bluuebunny/crossref_metadata_2025_split huggingface dataset:
PREDICTING INTERSTIMULUS INTERVALS BETWEEN SAMPLES FOR CAPSAICIN‐CONTAINING SALSA WITH A RANGE OF HEAT LEVELS
Authors: DOWELL KAREN J. , CHAMBERS EDGAR , MILLIKEN GEORGE A. , CHAMBERS DELORES H. 
Published: July 2005

ABSTRACT A model was developed to predict an optimal interstimulus interval during testing for samples of products (such as salsa) that contain capsaicin. Oral “heat burn” intensity for four levels of salsa (mild, 25,000 Scoville Heat Units [SHU]; medium, 70,000 SHU; hot, 130,000 SHU; and extra hot, 250,000 SHU) was evaluated over time using a trained, experienced five‐member descriptive sensory analysis panel. As capsaicin concentrations increased, the time it took for heat perception in the mouth to return to a negligible sensory value increased – a result of the higher amount of heat burn that must dissipate and a slower rate of decay after samples with more intense heat burn. Although a slight sensitization trend may occur with mild and medium salsas, and a slight trend toward desensitization may occur for the hot sample, the maximum intensity ratings after repeated tastings were not significantly different, and real perceptual differences may not exist. Two models were developed that can be used to predict the time required between samples – one based on SHU values and the other based on initial sensory heat score. This information can be used by sensory researchers to approximate the necessary interstimulus interval between salsa samples during sensory testing by trained panels to avoid carryover effects from one sample to another.
EFFECTS OF DIFFERENT FACTORS ON SENSORY ATTRIBUTES, OVERALL ACCEPTANCE AND PREFERENCE OF ROOIBOS (ASPALATHUS LINEARIS) TEA
Authors: DOS AYSEGUL , AYHAN ZEHRA , SUMNU GULUM 
Published: July 2005

ABSTRACT Effects of serving size, gender, age, tea type, tea‐making technique and water quality on the sensory attributes (appearance, aroma and taste), overall acceptability and preference of Rooibos tea were investigated. In general, there were significant effects of age and main factor interactions on the attributes and product acceptability (P ≤ 0.05). The interaction of serving size, gender and age affected the acceptability of Rooibos (P ≤ 0.05). Although there was significant difference between natural and vanilla‐flavored tea in terms of color, clarity, odor and taste (P ≤ 0.05), no difference was observed in the product acceptability (P > 0.05). The tea‐making technique only affected the odor, with traditionally brewed tea having lower intensity scores than the infused tea. The tea prepared using natural spring water was found to be clearer and had higher acceptability scores than the tea prepared using tap water (P ≤ 0.05). There was no existing significant preference for the natural Rooibos over the vanilla‐flavored one, and the traditionally brewed tea over the infused one; however, the tea prepared using the spring water was preferred over the one prepared using tap water.
Inactivation of the
FCY2
Gene Encoding Purine-Cytosine Permease Promotes Cross-Resistance to Flucytosine and Fluconazole in
Candida lusitaniae
Authors: Chapeland-Leclerc Florence , Bouchoux Julien , Goumar Abdelhak , Chastin Christiane , Villard Jean , Noël Thierry 
Published: July 2005

