bluuebunny/crossref_metadata_2025_split huggingface dataset:
Antileishmanial Activity of a Linalool-Rich Essential Oil fromCroton cajucara
Authors: Rosa Maria do Socorro S. , Mendonça-Filho Ricardo R. , Bizzo Humberto R. , Rodrigues Igor de Almeida , Soares Rosangela Maria A. , Souto-Padrón Thais , Alviano Celuta Sales , Lopes Angela Hampshire C. S. 
Published: May 2003

ABSTRACTThe in vitro leishmanicidal effects of a linalool-rich essential oil from the leaves ofCroton cajucaraagainstLeishmania amazonensiswere investigated. Morphological changes inL. amazonensispromastigotes treated with 15 ng of essential oil per ml were observed by transmission electron microscopy; leishmanial nuclear and kinetoplast chromatin destruction, followed by cell lysis, was observed within 1 h. Pretreatment of mouse peritoneal macrophages with 15 ng of essential oil per ml reduced by 50% the interaction between these macrophages andL. amazonensis, with a concomitant increase by 220% in the level of nitric oxide production by the infected macrophages. Treatment of preinfected macrophages with 15 ng of essential oil per ml reduced by 50% the interaction between these cells and the parasites, which led to a 60% increase in the amount of nitric oxide produced by the preinfected macrophages. These results provide new perspectives on the development of drugs with activities againstLeishmania, as linalool-rich essential oil is a strikingly potent leishmanicidal plant extract (50% lethal doses, 8.3 ng/ml for promastigotes and 8.7 ng/ml for amastigotes) which inhibited the growth ofL. amazonensispromastigotes at very low concentrations (MIC, 85.0 pg/ml) and which presented no cytotoxic effects against mammalian cells.
In Vitro Activities of Linezolid Combined with Other Antimicrobial Agents against Staphylococci, Enterococci, Pneumococci, and Selected Gram-Negative Organisms
Authors: Sweeney Michael T. , Zurenko Gary E. 
Published: May 2003

ABSTRACTThe activities of linezolid, an oxazolidinone antibacterial agent active against gram-positive organisms, alone and in combination with 35 antimicrobial agents were tested in vitro against methicillin-sensitive (n= 1 to 2 strains) and methicillin-resistant (n= 8 to 10)Staphylococcus aureusstrains; vancomycin-sensitive (n= 6) and vancomycin-resistant (n= 6 to 8)Enterococcus faecalisstrains; vancomycin-sensitive (n= 5) and vancomycin-resistant (n= 6)Enterococcus faeciumstrains; penicillin-sensitive (n= 2 to 5), penicillin-intermediate (n= 5 to 6), and penicillin-resistant (n= 5 to 6)Streptococcus pneumoniaestrains;Escherichia coli(n= 6); andKlebsiella pneumoniae(n= 6). The fractional inhibitory concentration indices of linezolid in combination with other antimicrobial agents for the organisms tested were generated on checkerboard broth microdilution plates prepared by a semiautomated method. Of 1,380 organism-drug combinations, 1,369 (99.2%) combinations of linezolid with 28 antimicrobial drugs were indifferent, 9 combinations (0.65%) of linezolid with 6 drugs (amoxicillin, erythromycin, imipenem, sparfloxacin, teicoplanin, and tetracycline) were synergistic, and 2 combinations (0.15%) of linezolid with 2 drugs (ofloxacin and sparfloxacin) were antagonistic. Overall, the in vitro data demonstrated that linezolid combined with other antimicrobial agents primarily produces an indifferent response, with infrequent occurrences of synergism and antagonism.
Experimental Study of LY333328 (Oritavancin), Alone and in Combination, in Therapy of Cephalosporin-Resistant Pneumococcal Meningitis
Authors: Cabellos Carmen , Fernàndez Antonio , Maiques Jose M. , Tubau Fe , Ardanuy Carmen , Viladrich Pedro F. , Liñares Josefina , Gudiol Francesc 
Published: May 2003

