bluuebunny/crossref_metadata_2025_split huggingface dataset:
Generation and structure determination of 5,6‐bis(methylthio)‐4,7‐diethylbenzo[1,2,3]trithiole dication MBT(2+)
Authors: Kimura Takeshi , Ito Kiyohito , Ogawa Satoshi , Sato Ryu , Kawai Yasushi 
Published: March 2005

Abstract5,6‐Bis(methylthio)‐4,7‐diethylbenzo‐[1,2,3]‐trithiole [MBT] was oxidized with two equivalents of SbCl5 to produce a dication, MBT(2+)ċ2SbCl, as a stable, dark‐brown solid. MBT(2+) was unexpectedly silent for 1H‐NMR in CD3CN, whereas it was active for ESR, suggesting that MBT(2+) is a triplet‐state dication MBT(2+)‐T. Meanwhile, treatment of 5‐ methylsulfinyl‐6‐methylthio‐4,7‐diethylbenzo[1,2,3]‐ trithiole [MBTMO] with D2SO4 produced MBT(2+), whose 1H‐NMR gave no signals, whereas the solution is active for ESR. These results imply that MBT(2+) prepared from MBTMO is a triplet‐state dication, and a singlet‐state dication, MBT(2+)‐S, initially generated by acidification of MBTMO, isomerized to the triplet‐state dication, MBT(2+)‐T. Since MBT(2+)‐T is active for ESR at room temperature, two molecules of MBT(2+)‐T should form a spin pair in the solution with a sufficient distance between the two radical centers. The structures of MBT(2+)‐S and MBT(2+)‐T were optimized with the DFT method at the B3LYP6‐31G** level. The total energy difference between them was calculated to be 7.90 kcal/mol; MBT(2+)‐T was shown to be more stable than MBT(2+)‐S. A treatment of MBTMO with SbCl5 gave a 1:1 complex. The structure of the complex was determined with X‐ray crystallography, which showed that the complex is the corresponding sulfonium salt, MBTMOċSbCl5. © 2005 Wiley Periodicals, Inc. Heteroatom Chem 16:111–222, 2005; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/hc.20078
Solvent‐free neat synthetic route to tetrahydroacridinones
Authors: Kidwai M. , Rastogi S. 
Published: March 2005

AbstractAn environmentally benign approach for the synthesis of acridines using inorganic solid supports and “neat reaction'' technology is described. These methodologies completely eliminate the use of solvent during the course of reaction. Moreover, microwave‐assisted reactions reduce the reaction time from hours to minutes with improved yield. © 2005 Wiley Periodicals, Inc. Heteroatom Chem 16:138–222, 2005; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/hc.20080
Interaction of 1,2‐alkadienephosphonic dialkyl esters with sulfenyl‐ and selenenylbromides
Authors: Enchev Dobromir D. 
Published: March 2005

AbstractThe reactivity of dialkyl esters of 1, 2‐alkadienephosphonic acids toward sulfenyl‐ and selenenyl‐bromides has been investigated. © 2005 Wiley Periodicals, Inc. Heteroatom Chem 16:156–222, 2005; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/hc.20083
Immune responses in mice of β‐galactosidase adsorbed or encapsulated in poly(lactic acid) and poly(lactic‐co‐glycolic acid) microspheres
Authors: Stivaktakis N. , Nikou K. , Panagi Z. , Beletsi A. , Leondiadis L. , Avgoustakis K. 
Published: March 2005

AbstractThe immune response induced in mice by β‐galactosidase (β‐gal) adsorbed or encapsulated on poly(lactic acid) (PLA) and poly(lactic‐co‐glycolic acid) (PLGA) microspheres was investigated. The encapsulated protein elicited higher antibody response than the protein adsorbed on the microspheres in the case of the PLA microspheres. However, the encapsulated protein elicited weaker antibody response than the adsorbed protein in the case of the PLGA (50:50) microspheres, probably because, in this case, the encapsulation process adversely affected protein immunogenicity. In the case of adsorbed β‐gal, higher antibody response was obtained with the PLA microspheres than with the PLGA (50:50) microspheres. This may be related to the lower rate of β‐gal desorption from the PLA microspheres. Based on the immunoglobulin G1/immunoglobulin G2a ratios and the stimulation indices for interferon‐γ and interleukin‐4, β‐gal encapsulated or adsorbed on PLA microspheres induced a Th1‐biased immune response whereas β‐gal encapsulated or adsorbed on PLGA (50:50) microspheres induced a Th2‐biased immune response. The results obtained indicate that more potent immune responses are obtained when the protein is encapsulated than adsorbed on the microspheres, providing that the encapsulation process does not adversely affect protein immunogenicity. Also, the type of polymer used to prepare the microspheres, but not the method of protein association with the microspheres, may affect the type of immune response. © 2005 Wiley Periodicals, Inc. J Biomed Mater Res 73A: 332–338, 2005
Accumulation and Oriented Transport of Ampicillin in Caco-2 Cells from Its Pivaloyloxymethylester Prodrug, Pivampicillin
Authors: Chanteux Hugues , Van Bambeke Françoise , Mingeot-Leclercq Marie-Paule , Tulkens Paul M. 
Published: March 2005

