bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of BCG vaccine on peritoneal endometriotic implants in a rat model of endometriosis
Authors: ITIL Ismail Mete , CIRPAN Teksin , AKERCAN Fuat , GAMAA Akram , KAZANDI Mert , KAZANDI Ali Can , YILDIZ Pinar Solmaz , ASKAR Niyazi
Published: January 2006

Objective:  To investigate the effect of Bacillus Calmette–Guerin (BCG) vaccine on peritoneal implantation of endometrial tissue in rats.

Methods:  Forty sexually mature virgin Wistar albino rats weighing 190–200 g were randomly assigned (double blind) to two groups. The rats in the first group were vaccinated with 0.1 mL BCG and those in the second group were injected with 0.1 mL saline into the tail, intracutaneously. All the rats underwent median laparotomy after 4 weeks of vaccination or injection. The right uterine horn was excised, and the two samples of endometrial tissue dissected from myometrium were implanted on each side of peritoneum at the 2 cm lateral line of the median laparotomy incision. The implanted peritoneal segments were excised after 8 weeks of laparotomy. The tissue samples were accepted, histologically, as endometriosis when both glands and stroma of endometrial tissue were seen in sections.

Results:  Thirty‐six implants from the study group and 34 implants from the control group were obtained. Ten and 23 implants were accepted as endometriosis in the study and control group, respectively. The number of endometriotic foci were significantly lower in the study group than in the control group (P = 0.01).

Conclusions:  Stimulation of the cellular immune response with BCG vaccine could exert an inhibitory effect on ectopic endometriotic implants.
Antisocial Behavior of Adoptees and Nonadoptees: Prediction from Early History and Adolescent Relationships
Authors: Grotevant Harold D. , van Dulmen Manfred H. M. , Dunbar Nora , Nelson‐Christinedaughter Justine , Christensen Mathew , Fan Xitao , Miller Brent C.
Published: January 2006

This study examined the contribution of demographic characteristics, early maltreatment, and peer and family relationships during adolescence to the prediction of aggressive and nonaggressive antisocial behavior (AASB and NAASB, respectively) during young adulthood; and determined whether adoption status has additional ability to predict ASB, once background, early experience, peer, and family variables were controlled. Data from adolescent and parent interviews were used from Waves 1 (predictors) and 3 (outcomes) of the National Longitudinal Study of Adolescent Health (Add Health). The sample included 337 adopted and 10,339 nonadopted adolescents whose mean ages were 15.8 at W1 and 21.7 at W3. Although AASB and NAASB were predicted by background characteristics, early maltreatment, peer relations, and family relationships, adoption status had little to no additional predictive power once the other variables were controlled.
Using TV as a Guide: Associations Between Television Viewing and Adolescents' Sexual Attitudes and Behavior
Authors: Ward L. Monique , Friedman Kimberly
Published: January 2006

Using both correlational and experimental methodology, this study examined contributions of TV viewing to adolescents' sexual attitudes and behavior. A sample of 244 high school students was assigned to view clips depicting either one of three sexual stereotypes or neutral content. Participants then completed measures assessing their attitudes about sexual roles and relationships, their regular TV viewing habits, and their sexual experiences. Results indicated that more frequent viewing of talk shows and of “sexy” prime‐time programs, and viewing TV more intently for companionship, were each associated with greater endorsement of sexual stereotypes. Additionally, more frequent viewing and stronger identification with popular TV characters were associated with greater levels of sexual experience. Laboratory exposure to specific stereotypical content lead to greater acceptance of gender and sexual stereotypes, as well. Implications for television's role as a sexual educator are discussed.
Cooperation without Trust: Overcoming Collective Action Barriers to Endangered Species Protection
Authors: Raymond Leigh
Published: January 2006

Mutual trust among individuals is frequently cited as an important factor in encouraging collective action, particularly in environmental policy settings. Yet the precise role of trust in the collective action process remains uncertain. This article explores the hypothesis that trust is overrated as a cause of cooperation. It initially tests this hypothesis through two case studies of voluntary collective action in a new context: the creation of multiactor Habitat Conservation Plans to protect endangered species. The two cases suggest that institutional mechanisms and political leadership can play an important role in encouraging collective action without relying on trust among cooperators. Besides their theoretical implications, the results suggest policymakers might spend more energy on creating incentives and assurance mechanisms to encourage collaboration, rather than the potentially fruitless task of building of social capital among rival stakeholders.
Preparation and identification of anti‐melatonin monoclonal antibodies
Authors: Yang Tangbin , Wang Jianhe , Qu Lina , Zhong Ping , Yuan Yanhong
Published: January 2006

Abstract:  Anti‐melatonin monoclonal antibodies (MAbs) of high titer were prepared by coupling melatonin to bovine serum albumin with formaldehyde and by immunizing BALB/c mice with multifocal intradermal injections and by fusing high titer antibody producing spleen cells with myeloma cells of SP2/0 origin. Five MAbs were selected for further characterization as classes and subclasses. After four successive limiting dilutions, antibodies were produced by these five clones with high affinities ranging from 109 to 1011/m. These clones were found to be of the immunoglobulin Ig G1 and IgG2b subclass with κ light chain. A systematic study of cross‐reactions with seven compounds (indole, aromatic and imidazole derivatives) showed that the antibody had a high specificity for melatonin, low reactivity with 6‐hydroxymelatonin and N‐acetyl‐5‐hydroxytryptamine, and no detectable reactivity with tryptamine, l‐tryptophan, 5‐methoxytryptamine and N‐acetyl‐l‐tryptophan. The roles of the indole nucleus and the side chain in the determination of the antigenic properties of the molecule are discussed. One of the MAbs, 4C9D7, was used to establish a competitive enzyme‐linked immunosobent assay for the detection of melatonin in supernatant.
Crosstalk between Src and major vault protein in epidermal growth factor‐dependent cell signalling
Authors: Kim Euikyung , Lee Seunghwan , Mian Md Firoz , Yun Sang Uk , Song Minseok , Yi Kye‐Sook , Ryu Sung Ho , Suh Pann‐Ghill
Published: January 2006

