprofen enantiomers, following the administration of the racemate.RS(±) carprofen was administered subcutaneously both alone and in combination with intramuscularly administered oxytetracycline in a four‐period crossover study. Oxytetracycline did not influence the pharmacokinetics ofR(−) andS(+) carprofen enantiomers, except for a lower maximum concentration (Cmax) ofS(+) carprofen in serum after co‐administration with oxytetracycline.S(+) enantiomer means for area under the serum concentration–time curve (AUC0–96hwere 136.9 and 128.3 μg·h/mL and means for the terminal half‐life (T½k10) were = 12.9 and 17.3 h for carprofen alone and in combination with oxytetracycline, respectively.S(+) carprofenAUC0–96hin both carprofen treatments and T½k10for carprofen alone were lower (P < 0.05) thanR(−) carprofen values, indicating a small degree of enantioselectivity in the disposition of the enantiomers. Carprofen inhibition of serum thromboxane B2ex vivowas small and significant only at a few sampling times, whereasin vivoexudate prostaglandin (PG)E2synthesis inhibition was greater and achieved overall significance between 36 and 72 h (P < 0.05). Inhibition ofPGE2correlated with mean time to achieve maximum concentrations in exudate of 54 and 42 h for both carprofen treatments forR(−) andS(+) enantiomers, respectively. Carprofen reduction of zymosan‐induced intradermal swelling was not statistically significant. These data provide a basis for the rational use of carprofen with oxytetracycline in calves and indicate that no alteration to carprofen dosage is required when the drugs are co‐administered.
The isolated perfused equine distal limb as anex vivomodel for pharmacokinetic studies
Authors: Friebe M. , Stahl J. , Kietzmann M. 
Published: August 2012

Even though intra‐articular injections play an important role in the treatment of joint‐related lameness in horses, little is known about pharmacokinetic properties of substances used. Therefore, anex vivomodel for pharmacokinetic studies was developed using distal forelimbs of slaughtered horses. The extremity was perfused with gassed Tyrode solution for up to 8 h. Tissue viability was confirmed by measurements of glucose consumption, lactate production, and lactate dehydrogenase activity in the perfusate. Standard criteria for tissue viability had been determined in preliminary experiments (n = 11), which also included histological examinations of the joint capsule. As the model's first implementation, the articular efflux rate of betamethasone (BM), administered asBMdisodium phosphate intra‐articularly to the fetlock joint (4 mgBM/joint), was investigated. The concentration ofBMin the venous perfusate of the radial vein was measured by means of high‐performance liquid chromatography. The averageBMefflux rate per minute was calculated to be 5.1 μg/min with values ranging from 9 μg/min to 2.9 μg/min. 7.5 h after i.a. application, 2.3 mgBMhad left the joint via the radial vein. Using this inexpensive setup, the presented model allows studying a variety of pharmacological topics without the ethical limitations of animal studies.
Early Diagnosis and Treatment of Patients with Symptomatic Acute Q Fever Do Not Prohibit IgG Antibody Responses to Coxiella burnetii
Authors: Wielders C. C. H. , Kampschreur L. M. , Schneeberger P. M. , Jager M. M. , Hoepelman A. I. M. , Leenders A. C. A. P. , Hermans M. H. A. , Wever P. C. 
Published: August 2012

ABSTRACTLittle is known about the effect of timing of antibiotic treatment on development of IgG antibodies following acute Q fever. We studied IgG antibody responses in symptomatic patients diagnosed either before or during development of the serologic response toCoxiella burnetii. Between 15 and 31 May 2009, 186 patients presented with acute Q fever, of which 181 were included in this retrospective study: 91 early-diagnosed (ED) acute Q fever patients, defined as negative IgM phase II enzyme-linked immunosorbent assay (ELISA) and positive PCR, and 90 late-diagnosed (LD) acute Q fever patients, defined as positive/dubious IgM phase II ELISA and positive immunofluorescence assay (IFA). Follow-up serology at 3, 6, and 12 months was performed using IFA (IgG phase I and II). High IgG antibody titers were defined as IgG phase II titers of ≥1:1,024 together with IgG phase I titers of ≥1:256. At 12 months, 28.6% of ED patients and 19.5% of LD patients had high IgG antibody titers (P= 0.17). No statistically significant differences were found in frequencies of IgG phase I and IgG phase II antibody titers at all follow-up appointments for adequately and inadequately treated patients overall, as well as for ED and LD patients analyzed separately. Additionally, no significant difference was found in frequencies of high antibody titers and between early (treatment started within 7 days after seeking medical attention) and late timing of treatment. This study indicates that early diagnosis and antibiotic treatment of acute Q fever do not prohibit development of the IgG antibody response.
Pilot Phase IB Clinical Trial of an Alhydrogel-Adsorbed Recombinant Ricin Vaccine
Authors: Vitetta Ellen S. , Smallshaw Joan E. , Schindler John 
Published: August 2012

