bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mild Heating of Amphotericin B-Desoxycholate: Effects on Ultrastructure, In Vitro Activity and Toxicity, and Therapeutic Efficacy in Severe Candidiasis in Leukopenic Mice
Authors: van Etten Els W. M. , van Vianen Wim , Roovers Patty , Frederik Peter 
Published: July 2002

ABSTRACT

Heated (20 min at 70°C) amphotericin B-desoxycholate (hAMB-DOC) was further characterized, as was another formulation obtained after centrifugation (60 min, 3000 ×
g
), hcAMB-DOC. Conventional AMB-DOC consisted of individual micelles (approximately 4 nm in diameter) and threadlike aggregated micelles, as revealed by cryo-transmission electron microscopy. For both hAMB-DOC and hcAMB-DOC, pleiomorphic cobweb structures were observed with a mean particle size of approximately 300 nm as determined by laser diffraction. The potent antifungal activity of AMB-DOC against
Candida albicans
is not reduced by heating. Effective killing of
C. albicans
(>99.9% within 6 h) was obtained at 0.1 mg/liter with each of the AMB formulations. For AMB-DOC, hAMB-DOC, and hcAMB-DOC, cation release (
86
Rb
+
) from
C. albicans
of ≥50% was observed at 0.8, 0.4, and 0.4 mg/liter, respectively. After heating of AMB-DOC, toxicity was reduced 16-fold as determined by red blood cell (RBC) lysis. For AMB-DOC, hAMB-DOC, and hcAMB-DOC, hemolysis of ≥50% was observed at 6.4, 102.4, and 102.4 mg/liter, respectively. In contrast, AMB-DOC and its derivates showed similar toxicities in terms of cation release from RBC. For AMB-DOC, hAMB-DOC, and hcAMB-DOC, cation release (
86
Rb
+
) of ≥50% was observed at 1.6, 0.8, and 0.8 mg/liter, respectively. In persistently leukopenic mice with severe invasive candidiasis, higher dosages of both hAMB-DOC and hcAMB-DOC were tolerated than those of conventional AMB-DOC (3 versus 0.8 mg/kg of body weight, respectively), resulting in significantly improved therapeutic efficacy. In conclusion, this new approach of heating AMB-DOC may be of great value for further optimizing the treatment of severe fungal infections.
Sodium Lauryl Sulfate Increases the Efficacy of a Topical Formulation of Foscarnet against Herpes Simplex Virus Type 1 Cutaneous Lesions in Mice
Authors: Piret Jocelyne , Désormeaux André , Cormier Hélène , Lamontagne Julie , Gourde Pierrette , Juhász Julianna , Bergeron Michel G. 
Published: July 2002

ABSTRACT
The influence of sodium lauryl sulfate (SLS) on the efficacies of topical gel formulations of foscarnet against herpes simplex virus type 1 (HSV-1) cutaneous infection has been evaluated in mice. A single application of the gel formulation containing 3% foscarnet given 24 h postinfection exerted only a modest effect on the development of herpetic skin lesions. Of prime interest, the addition of 5% SLS to this gel formulation markedly reduced the mean lesion score. The improved efficacy of the foscarnet formulation containing SLS could be attributed to an increased penetration of the antiviral agent into the epidermis. In vitro, SLS decreased in a concentration-dependent manner the infectivities of herpesviruses for Vero cells. SLS also inhibited the HSV-1 strain F-induced cytopathic effect. Combinations of foscarnet and SLS resulted in subsynergistic to subantagonistic effects, depending on the concentration used. Foscarnet in phosphate-buffered saline decreased in a dose-dependent manner the viability of cultured human skin fibroblasts. This toxic effect was markedly decreased when foscarnet was incorporated into the polymer matrix. The presence of SLS in the gel formulations did not alter the viabilities of these cells. The use of gel formulations containing foscarnet and SLS could represent an attractive approach to the treatment of herpetic mucocutaneous lesions, especially those caused by acyclovir-resistant strains.
Effects of Amoxicillin, Gentamicin, and Moxifloxacin on the Hemolytic Activity of
Staphylococcus aureus
In Vitro and In Vivo
Authors: Worlitzsch Dieter , Kaygin Hayal , Steinhuber Andrea , Dalhoff Axel , Botzenhart Konrad , Döring Gerd 
Published: July 2002