Vaults are highly conserved, ubiquitous ribonucleoprotein (RNP) particles with an unidentified function. For the three protein species (TEP1, VPARP, and MVP) and a small RNA that comprises vault, expression of the unique 100‐kDa major vault protein (MVP) is sufficient to form the basic vault structure. To identify and characterize proteins that interact with the Src homology 2 (SH2) domain of Src and potentially regulate Src activity, we used a pull‐down assay using GST–Src–SH2 fusion proteins. We found MVP as a Src–SH2 binding protein in human stomach tissue. Interaction of Src and MVP was also observed in 253J stomach cancer cells. A subcellular localization study using immunofluorescence microscopy shows that epidermal growth factor (EGF) stimulation triggers MVP translocation from the nucleus to the cytosol and perinuclear region where it colocalizes with Src. We found that the interaction between Src and MVP is critically dependent on Src activity and protein (MVP) tyrosyl phosphorylation, which are induced by EGF stimulation. Our results also indicate MVP to be a novel substrate of Src and phosphorylated in an EGF‐dependent manner. Interestingly, purified MVP inhibited the in vitro tyrosine kinase activity of Src in a concentration‐dependent manner. MVP overexpression downregulates EGF‐dependent ERK activation in Src overexpressing cells. To our knowledge, this is the first report of MVP interacting with a protein tyrosine kinase involved in a distinct cell signalling pathway. It appears that MVP is a novel regulator of Src‐mediated signalling cascades.
Detergent‐resistant membranes are platforms for actinoporin pore‐forming activity on intact cells
Authors: Alegre‐Cebollada Jorge , Rodríguez‐Crespo Ignacio , Gavilanes José G. , del Pozo Álvaro Martínez
Published: January 2006

Sticholysin II is a pore‐forming toxin produced by the sea anemone Stichodactyla helianthus. We studied its cytolytic activity on COS‐7 cells. Fluorescence spectroscopy and flow cytometry revealed that the toxin permeabilizes cells to propidium cations in a dose‐dependent and time‐dependent manner. This permeabilization is impaired by preincubation of cells with cyclodextrin. Isolation of detergent‐resistant cellular membranes showed that sticholysin II colocalizes with caveolin‐1 in fractions corresponding to raft‐like domains. The interaction of sticholysin II with such domains is only lipid dependent as it also occurs in the absence of any other membrane‐associated protein. Toxin binding to raft‐like lipid vesicles inhibited cell permeabilization. The results suggest that sticholysin II promotes pore formation in COS‐7 cells through interaction with membrane domains which behave like cellular rafts.
Mutations Conferring Aminoglycoside and Spectinomycin Resistance in
Borrelia burgdorferi
Authors: Criswell Daniel , Tobiason Virginia L. , Lodmell J. Stephen , Samuels D. Scott
Published: January 2006

We have isolated and characterized in vitro mutants of the Lyme disease agent
Borrelia burgdorferi
that are resistant to spectinomycin, kanamycin, gentamicin, or streptomycin, antibiotics that target the small subunit of the ribosome. 16S rRNA mutations A1185G and C1186U, homologous to
Escherichia coli
nucleotides A1191 and C1192, conferred >2,200-fold and 1,300-fold resistance to spectinomycin, respectively. A 16S rRNA A1402G mutation, homologous to
E. coli
A1408, conferred >90-fold resistance to kanamycin and >240-fold resistance to gentamicin. Two mutations were identified in the gene for ribosomal protein S12, at a site homologous to
E. coli
residue Lys-87, in mutants selected in streptomycin. Substitutions at codon 88, K88R and K88E, conferred 7-fold resistance and 10-fold resistance, respectively, to streptomycin on
B. burgdorferi
. The 16S rRNA A1185G and C1186U mutations, associated with spectinomycin resistance, appeared in a population of
B. burgdorferi
parental strain B31 at a high frequency of 6 × 10
−6
. These spectinomycin-resistant mutants successfully competed with the wild-type strain during 100 generations of coculture in vitro. The aminoglycoside-resistant mutants appeared at a frequency of 3 × 10
−9
to 1 ×10
−7
in a population and were unable to compete with wild-type strain B31 after 100 generations. This is the first description of mutations in the
B. burgdorferi
ribosome that confer resistance to antibiotics. These results have implications for the evolution of antibiotic resistance, because the 16S rRNA mutations conferring spectinomycin resistance have no significant fitness cost in vitro, and for the development of new selectable markers.
Novel Compounds Active against
Leishmania major
Authors: St. George Stephanie , Bishop Jeanette V. , Titus Richard G. , Selitrennikoff Claude P.
Published: January 2006

Leishmania major
is an important trypanosomatid pathogen that causes leishmaniasis, which is a serious disease in much of the Old World. Current treatments include a small number of antimony compounds that, while somewhat effective, are limited by serious side effects. We have screened a small portion of a unique chemical library and have found at least three novel compounds that are effective against
L. tarentolae
and
L. major
in vitro and in a murine macrophage model of
L. major
infection. These compounds were effective in both assays at doses significantly lower than those of sodium stibogluconate (Pentostam) and represent possible candidates for drug development.
Malaria Parasites Can Develop Stable Resistance to Artemisinin but Lack Mutations in Candidate Genes
atp6
(Encoding the Sarcoplasmic and Endoplasmic Reticulum Ca
2+
ATPase),
tctp
,
mdr1
, and
cg10
Authors: Afonso A. , Hunt P. , Cheesman S. , Alves A. C. , Cunha C. V. , do Rosário V. , Cravo P.
Published: January 2006

