bluuebunny/crossref_metadata_2025_split huggingface dataset:
Accumulation of oxidized peroxiredoxin 2 in red blood cells and its prevention
Authors: Bayer Simone B. , Hampton Mark B. , Winterbourn Christine C. 
Published: February 2015

BackgroundThe thiol protein peroxiredoxin 2 (Prx2) is a major red blood cell (RBC) antioxidant that breaks down hydroperoxides and in the process is converted to an oxidized disulfide. Our objective was to determine whether Prx2 becomes oxidized during storage of RBCs, to understand the underlying mechanism, and to find ways of preventing the accumulation of the oxidized form.Study design and MethodsRBCs were stored for up to 6 weeks under simulated blood banking conditions and Prx2 oxidation was monitored by nonreducing gel electrophoresis. The ability of the cells to reverse Prx2 oxidation after storage and to respond to added hydrogen peroxide was also evaluated.ResultsPrx2 remained predominantly reduced during the first 3 weeks of storage, and then the oxidized form accumulated progressively. In contrast to fresh cells, oxidation was not reversed by incubation with glucose. Storage of RBCs in a high‐pH, low‐chloride, and high‐phosphate/bicarbonate buffer (EAS‐76v6) largely prevented accumulation of oxidized Prx for at least 6 weeks, and dihydrolipoic acid (DHLA), but not Rejuvesol, N‐acetylcysteine, or α‐lipoic acid, was able to reverse or protect against Prx2 oxidation. Additional, Prx2 oxidation occurred when hydrogen peroxide was added. However, this was reversible, suggesting that the reductive capacity was compromised in some but not in all cells.ConclusionPrx2 remains mostly reduced in a high‐pH storage solution with buffering capacity. Addition of DHLA to stored RBCs might be advantageous. Prx2 redox status could be used as a biomarker for the quality of stored RBCs.
Bitten by a bug or a bag? Transfusion‐transmitted dengue: a rare complication in the bleeding surgical patient
Authors: Oh Han Boon , Muthu Vaishnavi , Daruwalla Zubin J. , Lee Shir Ying , Koay Evelyn S. , Tambyah Paul A. 
Published: February 2015

BACKGROUNDBlood‐borne infections remain a risk of blood transfusions. While routine screening of donated blood products has greatly reduced the risk of human immunodeficiency virus, hepatitis B, and hepatitis C transmission, arboviruses such as dengue, chikungunya, and the West Nile virus remain significant risks especially during outbreaks.CASE REPORTWe report a rare case of dengue documented to be acquired through a blood transfusion, which resulted in severe thrombocytopenia prolonging admission in hospital in a neurosurgical patient.RESULTSThe donor of one of the units of red blood cells presented with dengue fever 2 days after donating. Sanger sequencing confirmed DENV‐2 (dengue virus, Serotype 2) in both the donor and the patient samples and showed 100% nucleotide sequence identity between the two viruses, confirming transfusion‐transmitted dengue infection.CONCLUSIONThis case highlights the importance of arboviral screening of donor blood, especially for populations in endemic areas during outbreaks.
Plerixafor on demand in ten healthy family donors as a rescue strategy to achieve an adequate graft for stem cell transplantation
Authors: Gattillo Salvatore , Marktel Sarah , Rizzo Lorenzo , Malato Simona , Malabarba Lucia , Coppola Milena , Assanelli Andrea , Milani Raffaella , De Freitas Tiago , Corti Consuelo , Bellio Laura , Ciceri Fabio 
Published: February 2015

