bluuebunny/crossref_metadata_2025_split huggingface dataset:
Anti‐inflammatory and protective effects of saffron extract in ischaemia/reperfusion‐induced acute kidney injury
Authors: Mahmoudzadeh Leila , Najafi Houshang , Ashtiyani Saeed Changizi , Yarijani Zeynab Mohamadi 
Published: July 2016

AbstractAimInflammation is one of the major challenges in the management of ischaemia/reperfusion (I/R)‐induced acute kidney injury. Our aim was to assess the anti‐inflammatory and protective effects of saffron extract against I/R‐induced renal disturbances.MethodsA total of 35 male Wistar rats were randomly divided into five groups (n = 7) as sham, I/R and three groups of I/R that were pretreated with different doses of saffron extract (5 mg/kg, 10 mg/kg, or 20 mg/kg) intraperitoneally. The I/R‐induced renal inflammation was assessed by measuring leukocyte infiltration and mRNA expression levels of intercellular adhesion molecule‐1 and tumour necrotic factor‐alpha. For the assessment of oxidative stress, thiobarbituric acid reactive species and antioxidant capacity of kidneys were measured in the right kidneys. In addition, plasma creatinine and urea‐nitrogen concentrations were determined for renal functional disturbances. Statistical analysis was performed using one‐way analysis of variance using the Duncan post hoc test.ResultsThe I/R increased all of the measured parameters, except for the tissue level of ferric reducing/antioxidant power, which decreased. Pretreatment with saffron extract in all doses significantly reduced the severity of these disturbances in such a way that there were no significant differences between the FRAP level and urea‐nitrogen concentrations between the sham and all three saffron extract‐treated groups. However, the saffron extract could decrease the plasma creatinine concentration, malondialdehyde level, tumour necrotic factor‐alpha and intercellular adhesion molecule‐1 expression and leukocyte infiltration in a dose‐dependent manner.ConclusionThe present study showed anti‐inflammatory, anti‐oxidative and protective effects for the hydro‐ethanolic extract of saffron in I/R‐induced acute kidney injury.
Lactobacillus rhamnosus strain JB‐1 reverses restraint stress‐induced gut dysmotility
Authors: West C. , Wu R. Y. , Wong A. , Stanisz A. M. , Yan R. , Min K. K. , Pasyk M. , McVey Neufeld K.‐A. , Karamat M. I. , Foster J. A. , Bienenstock J. , Forsythe P. , Kunze W. A. 
Published: July 2016

AbstractBackgroundEnvironmental stress affects the gut with dysmotility being a common consequence. Although a variety of microbes or molecules may prevent the dysmotility, none reverse the dysmotility.MethodsWe have used a 1 hour restraint stress mouse model to test for treatment effects of the neuroactive microbe, L. rhamnosus JB‐1™. Motility of fluid‐filled ex vivo gut segments in a perfusion organ bath was recorded by video and migrating motor complexes measured using spatiotemporal maps of diameter changes.Key ResultsStress reduced jejunal and increased colonic propagating contractile cluster velocities and frequencies, while increasing contraction amplitudes for both. Luminal application of 10E8 cfu/mL JB‐1 restored motor complex variables to unstressed levels within minutes of application. L. salivarius or Na.acetate had no treatment effects, while Na.butyrate partially reversed stress effects on colonic frequency and amplitude. Na.propionate reversed the stress effects for jejunum and colon except on jejunal amplitude.Conclusions & InferencesOur findings demonstrate, for the first time, a potential for certain beneficial microbes as treatment of stress‐induced intestinal dysmotility and that the mechanism for restoration of function occurs within the intestine via a rapid drug‐like action on the enteric nervous system.
Deformation During the Electrosurgical Vessel Sealing Process
Authors: Wyatt H. L. , Pullin R. , Yang T. H. J. , Evans S. L. 
Published: July 2016