ABSTRACTThere is no FDA-approved vaccine for the potent plant toxin ricin. We have developed a recombinant ricin vaccine, RiVax. Without adjuvant it is safe and immunogenic in mice, rabbits, and humans. Based on our studies in mice, we now report the results of a small clinical trial with Alhydrogel-adsorbed RiVax.
Evaluation of Gamma Interferon and Antibody Tuberculosis Tests in Alpacas
Authors: Rhodes Shelley , Holder Tom , Clifford Derek , Dexter Ian , Brewer Jacky , Smith Noel , Waring Laura , Crawshaw Tim , Gillgan Steve , Lyashchenko Konstantin , Lawrence John , Clarke John , de la Rua-Domenech Ricardo , Vordermeier Martin 
Published: August 2012

ABSTRACTWe describe the performance of cell-based and antibody blood tests for the antemortem diagnosis of tuberculosis (TB) in South American camelids (SAC). The sensitivity and specificity of the gamma interferon (IFN-γ) release assay, two lateral flow rapid antibody tests (Stat-Pak and Dual Path Platform [DPP]), and two enzyme-linked immunosorbent assay (ELISA)-based antibody tests (Idexx and Enferplex) were determined using diseased alpacas fromMycobacterium bovisculture-confirmed breakdown herds and TB-free alpacas from geographical areas with no history of bovine TB, respectively. Our results show that while the sensitivities of the IFN-γ and antibody tests were similar (range of 57.7% to 66.7%), the specificity of the IFN-γ test (89.1%) was lower than those of any of the antibody tests (range of 96.4% to 97.4%). This lower specificity of the IFN-γ test was at least in part due to undisclosedMycobacterium microtiinfection in the TB-free cohort, which stimulates a positive purified protein derivative (PPD) response. The sensitivity of infection detection could be increased by combining two antibody tests, but even the use of all four antibody tests failed to detect all diseased alpacas. These antibody-negative alpacas were IFN-γ positive. We found that the maximum sensitivity could be achieved only by the combination of the IFN-γ test with two antibody tests in a “test package,” although this resulted in decreased specificity. The data from this evaluation of tests with defined sensitivity and specificity provide potential options for antemortem screening of SAC for TB in herd breakdown situations and could also find application in movement testing and tracing investigations.
Microbiome Diversity in the Bronchial Tracts of Patients with Chronic Obstructive Pulmonary Disease
Authors: Cabrera-Rubio Raúl , Garcia-Núñez Marian , Setó Laia , Antó Josep M. , Moya Andrés , Monsó Eduard , Mira Alex 
Published: August 2012

ABSTRACT

Culture of bacteria from bronchial secretions in respiratory patients has low sensitivity and does not allow for complete assessment of microbial diversity across different bronchial compartments. In addition, a significant number of clinical studies are based on sputum samples, and it is not known to what extent they describe the real diversity of the mucosa. In order to identify previously unrecognized lower airway bacteria and to investigate the complexity and distribution of microbiota in patients with chronic obstructive pulmonary disease (COPD), we performed PCR amplification and pyrosequencing of the 16S rRNA gene in patients not showing signs or symptoms of infection. Four types of respiratory samples (sputum, bronchial aspirate, bronchoalveolar lavage, and bronchial mucosa) were taken from each individual, obtaining on average >1,000 16S rRNA sequences per sample. The total number of genera per patient was >100, showing a high diversity, with
Streptococcus
,
Prevotella
,
Moraxella
,
Haemophilus
,
Acinetobacter
,
Fusobacterium
, and
Neisseria
being the most commonly identified. Sputum samples showed significantly lower diversity than the other three sample types. Lower-bronchial-tree samples, i.e., bronchoalveolar lavage and bronchial mucosa, showed a very similar bacterial compositions in contrast to sputum and bronchial aspirate samples. Thus, sputum and bronchial aspirate samples are upper bronchial tree samples that are not representative of the lower bronchial mucosa flora, and bronchoalveolar lavage samples showed the results closest to those for the bronchial mucosa. Our data confirm that the bronchial tree is not sterile in COPD patients and support the existence a different microbiota in the upper and lower compartments.
Standardized Methods and Quality Control Limits for Agar and Broth Microdilution Susceptibility Testing of Mycoplasma pneumoniae, Mycoplasma hominis, and Ureaplasma urealyticum
Authors: Waites Ken B. , Duffy Lynn B. , Bébéar Cécile M. , Matlow Anne , Talkington Deborah F. , Kenny George E. , Totten Patricia A. , Bade Donald J. , Zheng Xiaotian , Davidson Maureen K. , Shortridge Virginia D. , Watts Jeffrey L. , Brown Steven D. 
Published: August 2012

