bluuebunny/crossref_metadata_2025_split huggingface dataset:
Extracellular Hsp70 modulates the inflammatory response of cigarette smoke extract in NCI‐H292 cells
Authors: Hulina‐Tomašković Andrea , Rajković Marija Grdić , Somborac‐Bačura Anita , Čeri Andrea , Dabelić Sanja , Rumora Lada 
Published: October 2018

New Findings
What is the central question of this study?
Does extracellular heat shock protein 70 (eHsp70) alter cigarette smoke extract (CSE)‐induced inflammatory responses in NCI‐H292 bronchial epithelial cells?

What is the main finding and its importance?
eHsp70 modulates inflammatory responses and TLR2, TLR4 and Hsp70 gene expression, and protects NCI‐H292 cells against CSE‐induced cytotoxicity. eHsp70 might be implicated in development of inflammatory diseases affected by cigarette smoke, such as COPD.

AbstractOne of the major risk factors for development of chronic obstructive pulmonary disease (COPD) is cigarette smoke. Extracellular Hsp70 (eHsp70) is increased in sera of COPD patients, and can act as damage‐associated molecular pattern (DAMP). In this study, we explored inflammatory parameters (cytokine concentrations, Toll‐like receptor (TLR) 2 and 4 and Hsp70 expression, mitogen‐activated protein kinases (MAPKs) and nuclear factor κB (NF‐κB) activation, and cytotoxicity) after exposure of bronchial‐epithelial NCI‐H292 cells to cigarette smoke extract (CSE) alone (2.5 and 15%) and in combinations with recombinant human (rh) Hsp70 (0.3, 1 and 3 μg ml−1). We applied specific MAPKs, NF‐κB and Hsp70 inhibitors to elucidate rhHsp70 inflammation‐associated responses. CSE alone and combinations of 15% CSE with rhHsp70 stimulated IL‐1α, IL‐6 and IL‐8 release. However, rhHsp70 applied with 2.5% CSE decreased secretion of cytokines indicating antagonistic effects. Individual and combined treatments with 2.5% CSE suppressed TLR2 expression. CSE at 15% induced TLR2 and TLR4 gene expression, whereas rhHsp70 abolished that effect. rhHsp70 and 15% CSE alone reduced, while their combination increased, intracellular Hsp70 mRNA level. CSE alone and in combination with rhHsp70 activated extracellular signal‐regulated kinase and p38 MAPKs, while inhibition of MAPKs, NF‐κB and Hsp70 attenuated IL‐6 and IL‐8 secretion. CSE at 15% reduced cell viability and induced apoptosis, as shown by MTS and caspases‐3/7 assays. CSE at 2.5% alone stimulated lactate dehydrogenase release, but cellular membrane integrity remained intact in co‐treatments with rhHsp70. rhHsp70 might modulate the inflammatory response of CSE and could also protect NCI‐H292 cells against CSE cytotoxicity. Those effects are implemented via MAPK and NF‐κB signalling pathways.
Heart-Rate Variability in Elite Synchronized Swimmers
Authors: Solana-Tramunt Mònica , Morales Jose , Buscà Bernat , Carbonell Marina , Rodríguez-Zamora Lara 
Published: October 2018

