bluuebunny/crossref_metadata_2025_split huggingface dataset:
In Vitro and In Vivo Activities of Chios Mastic Gum Extracts and Constituents against
Helicobacter pylori
Authors: Paraschos Sotirios , Magiatis Prokopios , Mitakou Sofia , Petraki Kalliopi , Kalliaropoulos Antonios , Maragkoudakis Petros , Mentis Andreas , Sgouras Dionyssios , Skaltsounis Alexios-Leandros 
Published: November 2006

ABSTRACT

The extracts and pure major constituents of Chios mastic gum (resin of
Pistacia lentiscus
var.
chia
) were tested for their activities against
Helicobacter pylori
. A total mastic extract without polymer (TMEWP) was prepared after removal of the contained insoluble polymer in order to ameliorate solubility and enhance in vivo activity. Administration of TMEWP to
H. pylori
SS1-infected mice over the period of 3 months with an average dose of 0.75 mg/day led to an approximately 30-fold reduction in the
H. pylori
colonization (1.5 log CFU/g of tissue). However, no attenuation in the
H. pylori
-associated chronic inflammatory infiltration and the activity of chronic gastritis was observed. To further characterize potential active mastic constituents, the TMEWP was separated into an acidic and a neutral fraction. Both were extensively characterized by nuclear magnetic resonance and mass spectroscopy to elucidate the structure of the components contained within each fraction. After chromatographic separation, the acid fraction gave the major triterpenic acids, while the neutral fraction gave several triterpenic alcohols and aldehydes. Mastic extracts and isolated pure triterpenic acids were tested for in vitro activity against a panel of 11
H. pylori
clinical strains. The acid fraction was found to be the most active extract (minimum bactericidal concentration [MBC], 0.139 mg/ml), and the most active pure compound was isomasticadienolic acid (MBC, 0.202 mg/ml [0.443 mM]). Our results show that administration of TMEWP may be effective in reducing
H. pylori
colonization and that the major triterpenic acids in the acid extract may be responsible for such an activity.
Steady-State Pharmacokinetics of Micafungin and Voriconazole after Separate and Concomitant Dosing in Healthy Adults
Authors: Keirns J. , Sawamoto T. , Holum M. , Buell D. , Wisemandle W. , Alak A. 
Published: November 2006

ABSTRACT
We assessed the pharmacokinetics and interactions of steady-state micafungin (Mycamine) or placebo with steady-state voriconazole in 35 volunteers. The 90% confidence intervals around the least-squares mean ratios for micafungin pharmacokinetic parameters and placebo-corrected voriconazole pharmacokinetic parameters were within the 80%-to-125% limits, indicating an absence of drug interaction.
Tolerance to the Glycopeptides Vancomycin and Teicoplanin in Coagulase-Negative Staphylococci
Authors: Bourgeois Ingrid , Pestel-Caron Martine , Lemeland Jean-Francois , Pons Jean-Louis , Caron Francois 
Published: November 2006

ABSTRACT

Tolerance to vancomycin and teicoplanin in 90 clinical isolates of coagulase-negative staphylococci (CoNS) was investigated by time-kill curve methodology. Only six strains, belonging to the
Staphylococcus lugdunensis
species, exhibited tolerance. The seven other
S. lugdunensis
strains tested displayed weak susceptibility to the bactericidal activity of glycopeptides compared to the other CoNS. These phenomena are of concern, since
S. lugdunensis
is recognized as one of the most pathogenic CoNS.
Development and Characterization of a Novel Single-Cycle Recombinant-Virus Assay To Determine Human Immunodeficiency Virus Type 1 Coreceptor Tropism
Authors: Whitcomb Jeannette M. , Huang Wei , Fransen Signe , Limoli Kay , Toma Jonathan , Wrin Terri , Chappey Colombe , Kiss Linda D. B. , Paxinos Ellen E. , Petropoulos Christos J. 
Published: November 2006

