bluuebunny/crossref_metadata_2025_split huggingface dataset:
BAL9141, a Novel Extended-Spectrum Cephalosporin Active against Methicillin-Resistant
Staphylococcus aureus
in Treatment of Experimental Endocarditis
Authors: Entenza J. M. , Hohl P. , Heinze-Krauss I. , Glauser M. P. , Moreillon P. 
Published: July 2002

ABSTRACT

The therapeutic efficacy of BAL9141 (formerly Ro 63-9141), a novel cephalosporin with broad in vitro activity that also has activity against methicillin-resistant
Staphylococcus aureus
(MRSA), was investigated in rats with experimental endocarditis. The test organisms were homogeneously methicillin-resistant
S. aureus
strain COL transformed with the penicillinase-encoding plasmid pI524 (COL Bla+) and homogeneously methicillin-resistant, penicillinase-producing isolate P8-Hom, selected by serial exposure of parent strain P8 to methicillin. The MICs of BAL9141 for these organisms (2 mg/liter) were low, and BAL9141was bactericidal in time-kill curve studies after 24 h of exposure to either two, four, or eight times the MIC. Rats with experimental endocarditis were treated in a three-arm study with a continuous infusion of BAL5788 (formerly Ro 65-5788), a carbamate prodrug of BAL9141, or with amoxicillin-clavulanate or vancomycin. The rats were administered BAL9141 to obtain steady-state target levels of 20, 10, and 5 mg of per liter or were administered either 1.2 g of amoxicillin-clavulanate (ratio 5:1) every 6 h or 1 g of vancomycin every 12 h at changing flow rates to simulate the pharmacokinetics produced in humans by intermittent intravenous treatment. Treatment was started 12 h after bacterial challenge and lasted for 3 days. BAL9141 was successful in the treatment of experimental endocarditis due to either MRSA isolate COL Bla+ or MRSA isolate P8-Hom at the three targeted steady-state concentrations and sterilized >90% of cardiac vegetations (
P
< 0.005 versus controls;
P
< 0.05 versus amoxicillin-clavulanate and vancomycin treatment groups). These promising in vivo results with BAL9141 correlated with the high affinity of the drug for PBP 2a and its stability to penicillinase hydrolysis observed in vitro.
In Vitro Potentiation of Antibiotic Activities by a Catecholate Iron Chelator against Chloroquine-ResistantPlasmodium falciparum
Authors: Pradines Bruno , Ramiandrasoa Florence , Rolain Jean Marc , Rogier Christophe , Mosnier Joel , Daries William , Fusai Thierry , Kunesch Gerhard , Le Bras Jacques , Parzy Daniel 
Published: July 2002

ABSTRACTFR160, a catechol iron chelator, and tetracyclines or norfloxacin exert in vitro additive or synergistic activity against a chloroquine-resistantPlasmodium falciparumclone. FR160 shows antagonistic effects in association with macrolides, ofloxacin, and rifampin.
Involvement of Multidrug Resistance-Associated Protein 2 in Intestinal Secretion of Grepafloxacin in Rats
Authors: Naruhashi Kazumasa , Tamai Ikumi , Inoue Natsuko , Muraoka Hiromi , Sai Yoshimichi , Suzuki Nagao , Tsuji Akira 
Published: July 2002

ABSTRACTWe investigated the contribution of multidrug resistance-associated protein 2 (MRP2) to the secretory transport of grepafloxacin and compared its functional role with that of P-glycoprotein (P-gp) by using Sprague-Dawley rats (SDRs) and Eisai hyperbilirubinemic rats (EHBRs), in which MRP2 is hereditarily defective. In intestinal tissue from SDRs mounted in Ussing chambers, the level of transport in the direction from the serosal layer to the mucosal layer was twofold greater than that in the direction from the mucosal layer to the serosal layer. This secretory transport of grepafloxacin was diminished by both probenecid, an MRP2 inhibitor, and cyclosporine, a P-gp inhibitor. In intestinal tissue from EHBRs, the secretory transport of grepafloxacin was lower than that in intestinal tissue from SDRs and was inhibited by cyclosporine but not by probenecid. The absorption of grepafloxacin from intestinal loops in SDRs was in the order of duodenum > jejunum > ileum and was increased by cyclosporine but not by probenecid. The absorption in EHBRs was not higher than that in SDRs. The intestinal secretory clearance in SDRs after intravenous administration of grepafloxacin was shown to be greater for the ileum than for the duodenum, which is in good agreement with the previously reported regional expression profile of MRP2 mRNA. The intestinal secretory clearance was lower in EHBRs than in SDRs. Accordingly, in addition to P-gp, MRP2 might play a role in the secretory transport of grepafloxacin. The function of MRP2 in facilitating grepafloxacin transport in the secretory direction is more pronounced both in vitro and in vivo, while the restriction of entry from the lumen into the cell by MRP2 seems to be negligible, compared with that by P-gp, in the case of grepafloxacin.
Quantitative PCR Assay To Evaluate Ampicillin, Ofloxacin, and Doxycycline for Treatment of Experimental Leptospirosis
Authors: Truccolo Johann , Charavay Françoise , Merien Fabrice , Perolat Philippe 
Published: July 2002

