bluuebunny/crossref_metadata_2025_split huggingface dataset:
PARTICIPATION OF VASOPRESSIN IN THE DEVELOPMENT OF CEREBRAL VASOSPASM IN A RAT MODEL OF SUBARACHNOID HAEMORRHAGE
Authors: Trandafir Cristina C , Nishihashi Tsuyoshi , Wang Aimin , Murakami Shizuka , Ji Xu , Kurahashi Kazuyoshi 
Published: March 2004

SUMMARY1. Previous studies have suggested the involvement of arginine vasopressin (AVP) and inflammation in the development of cerebral vasospasm after subarachnoid haemorrhage (SAH). The aim of the present study was to clarify the role of AVP in the arterial narrowing following cerebral haemorrhage by examining the effect of SR 49059 (a V1 receptor antagonist) on the diameter of rat basilar artery exposed to SAH. The effect of the 5‐lipoxygenase inhibitor ZM 230487 on AVP‐induced contraction of rat basilar arteries was also investigated.2. After 1 h and 2 days from SAH induction, brains were removed and pictures of the basilar arteries were taken. The external diameter of the basilar artery was measured in the presence and absence of SR 49059 (1 mg/kg, i.v.). For in vitro experiments, the basilar arteries isolated from control and SAH rats (at 1 h and at 2 days from SAH induction) were cut into spiral preparations and the AVP (0.3 nmol/L)‐induced contraction in the presence of ZM 230487 was investigated. Each group analysed (i.e. control, SAH 1 h and SAH 2 days) consisted of eight rats.3. The diameter of rat basilar arteries decreased by 43 and 25% at 1 h and 2 days from SAH induction, respectively, compared with control. The administration of SR 49059 significantly reduced cerebral vasospasm. After SAH induction, the diameter of the basilar artery in SR 49059‐treated groups decreased by only 22% (at 1 h) and by 3% (at 2 days) compared with the control group (P < 0.01). In basilar arterial strips, ZM 230487 attenuated the vasopressin‐induced contraction in both control and SAH groups. However, SAH groups showed a significant resistance of the AVP‐induced contraction in the presence of ZM 230487 compared with control (P < 0.05).4. The results suggest that the cerebral vasospasm in SAH rats is due, at least in part, to endogenous AVP and may involve an increase in the activity of 5‐lipoxygenase. SR 49059 may represent a potential therapeutic strategy for the treatment of cerebral vasospasm.
ISCHAEMIA ENHANCES THE ROLE OF CA2+‐ACTIVATED K+ CHANNELS IN ENDOTHELIUM‐DEPENDENT AND NITRIC OXIDE‐MEDIATED DILATATION OF THE RAT HINDQUARTERS VASCULATURE
Authors: Woodman Owen L , Wongsawatkul Orapin 
Published: March 2004

SUMMARY1. We compared the effects of the nitric oxide synthase inhibitor NG‐nitro‐l‐arginine (l‐NOARG) and tetraethylammonium (TEA), a blocker of large conductance Ca2+‐activated K+ (BKCa) channels, on vasodilator responses to endothelium‐dependent (acetylcholine; ACh) and ‐independent (sodium nitroprusside; SNP) vasodilators. The mechanism of the vasodilator responses was determined in rat hindquarters under normal conditions (sham ischaemia) and after 2 h ischaemia followed by reperfusion with physiological saline.2. In sham ischaemia, the responses to ACh were significantly reduced by l‐NOARG (1 mmol/L) and TEA (1 mmol/L) and there was a further reduction in response the presence of both agents. Dilator responses to SNP were significantly enhanced by l‐NOARG, whereas TEA did not alter the SNP‐induced vasodilatation when given either alone or in the presence of l‐NOARG.3. After ischaemia, l‐NOARG caused a similar inhibition of ACh‐induced dilatation to that observed in sham ischaemia. However, TEA alone or combined with l‐NOARG caused a significantly greater inhibition of the ACh‐induced vasodilatation after ischaemia than observed in the sham ischaemia group. Tetraethylammonium alone did not affect the responses to SNP, but it did attenuate the enhanced dilatation observed in the presence of l‐NOARG.4. In the rat hindquarters vasculature, both nitric oxide and the opening of TEA‐sensitive K+ channels contribute to ACh‐induced endothelium‐dependent dilatation. In addition, a TEA‐sensitive mechanism was not involved in the SNP‐induced dilatation under normal conditions but, after ischaemia, if there is a further inhibition of endogenous nitric oxide by l‐NOARG, exogenous nitric oxide causes dilatation that is sensitive, in part, to TEA. Thus, the contribution of the opening of BKCa channels to endothelium‐dependent vasodilatation assumes greater importance after ischaemia and reperfusion. This may reflect an increased ability of nitric oxide or cGMP to open BKCa channels after ischaemia.
TollSim: Simulation and evaluation of toll stations
Authors: Correa E. , Metzner C. , Niño N. 
Published: March 2004