ABSTRACT

In a previous work, we described the possible relationship between a defect of purine-cytosine permease and the acquisition of a cross-resistance to the antifungal combination flucytosine (5FC) and fluconazole (FLC) in
Candida lusitaniae
(T. Noël, F. François, P. Paumard, C. Chastin, D. Brethes, and J. Villard, Antimicrob. Agents Chemother. 47:1275-1284, 2003). Using degenerate PCR and chromosome walking, we cloned two
FCY2
-like genes in
C. lusitaniae
. Northern blot analysis revealed that only one gene was expressed; it was named
FCY2
. The other one behaved as a pseudogene and was named
FCY21
. In order to better characterize the possible role of
FCY2
in cross-resistance to 5FC-FLC, disruption experiments with auxotrophic strain 6936
ura3
(
D95V
)
FCY2
with an integrative vector carrying the
URA3
gene and a partial sequence of the
C. lusitaniae FCY2
gene were undertaken. Southern blot analysis revealed that homologous recombination events occurred in all transformants analyzed at rates of 50% at resident locus
FCY2
and 50% at resident locus
URA3
, resulting in the genotypes
ura3 fcy2
::
URA3
and
ura3
::
URA3 FCY2
, respectively. It was then demonstrated that only transformants harboring a disrupted
fcy2
gene were resistant to 5FC, susceptible to FLC, and resistant to the 5FC-FLC combination. Finally, complementation experiments with a functional
FCY2
gene restored 5FC and FLC susceptibilities to the wild-type levels. The results of this study provide molecular evidence that inactivation of the sole
FCY2
gene promotes cross-resistance to the antifungal association 5FC-FLC in
C. lusitaniae
.
Efficacy of Telavancin in a Rabbit Model of Aortic Valve Endocarditis Due to Methicillin-Resistant
Staphylococcus aureus
or Vancomycin-Intermediate
Staphylococcus aureus
Authors: Madrigal Andres G. , Basuino Li , Chambers Henry F. 
Published: July 2005

ABSTRACT

The activities of telavancin and vancomycin were compared in vitro and in the rabbit model of aortic valve endocarditis against a methicillin-resistant
Staphylococcus aureus
strain, COL, and a vancomycin-intermediate
S. aureus
(VISA) strain, HIP 5836. Telavancin was bactericidal in time-kill studies at a concentration of 5 μg/ml against both COL and HIP5836. Vancomycin was bacteriostatic at 5 μg/ml and bactericidal at 10 μg/ml against COL and was bacteriostatic at 10 μg/ml against VISA strain HIP 5836. Compared to untreated controls, a twice-daily regimen of 30 mg/kg of telavancin reduced mean aortic valve vegetation titers of the COL strain by 4.7 log
10
CFU/g after 4 days of therapy and sterilized 6/11 vegetations compared to 3.4 log
10
CFU/g with 3/10 vegetations sterilized for a regimen of twice-daily vancomycin, 30 mg/kg; these differences were not statistically significant. Telavancin was significantly more effective than vancomycin in the VISA model, producing a 5.5 log
10
CFU/g reduction versus no reduction in CFU with vancomycin. In experiments comparing 2-day regimens of telavancin at 30 mg/kg and 50 mg/kg twice daily, organisms were rapidly eliminated from vegetations, but the effect was not different between the two doses. These results suggest that telavancin may be an effective treatment for endocarditis and other serious staphylococcal infections accompanied by bacteremia, including infections caused by staphylococci not susceptible to vancomycin.
Fluconazole MIC and the Fluconazole Dose/MIC Ratio Correlate with Therapeutic Response among Patients with Candidemia
Authors: Clancy Cornelius J. , Yu Victor L. , Morris Arthur J. , Snydman David R. , Nguyen M. Hong 
Published: July 2005

ABSTRACT

We tested 32
Candida
isolates recovered in the early 1990s from the bloodstreams of patients with candidemia for in vitro susceptibility to fluconazole and determined if MIC and/or the daily dose of fluconazole/MIC ratio correlated with the response to therapy. This is a unique data set since 87.5% (28/32) of patients were treated with fluconazole doses now considered to be inadequate (≤200 mg), which contributed to high therapeutic failure rates (53% [17/32]). The geometric mean MIC and dose/MIC ratio for isolates associated with therapeutic failure (11.55 μg/ml and 14.3, respectively) differed significantly from values associated with therapeutic success (0.95 μg/ml and 219.36 [
P
= 0.0009 and 0.0004, respectively]). The therapeutic success rates among patients infected with susceptible (MIC ≤ 8 μg/ml), susceptible-dose dependent (S-DD) (MIC = 16 or 32 μg/ml), and resistant (MIC ≥ 64 μg/ml) isolates were 67% (14/21), 20% (1/5), and 0% (0/6), respectively. A dose/MIC ratio >50 was associated with a success rate of 74% (14/19), compared to 8% (1/13) for a dose/MIC ratio ≤50 (
P
= 0.0003). Our data suggest that both fluconazole MIC and dose/MIC ratio correlate with the therapeutic response to fluconazole among patients with candidemia. In clinical practice, dose/MIC ratio might prove easier to interpret than breakpoint MICs, since it quantitates the effects of increasing fluconazole doses that are alluded to in the S-DD designation.
Pharmacodynamic Evidence that Ciprofloxacin Failure against Tuberculosis Is Not Due to Poor Microbial Kill but to Rapid Emergence of Resistance
Authors: Gumbo Tawanda , Louie Arnold , Deziel Mark R. , Drusano George L. 
Published: July 2005