Purpose: To determine whether heart-rate variability (HRV) was correlated with other training-load and training-tolerance markers for monitoring the effect of a training session on elite synchronized swimmers. Methods: The authors recorded the resting HRV of 12 elite swimmers (mean age = 21.5 [3.5] y) 3 times over 1 wk with a cadence of 48 h prior to the 2015 World Swimming Championships. They continuously monitored heart rate and obtained salivary cortisol (SC) samples before and after the last training session of the week. The authors measured capillary blood lactate (La) 2, 4, and 8 min after the last training session and monitored recovery HRV. They assessed rating of perceived exertion (RPE) over the entire session and tested the association between the highest La concentration (Lapeak), SC, and RPE and relative changes (Δ%) in the natural logarithm of the root-mean-square successive difference of intervals (LnRMSSD). The authors also calculated the smallest worthwhile change of the averaged pre and post LnRMSSD measurements. Results: There were periods of pronounced bradycardia (60.5 [16.7] beats/min) during training exercises corresponding to apneic exercise. The magnitude-based inferences showed nonclinically meaningful changes of LnRMSSD. Lapeak (6.8 [2.7] mmol/L) correlated positively with Δ%LnRMSSD and Δ%SC (r = .89, P = .001 and r = .61, P = .04, respectively). Conclusions: There was no change in LnRMSSD and Lapeak, Δ%SC, and RPE indicated reduced sympathetic activation and positive adaptation to the stress imposed by the session. Isolated HRV assessment may reveal a controversial interpretation of autonomic nervous system status or the training tolerance in elite synchronized swimming athletes due to the influence of the diving response.
Blood Flow Restriction Therapy Versus Standard Care for Reducing Quadriceps Atrophy After Anterior Cruciate Ligament Reconstruction
Authors: Lipker Lauren Anne , Persinger Caitlyn Rae , Michalko Bradley Steven , Durall Christopher J. 
Published: October 2018

Clinical Scenario: Quadriceps atrophy and weakness are common after anterior cruciate ligament reconstruction (ACLR). Blood flow restriction (BFR) therapy, alone or in combination with exercise, has shown some promise in promoting muscular hypertrophy. This review was conducted to ascertain the extent to which current evidence supports the use of BFR for reducing quadriceps atrophy following ACLR in comparison with standard care. Clinical Question: Is BFR more effective than standard care for reducing quadriceps atrophy after ACLR? Summary of Key Findings: The literature was searched for studies that directly compared BFR treatment to standard care in patients with ACLR. Three level I randomized control trial studies retrieved from the literature search met the inclusion criteria. Clinical Bottom Line: Reviewed data suggest that a short duration (13 d) of moderate-pressure BFR combined with low-resistance muscular training does not appear to measurably affect quadriceps cross-sectional area. However, a relatively long duration (15 wk) of moderate-pressure BFR combined with low-resistance muscular training may increase quadriceps cross-sectional area to a greater extent than low-resistance muscular training alone. The results of the third randomized control trial suggest that employing BFR while immobilized in the early postoperative period may reduce quadriceps atrophy following ACLR. Additional data are needed to establish if the benefits of BFR on quadriceps atrophy after ACLR outweigh the inherent risks and costs. Strength of Recommendation: All evidence for this review was level 1 (randomized control trial) based on the Centre for Evidence-Based Medicine criteria. However, the findings were inconsistent across the 3 studies regarding the effects of BFR on quadriceps atrophy resulting in a grade “B” strength of recommendation.
In Vitro Activities of Voriconazole (UK-109,496) and Four Other Antifungal Agents against 394 Clinical Isolates of
Candida
spp
Authors: Marco F. , Pfaller M. A. , Messer S. , Jones R. N. 
Published: October 2018

ABSTRACT

Voriconazole (formerly UK-109,496) is a new monotriazole antifungal agent which has potent activity against
Candida
,
Cryptococcus
, and
Aspergillus
species. We investigated the in vitro activity of voriconazole compared to those of fluconazole, itraconazole, amphotericin B, and flucytosine (5FC) against 394 bloodstream isolates of
Candida
(five species) obtained from more than 30 different medical centers. MICs of all antifungal drugs were determined by the method recommended by the National Committee for Clinical Laboratory Standards using RPMI 1640 test medium. Overall, voriconazole was quite active against all the yeast isolates (MIC at which 90% of the isolates are inhibited [MIC
90
], ≤0.5 μg/ml).
Candida albicans
was the most susceptible species (MIC
90
, 0.06 μg/ml) and
Candida glabrata
and
Candida krusei
were the least (MIC
90
, 1 μg/ml). Voriconazole was more active than amphotericin B and 5FC against all species except
C. glabrata
and was also more active than itraconazole and fluconazole. For isolates of
Candida
spp. with decreased susceptibility to fluconazole and itraconazole MICs of voriconazole were also higher. Based on these results, voriconazole has promising antifungal activity and further in vitro and in vivo investigations are warranted.
Granulocyte Colony-Stimulating Factor and Azole Antifungal Therapy in Murine Aspergillosis: Role of Immune Suppression
Authors: Graybill John R. , Bocanegra Rosie , Najvar Laura K. , Loebenberg David , Luther Mike F. 
Published: October 2018