ABSTRACT

Most human immunodeficiency virus type 1 (HIV-1) strains require either the CXCR4 or CCR5 chemokine receptor to efficiently enter cells. Blocking viral binding to these coreceptors is an attractive therapeutic target. Currently, several coreceptor antagonists are being evaluated in clinical trials that require characterization of coreceptor tropism for enrollment. In this report, we describe the development of an automated and accurate procedure for determining HIV-1 coreceptor tropism (Trofile) and its validation for routine laboratory testing. HIV-1 pseudoviruses are generated using full-length
env
genes derived from patient virus populations. Coreceptor tropism is determined by measuring the abilities of these pseudovirus populations to efficiently infect CD4
+
/U87 cells expressing either the CXCR4 or CCR5 coreceptor. Viruses exclusively and efficiently infecting CXCR4
+
/CD4
+
/U87 cells are designated X4-tropic. Conversely, viruses exclusively and efficiently infecting CCR5
+
/CD4
+
/U87 cells are designated R5-tropic. Viruses capable of infecting both CXCR4
+
/CD4
+
/U87 and CCR5
+
/CD4
+
/U87 cells are designated dual/mixed-tropic. Assay accuracy and reproducibility were established by evaluating the tropisms of well-characterized viruses and the variability among replicate results from samples tested repeatedly. The viral subtype, hepatitis B virus or hepatitis C virus coinfection, and the plasma viral load did not affect assay performance. Minority subpopulations with alternate tropisms were reliably detected when present at 5 to 10%. The plasma viral load above which samples can be amplified efficiently in the Trofile assay is 1,000 copies per ml of plasma. Trofile has been automated for high-throughput use; it can be used to identify patients most likely to benefit from treatment regimens that include a coreceptor inhibitor and to monitor patients on treatment for the emergence of resistant virus populations that switch coreceptor tropism.
Efficacy of Delayed Treatment with ST-246 Given Orally against Systemic Orthopoxvirus Infections in Mice
Authors: Quenelle Debra C. , Buller R. M. L. , Parker Scott , Keith Kathy A. , Hruby Dennis E. , Jordan Robert , Kern Earl R. 
Published: November 2006

ABSTRACT

ST-246 was evaluated for activity against cowpox virus (CV), vaccinia virus (VV), and ectromelia virus (ECTV) and had an in vitro 50% effective concentration (EC
50
) of 0.48 μM against CV, 0.05 μM against VV, and 0.07 μM against ECTV. The selectivity indices were >208 and >2,000 for CV and VV, respectively. The in vitro antiviral activity of ST-246 was significantly greater than that of cidofovir, which had an EC
50
of 41.1 μM against CV and 29.2 μM against VV, with selectivity indices of >7 and >10, respectively. ST-246 administered once daily by oral gavage to mice infected intranasally with CV beginning 4 h or delayed until 72 h postinoculation was highly effective when given for a 14-day duration using 100, 30, or 10 mg/kg of body weight. When 100 mg/kg of ST-246 was administered to VV-infected mice, a duration of 5 days was sufficient to significantly reduce mortality even when treatment was delayed 24 h postinoculation. Viral replication in liver, spleen, and kidney, but not lung, of CV- or VV-infected mice was reduced by ST-246 compared to levels for vehicle-treated mice. When 100 mg/kg of ST-246 was given once daily to mice infected by the intranasal route with ECTV, treatment for 10 days prevented mortality even when treatment was delayed up to 72 h after viral inoculation. Viral replication in target organs of ECTV-infected mice was also reduced.
Estimating True Antimalarial Efficacy by Heteroduplex Tracking Assay in Patients with Complex
Plasmodium falciparum
Infections
Authors: Kwiek Jesse J. , Alker Alisa P. , Wenink Emily C. , Chaponda Marjorie , Kalilani Linda V. , Meshnick Steven R. 
Published: November 2006