AbstractElectrosurgical vessel sealing is used throughout many surgical procedures with the benefits of the device widely reported. However, there is still significant variation in the quality of the resulting seal with limited understanding as to why. This study developed a methodology to use digital image correlation to capture the sealing process and to investigate the changes occurring throughout. Porcine carotid arteries were used throughout the study, with seals created using the Gyrus G400 generator and the PKS Open Seal device (Gyrus Medical Ltd, Cardiff, United Kingdom).The displacement across the surface of the blood vessel and the device jaws was measured, and the true maximum principal strain was computed. There was significant contraction of the tissue along the length of the blood vessel, with this occurring in pulses due to the waveform used to deliver the current. Additionally, there was a significant change in displacement between the device jaws (0.08 mm), a novel finding of the study. This change in displacement is indicative of a change in application force throughout sealing, which can have significant implications in the quality of the seal, and therefore the findings of this study can influence future device design.
Exhumation of the Dora Maira ultrahigh‐pressure unit by buoyant uprise within a low‐viscosity mantle oblique‐slip shear zone
Authors: Schmalholz Stefan M. , Schenker Filippo L. 
Published: July 2016

AbstractThe Brossasco‐Isasca subunit (BIU) of the Dora Maira massif is currently the only known continental crustal ultrahigh‐pressure (UHP) unit in the Western Alps. The peak pressure/temperature conditions are 3.5–4.5 GPa/~730 °C; exhumation from ~3.5 GPa to ~1 GPa occurred within 2.2 ± 1.8 Ma, but the exhumation mechanism is incompletely understood. We present a conceptual model for the buoyancy‐driven exhumation of the BIU inside a low‐viscosity, dense mantle shear zone weakened by increased strain rates due to simultaneous strike‐slip and subduction (oblique‐slip) of the European plate. Two‐dimensional thermo‐mechanical models simulate such a buoyant uprise of an ellipse inside an inclined layer. Simulations (i) show the feasibility of the conceptual model, (ii) fit the pressure/temperature/time record and (iii) constrain effective viscosities. The model is compatible with the (i) small volume of continental crustal UHP rock in the Western Alps, (ii) minor erosion during exhumation and (iii) strike‐slip deformation during the exhumation period.
Bacterial meningitis in solid organ transplant recipients: a population‐based prospective study
Authors: van Veen K.E.B. , Brouwer M.C. , van der Ende A. , van de Beek D. 
Published: July 2016

AbstractBackgroundSolid organ transplant (SOT) recipients are at risk of infections of the central nervous system. However, the incidence and clinical course of bacterial meningitis in SOT recipients are unclear. We studied occurrence, disease course, and prognosis of bacterial meningitis in SOT recipients in the Netherlands.MethodsAll patients with a medical history of solid organ transplantation were selected from our nationwide prospective cohort study on community‐acquired bacterial meningitis in patients >16 years old, performed from March 1, 2006 to October 31, 2014. Data on patient history, symptoms and signs on admission, treatment, and outcome were collected prospectively. For transplant recipients, additional information was collected retrospectively.ResultsWe identified 6 SOT recipients, all receiving renal transplants. The annual incidence of bacterial meningitis was 7‐fold higher (95% confidence interval [CI] 2.94–17.02, P < 0.001) for renal transplant recipients as compared with the general population (9.56 [95% CI 3.98–22.96] vs. 1.35 [95% CI 1.28–1.43] per 100,000 patients per year). One of the 6 patients (17%) presented with the classic presentation of bacterial meningitis (fever, neck stiffness, and change in mental status). Seizures were common, occurring in 33% of patients. Streptococcus pneumoniae and Listeria monocytogenes were identified in 2 patients each, and Escherichia coli and Pseudomonas aeruginosa were both identified once. Four of 6 patients (67%) had an unfavorable functional outcome.ConclusionBacterial meningitis is a rare but devastating complication of solid organ transplantation. SOT recipients are at high risk for developing meningitis, and recognition of this condition may be difficult, owing to atypical clinical manifestation.
Leukoreduced red blood cell transfusions do not induce platelet glycoprotein antibodies in patients with sickle cell disease
Authors: Nickel Robert Sheppard , Winkler Anne M. , Horan John T. , Hendrickson Jeanne E. 
Published: July 2016