ABSTRACTAn international multilaboratory collaborative study was conducted to develop standard media and consensus methods for the performance and quality control of antimicrobial susceptibility testing ofMycoplasma pneumoniae,Mycoplasma hominis, andUreaplasma urealyticumusing broth microdilution and agar dilution techniques. A reference strain from the American Type Culture Collection was designated for each species, which was to be used for quality control purposes. Repeat testing of replicate samples of each reference strain by participating laboratories utilizing both methods and different lots of media enabled a 3- to 4-dilution MIC range to be established for drugs in several different classes, including tetracyclines, macrolides, ketolides, lincosamides, and fluoroquinolones. This represents the first multilaboratory collaboration to standardize susceptibility testing methods and to designate quality control parameters to ensure accurate and reliable assay results for mycoplasmas and ureaplasmas that infect humans.
Nostrils of Healthy Volunteers Are Independent with Regard to Staphylococcus aureus Carriage
Authors: Kildow Beau J. , Conradie Johan P. , Robson Rachel L. 
Published: August 2012

ABSTRACT

The right and left nares of healthy adults (
n
= 251) were swabbed separately to determine carriage of
Staphylococcus aureus
in each nostril. Carriers were significantly more likely to carry
S. aureus
in one nostril than in both. Of those carrying
S. aureus
in both nostrils, 20% carried genetically distinct strains in each. Nostrils belonging to a single individual should not be assumed to be homogenous with respect to carriage of
S. aureus
.
A Novel Dirofilaria Species Causing Human and Canine Infections in Hong Kong
Authors: To Kelvin K. W. , Wong Samson S. Y. , Poon Rosana W. S. , Trendell-Smith Nigel J. , Ngan Antonio H. Y. , Lam Jacky W. K. , Tang Tommy H. C. , AhChong Ah-Kian , Kan Joshua Chi-Hang , Chan Kwok-Hung , Yuen Kwok-Yung 
Published: August 2012

ABSTRACTDirofilariasis is globally the commonest manifestation of zoonotic filariasis. We report the detection of a novel canine species causing human and canine dirofilariasis in Hong Kong. Three human cases occurring over 10 months were identified, one presenting with cervical lymphadenopathy, one with an abdominal subcutaneous mass, and one with a subconjunctival nodule. Transected worms recovered from the resected abdominal subcutaneous mass were morphologically compatible withDirofilaria. Thecox1gene sequences of the three human isolates were identical; however, they were only 96.2% and 89.3% identical to thecox1gene ofDirofilaria repensandDirofilaria immitis, respectively. Sequencing of the 18S-ITS1-5.8S gene cluster was successful in the intact worm, and the nucleotide sequences were 94.0% and 94.9% identical to those ofD. repensandD. immitis, respectively. Screening of the blood samples from 200 dogs and 100 cats showed the presence of the novelDirofilariaspecies in 3% (6/200) of the dogs' but none of the cats' blood samples. Nucleotide sequences of thecox1gene and 18S-ITS1-5.8S gene clusters of the dogs' samples were identical to those in the human samples. The sera of canines infected by this novelDirofilariaspecies were negative when tested with the SNAP 4DxD. immitisdetection kit, except in the case of dogs with a mixed infection withD. immitisas detected by PCR. The results from this study suggest that this novelDirofilariaspecies is a cause of filarial infection in humans and dogs in Hong Kong. We propose to name thisDirofilariaspecies “Candidatus Dirofilaria hongkongensis.”
Cutaneous Phaeohyphomycosis Caused by Paraconiothyrium cyclothyrioides
Authors: Gordon Rachel A. , Sutton Deanna A. , Thompson Elizabeth H. , Shrikanth Vandana , Verkley Gerard J. M. , Stielow J. Benjamin , Mays Rana , Oleske Deanna , Morrison L. Katie , Lapolla Whitney J. , Galfione Sarah , Tyring Stephen , Samathanam Christina A. , Fu Jianmin , Wickes Brian L. , Mulanovich Victor , Wanger Audrey , Arias Cesar A. 
Published: August 2012