ABSTRACT

Heteroduplex tracking assays (HTAs) of
Plasmodium falciparum
merozoite surface protein 1 block-2 were used to assess complexity of infection and treatment efficacy in a trial of three antimalarial treatments in 141 Malawian pregnant women. An elevated complexity of infection (COI) was associated with anemia, parasite burden, and human immunodeficiency virus infection but was not associated with age or gravidity. Comparisons of HTA patterns before and after treatment allowed the classification of 20 of 30 (66%) recurrent episodes as either definite treatment failures or reinfections. An elevated COI was strongly associated with treatment failure (
P
= 0.003). An algorithm was developed to assign a probability of failure for the 10 indeterminate participants, some of whose infections shared a single variant of high prevalence (>10%). By summing these probabilities, treatment efficacy was estimated.
Diversity of Ampicillin Resistance Genes and Antimicrobial Susceptibility Patterns in
Haemophilus influenzae
Strains Isolated in Korea
Authors: Kim In-Suk , Ki Chang-Seok , Kim Sunjoo , Oh Won Sup , Peck Kyong Ran , Song Jae-Hoon , Lee Kyungwon , Lee Nam Yong 
Published: November 2006

ABSTRACT

By Etest determination of the susceptibilities of 229
Haemophilus influenzae
strains isolated in Korea to 10 antibiotics, the isolates were found to be antibiotic nonsusceptible in the following order: ampicillin (58.1%), trimethoprim-sulfamethoxazole (52%), cefaclor (41.1%), clarithromycin (25.8%), chloramphenicol (14.0%), amoxicillin-clavulanic acid (13.5%), meropenem (11.7%), cefixime (10.9%), cefuroxime (9.2%), and levofloxacin (1.3%). The prevalences of each resistance class were 23.6% for β-lactamase-negative ampicillin-susceptible (BLNAS) strains; 37.6% for strains with the TEM-1 type β-lactamase gene; 1.3% for strains with the ROB-1 type β-lactamase gene; 29.3% for the β-lactamase-negative ampicillin-resistant (BLNAR) strains with a mutation in the
ftsI
gene, which encodes PBP 3; and 8.3% for β-lactamase-positive amoxicillin-clavulanate-resistant (BLPACR) strains, which showed both resistance mechanisms (i.e., a β-lactamase gene and a mutation in the
ftsI
gene). The MIC
50
s of all β-lactams, including cephem and meropenem agents, for the BLNAR strains were two to three times higher than those for the BLNAS strains. This study confirms that the prevalence of BLNAR and BLPACR strains is relatively high and for the first time confirms the presence of
H. influenzae
strains carrying
bla
ROB-1
in Korea. Even though mutations in another gene(s) might be involved in β-lactam resistance, these results suggest that mutations in the
ftsI
gene are important for the development of resistance to β-lactams in
H. influenzae
strains in Korea.
In Vitro Antimalarial Activity of Azithromycin, Artesunate, and Quinine in Combination and Correlation with Clinical Outcome
Authors: Noedl Harald , Krudsood Srivicha , Leowattana Wattana , Tangpukdee Noppadon , Thanachartwet Wipa , Looareesuwan Sornchai , Miller Robert Scott , Fukuda Mark , Jongsakul Krisada , Yingyuen Kritsanai , Sriwichai Sabaithip , Ohrt Colin , Knirsch Charles 
Published: November 2006