ABSTRACT

In
Staphylococcus aureus
infection hemolysis caused by the extracellular protein α-toxin encoded by
hla
is thought to contribute significantly to its multifactorial virulence. In vitro, subinhibitory concentrations of β-lactam antibiotics and fluoroquinolones increase the levels of
hla
and α-toxin expression, whereas aminoglycosides decrease the levels of
hla
and α-toxin expression. In the present study we investigated the effects of subinhibitory concentrations of amoxicillin, gentamicin, and moxifloxacin on
hla
and α-toxin expression and total hemolysis of
S. aureus
strain 8325-4, a high-level α-toxin producer, and its α-toxin-negative mutant, DU 1090, in vitro and in a rat model of chronic
S. aureus
infection. The levels of expression of
hla
and α-toxin and total hemolysis did not differ significantly when amoxicillin, gentamicin, or moxifloxacin was added to cultures of
S. aureus
strain 8325-4. In vivo, strain 8325-4 induced a significantly increased level of hemolysis in infected pouches compared to that in uninfected control pouches, but the hemolysis was reduced to control levels by treatment with doses of amoxicillin, gentamicin, or moxifloxacin that reduced bacterial numbers by 2 orders of magnitude. Additionally, the effects of subinhibitory concentrations of the three antibiotics on total hemolysis of four methicillin-resistant
S. aureus
and three methicillin-sensitive
S. aureus
(MSSA) clinical isolates were assessed in vitro. A significant increase in total hemolysis was observed for only one MSSA strain when it was treated with amoxicillin but not when it was treated with moxifloxacin or gentamicin. When purified α-toxin was incubated with purified human neutrophil elastase, α-toxin was cleaved nearly completely. The results suggest that the penicillin-induced increases in
S. aureus
α-toxin expression are strain dependent, that reduction of bacterial numbers in vivo counteracts this phenomenon effectively, and finally, that in localized
S. aureus
infections α-toxin activity is controlled by neutrophil elastase.
Effects of Cytokines and Fluconazole on the Activity of Human Monocytes against
Candida albicans
Authors: Baltch A. L. , Smith R. P. , Franke M. A. , Ritz W. J. , Michelsen P. B. , Bopp L. H. 
Published: July 2002

ABSTRACT

This study evaluates the effects of cytokines, used singly and in combination, on the microbicidal activity of human monocyte-derived macrophages (MDM) against intracellular
Candida albicans
in the presence and absence of fluconazole. In the absence of fluconazole, the addition of tumor necrosis factor alpha (TNF-α), interleukin-1β (IL-1β), gamma interferon (IFN-γ), or IL-4 had no effect on the growth of
C. albicans
. In contrast, the addition of granulocyte-macrophage colony-stimulating factor (GM-CSF) resulted in decreased growth (
P
< 0.05), while the addition of IL-10 resulted in increased growth (
P
< 0.01). In the presence of fluconazole, only the addition of IFN-γ resulted in an increase in the growth of
C. albicans
. In the presence or absence of fluconazole, all cytokine combinations except IFN-γ plus GM-CSF caused significant decreases in growth (
P
< 0.01). IL-10 and IL-4 did not influence the activity of TNF-α or IL-1β. In the absence or presence of
C. albicans
the addition of fluconazole, all of the cytokines studied, and combinations of fluconazole and selected cytokines caused increases in nitric oxide (NO) production (
P
< 0.01). Similar observations were made for superoxide (O
2
−
) only in the presence of
C. albicans
. The greatest concentrations of NO and O
2
−
were produced when
C. albicans
alone was present in the assays. Our results demonstrate that in the presence of low concentrations of fluconazole (0.1 times the MIC), selected cytokines and their combinations significantly increase the microbicidal activity of MDM against intracellular
C. albicans
.
P-113
d
, an Antimicrobial Peptide Active against
Pseudomonas aeruginosa
, Retains Activity in the Presence of Sputum from Cystic Fibrosis Patients
Authors: Sajjan Umadevi S. , Tran Linh T. , Sole Nuria , Rovaldi Christopher , Akiyama Alan , Friden Phillip M. , Forstner Janet F. , Rothstein David M. 
Published: July 2002

