bluuebunny/crossref_metadata_2025_split huggingface dataset:
Review article: regulation of TFF1 (pS2) expression in gastric epithelial cells
Authors: FUJII Y. , SHIMADA T. , KOIKE T. , HOSAKA K. , TABEI K. , NAMATAME T. , TAJIMA A. , YONEDA M. , TERANO A. , HIRAISHI H. 
Published: June 2006

SummaryTrefoil factor family (TFF) is a group of small peptides secreted by gastrointestinal epithelial cells.Among three known TFF peptides, TFF1 (formerly pS2) is expressed at a high level in gastric epithelial cells and plays an essential and critical role in maintaining the integrity of the gastric mucosa. Recent evidence also suggests that TFF1 acts as a tumour suppressor gene in the stomach. TFF1 was originally discovered as an oestrogen‐inducible gene in MCF‐7 breast cancer cells, and its expression is dependent on oestrogen in MCF‐7 and other hormone‐dependent breast cancer cells. Although gastric epithelial cells express oestrogen receptors (ERs), gastric TFF1 expression appears to be independent of oestrogen signalling. Instead, several cis‐regulatory elements are involved in the regulation of gastric TFF1 expression and balanced signalling from gp130, a common IL‐6 family coreceptor, has been shown to be necessary for the proper expression of TFF1 in the stomach.Epigenetic regulation, such as DNA methylation in the promoter region of the TFF1 gene, may be also important for tissue‐specific expression of TFF1 in the stomach. However, further studies are still needed to fully understand the detailed regulatory mechanisms of TFF1 expression in gastric epithelial cells.
Review article: fast acid control and rapid symptom relief for patients with gastro‐oesophageal reflux disease – the evidence from proton pump inhibitor studies
Authors: BYTZER P. 
Published: June 2006

SummaryBecause of their potent, rapid antisecretory effects, proton pump inhibitors (PPIs) are the mainstay of treatment for patients with gastro‐oesophageal reflux disease (GERD), providing fast symptom relief and increased mucosal healing.A review of the clinical data suggests that subpopulations of patients with GERD – non‐erosive symptomatic GERD (NERD), and erosive oesophagitis (EO) – derive significant benefits from fast‐acting PPIs. Patients with EO receiving fast‐acting PPIs experienced rapid relief of daytime and night‐time heartburn and related symptoms, with associated increases in quality of life (QoL). Similar benefits were observed for patients with NERD. Patients with EO and NERD showed significant symptom relief within the first day of treatment, which was most evident following lansoprazole, esomeprazole and rabeprazole. When used as long‐term on‐demand/intermittent therapy, fast‐acting PPIs significantly improved symptom relief and patient's QoL by reducing treatment discontinuation rates.In conclusion, fast‐acting antisecretory PPIs should be considered as optimal therapy for rapid symptom relief in different patient subpopulations with GERD.
Population Pharmacokinetic Assessment of a New Regimen of Mefloquine Used in Combination Treatment of Uncomplicated Falciparum Malaria
Authors: Ashley Elizabeth A. , Stepniewska Kasia , Lindegårdh Niklas , McGready Rose , Hutagalung Robert , Hae Rae , Singhasivanon Pratap , White Nicholas J. , Nosten François 
Published: June 2006