BACKGROUNDAlloimmunization to red blood cell (RBC) antigens after transfusion is well described in patients with sickle cell disease (SCD). We recently demonstrated that leukocyte‐reduced RBC transfusions appeared to induce human leukocyte antigen (HLA) antibodies in some children with SCD; now, we hypothesize that residual platelets contained in transfused RBC products may lead to platelet glycoprotein antibody formation.STUDY DESIGN AND METHODSA cross‐sectional study was conducted among never pregnant pediatric patients with SCD who either had received many RBC transfusions or had never received any transfusions. Serum was tested for antibodies to platelet‐specific glycoproteins using a commercial enzyme immunoassay.RESULTSPlatelet‐specific glycoprotein antibodies were found in 12 of 90 patients (13%) in the transfused group versus 5 of 24 patients (21%) in the never transfused group (p = 0.35). The prevalence of antibodies as well as the median standardized optical density for these two groups was not significantly different for any of the studied platelet glycoprotein antigens. There was no association with the presence of platelet‐specific glycoprotein antibodies with either RBC or HLA antibodies.CONCLUSIONSLeukocyte‐reduced RBC transfusions do not appear to induce platelet‐specific glycoprotein antibodies. The positive platelet‐specific glycoprotein antibody results from this study may represent platelet autoantibodies, platelet alloantibodies, or false‐positive reactions. A better understanding of the immunobiology of patients with SCD at baseline and after blood product exposure may help improve future transfusion and transplantation.
Effect of the β-Lactamase Inhibitor Vaborbactam Combined with Meropenem against Serine Carbapenemase-Producing Enterobacteriaceae
Authors: Castanheira Mariana , Rhomberg Paul R. , Flamm Robert K. , Jones Ronald N. 
Published: July 2016

ABSTRACT

Klebsiella pneumoniae
carbapenemase (KPC)-producing isolates have become increasingly prevalent worldwide, and these organisms are often multidrug resistant, limiting the therapeutic options available for treating infections. We evaluated the activity of meropenem combined with the serine β-lactamase inhibitor vaborbactam (formerly RPX7009) against 315 serine carbapenemase-producing
Enterobacteriaceae
(CPE) isolates by use of checkerboard-designed panels to assess the optimal inhibitor concentration (range tested, 0.5 to 32 μg/ml). Overall, meropenem alone (MIC
50
and MIC
90
, 16 and >64 μg/ml, respectively) inhibited only 2.2% of the isolates at ≤1 μg/ml (the CLSI susceptibility breakpoint) and 7.3% of the isolates at ≤2 μg/ml (the EUCAST breakpoint). Vaborbactam restored meropenem activity for 72.7 to 98.1% of CPE isolates at ≤2 μg/ml, and maximum potentiation was achieved with fixed concentrations of ≥8 μg/ml of the inhibitor (≥96.5% of isolates were inhibited at ≤2 μg/ml of meropenem-vaborbactam). Meropenem-vaborbactam with a fixed concentration of 8 μg/ml of the inhibitor (MIC
50
, ≤0.06 μg/ml for all organisms) inhibited 93.7% of the CPE isolates displaying elevated meropenem MICs at ≤1 μg/ml. Meropenem-vaborbactam MICs were elevated for isolates producing metallo-β-lactamases (MIC, 16 to >64 μg/ml) or displaying decreased expression of OmpK37 and/or elevated expression of the AcrAB-TolC efflux system (MIC, 16 μg/ml). Vaborbactam showed no antibacterial activity alone (all MICs, >64 μg/ml). Meropenem-vaborbactam appears to be a good candidate for further development and it could increase the options for treatment of serious infections caused by carbapenemase-producing pathogens.
The Role of Signaling via Aqueous Pore Formation in Resistance Responses to Amphotericin B
Authors: Cohen B. Eleazar 
Published: July 2016

ABSTRACT
Drug resistance studies have played an important role in the validation of antibiotic targets. In the case of the polyene antibiotic amphotericin B (AmB), such studies have demonstrated the essential role that depletion of ergosterol plays in the development of AmB-resistant (AmB-R) organisms. However, AmB-R strains also occur in fungi and parasitic protozoa that maintain a normal level of ergosterol at the plasma membrane. Here, I review evidence that shows not only that there is increased protection against the deleterious consequences of AmB-induced ion leakage across the membrane in these resistant pathogens but also that a set of events are activated that block the cell signaling responses that trigger the oxidative damage produced by the antibiotic. Such signaling events appear to be the consequence of a membrane-thinning effect that is exerted upon lipid-anchored Ras proteins by the aqueous pores formed by AmB. A similar membrane disturbance effect may also explain the activity of AmB on mammalian cells containing Toll-like receptors. These resistance mechanisms expand our current understanding of the role that the formation of AmB aqueous pores plays in triggering signal transduction responses in both pathogens and host immune cells.
A Novel Endonuclease Inhibitor Exhibits Broad-Spectrum Anti-Influenza Virus Activity
In Vitro
Authors: Jones Jeremy C. , Marathe Bindumadhav M. , Lerner Christian , Kreis Lukas , Gasser Rodolfo , Pascua Philippe Noriel Q. , Najera Isabel , Govorkova Elena A. 
Published: July 2016