ABSTRACT

Outbred ICR mice were immune suppressed either with hydrocortisone or with 5-fluorouracil and were infected intranasally with
Aspergillus fumigatus
. Beginning 3 days before infection some groups of mice were given recombinant human granulocyte colony-stimulating factor (G-CSF), SCH56592 (an antifungal triazole), or both. Corticosteroid-pretreated mice responded to SCH56592 and had reduced counts in lung tissue and prolonged survival. In these mice, G-CSF strongly antagonized the antifungal activity of SCH56592. Animals treated with both agents developed large lung abscesses with polymorphonuclear leukocytes and large amounts of
Aspergillus
. In contrast, mice made neutropenic with 5-fluorouracil and then infected with
A. fumigatus
conidia benefited from either G-CSF or triazoles, and the effect of the combination was additive rather than antagonistic. Host predisposing factors contribute in different ways to the outcome of growth factor therapy in aspergillosis.
In Vitro and In Vivo Efficacy of the Triazole TAK-187 against
Cryptococcus neoformans
Authors: Schell Wiley A. , De Almeida Gisele Madeira Duboc , Dodge Richard K. , Okonogi Kenji , Perfect John R. 
Published: October 2018

ABSTRACT

Multiple isolates of
Cryptococcus neoformans
, including those with fluconazole resistance, were tested to assess the in vitro activity of the new triazole TAK-187. MICs of TAK-187 were at least eightfold lower than those of fluconazole, and fungicidal concentrations for most isolates were 4 μg/ml or less. TAK-187 also was evaluated as intermittent therapy using two dosages in a rabbit model of experimental cryptococcal meningitis. Compared to daily treatment with fluconazole, as little as two doses of TAK-187 given 7 days apart were found to be effective. Plasma and cerebrospinal fluid TAK-187 concentrations were many times higher than MICs and fungicidal concentrations. Based upon its therapeutic efficacy and long half-life in the rabbit model, TAK-187 should be investigated for intermittent dosing in treatment or suppression of cryptococcal infections in humans.
gyrA
Mutations Associated with Fluoroquinolone Resistance in Eight Species of
Enterobacteriaceae
Authors: Weigel Linda M. , Steward Christine D. , Tenover Fred C. 
Published: October 2018