Resistance of
Plasmodium falciparum
to drugs such as chloroquine and sulfadoxine-pyrimethamine is a major problem in malaria control. Artemisinin (ART) derivatives, particularly in combination with other drugs, are thus increasingly used to treat malaria, reducing the probability that parasites resistant to the components will emerge. Although stable resistance to artemisinin has yet to be reported from laboratory or field studies, its emergence would be disastrous because of the lack of alternative treatments. Here, we report for the first time, to our knowledge, genetically stable and transmissible ART and artesunate (ATN)-resistant malaria parasites. Each of two lines of the rodent malaria parasite
Plosmodium chabaudi chabaudi
, grown in the presence of increasing concentrations of ART or ATN, showed 15-fold and 6-fold increased resistance to ART and ATN, respectively. Resistance remained stable after cloning, freeze-thawing, after passage in the absence of drug, and transmission through mosquitoes. The nucleotide sequences of the possible genetic modulators of ART resistance (
mdr1
,
cg10
,
tctp
, and
atp6
) of sensitive and resistant parasites were compared. No mutations in these genes were identified. In addition we investigated whether changes in the copy number of these genes could account for resistance but found that resistant parasites retained the same number of copies as their sensitive progenitors. We believe that this is the first report of a malaria parasite with genetically stable and transmissible resistance to artemisinin or its derivatives.
Diagnostic PCR Analysis of the Occurrence of Methicillin and Tetracycline Resistance Genes among
Staphylococcus aureus
Isolates from Phase 3 Clinical Trials of Tigecycline for Complicated Skin and Skin Structure Infections
Authors: Jones C. Hal , Tuckman Margareta , Howe Anita Y. M. , Orlowski Mark , Mullen Stanley , Chan Karen , Bradford Patricia A.
Published: January 2006

Diagnostic PCR assays were developed to track common genetic determinants of oxacillin resistance as well as resistance to classical tetracyclines in
Staphylococcus aureus
isolates from the recently completed worldwide phase 3 clinical trials of tigecycline. A total of 503 unique
S. aureus
strains isolated from complicated skin and skin structure infections were analyzed. The
mecA
gene was amplified from 120 strains (23.9%) determined to be resistant to oxacillin (MICs ≥ 4 μg/ml). The prevalence of the
mecA
gene was found to vary regionally from 6.5% to 50.9% among isolates originating in Eastern Europe and North America, respectively. The presence of a tetracycline resistance determinant,
tet
(M) or
tet
(K), among methicillin-resistant
S. aureus
(MRSA) isolates also varied regionally, with a range of 11.9% to 46.2% among isolates tested from North America and Eastern Europe, respectively. The occurrence of a tetracycline resistance marker in methicillin-susceptible
S. aureus
(MSSA) strains varied from 2.5 to 16.1% among the isolates tested across the regions of study. The presence of
tet
(M) or
tet
(K) had no discernible effect on the tigecycline MICs for either MRSA or MSSA strains, which is consistent with the ability of the glycylcyclines to retain activity in the presence of both the ribosomal protection and efflux mechanisms of resistance to the tetracyclines.
Discovery of FabH/FabF Inhibitors from Natural Products
Authors: Young Katherine , Jayasuriya Hiranthi , Ondeyka John G. , Herath Kithsiri , Zhang Chaowei , Kodali Srinivas , Galgoci Andrew , Painter Ronald , Brown-Driver Vickie , Yamamoto Robert , Silver Lynn L. , Zheng Yingcong , Ventura Judith I. , Sigmund Janet , Ha Sookhee , Basilio Angela , Vicente Francisca , Tormo José Rubén , Pelaez Fernando , Youngman Phil , Cully Doris , Barrett John F. , Schmatz Dennis , Singh Sheo B. , Wang Jun
Published: January 2006

Condensing enzymes are essential in type II fatty acid synthesis and are promising targets for antibacterial drug discovery. Recently, a new approach using a xylose-inducible plasmid to express antisense RNA in
Staphylococcus aureus
has been described; however, the actual mechanism was not delineated. In this paper, the mechanism of decreased target protein production by expression of antisense RNA was investigated using Northern blotting. This revealed that the antisense RNA acts posttranscriptionally by targeting mRNA, leading to 5′ mRNA degradation. Using this technology, a two-plate assay was developed in order to identify FabF/FabH target-specific cell-permeable inhibitors by screening of natural product extracts. Over 250,000 natural product fermentation broths were screened and then confirmed in biochemical assays, yielding a hit rate of 0.1%. All known natural product FabH and FabF inhibitors, including cerulenin, thiolactomycin, thiotetromycin, and Tü3010, were discovered using this whole-cell mechanism-based screening approach. Phomallenic acids, which are new inhibitors of FabF, were also discovered. These new inhibitors exhibited target selectivity in the gel elongation assay and in the whole-cell-based two-plate assay. Phomallenic acid C showed good antibacterial activity, about 20-fold better than that of thiolactomycin and cerulenin, against
S. aureus
. It exhibited a spectrum of antibacterial activity against clinically important pathogens including methicillin-resistant
Staphylococcus aureus
,
Bacillus subtilis
, and
Haemophilus influenzae
.
Inhibition of the Autolytic System by Vancomycin Causes Mimicry of Vancomycin-Intermediate
Staphylococcus aureus
-Type Resistance, Cell Concentration Dependence of the MIC, and Antibiotic Tolerance in Vancomycin-Susceptible
S. aureus
Authors: Sieradzki Krzysztof , Tomasz Alexander
Published: January 2006