ABSTRACT

Azithromycin when used in combination with faster-acting antimalarials has proven efficacious in treating
Plasmodium falciparum
malaria in phase 2 clinical trials. The aim of this study was to establish optimal combination ratios for azithromycin in combination with either dihydroartemisinin or quinine, to determine the clinical correlates of in vitro drug sensitivity for these compounds, and to assess the cross-sensitivity patterns. Seventy-three fresh
P. falciparum
isolates originating from patients from the western border regions of Thailand were successfully tested for their drug susceptibility in a histidine-rich protein 2 (HRP2) assay. With overall mean fractional inhibitory concentrations of 0.84 (95% confidence interval [CI] = 0.77 to 1.08) and 0.78 (95% CI = 0.72 to 0.98), the interactions between azithromycin and dihydroartemisinin, as well as quinine, were classified as additive, with a tendency toward synergism. The strongest tendency toward synergy was seen with a combination ratio of 1:547 for the combination with dihydroartemisinin and 1:44 with quinine. The geometric mean 50% inhibitory concentration (IC
50
) of azithromycin was 2,570.3 (95% CI = 2,175.58 to 3,036.58) ng/ml. The IC
50
s for mefloquine, quinine, and chloroquine were 11.42, 64.4, and 54.4 ng/ml, respectively, suggesting a relatively high level of background resistance in this patient population. Distinct correlations (
R
= 0.53;
P
= 0.001) between quinine in vitro results and parasite clearance may indicate a compromised sensitivity to this drug. The correlation with dihydroartemisinin data was weaker (
R
= 0.34;
P
= 0.038), and no such correlation was observed for azithromycin. Our in vitro data confirm that azithromycin in combination with artemisinin derivatives or quinine exerts additive to synergistic interactions, shows no cross-sensitivity with traditional antimalarials, and has substantial antimalarial activity on its own.
Posaconazole Enhances the Activity of Amphotericin B against
Aspergillus
Hyphae In Vitro
Authors: Perkhofer Susanne , Lugger Helene , Dierich Manfred P. , Lass-Flörl Cornelia 
Published: November 2006

ABSTRACT

The MICs and fractional inhibitory concentrations of posaconazole (POS) and voriconazole (VRZ), alone and in combination with amphotericin B (AMB), for the conidia and hyphae of 100
Aspergillus
isolates were evaluated. POS-AMB had more synergistic activity against hyphae (75% of isolates) than VRZ-AMB (37%) and significantly more synergistic activity against hyphae than against conidia (12%).
A Novel Nonnucleoside Analogue That Inhibits Human Immunodeficiency Virus Type 1 Isolates Resistant to Current Nonnucleoside Reverse Transcriptase Inhibitors
Authors: Zhang Zhijun , Xu Wen , Koh Yung-Hyo , Shim Jae Hoon , Girardet Jean-Luc , Yeh Li-Tain , Hamatake Robert K. , Hong Zhi 
Published: November 2006

ABSTRACT
Nonnucleoside reverse transcriptase (RT) inhibitors (NNRTIs) are important components of current combination therapies for human immunodeficiency virus type 1 (HIV-1) infection. However, their low genetic barriers against resistance development, cross-resistance, and serious side effects can compromise the benefits of the two current drugs in this class (efavirenz and nevirapine). In this study, we report a novel and potent NNRTI, VRX-480773, that inhibits viruses from efavirenz-resistant molecular clones and most NNRTI-resistant clinical HIV-1 isolates tested. In vitro mutation selection experiments revealed that longer times were required for viruses to develop resistance to VRX-480773 than to efavirenz. RT mutations selected by VRX-480773 after 3 months of cell culture in the presence of 1 nM VRX-480773 carried the Y181C mutation, resulting in a less-than-twofold increase in resistance to the compound. A virus containing the double mutation V106I-Y181C emerged after 4 months, causing a sixfold increase in resistance. Viruses containing additional mutations of D123G, F227L, and T369I emerged when the cultures were incubated with increasing concentrations of VRX-480773. Most of the resistant viruses selected by VRX-480773 are susceptible to efavirenz. Oral administration of VRX-480773 to dogs resulted in plasma concentrations that were significantly higher than those required for the inhibition of wild-type and mutant viruses. These results warrant further clinical development of VRX-480773 for the treatment of HIV infection in both NNRTI-naive and -experienced patients.
Isolation and Characterization of Human Immunodeficiency Virus Type 1 Resistant to the Small-Molecule CCR5 Antagonist TAK-652
Authors: Baba Masanori , Miyake Hiroshi , Wang Xin , Okamoto Mika , Takashima Katsunori 
Published: November 2006

