bluuebunny/crossref_metadata_2025_split huggingface dataset:
ASSOCIATION BETWEEN THE DIETARY LIPID INTAKE AND THE DEVELOPMENT OF ORAL PRECANCEROUS LESIONS IN UNIVERSITY STUDENTS
Authors: ACTIS ADRIANA , PEROVIC NILDA , BIGLIANI VIRGINIA , BERTOLOTTO PATRICIA 
Published: February 2007

ABSTRACTAlthough the effects of dietary lipids on cancer have been reported, no references were found with respect to oral precancerous lesions (OPLs). The purpose of this study was to analyze the association between the dietary lipids and the risk of developing OPL in university students. Ninety‐eight out of 658 examined subjects of both sexes, age range 18–45 years old, were distributed in 30 cases and 68 controls. After clinical diagnosis of OPL and selection of controls, a food frequency and non‐nutritional factor‐based questionnaires were applied to both groups. A positive association was observed for a low intake of total saturated fatty acids (FAs) (95% confidence interval [CI] = 1.31–24.40) and of stearic acid 18:0 (95% CI = 1.25–35.11) while an inverse association was found for butyric acid 4:0 (95% CI = 0.03–0.69). An inverse trend was observed for a high intake of saturated lauric acid 12:0 (90% CI = 0.11–0.97) and myristic acid 14:0 (90% CI = 0.07–0.96), total polyunsaturated (90% CI = 0.09–0.94) and polyunsaturated linoleic acid 18:2 (90% CI = 0.08–0.90) and ω‐3 tymnodonic acid 20:5 FAs (90% CI = 0.08–0.91) as well as a positive trend of a low intake of total fat (90% CI = 1.04–9.73) and monounsaturated palmitoleic acid 16:1 FA (90% CI = 1.06–10.52). Although further research is required, dietary lipids appear to be associated with the development of OPL in 18‐ to 45‐year‐old university students.
Fluoroquinolone Resistance in
Streptococcus pneumoniae
: Area Under the Concentration-Time Curve/MIC Ratio and Resistance Development with Gatifloxacin, Gemifloxacin, Levofloxacin, and Moxifloxacin
Authors: LaPlante Kerry L. , Rybak Michael J. , Tsuji Brian , Lodise Thomas P. , Kaatz Glenn W. 
Published: February 2007

ABSTRACT

The potential for resistance development in
Streptococcus pneumoniae
secondary to exposure to gatifloxacin, gemifloxacin, levofloxacin, and moxifloxacin at various levels was examined at high inoculum (10
8.5
to 10
9
log
10
CFU/ml) over 96 h in an in vitro pharmacodynamic (PD) model using two fluoroquinolone-susceptible isolates. The pharmacokinetics of each drug was simulated to provide a range of free areas under the concentration-time curves (
f
AUC) that correlated with various fluoroquinolone doses. Potential first (
parC
and
parE
)- and second-step (
gyrA
and
gyrB
) mutations in isolates with raised MICs were identified by sequence analysis. PD models simulating
f
AUC/MICs of 51 and ≤60, 34 and 37, ≤82 and ≤86, and ≤24 for gatifloxacin, gemifloxacin, levofloxacin, and moxifloxacin, respectively, against each isolate were associated with first-step
parC
(S52G, S79Y, and N91D) and second-step
gyrA
(S81Y and S114G) mutations. For each fluoroquinolone a delay of first- and second-step mutations was observed with increasingly higher
f
AUC/MIC ratios and recovery of topoisomerase mutations in
S. pneumoniae
was related to the
f
AUC/MIC exposure. Clinical doses of gatifloxacin, gemifloxacin, and moxifloxacin exceeded the
f
AUC/MIC resistance breakpoint against wild-type
S. pneumoniae
, whereas those of levofloxacin (500 and 750 mg) were associated with first- and second-step mutations. The exposure breakpoints for levofloxacin were significantly different (
P
< 0.001) from those of the newer fluoroquinolones gatifloxacin, gemifloxacin, and moxifloxacin. Additionally, moxifloxacin breakpoints were significantly lower (
P
< 0.002) than those of gatifloxacin. The order of resistance development determined from
f
AUC/MIC breakpoints was levofloxacin > gatifloxacin > moxifloxacin = gemifloxacin, which may be related to structural differences within the class.
Pharmacokinetics of Saquinavir, Atazanavir, and Ritonavir in a Twice-Daily Boosted Double-Protease Inhibitor Regimen
Authors: von Hentig Nils , Müller Axel , Rottmann Carsten , Wolf Timo , Lutz Thomas , Klauke Stephan , Kurowski Michael , Oertel Bruno , Dauer Brenda , Harder Sebastian , Staszewski Schlomo 
Published: February 2007