Treatment of the fully vancomycin-susceptible
Staphylococcus aureus
strain COL with subinhibitory concentrations of vancomycin allowed its continued growth but generated a phenotype reminiscent of some
S. aureus
isolates with vancomycin-intermediate
S. aureus
(VISA)-type resistance: the bacteria grew in multicellular clusters; electron microscopy showed inhibition of cell separation and accumulation of amorphous cell wall-like material at the bacterial surface. Titration of free vancomycin showed a gradual disappearance of the drug from the medium, which—eventually—coincided with an increase in the growth rate, burst in viable titer, and dispersal of cellular clusters. Addition of inhibitory concentrations of vancomycin to the same strain at a higher cell concentration caused a very different—antibiotic-tolerant—response: an immediate halt in growth, followed by a prolonged lag, during which there was neither a loss of viable titer or optical density nor a change in cell morphology but a gradual removal of vancomycin from the medium to the cell wall of the bacterium, from which the antibiotic could be recovered in a biologically active form. Eventually, the drug-treated culture resumed normal growth. The transient appearance of both the VISA phenotype and vancomycin tolerance could be traced to the inhibition of the autolytic system of the bacterium by vancomycin molecules attached to the cell wall, blocking the access of a staphylococcal murein hydrolase(s) to its cell wall substrate.
Horizontal Transfer of
bla
CMY
-Bearing Plasmids among Clinical
Escherichia coli
and
Klebsiella pneumoniae
Isolates and Emergence of Cefepime-Hydrolyzing CMY-19
Authors: Wachino Jun-ichi , Kurokawa Hiroshi , Suzuki Satowa , Yamane Kunikazu , Shibata Naohiro , Kimura Kouji , Ike Yasuyoshi , Arakawa Yoshichika
Published: January 2006

Nine
Escherichia coli
and 5
Klebsiella pneumoniae
clinical isolates resistant to various cephalosporins and cephamycins were identified in a Japanese general hospital between 1995 and 1997. All nine
E. coli
isolates and one
K. pneumoniae
isolate carried
bla
CMY-9
, while the other four
K. pneumoniae
isolates harbored a variant of
bla
CMY-9
, namely,
bla
CMY-19
. The pulsed-field gel electrophoresis patterns of the nine CMY-9-producing
E. coli
isolates were almost identical, suggesting their clonal relatedness, while those of the five
K. pneumoniae
isolates were divergent. Plasmid profiles, Southern hybridization, and conjugation assays revealed that the genes for the CMY-9 and the CMY-19 β-lactamases were located on very similar conjugative plasmids in
E. coli
and
K. pneumoniae
. The genetic environment of
bla
CMY-19
was identical to that of
bla
CMY-9
. A single amino acid substitution, I292S, adjacent to the H-10 helix region was observed between CMY-9 and CMY-19. This substitution was suggested to be responsible for the expansion of the hydrolyzing activity against several broad-spectrum cephalosporins, and this finding was consistent with the kinetic parameters determined with purified enzymes. These findings suggest that the
bla
CMY-19
genes found in the four
K. pneumoniae
isolates might have originated from
bla
CMY-9
gene following a point mutation and dispersed among genetically different
K. pneumoniae
isolates via a large transferable plasmid.
Influence of Apigenin on
gtf
Gene Expression in
Streptococcus mutans
UA159
Authors: Koo Hyun , Seils Jennifer , Abranches Jacqueline , Burne Robert A. , Bowen William H. , Quivey Robert G.
Published: January 2006

Apigenin, a potent inhibitor of glucosyltransferase activity, affects the accumulation of
Streptococcus mutans
biofilms in vitro by reducing the formation of insoluble glucans and enhancing the soluble glucan content of the polysaccharide matrix. In the present study, we investigated the influence of apigenin on
gtfB
,
gtfC
, and
gtfD
expression in
S. mutans
UA159. Apigenin (0.1 mM) significantly decreased the expression of
gtfB
and
gtfC
mRNA (
P
< 0.05); in contrast, it increased the expression of
gtfD
in
S. mutans
growing in the planktonic state. The protein levels of GTF B, GTF C, and GTF D in culture supernatants were also affected; less GTF B and C were detected, whereas the level of GTF D was significantly elevated (
P
< 0.05). A similar profile of
gtf
expression was obtained with biofilms, although an elevated concentration (1 mM) of apigenin was required to elicit the effects. The influence of apigenin on
gtf
gene expression was independent of any effect on GTF activity, did not involve inhibition of growth or effects on pH, and was not affected by addition of sucrose. The data show that apigenin modulates the genetic expression of virulence factors in
S. mutans.
In Vitro Antiretroviral Activity and In Vitro Toxicity Profile of SPD754, a New Deoxycytidine Nucleoside Reverse Transcriptase Inhibitor for Treatment of Human Immunodeficiency Virus Infection
Authors: Gu Z. , Allard B. , de Muys J. M. , Lippens J. , Rando R. F. , Nguyen-Ba N. , Ren C. , McKenna P. , Taylor D. L. , Bethell R. C.
Published: January 2006