ABSTRACT

Antiviral drugs are important in preventing and controlling influenza, particularly when vaccines are ineffective or unavailable. A single class of antiviral drugs, the neuraminidase inhibitors (NAIs), is recommended for treating influenza. The limited therapeutic options and the potential risk of antiviral resistance are driving the search for additional small-molecule inhibitors that act on influenza virus proteins. The acid polymerase (PA) of influenza viruses is a promising target for new antivirals because of its essential role in initiating virus transcription. Here, we characterized a novel compound, RO-7, identified as a putative PA endonuclease inhibitor. RO-7 was effective when added before the cessation of genome replication, reduced polymerase activity in cell-free systems, and decreased relative amounts of viral mRNA and genomic RNA during influenza virus infection. RO-7 specifically inhibited the ability of the PA endonuclease domain to cleave a nucleic acid substrate. RO-7 also inhibited influenza A viruses (seasonal and 2009 pandemic H1N1 and seasonal H3N2) and B viruses (Yamagata and Victoria lineages), zoonotic viruses (H5N1, H7N9, and H9N2), and NAI-resistant variants in plaque reduction, yield reduction, and cell viability assays in Madin-Darby canine kidney (MDCK) cells with nanomolar to submicromolar 50% effective concentrations (EC
50
s), low toxicity, and favorable selective indices. RO-7 also inhibited influenza virus replication in primary normal human bronchial epithelial cells. Overall, RO-7 exhibits broad-spectrum activity against influenza A and B viruses in multiple
in vitro
assays, supporting its further characterization and development as a potential antiviral agent for treating influenza.
Interspecies Dissemination of a Mobilizable Plasmid Harboring
bla
IMP-19
and the Possibility of Horizontal Gene Transfer in a Single Patient
Authors: Yamamoto Masaki , Matsumura Yasufumi , Gomi Ryota , Matsuda Tomonari , Tanaka Michio , Nagao Miki , Takakura Shunji , Uemoto Shinji , Ichiyama Satoshi 
Published: July 2016

ABSTRACT

Carbapenemase-producing Gram-negative bacilli have been a global concern over the past 2 decades because these organisms can cause severe infections with high mortality rates. Carbapenemase genes are often carried by mobile genetic elements, and resistance plasmids can be transferred through conjugation. We conducted whole-genome sequencing (WGS) to demonstrate that the same plasmid harboring a metallo-β-lactamase gene was detected in two different species isolated from a single patient. Metallo-β-lactamase-producing
Achromobacter xylosoxidans
(KUN4507), non-metallo-β-lactamase-producing
Klebsiella pneumoniae
(KUN4843), and metallo-β-lactamase-producing
K. pneumoniae
(KUN5033) were sequentially isolated from a single patient and then analyzed in this study. Antimicrobial susceptibility testing, molecular typing (pulsed-field gel electrophoresis and multilocus sequence typing), and conjugation analyses were performed by conventional methods. Phylogenetic and molecular clock analysis of
K. pneumoniae
isolates were performed with WGS, and the nucleotide sequences of plasmids detected from these isolates were determined using WGS. Conventional molecular typing revealed that KUN4843 and KUN5033 were identical, whereas the phylogenetic tree analysis revealed a slight difference. These two isolates were separated from the most recent common ancestor 0.74 years before they were isolated. The same resistance plasmid harboring
bla
IMP-19
was detected in metallo-β-lactamase-producing
A. xylosoxidans
and
K. pneumoniae
. Although this plasmid was not self-transferable, the conjugation of this plasmid from
A. xylosoxidans
to non-metallo-β-lactamase-producing
K. pneumoniae
was successfully performed. The susceptibility patterns for metallo-β-lactamase-producing
K. pneumoniae
and the transconjugant were similar. These findings supported the possibility of the horizontal transfer of plasmid-borne
bla
IMP-19
from
A. xylosoxidans
to
K. pneumoniae
in a single patient.
Beneficial Effects of Sodium Phenylbutyrate Administration during Infection with Salmonella enterica Serovar Typhimurium
Authors: Jellbauer Stefan , Perez Lopez Araceli , Behnsen Judith , Gao Nina , Nguyen Thao , Murphy Clodagh , Edwards Robert A. , Raffatellu Manuela 
Published: July 2016