ABSTRACT

Fluoroquinolone resistance (FQ-R) in clinical isolates of
Enterobacteriaceae
species has been reported with increasing frequency in recent years. Two mechanisms of FQ-R have been identified in gram-negative organisms: mutations in DNA gyrase and reduced intracellular drug accumulation. A single point mutation in
gyrA
has been shown to reduce susceptibility to fluoroquinolones. To determine the extent of
gyrA
mutations associated with FQ-R in enteric bacteria, one set of oligonucleotide primers was selected from conserved sequences in the flanking regions of the quinolone resistance-determining regions (QRDR) of
Escherichia coli
and
Klebsiella pneumoniae
. This set of primers was used to amplify and sequence the QRDRs from 8
Enterobacteriaceae
type strains and 60 fluoroquinolone-resistant clinical isolates of
Citrobacter freundii
,
Enterobacter aerogenes
,
Enterobacter cloacae
,
E. coli
,
K. pneumoniae
,
Klebsiella oxytoca
,
Providencia stuartii
, and
Serratia marcescens
. Although similarity of the nucleotide sequences of seven species ranged from 80.8 to 93.3%, when compared with that of
E. coli
, the amino acid sequences of the
gyrA
QRDR were highly conserved. Conservative amino acid substitutions were detected in the QRDRs of the susceptible type strains of
C. freundii
,
E. aerogenes
,
K. oxytoca
(Ser-83 to Thr), and
P. stuartii
(Asp-87 to Glu). Strains with ciprofloxacin MICs of >2 μg/ml expressed amino acid substitutions primarily at the Gly-81, Ser-83, or Asp-87 position. Fluoroquinolone MICs varied significantly for strains exhibiting identical
gyrA
mutations, indicating that alterations outside
gyrA
contribute to resistance. The type and position of amino acid alterations also differed among these six genera. High-level FQ-R frequently was associated with single
gyrA
mutations in all species of
Enterobacteriaceae
in this study except
E. coli.
In Vitro Studies of Pharmacodynamic Properties of Vancomycin against
Staphylococcus aureus
and
Staphylococcus epidermidis
Authors: Löwdin E. , Odenholt I. , Cars O. 
Published: October 2018

ABSTRACT

The bactericidal activities of vancomycin against two reference strains and two clinical isolates of
Staphylococcus aureus
and
Staphylococcus epidermidis
were studied with five different concentrations ranging from 2× to 64× the MIC. The decrease in the numbers of CFU at 24 h was at least 3 log
10
CFU/ml for all strains. No concentration-dependent killing was observed. The postantibiotic effect (PAE) was determined by obtaining viable counts for two of the reference strains, and the viable counts varied markedly: 1.2 h for
S. aureus
and 6.0 h for
S. epidermidis
. The determinations of the PAE, the postantibiotic sub-MIC effect (PA SME), and the sub-MIC effect (SME) for all strains were done with BioScreen C, a computerized incubator for bacteria. The PA SMEs were longer than the SMEs for all strains tested. A newly developed in vitro kinetic model was used to expose the bacteria to continuously decreasing concentrations of vancomycin. A filter prevented the loss of bacteria during the experiments. One reference strain each of
S. aureus
and
S. epidermidis
and two clinical isolates of
S. aureus
were exposed to an initial concentration of 10× the MIC of vancomycin with two different half-lives (
t
1/2
s): 1 or 5 h. The post-MIC effect (PME) was calculated as the difference in time for the bacteria to grow 1 log
10
CFU/ml from the numbers of CFU obtained at the time when the MIC was reached and the corresponding time for an unexposed control culture. The difference in PME between the strains was not as pronounced as that for the PAE. Furthermore, the PME was shorter when a
t
1/2
of 5 h (approximate terminal
t
1/2
in humans) was used. The PMEs at
t
1/2
s of 1 and 5 h were 6.5 and 3.6 h, respectively, for
S. aureus
. The corresponding figures for
S. epidermidis
were 10.3 and less than 6 h. The shorter PMEs achieved with a
t
1/2
of 5 h and the lack of concentration-dependent killing indicate that the time above the MIC is the parameter most important for the efficacy of vancomycin.
In Vitro Activities of 15 Antimicrobial Agents against Clinical Isolates of South African Enterococci
Authors: Struwig M. C. , Botha P. L. , Chalkley L. J. 
Published: October 2018

ABSTRACT

The activities of a panel of currently available antibiotics and the investigational agents LY 333328, linezolid, CL 331,002, CL 329,998, moxifloxacin (BAY 12-8039), trovafloxacin, and quinupristin-dalfopristin against 274 clinical isolates of enterococci were determined. No vancomycin resistance or β-lactamase production was observed. Except for 12 isolates (all non-
Enterococcus faecalis
) showing reduced susceptibility to quinupristin-dalfopristin (MIC, ≥4 μg/ml), the new agents exhibited promising in vitro antienterococcal activity.
MIC-Based Interspecies Prediction of the Antimicrobial Effects of Ciprofloxacin on Bacteria of Different Susceptibilities in an In Vitro Dynamic Model
Authors: Firsov Alexander A. , Vostrov Sergey N. , Shevchenko Alexander A. , Zinner Stephen H. , Cornaglia Giuseppe , Portnoy Yury A. 
Published: October 2018