ABSTRACT

Studies of early bactericidal activity provide a fast and economic way to evaluate the clinical efficacy of potential agents for the treatment of tuberculosis. Based on good early bactericidal activity data, ciprofloxacin entered further studies and is now recommended as part of treatment for multidrug-resistant tuberculosis. We examined the relationship between ciprofloxacin bactericidal activity and the emergence of resistance in an in vitro pharmacodynamic infection model in which we exposed
Mycobacterium tuberculosis
to simulated free-drug ciprofloxacin serum concentration-time profiles that mimic those encountered in humans treated with ciprofloxacin orally for 2 weeks.
Mycobacterium tuberculosis
cultures were sampled during the experiment in order to determine the effect of therapy on the total microbial population as well as the drug-resistant population. The ciprofloxacin regimen, which achieved a ratio of the area under the concentration time curve from 0 to 24 h to MIC of 80.4, resulted in a rapid microbial kill similar to that encountered in humans during studies of early bactericidal activity. However, despite this impressive bactericidal activity, resistance emerged quickly. By the end of the first week, most of the microbial population had been replaced by a ciprofloxacin-resistant population. Given the MICs encountered in clinical isolates of
M. tuberculosis
, we estimate that most clinically tolerable doses of ciprofloxacin will lead to emergence of resistance, especially when used as the only effective component of regimens given for treatment of multidrug-resistant tuberculosis. One of the explanations for why early bactericidal activity fails to predict sterilization may be the emergence of a resistant subpopulation, which only becomes ≥1% at the end of the early bactericidal activity studies.
In Vitro and In Vivo Evaluations of the Activities of Lauric Acid Monoester Formulations against
Staphylococcus aureus
Authors: Rouse Mark S. , Rotger Margalida , Piper Kerryl E. , Steckelberg James M. , Scholz Matthew , Andrews Jeffrey , Patel Robin 
Published: July 2005

ABSTRACT

Due to increasing mupirocin resistance, alternatives for
Staphylococcus aureus
nasal decolonization are needed. Lauric acid monoesters combined with lactic, mandelic, malic, or benzoic acid are being evaluated as possible alternatives. We determined the in vitro activity of 13 lauric acid monoester (LAM) formulations and mupirocin against 30 methicillin-susceptible
S. aureus
(MSSA) isolates and 30 methicillin-resistant
S. aureus
(MRSA) isolates. We then used a murine model of MRSA nasopharyngeal colonization to compare the in vivo activity of mupirocin with three LAM formulations. MSSA and MRSA MIC
90
values were 0.25 μg/ml for mupirocin and ≤4 μl/ml for all LAM formulations tested. Hsd:ICR mice were challenged with 10
8
CFU/naris MRSA. Five days later,
S. aureus
colonization was documented by culture. Treatment with bland, mupirocin, or one of three LAM ointments was then administered unblinded thrice daily for 2 days. Three days after treatment, both anterior nares were cultured for
S. aureus
. Administration of 128774-49E or 128774-53A was associated with greater eradication of MRSA carriage (24/34 [71%] or 33/40 [83%]) of animals, respectively) than bland ointment (12/38 [32%]) (
P
< 0.005). 128774-53A administration resulted in greater MRSA carriage eradication than mupirocin (19/38 [50%]) (
P
< 0.005) in this model. LAM formulations warrant evaluation for
S. aureus
nasal decolonization in humans.
Molecular Analysis of Cross-Resistance to Capreomycin, Kanamycin, Amikacin, and Viomycin in
Mycobacterium tuberculosis
Authors: Maus Courtney E. , Plikaytis Bonnie B. , Shinnick Thomas M. 
Published: July 2005