ABSTRACTThe objective of this study was to evaluate the pharmacokinetics of atazanavir (ATV), saquinavir (SQV), and ritonavir (RTV) in a boosted double-protease inhibitor (PI) therapy regimen without reverse transcriptase inhibitors (RTIs). The study design was as follows. Patients with limited RTI options received a PI combination of 300/100 mg ATV/RTV once daily and 1,000 mg SQV twice daily (group 1;n= 49) without RTI comedication. The results were compared to the plasma concentrations of PIs of patients taking either 300 mg ATV/100 mg RTV once daily plus RTIs (group 2;n= 72) or patients taking 1,000 mg SQV/100 mg RTV plus RTIs (group 3;n= 90). The study methods were as follows. Patients were given a 12/24-h pharmacokinetic assessment at steady state. Drug concentrations were measured by liquid chromatography-tandem mass spectrometry. The minimum and maximum concentrations (CminandCmax), area under the concentration-time curve under steady-state conditions (AUCss), elimination half-life, time of maximum concentration and lag time were subject to statistical analysis. The results show that patients treated with ATV/SQV/RTV exhibited significantly high SQV concentrations and moderate enhancement of the AUCssof ATV in comparison to those of patients of the control groups: for SQV in groups 1 and 3, the geometric mean (GM) of the AUCsswas 22,794 versus 15,759 ng·h/ml (GM ratio [GMR] = 1.45;P< 0.05), the GM of theCmaxwas 3,257 versus 2,331 ng/ml (GMR = 1.40;P< 0.05), and the GM of theCminwas 438 versus 437 ng/ml (GMR = 1.00); for ATV in groups 1 and 2, the GM of the AUCsswas 39,154 versus 33,626 ng·h/ml (GMR = 1.16), the GM of theCmaxwas 3,488 versus 2,924 ng/ml (GMR = 1.20), and the GM of theCminwas 515 versus 428 ng/ml (GMR = 1.21). RTV levels were comparable for all groups. A subgroup analysis detected only marginal differences in ATV plasma exposure if combined with tenofovir-disoproxilfumarate and without it. We conclude that our pharmacokinetic results support the use of a boosted double-PI regimen of ATV/SQV/RTV as a treatment option for patients who need antiretroviral therapy without RTIs.
Novel Synthetic Antimicrobial Peptides against
Streptococcus mutans
Authors: He Jian , Eckert Randal , Pharm Thanh , Simanian Maurice D. , Hu Chuhong , Yarbrough Daniel K. , Qi Fengxia , Anderson Maxwell H. , Shi Wenyuan 
Published: February 2007