BACKGROUNDIn allogeneic hematopoietic stem cell (HSC) transplantation, the collection of an appropriate number of HSCs while maintaining a high level of safety for healthy donors is fundamental. Inadequate HSC mobilization can be seen with the standard use of granulocyte–colony‐stimulating (G‐CSF). Plerixafor (PL) is a chemokine receptor CXC Type 4–stromal‐derived factor 1 inhibitor; its HSC‐mobilizing properties are synergistic with G‐CSF in poor mobilizing patients. The use of PL as adjuvant or alternative to G‐CSF in healthy donors has shown a good safety profile but is so far off‐label.STUDY DESIGN AND METHODSWe report 10 healthy HSC donors treated with PL because of insufficient response to G‐CSF alone or contraindication to G‐CSF. Eight donors did not mobilize enough CD34+ cells with G‐CSF alone because poor mobilizers or because insufficient HSCs were harvested according to the clinical need of the patient; in two cases G‐CSF administration and marrow harvest were unfeasible or contraindicated in the donor.RESULTSThe use of PL for mobilization increased the number of circulating CD34+ cells by 2.8‐fold and the CD34+/kg collection by 3.0‐fold. Only mild adverse events were reported (bone pain or discomfort) and not univocally attributable to PL. Rate of engraftment and graft‐versus‐host disease were similar to those seen in recipients of grafts from G‐CSF only–mobilized donors.CONCLUSIONWe exposed 10 allogeneic donors to mobilization with PL. PL was well tolerated in all cases and ensured procurement of an adequate graft for transplantation resulting in a normal hematopoietic engraftment.
The preanalytic phase in veterinary clinical pathology
Authors: Braun Jean‐Pierre , Bourgès‐Abella Nathalie , Geffré Anne , Concordet Didier , Trumel Cathy 
Published: February 2015

AbstractThis article presents the general causes of preanalytic variability with a few examples showing specialists and practitioners that special and improved care should be given to this too often neglected phase. The preanalytic phase of clinical pathology includes all the steps from specimen collection to analysis. It is the phase where most laboratory errors occur in human, and probably also in veterinary clinical pathology. Numerous causes may affect the validity of the results, including technical factors, such as the choice of anticoagulant, the blood vessel sampled, and the duration and conditions of specimen handling. While the latter factors can be defined, influence of biologic and physiologic factors such as feeding and fasting, stress, and biologic and endocrine rhythms can often not be controlled. Nevertheless, as many factors as possible should at least be documented. The importance of the preanalytic phase is often not given the necessary attention, although the validity of the results and consequent clinical decision making and medical management of animal patients would likely be improved if the quality of specimens submitted to the laboratory was optimized.
Dynamic exophthalmos and lateral strabismus in a dog caused by masticatory muscle myositis
Authors: Czerwinski Sarah L. , Plummer Caryn E. , Greenberg Shari M. , Craft William F. , Conway Julia A. , Perez Mayrim L. , Cooke Kirsten L. , Winter Matthew D. 
Published: February 2015

AbstractCase descriptionA 5.5‐year‐old neutered male mixed‐breed dog was presented for evaluation of a 5‐month history of deviation of the right globe upon opening the mouth and a 1‐month history of conjunctivitis in the same eye. Clinical findings, diagnostic imaging results, treatment and follow‐up are described.Clinical findingsWhen the mouth was opened, the right globe deviated rostrally and laterally. There was no pain or resistance to opening the mouth, or resistance to retropulsion of the globe. No other abnormalities were observed. Computed tomography was performed, revealing a contrast‐enhancing region associated with the right masseter muscle impinging into the right orbit; this was more pronounced with the mouth open. Cytology revealed a small number of mildly to moderately atypical mesenchymal cells. Histopathology was consistent with polyphasic myositis, with a predominance of lymphocytes and plasma cells. No infectious agents were identified. Serum antibody titers forToxoplasma gondiiandNeospora caninumwere negative. Serum titers for 2 M antibody were positive at 1:500, consistent with a diagnosis of masticatory muscle myositis.Treatment and outcomeTherapy with prednisone was initiated. During a follow‐up period of 5 months, there was no recurrence of clinical signs, and the dose of prednisone was reduced by 25%.Clinical significanceTo the authors' knowledge, this is the first reported case of masticatory muscle myositis causing dynamic exophthalmos and strabismus in a dog.
The effect of metabolic alkalosis on central and peripheral mechanisms associated with exercise‐induced muscle fatigue in humans
Authors: Siegler Jason C. , Marshall Paul 
Published: February 2015

New Findings

What is the central question of this study?
Does metabolic alkalosis affect central and peripheral mechanisms associated with exercise‐induced muscle fatigue in humans?