AbstractThis work presents a stochastic simulation model and experimentation for a toll system developed for a highly concurred highway toll in Venezuela, followed by a discussion of performance and economic indicators. Although mathematical models for resource problems have been developed, their use is not widespread, particularly in developing countries were toll systems are manually operated. The main objective of TollSim is to start building an infrastructure and infostructure to be used in a decision support system for management of traffic related issues in a technologically excluded region. The model was developed using an object‐oriented approach and implemented in MODSIM‐III, SIMGRAPHICSII and SIMDRAW.
Prospective evaluation of a cluster program for Finnish forestry and forest industries
Authors: Salo A. , Gustafsson T. , Mild P. 
Published: March 2004

AbstractIn this paper, we report a prospective evaluation process for a major research program for the Finnish forestry and forest industries. To a significant extent, this process was based on fifteen participatory workshops where tools of operational research — most notably multi‐criteria methods embedded in a group support system — were deployed to help representatives from industry, the research community, and public administration in the assessment of socio‐economic impacts and the identification of further research topics. Drawing upon this case study, we also analyze the preconditions, advantages, and limitations of similar kinds of participatory processes in the implementation of formative and summative evaluations.
A contribution to the development of strategic control and planning instruments: An acquisition case study
Authors: Chevalier A. , Kunsch P. L. , Brans J. P. 
Published: March 2004

AbstractThe present paper is part of the efforts made by the authors in recent years to develop strategic control and planning instruments in corporations using OR‐techniques like system dynamics, control theory, and group multicriteria decision aid. A more general framework called ‘adaptive control methodology’ (ACM) combines all these techniques. It has been presented in several papers. The objective of the present analysis is to calibrate this instrument and to tune it to the corporate needs by analysing real‐world applications. More specifically, several case studies have been investigated in large multinational organisations in the food sector. An acquisition case has been used for the calibration purpose. It is analysed in the paper from the ACM perspective to provide additional material for revisiting and improving the methodology.
An AHP/DEA method for measurement of the efficiency of R&D management activities in universities
Authors: Feng Y.J. , Lu H. , Bi K. 
Published: March 2004

AbstractIn order to develop a better tool for the assessment of the management performance of research and development (R&D) activities in research‐oriented universities, a combination of analysis hierarchical process (AHP) and data envelopment analysis (DEA) is proposed for the assessment of the efficiency of R&D management activities in universities. The measure consists of the measurement of a university's previous and present R&D strength by AHP and the assessment of the relative efficiency of its growth in R&D strength against those of other universities by DEA, in which the management basis of the measured universities is taken into consideration. The application of the measure to assess the R&D management efficiency of 29 universities in China indicates the universities which have improved their management work achieved a high efficiency value regardless of whether their original R&D strengths were strong or weak. Such a measure is proved to be helpful for motivating the universities to keep on improving their R&D management.
A surrogate indicator of criticality for stochastic project networks
Authors: Tavares L. V. , Ferreira J. A. , Coelho J. S. 
Published: March 2004