ABSTRACT

A fixed artesunate-mefloquine combination, comprising three daily doses of 8 mg of mefloquine/kg of body weight and 4 mg of artesunate/kg, has been developed recently. This study was designed to construct a population pharmacokinetic model describing this new dosage regimen of mefloquine given as loose tablets together with artesunate. In two randomized trials in Thailand which evaluated the efficacy, safety, and tolerability of this new regimen, the members of a subgroup of 50 patients were randomized to have capillary blood sampling before treatment and at five randomly assigned time points during the 63-day follow-up period. Mefloquine levels in capillary whole blood were assayed by liquid chromatography with UV detection. A pharmacokinetic model for mefloquine was constructed using mixed-effects modeling. A one-compartment model with first-order absorption and elimination was selected to describe the kinetic properties of mefloquine. For capillary whole-blood mefloquine, the area under the concentration curve (AUC) was 40% higher than previous estimates for patients given the equivalent conventional-dose regimen (mefloquine given as 15 mg/kg and then 10 mg/kg on the second and third days of treatment). The half-life (
t
1/2
) of the carboxylic acid metabolite was estimated as 26 days, and the metabolite was eliminated more slowly than the parent drug (population
t
1/2
estimate, 10.5 days). Splitting the 25 mg/kg dose of mefloquine into three doses of 8 mg/kg each resulted in improved oral bioavailability compared to the conventional split-dose regimen results. This new regimen is well tolerated and results in an equivalent therapeutic response.
Effect of a Selective Decontamination of the Digestive Tract Regimen Including Parenteral Cefepime on Establishment of Intestinal Colonization with Vancomycin-Resistant
Enterococcus
spp. and
Klebsiella pneumoniae
in Mice
Authors: Paterson David L. , Stiefel Usha , Donskey Curtis J. 
Published: June 2006

ABSTRACT

In mice, a selective decontamination of the digestive tract regimen consisting of orogastric tobramycin, polymyxin E, and amphotericin B in combination with subcutaneous cefepime inhibited gram-negative bacilli, including
Klebsiella pneumoniae
, and did not promote vancomycin-resistant
Enterococcus
spp. (VRE) colonization. However, concurrent administration of subcutaneous ampicillin-sulbactam resulted in promotion of VRE.
In Vivo Survival of Teicoplanin-Resistant
Staphylococcus aureus
and Fitness Cost of Teicoplanin Resistance
Authors: McCallum N. , Karauzum H. , Getzmann R. , Bischoff M. , Majcherczyk P. , Berger-Bächi B. , Landmann R. 
Published: June 2006

ABSTRACT

Glycopeptide resistance, in a set of in vitro step-selected teicoplanin-resistant mutants derived from susceptible
Staphylococcus aureus
SA113, was associated with slower growth, thickening of the bacterial cell wall, increased
N
-acetylglucosamine incorporation, and decreased hemolysis. Differential transcriptome analysis showed that as resistance increased, some virulence-associated genes became downregulated. In a mouse tissue cage infection model, an inoculum of 10
4
CFU of strain SA113 rapidly produced a high-bacterial-load infection, which triggered MIP-2 release, leukocyte infiltration, and reduced leukocyte viability. In contrast, with the same inoculum of the isogenic glycopeptide-resistant derivative NM67, CFU initially decreased, resulting in the elimination of the mutant in three out of seven cages. In the four cages in which NM67 survived, it partially regained wild-type characteristics, including thinning of the cell wall, reduced
N
-acetylglucosamine uptake, and increased hemolysis; however, the survivors also became teicoplanin hypersusceptible. The elimination of the teicoplanin-resistant mutants and selection of teicoplanin-hypersusceptible survivors in the tissue cages indicated that glycopeptide resistance imposes a fitness burden on
S. aureus
and is selected against in vivo, with restoration of fitness incurring the price of resistance loss.
Antimicrobial Activity and Spectrum of Cefovecin, a New Extended- Spectrum Cephalosporin, against Pathogens Collected from Dogs and Cats in Europe and North America
Authors: Stegemann M. R. , Passmore C. A. , Sherington J. , Lindeman C. J. , Papp G. , Weigel D. J. , Skogerboe T. L. 
Published: June 2006