ABSTRACT

Streptococcus mutans
, a common oral pathogen and the causative agent of dental caries, has persisted and even thrived on the tooth surface despite constant removal and eradication efforts. In this study, we generated a number of synthetic antimicrobial peptides against this bacterium via construction and screening of several structurally diverse peptide libraries where the hydrophobicity and charge within each library was varied incrementally in order to generate a collection of peptides with different biochemical characteristics. From these libraries, we identified multiple peptides with robust killing activity against
S. mutans
. To further improve their effectiveness, the most bactericidal peptides from each library were synthesized together as one molecule, in various combinations, with and without a flexible peptide linker between each antimicrobial region. Many of these “fusion” peptides had enhanced killing activities in comparison with those of the original nonconjoined molecules. The results presented here illustrate that small libraries of biochemically constrained peptides can be used to generate antimicrobial peptides against
S. mutans
, several of which may be likely candidates for the development of anticaries agents.
EDP-420, a Bicyclolide (Bridged Bicyclic Macrolide), Is Active against
Mycobacterium avium
Authors: Bermudez Luiz E. , Motamedi Nima , Chee Christopher , Baimukanova Gyulnar , Kolonoski Peter , Inderlied Clark , Aralar Priscilla , Wang Guoqiang , Phan Ly Tam , Young Lowell S. 
Published: February 2007

ABSTRACT

Infection caused by
Mycobacterium avium
complex (MAC) is common in patients with immunosuppression, such as AIDS, and deficiencies of gamma interferon and interleukin-12, as well as patients with chronic lung diseases. Treatment of MAC disease is limited since few drugs show in vivo activity. We tested a new bridged bicyclic macrolide, EDP-420, against MAC in vitro and in beige mice. EDP-420 was inhibitory in vitro at a concentration ranging from 2 to 8 μg/ml (MIC
50
of 4 μg/ml and MIC
90
of 8 μg/ml). In macrophages, EDP-420 was inhibitory at 0.5 μg/ml, suggesting that the drug concentrates intracellularly. Mice infected with macrolide-susceptible MAC strain 101 were given 100 mg of EDP-420/kg of body weight daily for 4 weeks and showed a significant reduction in the number of bacteria in both liver and spleen which was greater than the reduction observed with clarithromycin treatment at the same dose (
P
< 0.05). However, macrolide-resistant MAC 101 did not respond to EDP-420 treatment. A combination of EDP-420 with mefloquine was shown to be indifferent; mefloquine alone was active against macrolide-resistant MAC. The frequency of resistance to EDP-420 in MAC 101 was 10
−9
, which is significantly less than the emergence of resistance to clarithromycin, ∼10
−7
(
P
< 0.05). Further evaluation of EDP-420 in the treatment of MAC disease is warranted.
Efficacy of Oseltamivir Therapy in Ferrets Inoculated with Different Clades of H5N1 Influenza Virus
Authors: Govorkova Elena A. , Ilyushina Natalia A. , Boltz David A. , Douglas Alan , Yilmaz Neziha , Webster Robert G. 
Published: February 2007

ABSTRACTHighly pathogenic H5N1 influenza viruses have infected an increasing number of humans in Asia, with high mortality rates and the emergence of multiple distinguishable clades. It is not known whether antiviral drugs that are effective against contemporary human influenza viruses will be effective against systemically replicating viruses, such as these pathogens. Therefore, we evaluated the use of the neuraminidase (NA) inhibitor oseltamivir for early postexposure prophylaxis and for treatment in ferrets exposed to representatives of two clades of H5N1 virus with markedly different pathogenicities in ferrets. Ferrets were protected from lethal infection with the A/Vietnam/1203/04 (H5N1) virus by oseltamivir (5 mg/kg of body weight/day) given 4 h after virus inoculation, but higher daily doses (25 mg/kg) were required for treatment when it was initiated 24 h after virus inoculation. For the treatment of ferrets inoculated with the less pathogenic A/Turkey/15/06 (H5N1) virus, 10 mg/kg/day of oseltamivir was sufficient to reduce the lethargy of the animals, significantly inhibit inflammation in the upper respiratory tract, and block virus spread to the internal organs. Importantly, all ferrets that survived the initial infection were rechallenged with homologous virus after 21 days and were completely protected from infection. Direct sequencing of the NA or HA1 gene segments in viruses isolated from ferret after treatment showed no amino acid substitutions known to cause drug resistance in conserved residues. Thus, early oseltamivir treatment is crucial for protection against highly pathogenic H5N1 viruses and the higher dose may be needed for the treatment of more virulent viruses.
Role for Gingipains inPorphyromonas gingivalisTraffic to Phagolysosomes and Survival in Human Aortic Endothelial Cells
Authors: Yamatake Kumiko , Maeda Maki , Kadowaki Tomoko , Takii Ryosuke , Tsukuba Takayuki , Ueno Takashi , Kominami Eiki , Yokota Sadaki , Yamamoto Kenji 
Published: February 2007