ABSTRACT

Antimicrobial peptides are a source of novel agents that could be useful for treatment of the chronic lung infections that afflict cystic fibrosis (CF) patients. Efficacy depends on antimicrobial activity against the major pathogens of CF patients,
Pseudomonas aeruginosa, Staphylococcus aureus
, and
Haemophilus influenzae
, in the environment of the CF patient's airway. We describe the in vitro efficacies of derivatives of histatins, which are histidine-rich peptides produced by the salivary glands of humans and higher primates. P-113, a peptide containing 12 of the 24 amino acid residues of the parent molecule, histatin 5, retained full antibacterial activity and had a good spectrum of activity in vitro against the prominent pathogens of CF patients. However, P-113 was not active in the presence of purulent sputum from CF patients. In contrast, P-113
d
, the mirror-image peptide with the amino acid residues in the
d
configuration, was stable in sputum, was as active as P-113 against pathogens of CF patients in the absence of sputum and retained significant activity in the presence of sputum from CF patients. Recombinant human DNase, which effectively liquefies sputum, enhanced the activity of P-113
d
in undiluted sputum against both exogenous (added) bacteria and endogenous bacteria. Because of its properties, P-113
d
shows potential as an inhalant in chronic suppressive therapy for CF patients.
Inhibition of Herpes Simplex Virus Reactivation by Dipyridamole
Authors: Tenser Richard B. , Gaydos Andrew , Hay Kathleen A. 
Published: July 2002

ABSTRACT
Herpes simplex virus (HSV) reactivation from latency was investigated. Reactivation of thymidine kinase-negative HSV, which is defective for reactivation, was greatly enhanced by thymidine (TdR). The reactivation-enhancing effect of TdR was blocked by dipyridamole (DPM), a known nucleoside transport inhibitor. DPM also inhibited wild-type HSV reactivation, suggesting potential antiviral use.
Spontaneous Mutations That Confer Antibiotic Resistance in
Helicobacter pylori
Authors: Wang Ge , Wilson Trevor J. M. , Jiang Qin , Taylor Diane E. 
Published: July 2002

ABSTRACT

In this study, we systematically examined in vitro frequencies and spectra of the spontaneous mutations in
Helicobacter pylori
that confer resistance to clarithromycin (Cla
r
), metronidazole (Mtz
r
), amoxicillin (Amx
r
), ciprofloxacin (Cip
r
), and rifampin (Rif
r
). The mutation rate of Rif
r
or Cip
r
determined in a fluctuation assay is 1 × 10
−8
to 2 × 10
−8
per cell per division. In contrast, the mutation rates of Cla
r
, Mtz
r
, and Amx
r
are much lower (<10
−9
). However, Mtz
r
mutants could be readily selected in vitro by using the serial passage method, suggesting that the mutagenic effect and selective effect of a sublethal dose of metronidazole contribute to the rapid development of Mtz
r
. Analysis of spontaneous Rif
r
, Cla
r
, and Cip
r
mutants confirmed previous results indicating that mutations within the
rpoB
gene, the 23S rRNA gene, and the
gyrA
gene, respectively, are responsible; also, several new mutant alleles were identified. Mtz
r
mutants resulted most frequently, but not always, from mutations in the
rdxA
gene. DNA fragments containing each mutant allele could readily transform susceptible
H. pylori
strains to resistance, confirming that each mutant allele is responsible for the resistance phenotype.
Comparison of Efficacies of Cysteine Protease Inhibitors against Five Strains of
Plasmodium falciparum
Authors: Singh Ajay , Rosenthal Philip J. 
Published: July 2002

