bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comparative Pharmacokinetics, Tissue Distributions, and Effects on Renal Function of Novel Polymeric Formulations of Amphotericin B and Amphotericin B-Deoxycholate in Rats
Authors: Echevarría Iciar , Barturen Celia , Renedo María Jesús , Trocóniz Iñaki F. , Dios-Viéitez M. Carmen 
Published: July 2002

ABSTRACT
The pharmacokinetic profiles of a traditional formulation of amphotericin B (Fungizone) and novel nanosphere and mixed micelle delivery systems developed for amphotericin B were compared and described. Six groups of male Wistar rats received intravenous injections of the different formulations. Plasma and tissue samples were obtained at 11 different times after dosing, with three animals used each time. The amphotericin B concentrations in plasma and tissues were analyzed by high-performance liquid chromatography. The plasma drug concentration-time profiles were best described by a two-compartment model. Models that described the observed single or double peak disposition kinetics in kidney, liver, and spleen were also developed. Parameter estimates from those models show that components of the formulation such as poloxamer 188, which is present in all new formulations, seem to play an important role in the rate of drug uptake by the tissues; in general, the levels of amphotericin B in tissues were increased after the administration of the new formulations compared with those after the administration of Fungizone. The increment in the baseline plasma creatinine level was used as an index of renal function. All formulations increased this baseline value, but the novel formulations exhibited fewer renal effects than Fungizone did. However, a direct relationship between drug exposure in the kidneys and development of renal damage could not be found.
Clarithromycin Inhibits NF-κB Activation in Human Peripheral Blood Mononuclear Cells and Pulmonary Epithelial Cells
Authors: Ichiyama Takashi , Nishikawa Miki , Yoshitomi Tomomi , Hasegawa Shunji , Matsubara Tomoyo , Hayashi Takashi , Furukawa Susumu 
Published: July 2002

ABSTRACTMacrolide antibiotics modulate the production of proinflammatory cytokines in vivo and in vitro. Transcription of the genes for these proinflammatory cytokines is regulated by nuclear factor κB (NF-κB). We examined whether or not clarithromycin inhibits the activation of NF-κB induced by tumor necrosis factor alpha (TNF-α) or staphylococcal enterotoxin A (SEA) in human monocytic U-937 cells, a T-cell line (Jurkat), a pulmonary epithelial cell line (A549), and peripheral blood mononuclear cells (PBMC). Flow cytometry revealed that clarithromycin suppresses NF-κB activation induced by TNF-α in U-937 and Jurkat cells in a concentration-related manner. Western blot analysis also demonstrated that clarithromycin inhibits NF-κB activation induced by TNF-α in U-937, Jurkat, and A549 cells and PBMC and by SEA in PBMC. Western blot analysis of cytoplasmic extracts of A549 cells revealed that this inhibition is not linked to preservation of expression of the IκBα protein. The chloramphenicol acetyltransferase assay indicated that NF-κB-dependent reporter gene expression is suppressed in U-937 cells pretreated with clarithromycin. These findings are consistent with the idea that clarithromycin suppresses the production of proinflammatory cytokines via inhibition of NF-κB activation.
Aminoglycoside Resistance Genes
aph(2")-Ib
and
aac(6′)-Im
Detected Together in Strains of both
Escherichia coli
and
Enterococcus faecium
Authors: Chow Joseph W. , Kak Vivek , You Il , Kao Susan J. , Petrin Joanne , Clewell Don B. , Lerner Stephen A. , Miller George H. , Shaw Karen J. 
Published: July 2002