ABSTRACT

Cefovecin is a new extended-spectrum semisynthetic cephalosporin indicated for the treatment of bacterial infections in dogs and cats. This study evaluated the in vitro activity and spectrum of cefovecin against 2,641 recent clinical isolates (1,660 canine and 981 feline isolates) from Europe and the United States. MIC determinations against cefovecin and other reference antimicrobials were performed by broth microdilution methods recommended by the Clinical and Laboratory Standards Institute (CLSI, formerly NCCLS). Cefovecin demonstrated bactericidal activity against both gram-positive and gram-negative pathogens. Cefovecin exhibited in vitro activity against all major aerobic and anaerobic bacterial pathogens associated with skin, urinary tract, and periodontal infections in dogs and cats. The MIC
90
values of cefovecin against
Staphylococcus intermedius
,
Escherichia coli
, and
Pasteurella multocida
were 0.25 μg/ml, 1.0 μg/ml, and 0.06 μg/ml, respectively. No significant differences were observed in terms of the activities of cefovecin against pathogens from different European countries and against pathogens of European and U.S. origin.
Activity of LBM415 Compared to Those of 11 Other Agents against
Haemophilus
Species
Authors: Bogdanovich Tatiana , Smith Kathy A. , Clark Catherine , Pankuch Glenn A. , Lin Gengrong , McGhee Pamela , Dewasse Bonifacio , Appelbaum Peter C. 
Published: June 2006

ABSTRACT

When tested against 254
Haemophilus influenzae
strains, LBM415, a peptide deformylase inhibitor, gave MIC
50
and MIC
90
values of 2.0 μg/ml and 8.0 μg/ml, respectively. The MICs were independent of β-lactam or quinolone susceptibility and the presence or absence of macrolide efflux or ribosomal protein mutations. The MICs of LBM415 against 23
H. parainfluenzae
strains were similar to those against
H. influenzae
. In contrast, erythromycin, azithromycin, and clarithromycin gave unimodal MIC distributions, and apart from β-lactamase-negative, ampicillin-resistant strains, all strains were susceptible to the β-lactams tested. Apart from selected quinolone-resistant strains, all strains were susceptible to ciprofloxacin, levofloxacin, gatifloxacin, moxifloxacin, and gemifloxacin. Resistance to trimethoprim-sulfamethoxazole was common. The potencies of all drugs against 23
H. parainfluenzae
strains were similar to those against
H. influenzae
. Time-kill studies with 10
Haemophilus
strains showed LBM415 to be bactericidal at 2× the MIC against 8 of 10 strains after 24 h. For comparison, the macrolides and β-lactams were bactericidal against 8 to 10 strains each at 2× the MIC after 24 h. Quinolones were bactericidal against all 10 strains tested at 2× the MIC after 24 h. Against six
H. influenzae
strains, postantibiotic effects for LBM415 lasted between 0.8 and 2.2 h. In multistep resistance selection studies, LBM415 produced resistant clones in 7 of the 10 strains tested, with MICs ranging from 4 to 64 μg/ml. No mutations in deformylase (
def
) and formyltransferase (
fmt
) genes were detected in any of the LBM415-resistant mutants.
Absorption, Metabolism, and Excretion of [
14
C]Viramidine in Humans
Authors: Lin Chin-chung , Xu Christine , Zhu Nanqun , Yeh Li-Tain 
Published: June 2006

ABSTRACT

Absorption, metabolism, and excretion of [
14
C]viramidine, a prodrug of ribavirin, were studied in humans following a single oral dose (600 mg). Viramidine was rapidly absorbed, with a time to maximum concentration of the drug in plasma of 1.5 h. Viramidine and ribavirin accounted for only 4.3% and 42% of plasma area under the concentration-time curve (AUC) for radioactivity, respectively, indicating extensive conversion of viramidine to ribavirin, followed by further metabolism of ribavirin. The drug was largely trapped in red blood cells (RBC), with an RBC-to-plasma radioactivity AUC
0-∞
ratio of 108. Excretion of total radioactivity in urine and feces accounted for 50.8% and 26.1% of the dose, respectively. The metabolic profile in urine (0 to 24 h) indicated that viramidine was excreted primarily as triazole carboxamide (TCONH
2
), triazole carboxylic acid nucleoside (TCOOH), and ribavirin with a small amount of unchanged viramidine, which each accounted for 64.1%, 17.0%, 15.7%, and 3.2% of urinary radioactivity, respectively. The amounts of unchanged viramidine (3.4% of dose) and ribavirin (10% of dose) in urine were small after oral administration of viramidine.
In Vitro Selection and In Vivo Efficacy of Piperazine- and Alkanediamide-Linked Bisbenzamidines against
Pneumocystis
Pneumonia in Mice
Authors: Cushion Melanie T. , Walzer Peter D. , Ashbaugh Alan , Rebholz Sandra , Brubaker Ronald , Vanden Eynde Jean Jacques , Mayence Annie , Huang Tien L. 
Published: June 2006

