bluuebunny/crossref_metadata_2025_split huggingface dataset:
Dothistroma (red‐band) needle blight of pines and the dothistromin toxin: a review
Authors: Bradshaw R. E. 
Published: May 2004

SummaryDothistroma (red‐band) needle blight has been a problem in plantations of exotic pines in the southern hemisphere for many decades. The prevalence of this disease is currently increasing in the northern hemisphere and is now affecting trees in their native ranges. The fungal pathogen Mycosphaerella pini with its anamorph Dothistroma pini, which is responsible for the disease, produces a toxin, dothistromin, that is closely related to the potent carcinogen, aflatoxin. Understandably this has provoked concern about possible effects on the health of forestry workers. This review gives a broad coverage of literature on both disease and toxin. The fungus has a complicated taxonomy with many synonyms and in most countries only the anamorph is found. It is a necrotrophic pathogen that kills needle tissue and completes its life cycle in the lesion thus formed. Dispersal of the disease is normally by rain splash of conidiospores but there is evidence that long range dispersal has occurred by transport of contaminated plant tissue and by wind/cloud dispersal of spores in air currents. The severity of disease is affected by humidity, temperature and light. There is variation in susceptibility of different Pinus species and some achieve increased resistance with age. The current method of control in southern hemisphere plantation forests is through spraying with copper fungicides and, with P. radiata, increased disease resistance has been achieved through a breeding programme. The dothistromin toxin is a difuroanthraquinone and is similar in structure to the aflatoxin precursor versicolorin B. Part of a gene cluster encoding dothistromin biosynthetic genes has been cloned and this has confirmed parallels between the dothistromin and aflatoxin biosynthetic pathways. Dothistromin produces damaging oxygen radicals by reductive oxygen activation rather than by photosensitization, but is also thought to exert its toxic effects on specific cellular targets. Studies have shown that dothistromin is a weak mutagen and clastogen and is therefore a potential carcinogen. Although the risks to forest workers are considered very low it is prudent to avoid unnecessary exposure during periods when dothistromin levels are likely to be at their peak.
A Knowledge Transfer Strategy for Public Health Decision Makers
Authors: Dobbins M. , DeCorby K. , Twiddy T. 
Published: May 2004

ABSTRACT Purpose: The purpose of this study was to discover public health decision makers' preferences for content, format, and channels for receiving research knowledge, so as to begin development of a comprehensive national public health knowledge transfer strategy. A preliminary knowledge transfer strategy developed in part from the views expressed by public health decision makers in an earlier study (Dobbins et al. 2002b) was used as a foundation on which to base discussions. The research team believes strongly that consultation with potential users is crucial to ensure the conduct of relevant and timely research as well as the development of an effective knowledge transfer strategy. Methods: Nine focus groups of five to seven participants were held in seven Canadian cities. Participants included medical officers of health, public health managers and directors, health promotion mangers, and health policymakers at provincial and federal levels. A semi‐structured, open‐ended interview guide was used to facilitate the discussion. The focus groups were audiotaped, and results were analyzed independently by two members of the research team who then developed key themes through a consensus process. Results: Generally, participants spoke positively about the knowledge transfer strategy to which they were exposed. In addition, they supported the development of a registry of reviews evaluating the effectiveness of public health interventions rated by methodological quality of the evidence, with a summary statement of the reviews highlighting the results along with specific implications for practice. Participants also indicated they wanted to receive personalized updates of new reviews in their area of interest. Finally, the results highlighted a significant challenge related to knowledge management indicating opportunities for ongoing professional development and training. Conclusions: These findings were used to create an online registry of reviews evaluating the effectiveness of public health and health promotion interventions. The registry is one component of a comprehensive national public health knowledge transfer strategy.
Determination of the In Vivo Pharmacodynamic Profile of Cefepime against Extended-Spectrum-Beta-Lactamase-Producing
Escherichia coli
at Various Inocula
Authors: Maglio Dana , Ong Christine , Banevicius Mary Anne , Geng Qiuming , Nightingale Charles H. , Nicolau David P. 
Published: May 2004