ABSTRACT

Escherichia coli
SCH92111602 expresses an aminoglycoside resistance profile similar to that conferred by the
aac(6′)-Ie-aph(2")-Ia
gene found in gram-positive cocci and was found to contain the aminoglycoside resistance genes
aph(2")-Ib
and
aac(6′)-Im
(only 44 nucleotides apart).
aph(2")-Ib
had been reported previously in
Enterococcus faecium
SF11770.
aac(6′)-Im
had not been detected previously in enterococci and was found to be present also 44 nucleotides downstream from
aph(2")-Ib
in
E. faecium
SF11770.
aph(2")-Ib
and
aac(6′)-Im
are separate open reading frames, each with its own putative ribosome binding site, whereas
aac(6′)-Ie-aph(2")-Ia
appears to be a fusion of two genes with just one start and one stop codon. The deduced AAC(6′)-Im protein exhibits 56% identity and 80% similarity to the AAC(6′)-Ie domain of the bifunctional enzyme AAC(6′)-APH(2"). Our results document the existence of a member of the
aph(2")
family of genes in gram-negative bacteria and provide evidence suggesting the horizontal transfer of
aph(2")-Ib
and
aac(6′)-Im
as a unit between gram-positive and gram-negative bacteria.
Antioxidant Functions Required for Insusceptibility of
Saccharomyces cerevisiae
to Tetracycline Antibiotics
Authors: Angrave Fiona E. , Avery Simon V. 
Published: July 2002

ABSTRACT

Cu,Zn superoxide dismutase (Sod1) is required for insusceptibility of
Saccharomyces cerevisiae
to oxytetracycline (OTC). Here we report that Sod1 is also required for insusceptibility to doxycycline (DOX). Furthermore, among a range of antioxidant and redox balance mutants,
mac1
and
ctr1
deletion strains exhibited marked sensitization to OTC and DOX. Certain mutants exhibited a slight sensitivity to methacycline and minocycline. Addition of copper suppressed antibiotic sensitivity. Thus, intracellular copper as well as superoxide dismutase can be critical for eukaryotic tolerance of several tetracycline antibiotics.
Population Pharmacokinetics and Use of Monte Carlo Simulation To Evaluate Currently Recommended Dosing Regimens of Ciprofloxacin in Adult Patients with Cystic Fibrosis
Authors: Montgomery Megan J. , Beringer Paul M. , Aminimanizani Amir , Louie Stan G. , Shapiro Bertrand J. , Jelliffe Roger , Gill Mark A. 
Published: July 2002

ABSTRACT

Pharmacodynamic data on ciprofloxacin indicate that a target area under the concentration-time curve from 0 to 24 h (AUC
0–24
)/MIC ratio of ≥125 is necessary to achieve optimal bactericidal activity for the treatment of gram-negative pneumonia. The purpose of this prospective study was to (i) develop a pharmacokinetic (PK) model to be utilized for therapeutic drug monitoring (TDM) of ciprofloxacin and (ii) evaluate current ciprofloxacin dosing regimens for pneumonias in cystic fibrosis (CF) patients. Twelve adult CF patients received a single 400-mg dose of IV ciprofloxacin. Six blood samples were obtained over a 12-h interval. Serum drug concentrations were determined by high-pressure liquid chromotography and were fitted to one- and two-compartment models by using NPEM2. Ciprofloxacin MIC data for
Pseudomonas aeruginosa
were obtained from 1,213 CF patients enrolled in a large clinical trial. A Monte Carlo simulation was performed to estimate the fractional attainment of an AUC
0–24
/MIC ratio of ≥125. A two-compartment model best describes the serum drug concentration data. The mean fitted PK parameter values are volume of distribution in the central compartment, 0.29 liter/kg; volume of distribution at steady state, 1.1 liters/kg; total clearance, 0.34 liter/h/kg; distributional clearance, 0.89 liter/h/kg; half-life at α phase, 0.16 h; and half-life at β phase, 2.9 h. The overall fractional attainment of achieving an AUC
0–24
/MIC ratio of ≥125 against
P. aeruginosa
isolates with ciprofloxacin (400 mg every 12 h [q12h] and 8 qh) were 10 and 30%, respectively. A clinical breakpoint MIC of <0.5 μg/ml for susceptibility is suggested, based on an examination of the fractional attainment of the AUC
0–24
/MIC target at each MIC. The recommended doses of 400 mg q8h or q12h may be inadequate to treat an acute pulmonary exacerbation when given alone. The poor and variable AUC
0–24
/MIC ratios support the use of TDM to monitor and adjust the dosage to optimize the efficacy of ciprofloxacin therapy in these patients.
Antileishmanial Activity of an Indole Alkaloid fromPeschiera australis
Authors: Delorenzi Jan Carlo , Attias Márcia , Gattass Cerli R. , Andrade Marcelo , Rezende Cláudia , da Cunha Pinto Ângelo , Henriques Amélia T. , Bou-Habib Dumith C. , Saraiva Elvira M. B. 
Published: July 2002