ABSTRACT
Using a rabbit model of meningitis, we sought to determine the efficacy of LY333328, a semisynthetic glycopeptide, in the treatment of cephalosporin-resistant pneumococcal meningitis. LY333328 was administered at a dose of 10 mg/kg of body weight/day, alone and in combination with ceftriaxone at 100 mg/kg/day with or without dexamethasone at 0.25 mg/kg/day. The therapeutic groups were treated with LY333328 with or without dexamethasone and LY333328-ceftriaxone with or without dexamethasone. Rabbits were inoculated with a cephalosporin-resistant pneumococcal strain (ceftriaxone MIC, 2 μg/ml; penicillin MIC, 4 μg/ml; LY333328 MIC, 0.008 μg/ml) and were treated over a 26-h period beginning 18 h after inoculation. The bacterial counts in cerebrospinal fluid (CSF), the white blood cell count, the lactic acid concentration, the CSF LY333328 concentration, and bactericidal and bacteriostatic activities were determined at different time points. In vitro, LY333328 was highly bactericidal and its use in combination with ceftriaxone at one-half the MIC was synergistic. In the rabbit model, LY333328 alone was an excellent treatment for cephalosporin-resistant pneumococcal meningitis, with a rapid decrease in colony counts and no therapeutic failures. The use of LY333328 in combination with ceftriaxone improved the activity of LY333328, but no synergistic effect was observed. The combination of LY333328 with dexamethasone was also rapidly bactericidal, but two therapeutic failures were observed. The combination of LY333328 with ceftriaxone and dexamethasone was effective, without therapeutic failures.
Ribavirin and Alpha Interferon Enhance Death Receptor-Mediated Apoptosis and Caspase Activation in Human Hepatoma Cells
Authors: Schlosser Stephan F. , Schuler Markus , Berg Christoph P. , Lauber Kirsten , Schulze-Osthoff Klaus , Schmahl Friedrich Wilhelm , Wesselborg Sebastian 
Published: May 2003

ABSTRACTThe molecular mechanisms underlying the clinical effects of alpha interferon (IFN) and ribavirin are not understood. Elimination of infected cells occurs in part by cytotoxic T lymphocytes (CTLs) expressing CD95 ligand and thereby attacking target cells which are positive for the death receptor CD95. Since many viruses have evolved mechanisms to inhibit apoptosis, the opposite, namely, promotion of apoptosis, could be a strategy to strengthen the host antiviral response. In the present study, we have asked whether the antiviral substances IFN and ribavirin could support CD95-mediated apoptosis by interfering with the activation of caspases, a family of proteases known for their essential role in apoptosis. HepG2 cells, stimulated with the agonistic anti-CD95 antibody, served as a minimal model to mimic the CD95 stimulation ocurring during a CTL attack of target cells in vivo. Apoptosis was quantitated by flow cytometric detection of hypodiploid nuclei. Caspase activity was measured by cytofluorometry, immunocytochemistry, and immunoblot analysis. IFN and ribavirin sensitized HepG2 cells for CD95-mediated apoptosis. This effect was correlated with an increase in CD95-mediated caspase activation and enhanced cleavage of the caspase substrate poly(ADP-ribose) polymerase. Furthermore, the positive effect on CD95-mediated caspase activation by IFN and ribavirin was confirmed by immunocytochemistry for activated caspase-3 and by immunoblot detection of activated caspase-3, caspase-7, and caspase-8. Our data demonstrate that the antiviral substances IFN and ribavirin are able to sensitize for CD95-mediated apoptosis. IFN and ribavirin also enhance CD95-mediated caspase activation, which might in part be responsible for the apoptosis-promoting effect of these antiviral compounds.
Antiviral Activity and Pharmacokinetics of 1-(2,3-Dideoxy-2-Fluoro-β-
l
-Glyceropent-2-Enofuranosyl)Cytosine
Authors: Chen Huachun , Pai S. Balakrishna , Hurwitz Selwyn J. , Chu Chung K. , Glazkova Yuliya , McClure Harold M. , Feitelson Mark , Schinazi Raymond F. 
Published: May 2003