ABSTRACTTAK-652, a novel small-molecule chemokine receptor antagonist, is a highly potent and selective inhibitor of CCR5-using (R5) human immunodeficiency virus type 1 (HIV-1) replication in vitro. Since TAK-652 is orally bioavailable and has favorable pharmacokinetic profiles in humans, it is considered a promising candidate for an entry inhibitor of HIV-1. To investigate the resistance to TAK-652, peripheral blood mononuclear cells were infected with the R5 HIV-1 primary isolate KK and passaged in the presence of escalating concentrations of the compound for more than 1 year. After 67 weeks of cultivation, the escape virus emerged even in the presence of a high concentration of TAK-652. This virus displayed more than 200,000-fold resistance to TAK-652 compared with the wild type. The escape virus appeared to have cross-resistance to the structurally related compound TAK-779 but retained full susceptibility to TAK-220, which is from a different class of CCR5 antagonists. Furthermore, the escape virus was unable to use CXCR4 as a coreceptor. Analysis for Env amino acid sequences of escape viruses at certain points of passage revealed that amino acid changes accumulated with an increasing number of passages. Several amino acid changes not only in the V3 region but also in other Env regions seemed to be required for R5 HIV-1 to acquire complete resistance to TAK-652.
Multistep Resistance Selection and Postantibiotic-Effect Studies of the Antipneumococcal Activity of LBM415 Compared to Other Agents
Authors: Kosowska-Shick Klaudia , Credito Kim L. , Pankuch Glenn A. , DeWasse Bonifacio , McGhee Pamela , Appelbaum Peter C. 
Published: November 2006

ABSTRACT

LBM415 is a peptide deformylase inhibitor active against gram-positive bacterial species and some gram-negative species. In multiselection studies, LBM415 had low MICs against all
Streptococcus pneumoniae
strains tested, regardless of their genotype, and selected resistant clones after 14 to 50 days. MIC increases correlated with changes mostly in the
70
GXGXAAXQ
77
motif in peptide deformylase. The postantibiotic effect of LBM415 ranged from 0.3 to 1.4 h.
Leishmania donovani
Polyamine Biosynthetic Enzyme Overproducers as Tools To Investigate the Mode of Action of Cytotoxic Polyamine Analogs
Authors: Roberts Sigrid C. , Jiang Yuqui , Gasteier Judith , Frydman Benjamin , Marton Laurence J. , Heby Olle , Ullman Buddy 
Published: November 2006

ABSTRACT

A number of anticancer and antiparasitic drugs are postulated to target the polyamine biosynthetic pathway and polyamine function, but the exact mode of action of these compounds is still being elucidated. To establish whether polyamine analogs specifically target enzymes of the polyamine pathway, a model was developed using strains of the protozoan parasite
Leishmania donovani
that overproduce each of the polyamine biosynthetic enzymes. Promastigotes overexpressing episomal constructs encoding ornithine decarboxylase (ODC),
S
-adenosylmethionine decarboxylase (ADOMETDC), or spermidine synthase (SPDSYN) revealed robust overproduction of the corresponding polyamine biosynthetic enzyme. Polyamine pools, however, were either unchanged or only marginally affected, implying that regulatory mechanisms must exist. The ODC, ADOMETDC, and SPDSYN overproducer strains exhibited a high level of resistance to difluoromethylornithine, 5′-{[(
Z
)-4-amino-2-butenyl]methylamino}-5′-deoxyadenosine, and
n
-butylamine, respectively, confirming previous observations that these agents specifically target polyamine enzymes. Conversely, augmented levels of polyamine biosynthetic enzymes did not affect the sensitivity of
L. donovani
promastigotes to pentamidine, berenil, and mitoguazone, drugs that were postulated to target the polyamine pathway, implying alternative and/or additional targets for these agents. The sensitivities of wild-type and overproducing parasites to a variety of polyamine analogs were also tested. The polyamine enzyme-overproducing lines offer a rapid cell-based screen for assessing whether synthetic polyamine analogs exert their mechanism of action predominantly on the polyamine biosynthetic pathway in
L. donovani
. Furthermore, the drug resistance engendered by the amplification of target genes and the overproduction of the encoded protein offers a general strategy for evaluating and developing therapeutic agents that target specific proteins in
Leishmania
.
Contribution of FliC to Epithelial Cell Invasion by Enterohemorrhagic
Escherichia coli
O113:H21
Authors: Luck Shelley N. , Badea Luminita , Bennett-Wood Vicki , Robins-Browne Roy , Hartland Elizabeth L. 
Published: November 2006