ABSTRACT

Bisbenzamidines, such as pentamidine isethionate, are aromatic dicationic compounds that are active against
Pneumocystis
and other microbes but are oftentimes toxic to the host. To identify potential anti-
Pneumocystis
agents, we synthesized bisbenzamidine derivatives in which the parent compound pentamidine was modified by a 1,4-piperazinediyl, alkanediamide, or 1,3-phenylenediamide moiety as the central linker. Several of the compounds were more active against
P. carinii
and less toxic than pentamidine in cytotoxicity assays. For this study, we evaluated nine bisbenzamidine derivatives representing a range of in vitro activities, from highly active to inactive, for the treatment of pneumocystosis in an immunosuppressed mouse model. Six of these in vitro-active compounds, 01, 02, 04, 06, 100, and 101, exhibited marked efficacies against infection at a dose of 10 mg/kg of body weight, and four compounds, 01, 04, 100, and 101, showed significant increases in survival versus that of untreated infected control mice. Compound 100 was highly efficacious against the infection at 20 mg/kg and 40 mg/kg, with >1,000-fold reductions in burden, and resulted in improved survival curves versus those for pentamidine-treated mice (at the same doses). All six bisbenzamidine compounds that exhibited high in vitro activity significantly decreased the infection in vivo; two compounds, 12 and 102, with marked to moderate in vitro activities had slight or no activity in vivo, while compound 31 was inactive in vitro and was also inactive in vivo. Thus, the selection of highly active compounds from in vitro cytotoxicity assays was predictive of activity in the mouse model of
Pneumocystis
pneumonia. We conclude that a number of these bisbenzamidine compounds, especially compound 100, may show promise as new anti-
Pneumocystis
drugs.
The Cfr rRNA Methyltransferase Confers Resistance to Phenicols, Lincosamides, Oxazolidinones, Pleuromutilins, and Streptogramin A Antibiotics
Authors: Long Katherine S. , Poehlsgaard Jacob , Kehrenberg Corinna , Schwarz Stefan , Vester Birte 
Published: June 2006

ABSTRACTA novel multidrug resistance phenotype mediated by the Cfr rRNA methyltransferase is observed inStaphylococcus aureusandEscherichia coli. Thecfrgene has previously been identified as a phenicol and lincosamide resistance gene on plasmids isolated fromStaphylococcusspp. of animal origin and recently shown to encode a methyltransferase that modifies 23S rRNA at A2503. Antimicrobial susceptibility testing shows thatS. aureusandE. colistrains expressing thecfrgene exhibit elevated MICs to a number of chemically unrelated drugs. The phenotype is named PhLOPSAfor resistance to the following drug classes:Phenicols,Lincosamides,Oxazolidinones,Pleuromutilins, andStreptograminAantibiotics. Each of these five drug classes contains important antimicrobial agents that are currently used in human and/or veterinary medicine. We find that binding of the PhLOPSAdrugs, which bind to overlapping sites at the peptidyl transferase center that abut nucleotide A2503, is perturbed upon Cfr-mediated methylation. Decreased drug binding to Cfr-methylated ribosomes has been confirmed by footprinting analysis. No other rRNA methyltransferase is known to confer resistance to five chemically distinct classes of antimicrobials. In addition, the findings described in this study represent the first report of a gene conferring transferable resistance to pleuromutilins and oxazolidinones.
Clonal Dissemination of a CTX-M-15 β-Lactamase-Producing
Escherichia coli
Strain in the Paris Area, Tunis, and Bangui
Authors: Lavollay M. , Mamlouk K. , Frank T. , Akpabie A. , Burghoffer B. , Ben Redjeb S. , Bercion R. , Gautier V. , Arlet G. 
Published: June 2006