ABSTRACT

1-(2,3-Dideoxy-2-fluoro-β-
l
-glyceropent-2-enofuranosyl)cytosine (
l
-2′-Fd4C) is an
l
-nucleoside analogue with both anti-human immunodeficiency virus (HIV) and anti-hepatitis B virus (HBV) activity with median effective concentrations of 0.12 μM in peripheral blood mononuclear cells and 0.002 μM in HepG2-2.2.15 cells, respectively. The purpose of this study was to examine the antihepadnavirus potency and pharmacokinetics of
l
-2′-Fd4C in vivo. HBV-transgenic mice treated intraperitoneally with
l
-2′-Fd4C showed a reduction of HBV levels in their blood comparable to that produced by lamivudine. The pharmacokinetics of
l
-2′-Fd4C in rhesus monkeys was evaluated after intravenous and oral administration. The concentrations in plasma declined in a biexponential manner after intravenous administration, with a long terminal-phase half-life of 5.02 h. The steady-state volumes of distribution and systemic clearance were 1.09 liter · kg
−1
and 0.25 liter · h
−1
· kg
−1
, respectively, with a renal clearance of 0.16 liter · h
−1
· kg
−1
. The oral bioavailability was approximately 44%. About 53% of the compound administered intravenously and 19% of that administered orally were recovered unchanged in the urine within the 24-h urine collection period, and no other metabolite was detected. The compound penetrated the central nervous system at concentrations that exceeded the median effective antiviral concentration against HIV in cell cultures. Based upon these observations, further testing to develop this agent for treatment of HIV and HBV infections is warranted.
Indinavir, Efavirenz, and Abacavir Pharmacokinetics in Human Immunodeficiency Virus-Infected Subjects
Authors: DiCenzo Robert , Forrest Alan , Squires Kathleen E. , Hammer Scott M. , Fischl Margaret A. , Wu Hulin , Cha Raymond , Morse Gene D. 
Published: May 2003

ABSTRACT

Adult AIDS Clinical Trials Group (AACTG) Protocol 886 examined the dispositions of indinavir, efavirenz, and abacavir in human immunodeficiency virus-infected subjects who received indinavir at 1,000 mg every 8 h (q8h) and efavirenz at 600 mg q24h or indinavir at 1,200 mg and efavirenz at 300 mg q12h with or without abacavir 300 at mg q12h. Thirty-six subjects participated. The median minimum concentration in plasma (
C
min
) for indinavir administered at 1,200 mg q12h was 88.1 nM (interquartile range [IR], 61.7 to 116.5 nM), whereas the median
C
min
for indinavir administered at 1,000 mg q8h was 139.3 nM (IR, 68.8 to 308.7 nM) (
P
= 0.19). Compared to the minimum
C
min
range for wild-type virus (80 to 120 ng/ml) estimated by the AACTG Adult Pharmacology Committee, the
C
min
for indinavir administered at 1,200 mg q12h (54 ng/ml) is inadequate. The apparent oral clearance (CL/F) (
P
= 0.28), apparent volume of distribution at steady state (
V
ss
/F) (
P
= 0.25), and half-life (
t
1/2
) (
P
= 0.80) of indinavir did not differ between regimens. The levels of efavirenz exposure were similar between regimens. For efavirenz administered at 600 mg q24h and 300 mg q12h, the median maximum concentrations in plasma (
C
max
s) were 8,968 nM (IR, 5,784 to 11,768 nM) and 8,317 nM (6,587 to 10,239 nM), respectively (
P
= 0.66), and the
C
min
s were 4,289 nM (IR, 2,462 to 5,904 nM) and 4,757 nM (IR, 3,088 to 6,644 nM), respectively (
P
= 0.29). Efavirenz pharmacokinetic parameters such as CL/F (
P
= 0.62),
V
ss
/F (
P
= 0.33), and
t
1/2
(
P
= 0.37) were similar regardless of the dosing regimen. The median
C
max
,
C
min
, CL/F,
V
ss
/
F
, and
t
1/2
for abacavir were 6,852 nM (IR, 5,702 to 7,532), 21.0 nM (IR, 21.0 to 87.5), 43.7 liters/h (IR, 37.9 to 55.2), 153.9 liters (IR, 79.6 to 164.4), and 2.0 h (IR, 1.8 to 2.8), respectively. In summary, when indinavir was given with efavirenz, the trough concentration of indinavir after administration of 1,200 mg q12h was inadequate. Abacavir did not influence the pharmacokinetics or exposure parameters of either indinavir or efavirenz. The levels of efavirenz exposure were similar in subjects receiving efavirenz q12h or q24h.
Generation of Stable Cell Lines Expressing Lamivudine-Resistant Hepatitis B Virus for Antiviral-Compound Screening
Authors: Walters Kathie-Anne , Tipples Graham A. , Allen Marchelle I. , Condreay Lynn D. , Addison William R. , Tyrrell Lorne 
Published: May 2003