ABSTRACTIn this study, we show the leishmanicidal effects of a chloroform fraction (CLF) and a purified indole alkaloid obtained from crude stem extract ofPeschiera australisagainstLeishmania amazonensis, a causative agent of cutaneous leishmaniasis in the New World. In a bioassay-guided chemical fractionation, the leishmanicidal activity in CLF completely and irreversibly inhibited promastigote growth. This fraction was also active against amastigotes in infected murine macrophages. Chemical analysis of CLF identified an iboga-type indole alkaloid coronaridine as one of its major compounds. Coronaridine showed potent antileishmanial activity, inhibiting promastigote and amastigote growth. Promastigotes and amastigotes treated with CLF or coronaridine showed pronounced alterations in their mitochondria as assessed by transmission electron microscopy.
Antimicrobial Resistance among Clinical Isolates of
Streptococcus pneumoniae
in the United States during 1999–2000, Including a Comparison of Resistance Rates since 1994–1995
Authors: Doern Gary V. , Heilmann Kristopher P. , Huynh Holly K. , Rhomberg Paul R. , Coffman Stacy L. , Brueggemann Angela B. 
Published: July 2002

ABSTRACT

A total of 1,531 recent clinical isolates of
Streptococcus pneumoniae
were collected from 33 medical centers nationwide during the winter of 1999–2000 and characterized at a central laboratory. Of these isolates, 34.2% were penicillin nonsusceptible (MIC ≥ 0.12 μg/ml) and 21.5% were high-level resistant (MIC ≥ 2 μg/ml). MICs to all beta-lactam antimicrobials increased as penicillin MICs increased. Resistance rates among non-beta-lactam agents were the following: macrolides, 25.2 to 25.7%; clindamycin, 8.9%; tetracycline, 16.3%; chloramphenicol, 8.3%; and trimethoprim-sulfamethoxazole (TMP-SMX), 30.3%. Resistance to non-beta-lactam agents was higher among penicillin-resistant strains than penicillin-susceptible strains; 22.4% of
S. pneumoniae
were multiresistant. Resistance to vancomycin and quinupristin-dalfopristin was not detected. Resistance to rifampin was 0.1%. Testing of seven fluoroquinolones resulted in the following rank order of in vitro activity: gemifloxacin > sitafloxacin > moxifloxacin > gatifloxacin > levofloxacin = ciprofloxacin > ofloxacin. For 1.4% of strains, ciprofloxacin MICs were ≥4 μg/ml. The MIC
90
s (MICs at which 90% of isolates were inhibited) of two ketolides were 0.06 μg/ml (ABT773) and 0.12 μg/ml (telithromycin). The MIC
90
of linezolid was 2 μg/ml. Overall, antimicrobial resistance was highest among middle ear fluid and sinus isolates of
S. pneumoniae
; lowest resistance rates were noted with isolates from cerebrospinal fluid and blood. Resistant isolates were most often recovered from children 0 to 5 years of age and from patients in the southeastern United States. This study represents a continuation of two previous national studies, one in 1994–1995 and the other in 1997–1998. Resistance rates with
S. pneumoniae
have increased markedly in the United States during the past 5 years. Increases in resistance from 1994–1995 to 1999–2000 for selected antimicrobial agents were as follows: penicillin, 10.6%; erythromycin, 16.1%; tetracycline, 9.0%; TMP-SMX, 9.1%; and chloramphenicol, 4.0%, the increase in multiresistance was 13.3%. Despite awareness and prevention efforts, antimicrobial resistance with
S. pneumoniae
continues to increase in the United States.
In Vitro Activities of Antibiotics against
Plasmodium falciparum
Are Inhibited by Iron
Authors: Pradines Bruno , Rogier Christophe , Fusai Thierry , Mosnier Joel , Daries William , Barret Eric , Parzy Daniel 
Published: July 2002