ABSTRACT

Capreomycin, kanamycin, amikacin, and viomycin are drugs that are used to treat multidrug-resistant tuberculosis. Each inhibits translation, and cross-resistance to them is a concern during therapy. A recent study revealed that mutation of the
tlyA
gene, encoding a putative rRNA methyltransferase, confers capreomycin and viomycin resistance in
Mycobacterium tuberculosis
bacteria. Mutations in the 16S rRNA gene (
rrs
) have been associated with resistance to each of the drugs; however, reports of cross-resistance to the drugs have been variable. We investigated the role of
rrs
mutations in capreomycin resistance and examined the molecular basis of cross-resistance to the four drugs in
M. tuberculosis
laboratory-generated mutants and clinical isolates. Spontaneous mutants were generated to the drugs singularly and in combination by plating on medium containing one or two drugs. The frequencies of recovery of the mutants on single- and dual-drug plates were consistent with single-step mutations. The
rrs
genes of all mutants were sequenced, and the
tlyA
genes were sequenced for mutants selected on capreomycin, viomycin, or both; MICs of all four drugs were determined. Three
rrs
mutations (A1401G, C1402T, and G1484T) were found, and each was associated with a particular cross-resistance pattern. Similar mutations and cross-resistance patterns were found in drug-resistant clinical isolates. Overall, the data implicate
rrs
mutations as a molecular basis for resistance to each of the four drugs. Furthermore, the genotypic and phenotypic differences seen in the development of cross-resistance when
M. tuberculosis
bacteria were exposed to one or two drugs have implications for selection of treatment regimens.
Peptide Nucleic Acid Antisense Oligomer as a Therapeutic Strategy against Bacterial Infection: Proof of Principle Using Mouse Intraperitoneal Infection
Authors: Tan Xin-Xing , Actor Jeffrey K. , Chen Yin 
Published: July 2005

ABSTRACTAntisense oligodeoxynucleotides (ODNs) and their analogs have been successfully utilized to inhibit gene expression and bacterial growth in vitro or in cell culture. In this study,acpP-targeting antisense peptide nucleic acid (PNA) and its peptide conjugate were tested as potential antibacterial agents in two groups of experiments using a mouse model. In the first group,Escherichia colimutant strain SM101 with a defective outer membrane was used to induce bacteremia and peritonitis in BALB/c mice by intraperitoneal (i.p.) injection. The resulting bacteremia was fatal within 48 h. A single i.p injection of 5 nmol (or more) of PNA administered 30 min before bacterial challenge significantly reduced the bacterial load in mouse blood. Reductions in serum concentrations of the proinflammatory cytokines tumor necrosis factor alpha, interleukin-1β (IL-1β), IL-6, and IL-12 were also observed. PNA treatment was effective in rescuing 100% of infected animals. In the second group, bacteremia in BALB/c mice was induced by i.p. injection ofE. coliwild-type strain K-12. The infected mice were treated by a single intravenous injection of peptide-PNA conjugate 30 min after bacterial challenge. Treatment with the peptide-PNA conjugate significantly reduced the K-12 load, with modest reduction in cytokine concentrations. The conjugate treatment was also able to rescue up to 60% of infected animals. This report is the first demonstration of ODNs' antibacterial efficacy in an animal disease model. The ability of PNA and its peptide conjugate to inhibit bacterial growth and to prevent fatal infection demonstrates the potential for this new class of antibacterial agents.
Activity of the De Novo Engineered Antimicrobial Peptide WLBU2 against
Pseudomonas aeruginosa
in Human Serum and Whole Blood: Implications for Systemic Applications
Authors: Deslouches Berthony , Islam Kazi , Craigo Jodi K. , Paranjape Shruti M. , Montelaro Ronald C. , Mietzner Timothy A. 
Published: July 2005

