bluuebunny/crossref_metadata_2025_split huggingface dataset:
Successful Salvage of Central Venous Catheters in Patients with Catheter-Related or Central Line-Associated Bloodstream Infections by Using a Catheter Lock Solution Consisting of Minocycline, EDTA, and 25% Ethanol
Authors: Raad Issam , Chaftari Anne-Marie , Zakhour Ramia , Jordan Mary , Al Hamal Zanaib , Jiang Ying , Yousif Ammar , Garoge Kumait , Mulanovich Victor , Viola George M. , Kanj Soha , Pravinkumar Egbert , Rosenblatt Joel , Hachem Ray 
Published: March 2016

ABSTRACT

In cancer patients with long-term central venous catheters (CVC), removal and reinsertion of a new CVC at a different site might be difficult because of the unavailability of accessible vascular sites.
In vitro
and animal studies showed that a minocycline-EDTA-ethanol (M-EDTA-EtOH) lock solution may eradicate microbial organisms in biofilms, hence enabling the treatment of central line-associated bloodstream infections (CLABSI) while retaining the catheter
in situ
. Between April 2013 and July 2014, we enrolled 30 patients with CLABSI in a prospective study and compared them to a historical group of 60 patients with CLABSI who had their CVC removed and a new CVC inserted. Each catheter lumen was locked with an M-EDTA-EtOH solution for 2 h administered once daily, for a total of 7 doses. Patients who received locks had clinical characteristics that were comparable to those of the control group. The times to fever resolution and microbiological eradication were similar in the two groups. Patients with the lock intervention received a shorter duration of systemic antibiotic therapy than that of the control patients (median, 11 days versus 16 days, respectively;
P
< 0.0001), and they were able to retain their CVCs for a median of 74 days after the onset of bacteremia. The M-EDTA-EtOH lock was associated with a significantly decreased rate of mechanical and infectious complications compared to that of the CVC removal/reinsertion group, who received a longer duration of systemic antimicrobial therapy. (This study has been registered at ClinicalTrials.gov under registration no. NCT01539343.)
In Vitro
and
In Vivo
Activities of 2,3-Diarylsubstituted Quinoxaline Derivatives against Leishmania amazonensis
Authors: Kaplum Vanessa , Cogo Juliana , Sangi Diego Pereira , Ueda-Nakamura Tânia , Corrêa Arlene Gonçalves , Nakamura Celso Vataru 
Published: March 2016

ABSTRACT

Leishmaniasis is endemic in 98 countries and territories worldwide. The therapies available for leishmaniasis have serious side effects, thus prompting the search for new therapies. The present study investigated the antileishmanial activities of 2,3-diarylsubstituted quinoxaline derivatives against
Leishmania amazonensis
. The antiproliferative activities of 6,7-dichloro-2,3-diphenylquinoxaline (LSPN329) and 2,3-di-(4-methoxyphenyl)-quinoxaline (LSPN331) against promastigotes and intracellular amastigotes were assessed, and the cytotoxicities of LSPN329 and LSPN331 were determined. Morphological and ultrastructural alterations were examined by electron microscopy, and biochemical alterations, reflected by the mitochondrial membrane potential (ΔΨm), mitochondrial superoxide anion (O
2
·
−
) concentration, the intracellular ATP concentration, cell volume, the level of phosphatidylserine exposure on the cell membrane, cell membrane integrity, and lipid inclusions, were evaluated.
In vivo
antileishmanial activity was evaluated in a murine cutaneous leishmaniasis model. Compounds LSPN329 and LSPN331 showed significant selectivity for promastigotes and intracellular amastigotes and low cytotoxicity. In promastigotes, ultrastructural alterations were observed, including an increase in lipid inclusions, concentric membranes, and intense mitochondrial swelling, which were associated with hyperpolarization of ΔΨm, an increase in the O
2
·
−
concentration, decreased intracellular ATP levels, and a decrease in cell volume. Phosphatidylserine exposure and DNA fragmentation were not observed. The cellular membrane remained intact after treatment. Thus, the multifactorial response that was responsible for the cellular collapse of promastigotes was based on intense mitochondrial alterations. BALB/c mice treated with LSPN329 or LSPN331 showed a significant decrease in lesion thickness in the infected footpad. Therefore, the antileishmanial activity and mitochondrial mechanism of action of LSPN329 and LSPN331 and the decrease in lesion thickness
in vivo
brought about by LSPN329 and LSPN331 make them potential candidates for new drug development for the treatment of leishmaniasis.
Assessing Predictive Performance of Published Population Pharmacokinetic Models of Intravenous Tobramycin in Pediatric Patients
Authors: Bloomfield Celeste , Staatz Christine E. , Unwin Sean , Hennig Stefanie 
Published: March 2016

