bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Systematic Review of Dietary Protein During Caloric Restriction in Resistance Trained Lean Athletes: A Case for Higher Intakes
Authors: Helms Eric R. , Zinn Caryn , Rowlands David S. , Brown Scott R. 
Published: May 2014

Caloric restriction occurs when athletes attempt to reduce body fat or make weight. There is evidence that protein needs increase when athletes restrict calories or have low body fat.Purpose:The aims of this review were to evaluate the effects of dietary protein on body composition in energy-restricted resistance-trained athletes and to provide protein recommendations for these athletes.Methods:Database searches were performed from earliest record to July 2013 using the terms protein, and intake, or diet, and weight, or train, or restrict, or energy, or strength, and athlete. Studies (N = 6) needed to use adult (≥ 18 yrs), energy-restricted, resistance-trained (> 6 months) humans of lower body fat (males ≤ 23% and females ≤ 35%) performing resistance training. Protein intake, fat free mass (FFM) and body fat had to be reported.Results:Body fat percentage decreased (0.5–6.6%) in all study groups (N = 13) and FFM decreased (0.3–2.7kg) in nine of 13. Six groups gained, did not lose, or lost nonsignificant amounts of FFM. Five out of these six groups were among the highest in body fat, lowest in caloric restriction, or underwent novel resistance training stimuli. However, the one group that was not high in body fat that underwent substantial caloric restriction, without novel training stimuli, consumed the highest protein intake out of all the groups in this review (2.5–2.6g/kg).Conclusions:Protein needs for energy-restricted resistance-trained athletes are likely 2.3–3.1g/kg of FFM scaled upwards with severity of caloric restriction and leanness.
Effect of Sodium Bicarbonate and Beta-Alanine on Repeated Sprints During Intermittent Exercise Performed in Hypoxia
Authors: Saunders Bryan , Sale Craig , Harris Roger C. , Sunderland Caroline 
Published: May 2014

Purpose:To investigate the separate and combined effects of sodium bicarbonate and beta-alanine supplementation on repeated sprints during simulated match play performed in hypoxia.Methods:Study A: 20 recreationally active participants performed two trials following acute supplementation with either sodium bicarbonate (0.3 g·kg−1BM) or placebo (maltodextrin). Study B: 16 recreationally active participants were supplemented with either a placebo or beta-alanine for 5 weeks (6.4 g·day−1 for 4 weeks, 3.2 g·day−1 for 1 week), and performed one trial before supplementation (with maltodextrin) and two following supplementation (with sodium bicarbonate and maltodextrin). Trials consisted of 3 sets of 5 × 6 s repeated sprints performed during a football specific intermittent treadmill protocol performed in hypoxia (15.5% O2). Mean (MPO) and peak (PPO) power output were recorded as the performance measures.Results:Study A: Overall MPO was lower with sodium bicarbonate than placebo (p = .02, 539.4 ± 84.5 vs. 554.0 ± 84.6 W), although there was no effect across sets (all p > .05). Study B: There was no effect of beta-alanine, or cosupplementation with sodium bicarbonate, on either parameter, although there was a trend toward higher MPO with sodium bicarbonate (p = .07).Conclusions:The effect of sodium bicarbonate on repeated sprints was equivocal, although there was no effect of beta-alanine or cosupplementation with sodium bicarbonate. Individual variation may have contributed to differences in results with sodium bicarbonate, although the lack of an effect with beta-alanine suggests this type of exercise may not be influenced by increased buffering capacity.
Inhibition of Foamy Virus Reverse Transcriptase by Human Immunodeficiency Virus Type 1 RNase H Inhibitors
Authors: Corona Angela , Schneider Anna , Schweimer Kristian , Rösch Paul , Wöhrl Birgitta M. , Tramontano Enzo 
Published: May 2014