ABSTRACT

Cationic amphipathic peptides have been extensively investigated as a potential source of new antimicrobials that can complement current antibiotic regimens in the face of emerging drug-resistant bacteria. However, the suppression of antimicrobial activity under certain biologically relevant conditions (e.g., serum and physiological salt concentrations) has hampered efforts to develop safe and effective antimicrobial peptides for clinical use. We have analyzed the activity and selectivity of the human peptide LL37 and the de novo engineered antimicrobial peptide WLBU2 in several biologically relevant conditions. The host-derived synthetic peptide LL37 displayed high activity against
Pseudomonas aeruginosa
but demonstrated staphylococcus-specific sensitivity to NaCl concentrations varying from 50 to 300 mM. Moreover, LL37 potency was variably suppressed in the presence of 1 to 6 mM Mg
2+
and Ca
2+
ions. In contrast, WLBU2 maintained its activity in NaCl and physiologic serum concentrations of Mg
2+
and Ca
2+
. WLBU2 is able to kill
P. aeruginosa
(10
6
CFU/ml) in human serum, with a minimum bactericidal concentration of <9 μM. Conversely, LL37 is inactive in the presence of human serum. Bacterial killing kinetic assays in serum revealed that WLBU2 achieved complete bacterial killing in 20 min. Consistent with these results was the ability of WLBU2 (15 to 20 μM) to eradicate bacteria from ex vivo samples of whole blood. The selectivity of WLBU2 was further demonstrated by its ability to specifically eliminate
P. aeruginosa
in coculture with human monocytes or skin fibroblasts without detectable adverse effects to the host cells. Finally, WLBU2 displayed potent efficacy against
P. aeruginosa
in an intraperitoneal infection model using female Swiss Webster mice. These results establish a potential application of WLBU2 in the treatment of bacterial sepsis.
Ciprofloxacin Induction of a Susceptibility Determinant in
Pseudomonas aeruginosa
Authors: Brazas Michelle D. , Hancock Robert E. W. 
Published: July 2005

ABSTRACT

With few novel antimicrobials in development, resistance to the current selection of antibiotics increasingly encroaches on our ability to control microbial infections. One limitation in our understanding of the basis of the constraints on current therapies is our poor understanding of antibiotic interactions with bacteria on a global scale. Custom DNA microarrays were used to characterize the response of
Pseudomonas aeruginosa
to ciprofloxacin, a fluoroquinolone commonly used in therapy against chronic infections by this intrinsically resistant bacterium. Of the approximately 5,300 open reading frames (ORFs) on the array, 941 genes showed statistically significant (
P
≤ 0.05) differential expression in response to 0.3× MIC of ciprofloxacin; 554 were promoted and 387 were repressed. Most striking among the responsive genes was the region between PA0613 and PA0648, which codes for the bacteriophage-like R2/F2 pyocins. In this region, virtually every ORF was increased by 0.3× MIC of ciprofloxacin and even more dramatically up-regulated (7- to 19-fold) following treatment with 1× MIC of ciprofloxacin. Pyocin gene expression was confirmed with
lux
reporter mutants and real-time PCR studies; pyocin-like particles were also present in transmission electron micrographs of supernatants from cells treated with 1× MIC of ciprofloxacin. Interestingly, mutants in this region exhibited ≥8-fold-increased resistance to ciprofloxacin and other fluoroquinolones, demonstrating that this region is a susceptibility determinant. Since this region is known to be variably present in the genomes of clinical isolates of
P. aeruginosa
(R. K. Ernst et al., Environ. Microbiol.
5:
1341-1349, 2003, and M. C. Wolfgang et al., Proc. Natl. Acad. Sci. USA
100:
8484-8489, 2003), these findings demonstrate that the R2/F2 pyocin region is a “loaded gun” that can mediate fluoroquinolone susceptibility in
P. aeruginosa
.
Effect of Ciprofloxacin-Induced Prostaglandin E2on Interleukin-18-Treated Monocytes
Authors: Takahashi Hideo Kohka , Iwagaki Hiromi , Xue Dong , Katsuno Goutarou , Sugita Sachi , Mizuno Kenji , Mori Shuji , Saito Shinya , Yoshino Tadashi , Tanaka Noriaki , Nishibori Masahiro 
Published: July 2005