ABSTRACT
Several population pharmacokinetic models describe the dose-exposure relationship of tobramycin in pediatric patients. Before the implementation of these models in clinical practice for dosage adjustment, their predictive performance should be externally evaluated. This study tested the predictive performance of all published population pharmacokinetic models of tobramycin developed for pediatric patients with an independent patient cohort. A literature search was conducted to identify suitable models for testing. Demographic and pharmacokinetic data were collected retrospectively from the medical records of pediatric patients who had received intravenous tobramycin. Tobramycin exposure was predicted from each model. Predictive performance was assessed by visual comparison of predictions to observations, by calculation of bias and imprecision, and through the use of simulation-based diagnostics. Eight population pharmacokinetic models were identified. A total of 269 concentration-time points from 41 pediatric patients with cystic fibrosis were collected for external evaluation. Three models consistently performed best in all evaluations and had mean errors ranging from −0.4 to 1.8 mg/liter, relative mean errors ranging from 4.9 to 29.4%, and root mean square errors ranging from 47.8 to 66.9%. Simulation-based diagnostics supported these findings. Models that allowed a two-compartment disposition generally had better predictive performance than those that used a one-compartment disposition model. Several published models of the pharmacokinetics of tobramycin showed reasonable low levels of bias, although all models seemed to have some problems with imprecision. This suggests that knowledge of typical pharmacokinetic behavior and patient covariate values alone without feedback concentration measurements from individual patients is not sufficient to make precise predictions.
Effects of Saline, an Ambient Acidic Environment, and Sodium Salicylate on OXA-Mediated Carbapenem Resistance in Acinetobacter baumannii
Authors: Zander Esther , Seifert Harald , Higgins Paul G. 
Published: March 2016

ABSTRACT

Different physiological conditions, such as NaCl, low pH, and sodium salicylate, have been shown to affect antibiotic resistance determinants in
Acinetobacter baumannii
isolates. Therefore, the aim of this study was to investigate the effects of NaCl, sodium salicylate, and low pH on the susceptibility of
A. baumannii
to carbapenem. We cloned genes encoding oxacillinases (OXA) of different subclasses, with their associated promoters, from carbapenem-resistant
A. baumannii
isolates into the same vector and transferred them to the
A. baumannii
reference strains ATCC 19606 and ATCC 17978. Carbapenem MICs were determined at least in triplicate by agar dilution under standard conditions, as well as in the presence of 200 mM NaCl or 16 mM sodium salicylate, or at pH 5.8. OXA-58-like gene expression was determined by reverse transcription-quantitative PCR (qRT-PCR). Under some experimental conditions, significant MIC reductions were shown for some transformants but not for others. Only in one instance were all transformants harboring the same OXA affected by the same condition: at pH 5.8, the imipenem and meropenem MICs for strains expressing OXA-58-like enzymes decreased from a resistant level (32 to 64 mg/liter) to an intermediate-susceptible level (8 mg/liter). However,
bla
OXA-58-like
gene expression remained the same. MICs for both wild-type reference strains were not affected by the conditions tested. Our results indicate that the effects of the experimental conditions tested on OXA
in vivo
are mostly strain dependent. MICs were not reduced to wild-type levels, suggesting that the conditions tested do not lead to complete OXA inhibition in the bacterial cell.
N
-Formyl-Perosamine Surface Homopolysaccharides Hinder the Recognition of Brucella abortus by Mouse Neutrophils
Authors: Mora-Cartín Ricardo , Chacón-Díaz Carlos , Gutiérrez-Jiménez Cristina , Gurdián-Murillo Stephany , Lomonte Bruno , Chaves-Olarte Esteban , Barquero-Calvo Elías , Moreno Edgardo 
Published: March 2016