ABSTRACT

Falcipain-2, a cysteine protease and essential hemoglobinase of
Plasmodium falciparum
, is a potential antimalarial drug target. We compared the falcipain-2 sequences and sensitivities to cysteine protease inhibitors of five parasite strains that differ markedly in sensitivity to established antimalarial drugs. The sequence of falcipain-2 was highly conserved, and the sensitivities of all of the strains to falcipain-2 inhibitors were very similar. Thus, cross-resistance between cysteine protease inhibitors and other antimalarial agents is not expected in parasites that are now circulating and falcipain-2 remains a promising chemotherapeutic target.
Large Drug Resistance Virulence Plasmids of Clinical Isolates ofSalmonella entericaSerovar Choleraesuis
Authors: Chu Chishih , Chiu Cheng-Hsun , Wu Wan-Yu , Chu Chi-Hong , Liu Tsui-Ping , Ou Jonathan T. 
Published: July 2002

ABSTRACTSalmonella entericaserovar Choleraesuis generally causes systemic human salmonellosis without diarrhea, and therefore, antimicrobial treatment is essential for such patients. The drug resistance information on this organism is thus of high value. Serovar Choleraesuis usually harbors a virulence plasmid (pSCV) of 50 kb in size. Of the 16 clinical isolates identified to be serovar Choleraesuis, all except one harbored a pSCV and seven of them carried a pSCV of more than 125 kb in size. A pSCV was defined as a plasmid carryingspvCand characteristic deletions detected by PCR and by DNA-DNA hybridization (for the former criterion). The results of PCR, restriction fragment profiles, and Southern DNA-DNA hybridizations of the profiles all indicated that such larger pSCVs were derived from the 50-kb plasmid recombined with non-pSCVs found in some clinical isolates. Fifteen of the 17 strains, including a laboratory strain, were then tested for drug resistance against 16 antibiotics with E-test and the dilution method. The laboratory strain, which harbored a 50-kb pSCV and a 6-kb non-pSCV, was resistant only to sulfonamides (SUL), and its resistance gene,sulII, checked with PCR and DNA-DNA hybridization, was located on the 6-kb non-pSCV. All 14 clinical strains were resistant to multiple drugs. Of the 14, 7 were resistant to SUL, and the resistance gene was located on a plasmid. ThesulIIgene, but notblaTEM-1, was carried only on the 6-kb non-pSCV. Of the remaining six large plasmids, three of 90 kb, two of 136 kb, and one of 140 kb, the last three were pSCVs and carried the other SUL gene (sulI) and theblaTEM-1gene. The six strains were also resistant to trimethoprim-sulfamethoxazole. None of the 50-kb pSCVs carried resistance genes. These drug resistance genes on the large pSCVs were apparently also acquired through recombination.
Diversity of SHV and TEM β-Lactamases in
Klebsiella pneumoniae
: Gene Evolution in Northern Taiwan and Two Novel β-Lactamases, SHV-25 and SHV-26
Authors: Chang Feng-Yee , Siu L. K. , Fung Chang-Phone , Huang Min-Hua , Ho Monto 
Published: July 2002

ABSTRACT

A total of 113 blood culture isolates of
Klebsiella pneumoniae
from 10 hospitals in northern Taiwan were studied for SHV and TEM β-lactamase production.
bla
SHV
was amplified from all isolates by PCR. TEM-type resistance, was found in 32 of the isolates and was of the TEM-1 type in all isolates. SHV-1, -2, -5, -11, and -12 and two novel enzymes were identified. These novel enzymes were designated SHV-25 and SHV-26 and had pIs of 7.5 and 7.6, respectively. Amino acid differences in comparison to the amino acid sequence of
bla
SHV-1
were found at positions T18A (ThrACC→AlaGCC), L35Q (LeuCTA→GluCAA), and M129V (MetATG→ValGTG) for SHV-25 and at position A187T (AlaGCC→ThrACC) for SHV-26. The results of substrate profiles and MIC determinations showed that the novel enzymes did not hydrolyze extended-spectrum cephalosporins, rendering the isolates susceptible to these agents. Inhibition profiles revealed that the 50% inhibitory concentration for SHV-26 was higher than those for SHV-1 and SHV-25, resulting in an intermediate resistance to amoxicillin-clavulanic acid. Forty-nine ribotypes were identified, suggesting that major clonal spread had not occurred in any of the hospitals. According to the amino acid sequence, SHV β-lactamases in Taiwan may basically be derived through stepwise mutation from SHV-1 or SHV-11 and further subdivided by four routes. The stepwise mutations initiated from SHV-1 or SHV-11 to SHV-2, SHV-5, and SHV-12 comprise the evolutionary change responsible for extended-spectrum β-lactamase (ESBL) production in Taiwan. The stepwise mutations that lead to a non-ESBL (SHV-25) and the β-lactamase (SHV-26) with reduced susceptibility to clavulanic acid are possibly derived from SHV-11 and SHV-1, respectively. The results suggest a stepwise evolution of SHV β-lactamases in Taiwan.
In Vitro Activities of 10 Antifungal Drugs against 508 Dermatophyte Strains
Authors: Fernández-Torres B. , Carrillo A. J. , Martı́n E. , Del Palacio A. , Moore M. K. , Valverde A. , Serrano M. , Guarro J. 
Published: July 2002