ABSTRACT

The in vitro activities of cyclines (tetracycline, doxycycline, minocycline, oxytetracycline, and rolitetracycline), macrolides (erythromycin, spiramycin, roxithromycin, and lincomycin), quinolones (norfloxacin and ofloxacin), rifampin, thiamphenicol, tobramycin, metronidazole, vancomycin, phosphomycin, and cephalosporins (cephalexin, cefaclor, cefamandole, cefuroxime, ceftriazone, cefotaxime, and cefoxitin) were evaluated on
Plasmodium falciparum
clones, using an isotopic, micro-drug susceptibility test. Only tetracyclines, macrolides, quinolones, and rifampin demonstrated in vitro activity against
P. falciparum
, which increased after a prolonged exposure (96 or 144 h). In the presence of iron (FeCl
3
), only the activities of tetracyclines and norfloxacin were decreased. Their in vitro activity against intraerythrocytic stages of multidrug-resistant
P. falciparum
and their efficacy in vivo favor the use of antibiotics as antimalarial drugs. However, due to their slow antimalarial action and to the fact that they act better after prolonged contact, they probably need to be administered in conjunction with a rapidly acting antimalarial drug, such as a short course of chloroquine or quinine.
Molecular Characterization of a Novel Plasmid-Encoded Cefotaximase (CTX-M-12) Found in Clinical
Klebsiella pneumoniae
Isolates from Kenya
Authors: Kariuki S. , Corkill J. E. , Revathi G. , Musoke R. , Hart C. A. 
Published: July 2002

ABSTRACT

Nine
Klebsiella pneumoniae
isolates, six from blood and three from cerebrospinal fluid of newborn babies at Kenyatta National Hospital, Nairobi, Kenya, were analyzed for the mechanism of cephalosporin resistance. By using pulsed-field gel electrophoresis of
Xba
I-digested chromosomal DNA, all the nine isolates were found to be clonal. PCR and direct sequencing revealed a novel extended-spectrum β-lactamase, which we designated CTX-M-12. It has a more potent hydrolytic activity against cefotaxime than against ceftazidime and a pI of 9.0 and is encoded on a large self-transferable ca. 160-kbp plasmid.
Resistance to Linezolid: Characterization of Mutations in rRNA and Comparison of Their Occurrences in Vancomycin-Resistant Enterococci
Authors: Prystowsky Jason , Siddiqui Farida , Chosay John , Shinabarger Dean L. , Millichap John , Peterson Lance R. , Noskin Gary A. 
Published: July 2002

ABSTRACT

To assess the potential for emergence of resistance during the use of linezolid, we tested 10 clinical isolates of vancomycin-resistant enterococci (VRE) (four
Enterococcus faecalis
, five
Enterococcus faecium
, and one
Enterococcus gallinarum
) as well as a vancomycin-susceptible control (ATCC 29212) strain of
E. faecalis
. The enterococci were exposed to doubling dilutions of linezolid for 12 passes. After the final passage, the linezolid plate growing VRE contained a higher drug concentration with
E. faecalis
than with
E. faecium
. DNA sequencing of the 23S rRNA genes revealed that linezolid resistance in three
E. faecalis
isolates was associated with a guanine to uracil transversion at bp 2576, while the one
E. faecium
isolate for which the MIC was 16 μg/ml contained a guanine to adenine transition at bp 2505.
Sodium Lauryl Sulfate Abrogates Human Immunodeficiency Virus Infectivity by Affecting Viral Attachment
Authors: Bestman-Smith Julie , Piret Jocelyne , Désormeaux André , Tremblay Michel J. , Omar Rabeea F. , Bergeron Michel G. 
Published: July 2002