ABSTRACTRNase H plays an essential role in the replication of human immunodeficiency virus type 1 (HIV-1). Therefore, it is a promising target for drug development. However, the identification of HIV-1 RNase H inhibitors (RHIs) has been hampered by the open morphology of its active site, the limited number of available RNase H crystal structures in complex with inhibitors, and the fact that, due to the high concentrations of Mg2+needed for protein stability, HIV-1 RNase H is not suitable for nuclear magnetic resonance (NMR) inhibitor studies. We recently showed that the RNase H domains of HIV-1 and prototype foamy virus (PFV) reverse transcriptases (RTs) exhibit a high degree of structural similarity. Thus, we examined whether PFV RNase H can serve as an HIV-1 RNase H model for inhibitor interaction studies. Five HIV-1 RHIs inhibited PFV RNase H activity at low-micromolar concentrations similar to those of HIV-1 RNase H, suggesting pocket similarity of the RNase H domains. NMR titration experiments with the PFV RNase H domain and the RHI RDS1643 (6-[1-(4-fluorophenyl)methyl-1H-pyrrol-2-yl)]-2,4-dioxo-5-hexenoic acid ethyl ester) were performed to determine its binding site. Based on these results and previous data,in silicodocking analysis showed a putative RDS1643 binding region that reaches into the PFV RNase H active site. Structural overlays were performed with HIV-1 and PFV RNase H to propose the RDS1643 binding site in HIV-1 RNase H. Our results suggest that this approach can be used to establish PFV RNase H as a model system for HIV-1 RNase H in order to identify putative inhibitor binding sites in HIV-1 RNase H.
In Vivo
Assessment of Drug Efficacy against Mycobacterium abscessus Using the Embryonic Zebrafish Test System
Authors: Bernut Audrey , Le Moigne Vincent , Lesne Tiffany , Lutfalla Georges , Herrmann Jean-Louis , Kremer Laurent 
Published: May 2014

ABSTRACT

Mycobacterium abscessus
is responsible for a wide spectrum of clinical syndromes and is one of the most intrinsically drug-resistant mycobacterial species. Recent evaluation of the
in vivo
therapeutic efficacy of the few potentially active antibiotics against
M. abscessus
was essentially performed using immunocompromised mice. Herein, we assessed the feasibility and sensitivity of fluorescence imaging for monitoring the
in vivo
activity of drugs against acute
M. abscessus
infection using zebrafish embryos. A protocol was developed where clarithromycin and imipenem were directly added to water containing fluorescent
M. abscessus
-infected embryos in a 96-well plate format. The status of the infection with increasing drug concentrations was visualized on a spatiotemporal level. Drug efficacy was assessed quantitatively by measuring the index of protection, the bacterial burden (CFU), and the number of abscesses through fluorescence measurements. Both drugs were active in infected embryos and were capable of significantly increasing embryo survival in a dose-dependent manner. Protection from bacterial killing correlated with restricted mycobacterial growth in the drug-treated larvae and with reduced pathophysiological symptoms, such as the number of abscesses within the brain. In conclusion, we present here a new and efficient method for testing and compare the
in vivo
activity of two clinically relevant drugs based on a fluorescent reporter strain in zebrafish embryos. This approach could be used for rapid determination of the
in vivo
drug susceptibility profile of clinical isolates and to assess the preclinical efficacy of new compounds against
M. abscessus
.
Penetration of Daptomycin into Bone and Synovial Fluid in Joint Replacement
Authors: Montange D. , Berthier F. , Leclerc G. , Serre A. , Jeunet L. , Berard M. , Muret P. , Vettoretti L. , Leroy J. , Hoen B. , Chirouze C. 
Published: May 2014

ABSTRACT

Daptomycin exhibits clinical activity in the treatment of infections with Gram-positive organisms, including infections due to methicillin-resistant
Staphylococcus aureus
. However, little is known about its penetration into bone and synovial fluid. The aim of our study was to assess the penetration of daptomycin into bone and synovial fluid after a single intravenous administration. This study was conducted in 16 patients who underwent knee or hip replacement and received a single intravenous dose of 8 mg of daptomycin per kg of body weight prior to surgery. Plasma daptomycin concentrations were measured 1 h after the end of daptomycin infusion and when bone fragments were removed. Daptomycin concentrations were also measured on bone fragments and synovial fluid collected at the same time during surgery. All samples were analyzed with a diode array–high-performance liquid chromatography (HPLC) method. After a single-dose intravenous infusion, bone daptomycin concentrations were above the MIC of daptomycin for
Staphylococcus aureus
in all subjects, and the median bone penetration percentage was 9.0% (interquartile range [IQR], 4.4 to 11.4). These results support the use of daptomycin in the treatment of
Staphylococcus aureus
bone and joint infections.
Posaconazole Tablet Pharmacokinetics: Lack of Effect of Concomitant Medications Altering Gastric pH and Gastric Motility in Healthy Subjects
Authors: Kraft Walter K. , Chang Peter S. , van Iersel Marlou L. P. S. , Waskin Hetty , Krishna Gopal , Kersemaekers Wendy M. 
Published: May 2014