ABSTRACTThe susceptibility ofLeptospira interrogansserovar icterohaemorrhagiae strain Verdun to selected antibiotics used in medical practice (ampicillin, doxycycline, and ofloxacin) was evaluated in a Syrian hamster model, to determine the efficacy of these antibiotics during the course of the disease. A quantitative PCR assay was used to monitor the density of leptospires in blood and in target organs (liver, kidney, lung, heart, and spleen). Our results demonstrated the ability of ampicillin at a high dose (100 mg/kg of body weight) to clear leptospires from the host, except from kidneys and heart, where 102leptospires/g remained at day 6. Ofloxacin (30 mg/kg) was unable to clear bacteria from blood or kidneys. With doxycycline (10 mg/kg), the clearance of leptospires occurred in 2 days in all the target organs studied, with the exception of liver, which required 3 days. Our data demonstrate the value of monitoring the kinetics of experimental leptospiral infection in order to accurately evaluate the efficacy of antibiotics. We have demonstrated the potential value of doxycycline for the treatment of leptospirosis cases, except in circumstances where it is contraindicated. This experimental model could be used to define better therapeutic strategies for human leptospirosis, by testing associations or new formulations of antibiotics.
A Chemically Modified Tetracycline (CMT-3) Is a New Antifungal Agent
Authors: Liu Yu , Ryan Maria E. , Lee Hsi-Ming , Simon Sanford , Tortora George , Lauzon Carol , Leung Michael K. , Golub Lorne M. 
Published: July 2002

ABSTRACT

Several chemically modified tetracycline analogs (CMTs), which were chemically modified to eliminate their antibacterial efficacy, were unexpectedly found to have antifungal properties. Of 10 CMTs screened in vitro, all exhibited antifungal activities, although their efficacies varied. Among these compounds, CMT-315, -3, and -308 were found to be the most potent as antifungal agents. The MICs of CMT-3 against 47 strains of fungi in vitro were determined by using amphotericin B (AMB) and doxycycline as positive and negative controls, respectively. The MICs of CMT-3 were generally found to be between 0.25 and 8.00 μg/ml, a range that approximates the blood levels of this drug when administrated orally to humans. Of all the yeast species tested to date,
Candida albicans
showed the greatest sensitivity to CMT-3. The filamentous species most susceptible to CMT-3 were found to be
Epidermophyton floccosum
,
Microsporum gypseum
,
Pseudallescheria boydii
, a
Penicillium
sp.,
Scedosporium apiospermum
, a
Tricothecium
sp., and
Trichophyton rubrum
. Growth inhibition of
C. albicans
by CMT-3, determined by a turbidity assay, indicated a 50% inhibitory concentration of 1 μg/ml. Thirty-nine strains, including 20 yeasts and 19 molds, were used to measure viability (the ability to grow after treatment with a drug) inhibition by CMT-3 and AMB. CMT-3 exhibited fungicidal activity against most of these fungi, especially the filamentous fungi. Eighty-four percent (16 of 19) of the filamentous fungi tested showed more than 90% inhibition of viability by CMT-3. In contrast, AMB showed fungicidal activity against all yeasts tested. However, most of the filamentous fungi (16 of 19) showed less than 50% inhibition of viability by AMB, indicating that AMB is fungistatic against most of these filamentous fungi. To begin to identify the sites in fungal cells affected by CMT-3,
C. albicans
and a
Penicillium
sp. were incubated with the compound at 35°C, and then the fluorescence of CMT-3 was observed by confocal laser scanning electron microscopy. CMT-3 appeared to have widespread intracellular distribution throughout
C. albicans
and the
Penicillium
sp. The mechanisms of the antifungal activity of CMT-3 are now being explored.
In Vitro Activities of Free and Lipid Formulations of Amphotericin B and Nystatin against Clinical Isolates ofCoccidioides immitisat Various Saprobic Stages
Authors: González Gloria M. , Tijerina Rolando , Sutton Deanna A. , Graybill John R. , Rinaldi Michael G. 
Published: July 2002