ABSTRACTPivampicillin (PIVA), an acyloxymethylester of ampicillin, is thought to enhance the oral bioavailability of ampicillin because of its greater lipophilicity compared to that of ampicillin. The fate of PIVA in intestinal cells and the exact location of its conversion into ampicillin have, however, never been unambiguously established. Polarized Caco-2 cells have been used to examine the handling of PIVA and the release of ampicillin from PIVA by the intestinal epithelium. Experiments were limited to 3 h. Cells incubated with PIVA (apical pole) showed a fast accumulation of ampicillin and transport toward the basolateral medium, whereas PIVA itself was only poorly accumulated and transported. Cells incubated with free ampicillin accumulated and transported only minimal amounts of this drug. Release of ampicillin from cells incubated with PIVA was unaffected by PEPT1 and OCTN2 inhibitors but was sharply decreased after ATP depletion or addition of bis(4-nitrophenyl)-phosphate (BNPP; an esterase inhibitor). PIVA incubated with Caco-2 lysates released free ampicillin, and this release was inhibited by BNPP. Efflux studies showed that the ampicillin that accumulated in cells after incubation with PIVA was preferentially transported out of the cells through the basolateral pole. This efflux was decreased by multidrug resistance-associated protein (MRP) inhibitors (probenecid, MK-571) and by ATP depletion. A phthalimidomethylester of ampicillin that resists cellular esterases failed to cause any significant release (cell lysate) or transport (polarized Caco-2 cells) of ampicillin. These results show that when PIVA is given to Caco-2 cells from their apical pole, ampicillin is released intracellularly and that ampicillin is thereafter preferentially effluxed into the basolateral medium through an MRP-like transporter.
Glycerol Monolaurate Inhibits Virulence Factor Production in
Bacillus anthracis
Authors: Vetter Sara M. , Schlievert Patrick M. 
Published: March 2005

ABSTRACT

Anthrax, caused by
Bacillus anthracis
, has been brought to the public's attention because of the 2001 bioterrorism attacks. However, anthrax is a disease that poses agricultural threats in the United States as well as human populations in Europe, China, Africa, and Australia. Glycerol monolaurate (GML) is a compound that has been shown to inhibit exotoxin production by
Staphylococcus aureus
and other gram-positive bacteria. Here, we study the effects of GML on growth and toxin production in
B. anthracis
. The Sterne strain of
B. anthracis
was grown to post-exponential phase with 0-, 10-, 15-, or 20-μg/ml concentrations of GML and then assayed quantitatively for protective antigen (PA) and lethal factor (LF). After 8 h, GML at concentrations greater than 20 μg/ml was bacteriostatic to growth of the organism. However, a 10-μg/ml concentration of GML was not growth inhibitory, but amounts of PA and LF made were greatly reduced. This effect was not global for all proteins when total secreted protein from culture fluids was examined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Through quantitative reverse transcription-PCR assays, this toxin-inhibitory effect was shown to occur at the transcriptional level, since amounts of mRNA for
pagA
(PA),
lef
(LF), and
cya
(edema factor) were reduced. Surprisingly, mRNA levels of
atxA
, a regulator of exotoxin gene expression, rose in the presence of GML. These data will be useful in developing therapeutic tools to treat anthrax disease, whether in animals or humans. These results also suggest that mechanisms of virulence regulation exist independent of
atxA
.
Reduced Azole Susceptibility in Genotype 3
Candida dubliniensis
Isolates Associated with Increased Cd
CDR1
and Cd
CDR2
Expression
Authors: Pinjon Emmanuelle , Jackson Colin J. , Kelly Steven L. , Sanglard Dominique , Moran Gary , Coleman David C. , Sullivan Derek J. 
Published: March 2005