ABSTRACT

Cefepime was evaluated in vivo against two inoculum sizes of four strains of
Escherichia coli
that produced extended-spectrum beta-lactamases (ESBLs) in a murine neutropenic thigh infection model to characterize the pharmacodynamic activity of cefepime in the presence of ESBL-producing bacteria and to evaluate if differences in lengths of cefepime exposure are required with various inocula. Three strains possessed a single enzyme each: TEM-10, TEM-12, and TEM-26. The fourth strain possessed two TEM-derived ESBLs and a third uncharacterized enzyme. Two non-ESBL-producing
E. coli
strains were included for comparison. Mice received various doses of cefepime to achieve a spectrum of percentages of time the drug was above the MIC (%
T
>MICs) for each isolate at both inocula. No significant difference in cefepime exposure was required to achieve similar bactericidal effects for ESBL- and non-ESBL-producing isolates when the starting inoculum was 10
5
CFU of
E. coli
per thigh. The increased MICs observed in vitro for the ESBL-producing strains at 10
7
CFU/ml did not predict the amount of exposure required to achieve a comparable level of bactericidal activity in vivo at the corresponding starting inoculum of 10
7
CFU/thigh. Compared to the cefepime exposure in tests with the lower inoculum (10
5
CFU/thigh), less exposure was required when the starting inoculum was 10
7
CFU/thigh (%
T
>MIC, 6% versus 26%), such that similar doses (in milligrams per kilogram of body weight) produced similar bactericidal effects with both inocula of ESBL-producing isolates. Equivalent exposures of cefepime produced similar effects against the microorganisms regardless of the presence of ESBL production. Pharmacodynamic profiling undertaken with conventional cefepime MIC determinations predicted in vivo microbial outcomes at both inoculum sizes for the ESBL-producing isolates evaluated in this study. These data support the use of conventional MIC determinations in the pharmacodynamic assessment of cefepime.
Anti-Inflammatory Effects of Moxifloxacin on Activated Human Monocytic Cells: Inhibition of NF-κB and Mitogen-Activated Protein Kinase Activation and of Synthesis of Proinflammatory Cytokines
Authors: Weiss Taly , Shalit Itamar , Blau Hannah , Werber Sara , Halperin Drora , Levitov Avital , Fabian Ina 
Published: May 2004

ABSTRACTWe previously showed that moxifloxacin (MXF) exerts protective anti-inflammatory effects in immunosuppressed mice infected withCandida albicansby inhibiting interleukin-8 (IL-8) and tumor necrosis factor alpha (TNF-α) production in the lung. Immunohistochemistry demonstrated inhibition of nuclear factor (NF)-κB translocation in lung epithelium and macrophages in MXF-treated mice. In the present study we investigated the effects of MXF on the production of proinflammatory cytokines (i.e., IL-8, TNF-α, and IL-1β) by activated human peripheral blood monocytes and THP-1 cells and analyzed the effects of the drug on the major signal transduction pathways associated with inflammation: NF-κB and the mitogen-activated protein kinases ERK and c-Jun N-terminal kinase (JNK). The levels of IL-8, TNF-α, and IL-1β secretion rose 20- and 6.7-fold in lipopolysaccharide (LPS)-activated monocytes and THP-1 cells, respectively. MXF (5 to 20 μg/ml) significantly inhibited cytokine production by 14 to 80% and 15 to 73% in monocytes and THP-1 cells, respectively. In THP-1 cells, the level of NF-κB nuclear translocation increased fourfold following stimulation with LPS-phorbol myristate acetate (PMA), and this was inhibited (38%) by 10 μg of MXF per ml. We then assayed the degradation of inhibitor (I)-κB by Western blotting. LPS-PMA induced degradation of I-κB by 73%, while addition of MXF (5 μg/ml) inhibited I-κB degradation by 49%. Activation of ERK1/2 and the 46-kDa p-JNK protein was enhanced by LPS and LPS-PMA and was significantly inhibited by MXF (54 and 42%, respectively, with MXF at 10 μg/ml). We conclude that MXF suppresses the secretion of proinflammatory cytokines in human monocytes and THP-1 cells and that it exerts its anti-inflammatory effects in THP-1 cells by inhibiting NF-κB, ERK, and JNK activation. Its anti-inflammatory properties should be further assessed in clinical settings.
Reactivity of Platelia
Aspergillus
Galactomannan Antigen with Piperacillin-Tazobactam: Clinical Implications Based on Achievable Concentrations in Serum
Authors: Singh Nina , Obman Asia , Husain Shahid , Aspinall Sherrie , Mietzner Sue , Stout Janet E. 
Published: May 2004