ABSTRACT

Brucella abortus
is an intracellular pathogen of monocytes, macrophages, dendritic cells, and placental trophoblasts. This bacterium causes a chronic disease in bovines and in humans. In these hosts, the bacterium also invades neutrophils; however, it fails to replicate and just resists the killing action of these leukocytes without inducing significant activation or neutrophilia. Moreover,
B. abortus
causes the premature cell death of human neutrophils. In the murine model, the bacterium is found within macrophages and dendritic cells at early times of infection but seldom in neutrophils. Based on this observation, we explored the interaction of mouse neutrophils with
B. abortus
. In contrast to human, dog, and bovine neutrophils, naive mouse neutrophils fail to recognize smooth
B. abortus
bacteria at early stages of infection. Murine normal serum components do not opsonize smooth
Brucella
strains, and neutrophil phagocytosis is achieved only after the appearance of antibodies. Alternatively, mouse normal serum is capable of opsonizing rough
Brucella
mutants. Despite this, neutrophils still fail to kill
Brucella
, and the bacterium induces cell death of murine leukocytes. In addition, mouse serum does not opsonize
Yersinia enterocolitica
O:9, a bacterium displaying the same surface polysaccharide antigen as smooth
B. abortus
. Therefore, the lack of murine serum opsonization and absence of murine neutrophil recognition are specific, and the molecules responsible for the
Brucella
camouflage are
N
-formyl-perosamine surface homopolysaccharides. Although the mouse is a valuable model for understanding the immunobiology of brucellosis, direct extrapolation from one animal system to another has to be undertaken with caution.
Teichoic Acid Polymers Affect Expression and Localization of
dl
-Endopeptidase LytE Required for Lateral Cell Wall Hydrolysis in Bacillus subtilis
Authors: Kasahara Jun , Kiriyama Yuuka , Miyashita Mari , Kondo Takuma , Yamada Takeshi , Yazawa Kazuya , Yoshikawa Ritsuko , Yamamoto Hiroki 
Published: March 2016

ABSTRACT

In
Bacillus subtilis
, the
dl
-endopeptidase LytE is responsible for lateral peptidoglycan hydrolysis during cell elongation. We found that σ
I
-dependent transcription of
lytE
is considerably enhanced in a strain with a mutation in
ltaS
, which encodes a major lipoteichoic acid (LTA) synthase. Similar enhancements were observed in mutants that affect the glycolipid anchor and wall teichoic acid (WTA) synthetic pathways. Immunofluorescence microscopy revealed that the LytE foci were considerably increased in these mutants. The localization patterns of LytE on the sidewalls appeared to be helix-like in LTA-defective or WTA-reduced cells and evenly distributed on WTA-depleted or -defective cell surfaces. These results strongly suggested that LTA and WTA affect both σ
I
-dependent expression and localization of LytE. Interestingly, increased LytE localization along the sidewall in the
ltaS
mutant largely occurred in an MreBH-independent manner. Moreover, we found that cell surface decorations with LTA and WTA are gradually reduced at increased culture temperatures and that LTA rather than WTA on the cell surface is reduced at high temperatures. In contrast, the amount of LytE on the cell surface gradually increased under heat stress conditions. Taken together, these results indicated that reductions in these anionic polymers at high temperatures might give rise to increases in SigI-dependent expression and cell surface localization of LytE at high temperatures.

IMPORTANCE
The bacterial cell wall is required for maintaining cell shape and bearing environmental stresses. The Gram-positive cell wall consists of mesh-like peptidoglycan and covalently linked wall teichoic acid and lipoteichoic acid polymers. It is important to determine if these anionic polymers are required for proliferation and environmental adaptation. Here, we demonstrated that these polymers affect the expression and localization of a peptidoglycan hydrolase LytE required for lateral cell wall elongation. Moreover, we found that cell surface decorations with teichoic acid polymers are substantially decreased at high temperatures and that the peptidoglycan hydrolase is consequently increased. These findings suggest that teichoic acid polymers control lateral peptidoglycan hydrolysis by LytE, and bacteria drastically change their cell wall content to adapt to their environment.
Effects of Lipopolysaccharide Core Sugar Deficiency on Colanic Acid Biosynthesis in Escherichia coli
Authors: Ren Ge , Wang Zhou , Li Ye , Hu Xiaoqing , Wang Xiaoyuan 
Published: March 2016