ABSTRACT

Candida dubliniensis
is a recently identified yeast species primarily associated with oral carriage and infection in individuals infected with the human immunodeficiency virus. The species can be divided into at least four genotypes on the basis of the nucleotide sequence of the internal transcribed spacer region of the rRNA operon. Previous studies have shown that a small number of clinical isolates belonging to genotype 1 are resistant to the commonly used antifungal drug fluconazole. The aim of the present study was to investigate the molecular mechanisms responsible for reduced susceptibility to azole drugs in
C. dubliniensis
genotype 3 isolates obtained from a patient with fluconazole-recalcitrant oral candidiasis. Four isolates from a single clinical sample, one susceptible, the other three exhibiting reduced susceptibilities to fluconazole, itraconazole, ketoconazole, voriconazole, and posaconazole, were examined. Results showed that reduced susceptibility to azole drugs was associated with an increase in the expression of the multidrug transporters Cd
CDR1
and Cd
CDR2
which correlated with reduced intracellular accumulation of radiolabeled fluconazole and an increase in the activity of energy-dependent efflux mechanisms. In contrast to observations made in previous studies, overexpression of the multidrug transporter Cd
MDR1
was not observed. Despite a thorough investigation of all commonly encountered mechanisms of azole resistance, no other mechanism could be associated with reduced susceptibility to azole drugs in the clinical isolates studied. This is the first report of Cd
CDR2
involvement in azole resistance in
C. dubliniensis
.
Development of a Cell-Based High-Throughput Specificity Screen Using a Hepatitis C Virus-Bovine Viral Diarrhea Virus Dual Replicon Assay
Authors: O'Boyle Donald R. , Nower Peter T. , Lemm Julie A. , Valera Lourdes , Sun Jin-Hua , Rigat Karen , Colonno Richard , Gao Min 
Published: March 2005

ABSTRACT
The hepatitis C virus (HCV) replicon is a unique system for the development of a high-throughput screen (HTS), since the analysis of inhibitors requires the quantification of a decrease in a steady-state level of HCV RNA. HCV replicon replication is dependent on host cell factors, and any toxic effects may have a significant impact on HCV replicon replication. Therefore, determining the antiviral specificity of compounds presents a challenge for the identification of specific HCV inhibitors. Here we report the development of an HCV/bovine viral diarrhea virus (BVDV) dual replicon assay suitable for HTS to address these issues. The HCV reporter enzyme is the endogenous NS3 protease contained within the HCV genome, while the BVDV reporter enzyme is a luciferase enzyme engineered into the BVDV genome. The HTS uses a mixture of HCV and BVDV replicon cell lines placed in the same well of a 96-well plate and isolated in the same cell backgrounds (Huh-7). The format consists of three separate but compatible assays: the first quantitates the amount of cytotoxicity based upon the conversion of Alamar blue dye via cellular enzymes, while the second indirectly quantitates HCV replicon replication through measurement of the amount of NS3 protease activity present. The final assay measures the amount of luciferase activity present from the BVDV replicon cells, as an indicator of the specificity of the test compounds. This HCV/BVDV dual replicon assay provides a reliable format to determine the potency and specificity of HCV replicon inhibitors.
Comparative Safety Evaluation of the Candidate Vaginal Microbicide C31G
Authors: Catalone Bradley J. , Kish-Catalone Tina M. , Neely Elizabeth B. , Budgeon Lynn R. , Ferguson Mary L. , Stiller Catherine , Miller Shendra R. , Malamud Daniel , Krebs Fred C. , Howett Mary K. , Wigdahl Brian 
Published: March 2005

ABSTRACT
C31G is currently the focus of clinical trials designed to evaluate this agent as a microbicidal and spermicidal agent. In the following studies, the in vivo safety of C31G was assessed with a Swiss Webster mouse model of cervicovaginal toxicity and correlated with results from in vitro cytotoxicity experiments and published clinical observations. A single exposure of unformulated 1% C31G resulted in mild-to-moderate epithelial disruption and inflammation at 2 and 4 h postapplication. The columnar epithelium of the cervix was the primary site of damage, while no perturbation of the vaginal mucosa was observed. In contrast, application of unformulated 1.7% C31G resulted in greater levels of inflammation in the cervical epithelium at 2 h postapplication and severe epithelial disruption that persisted to 8 h postapplication. Application of a nonionic aqueous gel formulation containing 1% C31G resulted in no apparent cervicovaginal toxicity at any time point evaluated. However, formulation of 1.7% C31G did not substantially reduce the toxicity associated with unformulated C31G at that concentration. These observations correlate with findings gathered during a recent clinical trial, in which once-daily applications resulted in no adverse events in women receiving the formulation containing 1% C31G, compared to moderate-to-severe adverse events in 30% of women receiving the 1.7% C31G formulation. The Swiss Webster mouse model was able to effectively discriminate between concentrations and formulations of C31G that produced distinct clinical effects in human trials. The Swiss Webster animal model may be a highly valuable tool for preclinical evaluation of candidate vaginal microbicides.
Treatment with Benznidazole during the Chronic Phase of Experimental Chagas' Disease Decreases Cardiac Alterations
Authors: Garcia Simone , Ramos Carolina O. , Senra Juliana F. V. , Vilas-Boas Fabio , Rodrigues Maurício M. , Campos-de-Carvalho Antonio C. , Ribeiro-dos-Santos Ricardo , Soares Milena B. P. 
Published: March 2005