ABSTRACT

Posaconazole oral suspension is an extended-spectrum triazole that should be taken with food to maximize absorption. A new posaconazole tablet formulation has demonstrated improved bioavailability over the oral suspension in healthy adults in a fasting state. This study evaluated the effects of concomitant medications altering gastric pH (antacid, ranitidine, and esomeprazole) and gastric motility (metoclopramide) on the pharmacokinetics of posaconazole tablets. This was a prospective open-label 5-way crossover study in 20 healthy volunteers. In each treatment period, a single 400-mg dose (4 100-mg tablets) of posaconazole was administered alone or with 20 ml antacid (2 g of aluminum hydroxide and 2 g of magnesium hydroxide), ranitidine (150 mg), esomeprazole (40 mg), or metoclopramide (15 mg). There was a ≥10-day washout between treatment periods. Posaconazole exposure, time to maximum concentration of drug in serum (
T
max
), and apparent terminal half-life (
t
1/2
) were similar when posaconazole was administered alone or with medications affecting gastric pH and gastric motility. Geometric mean ratios (90% confidence intervals [CIs]) of the area under the concentration-time curve from time zero to infinity (AUC
0–inf
) (posaconazole with medications affecting gastric pH and gastric motility versus posaconazole alone) were 1.03 (0.88–1.20) with antacid, 0.97 (0.84–1.12) with ranitidine, 1.01 (0.87–1.17) with esomeprazole, and 0.93 (0.79–1.09) with metoclopramide. Geometric mean ratios (90% CIs) of the maximum concentration of drug in serum (
C
max
) were 1.06 (0.90–1.26) with antacid, 1.04 (0.88–1.23) with ranitidine, 1.05 (0.89–1.24) with esomeprazole, and 0.86 (0.73–1.02) with metoclopramide. In summary, in healthy volunteers, the pharmacokinetics of a single 400-mg dose of posaconazole tablets was not altered to a clinically meaningful extent when posaconazole was administered alone or with medications affecting gastric pH or gastric motility.
Pediatric Infection and Intestinal Carriage Due to Extended-Spectrum-Cephalosporin-Resistant Enterobacteriaceae
Authors: Zerr Danielle M. , Qin Xuan , Oron Assaf P. , Adler Amanda L. , Wolter Daniel J. , Berry Jessica E. , Hoffman Lucas , Weissman Scott J. 
Published: May 2014

ABSTRACTThe objective of this study is to describe the epidemiology of intestinal carriage with extended-spectrum-cephalosporin-resistantEnterobacteriaceaein children with index infections with these organisms. Patients with resistantEscherichia coliorKlebsiellabacteria isolated from the urine or a normally sterile site between January 2006 and December 2010 were included in this study. Available infection and stool isolates underwent phenotypic and molecular characterization. Clinical data relevant to the infections were collected and analyzed. Overall, 105 patients were identified with 106 extended-spectrum-cephalosporin-resistantE. coli(n= 92) orKlebsiella(n= 14) strains isolated from urine or a sterile site. Among the 27 patients who also had stool screening for resistantEnterobacteriaceae, 17 (63%) had intestinal carriage lasting a median of 199 days (range, 62 to 1,576). There were no significant differences in demographic, clinical, and microbiological variables between those with and those without intestinal carriage. Eighteen (17%) patients had 37 subsequent resistantEnterobacteriaceaeinfections identified: 31 urine and 6 blood. In a multivariable analysis, antibiotic intake in the 91 days prior to subsequent urine culture was significantly associated with subsequent urinary tract infection with a resistant organism (hazard ratio, 14.3; 95% confidence interval [CI], 1.6 to 130.6). Intestinal carriage and reinfection were most commonly due to bacterial strains of the same sequence type and with the same resistance determinants as the index extended-spectrum-cephalosporin-resistantEnterobacteriaceae, but carriage and reinfection with different resistantEnterobacteriaceaestrains also occurred.
Limited Activity of Clofazimine as a Single Drug in a Mouse Model of Tuberculosis Exhibiting Caseous Necrotic Granulomas
Authors: Irwin Scott M. , Gruppo Veronica , Brooks Elizabeth , Gilliland Janet , Scherman Michael , Reichlen Matthew J. , Leistikow Rachel , Kramnik Igor , Nuermberger Eric L. , Voskuil Martin I. , Lenaerts Anne J. 
Published: May 2014