ABSTRACTThe microbicidal activity of sodium lauryl sulfate (SLS) against human immunodeficiency virus type 1 (HIV-1) was studied in cultured cells. Pretreatment of HIV-1NL4-3with SLS decreased, in a concentration-dependent manner, its infectivity when using 1G5 as target cells. In the absence of a viral pretreatment period or when 1G5 cells were pretreated with SLS, the surfactant-induced inactivation of viral infectivity was less pronounced, especially at concentrations between 375 and 550 μM. SLS had no effect on HIV-1 when the virus was adsorbed to 1G5 cells by a 2-h incubation period. SLS almost completely inhibited the fusion process by decreasing the attachment of HIV-1 to target cells. SLS also inhibited the infectivity of HIV-1-based luciferase reporter viruses pseudotyped with the amphotropic murine leukemia virus envelope (which enters cells in a CD4-, CCR5-, and CXCR4-independent manner), indicating that SLS may inactivate other envelope viruses. In contrast, no effect was seen with vesicular stomatitis virus envelope glycoprotein G (which enters cells through receptor-mediated endocytosis) pretreated with up to 700 μM SLS. SLS also decreased, in a dose-dependent manner, the HIV-1-dependent syncytium formation between 1G5 and J1.1 cells after a 24-h incubation. The reduction of luciferase activity was more pronounced when J1.1 cells (which express HIV-1 proteins on their surface) were pretreated with SLS rather than 1G5 cells. Taken together, our results suggest that SLS could represent a candidate of choice for use in vaginal microbicides to prevent the sexual transmission of HIV and possibly other pathogens causing sexually transmitted diseases.
Pretreatment of Mice with Clindamycin Improves Survival of Endotoxic Shock by Modulating the Release of Inflammatory Cytokines
Authors: Hirata Norio , Hiramatsu Kazufumi , Kishi Kenji , Yamasaki Tohru , Ichimiya Tomoku , Nasu Masaru 
Published: July 2002

ABSTRACTSuppression of endotoxin release and subsequent production of inflammatory cytokines is crucial in the treatment of septic shock. We investigated the effect of clindamycin (CLI) on endotoxic shock induced in mice byEscherichia colilipopolysaccharide (LPS). Mice were treated with CLI (160 to 600 mg/kg) or saline and then injected withE. coliLPS andd-(+)-galactosamine intraperitoneally 0.5 h after CLI administration. Pretreatment with CLI significantly improved survival in a dose-dependent manner (CLI, at 160, 300, and 440 mg/kg) and significantly lowered the peak concentrations of tumor necrosis factor alpha and interleukin-1β(IL-1β) in serum. However, the peak concentrations of IL-6 in the sera of CLI-treated mice were higher than in control mice. Our findings suggest that CLI alters LPS-induced inflammatory cytokine production and suppresses endotoxin-induced mortality in this murine model.
Evaluation of a Cyclic GMP-Dependent Protein Kinase Inhibitor in Treatment of Murine Toxoplasmosis: Gamma Interferon Is Required for Efficacy
Authors: Nare Bakela , Allocco John J. , Liberator Paul A. , Donald Robert G. K. 
Published: July 2002

ABSTRACTThe trisubstituted pyrrole 4-[2-(4-fluorophenyl)-5-(1-methylpiperidine-4-yl)-1H-pyrrol-3-yl]pyridine (compound 1) is a potent inhibitor of cyclic GMP-dependent protein kinases from Apicomplexan protozoa and displays cytostatic activity againstToxoplasma gondiiin vitro.Compound 1 has now been evaluated againstT. gondiiinfections in the mouse and appeared to protect the animals when given intraperitoneally at 50 mg/kg twice daily for 10 days. However, samples from brain, spleen, and lung taken from infected treated mice revealed the presence of parasites after cessation of administration of compound 1, indicating that a transient asymptomatic parasite recrudescence occurs in all survivors. The ability of mice to controlToxoplasmainfection after compound 1 treatment has been terminated suggested that the mouse immune system plays a synergistic role with chemotherapy in controlling the infection. To explore this possibility, gamma interferon (IFN-γ)-knockout mice were infected with parasites and treated with compound 1, and survival was compared to that of normal mice. IFN-γ-knockout mice were protected againstT. gondiithroughout the treatment phase but died during the posttreatment phase in which peak recrudescence was observed in treated immunocompetent mice. These data suggest that an IFN-γ-dependent immune response was essential for controlling and resolving parasite recrudescence in mice treated with compound 1. In addition, when compound 1-cured immunocompetent mice were rechallenged with a lethal doseof T. gondii,all survived (n= 32). It appears that the cytostatic nature of compound 1 provides an “immunization” phase during chemotherapy which allows the mice to survive the recrudescence and any subsequent challenge with a lethal dose ofT. gondii.
An
Enterococcus faecalis
ABC Homologue (Lsa) Is Required for the Resistance of This Species to Clindamycin and Quinupristin-Dalfopristin
Authors: Singh Kavindra V. , Weinstock George M. , Murray Barbara E. 
Published: July 2002