ABSTRACTWe investigated the susceptibilities of hyphal, mixed hyphal, ungerminated arthroconidial, and germinated arthroconidial populations ofCoccidioides immitisto lipid formulations of amphotericin B and nystatin and their conventional preparations, utilizing the National Committee for Clinical Laboratory Standards M38-P broth macrodilution method. The differences in effects of the three different growth stages of the saprobic phase ofC. immitison the MIC/minimum lethal concentration (MLC) ratio were not statistically significant for any of the antifungal agents tested. These results suggest that either inocula could be used for in vitro susceptibility studies withC. immitis.
Single-Dose Pharmacokinetics of Amprenavir Coadministered with Grapefruit Juice
Authors: Demarles D. , Gillotin C. , Bonaventure-Paci S. , Vincent I. , Fosse S. , Taburet A. M. 
Published: July 2002

ABSTRACT

In this crossover study in 12 healthy volunteers, coadministration of amprenavir (1,200 mg; single dose) with grapefruit juice slightly reduced the maximum concentration of drug in serum (
C
max
) compared to administration with water (7.11 versus 9.10 μg/ml), slightly increased the time to
C
max
(1.13 versus 0.75 h), and did not affect the area under the concentration-time curve from 0 to 12 h (AUC
0-12
), the AUC
0-∞
, or the concentration at 12 h. Therefore, grapefruit juice does not clinically significantly affect amprenavir pharmacokinetics.
In Vitro Activity of Linezolid against
Clostridium difficile
Authors: Peláez T. , Alonso R. , Pérez C. , Alcalá L. , Cuevas O. , Bouza E. 
Published: July 2002

ABSTRACT

We examined the in vitro activity of linezolid against
Clostridium difficile,
including isolates with reduced susceptibility to metronidazole or vancomycin. The MIC at which 50% of the isolates were inhibited (MIC
50
) and MIC
90
were 0.5 and 2 μg/ml, respectively (range, 0.03 to 4 μg/ml). MICs were always ≤ 4 μg/ml, and thus, all isolates were considered susceptible.
Histidine-Rich Protein II: a Novel Approach to Malaria Drug Sensitivity Testing
Authors: Noedl Harald , Wernsdorfer Walther H. , Miller Robert Scott , Wongsrichanalai Chansuda 
Published: July 2002

ABSTRACT

The production of histidine-rich protein II (HRP2), a histidine- and alanine-rich protein produced by
Plasmodium falciparum
, is closely associated with the development and proliferation of the parasite and therefore is perfectly suited to reflect growth inhibition as a measure of drug susceptibility. It was the aim of the present study to develop a malaria drug sensitivity assay based on the measurement of HRP2 in a simple enzyme-linked immunosorbent assay (ELISA). The new test proved to be as reliable as traditional in vitro assays, while it was considerably easier to establish and perform. Parasites are incubated at an initial level of parasitemia of 0.01 to 0.1% on microculture plates predosed with ascending concentrations of antimalarial drugs. After incubation for 48 to 72 h, the samples are freeze-thawed and transferred to ELISA plates. The complete ELISA takes about 2.5 h to perform, may be carried out with commercially available test kits, and requires relatively little technical equipment. In correlation analysis, the results closely paralleled those obtained by the isotopic assay (
R
= 0.892;
P
< 0.0001) and World Health Organization schizont maturation tests (
R
= 0.959;
P
< 0.0001). The novel HRP2 drug susceptibility assay proved to be very sensitive, simple to establish, and highly reproducible. It can be used for a wide range of applications, from epidemiological studies to the screening of new drugs, and may have the potential to replace traditional in vitro techniques. Standard operating procedures, updated information, and analytical software are available from
http://malaria.farch.net
.
Comparison of the Effects of Deferiprone versus Deferoxamine on Growth and Virulence of
Yersinia enterocolitica
Authors: Lesic Biliana , Foulon Jeannine , Carniel Elisabeth 
Published: July 2002

ABSTRACT

Deferoxamine, a drug used to treat patients with iron overload, has the capacity to promote systemic
Y. enterocolitica
infections in humans. The aim of this study was to determine whether deferiprone, the only orally active alternative treatment, has the same potential. When
Y. enterocolitica
IP864 was grown in an iron-poor chemically defined medium, addition of deferoxamine promoted its growth, while various concentrations of deferiprone did not display this activity. Similarly, on iron-poor agar plates, various
Y. enterocolitica
strains were able to grow around paper disks impregnated with deferoxamine in a dose-dependent manner, while no growth was observed around the deferiprone disks. In a mouse experimental model of infection, the 50% lethal dose (LD
50
) of strain IP864 was decreased by more than 5 log units in mice pretreated with deferoxamine, while a deferiprone pretreatment did not affect it. Therefore, in contrast to deferoxamine, deferiprone does not enhance growth of pathogenic
Y. enterocolitica
in vitro and does not have the potential to promote
Y. enterocolitica
septicemia in a mouse model of infection. Deferiprone may thus represent a useful alternative iron-chelation therapy during invasive
Y. enterocolitica
infections.
Antitrypanosomal Activities of Proteasome Inhibitors
Authors: Nkemgu-Njinkeng Joseph , Rosenkranz Vera , Wink Michael , Steverding Dietmar 
Published: July 2002