ABSTRACT

Sodium phenylbutyrate (PBA) is a derivative of the short-chain fatty acid butyrate and is approved for treatment of urea cycle disorders and progressive familial intrahepatic cholestasis type 2. Previously known functions include histone deacetylase inhibitor, endoplasmic reticulum stress inhibitor, ammonia sink, and chemical chaperone. Here, we show that PBA has a previously undiscovered protective role in host mucosal defense during infection. Administration of PBA to Taconic mice resulted in the increase of intestinal
Lactobacillales
and segmented filamentous bacteria (SFB), as well as an increase of interleukin 17 (IL-17) production by intestinal cells. This effect was not observed in Jackson Laboratory mice, which are not colonized with SFB. Because previous studies showed that IL-17 plays a protective role during infection with mucosal pathogens, we hypothesized that Taconic mice treated with PBA would be more resistant to infection with
Salmonella enterica
serovar Typhimurium (
S
. Typhimurium). By using the streptomycin-treated mouse model, we found that Taconic mice treated with PBA exhibited significantly lower
S
. Typhimurium intestinal colonization and dissemination to the reticuloendothelial system, as well as lower levels of inflammation. The lower levels of
S
. Typhimurium gut colonization and intestinal inflammation were not observed in Jackson Laboratory mice. Although PBA had no direct effect on bacterial replication, its administration reduced
S
. Typhimurium epithelial cell invasion and lowered the induction of the proinflammatory cytokine IL-23 in macrophage-like cells. These effects likely contributed to the better outcome of infection in PBA-treated mice. Overall, our results suggest that PBA induces changes in the microbiota and in the mucosal immune response that can be beneficial to the host during infection with
S
. Typhimurium and possibly other enteric pathogens.
CagA Phosphorylation in Helicobacter pylori-Infected B Cells Is Mediated by the Nonreceptor Tyrosine Kinases of the Src and Abl Families
Authors: Krisch Linda M. , Posselt Gernot , Hammerl Peter , Wessler Silja 
Published: July 2016

ABSTRACT

CagA is one of the most important virulence factors of the human pathogen
Helicobacter pylori
. CagA expression can be associated with the induction of severe gastric disorders such as gastritis, ulceration, gastric cancer, or mucosa-associated lymphoid tissue (MALT) lymphoma. After translocation through a type IV secretion system into epithelial cells, CagA is tyrosine phosphorylated by kinases of the Src and Abl families, leading to drastic cell elongation and motility. While the functional role of CagA in epithelial cells is well investigated, knowledge about CagA phosphorylation and its associated signal transduction pathways in B cells is only marginal. Here, we established the B cell line MEC1 derived from a B cell chronic lymphocytic leukemia (B-CLL) patient as a new infection model to study the signal transduction in B cells controlled by
H. pylori
. We observed that CagA was rapidly injected, strongly tyrosine phosphorylated, and cleaved into a 100-kDa N-terminal and a 40-kDa C-terminal fragment. To identify upstream signal transduction pathways of CagA phosphorylation in MEC1 cells, pharmacological inhibitors were employed to specifically target Src and Abl kinases. We observed that CagA phosphorylation was strongly inhibited upon treatment with an Src inhibitor and slightly diminished when the Abl kinase inhibitor imatinib mesylate (Gleevec) was applied. The addition of dasatinib to block c-Abl and Src kinases led to a complete loss of CagA phosphorylation. In conclusion, these results demonstrate an important role for Src and Abl tyrosine kinases in CagA phosphorylation in B cells, which represent druggable targets in
H. pylori
-mediated gastric MALT lymphoma.