ABSTRACTCiprofloxacin, a fluorinated 4-quinolone, is useful for the clinical treatment of infections due to its antibacterial properties and also modulates the immune response of monocytes isolated from human peripheral blood mononuclear cells. In the present study, we found that ciprofloxacin induced the production of prostaglandin E2in monocytes in a concentration-dependent manner regardless of the presence of interleukin-18 by enhancing the expression of cyclooxygenase-2 protein and that this in turn led to the elevation of intercellular cyclic AMP in monocytes via the stimulation of prostaglandin receptors. The prostaglandin E2and cyclic AMP production increased by ciprofloxacin was inhibited by indomethacin, a nonselective cyclooxygenase-2 inhibitor, and NS398, a selective cyclooxygenase-2 inhibitor. In addition, ciprofloxacin suppressed the interleukin-18-induced production of tumor necrosis factor alpha, gamma interferon, and interleukin-12 in peripheral blood mononuclear cells by inhibiting the expression of intercellular adhesion molecule 1, B7.1, B7.2, and CD40 on monocytes, and this effect could be reversed by the addition of indomethacin or NS398. These results indicate that ciprofloxacin exerts immunomodulatory activity via the production of prostaglandin E2and imply therapeutic potential of ciprofloxacin for the treatment of systemic inflammatory responses initiated by interleukin-18.
In Vitro and In Vivo Antibacterial Activities of CS-023 (RO4908463), a Novel Parenteral Carbapenem
Authors: Koga Tetsufumi , Abe Tomomi , Inoue Harumi , Takenouchi Takashi , Kitayama Akiko , Yoshida Tatsuhiko , Masuda Nobuhisa , Sugihara Chika , Kakuta Masayo , Nakagawa Miyuki , Shibayama Takahiro , Matsushita Yoko , Hirota Takashi , Ohya Satoshi , Utsui Yukio , Fukuoka Takashi , Kuwahara Syogo 
Published: July 2005

ABSTRACT

CS-023 (RO4908463, formerly R-115685) is a novel 1β-methylcarbapenem with 5-substituted pyrrolidin-3-ylthio groups, including an amidine moiety at the C-2 position. Its antibacterial activity was tested against 1,214 clinical isolates of 32 species and was compared with those of imipenem, meropenem, ceftazidime, ceftriaxone, ampicillin, amikacin, and levofloxacin. CS-023 exhibited a broad spectrum of activity against gram-positive and -negative aerobes and anaerobes, including methicillin-resistant
Staphylococcus aureus
(MRSA), methicillin-resistant
Staphylococcus epidermidis
, penicillin-resistant
Streptococcus pneumoniae
(PRSP), β-lactamase-negative ampicillin-resistant
Haemophilus influenzae
, and
Pseudomonas aeruginosa
. CS-023 showed the most potent activity among the compounds tested against
P. aeruginosa
and MRSA, with MICs at which 90% of isolates tested were inhibited of 4 μg/ml and 8 μg/ml, respectively. CS-023 was stable against hydrolysis by the β-lactamases from
Enterobacter cloacae
and
Proteus vulgaris
. CS-023 also showed potent activity against extended-spectrum β-lactamase-producing
Escherichia coli
. The in vivo efficacy of CS-023 was evaluated with a murine systemic infection model induced by 13 strains of gram-positive and -negative pathogens and a lung infection model induced by 2 strains of PRSP (serotypes 6 and 19). Against the systemic infections with PRSP, MRSA, and
P. aeruginosa
and the lung infections, the efficacy of CS-023 was comparable to those of imipenem/cilastatin and vancomycin (tested against lung infections only) and superior to those of meropenem, ceftriaxone, and ceftazidime (tested against
P. aeruginosa
infections only). These results suggest that CS-023 has potential for the treatment of nosocomial bacterial infections by gram-positive and -negative pathogens, including MRSA and
P. aeruginosa
.