ABSTRACTGingipains are cysteine proteinases that are responsible for the virulence ofPorphyromonas gingivalis. Recent studies have shown thatP. gingivalisis trapped within autophagic compartments of infected cells, where it promotes survival. In this study we investigated the role of gingipains in the intracellular trafficking and survival of this bacterium in human aortic endothelial cells and any possible involvement of these enzymes in the autophagic pathway. Although autophagic events were enhanced by infection with either wild-type (WT)P. gingivalisstrains (ATCC 33277, 381, and W83) or an ATCC 33277 mutant lacking gingipains (KDP136), we have found that more than 90% of intracellular WT and KDP136 colocalized with cathepsin B, a lysosome marker, and only a few of the internalized cells colocalized with LC3, an autophagosome marker, during the 0.5- to 4-h postinfection period. This was further substantiated by immunogold electron microscopic analyses, thus implying thatP. gingivalisevades the autophagic pathway and instead directly traffics to the endocytic pathway to lysosomes. At the late stages after infection, WT strains in phagolysosomes retained their double-membrane structures. KDP136 in these compartments, however, lost its double-membrane structures, representing a characteristic feature of its vulnerability to rupture. Together with the ultrastructural observations, we found that the number of intracellular viable WT cells decreased more slowly than that of KDP136 cells, thus suggesting that gingipains contribute to bacterial survival, but not to trafficking, within the infected cells.
Enhancement of Macrophage Stimulation by Lipoteichoic Acid and the Costimulant Hemoglobin Is Dependent on Toll-Like Receptors 2 and 4
Authors: Cox Kathleen H. , Ofek Itzhak , Hasty David L. 
Published: February 2007

ABSTRACTMacrophage stimulation by lipoteichoic acid (LTA) and hemoglobin (Hb) requires Toll-like receptors 2 and 4 (TLR2 and -4). There are two distinct temporal phases of interleukin-6 (IL-6) production. The first results in a slight enhancement of IL-6 secretion in response to LTA plus Hb compared to that with LTA alone and is TLR4 independent. The second requires TLR4 and accounts for most of the additional stimulation seen with LTA plus Hb.
The Phase-Variable Allele of the Pilus Glycosylation Gene
pglA
Is Not Strongly Associated with Strains of
Neisseria gonorrhoeae
Isolated from Patients with Disseminated Gonococcal Infection
Authors: Power P. M. , Ku S. C. , Rutter K. , Warren M. J. , Limnios E. A. , Tapsall J. W. , Jennings M. P. 
Published: February 2007

ABSTRACT

The
Neisseria gonorrhoeae pglA
gene has two alleles, one of which is phase variable. A previous study reported that all disseminated gonococcal infection (DGI) isolates contained the phase-variable allele and proposed a causal link. In the present study of 81 strains no absolute correlation between DGI and the phase-variable
pglA
allele was observed.
Neisseria gonorrhoeae
Catalase Is Not Required for Experimental Genital Tract Infection despite the Induction of a Localized Neutrophil Response
Authors: Soler-García Ángel A. , Jerse Ann E. 
Published: February 2007