What is the main finding and its importance?
Inducing metabolic alkalosis before exercise preserved voluntary activation, but not muscle excitation, after a 2 min maximal voluntary contraction (MVC) followed by ischaemia. An effect of pH was also observed in maximal rates of torque development, where alkalosis mitigated the reduction in maximal rates of torque development after the initial 2 min MVC. For the first time, these results demonstrate a differential effect of pH on voluntary activation as well as maximal rates of torque development after sustained, maximal voluntary knee extension in humans.

The increased concentration of protons during fatiguing exercise may contribute to increased activation of group III and IV afferents and subsequently reduced central drive, but this has yet to be confirmed in exercising humans. Here, we determined whether inducing metabolic alkalosis differentially affects descending central drive after fatiguing exercise and whether this effect may, in part, be explained by attenuating group III and IV afferent firing. Eleven men performed a maximal 2 min voluntary knee extension (MVC) followed by a 2 min rest and subsequent 1 min MVC with an occlusive cuff either in placebo [PLA; 0.3 g (kg body weight)−1 calcium carbonate] or alkalosis conditions [ALK; 0.3 g (kg body weight)−1 sodium bicarbonate]. Femoral nerve stimulation was applied before exercise, after the 2 min MVC and at 40–60 s intervals throughout the remainder of the protocol to explore central and peripheral mechanisms associated with reductions in maximal force and rate of torque development. Although voluntary activation declined to a similar extent after the 2 min MVC, during the ischaemic period voluntary activation was higher during ALK (PLA, 57 ± 8%; ALK, 76 ± 5%). Maximal voluntary torque declined at similar rates during the task (203 ± 19 N m), but maximal rate of torque development was significantly higher in the ALK conditions after the 2 min MVC (mean difference of 177 ± 60 N m s−1). These results demonstrate the effect of pH on voluntary activation as well as maximal rates of torque development after sustained, maximal voluntary knee extension in humans.
In Vivo
Activities of Simulated Human Doses of Cefepime and Cefepime-AAI101 against Multidrug-Resistant Gram-Negative Enterobacteriaceae
Authors: Crandon Jared L. , Nicolau David P. 
Published: February 2015

ABSTRACT

The combination of cefepime with AAI101, a novel extended-spectrum β-lactamase inhibitor, possesses potent
in vitro
activity against many resistant Gram-negative pathogens. Against a panel of 20 mostly carbapenemase-producing cefepime-nonsusceptible strains of the family
Enterobacteriaceae
, we evaluated the MICs of cefepime in the presence of various fixed AAI101 concentrations (1, 2, 4, 8, and 16 mg/liter) and the
in vivo
efficacy of simulated human doses of cefepime and cefepime-AAI101 in a neutropenic murine thigh infection model. At 2 h after inoculation, mice were dosed with regimens that provided a profile mimicking the free drug concentration-time profile observed in humans given cefepime at 2 g every 8 h (q8h; as a 30-min infusion) or cefepime-AAI101 at 2 g/0.5 g q8h (as a 30-min infusion). Efficacy was determined by calculation of the change in thigh bacterial density (log
10
number of CFU) after 24 h relative to the starting inoculum (0 h). After 24 h, bacterial growth of 2.7 ± 0.1 log
10
CFU (mean ± standard error) was observed in control animals. Efficacy for cefepime monotherapy was observed against only 3 isolates, whereas increases in bacterial density similar to that in the control animals were noted for the remaining 17 strains (all with cefepime MICs of ≥64 mg/liter). The humanized cefepime-AAI101 dosing regimen resulted in bacterial reductions of ≥0.5 log
10
CFU for 12 of the 20 strains. Evaluation of efficacy as a function of the fraction of the dosing interval during which free drug concentrations were above the MIC determined with different fixed concentrations of AAI101 suggested that a fixed concentration of 8 mg/liter AAI101 is most predictive of
in vivo
activity for the studied regimen.
Persistence and Epidemic Propagation of a Pseudomonas aeruginosa Sequence Type 235 Clone Harboring an IS
26
Composite Transposon Carrying the
bla
IMP-1
Integron in Hiroshima, Japan, 2005 to 2012
Authors: Shimizu Wataru , Kayama Shizuo , Kouda Shuntaro , Ogura Yoshitoshi , Kobayashi Kanao , Shigemoto Norifumi , Shimada Norimitsu , Yano Raita , Hisatsune Junzo , Kato Fuminori , Hayashi Tetsuya , Sueda Taijiro , Ohge Hiroki , Sugai Motoyuki 
Published: February 2015