ABSTRACT
We have tested 508 strains belonging to 24 species of dermatophytes against 10 antifungal drugs following mainly the NCCLS (M38-P) standard for filamentous fungi. However, several important factors, such as the temperature (28 versus 35°C) and time of incubation (4 to 10 days versus 21 to 74 h), have been modified. The antifungals used were itraconazole, ketoconazole, miconazole, clotrimazole, voriconazole, terbinafine, amphotericin B, fluconazole, UR-9825, and G-1. In general, with the exception of fluconazole and G-1, all antifungals were shown to be highly effective.
GES-2, a Class A β-Lactamase from
Pseudomonas aeruginosa
with Increased Hydrolysis of Imipenem
Authors: Poirel Laurent , Weldhagen Gerhard F. , Naas Thierry , De Champs Christophe , Dove Michael G. , Nordmann Patrice 
Published: July 2002

ABSTRACT

Pseudomonas aeruginosa
GW-1 was isolated in 2000 in South Africa from blood cultures of a 38-year-old female who developed nosocomial pneumonia. This isolate harbored a self-transferable ca. 100-kb plasmid that conferred an expanded-spectrum cephalosporin resistance profile associated with an intermediate susceptibility to imipenem. A β-lactamase gene,
bla
GES-2
, was cloned from whole-cell DNA of
P. aeruginosa
GW-1 and expressed in
Escherichia coli
. GES-2, with a pI value of 5.8, hydrolyzed expanded-spectrum cephalosporins, and its substrate profile was extended to include imipenem compared to that of GES-1, identified previously in
Klebsiella pneumoniae
. GES-2 activity was less inhibited by clavulanic acid, tazobactam and imipenem than GES-1. The GES-2 amino acid sequence differs from that of GES-1 by a glycine-to-asparagine substitution in position 170 located in the omega loop of Ambler class A enzymes. This amino acid change may explain the extension of the substrate profile of the plasmid-encoded β-lactamase GES-2.
Accumulation of 10 Fluoroquinolones by Wild-Type or Efflux Mutant
Streptococcus pneumoniae
Authors: Piddock Laura J. V. , Johnson M. M. 
Published: July 2002