AbstractThe study of the delay that can be caused by any activity of a stochastic project network is a key topic because of the increasing importance of risk and time control in project management. The main concept adopted for this purpose has been the notion of critical activity developed for deterministic project networks but, in this paper, the inadequacy of the concept critical activity for stochastic project networks is shown and a new surrogate indicator of criticality (SIC) is built, using a regression model applied to a large set of generated project networks. This new indicator explains more than 90% of the initial variance estimated for more than 80,000 activities belonging to a wide range of project networks (580 nets), with very different morphological types.
Antiretroviral Spermicide WHI-07 Prevents Vaginal and Rectal Transmission of Feline Immunodeficiency Virus in Domestic Cats
Authors: D'Cruz Osmond J. , Waurzyniak Barbara , Uckun Fatih M. 
Published: March 2004

ABSTRACT

WHI-07 [5-bromo-6-methoxy-5,6-dihydro-3′-azidothymidine-5′-(
p
-bromophenyl)-methoxy alaninyl phosphate] is a novel dual-function aryl phosphate derivative of zidovudine with potent anti-human immunodeficiency virus (HIV) and spermicidal activities. WHI-07 was active against the feline immunodeficiency virus (FIV). This study evaluated whether topical application of WHI-07 as a single agent and in combination with an organometallic vanadium complex, vanadocene dithiocarbamate (VDDTC), via a nontoxic gel microemulsion can block vaginal as well as rectal transmission of feline AIDS (FAIDS) by chronically FIV-infected feline T cells in the natural host model. Genital transmission of FIV was monitored in recipient cats by the appearance of viral antibodies to FIV Gag proteins and by virus isolation of blood leukocytes as measured by FIV reverse transcriptase activity and FIV-specific PCR. Microbicidal activity was considered effective when the treated cats did not show evidence of FIV infection for up to 18 weeks postchallenge. An aggregate analysis of 46 specific-pathogen-free cats revealed that a single dose of the infected cell inoculum efficiently transmitted FIV infection when delivered into the vagina (100%) or rectum (66%). Pretreatment of the vagina or rectum with 2% WHI-07 alone or in combination with 0.25% VDDTC significantly (
P
= 0.004) protected cats from genital transmission by the highly infectious inoculum (7 million FIV
Bangston
-infected feline T cells). Collectively, using the vaginal and rectal transmucosal model for FAIDS, our studies demonstrated that WHI-07 either alone or in combination with a vanadocene has clinical potential for the development of a dual-function anti-HIV microbicide for sexually active women.
The
Candida albicans
Lanosterol 14-α-Demethylase (
ERG11
) Gene Promoter Is Maximally Induced after Prolonged Growth with Antifungal Drugs
Authors: Song Jia L. , Harry Jo Beth , Eastman Richard T. , Oliver Brian G. , White Theodore C. 
Published: March 2004

ABSTRACT

The azole antifungal drugs that target lanosterol 14-α-demethylase, encoded by the
ERG11
gene, are used to treat a variety of infections caused by
Candida albicans.
Azoles are known to induce expression of
ERG11
mRNA. The
ERG11
promoter was cloned 5′ of the luciferase-coding region, and the induction of
ERG11
expression by azoles was monitored by luciferase assays. Maximal induction of the
ERG11
promoter by azoles occurs not during logarithmic growth but after the diauxic shift and requires azoles to be present throughout logarithmic growth. The effects of pH, carbon source, and aerobic or anaerobic growth on induction of the
ERG11
promoter by azoles were analyzed. Treatment with terbinafine and fenpropimorph, which target other enzymes in the ergosterol biosynthetic pathway, also resulted in a delayed induction of
ERG11
promoter activity. Nascent sterol synthesis was shown to parallel
ERG11
promoter activity, and total sterols were reduced coincident with the timing of
ERG11
promoter activation. These results as a whole suggest that expression of the
ERG11
promoter is regulated in response to sterol depletion.
Dynamics and Spatial Distribution of β-Lactamase Expression in
Pseudomonas aeruginosa
Biofilms
Authors: Bagge Niels , Hentzer Morten , Andersen Jens Bo , Ciofu Oana , Givskov Michael , Høiby Niels 
Published: March 2004