ABSTRACT

Multiple predictors of fluoroquinolone antimicrobial effects (AMEs) are not usually examined simultaneously in most studies. To compare the predictive potentials of the area under the concentration-time curve (AUC)-to-MIC ratio (AUC/MIC), the AUC above MIC (AUC
eff
), and the time above MIC (
T
eff
), the kinetics of killing and regrowth of four bacterial strains exposed to monoexponentially decreasing concentrations of ciprofloxacin were studied in an in vitro dynamic model. The MICs of ciprofloxacin for clinical isolates of
Staphylococcus aureus
,
Escherichia coli
11775 (I) and 204 (II), and
Pseudomonas aeruginosa
were 0.6, 0.013, 0.08, and 0.15 μg/ml, respectively. The simulated values of AUC were designed to provide similar 1,000-fold (
S. aureus
,
E. coli
I, and
P. aeruginosa
) or 2,000-fold (
E. coli
II) ranges of the AUC/MIC. In each case except for the highest AUC/MIC ratio, the observation periods included complete regrowth in the time-kill curve studies. The AME was expressed by its intensity,
I
E
(the area between the control growth and time-kill and regrowth curves up to the point where the viable counts of regrowing bacteria are close to the maximum values observed without drug). For most AUC ranges the
I
E
-AUC curves were fitted by an
E
max
(maximal effect) model, whereas the effects observed at very high AUCs were greater than those predicted by the model. The AUCs that produced 50% of maximal AME were proportional to the MICs for the strains studied, but maximal AMEs (
I

E
max

) and the extent of sigmoidicity (
s
) were not related to the MIC. Both
T
eff
and log AUC/MIC correlated well with
I
E
(
r
2
= 0.98 in both cases) in a species-independent fashion. Unlike
T
eff
or log AUC/MIC, a specific relationship between
I
E
and log AUC
eff
was inherent in each strain. Although each
I
E
and log AUC
eff
plot was fitted by linear regression (
r
2
= 0.97 to 0.99), these plots were not superimposed and therefore are bacterial species dependent. Thus, AUC/MIC and
T
eff
were better predictors of ciprofloxacin’s AME than AUC
eff
. This study suggests that optimal predictors of the AME produced by a given quinolone (intraquinolone predictors) may be established by examining its AMEs against bacteria of different susceptibilities.
T
eff
was shown previously also to be the best interquinolone predictor, but unlike AUC/MIC, it cannot be used to compare different quinolones. AUC/MIC might be the best predictor of the AME in comparisons of different quinolones.
Effects of
Salmonella typhimurium
Infection and Ofloxacin Treatment on Glucose and Glutamine Metabolism in Caco-2/TC-7 Cells
Authors: Posho Leta , Delbos-Bocage Laurence , Gueylard Delphine , Farinotti Robert , Carbon Claude 
Published: October 2018