ABSTRACT

Lamivudine [β-
l
-(−)-2′,3′-dideoxy-3′-thiacytidine] is a potent inhibitor of hepadnavirus replication and is used both to treat chronic hepatitis B virus (HBV) infections and to prevent reinfection of transplanted livers. Unfortunately, lamivudine-resistant HBV variants do arise during prolonged therapy, indicating a need for additional antiviral drugs. Replication-competent HBV constructs containing the reverse transcriptase domain L180M/M204V and M204I (rtL180M/M204V and rtM204I) mutations associated with lamivudine resistance were used to produce stable cell lines that express the resistant virus. These cell lines contain stable integrations of HBV sequences and produce both intracellular and extracellular virus. HBV produced by these cell lines was shown to have a marked decrease in sensitivity to lamivudine, with 450- and 3,000-fold shifts in the 50% inhibitory concentrations for the rtM204I and rtL180M/M204V viruses, respectively, compared to that for the wild-type virus. Drug assays indicated that the lamivudine-resistant virus exhibited reduced sensitivity to penciclovir [9-(4-hydroxy-3-hydroxymethyl-but-1-yl) guanine] but was still inhibited by the nucleoside analogues CDG (carbocyclic 2′-deoxyguanosine) and abacavir {[1
S
,4
R
]-4-[2-amino-6-(cyclopropylamino)-9
H
-purin-9-yl]-2-cyclopentene-1-methanol}. Screening for antiviral compounds active against the lamivudine-resistant HBV can now be done with relative ease.
Activities of Ertapenem, a New Long-Acting Carbapenem, against Penicillin-Sensitive or -Resistant Pneumococci in Experimental Meningitis
Authors: Cottagnoud P. , Pfister M. , Cottagnoud M. , Acosta F. , Täuber M. G. 
Published: May 2003

ABSTRACT

The penetration of ertapenem, a new carbapenem with a long half-life, reached 7.1 and 2.4% into inflamed and noninflamed meninges, respectively. Ertapenem had excellent antibacterial activity in the treatment of experimental meningitis due to penicillin-sensitive and -resistant pneumococci, leading to a decrease of 0.69 ± 0.17 and 0.59 ± 0.22 log
10
CFU/ml · h, respectively, in the viable cell counts in the cerebrospinal fluid. The efficacy of ertapenem was comparable to that of standard regimens (ceftriaxone monotherapy against the penicillin-sensitive strain and ceftriaxone combined with vancomycin against the penicillin-resistant strain). In vitro, ertapenem in concentrations above the MIC was highly bactericidal against both strains. Even against a penicillin- and quinolone-resistant mutant, ertapenem had similar bactericidal activity in vitro.
Efficacy of Albaconazole (UR-9825) in Treatment of DisseminatedScedosporium prolificansInfection in Rabbits
Authors: Capilla Javier , Yustes Clara , Mayayo Emili , Fernández Belkys , Ortoneda Montserrat , Javier Pastor F. , Guarro Josep 
Published: May 2003

ABSTRACTThere are no effective therapeutics for treating invasiveScedosporium prolificansinfections. Doses of 15, 25, and 50 mg/kg of body weight/day for the new triazole albaconazole (ABC) were evaluated in an immunocompetent rabbit model of systemic infection with this mold. Treatments were begun 1 day after challenge and given for 10 days. ABC at any dose was more effective than amphotericin B (AMB) at 0.8 mg/kg/day at clearingS. prolificansfrom tissue (P< 0.007). The percentages of survival at 25 mg of ABC/kg/day were similar to those obtained with AMB. Rabbits showed 100% survival when they were treated with 50 mg of ABC per kg (P< 0.0001 versus control group), and only this dosage was able to reduce tissue burden significantly in the five organs studied, i.e., spleen, kidneys, liver, lungs, and brain.
Pharmacokinetic-Pharmacodynamic Modeling of the Electroencephalogram Effect of Norfloxacin in Rats
Authors: Chenel Marylore , Barbot Agnès , Dupuis Antoine , Mimoz Olivier , Paquereau Joël , Bouquet Serge , Couet William 
Published: May 2003