ABSTRACT

A 9-year surveillance for multidrug-resistant (MDR)
Pseudomonas aeruginosa
in the Hiroshima region showed that the number of isolates harboring the metallo-β-lactamase gene
bla
IMP-1
abruptly increased after 2004, recorded the highest peak in 2006, and showed a tendency to decline afterwards, indicating a history of an epidemic. PCR mapping of the variable regions of the integrons showed that this epidemic was caused by the clonal persistence and propagation of an MDR
P. aeruginosa
strain harboring the
bla
IMP-1
gene and an aminoglycoside 6′-
N
-acetyltransferase gene,
aac(6
′
)-Iae
in a class I integron (In113), whose integrase gene
intl1
was disrupted by an IS
26
insertion. Sequence analysis of the representative strain PA058447 resistance element containing the In113-derived gene cassette array showed that the element forms an IS
26
transposon embedded in the chromosome. It has a Tn
21
backbone and is composed of two segments sandwiched by three IS
26
s. In Japan, clonal nationwide expansion of an MDR
P. aeruginosa
NCGM2.S1 harboring chromosomally encoded In113 with intact
intl1
is reported. Multilocus sequence typing and genomic comparison strongly suggest that PA058447 and NCGM2.S1 belong to the same clonal lineage. Moreover, the structures of the resistance element in the two strains are very similar, but the sites of insertion into the chromosome are different. Based on tagging information of the IS
26
present in both resistance elements, we suggest that the MDR
P. aeruginosa
clone causing the epidemic in Hiroshima for the past 9 years originated from a common ancestor genome of PA058447 and NCGM2.S1 through an IS
26
insertion into
intl1
of In113 and through IS
26
-mediated genomic rearrangements.
Relationship between Azithromycin Susceptibility and Administration Efficacy for Nontypeable Haemophilus influenzae Respiratory Infection
Authors: Euba Begoña , Moleres Javier , Viadas Cristina , Barberán Montserrat , Caballero Lucía , Grilló María-Jesús , Bengoechea José Antonio , de-Torres Juan Pablo , Liñares Josefina , Leiva José , Garmendia Junkal 
Published: February 2015