ABSTRACT

Enterococcus faecalis
isolates are resistant to clindamycin (CLI) and quinupristin-dalfopristin (Q-D), and this is thought to be a species characteristic. Disruption of a gene (
abc-23
, now designated
lsa
, for “lincosamide and streptogramin A resistance”) of
E. faecalis
was associated with a ≥40-fold decrease in MICs of Q-D (to 0.75 μg/ml), CLI (to 0.12 to 0.5 μg/ml), and dalfopristin (DAL) (to 4 to 8 μg/ml) for the wild-type
E. faecalis
parental strain (Q-D MIC, 32 μg/ml; CLI MIC, 32 to 48 μg/ml; DAL MIC, 512 μg/ml). Complementation of the disruption mutant with
lsa
on a shuttle plasmid resulted in restoration of the MICs of CLI, Q-D, and DAL to wild-type levels. Under high-stringency conditions,
lsa
was found in 180 of 180 isolates of
E. faecalis
but in none of 189 other enterococci. Among 19
erm
(B)-lacking
Enterococcus faecium
strains, 9 (47%) were highly susceptible to CLI (MIC, 0.06 to 0.25 μg/ml) and had DAL MICs of 4 to 16 μg/ml; for the remaining
erm
(B)-lacking
E. faecium
strains, the CLI and DAL MICs were 4 to >256 and 2 to >128 μg/ml, respectively. In contrast, none of 32
erm
(B)-lacking
E. faecalis
strains were susceptible (CLI MIC range, 16 to 32 μg/ml; DAL MIC range, ≥32 μg/ml). When
lsa
was introduced into an
E. faecium
strain initially susceptible to CLI, the MICs of CLI and DAL increased ≥60-fold and that of Q-D increased 6-fold (to 3 to 6 μg/ml). Introduction of
lsa
into two DAL-resistant (MICs, >128 μg/ml), Q-D-susceptible (MICs, 0.5 and 1.5 μg/ml)
E. faecium
strains (CLI MICs, 12 and >256 μg/ml) resulted in an increase in the Q-D MICs from 3- to 10-fold (to 8 and >32 μg/ml), respectively. Although efflux was not studied, the similarity (41 to 64%) of the predicted Lsa protein to ABC proteins such as Vga(A), Vga(B), and Msr(A) of
Staphylococcus aureus
and YjcA of
Lactococcus lactis
and the presence of Walker A and B ATP-binding motifs suggest that this resistance may be related to efflux of these antibiotics. In conclusion,
lsa
appears to be an intrinsic gene of
E. faecalis
that explains the characteristic resistance of this species to CLI and Q-D.
Nonradiolabeling Assay for WaaP, an Essential Sugar Kinase Involved in Biosynthesis of Core Lipopolysaccharide of
Pseudomonas aeruginosa
Authors: Zhao Xin , Wenzel Cory Q. , Lam Joseph S. 
Published: July 2002

ABSTRACT

waaP
is present in the lipopolysaccharide (LPS) core gene clusters of a wide range of gram-negative bacteria, and is an essential gene in
Pseudomonas aeruginosa
. The WaaP protein is a sugar kinase that adds phosphate to heptose I in the core oligosaccharide. This study describes the standardization and utility of a chemiluminescence-based enzyme-linked immunosorbent assay for the detection of WaaP kinase activity. Important features of the assay include high sensitivity, the preparation of dephosphorylated LPS as a substrate, and the use of monoclonal antibody 7-4 that specifically recognizes phosphate substituents in the LPS core.