ABSTRACT

New drugs and drugs with a novel mechanism of action are desperately needed to shorten the duration of tuberculosis treatment, to prevent the emergence of drug resistance, and to treat multiple-drug-resistant strains of
Mycobacterium tuberculosis
. Recently, there has been renewed interest in clofazimine (CFZ). In this study, we utilized the C3HeB/FeJ mouse model, possessing highly organized, hypoxic pulmonary granulomas with caseous necrosis, to evaluate CFZ monotherapy in comparison to results with BALB/c mice, which form only multifocal, coalescing cellular aggregates devoid of caseous necrosis. While CFZ treatment was highly effective in BALB/c mice, its activity was attenuated in the lungs of C3HeB/FeJ mice. This lack of efficacy was directly related to the pathological progression of disease in these mice, since administration of CFZ prior to the formation of hypoxic, necrotic granulomas reconstituted bactericidal activity in this mouse strain. These results support the continued use of mouse models of tuberculosis infection which exhibit a granulomatous response in the lungs that more closely resembles the pathology found in human disease.
Anti-Candida Activity of Fluoxetine Alone and Combined with Fluconazole: a Synergistic Action against Fluconazole-Resistant Strains
Authors: Oliveira Ana S. , Gaspar Carlos A. , Palmeira-de-Oliveira Rita , Martinez-de-Oliveira José , Palmeira-de-Oliveira Ana 
Published: May 2014

ABSTRACT

The purpose of this work was to determine the antimicrobial activity of fluoxetine, alone and combined with fluconazole, against 29
Candida
strains isolated from patients with vulvovaginal candidiasis. MIC and minimum lethal concentration values ranged from 9.8 to 625 μg/ml for all strains tested. The combination of fluconazole with fluoxetine resulted in synergistic activity against six
Candida
strains, with fractional inhibitory index (FIX) values between 0.15 and 0.31. An indifferent effect was found for the remaining strains, with FIX values between 0.63 and 1.
Impact of Different Antimicrobial Therapies on Clinical and Fiscal Outcomes of Patients with Bacteremia Due to Vancomycin-Resistant Enterococci
Authors: Hayakawa Kayoko , Martin Emily T. , Gudur Uma Mahesh , Marchaim Dror , Dalle Dalia , Alshabani Khaled , Muppavarapu Kalyan Srinivas , Jaydev Fnu , Bathina Pradeep , Sundaragiri Pranathi Rao , Rajuri Shashi Dhar , Khatri Jaikumar , Pogue Jason M. , Lephart Paul R. , Rybak Michael J. , Kaye Keith S. 
Published: May 2014

ABSTRACT

Vancomycin-resistant enterococci (VRE) are a growing health problem, and uncertainties exist regarding the optimal therapy for bloodstream infection due to VRE. We conducted systematic comparative evaluations of the impact of different antimicrobial therapies on the outcomes of patients with bloodstream infections due to VRE. A retrospective study from January 2008 to October 2010 was conducted at Detroit Medical Center. Unique patients with blood cultures due to VRE were included and reviewed. Three major therapeutic classes were analyzed: daptomycin, linezolid, and β-lactams. Three multivariate models were conducted for each outcome, matching for a propensity score predicting the likelihood of receipt of one of the therapeutic classes. A total of 225 cases of bacteremia due to VRE were included, including 86 (38.2%) cases of VR
Enterococcus faecalis
and 139 (61.8%) of VR
Enterococcus faecium
. Bacteremia due to VR
E. faecalis
was more frequent among subjects treated with β-lactams than among those treated with daptomycin or linezolid. The median dose of daptomycin was 6 mg/kg of body weight (range, 6 to 12 mg/kg). After controlling for propensity score and bacteremia due to VR
E. faecalis
, differences in mortality were nonsignificant among the treatment groups. Therapy with daptomycin was associated with higher median variable direct cost per day than that for linezolid. This large study revealed the three therapeutic classes (daptomycin, linezolid, and β-lactams) are similarly efficacious in the treatment of bacteremia due to susceptible strains of VRE.
Reduced Emergence of Isoniazid Resistance with Concurrent Use of Thioridazine against Acute Murine Tuberculosis
Authors: Dutta Noton K. , Pinn Michael L. , Karakousis Petros C. 
Published: May 2014