ABSTRACT

A previously developed pharmacokinetic-pharmacodynamic (PK-PD) modeling approach was used to investigate the epileptogenic activity of norfloxacin as a representative antibiotic with concentration-dependent antimicrobial activity. Rats received an intravenous infusion of norfloxacin at a rate of 5 mg kg of body weight
−1
min
−1
over 30 min. Blood samples were collected for drug assay, and an electroencephalogram (EEG) was recorded during infusion and postinfusion. An important delay was observed between concentrations of norfloxacin in plasma and the EEG effect. Indirect effect models failed to describe these data, which were successfully fitted by using an effect compartment model with a spline function to describe the relationship between effect and concentration at the effect site, as previously observed with imipenem. The robustness of the PK-PD model was then assessed by keeping the dose constant but increasing the duration of infusion to 120 and 240 min. Although this was accompanied by PK modifications, PD parameters did not vary significantly, and the PK-PD model still applied. In conclusion, the successful PK-PD modeling of the norfloxacin EEG effect in rats should be considered to predict and reduce the epileptogenic risk associated with this antibiotic as a representative fluoroquinolone (E. Fuseau and L. B. Sheiner, Clin. Pharmacol. Ther. 35:733-741, 1984).
High Prevalence of Antimicrobial Resistance in Rapidly Growing Mycobacteria in Taiwan
Authors: Yang Shun-Cheng , Hsueh Po-Ren , Lai Hsin-Chih , Teng Lee-Jene , Huang Li-Min , Chen Jong-Min , Wang Shu-Kuan , Shie Der-Chuen , Ho Shen-Wu , Luh Kwen-Tay 
Published: May 2003

ABSTRACT

An increasing number of clinical isolations of rapidly growing mycobacteria (RGM) at the National Taiwan University Hospital were noted from 1992 to 2001. Broth microdilution MICs of 15 antimicrobial agents were determined for 200 clinical isolates of RGM, including the
Mycobacterium fortuitum
group (69 isolates),
M. chelonae
(39 isolates), and
M. abscessus
(92 isolates). Our results showed that the resistance rates of these isolates to the currently available agents were remarkably high. Amikacin was active against nearly all RGM isolates. Clarithromycin was usually active against
M. abscessus
(79% susceptibility) and the
M. fortuitum
group (65% susceptibility). The majority of
M. fortuitum
group isolates were susceptible to ciprofloxacin (62%) and imipenem (61%). The susceptibilities to other conventional anti-RGM agents of these isolates were poor but differed markedly by species. The newer fluoroquinolones (levofloxacin, moxifloxacin, and gatifloxacin) and meropenem showed better in vitro activities against the
M. fortuitum
group isolates than against the other two species of RGM. Linezolid had fairly good activity against these RGM isolates, particularly against
M. chelonae
isolates (82% susceptible). Telithromycin had poor activity against these RGM isolates (the MICs at which 50% of the isolates tested are inhibited [MIC
50
s] were 32 to 64 μg/ml, and the MIC
90
s were >64 μg/ml).
In Vitro Activities of Telithromycin and 10 Oral Agents against Aerobic and Anaerobic Pathogens Isolated from Antral Puncture Specimens from Patients with Sinusitis
Authors: Goldstein Ellie J. C. , Citron Diane M. , Merriam C. Vreni , Warren Yumi , Tyrrel Kerin L. , Fernandez Helen 
Published: May 2003

ABSTRACT

A study of the comparative in vitro activity of telithromycin, a new ketolide, against 155 aerobic and 171 anaerobic antral sinus puncture isolates showed it to be active against a broad range of sinus pathogens. All pneumococci, including erythromycin-resistant strains, were susceptible to telithromycin at ≤0.5 μg/ml; all
Haemophilus influenzae
and
Eikenella corrodens
strains were inhibited by ≤4 μg of telithromycin/ml; all
Moraxella
spp. and beta-lactamase-producing
Prevotella
species strains were inhibited by ≤0.25 and 0.5 μg of telithromycin/ml, respectively. Among all anaerobes tested, 94% (160 of 171 strains) were susceptible to ≤4 μg of telithromycin/ml; however, 8 of 17 (47%)
Fusobacterium
strains, 2
Veillonella
strains, and 1
Peptostreptococcus micros
strain required >4 μg of telithromycin/ml for inhibition. Telithromycin may offer a therapeutic alternative for sinus infections, including those due to erythromycin-resistant pneumococci.
In Vitro Activities of Dalbavancin and Nine Comparator Agents against Anaerobic Gram-Positive Species and Corynebacteria
Authors: Goldstein Ellie J. C. , Citron Diane M. , Merriam C. Vreni , Warren Yumi , Tyrrell Kerin , Fernandez Helen T. 
Published: May 2003