ABSTRACTNontypeableHaemophilus influenzae(NTHI) is an opportunistic pathogen that is an important cause of acute exacerbations of chronic obstructive pulmonary disease (AECOPD). COPD is an inflammatory disease of the airways, and exacerbations are acute inflammatory events superimposed on this background of chronic inflammation. Azithromycin (AZM) is a macrolide antibiotic with antibacterial and anti-inflammatory properties and a clinically proven potential for AECOPD prevention and management. Relationships between AZM efficacy and resistance by NTHI and between bactericidal and immunomodulatory effects on NTHI respiratory infection have not been addressed. In this study, we employed two pathogenic NTHI strains with different AZM susceptibilities (NTHI 375 [AZM susceptible] and NTHI 353 [AZM resistant]) to evaluate the prophylactic and therapeutic effects of AZM on the NTHI-host interplay. At the cellular level, AZM was bactericidal toward intracellular NTHI inside alveolar and bronchial epithelia and alveolar macrophages, and it enhanced NTHI phagocytosis by the latter cell type. These effects correlated with the strain MIC of AZM and the antibiotic dose. Additionally, the effect of AZM on NTHI infection was assessed in a mouse model of pulmonary infection. AZM showed both preventive and therapeutic efficacies by lowering NTHI 375 bacterial counts in lungs and bronchoalveolar lavage fluid (BALF) and by reducing histopathological inflammatory lesions in the upper and lower airways of mice. Conversely, AZM did not reduce bacterial loads in animals infected with NTHI 353, in which case a milder anti-inflammatory effect was also observed. Together, the results of this work link the bactericidal and anti-inflammatory effects of AZM and frame the efficacy of this antibiotic against NTHI respiratory infection.
Synthesis of a Sugar-Based Thiosemicarbazone Series and Structure-Activity Relationship versus the Parasite Cysteine Proteases Rhodesain, Cruzain, and Schistosoma mansoni Cathepsin B1
Authors: Fonseca Nayara Cristina , da Cruz Luana Faria , da Silva Villela Filipe , do Nascimento Pereira Glaécia Aparecida , de Siqueira-Neto Jair Lage , Kellar Danielle , Suzuki Brian M. , Ray Debalina , de Souza Thiago Belarmino , Alves Ricardo José , Júnior Policarpo Ademar Sales , Romanha Alvaro José , Murta Silvane Maria Fonseca , McKerrow James H. , Caffrey Conor R. , de Oliveira Renata Barbosa , Ferreira Rafaela Salgado 
Published: February 2015

ABSTRACT

The pressing need for better drugs against Chagas disease, African sleeping sickness, and schistosomiasis motivates the search for inhibitors of cruzain, rhodesain, and
Schistosoma mansoni
CB1 (SmCB1), the major cysteine proteases from
Trypanosoma cruzi
,
Trypanosoma brucei
, and
S. mansoni
, respectively. Thiosemicarbazones and heterocyclic analogues have been shown to be both antitrypanocidal and inhibitory against parasite cysteine proteases. A series of compounds was synthesized and evaluated against cruzain, rhodesain, and SmCB1 through biochemical assays to determine their potency and structure-activity relationships (SAR). This approach led to the discovery of 6 rhodesain, 4 cruzain, and 5 SmCB1 inhibitors with 50% inhibitory concentrations (IC
50
s) of ≤10 μM. Among the compounds tested, the thiosemicarbazone derivative of peracetylated galactoside (compound 4i) was discovered to be a potent rhodesain inhibitor (IC
50
= 1.2 ± 1.0 μM). The impact of a range of modifications was determined; removal of thiosemicarbazone or its replacement by semicarbazone resulted in virtually inactive compounds, and modifications in the sugar also diminished potency. Compounds were also evaluated
in vitro
against the parasites
T. cruzi
,
T. brucei
, and
S. mansoni
, revealing active compounds among this series.
Chemical Inhibition of Bacterial Ribosome Biogenesis Shows Efficacy in a Worm Infection Model
Authors: Stokes Jonathan M. , Selin Carrie , Cardona Silvia T. , Brown Eric D. 
Published: February 2015

ABSTRACT

The development of antibacterial compounds that perturb novel processes is an imperative in the challenge presented by widespread antibiotic resistance. While many antibiotics target the ribosome, molecules that inhibit ribosome assembly have yet to be used in this manner. Here we show that a novel inhibitor of ribosome biogenesis, lamotrigine, is capable of rescuing
Caenorhabditis elegans
from an established
Salmonella
infection, revealing that ribosome biogenesis is a promising target for the development of new antibiotics.
Drug Resistance of Clinical Varicella-Zoster Virus Strains Confirmed by Recombinant Thymidine Kinase Expression and by Targeted Resistance Mutagenesis of a Cloned Wild-Type Isolate
Authors: Brunnemann Anne-Kathrin , Bohn-Wippert Kathrin , Zell Roland , Henke Andreas , Walther Martin , Braum Oliver , Maschkowitz Gregor , Fickenscher Helmut , Sauerbrei Andreas , Krumbholz Andi 
Published: February 2015