SPD754 (AVX754) is a deoxycytidine analogue nucleotide reverse transcriptase inhibitor (NRTI) in clinical development. These studies characterized the in vitro activity of SPD754 against NRTI-resistant human immunodeficiency virus type 1 (HIV-1) and non-clade B HIV-1 isolates, its activity in combination with other antiretrovirals, and its potential myelotoxicity and mitochondrial toxicity. SPD754 was tested against 50 clinical HIV-1 isolates (5 wild-type isolates and 45 NRTI-resistant isolates) in MT-4 cells using the Antivirogram assay. SPD754 susceptibility was reduced 1.2- to 2.2-fold against isolates resistant to zidovudine (M41L, T215Y/F, plus a median of three additional nucleoside analogue mutations [NAMs]) and/or lamivudine (M184V) and was reduced 1.3- to 2.8-fold against isolates resistant to abacavir (L74V, Y115F, and M184V plus one other NAM) or stavudine (V75T/M, M41L, T215F/Y, and four other NAMs). Insertions at amino acid position 69 and Q151M mutations (with or without M184V) reduced SPD754 susceptibility 5.2-fold and 14- to 16-fold, respectively (these changes gave values comparable to or less than the corresponding values for zidovudine, lamivudine, abacavir, and didanosine). SPD754 showed similar activity against isolates of group M HIV-1 clades, including A/G, B, C, D, A(E), D/F, F, and H. SPD754 showed additive effects in combination with other NRTIs, tenofovir, nevirapine, or saquinavir. SPD754 had no significant effects on cell viability or mitochondrial DNA in HepG2 or MT-4 cells during 28-day exposure at concentrations up to 200 μM. SPD754 showed a low potential for myelotoxicity against human bone marrow. In vitro, SPD754 retained activity against most NRTI-resistant HIV-1 clinical isolates and showed a low propensity to cause myelotoxicity and mitochondrial toxicity.
Safety and Pharmacokinetics of Intravenous Anidulafungin in Children with Neutropenia at High Risk for Invasive Fungal Infections
Authors: Benjamin Daniel K. , Driscoll Timothy , Seibel Nita L. , Gonzalez Corina E. , Roden Maureen M. , Kilaru Rahki , Clark Kay , Dowell James A. , Schranz Jennifer , Walsh Thomas J.
Published: January 2006

Anidulafungin is an echinocandin with activity against
Candida
species and
Aspergillus
species. Adult dosages under study are 50 mg/day for esophageal candidiasis and 100 mg/day for invasive candidiasis and aspergillosis. Little is known, however, about the safety and pharmacokinetics of anidulafungin in children. A multicenter, ascending-dosage study of neutropenic pediatric patients was therefore conducted. Patients were divided into two age cohorts (2 to 11 years and 12 to 17 years) and were enrolled into sequential groups to receive 0.75 or 1.5 mg/kg of body weight/day. Blood samples were obtained following the first and fifth doses. Anidulafungin was assayed in plasma, and pharmacokinetic parameters were determined. Safety was assessed using National Cancer Institute (NCI) common toxicity criteria. Pharmacokinetic parameters were determined for 12 patients at each dosage (0.75 mg/kg/day or 1.5 mg/kg/day). Concentrations and drug exposures were similar for patients between age cohorts, and weight-adjusted clearance was consistent across age. No drug-related serious adverse events were observed. One patient had fever (NCI toxicity grade of 3), and one patient had facial erythema, which resolved with slowing the infusion rate. Anidulafungin in pediatric patients was well tolerated and can be dosed based on body weight. Pediatric patients receiving 0.75 mg/kg/day or 1.5 mg/kg/day have anidulafungin concentration profiles similar to those of adult patients receiving 50 or 100 mg/day, respectively.
Potencies of Human Immunodeficiency Virus Protease Inhibitors In Vitro againstPlasmodium falciparumand In Vivo against Murine Malaria
Authors: Andrews Katherine T. , Fairlie David P. , Madala Praveen K. , Ray John , Wyatt David M. , Hilton Petrina M. , Melville Lewis A. , Beattie Lynette , Gardiner Donald L. , Reid Robert C. , Stoermer Martin J. , Skinner-Adams Tina , Berry Colin , McCarthy James S.
Published: January 2006

Parasite resistance to antimalarial drugs is a serious threat to human health, and novel agents that act on enzymes essential for parasite metabolism, such as proteases, are attractive targets for drug development. Recent studies have shown that clinically utilized human immunodeficiency virus (HIV) protease inhibitors can inhibit the in vitro growth ofPlasmodium falciparumat or below concentrations found in human plasma after oral drug administration. The most potent in vitro antimalarial effects have been obtained for parasites treated with saquinavir, ritonavir, or lopinavir, findings confirmed in this study for a genetically distinctP. falciparumline (3D7). To investigate the potential in vivo activity of antiretroviral protease inhibitors (ARPIs) against malaria, we examined the effect of ARPI combinations in a murine model of malaria. In mice infected withPlasmodium chabaudiAS and treated orally with ritonavir-saquinavir or ritonavir-lopinavir, a delay in patency and a significant attenuation of parasitemia were observed. Using modeling and ligand docking studies we examined putative ligand binding sites of ARPIs in aspartyl proteases ofP. falciparum(plasmepsins II and IV) andP. chabaudi(plasmepsin) and found that these in silico analyses support the antimalarial activity hypothesized to be mediated through inhibition of these enzymes. In addition, in vitro enzyme assays demonstrated thatP. falciparumplasmepsins II and IV are both inhibited by the ARPIs saquinavir, ritonavir, and lopinavir. The combined results suggest that ARPIs have useful antimalarial activity that may be especially relevant in geographical regions where HIV andP. falciparuminfections are both endemic.
Quinolones Induce Partial or Total Loss of Pathogenicity Islands in Uropathogenic
Escherichia coli
by SOS-Dependent or -Independent Pathways, Respectively
Authors: Soto S. M. , Jimenez de Anta M. T. , Vila J.
Published: January 2006