ABSTRACT

Seven peptidyl proteasome inhibitors were tested for in vitro activity against
Trypanosoma brucei
bloodstream forms. Two compounds showed activity in the low nanomolar range. In general, trypanosomes were more susceptible to the compounds than were human HL-60 cells. The data support the potential of proteasome inhibitors for rational antitrypanosomal drug development.
Quantifying Translocation ofListeria monocytogenesin Rats by Using Urinary Nitric Oxide-Derived Metabolites
Authors: Sprong R. Corinne , Hulstein Marco F. E. , van der Meer Roelof 
Published: July 2002

ABSTRACTThe urinary nitric oxide metabolites NO2−and NO3−(summed as NOx) are a noninvasive, quantitative biomarker of translocation of salmonella from the intestinal lumen to systemic organs.Listeria monocytogenesis a food-borne gram-positive pathogen that can also cross the intestinal epithelium. In this study, we tested the efficacy of urinary NOxas a marker of listeria translocation. Rats (eight per group) were orally infected with increasing doses ofL. monocytogenes; control rats received heat-killed listeria. The kinetics of urinary NOxand population levels of listeria in feces were determined for 7 days. Another group of rats was killed 1 day after infection to verify translocation by culturing viable listeria from systemic organs. Oral administration of increasing doses ofL. monocytogenesresulted in a time- and dose-dependent increase in urinary NOxexcretion. Translocation was a prerequisite for inducing a NOxresponse, since heat-killedL. monocytogenesdid not elevate NOxexcretion in urine. Fecal counts of listeria also showed dose and time dependency. Moreover, the number of viableL. monocytogenescells in mesenteric lymph nodes also increased in a dose-dependent manner and correlated with urinary NOx. In conclusion, urinary NOxis a quantitative, noninvasive biomarker of listeria translocation.
Loss of O157 O Antigenicity of Verotoxin-Producing
Escherichia coli
O157:H7 Surviving under Starvation Conditions
Authors: Hara-Kudo Yukiko , Miyahara Michiko , Kumagai Susumu 
Published: July 2002

ABSTRACT

Verotoxin (VT)-producing
Escherichia coli
O157:H7 was culturable on agar media after being left in water for 21 months. However, there were a number of colonies which had lost O157 O antigenicity. These colonies produced VTs, which are pathogenic to humans. These observations suggest that the immunologic methods based on O157 O antigenicity are unable to detect and isolate VT-producing
E. coli
in foods and other environments if the organism has been under starvation conditions for a long period.
Genetically Modified
Vibrio harveyi
Strains as Potential Bioindicators of Mutagenic Pollution of Marine Environments
Authors: Czyz˙ Agata , Jasiecki Jacek , Bogdan Adam , Szpilewska Hanna , We˛grzyn Grzegorz 
Published: July 2002

ABSTRACT

For biodetection of mutagenic pollution of marine environments, an organism naturally occurring in these habitats should be used. We found that marine bacterium
Vibrio harveyi
may be an appropriate bioindicator of mutagenic pollution. For positive selection of mutants, we developed a simple method for isolation of
V. harveyi
mutants resistant to neomycin. We constructed genetically modified
V. harveyi
strains that produce significantly more neomycin-resistant mutants upon treatment with low concentrations of mutagens than the wild-type counterpart. The sensitivity of the mutagenicity test with the
V. harveyi
strains is at least comparable to (if not higher than) that of the commonly used Ames test, which uses
Salmonella enterica
serovar Typhimurium strains. Therefore, we consider that the
V. harveyi
strains described in this report could be used as potential bioindicators of mutagenic pollution of marine environments.
Cotransformation of
Trichoderma harzianum
with β-Glucuronidase and Green Fluorescent Protein Genes Provides a Useful Tool for Monitoring Fungal Growth and Activity in Natural Soils
Authors: Bae Yeoung-Seuk , Knudsen Guy R. 
Published: July 2002