ABSTRACT

Chagas' disease, caused by
Trypanosoma cruzi
infection, is one of the main causes of death due to heart failure in Latin American countries. Benznidazole, the chemotherapeutic agent most often used for the treatment of chagasic patients, is highly toxic and has limited efficacy, especially in the chronic phase of the disease. In the present study we used a mouse model of chronic Chagas' disease to investigate the effects of benznidazole treatment during the chronic phase on disease progression. The hearts of benznidazole-treated mice had decreased parasitism and myocarditis compared to the hearts of untreated chagasic mice. Both groups of
Trypanosoma cruzi
-infected mice had significant alterations in their electrocardiograms compared to those of the healthy mice. However, untreated mice had significantly higher cardiac conduction disturbances than benznidazole-treated mice, including intraventricular conduction disturbances, atrioventricular blocks, and extrasystoles. The levels of antibodies against
T. cruzi
antigens (epimastigote extract, P
2
β, and
trans
-sialidase) as well as antibodies against peptides of the second extracellular loops of β
1
-adrenergic and M
2
-muscarinic cardiac receptors were also lower in the sera from benznidazole-treated mice than in the sera from untreated mice. These results demonstrate that treatment with benznidazole in the chronic phase of infection prevents the development of severe chronic cardiomyopathy, despite the lack of complete parasite eradication. In addition, our data highlight the role of parasite persistence in the development of chronic Chagas' disease and reinforce the importance of
T. cruzi
elimination in order to decrease or prevent the development of severe chagasic cardiomyopathy.
Molecular Mechanisms by Which rRNA Mutations Confer Resistance to Clindamycin
Authors: Poehlsgaard Jacob , Pfister Peter , Böttger Erik C. , Douthwaite Stephen 
Published: March 2005

ABSTRACT

The mechanisms by which rRNA mutations confer clindamycin resistance were examined in
Mycobacterium smegmatis
strains containing homogeneous populations of ribosomes with base substitutions at nucleotides A2058 and A2059. Computer graphic predictions based on structural studies correlate with the resistance phenotypes for six of seven strains with unique rRNA mutations.
Novel TEM-Type Extended-Spectrum β-Lactamase, TEM-134, in a
Citrobacter koseri
Clinical Isolate
Authors: Perilli Mariagrazia , Mugnaioli Claudia , Luzzaro Francesco , Fiore Marianna , Stefani Stefania , Rossolini Gian Maria , Amicosante Gianfranco 
Published: March 2005

ABSTRACT

A new natural TEM derivative with extended-spectrum β-lactamase activity, TEM-134, was identified in a ceftazidime-resistant clinical isolate of
Citrobacter koseri
. Compared to TEM-1, TEM-134 contains the following mutations: Q39K, E104K, R164H, and G238S. The
bla
TEM-134
gene was not transferable by conjugation and, apparently, was chromosomally encoded. Expression studies with
Escherichia coli
revealed efficient cefotaximase and ceftazidimase activity for TEM-134.
Efficacy and Safety of Generic Amphotericin B in Experimental Pulmonary Aspergillosis
Authors: Petraitis Vidmantas , Petraitiene Ruta , Lin Pengxin , Calis Karim , Kelaher Amy M. , Muray Heidi A. , Mya-San Christine , Mickiene Diana , Bacher John , Walsh Thomas J. 
Published: March 2005