ABSTRACT

Paraconiothyrium cyclothyrioides
is a recently described coelomycetous fungal species. We present a case in a renal transplant patient with chronic skin lesions of the lower extremities caused by
P. cyclothyrioides
. Treatment with posaconazole led to complete resolution of the lesions.
P. cyclothyrioides
should be considered an opportunistic human pathogen in immunocompromised patients.
Evaluation of Two Hepatitis C Virus Genotyping Assays Based on the 5′ Untranslated Region (UTR): the Limitations of 5′ UTR-Based Assays and the Need for a Supplementary Sequencing-Based Approach
Authors: Hong Sung Kuk , Cho Sung Im , Ra Eun Kyung , Kim Eui-Chong , Park Joon Sung , Park Sung Sup , Seong Moon-Woo 
Published: August 2012

ABSTRACTWe evaluated two genotyping methodologies that characterize the 5′ untranslated region (5′ UTR) of the hepatitis C virus (HCV) genome. The limitations of these genotype assays need to be thoroughly evaluated, and sequencing-based approaches may be needed to complement these methods in clinical settings.
Sensing and Control of Bluetongue Virus Infection in Epithelial Cells via RIG-I and MDA5 Helicases
Authors: Chauveau Emilie , Doceul Virginie , Lara Estelle , Adam Micheline , Breard Emmanuel , Sailleau Corinne , Viarouge Cyril , Desprat Alexandra , Meyer Gilles , Schwartz-Cornil Isabelle , Ruscanu Suzana , Charley Bernard , Zientara Stéphan , Vitour Damien 
Published: August 2012

ABSTRACTBluetongue virus (BTV), an arthropod-borne member of theReoviridaefamily, is a double-stranded RNA virus that causes an economically important livestock disease that has spread across Europe in recent decades. Production of type I interferon (alpha/beta interferon [IFN-α/β]) has been reportedin vivoandin vitroupon BTV infection. However, the cellular sensors and signaling pathways involved in this process remain unknown. Here we studied the mechanisms responsible for the production of IFN-β in response to BTV serotype 8. Upon BTV infection of A549 cells, expression of IFN-β and other proinflammatory cytokines was strongly induced at both the protein and mRNA levels. This response appeared to be dependent on virus replication, since exposure to UV-inactivated virus failed to induce IFN-β. We also demonstrated that BTV infection activated the transcription factors IFN regulatory factor 3 and nuclear factor κB. We investigated the role of several pattern recognition receptors in this response and showed that expression of IFN-β was greatly reduced after small-interfering-RNA-mediated knockdown of the RNA helicase encoded by retinoic acid-inducible gene I (RIG-I) or melanoma differentiation-associated gene 5 (MDA5). In contrast, silencing of MyD88, Toll-like receptor 3, or the recently described DexD/H-box helicase DDX1 sensor had no or a weak effect on IFN-β induction, suggesting that the RIG-I-like receptor pathway is specifically engaged for BTV sensing. Moreover, we also showed that overexpression of either RIG-I or MDA5 impaired BTV expression in infected A549 cells. Overall, this indicates that RIG-I and MDA5 can both contribute to the recognition and control of BTV infection.
Cytomegalovirus CC Chemokine Promotes Immune Cell Migration
Authors: Vomaske Jennifer , Denton Michael , Kreklywich Craig , Andoh Takeshi , Osborn Jessica M. , Chen Daniel , Messaoudi Ilhem , Orloff Susan L. , Streblow Daniel N. 
Published: August 2012

ABSTRACT

Cytomegaloviruses manipulate the host chemokine/receptor axis by altering cellular chemokine expression and by encoding multiple chemokines and chemokine receptors. Similar to human cytomegalovirus (HCMV), rat cytomegalovirus (RCMV) encodes multiple CC chemokine-analogous proteins, including r129 (HCMV UL128 homologue) and r131 (HCMV UL130 and MCMV m129/130 homologues). Although these proteins play a role in CMV entry, their function as chemotactic cytokines remains unknown. In the current study, we examined the role of the RCMV chemokine r129 in promoting cellular migration and in accelerating transplant vascular sclerosis (TVS) in our rat heart transplant model. We determined that r129 protein is released into culture supernatants of infected cells and is expressed with late viral gene kinetics during RCMV infection and highly expressed in heart and salivary glands during
in vivo
rat infections. Using the recombinant r129 protein, we demonstrated that r129 induces migration of lymphocytes isolated from rat peripheral blood, spleen, and bone marrow and from a rat macrophage cell line. Using antibody-mediated cell sorting of rat splenocytes, we demonstrated that r129 induces migration of naïve/central memory CD4
+
T cells. Through ligand-binding assays, we determined that r129 binds rat CC chemokine receptors CCR3, CCR4, CCR5, and CCR7. In addition, mutational analyses identified functional domains of r129 resulting in recombinant proteins that fail to induce migration (r129-ΔNT and -C31A) or alter the chemotactic ability of the chemokine (r129-F43A). Two of the mutant proteins (r129-C31A and -ΔNT) also act as dominant negatives by inhibiting migration induced by wild-type r129. Furthermore, infection of rat heart transplant recipients with RCMV containing the r129-ΔNT mutation prevented CMV-induced acceleration of TVS. Together our findings indicate that RCMV r129 is highly chemotactic, which has important implications during RCMV infection and reactivation and acceleration of TVS.
HIV-1 Replication and APOBEC3 Antiviral Activity Are Not Regulated by P Bodies
Authors: Phalora Prabhjeet K. , Sherer Nathan M. , Wolinsky Steven M. , Swanson Chad M. , Malim Michael H. 
Published: August 2012