ABSTRACT

The possible reactivities of commonly used antibiotics of fungal, nonfungal, and nonmicrobial or synthetic sources with the Platelia
Aspergillus
galactomannan assay were assessed. For drugs that tested positive, the minimal concentration of the antibiotic in serum that yielded a positive test (index, >0.5) was determined. At undiluted concentrations, piperacillin and multiple lots of piperacillin-tazobactam tested positive, whereas amoxicillin, ampicillin-sulbactam, nafcillin, cefazolin, ceftazidime, erythromycin, gentamicin, and levofloxacin tested negative. All three lots of piperacillin-tazobactam and all bags within each lot tested positive, with a mean index value of 5.168. At achievable concentrations in serum, however, only one of three lots of piperacillin-tazobactam yielded a positive test. Concentrations of 75, 150, and 300 μg/ml of serum tested positive with the Platelia
Aspergillus
enzyme immunoassay, whereas lower concentrations, mimicking the trough levels, tested negative. Thus, while achievable serum piperacillin-tazobactam concentrations may potentially result in a positive test for galactomannan, the timing of the collection of serum samples from patients may influence the test results, with reactivity being less likely in samples collected at trough levels or prior to the administration of a dose of the antibiotic.
Susceptibility of
Candida
Species to Photodynamic Effects of Photofrin
Authors: Bliss Joseph M. , Bigelow Chad E. , Foster Thomas H. , Haidaris Constantine G. 
Published: May 2004

ABSTRACT

The in vitro susceptibility of pathogenic
Candida
species to the photodynamic effects of the clinically approved photosensitizing agent Photofrin was examined. Internalization of Photofrin by
Candida
was confirmed by confocal fluorescence microscopy, and the degree of uptake was dependent on incubation concentration. Uptake of Photofrin by
Candida
and subsequent sensitivity to irradiation was influenced by culture conditions. Photofrin uptake was poor in
C. albicans
blastoconidia grown in nutrient broth. However, conversion of blastoconidia to filamentous forms by incubation in defined tissue culture medium resulted in substantial Photofrin uptake. Under conditions where Photofrin was effectively taken up by
Candida
, irradiated organisms were damaged in a drug dose- and light-dependent manner. Uptake of Photofrin was not inhibited by azide, indicating that the mechanism of uptake was not dependent on energy provided via electron transport. Fungal damage induced by Photofrin-mediated photodynamic therapy (PDT) was determined by evaluation of metabolic activity after irradiation. A strain of
C. glabrata
took up Photofrin poorly and was resistant to killing after irradiation. In contrast, two different strains of
C. albicans
displayed comparable levels of sensitivity to PDT. Furthermore, a reference strain of
C. krusei
that is relatively resistant to fluconazole compared to
C. albicans
was equally sensitive to
C. albicans
at Photofrin concentrations of ≥3 μg/ml. The results indicate that photodynamic therapy may be a useful adjunct or alternative to current anti-
Candida
therapeutic modalities, particularly for superficial infections on surfaces amenable to illumination.
Biochemical Characterization of the Naturally Occurring Oxacillinase OXA-50 ofPseudomonas aeruginosa
Authors: Girlich Delphine , Naas Thierry , Nordmann Patrice 
Published: May 2004

ABSTRACTTheblaOXA-50gene (formerly known as the PA5514 gene) is an oxacillinase gene identified in silico in the genome ofPseudomonas aeruginosaPAO1. By using a mutant strain ofP. aeruginosaPAO1 that had an inactivatedblaAmpCcephalosporinase gene, theblaOXA-50gene was shown to be expressed constitutively inP. aeruginosa. This β-lactamase gene was cloned onto a multicopy plasmid and expressed inP. aeruginosaandEscherichia coli. It conferred decreased susceptibility to ampicillin and ticarcillin and, interestingly, to moxalactam and meropenem inP. aeruginosabut not inE. coli. Overexpression and purification enabled us to determine the molecular mass (25 kDa), the pI value (8.6), and the hydrolysis spectrum of the OXA-50 β-lactamase. It is a narrow-spectrum oxacillinase that uncommonly hydrolyzes imipenem, although at a low level. Very similar oxacillinase genes were identified in allP. aeruginosaisolates from various geographical origins tested. The weak variability of the nucleotide sequence of this gene (0 to 2%) corresponded to that found for the naturally occurringblaAmpCcephalosporinase gene ofP. aeruginosa. The study indicated thatP. aeruginosaharbors two naturally encoded β-lactamase genes, one of which encodes an inducible cephalosporinase and the other of which encodes a constitutively expressed oxacillinase.
Novel Pharmacokinetic-Pharmacodynamic Model forPrediction of Outcomes with an Extended-Release FormulationofCiprofloxacin
Authors: Meagher Alison K. , Forrest Alan , Dalhoff Axel , Stass Heino , Schentag Jerome J. 
Published: May 2004