ABSTRACT

The effects of both
Salmonella typhimurium
infection and 5 mM ofloxacin treatment on 2 mM glutamine and 5 mM glucose metabolism in the enterocyte-like Caco-2/TC-7 cell line were studied. These cells utilized glutamine (212.07 ± 16.75 [mean ± standard deviation] nmol per h per 10
6
viable cells) and, to a lesser extent, glucose (139.63 ± 11.52 nmol per h per 10
6
viable cells). Metabolism of these substrates in Caco-2/TC-7 cells resembled that in rat, pig, or human enterocytes. Infection by
S. typhimurium
C53-enhanced glucose and glutamine substrate utilization by 32 and 22%, respectively and enhanced glucose and glutamine substrate oxidation by eight- and twofold, respectively. These increases in glucose and glutamine metabolism (especially glucose metabolism) were due in part to the metabolism of intracellular bacteria and/or to the activation of cellular metabolism. Substrate metabolism (especially glucose metabolism) in C53-infected cells was partially reduced by treatment with ofloxacin. It was concluded that cellular fuel metabolism is stimulated at the earliest stage of infection (3 to 4 h) and that treatment with 5 mM ofloxacin does not completely restore substrate metabolism to the levels observed in uninfected cells, possibly because this treatment does not eradicate intracellular
S. typhimurium
completely.
Central Role of Hemoglobin Degradation in Mechanisms of Action of 4-Aminoquinolines, Quinoline Methanols, and Phenanthrene Methanols
Authors: Mungthin Mathirut , Bray Patrick G. , Ridley Robert G. , Ward Stephen A. 
Published: October 2018

ABSTRACTWe have used a specific inhibitor of the malarial aspartic proteinase plasmepsin I and a nonspecific cysteine proteinase inhibitor to investigate the importance of hemoglobin degradation in the mechanism of action of chloroquine, amodiaquine, quinine, mefloquine (MQ), halofantrine, and primaquine. Both proteinase inhibitors antagonized the antiparasitic activity of all drugs tested with the exception of primaquine. An inhibitor of plasmepsin I, Ro40-4388, reduced the incorporation of radiolabelled chloroquine and quinine into malarial pigment by 95%, while causing a 70% reduction in the incorporation of radiolabelled MQ. Cysteine proteinase inhibitor E64 reduced the incorporation of chloroquine and quinine into malarial pigment by 60 and 40%, respectively. This study provides definitive support for the central role of hemoglobin degradation in the mechanism of action of the 4-aminoquinolines and the quinoline and phenanthrene methanol antimalarials.
Quinolone Resistance Mutations in the GrlB Protein of
Staphylococcus aureus
Authors: Tanaka Mayumi , Onodera Yoshikuni , Uchida Yoko , Sato Kenichi 
Published: October 2018

ABSTRACT

Two altered GrlB proteins (one with an Asp-432→Asn alteration and one with an Asn-470→Asp alteration) of
Staphylococcus aureus
were purified as fusion proteins to maltose-binding protein. The 50% inhibitory concentrations of levofloxacin were 14 and 3.4 μg/ml against topoisomerase IV containing GrlB proteins with alterations at positions 432 and 470, respectively. These results suggest that the alteration of Asp to Asn at position 432 may be responsible for quinolone resistance.
Outbreak of Ceftazidime-Resistant
Klebsiella pneumoniae
in a Pediatric Hospital in Warsaw, Poland: Clonal Spread of the TEM-47 Extended-Spectrum β-Lactamase (ESBL)-Producing Strain and Transfer of a Plasmid Carrying the SHV-5-Like ESBL-Encoding Gene
Authors: Gniadkowski Marek , Pałucha Andrzej , Grzesiowski Paweł , Hryniewicz Waleria 
Published: October 2018

ABSTRACT

In 1996 a large, 300-bed pediatric hospital in Warsaw, Poland, started a program of monitoring infections caused by extended-spectrum β-lactamase (ESBL)-producing microorganisms. Over the first 3-month period eight
Klebsiella pneumoniae
isolates were identified as being resistant to ceftazidime. Six of these were found to produce the TEM-47 ESBL, which we first described in a
K. pneumoniae
strain recovered a year before in a pediatric hospital in Łódź, Poland, which is 140 km from Warsaw. Typing results revealed a very close relatedness among all these isolates, which suggested that the clonal outbreak in Warsaw was caused by a strain possibly imported from Łódź. The remaining two isolates expressed the SHV-5-like ESBL, which resulted from the horizontal transfer of a plasmid carrying the
bla
SHV
gene between nonrelated strains. The data presented here exemplify the complexity of the epidemiological situation concerning ESBL producers typical for large Polish hospitals, in which no ESBL-monitoring programs were in place prior to 1995.