ABSTRACT

One hundred twenty CTX-M-15-producing
Escherichia coli
strains isolated in 10 different hospitals from Paris (France), in the Hospital Charles Nicolle in Tunis (Tunisia), and in the Pasteur Institute in Bangui, Central African Republic (CAR), between 2000 and 2004 were studied. Eighty isolates, recovered from the three countries, were clonally related by repetitive extragenic palindromic PCR and pulsed-field gel electrophoresis. Various resistance profiles were identified among these clonal strains. After conjugation or electroporation of plasmids from
E. coli
strains representative of each profile and each geographic region, we observed seven resistance profiles in the recipient strains. Incompatibility typing showed that all the plasmids transferred from the clonal strains studied, except one, belonged to the incompatibility group FII. They all shared a multidrug resistance region (MDR) resembling the MDR region located in pC15-1a, a plasmid associated with an outbreak of a CTX-M-15-producing
E. coli
strain in Canada. They also shared the common backbone of an apparent mosaic plasmid, including several features present in pC15-1a and in pRSB107, a plasmid isolated from a sewage treatment plant. This study suggests that although the plasmid-borne
bla
CTX-M-15
gene could be transferred horizontally, its dissemination between France, Tunisia, and CAR was due primarily to its residence in an
E. coli
clone with a strong propensity for dissemination.
A Phe389Leu Substitution in ErgA Confers Terbinafine Resistance in
Aspergillus fumigatus
Authors: Rocha E. M. F. , Gardiner R. E. , Park S. , Martinez-Rossi N. M. , Perlin D. S. 
Published: June 2006

ABSTRACT

Replacement of phenylalanine with leucine at position 391 in squalene epoxidase was identified as being responsible for terbinafine resistance in mutants of
Aspergillus nidulans
. The equivalent mutation was engineered into the
ergA
gene of
Aspergillus fumigatus
, resulting in an F389L substitution that also conferred resistance to this pathogenic mold.
Effect of Cell Culture Conditions on the Anticytomegalovirus Activity of Maribavir
Authors: Chou Sunwen , Van Wechel Laura C. , Marousek Gail I. 
Published: June 2006

ABSTRACT
The cytomegalovirus UL97 kinase inhibitor maribavir suppressed viral growth more effectively in lung fibroblasts than in skin fibroblasts, and some cellular kinase inhibitors enhanced its antiviral activity. These effects influence the phenotypic assay of drug susceptibility and suggest the possibility of therapeutically useful combinations of maribavir and cellular kinase inhibitors.
Enteroviral Meningitis: Natural History and Outcome of Pleconaril Therapy
Authors: Desmond R. A. , Accortt N. A. , Talley L. , Villano S. A. , Soong S.-J. , Whitley R. J. 
Published: June 2006

ABSTRACT

Enteroviral meningitis causes appreciable morbidity in adults, including hospitalization, decreased activity, and headache. Limited data define the natural history of disease. No antiviral therapeutic agent has demonstrated improved outcome in controlled clinical trials. Pleconaril, an inhibitor of enterovirus replication, was tested in two placebo-controlled clinical trials. Of 607 randomized patients in a multicenter, double-blind placebo-controlled study of pleconaril (200 mg three times daily versus an identical-appearing placebo), 240 patients were confirmed to have enterovirus infection. The time to headache resolution was evaluated by using Kaplan-Meier survival methodology. A Cox regression model evaluated multivariate factors associated with disease resolution. Resolution of headache in patients with concomitant moderate to severe nausea at baseline occurred at a median of 9.5 days in the absence of therapy and was reduced to 7.0 days for pleconaril recipients (
P
= 0.009). For a headache score of >5 alone, treated patients resolved headache significantly more rapidly (
P
= 0.005). Males resolved headache 50% faster than females. Regardless of randomization group, patients with a baseline headache score of 5 or greater resolved headache 50% more slowly than patients with a baseline headache score of 4. No differences in either clinical or laboratory adverse events were noted. Over 50% of untreated patients had a persistent headache that was greater than 1 week in duration. Pleconaril shortened the course of illness compared to placebo recipients, especially in the early disease course. However, the benefit was achieved only modestly in a subgroup analysis of patients with more severe disease after adjusting for confounding variables.
Activities of Ceftobiprole and Other β-Lactams against
Streptococcus pneumoniae
Clinical Isolates from the United States with Defined Substitutions in Penicillin-Binding Proteins PBP 1a, PBP 2b, and PBP 2x
Authors: Davies Todd A. , Shang Wenchi , Bush Karen 
Published: June 2006