Escherichia coli
is the most common microorganism causing urinary tract infections. Quinolone-resistant
E. coli
strains have fewer virulence factors than quinolone-susceptible strains. Several urovirulence genes are located in pathogenicity islands (PAIs). We investigated the capacity of quinolones to induce loss of virulence factors such as hemolysin, cytotoxic necrotizing factor 1, P fimbriae, and autotransporter Sat included in PAIs in three uropathogenic
E. coli
strains. In a multistep selection, all strains lost hemolytic capacity at between 1 and 4 passages when they were incubated with subinhibitory concentrations of ciprofloxacin, showing a partial or total loss of the PAI containing the
hly
(hemolysin) and
cnf-1
(cytotoxic necrotizing factor 1) genes. RecA
−
mutants were obtained from the two
E. coli
strains with partial or total loss of the PAI. The inactivation of the RecA protein affected only the partial loss of the PAI induced by quinolones. No spontaneous loss of PAIs was observed on incubation in the absence of quinolones in either the wild-type or mutant
E. coli
strains. Quinolones induce partial or total loss of PAIs in vitro in uropathogenic
E. coli
by SOS-dependent or -independent pathways, respectively.
Involvement of the Putative ATP-Dependent Efflux Proteins PatA and PatB in Fluoroquinolone Resistance of a Multidrug-Resistant Mutant of
Streptococcus pneumoniae
Authors: Marrer Estelle , Schad Karen , Satoh Andreas T. , Page Malcolm G. P. , Johnson Maggie M. , Piddock Laura J. V.
Published: January 2006

The multidrug-resistant mutant
Streptococcus pneumoniae
M22 constitutively overexpresses two genes (
patA
and
patB
) that encode proteins homologous to known efflux proteins belonging to the ABC transporter family. It is shown here that PatA and PatB were strongly induced by quinolone antibiotics and distamycin in fluoroquinolone-sensitive strains. PatA was very important for growth of
S. pneumoniae
, and it could not be disrupted in strain M22. PatB appeared to control metabolic activity, particularly in amino acid biosynthesis, and it may have a pivotal role in coordination of the response to quinolone antibiotics. The induction of PatA and PatB by antibiotics showed a pattern similar to that exhibited by SP1861, a homologue of ABC-type transporters of choline and other osmoprotectants. A second group of quinolone-induced transporter genes comprising SP1587 and SP0287, which are homologues of, respectively, oxalate/formate antiporters and xanthine or uracil permeases belonging to the major facilitator family, showed a different pattern of induction by other antibiotics. There was no evidence for the involvement of PmrA, the putative proton-dependent multidrug transporter that has been implicated in norfloxacin resistance, in the response to quinolone antibiotics in either the resistant mutant or the fluoroquinolone-sensitive strains.
Rational Design of Anticytoadherence Inhibitors forPlasmodium falciparumBased on the Crystal Structure of Human Intercellular Adhesion Molecule 1
Authors: Dormeyer Matthias , Adams Yvonne , Kramer Bernd , Chakravorty Srabasti , Tse Man Tsuey , Pegoraro Stefano , Whittaker Lisa , Lanzer Michael , Craig Alister
Published: January 2006

Adhesion ofPlasmodium falciparum-infected erythrocytes (IE) to host endothelium has been associated with pathology in malaria. Although the interaction with endothelial cells can be complex due to the relatively large number of host receptors available for binding, specific proteins have been identified that are more commonly used than others. For example, binding to intercellular adhesion molecule 1 (ICAM 1) is found frequently in parasites from pediatric cases of malaria. The binding site forP. falciparum-infected erythrocytes on ICAM 1 has been mapped in some detail and is distinct from the site for lymphocyte function-associated antigen 1 (LFA-1). Part of the ICAM 1 binding site forP. falciparum-infected erythrocytes (the DE loop) was used to screen a library of compounds based on its structure (derived from the crystal structure of human ICAM 1). This resulted in the identification of 36 structural mimeotopes as potential competitive inhibitors of binding. One of these compounds, (+)-epigalloyl-catechin-gallate [(+)-EGCG], was found to inhibit IE adhesion to ICAM 1 in a dose-dependent manner with two variant ICAM 1-binding parasite lines, providing the first example of a potential mimeotope-based anticytoadherence inhibitor forPlasmodium falciparum.
Doxycycline Attenuated Pulmonary Fibrosis Induced by Bleomycin in Mice
Authors: Fujita Masaki , Ye Qing , Ouchi Hiroshi , Harada Eiji , Inoshima Ichiro , Kuwano Kazuyoshi , Nakanishi Yoichi
Published: January 2006

The administration of doxycycline prior to bleomycin in mice attenuated pulmonary fibrosis. Bronchoalveolar neutrophil influx and gelatinase activity, but not caseinolytic activity, were attenuated by doxycycline. Established fibrosis was not affected by doxycycline. Thus, doxycycline might be useful for slowing down pulmonary fibrosis by biological activity other than antibacterial activity.
Practical Preclinical Model for Assessing the Potential for Unconjugated Hyperbilirubinemia Produced by Human Immunodeficiency Virus Protease Inhibitors
Authors: Kempf Dale J. , Waring Jeffrey F. , Morfitt David C. , Werner Paige , Ebert Brian , Mitten Michael , Nguyen Bach , Randolph John T. , DeGoey David A. , Klein Larry L. , Marsh Kennan
Published: January 2006

A practical preclinical model for the hyperbilirubinemia produced by human immunodeficiency virus protease inhibitors has been developed. Indinavir and atazanavir produced significant hyperbilirubinemia, whereas amprenavir, the negative control, was indistinguishable from the ritonavir booster dose. This model was used to disqualify an exploratory protease inhibitor from development.
Single- and Multistep Resistance Selection Studies on the Activity of Retapamulin Compared to Other Agents against
Staphylococcus aureus
and
Streptococcus pyogenes
Authors: Kosowska-Shick Klaudia , Clark Catherine , Credito Kim , McGhee Pamela , Dewasse Bonifacio , Bogdanovich Tatiana , Appelbaum Peter C.
Published: January 2006