ABSTRACT

The development of resistance to β-lactam antibiotics is a problem in the treatment of chronic
Pseudomonas aeruginosa
infection in the lungs of patients with cystic fibrosis. The main resistance mechanism is high-level expression of the chromosomally encoded AmpC β-lactamase of
P. aeruginosa
cells growing in biofilms. Several genes have been shown to influence the level of
ampC
expression, but little is known about the regulation of
ampC
expression in
P. aeruginosa
biofilms. To study the expression of
ampC
in
P. aeruginosa
biofilms, we constructed a reporter that consisted of the fusion of the
ampC
promoter to
gfp
(ASV) encoding an unstable version of the green fluorescent protein. In vitro biofilms of
P. aeruginosa
were exposed to the β-lactam antibiotics imipenem and ceftazidime. Sub-MICs of imipenem significantly induced the monitor system of the biofilm bacteria in the peripheries of the microcolonies, but the centers of the microcolonies remained uninduced. However, the centers of the microcolonies were physiologically active, as shown by experiments with another monitor construction consisting of an arabinose-inducible promoter fused to
gfp
(ASV). The whole biofilm was induced in the presence of increased imipenem concentrations. Ceftazidime induced the monitor system of the biofilm bacteria as well, but only bacteria in the peripheries of the microcolonies were induced in the presence of even very high concentrations. The experiments illustrate for the first time the dynamic and spatial distributions of β-lactamase induction in
P. aeruginosa
cells growing in biofilms. Thus, our experiments show that
P. aeruginosa
cells growing in biofilms constitute a heterogeneous population unit which may create different antibiotic-selective environments for the bacteria in the biofilm.
Ambler Class A Extended-Spectrum Beta-Lactamase-Producing
Escherichia coli
and
Klebsiella
spp. in Canadian Hospitals
Authors: Mulvey Michael R. , Bryce Elizabeth , Boyd David , Ofner-Agostini Marianna , Christianson Sara , Simor Andrew E. , Paton Shirley 
Published: March 2004

ABSTRACT

This report describes a study carried out to gain baseline information on the molecular characteristics of extended-spectrum beta-lactamase (ESBL)-producing
Escherichia coli
and
Klebsiella
spp. in Canada. A total of 29,323
E. coli
and 5,156
Klebsiella
sp. isolates were screened at 12 participating sites. Of these, 505 clinically significant, nonrepeat isolates displaying reduced susceptibility to the NCCLS-recommended beta-lactams were submitted to a central laboratory over a 1-year period ending on 30 September 2000. A total of 116 isolates were confirmed to be ESBL producers. PCR and sequence analysis revealed the presence of TEM-11 (
n
= 1), TEM-12 (
n
= 1), TEM-29 (
n
= 1), TEM-52 (
n
= 4), CTX-M-13 (
n
= 1), CTX-M-14 (
n
= 15), CTX-M-15 (
n
= 11), SHV-2 (
n
= 2), SHV-2a (
n
= 12), SHV-5 (
n
= 6), SHV-12 (
n
= 45), and SHV-30 (
n
= 2). Five novel beta-lactamases were identified and designated TEM-115 (
n
= 2), TEM-120 (
n
= 1), SHV-40 (
n
= 2), SHV-41 (
n
= 4), and SHV-42 (
n
= 1). In addition, no molecular mechanism was identified for five isolates displaying an ESBL phenotype. Macrorestriction analysis of all ESBL isolates was conducted, as was restriction fragment length polymorphism analysis of plasmids harboring ESBLs. Although a “clonal” distribution of isolates was observed at some individual sites, there was very little evidence suggesting intrahospital spread. In addition, examples of identical or closely related plasmids that were identified at geographically distinct sites across Canada are given. However, there was considerable diversity with respect to plasmid types observed.
Chemosensitization of Fluconazole Resistance in
Saccharomyces cerevisiae
and Pathogenic Fungi by a
d
-Octapeptide Derivative
Authors: Niimi K. , Harding D. R. K. , Parshot R. , King A. , Lun D. J. , Decottignies A. , Niimi M. , Lin S. , Cannon R. D. , Goffeau A. , Monk B. C. 
Published: March 2004