ABSTRACT

A method for measuring fluoroquinolone accumulation by
Streptococcus pneumoniae
was rigorously examined. The accumulation of ciprofloxacin, clinafloxacin, gatifloxacin, grepafloxacin, levofloxacin, moxifloxacin, norfloxacin, ofloxacin, sitafloxacin, and trovafloxacin in the presence and absence of either carbonyl cyanide
m
-chlorophenyl-hydrazone (CCCP) or reserpine was determined for two wild-type fluoroquinolone-susceptible capsulated
S. pneumoniae
strains (M3 and M4) and the noncapsulated strain R6. Two efflux mutants, R6N (which overexpresses PmrA) and a mutant of M4, M22 (no expression of PmrA), were also examined. Essentially, the fluoroquinolones fell into two groups. (i) One group consisting of ciprofloxacin, grepafloxacin, and norfloxacin accumulated to 72 to 92 ng/mg (dry weight) of cells in all strains. (ii) The remainder of the agents accumulated to 3 to 30 ng/mg (dry weight) of cells. With a decrease in hydrophobicity, there was a decrease in the concentration accumulated. With an increase in the molecular weight of the free form of each agent, there was also a decrease in the concentration accumulated. The strains differed in their responses to reserpine and CCCP. For the three fluoroquinolone-susceptible strains, only reserpine had a significant effect upon accumulation of moxifloxacin and clinafloxacin by M3 and showed no effect for the other agents and strains. For M3 and M4, CCCP enhanced the concentration of ciprofloxacin and norfloxacin accumulated, whereas for R6, the effect was only statistically significant for ofloxacin. Efflux mutant M22 accumulated less ciprofloxacin, gatifloxacin, and ofloxacin than M4 did. M22 accumulated more norfloxacin than M4 did. Reserpine and CCCP had variable effects as for the other strains. Differences in the accumulation of fluoroquinolones by R6 and R6N were highly dependent upon growth phase, and only for norfloxacin was there a significant difference between two strains.
Antibacterial Activity of Licochalcone A against Spore-Forming Bacteria
Authors: Tsukiyama Ryo-Ichi , Katsura Harumi , Tokuriki Nozomu , Kobayashi Makio 
Published: July 2002

ABSTRACTLicochalcone A was isolated from the roots of licorice,Glycyrrhiza inflata, which has various uses in the food and pharmaceutical industries; isolation was followed by extraction with ethanol and column chromatography with silica gel. In this study, the activities of licochalcone A against some food contaminant microorganisms were evaluated in vitro. The vegetative cell growth ofBacillus subtiliswas inhibited in a licochalcone A concentration-dependent manner and was completely prevented by 3 μg of licochalcone A/ml. Licochalcone A showed a high level of resistance to heating at 80 to 121°C for 15 min. Licochalcone A did not inhibit the germination of heat-treated spores ofB. subtilisinduced byl-alanine. Licochalcone A showed effects against all gram-positive bacteria tested and especially was effective against allBacillusspp. tested, with MICs of 2 to 3 μg/ml, but was not effective against gram-negative bacteria or eukaryotes at 50 μg/ml. Although the cationic antimicrobial peptides protamine and ε-poly-l-lysine resulted in the loss of antimicrobial activity in the presence of either 3% (wt/vol) NaCl or protease at 20 μg/ml, the antibacterial activity of licochalcone A was resistant to these conditions. Thus, licochalcone A could be a useful compound for the development of antibacterial agents for the preservation of foods containing high concentrations of salts and proteases, in which cationic peptides might be less effective.
In Vitro
Plasmodium falciparum
Drug Sensitivity Assay: Inhibition of Parasite Growth by Incorporation of Stomatocytogenic Amphiphiles into the Erythrocyte Membrane
Authors: Ziegler Hanne L. , Stærk Dan , Christensen Jette , Hviid Lars , Hägerstrand Henry , Jaroszewski Jerzy W. 
Published: July 2002

ABSTRACT

Lupeol, which shows in vitro inhibitory activity against
Plasmodium falciparum
3D7 strain with a 50% inhibitory concentration (IC
50
) of 27.7 ± 0.5 μM, was shown to cause a transformation of the human erythrocyte shape toward that of stomatocytes. Good correlation between the IC
50
value and the membrane curvature changes caused by lupeol was observed. Preincubation of erythrocytes with lupeol, followed by extensive washing, made the cells unsuitable for parasite growth, suggesting that the compound incorporates into erythrocyte membrane irreversibly. On the other hand, lupeol-treated parasite culture continued to grow well in untreated erythrocytes. Thus, the antiplasmodial activity of lupeol appears to be indirect, being due to stomatocytic transformation of the host cell membrane and not to toxic effects via action on a drug target within the parasite. A number of amphiphiles that cause stomatocyte formation, but not those causing echinocyte formation, were shown to inhibit growth of the parasites, apparently via a mechanism similar to that of lupeol. Since antiplasmodial agents that inhibit parasite growth through erythrocyte membrane modifications must be regarded as unsuitable as leads for development of new antimalarial drugs, care must be exercised in the interpretation of results of screening of plant extracts and natural product libraries by an in vitro
Plasmodium
toxicity assay.