Retapamulin had the lowest rate of spontaneous mutations by single-step passaging and the lowest parent and selected mutant MICs by multistep passaging among all drugs tested for all
Staphylococcus aureus
strains and three
Streptococcus pyogenes
strains which yielded resistant clones. Retapamulin has a low potential for resistance selection in
S. pyogenes
, with a slow and gradual propensity for resistance development in
S. aureus
.
Tissue Penetration of Telavancin after Intravenous Administration in Healthy Subjects
Authors: Sun Heather K. , Duchin Kenneth , Nightingale Charles H. , Shaw Jeng-Pyng , Seroogy Julie , Nicolau David P.
Published: January 2006

The pharmacokinetic disposition of telavancin administered 7.5 mg/kg of body weight every 24 h was determined in plasma and skin blister fluid. The mean penetration of telavancin into blister fluid was 40%. This study reveals that adequate concentrations are achieved in both plasma and blister fluid for pathogens frequently implicated in skin and soft tissue infections.
PCR Classification of CTX-M-Type β-Lactamase Genes Identified in Clinically Isolated Gram-Negative Bacilli in Japan
Authors: Shibata Naohiro , Kurokawa Hiroshi , Doi Yohei , Yagi Tetsuya , Yamane Kunikazu , Wachino Jun-ichi , Suzuki Satowa , Kimura Kouji , Ishikawa Satoshi , Kato Haru , Ozawa Yoshiyuki , Shibayama Keigo , Kai Kumiko , Konda Toshifumi , Arakawa Yoshichika
Published: January 2006

Of 1,456 strains isolated from 2001 to 2003 demonstrating resistance to either oxyimino-cephalosporin, 317 strains, isolated in 57 of 132 clinical facilities, were found to harbor
bla
CTX-M
genes by PCR. Fifty-seven, 161, and 99 strains harbored
bla
CTX-M
genes belonging to the
bla
CTX-M-1
,
bla
CTX-M-2
, and
bla
CTX-M-9
clusters, respectively.
A randomised control study of a fully automated internet based smoking cessation programme
Authors: Swartz L H G , Noell J W , Schroeder S W , Ary D V
Published: January 2006

Objective:The objective of this project was to test the short term (90 days) efficacy of an automated behavioural intervention for smoking cessation, the “1-2-3 Smokefree” programme, delivered via an internet website.

Design:Randomised control trial. Subjects surveyed at baseline, immediately post-intervention, and 90 days later.

Settings:The study and the intervention occurred entirely via the internet site. Subjects were recruited primarily via worksites, which referred potential subjects to the website.

Subjects:The 351 qualifying subjects were notified of the study via their worksite and required to have internet access. Additionally, subjects were required to be over 18 years of age, smoke cigarettes, and be interested in quitting smoking in the next 30 days. Eligible subjects were randomly assigned individually to treatment or control condition by computer algorithm.

Intervention:The intervention consisted of a video based internet site that presented current strategies for smoking cessation and motivational materials tailored to the user’s race/ethnicity, sex, and age. Control subjects received nothing for 90 days and were then allowed access to the programme.

Main outcome measures:The primary outcome measure was abstinence from smoking at 90 day follow up.

Results:At follow up, the cessation rate at 90 days was 24.1% (n  =  21) for the treatment group and 8.2% (n  =  9) for the control group (p  =  0.002). Using an intent-to-treat model, 12.3% (n  =  21) of the treatment group were abstinent, compared to 5.0% (n  =  9) in the control group (p  =  0.015).

Conclusions:These evaluation results suggest that a smoking cessation programme, with at least short term efficacy, can be successfully delivered via the internet.
22 years on: the impact and relevance of the UK No Smoking Day
Authors: Owen L , Youdan B
Published: January 2006

Objectives:To evaluate the impact and relevance of the national awareness day “No Smoking Day” 22 years after it was launched.

Design:Triangulation of data from a variety of sources. Retrospective surveys conducted one week and three months after No Smoking Day, media coverage, website activity, and volume of calls to national smokers’ helplines.

Main outcome measures:Self reports of awareness and smoking behaviour changes one week and three months after No Smoking Day. Volume of media coverage, visits to No Smoking Day website, and volumes of calls to smokers’ helplines.

Results:Follow up at one week indicates awareness of No Smoking Day is lower in 2004 than in 1986 but still high at 70% for all smokers. The decline in participation from 18% of aware smokers in 1994 to 7% in 2001 has been reversed and in 2005 19% quit or reduced their smoking on No Smoking Day. Three months after No Smoking Day awareness was 78% in 2004, lower than in previous studies but still high and equivalent to 9 965 000 smokers when applied to the population estimate of UK smokers. Likewise participation has decreased but at 14% in 2004 is equivalent to an estimated 1 840 000 (1 in 7 of UK smokers) claiming to quit or reduce their consumption on the Day. Among those who participated, 11% were still not smoking more than three months after the Day, equivalent to an estimated 85 000 smokers (0.7% of UK smokers). Media volume has increased even though campaign spend has remained relatively constant and calls to national smokers’ helplines on No Smoking Day are typically four times those received on an average day.

Conclusions:These data suggest that after 22 years No Smoking Day continues to be successful in reaching smokers. With a budget insufficient to pay for advertising, this public awareness campaign supported by local activities appears to be effective in helping smokers to stop.
New tobacco products: do smokers like them?
Authors: Caraballo R S , Pederson L L , Gupta N
Published: January 2006

Background:There is little information about smokers who tried potentially reduced exposure products (PREPs) (Eclipse®, Omni®, Advance Lights®, Accord®, or Ariva®), why they tried them, if they liked these products, and if they will continue to use them.

Objectives:The objectives of this qualitative study were to understand: (1) how smokers who tried PREPs learned about them, (2) reasons for first trying PREPs, (3) which PREP(s) they tried, (4) what they thought of the product at first trial, (5) reasons for continuing or discontinuing use, and (6) whether they would recommend PREPs to others.