ABSTRACT

Enterohemorrhagic
Escherichia coli
(EHEC) O113:H21 can invade epithelial cells. In this study, we found that invasion but not adherence was inhibited by anti-FliC
H21
specific antibodies. In addition, deletion of

fliC
H21

from EHEC O113:H21 resulted in an eightfold decrease in invasion that was restored upon transcomplementation with

fliC
H21

but not with

fliC
H6

. These results suggested that FliC plays an important role in the pathogenesis of infections caused by EHEC O113:H21 by allowing bacteria to penetrate the intestinal epithelium.
Susceptibility of Prostate Epithelial Cells toChlamydia muridarumInfection and Their Role in Innate Immunity by Recruitment of Intracellular Toll-Like Receptors 4 and 2 and MyD88 to the Inclusion
Authors: Mackern-Oberti Juan Pablo , Maccioni Mariana , Cuffini Cecilia , Gatti Gerardo , Rivero Virginia E. 
Published: November 2006

ABSTRACTAlthoughChlamydiainfections are widespread throughout the world, data about immunopathogenesis of genitourinary tract infections in males are very limited. In the present work we present an in vitro model of male genital tract-derived epithelial cells, more precisely prostate epithelial cells (PEC), to analyze if they are susceptible and able to respond toChlamydia muridaruminfection. Our results demonstrate that rat PEC are susceptible toC. muridaruminfection and respond to this pathogen by up-regulating different proinflammatory cytokine and chemokine genes that could participate in the recruitment and local activation of immune cells, therefore influencing innate and adaptive immune responses duringChlamydiainfection. Moreover, we analyzed the expression of Toll-like receptor 4 (TLR4), TLR2, and related molecules on PEC and the effect ofC. muridaruminfection on their expression. Our results demonstrate that PEC express significant levels of TLR4, CD14, TLR2, and the adaptor molecule MyD88 and up-regulate these proteins in response toC. muridaruminfection. Indeed, TLR4, CD14, TLR2, and the adaptor MyD88 are specifically recruited to the vicinity of the bacterial inclusion, suggesting that these TLRs are actively engaged in signaling from this intracellular location in these cells. This is, to our knowledge, the first time that an in vitro model of infection withChlamydiaof male tract-derived epithelial cells has been achieved, and it provides the opportunity to determine how these cells respond and participate in modulating innate and adaptive immune response duringChlamydiainfections.
The Translocated
Salmonella
Effector Proteins SseF and SseG Interact and Are Required To Establish an Intracellular Replication Niche
Authors: Deiwick Jörg , Salcedo Suzana P. , Boucrot Emmanuel , Gilliland Sarah M. , Henry Thomas , Petermann Nele , Waterman Scott R. , Gorvel Jean-Pierre , Holden David W. , Méresse Stéphane 
Published: November 2006

ABSTRACT

The facultative intracellular pathogen
Salmonella enterica
causes a variety of diseases, including gastroenteritis and typhoid fever. Inside epithelial cells,
Salmonella
replicates in vacuoles, which localize in the perinuclear area in close proximity to the Golgi apparatus. Among the effector proteins translocated by the
Salmonella
pathogenicity island 2-encoded type III secretion system, SifA and SseG have been shown necessary but not sufficient to ensure the intracellular positioning of
Salmonella
vacuoles. Hence, we have investigated the involvement of other secreted effector proteins in this process. Here we show that SseF interacts functionally and physically with SseG but not SifA and is also required for the perinuclear localization of
Salmonella
vacuoles. The observations show that the intracellular positioning of
Salmonella
vacuoles is a complex phenomenon resulting from the combined action of several effector proteins.