ABSTRACT

Trichoderma harzianum
was cotransformed with genes encoding green fluorescent protein (GFP), β-glucuronidase (GUS), and hygromycin B (
hygB
) resistance, using polyethylene glycol-mediated transformation. One cotransformant (ThzID1-M3) was mitotically stable for 6 months despite successive subculturing without selection pressure. ThzID1-M3 morphology was similar to that of the wild type; however, the mycelial growth rate on agar was reduced. ThzID1-M3 was formed into calcium alginate pellets and placed onto buried glass slides in a nonsterile soil, and its ability to grow, sporulate, and colonize sclerotia of
Sclerotinia sclerotiorum
was compared with that of the wild-type strain. Wild-type and transformant strains both colonized sclerotia at levels above those of indigenous
Trichoderma
spp. in untreated controls. There were no significant differences in colonization levels between wild-type and cotransformant strains; however, the presence of the GFP and GUS marker genes permitted differentiation of introduced
Trichoderma
from indigenous strains. GFP activity was a useful tool for nondestructive monitoring of the hyphal growth of the transformant in a natural soil. The green color of cotransformant hyphae was clearly visible with a UV epifluorescence microscope, while indigenous fungi in the same samples were barely visible. Green-fluorescing conidiophores and conidia were observed within the first 3 days of incubation in soil, and this was followed by the formation of terminal and intercalary chlamydospores and subsequent disintegration of older hyphal segments. Addition of 5-bromo-4-chloro-3-indolyl-β-
d
-glucuronic acid (X-Gluc) substrate to recovered glass slides confirmed the activity of GUS as well as GFP in soil. Our results suggest that cotransformation with GFP and GUS can provide a valuable tool for the detection and monitoring of specific strains of
T. harzianum
released into the soil.
Antagonistic Activity ofLactobacillus acidophilusLB against IntracellularSalmonella entericaSerovar Typhimurium Infecting Human Enterocyte-Like Caco-2/TC-7 Cells
Authors: Coconnier Marie-Hélène , Liévin Vanessa , Lorrot Mathie , Servin Alain L. 
Published: July 2002

ABSTRACTTo gain further insight into the mechanism by which lactobacilli develop antimicrobial activity, we have examined howLactobacillus acidophilusLB inhibits the promoted cellular injuries and intracellular lifestyle ofSalmonella entericaserovar Typhimurium SL1344 infecting the cultured, fully differentiated human intestinal cell line Caco-2/TC-7. We showed that the spent culture supernatant of strain LB (LB-SCS) decreases the number of apical serovar Typhimurium-induced F-actin rearrangements in infected cells. LB-SCS treatment efficiently decreased transcellular passage ofS. entericaserovar Typhimurium. Moreover, LB-SCS treatment inhibited intracellular growth of serovar Typhimurium, since treated intracellular bacteria displayed a small, rounded morphology resembling that of resting bacteria. We also showed that LB-SCS treatment inhibits adhesion-dependent serovar Typhimurium-induced interleukin-8 production.
Physiologic Determinants of Radiation Resistance in
Deinococcus radiodurans
Authors: Venkateswaran Amudhan , McFarlan Sara C. , Ghosal Debabrota , Minton Kenneth W. , Vasilenko Alexander , Makarova Kira , Wackett Lawrence P. , Daly Michael J. 
Published: July 2002

ABSTRACT

Immense volumes of radioactive wastes, which were generated during nuclear weapons production, were disposed of directly in the ground during the Cold War, a period when national security priorities often surmounted concerns over the environment. The bacterium
Deinococcus radiodurans
is the most radiation-resistant organism known and is currently being engineered for remediation of the toxic metal and organic components of these environmental wastes. Understanding the biotic potential of
D. radiodurans
and its global physiological integrity in nutritionally restricted radioactive environments is important in development of this organism for in situ bioremediation. We have previously shown that
D. radiodurans
can grow on rich medium in the presence of continuous radiation (6,000 rads/h) without lethality. In this study we developed a chemically defined minimal medium that can be used to analyze growth of this organism in the presence and in the absence of continuous radiation; whereas cell growth was not affected in the absence of radiation, cells did not grow and were killed in the presence of continuous radiation. Under nutrient-limiting conditions, DNA repair was found to be limited by the metabolic capabilities of
D. radiodurans
and not by any nutritionally induced defect in genetic repair. The results of our growth studies and analysis of the complete
D. radiodurans
genomic sequence support the hypothesis that there are several defects in
D. radiodurans
global metabolic regulation that limit carbon, nitrogen, and DNA metabolism. We identified key nutritional constituents that restore growth of
D. radiodurans
in nutritionally limiting radioactive environments.