ABSTRACT

Hyperexpression of the
Saccharomyces cerevisiae
multidrug ATP-binding cassette (ABC) transporter Pdr5p was driven by the
pdr1-3
mutation in the Pdr1p transcriptional regulator in a strain (AD/PDR5
+
) with deletions of five other ABC-type multidrug efflux pumps. The strain had high-level fluconazole (FLC) resistance (MIC, 600 μg ml
−1
), and plasma membrane fractions showed oligomycin-sensitive ATPase activity up to fivefold higher than that shown by fractions from an isogenic
PDR5
-null mutant (FLC MIC, 0.94 μg ml
−1
). In vitro inhibition of the Pdr5p ATPase activity and chemosensitization of cells to FLC allowed the systematic screening of a 1.8-million-member designer
d-
octapeptide combinatorial library for surface-active Pdr5p antagonists with modest toxicity against yeast cells. Library deconvolution identified the 4-methoxy-2,3,6-trimethylbenzensulfonyl-substituted
d-
octapeptide KN20 as a potent Pdr5p ATPase inhibitor (concentration of drug causing 50% inhibition of enzyme activity [IC
50
], 4 μM) which chemosensitized AD/PDR5
+
to FLC, itraconazole, and ketoconazole. It also inhibited the ATPase activity of other ABC transporters, such as
Candida albicans
Cdr1p (IC
50
, 30 μM) and Cdr2p (IC
50
, 2 μM), and chemosensitized clinical isolates of pathogenic
Candida
species and
S. cerevisiae
strains that heterologously hyperexpressed either ABC-type multidrug efflux pumps, the
C. albicans
major facilitator superfamily-type drug transporter Ben
R
p, or the FLC drug target lanosterol 14α-demethylase (Erg11p). Although KN20 also inhibited the
S. cerevisiae
plasma membrane proton pump Pma1p (IC
50
, 1 μM), the peptide concentrations required for chemosensitization made yeast cells permeable to rhodamine 6G. KN20 therefore appears to indirectly chemosensitize cells to FLC by a nonlethal permeabilization of the fungal plasma membrane.
Disposition of Caspofungin, a Novel Antifungal Agent, in Mice, Rats, Rabbits, and Monkeys
Authors: Sandhu Punam , Xu Xin , Bondiskey Peter J. , Balani Suresh K. , Morris Michael L. , Tang Yui S. , Miller Alisha R. , Pearson Paul G. 
Published: March 2004