ABSTRACT
The APOBEC3 cytidine deaminases play a critical role in host-mediated defense against exogenous viruses, most notably, human immunodeficiency virus type-1 (HIV-1) and endogenous transposable elements. APOBEC3G and APOBEC3F interact with numerous proteins that regulate cellular RNA metabolism, including components of the RNA-induced silencing complex (RISC), and colocalize with a subset of these proteins to mRNA processing bodies (P bodies), which are sites of mRNA translational repression and decay. We sought to determine the role of P bodies and associated proteins in HIV-1 replication and APOBEC3 antiviral activity. While we established a positive correlation between APOBEC3 protein incorporation into virions and localization to P bodies, depletion of the P-body components DDX6 or Lsm1 did not affect HIV-1 replication, APOBEC3 packaging into virions or APOBEC3 protein mediated inhibition of HIV-1 infectivity. In addition, neither HIV-1 genomic RNA nor Gag colocalized with P-body proteins. However, simultaneous depletion of multiple Argonaute family members, the effector proteins of RISC, could modestly increase viral infectivity. Because some APOBEC3 proteins interact with several Argonaute proteins, we also tested whether they could modulate microRNA (miRNA) activity. We found no evidence for the specific regulation of miRNA function by the APOBEC3 proteins, though more general effects on transfected gene expression were observed. In sum, our results indicate that P bodies and certain associated proteins do not regulate HIV-1 replication or APOBEC3 protein antiviral activity. Localization to P bodies may therefore provide a means of sequestering APOBEC3 enzymatic activity away from cellular DNA or may be linked to as yet unidentified cellular functions.
Monitoring of S Protein Maturation in the Endoplasmic Reticulum by Calnexin Is Important for the Infectivity of Severe Acute Respiratory Syndrome Coronavirus
Authors: Fukushi Masaya , Yoshinaka Yoshiyuki , Matsuoka Yusuke , Hatakeyama Seisuke , Ishizaka Yukihito , Kirikae Teruo , Sasazuki Takehiko , Miyoshi-Akiyama Tohru 
Published: August 2012

ABSTRACT
Severe acute respiratory syndrome coronavirus (SARS-CoV) is the etiological agent of SARS, a fatal pulmonary disorder with no effective treatment. We found that SARS-CoV spike glycoprotein (S protein), a key molecule for viral entry, binds to calnexin, a molecular chaperone in the endoplasmic reticulum (ER), but not to calreticulin, a homolog of calnexin. Calnexin bound to most truncated mutants of S protein, and S protein bound to all mutants of calnexin. Pseudotyped virus carrying S protein (S-pseudovirus) produced by human cells that were treated with small interfering RNA (siRNA) for calnexin expression (calnexin siRNA-treated cells) showed significantly lower infectivity than S-pseudoviruses produced by untreated and control siRNA-treated cells. S-pseudovirus produced by calnexin siRNA-treated cells contained S protein modified with N-glycan side chains differently from other two S proteins and consisted of two kinds of viral particles: those of normal density with little S protein and those of high density with abundant S protein. Treatment with peptide-N-glycosidase F (PNGase F), which removes all types of N-glycan side chains from glycoproteins, eliminated the infectivity of S-pseudovirus. S-pseudovirus and SARS-CoV produced in the presence of α-glucosidase inhibitors, which disrupt the interaction between calnexin and its substrates, showed significantly lower infectivity than each virus produced in the absence of those compounds. In S-pseudovirus, the incorporation of S protein into viral particles was obviously inhibited. In SARS-CoV, viral production was obviously inhibited. These findings demonstrated that calnexin strictly monitors the maturation of S protein by its direct binding, resulting in conferring infectivity on SARS-CoV.