ABSTRACT

Dalbavancin is a novel semisynthetic glycopeptide with enhanced activity against gram-positive species. Its comparative in vitro activities and those of nine comparator agents, including daptomycin, vancomycin, linezolid, and quinupristin-dalfopristin, against 290 recent gram-positive clinical isolates strains, as determined by the NCCLS agar dilution method, were studied. The MICs of dalbavancin at which 90% of various isolates tested were inhibited were as follows:
Actinomyces
spp., 0.5 μg/ml;
Clostridium clostridioforme
, 8 μg/ml;
C. difficile
, 0.25 μg/ml;
C. innocuum
, 0.25 μg/ml;
C. perfringens
, 0.125 μg/ml;
C. ramosum
, 1 μg/ml;
Eubacterium
spp., 1 μg/ml;
Lactobacillus
spp., >32 μg/ml,
Propionibacterium
spp., 0.5 μg/ml; and
Peptostreptococcus
spp., 0.25 μg/ml. Dalbavancin was 1 to 3 dilutions more active than vancomycin against most strains. Dalbavancin exhibited excellent activity against gram-positive strains tested and warrants clinical evaluation.
Chlamydia pneumoniae
Resists Antibiotics in Lymphocytes
Authors: Yamaguchi Hiroyuki , Friedman Herman , Yamamoto Mayumi , Yasuda Keigo , Yamamoto Yoshimasa 
Published: May 2003

ABSTRACT

Chlamydia pneumoniae
infection of lymphocytes in blood has been well documented, and it is apparent that control of this pathogen in these cells may be critical in the development of chronic inflammatory diseases associated with infection by this bacterium. The activity of antibiotics against
C. pneumoniae
in lymphocytes was assessed in this study by utilizing an in vitro infection model with lymphoid cells. The results obtained indicated that although all of the antibiotics tested showed remarkable activity against bacterial growth in epithelial cells,
C. pneumoniae
in lymphocytes was less susceptible to antibiotics than was bacterial growth in epithelial cells, which are widely used for the evaluation of anti-
C. pneumoniae
antibiotics.
Lack of Vancomycin Tolerance in
Streptococcus pneumoniae
Strains Isolated in Barcelona, Spain, from 1999 to 2001
Authors: Ortega Mar , Marco Francesc , Soriano Alex , García Elisa , Martínez José A. , Mensa Josep 
Published: May 2003

ABSTRACT

To evaluate the incidence of vancomycin tolerance among
Streptococcus pneumoniae
isolates, we performed killing curve studies with 633 isolates. The penicillin MIC was ≥0.12 mg/liter for 481 (76%) of the isolates. All strains were susceptible to vancomycin. Killing curve studies were performed with a vancomycin concentration of 2.5 mg/liter. The Tupelo strain was used for quality control. No vancomycin-tolerant strain was detected.
RNA III Inhibiting Peptide Inhibits In Vivo Biofilm Formation by Drug-Resistant
Staphylococcus aureus
Authors: Giacometti Andrea , Cirioni Oscar , Gov Yael , Ghiselli Roberto , Del Prete Maria Simona , Mocchegiani Federico , Saba Vittorio , Orlando Fiorenza , Scalise Giorgio , Balaban Naomi , Dell'Acqua Giorgio 
Published: May 2003

ABSTRACT

Staphylococcus aureus
is a prevalent cause of bacterial infections associated with indwelling medical devices. RNA III inhibiting peptide (RIP) is known to inhibit
S. aureus
pathogenesis by disrupting quorum-sensing mechanisms. RIP was tested in the present study for its ability to inhibit
S. aureus
biofilm formation in a rat Dacron graft model. The activity of RIP was synergistic with those of antibiotics for the complete prevention of drug-resistant
S. aureus
infections.