ABSTRACT

When 10
Escherichia coli
mutant strains with defects in lipopolysaccharide (LPS) core biosynthesis were grown on agar medium at 30°C, four of them, the Δ
waaF
, Δ
waaG
, Δ
waaP
, and Δ
waaB
strains, formed mucoid colonies, while the other six, the Δ
waaU
, Δ
waaR
, Δ
waaO
, Δ
waaC
, Δ
waaQ
, and Δ
waaY
strains, did not. Using light microscopy with tannin mordant staining, the presence of exopolysaccharide around the cells of the mutants that formed mucoid colonies could be discerned. The Δ
waaF
mutant produced the largest amounts of exopolysaccharide, regardless of whether it was grown on agar or in liquid medium. The exopolysaccharide was isolated from the liquid growth medium of Δ
waaF
cells, hydrolyzed, and analyzed by high-performance liquid chromatography with an ion-exchange column, and the results indicated that the exopolysaccharide was consistent with colanic acid. When the key genes related to the biosynthesis of colanic acid, i.e.,
wza
,
wzb
,
wzc
, and
wcaA
, were deleted in the Δ
waaF
background, the exopolysaccharide could not be produced any more, further confirming that it was colanic acid. Colanic acid could not be produced in strains in which
rcsA
,
rcsB
,
rcsD
, or
rcsF
was deleted in the Δ
waaF
background, but a reduced level of colanic acid production was detected when the
rcsC
gene was deleted, suggesting that a change of lipopolysaccharide structure in Δ
waaF
cells might be sensed by the RcsCDB phosphorelay system, leading to the production of colanic acid. The results demonstrate that
E. coli
cells can activate colanic acid production through the RcsCDB phosphorelay system in response to a structural deficiency of lipopolysaccharide.

IMPORTANCE
Lipopolysaccharide and colanic acid are important forms of exopolysaccharide for
Escherichia coli
cells. Their metabolism and biological significance have been investigated, but their interrelation with the cell stress response process is not understood. This study demonstrates, for the first time, that
E. coli
cells can activate colanic acid production through the RcsCDB phosphorelay system in response to a structural change of lipopolysaccharide, suggesting that bacterial cells can monitor the outer membrane integrity, which is essential for cell survival and damage repair.
Fortification of alcoholic beverages (12% v/v) with tea (Camellia sinensis) reduces harmful effects of alcohol ingestion and metabolism in mouse model
Authors: Ochanda S O , Rashid K , Wanyoko J K , Ngotho M , Faraj A K , Onyango C A , Wachira F N , Maranga D N 
Published: March 2016

BackgroundAn animal model was used to study the health benefits inherent in tea fortified alcoholic beverages fed to laboratory mice.ObjectivesAn investigation of the effects of tea fortified alcoholic beverages 12% alcohol (v/v) on antioxidant capacity and liver dysfunction indicators in white Swiss mice including packed cell volume (PCV), albumin, total protein, alkaline phosphatase (ALP) and glutathione (GSH) was carried out.MethodsPlain, black, green and purple tea fortified alcohols were developed with varying tea concentrations of 1, 2 and 4 g/250 mL in 12% v/v. Control alcoholic beverages without teas were also developed. A permit (number IRC/13/12) was obtained for the animal research from the National Museums of Kenya, Institute of Primate Research prior to the start of the study. Alcoholic beverages were orally administered every 2 days for 4 weeks at 1 mL per mouse, and thereafter animals were euthanised and liver and blood samples harvested for analyses. Assays on body weight (bwt), packed cell volume (PCV) albumin, total protein, ALP and GSH were performed. Results were statistically analysed using GraphPad statistical package and significant differences of means of various treatments determined.ResultsConsumption of tea fortified alcohols significantly decreased (p=0.0001)bwtat 0.32–9.58% and PCV at 5.56–22.75% for all teas. Total protein in serum and liver of mice fed on different tea fortified alcohols ranged between 6.26 and 9.24 g/dL and 2.14 and 4.02 g/dL, respectively. Albumin, ALP and GSH range was 0.92–2.88 µg/L, 314.98–473.80 µg/L and 17.88–28.62 µM, respectively. Fortification of alcoholic beverages lowered liver ALP, replenished antioxidants and increased liver albumin, improving the nutritional status of the mice.ConclusionsThe findings demonstrate tea's hepatoprotective mechanisms against alcohol-induced injury through promotion of endogenous antioxidants. The beneficial effects of tea in the fortified alcoholic beverages could be used to develop safer alcoholic beverages.