ABSTRACT
The recent shortage of the brand name drug Fungizone has necessitated a change to generic formulations of amphotericin B deoxycholate. Clinical trials cannot be conducted in a timely manner to provide data on the safety and efficacy of these formulations. We therefore compared generic amphotericin B and Fungizone for activity and safety in the treatment of experimental invasive pulmonary aspergillosis (IPA) in persistently neutropenic rabbits. Fungizone and generic amphotericin B are similar in efficacy, pharmacokinetics, and safety in the treatment of experimental IPA.
Neck injuries presenting to emergency departments in the United States from 1990 to 1999 for ice hockey, soccer, and American football
Authors: Delaney J S , Al-Kashmiri A 
Published: March 2005

Objective:To examine the number and rate of neck injuries in the community as a whole for ice hockey, soccer, and American football by analysing data from patients presenting to emergency departments in the United States from 1990 to 1999.Methods:Data compiled for the US Consumer Product Safety Commission were used to generate estimates for the total number of neck injuries and the more specific diagnoses of neck fractures, dislocations, contusions, sprains, strains, and lacerations occurring nationally from 1990 to 1999. These data were combined with yearly participation figures to generate rates of injury presenting to emergency departments for each sport.Results:There were an estimated 5038 neck injuries from ice hockey, 19 341 from soccer, and 114 706 from American football. These could be broken down as follows: 4964 contusions, sprains, or strains from ice hockey, 17 927 from soccer, and 104 483 from football; 105 neck fractures or dislocations from ice hockey, 214 from soccer, and 1588 from football; 199 neck lacerations for ice hockey, 0 for soccer, and 621 for football. The rates for total neck injuries and combined neck contusions, sprains, or strains were higher for football than for ice hockey or soccer in all years for which data were available.Conclusion:The rate of neck injury in the United States was higher in football than in ice hockey or soccer in the time period studied.
The federal initiative to halt the sale of tobacco to children—the Synar Amendment, 1992–2000: lessons learned
Authors: DiFranza J R , Dussault G F 
Published: March 2005

Background:The Synar Amendment was enacted by the US Congress in 1992 to require states and territories to establish and enforce laws prohibiting the sale of tobacco to minors.Objective:To describe state and federal efforts to comply with the Synar mandate.Methods:State and federal actions were examined for the eight years following enactment.Data sources:Federal documents from 1992–2003, annual block grant applications from 59 states and territories describing activities during federal fiscal years 1995–2000.Measures:Whether applicants made a good faith effort to comply by enacting a law, enforcing it with inspections and penalties, conducting a valid survey and meeting violation rate targets set by the Department of Health and Human Services (DHHS).Results:Between 1996 and 2000, 26 states had made a good faith effort to comply with Synar every year. In 2000, 57 jurisdictions (excluding Maryland and Montana) had established laws without loopholes, 57 conducted a valid survey, and 54 actively enforced their laws. By 2002, violation rates had dropped substantially everywhere but Alaska and a few small territories. No state reached the violation rate goal of 20% without penalising violators.Conclusions:The Synar Amendment has resulted in the universal adoption of laws prohibiting tobacco sales to minors and almost universal enforcement of those laws, resulting in dramatically reduced violation rates. Implementation was slowed significantly by a lack of good faith effort in many states and by DHHS’s decision not to require states to enforce their laws by penalising lawbreakers.
Tobacco on campus: industry marketing and tobacco control policy among post-secondary institutions in Canada
Authors: Hammond D , Tremblay I , Chaiton M , Lessard E , Callard C 
Published: March 2005

Objective:Post-secondary institutions provide a unique opportunity to implement and evaluate leading edge tobacco policies, while influencing a key group of young adults. To date, however, we know little about the tobacco control environment at post-secondary institutions outside the USA.Design:Telephone surveys were conducted with campus informants from 35 post-secondary institutions in Canada to evaluate tobacco control policies and the presence of tobacco marketing on campus.Main outcome measures:Tobacco marketing on campus, tobacco control policies, and attitudes towards tobacco control.Results:The findings indicate that tobacco marketing is prevalent among post-secondary institutions in Canada. Every university and half of all colleges surveyed had participated in some form of tobacco marketing in the past year. Among universities, 80% had run a tobacco advertisement in their paper and 18% had hosted a tobacco sponsored nightclub event. Tobacco control policies varied considerably between institutions. Although several campuses had introduced leading edge policies, such as campus wide outdoor smoking restrictions and tobacco sales bans, there is a general lack of awareness of tobacco issues among campus decision makers and fundamental public health measures, such as indoor smoke-free policies, have yet to be introduced in many cases.Conclusions:Post-secondary institutions in Canada remain tobacco friendly environments. Without increased direction and support from the public health community, post-secondary institutions will continue to lag behind, rather than lead current policy standards.