ABSTRACT

Neisseria gonorrhoeae
produces several antioxidant defenses, including high levels of catalase, which may facilitate the persistence during an inflammatory response via neutralization of H
2
O
2
produced by phagocytes. In vivo testing of the role of catalase in gonococcal survival is critical since several physiological factors impact interactions between
N. gonorrhoeae
and polymorphonuclear leukocytes (PMNs). Here we assessed the importance of gonococcal catalase in a surrogate model of female genital tract infection. Female BALB/c mice were treated with 17-β estradiol to promote susceptibility to
N. gonorrhoeae
and inoculated intravaginally with wild-type gonococci or a catalase (
kat
) deletion mutant. A localized PMN influx occurred in an average of 43 and 81% of mice infected with wild-type or
kat
mutant gonococci, respectively, and PMNs associated with numerous wild-type or catalase-deficient bacteria were observed in vaginal smears. The combined results of six experiments showed a significant difference in the number of days wild-type bacteria were recovered compared to the catalase-deficient gonococci. However, there was much variability between experiments, and we found no correlation between PMN influx, colonization load, and clearance of wild-type or
kat
mutant bacteria. Estradiol treatment did not impair bacterial uptake, the luminol-dependent chemiluminescence response, or the killing capacity of isolated murine PMNs against
N. gonorrhoeae
or
Staphylococcus aureus
. Our data suggest
N. gonorrhoeae
is not significantly challenged by H
2
O
2
produced by PMNs in the murine lower genital tract; alternatively, redundant defense mechanisms may protect the gonococcus from reactive oxygen species during infection.
Pet, a Non-AB Toxin, Is Transported and Translocated into Epithelial Cells by a Retrograde Trafficking Pathway
Authors: Navarro-García Fernando , Canizalez-Roman Adrián , Burlingame Kaitlin E. , Teter Ken , Vidal Jorge E. 
Published: February 2007

ABSTRACT

The plasmid-encoded toxin (Pet) of enteroaggregative
Escherichia coli
is a 104-kDa autotransporter protein that exhibits proteolytic activity against the actin-binding protein α-fodrin. Intracellular cleavage of epithelial fodrin by Pet disrupts the actin cytoskeleton, causing both cytotoxic and enterotoxic effects. Intoxication requires the serine protease activity of Pet and toxin endocytosis from clathrin-coated pits. The additional events in the intracellular trafficking of Pet are largely uncharacterized. Here, we determined by confocal microscopy that internalized Pet is transferred from the early endosomes to the Golgi apparatus and then travels to the endoplasmic reticulum (ER). Pet associates with the Sec61p translocon before it moves into the cytosol as an intact, 104-kDa protein. This translocation process contrasts with the export of other ER-translocating toxins, in which only the catalytic A subunit of the AB toxin enters the cytosol. However, like intoxication with these AB toxins, Pet intoxication was inhibited in a subset of mutant CHO cell lines with aberrant activity in the ER-associated degradation pathway of ER-to-cytosol translocation. This is the first report which documents the cell surface-to-ER and ER-to-cytosol trafficking of a bacterial non-AB toxin.
The Glycan Moieties and the N-Terminal Polypeptide Backbone of a Fimbria-Associated Adhesin, Fap1, Play Distinct Roles in the Biofilm Development of
Streptococcus parasanguinis
Authors: Wu Hui , Zeng Meiqin , Fives-Taylor Paula 
Published: February 2007