ABSTRACT

The
pharmacokinetics of an extended-release (XR) formulation of
ciprofloxacin has been compared to that of the immediate-release (IR)
product in healthy volunteers. The only significant difference in
pharmacokinetic parameters between the two formulations was seen in the
rate constant of absorption, which was approximately 50% greater
with the IR formulation. The geometric mean plasma ciprofloxacin
concentrations were applied to an in vitro
pharmacokinetic-pharmacodynamic model exposing three different clinical
strains of
Escherichia coli
(MICs, 0.03, 0.5, and 2.0
mg/liter) to 24 h of simulated concentrations in plasma. A
novel mathematical model was derived to describe the time course of
bacterial CFU, including capacity-limited replication and first-order
rate of bacterial clearance, and to model the effects of ciprofloxacin
concentrations on these processes. A “mixture model”
was employed which allowed as many as three bacterial subpopulations to
describe the total bacterial load at any moment. Comparing the two
formulations at equivalent daily doses, the rates and extents of
bacterial killing were similar with the IR and XR formulations at MICs
of 0.03 and 2.0 mg/liter. At an MIC of 0.5 mg/liter, however, the
1,000-mg/day XR formulation showed a moderate advantage in
antibacterial effect: the area under the CFU-time curve was 45%
higher for the IR regimen; the nadir log CFU and 24-h log CFU values
for the IR regimen were 3.75 and 2.49, respectively; and those for XR
were 4.54 and 3.13, respectively. The mathematical model explained the
differences in bacterial killing rate for two regimens with identical
AUC/MIC
ratios.
High Prevalence of Antimicrobial Resistance among Clinical
Streptococcus pneumoniae
Isolates in Asia (an ANSORP Study)
Authors: Song Jae-Hoon , Jung Sook-In , Ko Kwan Soo , Kim Na Young , Son Jun Seong , Chang Hyun-Ha , Ki Hyun Kyun , Oh Won Sup , Suh Ji Yoeun , Peck Kyong Ran , Lee Nam Yong , Yang Yonghong , Lu Quan , Chongthaleong Anan , Chiu Cheng-Hsun , Lalitha M. K. , Perera Jennifer , Yee Ti Teow , Kumarasinghe Gamini , Jamal Farida , Kamarulzaman Adeeba , Parasakthi Navaratnam , Van Pham Hung , Carlos Celia , So Thomas , Ng Tak Keung , Shibl Atef 
Published: May 2004

ABSTRACT

A total of 685 clinical
Streptococcus pneumoniae
isolates from patients with pneumococcal diseases were collected from 14 centers in 11 Asian countries from January 2000 to June 2001. The in vitro susceptibilities of the isolates to 14 antimicrobial agents were determined by the broth microdilution test. Among the isolates tested, 483 (52.4%) were not susceptible to penicillin, 23% were intermediate, and 29.4% were penicillin resistant (MICs ≥ 2 mg/liter). Isolates from Vietnam showed the highest prevalence of penicillin resistance (71.4%), followed by those from Korea (54.8%), Hong Kong (43.2%), and Taiwan (38.6%). The penicillin MICs at which 90% of isolates are inhibited (MIC
90
s) were 4 mg/liter among isolates from Vietnam, Hong Kong, Korea, and Taiwan. The prevalence of erythromycin resistance was also very high in Vietnam (92.1%), Taiwan (86%), Korea (80.6%), Hong Kong (76.8%), and China (73.9%). The MIC
90
s of erythromycin were >32 mg/liter among isolates from Korea, Vietnam, China, Taiwan, Singapore, Malaysia, and Hong Kong. Isolates from Hong Kong showed the highest rate of ciprofloxacin resistance (11.8%), followed by isolates from Sri Lanka (9.5%), the Philippines (9.1%), and Korea (6.5%). Multilocus sequence typing showed that the spread of the Taiwan
19F
clone and the Spain
23F
clone could be one of the major reasons for the rapid increases in antimicrobial resistance among
S. pneumoniae
isolates in Asia. Data from the multinational surveillance study clearly documented distinctive increases in the prevalence rates and the levels of antimicrobial resistance among
S. pneumoniae
isolates in many Asian countries, which are among the highest in the world published to date.
Efficacy of Oral Ramoplanin for Inhibition of Intestinal Colonization by Vancomycin-Resistant Enterococci in Mice
Authors: Stiefel Usha , Pultz Nicole J. , Helfand Marion S. , Donskey Curtis J. 
Published: May 2004