ABSTRACT

In this study, approaches were developed to examine the phenotypes of nonviable clinical varicella-zoster virus (VZV) strains with amino acid substitutions in the thymidine kinase (TK) (open reading frame 36 [ORF36]) and/or DNA polymerase (Pol) (ORF28) suspected to cause resistance to antivirals. Initially, recombinant TK proteins containing amino acid substitutions described as known or suspected causes of antiviral resistance were analyzed by measuring the TK activity by applying a modified commercial enzyme immunoassay. To examine the effects of these TK and Pol substitutions on the replication of recombinant virus strains, the method of
en passant
mutagenesis was used. Targeted mutations within ORF36 and/or ORF28 and an autonomously expressed gene of the monomeric red fluorescent protein for plaque identification were introduced into the European wild-type VZV strain HJO. Plaque reduction assays revealed that the amino acid substitutions with unknown functions in TK, Q303stop, N334stop, A163stop, and the deletion of amino acids 7 to 74 aa (Δaa 7 to 74), were associated with resistance against acyclovir (ACV), penciclovir, or brivudine, whereas the L73I substitution and the Pol substitutions T237K and A955T revealed sensitive viral phenotypes. The results were confirmed by quantitative PCR by measuring the viral load under increasing ACV concentrations. In conclusion, analyzing the enzymatic activities of recombinant TK proteins represent a useful tool for evaluating the significance of amino acid substitutions in the antiviral resistance of clinical VZV strains. However, direct testing of replication-competent viruses by the introduction of nonsynonymous mutations in a VZV bacterial artificial chromosome using
en passant
mutagenesis led to reliable phenotypic characterization results.
In-Feed Supplementation of
trans
-Cinnamaldehyde Reduces Layer-Chicken Egg-Borne Transmission of Salmonella enterica Serovar Enteritidis
Authors: Upadhyaya Indu , Upadhyay Abhinav , Kollanoor-Johny Anup , Mooyottu Shankumar , Baskaran Sangeetha A. , Yin Hsin-Bai , Schreiber David T. , Khan Mazhar I. , Darre Michael J. , Curtis Patricia A. , Venkitanarayanan Kumar 
Published: February 2015

ABSTRACT

Salmonella enterica
serovar Enteritidis is a major foodborne pathogen in the United States, causing gastroenteritis in humans, primarily through consumption of contaminated eggs. Chickens are the reservoir host of
S
. Enteritidis. In layer hens,
S
. Enteritidis colonizes the intestine and migrates to various organs, including the oviduct, leading to egg contamination. This study investigated the efficacy of in-feed supplementation with
trans
-cinnamaldehyde (TC), a generally recognized as safe (GRAS) plant compound obtained from cinnamon, in reducing
S
. Enteritidis cecal colonization and systemic spread in layers. Additionally, the effect of TC on
S
. Enteritidis virulence factors critical for macrophage survival and oviduct colonization was investigated
in vitro
. The consumer acceptability of eggs was also determined by a triangle test. Supplementation of TC in feed for 66 days at 1 or 1.5% (vol/wt) for 40- or 25-week-old layer chickens decreased the amounts of
S
. Enteritidis on eggshell and in yolk (
P
< 0.001). Additionally,
S
. Enteritidis persistence in the cecum, liver, and oviduct in TC-supplemented birds was decreased compared to that in controls (
P
< 0.001). No significant differences in feed intake, body weight, or egg production in birds or in consumer acceptability of eggs were observed (
P
> 0.05).
In vitro
cell culture assays revealed that TC reduced
S
. Enteritidis adhesion to and invasion of primary chicken oviduct epithelial cells and reduced
S
. Enteritidis survival in chicken macrophages (
P
< 0.001). Follow-up gene expression analysis using real-time quantitative PCR (qPCR) showed that TC downregulated the expression of
S
. Enteritidis virulence genes critical for chicken oviduct colonization (
P
< 0.001). The results suggest that TC may potentially be used as a feed additive to reduce egg-borne transmission of
S
. Enteritidis.