ABSTRACTThe metabolism, excretion, and pharmacokinetics of caspofungin (Cancidas; Merck & Co., Inc.) were investigated after administration of a single intravenous dose to mice, rats, rabbits, and monkeys. Caspofungin had a low plasma clearance (0.29 to 1.05 ml/min/kg) and a long terminal elimination half-life (11.7 h to 59.7 h) in all preclinical species. The elimination kinetics of caspofungin were multiphasic and displayed an initial distribution phase followed by a dominant β-elimination phase. The presence of low levels of prolonged radioactivity in plasma was observed and was partially attributable to the chemical degradation product M0. Excretion studies with [3H]caspofungin indicated that the hepatic and renal routes play an important role in the elimination of caspofungin, as a large percentage of the radiolabeled dose was recovered in urine and feces. Excretion of radioactivity in all species studied was slow, and low levels of radioactivity were detected in daily urine and fecal samples throughout a prolonged collection period. Although urinary profiles indicated the presence of several metabolites (M0, M1, M2, M3, M4, M5, and M6), the majority of the total radioactivity was associated with the polar metabolites M1 [4(S)-hydroxy-4-(4-hydroxyphenyl)-l-threonine] and M2 [N-acetyl-4(S)-hydroxy-4-(4-hydroxyphenyl)-l-threonine]. Caspofungin was thus primarily eliminated by metabolic transformation; however, the rate of metabolism was slow. These results suggest that distribution plays a prominent role in determining the plasma pharmacokinetics and disposition of caspofungin, as very little excretion or biotransformation occurred during the early days after dose administration, a period during which concentrations in plasma fell substantially. The disposition of caspofungin in preclinical species was similar to that reported previously in humans.
Antimicrobial and DNA Gyrase-Inhibitory Activities of Novel Clorobiocin Derivatives Produced by Mutasynthesis
Authors: Galm Ute , Heller Stefanie , Shapiro Stuart , Page Malcolm , Li Shu-Ming , Heide Lutz 
Published: March 2004

ABSTRACT

Twenty-eight novel clorobiocin derivatives obtained from mutasynthesis experiments were investigated for their inhibitory activity towards
Escherichia coli
DNA gyrase and for their antibacterial activities towards clinically relevant gram-positive and gram-negative bacteria in comparison to novobiocin and clorobiocin. Clorobiocin was the most active compound both against
E. coli
DNA gyrase in vitro and against bacterial growth. All tested modifications of the 3-dimethylallyl-4-hydroxybenzoyl moiety reduced biological activity. The highest activities were shown by compounds containing a hydrophobic alkyl substituent at position 3 of the 4-hydroxybenzoyl moiety. Polar groups in this side chain, especially amide functions, strongly reduced antibacterial activity. Replacement of the alkyl side chain with a halogen atom or a methoxy group at the same position markedly reduced activity. Transfer of the pyrrole carboxylic acid moiety from O-3" to O-2" of
l
-noviose moderately reduced activity, whereas the complete absence of the pyrrole carboxylic acid moiety led to a loss of activity. Desclorobiocin derivatives lacking the chlorine atom at C-8 of the 3-amino-4,7-dihydroxycoumarin moiety also showed low activity. Lack of a methyl group at O-4" of
l
-noviose resulted in an inactive compound. From these findings it appears that clorobiocin represents a “highly evolved” structure optimized for bacterial transport and DNA gyrase inhibition.
Role of Topoisomerase Mutations and Efflux in Fluoroquinolone Resistance of
Bacteroides fragilis
Clinical Isolates and Laboratory Mutants
Authors: Ricci Vito , Peterson Marnie L. , Rotschafer John C. , Wexler Hannah , Piddock Laura J. V. 
Published: March 2004

ABSTRACT

Twelve laboratory mutants and 32 ciprofloxacin-resistant isolates of
Bacteroides fragilis
were examined for the mechanism(s) of fluoroquinolone resistance. Five mutants had mutations in
gyrA
. One mutant and two clinical isolates contained a mutation in
gyrB.
Eight mutants and five clinical isolates accumulated significantly less ciprofloxacin than did wild-type isolates; the mutants and clinical isolates were restored to wild-type characteristics when carbonyl cyanide
m
-chlorophenylhydrazone was used.
Evidence for a Chromosomally Located Third Integron in
Salmonella enterica
Serovar Typhimurium DT104b
Authors: Daly M. , Buckley J. , Power E. , Fanning S. 
Published: March 2004

ABSTRACT

Salmonella enterica
serovar Typhimurium isolates of phage types DT104 and DT104b are frequently associated with multiple antimicrobial resistance. We describe the characterization of a class 1 integron containing
dfrA1
and
aadA1
, genes from two
Salmonella
serovar Typhimurium DT104b isolates. Genetic mapping located the integron to the bacterial chromosome in each case.