ABSTRACT

Ramoplanin is a glycolipodepsipeptide antibiotic with activity against gram-positive bacteria that is in clinical trials for prevention of vancomycin-resistant
Enterococcus
(VRE) bloodstream infections and treatment of
Clostridium difficile
diarrhea. Orally administered ramoplanin suppresses VRE intestinal colonization, but recurrences after discontinuation of treatment have frequently been observed. We used a mouse model to examine the efficacy of ramoplanin for inhibition of VRE colonization and evaluated the etiology of recurrences of colonization. Eight days of treatment with ramoplanin (100 μg/ml) in drinking water suppressed VRE to undetectable levels, but 100% of mice developed recurrent colonization; a higher dose of 500 μg/ml in water was associated with recurrent colonization in 50% of mice. Two of eight (25%) mice treated with the 100-μg/ml dose of ramoplanin had low levels of VRE in their cecal tissues on day 8 despite undetectable levels in stool and cecal contents. Mice that received prior ramoplanin treatment did not develop VRE overgrowth when challenged with 10
7
CFU of oral VRE 1, 2, or 4 days later. In communal cages, rapid cross-transmission and overgrowth of VRE was observed among clindamycin-treated mice; ramoplanin treatment effectively suppressed VRE overgrowth in such communal cages. Ramoplanin treatment promoted increased density of indigenous
Enterobacteriaceae
and overgrowth of an exogenously administered
Klebsiella pneumoniae
isolate. These results demonstrate the efficacy of ramoplanin for inhibition of VRE colonization and suggest that some recurrences occur due to reexpansion of organisms that persist within the lining of the colon. Ramoplanin treatment may be associated with overgrowth of gram-negative bacilli.
Structure and Association of Human Lactoferrin Peptides withEscherichia coliLipopolysaccharide
Authors: Chapple Daniel S. , Hussain Rohanah , Joannou Christopher L. , Hancock Robert E. W. , Odell Edward , Evans Robert W. , Siligardi Giuliano 
Published: May 2004

ABSTRACTAn 11-amino-acid amphipathic synthetic peptide homologous to a helical region on helix 1 of human lactoferrin HLP-2 exhibited bactericidal activity againstEscherichia coliserotype O111, whereas an analogue synthesized with Pro substituted for Met, HLP-6, had greatly reduced antimicrobial activity. The bactericidal activity of HLP-2 was 10-fold greater than that of HLP-6 in both buffer and growth medium by time-kill assays. These assays also showed a pronounced lag phase that was both concentration and time dependent and that was far greater for HLP-2 than for HLP-6. Both peptides, however, were shown to be equally efficient in destabilizing the outer membrane when the hydrophobic probe 1-N-phenylnaphthylamine was used and to have the same lipopolysaccharide (LPS) binding affinity, as shown by polymyxin B displacement. Circular dichroism (CD) spectroscopy was used to study the structure and the organization of the peptides in solution and upon interaction withE. coliLPS. In the presence of LPS, HLP-2 and HLP-6 were found to bind and adopt a β-strand conformation rather than an α-helix, as shown by nonimmobilized ligand interaction assay-CD spectroscopy. Furthermore, this assay was used to show that there is a time-dependent association of peptide that results in an ordered formation of peptide aggregates. The rate of interpeptide association was far greater in HLP-2 LPS than in HLP-6 LPS, which was consistent with the lag phase observed on the killing curves. These results allow us to propose a mechanism by which HLP-2 folds and self-assembles at the outer membrane surface before exerting its activity.