ABSTRACT

Fap1, a fimbria-associated glycoprotein, is essential for biofilm formation of
Streptococcus parasanguinis
and mediates bacterial attachment to saliva-coated hydroxylapatite, an in vitro tooth model (E. H. Froeliger and P. M. Fives-Taylor, Infect. Immun. 69:2512-2519, 2001; H. Wu and P. M. Fives-Taylor, Mol. Microbiol. 34:1070-1081, 1999; H. Wu et al., Mol. Microbiol. 28:487-500, 1998). Fap1 belongs to a growing family of high-molecular-weight serine-rich proteins found in streptococcal and staphylococcal species and possesses two serine-rich repeat regions. The glycan moiety of Fap1 appears to be O linked within the repeat regions (A. E. Stephenson et al., Mol. Microbiol. 43:147-157, 2002). In the present study, we identified a gene cluster immediately upstream of
fap1
that encodes three putative glycosyltransferases and one nucleotide-sugar synthetase-like protein. Inactivation of one glycosyltransferase gene
galT2
abolished the expression of two glycan epitopes; however, it did not alter bacterial ability to adhere to both SHA and saliva-conditioned biofilm surfaces. In contrast, the biofilms formed by the
galT2
mutant were shallow and had a 70% decrease in biomass accumulation, suggesting that these glycan moieties mediated by GalT2 are not required for the initial adhesion but are important for biofilm formation. A recombinant N-terminal Fap1 polypeptide was shown to interact with a 53-kDa salivary protein and block and displace bacterial attachment, further demonstrating the role of the Fap1 polypeptide in bacterial adhesion. Taken together, these results suggest that Fap1 glycosylation plays an important role in bacterial biofilm formation, whereas the nonglycosylated Fap1 peptide mediates bacterial initial attachment during the process of biofilm formation.
Influence of Neutropenia on the Course of Serotype 8 Pneumococcal Pneumonia in Mice
Authors: Marks Matthew , Burns Tamika , Abadi Maria , Seyoum Beza , Thornton Justin , Tuomanen Elaine , Pirofski Liise-anne 
Published: February 2007

ABSTRACTPolymorphoneutrophils (PMNs) are important effector cells in host defense against pneumonia. However, PMNs can also induce inflammation and tissue damage. To investigate the contribution of PMNs to host defense against pneumococcal pneumonia, we determined the effect of the PMN-depleting rat monoclonal antibody RB6-8C5 (RB6) on survival and inflammatory and cellular response in the lungs to a lethal intranasal infection with a serotype 8 pneumococcus in BALB/c mice. Control mice received rat immunoglobulin G (rIgG). Strikingly, the survival of RB6-treated mice was significantly prolonged compared to that of rIgG-treated mice. Although the numbers of CFU in the lungs were statistically similar in both groups 4, 24, and 32 h after infection, rIgG-treated mice developed higher levels of bacteremia, and histopathological examination of the lungs of infected mice revealed marked differences between RB6- and rIgG-treated mice. RB6-treated mice had focal, perivascular lesions without accompanying parenchymal inflammation, and rIgG-treated mice had diffuse, interstitial parenchymal inflammation. Lung homogenates from the rIgG-treated mice had more leukocytes and significantly more total and apoptotic PMNs as determined by fluorescence-activated cell sorter analysis with Annexin V and terminal deoxynucleotidyltransferase-mediated dUTP-biotin nick end labeling staining of lung tissue samples. Studies with a pneumolysin-deficient mutant of the serotype 8 strain we used also demonstrated the prolonged survival of RB6- compared to rIgG-treated mice. Taken together, our findings suggest that PMNs enhance the likelihood of early death and alter the pathological response to pneumococcal lung infection in BALB/c mice with serotype 8 pneumonia without significantly affecting bacterial clearance or the cytokine response.
Bile Salts Stimulate Recruitment of IpaB to the
Shigella flexneri
Surface, Where It Colocalizes with IpaD at the Tip of the Type III Secretion Needle
Authors: Olive Andrew J. , Kenjale Roma , Espina Marianela , Moore David S. , Picking Wendy L. , Picking William D. 
Published: February 2007

ABSTRACT

Shigella flexneri
uses its type III secretion apparatus (TTSA) to deliver invasins into human cells. This TTSA possesses an external needle with IpaD at its tip. We now show that deoxycholate promotes the stable recruitment of IpaB to the needle tip without inducing a rapid burst of type III secretion. The maintenance of IpaB at the needle tip requires a stable association of IpaD with the
Shigella
surface. This is the first demonstration of a translocator protein being stably associated with the TTSA needle.