ABSTRACT

The activities of ceftobiprole and other β-lactams were examined with 30
Streptococcus pneumoniae
isolates containing multiple
pbp1a
,
pbp2b
, and
pbp2x
mutations. The highest ceftobiprole MIC was 1 μg/ml, while the comparator MICs were 16 to 64 μg/ml. Fifty percent inhibitory concentrations for penicillin-binding protein 2x were 0.5 μg/ml (ceftobiprole) and 4 μg/ml (ceftriaxone) in a penicillin- and ceftriaxone-resistant isolate.
Interactions between Glycopeptides and β-Lactams against Isogenic Pairs of Teicoplanin-Susceptible and -Resistant Strains of
Staphylococcus haemolyticus
Authors: Vignaroli Carla , Biavasco Francesca , Varaldo Pietro E. 
Published: June 2006

ABSTRACT

Four isogenic derivatives with stably increased glycopeptide MICs (all become resistant to teicoplanin) were obtained from four glycopeptide-susceptible clinical isolates of
Staphylococcus haemolyticus
. All strains were extensively analyzed and compared for a number of distinctive features. In particular, the results provided insights into the puzzling issue of antistaphylococcal interactions between glycopeptides and β-lactams, especially the paradox of double zones around β-lactam disks and the relationships between autolysis rate and type of interaction.
Interaction between Posaconazole and Caspofungin in Concomitant Treatment of Mice with Systemic
Aspergillus
Infection
Authors: Cacciapuoti Anthony , Halpern Judith , Mendrick Cara , Norris Christine , Patel Reena , Loebenberg David 
Published: June 2006

ABSTRACT

The interaction of posaconazole and caspofungin was evaluated in concomitant treatment of
Aspergillus fumigatus
(two strains) or
A. flavus
(one strain) systemic infections in immunocompetent mice. Survival curves for mice treated with the combinations were compared statistically with those for mice treated with the component monotherapies. No antagonism was observed.
Impact of Antimicrobial Dosing Regimen on Evolution of Drug Resistance In Vivo: Fluconazole andCandida albicans
Authors: Andes D. , Forrest A. , Lepak A. , Nett J. , Marchillo K. , Lincoln L. 
Published: June 2006

ABSTRACTNumerous factors have been theorized to affect the development of antimicrobial resistance, including those specific to the host, the organism, the environment, the drug, and the drug prescriber. One variable under the control of the prescriber is the drug dosing regimen. Dosing regimens can vary in dose level, dosing interval, and treatment duration. The current studies examined the relationships between antimicrobial dosing regimens and resistance development by use of an in vivo model. A murine model of systemicCandida albicansinfection was used to examine resistance emergence during exposure to the triazole antifungal fluconazole. Data from this experimental model demonstrated that the more frequently administered dosing prevented selection of the isogenic resistant cell populations. Conversely, dosing regimens producing prolonged sub-MIC effects appeared to contribute to the outgrowth of isogenic resistant strains. The association between dosing and resistance emergence observed in the current investigation is disparate from that described for antimicrobial compounds with cidal killing characteristics. The inhibitory or static antimicrobial activity of the triazole compounds may explain these differences.