ABSTRACT

The repurposing of existing drugs is being pursued as a means by which to accelerate the development of novel regimens for the treatment of drug-susceptible and drug-resistant tuberculosis (TB). In the current study, we assessed the activity of the antipsychotic drug thioridazine (TRZ) in combination with the standard regimen in a well-validated murine TB model. Single-dose and steady-state pharmacokinetic studies were performed in BALB/c mice to establish human-equivalent doses of TRZ. To determine the bactericidal activity of TRZ against TB in BALB/c mice, three separate studies were performed, including a dose-ranging study of TRZ monotherapy and efficacy studies of human-equivalent doses of TRZ with and without isoniazid (INH) or rifampin (RIF). Therapeutic efficacy was assessed by the change in mycobacterial load in the lung. The human-equivalent dose of thioridazine was determined to be 25 mg/kg of body weight, which was well tolerated in mice. TRZ was found to accumulate at high concentrations in lung tissue relative to serum levels. We observed modest synergy during coadministration of TRZ with INH, and the addition of TRZ reduced the emergence of INH-resistant mutants in mouse lungs. In conclusion, this study further illustrates the opportunity to reevaluate the contribution of TRZ to the sterilizing activity of combination regimens to prevent the emergence of drug-resistant
M. tuberculosis
.
Candida glabrata Intra-Abdominal Candidiasis Is Characterized by Persistence within the Peritoneal Cavity and Abscesses
Authors: Cheng Shaoji , Clancy Cornelius J. , Hartman Douglas J. , Hao Binghua , Nguyen M. Hong 
Published: May 2014

ABSTRACT

The pathogenesis of
Candida glabrata
infections is poorly understood. We studied the pathogenesis of intra-abdominal candidiasis (IAC) in mice that were infected intraperitoneally with
C. glabrata
and sterile feces.
C. glabrata
BG2 (5 × 10
8
CFU) caused a 100% mortality rate. Sublethal inocula of BG2 (1 × 10
8
or 1 × 10
7
CFU) caused peritonitis that progressed to abscesses. Three clinical
C. glabrata
strains (5 × 10
8
CFU) caused 80 to 100% mortality rates, while a fourth (strain 346) caused a 29% mortality rate. Following sublethal inocula (1 × 10
7
CFU), the intra-abscess burdens of virulent strain 356 were ∼1 log greater than those of strain 346. A
C. glabrata
Δ
plb1-2
mutant (phospholipase B genes disrupted) killed mice as well as BG2 did. When sublethal inocula were used, however, the Δ
plb1-2
mutant was associated with more rapid abscess resolution and lower intra-abscess burdens; these findings were reversed by
PLB1
and
PLB2
reinsertion. The Δ
plb1-2
mutant was also more susceptible than BG2 to killing by human neutrophils
in vitro
. BG2 and the Δ
plb1-2
mutant were indistinguishable during hematogenously disseminated candidiasis.
C. albicans
SC5314 was more virulent than
C. glabrata
BG2 during IAC, causing a 100% mortality rate following a challenge with 5 × 10
7
CFU. In contrast, a sublethal inoculum (1 × 10
7
CFU) of BG2 caused less neutrophil infiltration and greater burdens in peritoneal fluid than SC5314 did and abscesses that persisted longer and contained greater burdens. In conclusion, a mouse model of
C. glabrata
IAC mimics disease in humans and distinguishes the relative virulence of clinical and gene disruption strains.
C. glabrata
differed from
C. albicans
during IAC by being less lethal and eliciting dampened neutrophil responses but resulting in more persistent peritonitis and abscesses.
Bile Acids and Bicarbonate Inversely Regulate Intracellular Cyclic di-GMP in Vibrio cholerae
Authors: Koestler Benjamin J. , Waters Christopher M. 
Published: May 2014

ABSTRACT

Vibrio cholerae
is a Gram-negative bacterium that persists in aquatic reservoirs and causes the diarrheal disease cholera upon entry into a human host.
V. cholerae
employs the second messenger molecule 3′,5′-cyclic diguanylic acid (c-di-GMP) to transition between these two distinct lifestyles. c-di-GMP is synthesized by diguanylate cyclase (DGC) enzymes and hydrolyzed by phosphodiesterase (PDE) enzymes. Bacteria typically encode many different DGCs and PDEs within their genomes. Presumably, each enzyme senses and responds to cognate environmental cues by alteration of enzymatic activity. c-di-GMP represses the expression of virulence factors in
V. cholerae
, and it is predicted that the intracellular concentration of c-di-GMP is low during infection. Contrary to this model, we found that bile acids, a prevalent constituent of the human proximal small intestine, increase intracellular c-di-GMP in
V. cholerae
. We identified four c-di-GMP turnover enzymes that contribute to increased intracellular c-di-GMP in the presence of bile acids, and deletion of these enzymes eliminates the bile induction of c-di-GMP and biofilm formation. Furthermore, this bile-mediated increase in c-di-GMP is quenched by bicarbonate, the intestinal pH buffer secreted by intestinal epithelial cells. Our results lead us to propose that
V. cholerae
senses distinct microenvironments within the small intestine using bile and bicarbonate as chemical cues and responds by modulating the intracellular concentration of c-di-GMP.