Design:In October 2002, 16 focus group sessions were conducted with current cigarette smokers aged 30–50 years: eight groups in Chattanooga, Tennessee, and eight in Dallas, Texas. Specific focus groups were composed of white men, white women, African American men, African American women, Hispanic men, or Hispanic women.

Results:The majority of the participants learned about PREPs through advertising or promotion, family, friends, and co-workers; major reasons given for first trying PREPs were that the products were free or inexpensive, they wanted to stop smoking, they believed the product claims of fewer health risks, or they were curious; most of them tried Eclipse®probably because the focus groups were conducted in the same cities where Eclipse®was introduced; most participants did not like PREPs; most discontinued the use of PREPS, some who continued to use them did so infrequently and also kept smoking their regular brands of cigarettes; and most would not recommend PREPs, although a few might recommend them to specific groups (for example, new smokers, the young, women, curious or health conscious people).

Conclusions:Although most established smokers did not like the PREPs they tried and will not recommend them to anyone, a minority of established smokers believe that there may be a market for these products.
Smokers’ reactions to reduced ignition propensity cigarettes
Authors: O’Connor R J , Giovino G A , Fix B V , Hyland A , Hammond D , Fong G T , Bauer U , Cummings K M
Published: January 2006

Background:On 28 June 2004, New York State (NY) became the first jurisdiction to require cigarettes to meet a reduced ignition propensity (RIP) standard. This law resulted in cigarette manufacturers modifying nearly all of their brands sold in NY. However, the same cigarette brands sold in other states were not modified to meet the RIP standard.

Objectives:This paper examines relationships between the RIP law and smokers’ awareness of changes in the performance of their cigarettes (that is, going out more frequently, change in taste), and smoking behaviour.

Methods:Data for this analysis come from a nationwide survey of 2088 adult smokers (> 18 years of age) conducted in the USA between July and December 2004. 143 of the smokers included in the survey were residents of NY while the remainder were from other states (n  =  1945). Survey participants were asked whether their cigarettes “ever go out between puffs” and whether they had noticed any change in the taste of their cigarettes in the past 12 months.

Results:NY smokers were three times more likely than smokers in other states to report that their cigarettes often went out between puffs (17.3%v5.6%). However, NY smokers appeared no more likely to report noticing differences in cigarette taste, an intention to quit smoking, or to have made quit attempts.

Conclusions:A significant minority of smokers in NY reported noticing changes in the performance of their cigarettes following the RIP law, as would be expected. However, the RIP law appears to have had no impact on the smoking habits of New Yorkers, countering arguments made by cigarette manufacturers that the law would impact consumer acceptability.
THE SHADOW OF LIGHT: FURTHER EXPERIMENTAL EVIDENCES
Authors: CARDONE F. , MIGNANI R. , PERCONTI W. , PETRUCCI A. , SCRIMAGLIO R.
Published: January 2006

We report the results of a double-slit-like experiment in the infrared range, which confirm those of a previous one by evidencing an anomalous behaviour of photon systems under particular (energy and space) constraints. These outcomes (independently confirmed by crossing photon beam experiments in both the optical and the microwave range) apparently rule out the Copenhagen interpretation of the quantum wave, i.e. the probability wave, by admitting an interpretation in terms of the Einstein–de Broglie–Bohm hollow wave for photons. Moreover, this second experiment further supports the interpretation of the hollow wave as a deformation of the Minkowski space-time geometry.
Mode-Locked Fiber Lasers Using Adjustable Saturable Absorption in Vertically Aligned Carbon Nanotubes
Authors: Yamashita Shinji , Inoue Yusuke , Maruyama Shigeo , Murakami Youichi , Yaguchi Hiroshi , Kotake Tomoharu , Set Sze Y.
Published: January 2006

We report an adjustable saturable absorber based on vertically aligned single-walled carbon nanotubes (SWNTs). Using the low-temperature alcohol catalytic chemical vapor deposition (CVD) method, high-quality vertically aligned SWNTs were directly synthesized onto quartz substrates. The saturable absorption is adjustable by changing the decline angle of the substrate. We applied it as a mode-locker in the passively mode-locked fiber lasers, and optimized the operation by declining the vertically aligned SWNT sample.
Analytical Model of Organic Field-Effect Transistor Based on Gradual Channel Approximation with Field-Dependent Mobility
Authors: Nishizawa Hideyuki , Majima Yutaka
Published: January 2006

We developed an analytical model of an organic field-effect transistor (OFET) based on the gradual channel approximation with electric field (E)-dependent mobility µ=µ0 exp
(β√E). The theoretical drain current–drain voltage curves are in good agreement with the measurements of pentacene OFETs, and the prefactor mobility µ0 at temperatures ranging from 233 to 303 K was evaluated. The electric-field- and temperature-dependent carrier transports are discussed independently in terms of µ0 on the basis of this model.
Lead-Free Barium Titanate Ceramics with Large Piezoelectric Constant Fabricated by Microwave Sintering
Authors: Takahashi Hirofumi , Numamoto Yoshiki , Tani Junji , Matsuta Kazuya , Qiu Jinhao , Tsurekawa Sadahiro
Published: January 2006

A lead-free barium titanate (BaTiO3) ceramics with a high density and a large piezoelectric constant, d
33, as manufactured at 1320°C by microwave sintering, using a pure fine powder with a particle size of 100 nm produced by hydrothermal synthesis. The density of the ceramic with a 3.4 µm grain size was more than 98.3% of the theoretical value. The ceramic after poling had a dielectric constant of ε
33

T
/ε
0 =4200, an electromechanical coupling factor planar mode of k

p
=36% and d
33 =350 pC/N. The value of d
33 is the largest one ever reported for lead-free BaTiO3 ceramics.