bluuebunny/crossref_metadata_2025_split huggingface dataset:
Ultrapure dialysis fluid: Improving conventional and daily dialysis
Authors: Ledebo Ingrid 
Published: April 2004

AbstractDialysis fluid of standard quality contains a certain amount of bacteria and endotoxin. This has been considered acceptable because the dialysis membrane was believed to be a protective barrier to blood. However, improved methods for detection of cellular activation have demonstrated that bacterial products in the dialysate may stimulate monocytes to produce cytokines with most dialysis membranes. Ultrapure dialysis fluid is practically free from bacteria and endotoxin (< 0.1 CFU/mL and < 0.03 EU/mL) and can be prepared from standard‐quality dialysis fluid using a single step of controlled ultrafiltration. The European guidelines for hemodialysis (HD) set the use of ultrapure dialysis fluid as the goal for all dialysis modalities. Several clinical studies report improved inflammatory status in HD patients when ultrapure dialysis fluid is used, compared with standard‐quality dialysate. The benefits include less frequent occurrence of carpal tunnel syndrome, lower C‐reactive protein values, reduced need for erythropoietin, better nutritional status, and even better preservation of residual renal function. For patients on daily dialysis, dialysate quality is especially important because such patients are often treated at home where quality control of incoming water may be less rigorous, and increased treatment frequency leads to exposure to larger volumes of dialysis fluid than with conventional dialysis. The use of ultrapure dialysis fluid together with low‐complement‐activating membranes maximizes the biocompatibility of a dialysis treatment, a goal of treatment, although there is a lack of evidence to date supporting a beneficial effect on mortality. From a physiologic point of view the reduced inflammatory stimulus that can be achieved with ultrapure dialysis fluid is highly desirable. In addition, achieving ultrapure dialysis fluid is realistic, because today it can be practically and economically prepared using modern equipment and applying appropriate microbiologic surveillance techniques.
Hemofiltration as a treatment for end‐stage renal disease
Authors: Zimmerman Deborah L 
Published: April 2004

AbstractPatients treated for end‐stage renal disease (ESRD) have a poorer quality of life and a higher mortality rate than patients in the general population. In addition, the cost to provide ESRD care is tremendous. Daily hemodialysis programs have been associated with improvements in the patient's quality of life, anemia management, blood pressure, nutrition, and left ventricular hypertrophy. In addition, especially when treated at home, cost savings are possible. Daily hemofiltration may offer additional benefits with enhanced middle‐molecule clearance, improved cardiovascular stability, and perhaps a further reduction in cost. Finally, ease of use of the NxStage System One may encourage patients to undergo their treatment at home.
Role of a Mutation at Position 167 of CTX-M-19 in Ceftazidime Hydrolysis
Authors: Kimura Soichiro , Ishiguro Masaji , Ishii Yoshikazu , Alba Jimena , Yamaguchi Keizo 
Published: April 2004

ABSTRACT

CTX-M-19 is a recently identified ceftazidime-hydrolyzing extended-spectrum β-lactamase, which differs from the majority of CTX-M-type β-lactamases that preferentially hydrolyze cefotaxime but not ceftazidime. To elucidate the mechanism of ceftazidime hydrolysis by CTX-M-19, the β-lactam MICs of a CTX-M-19 producer, and the kinetic parameters of the enzyme were confirmed. We reconfirmed here that CTX-M-19 is also stable at a high enzyme concentration in the presence of bovine serum albumin (20 μg/ml). Under this condition, we obtained more accurate kinetic parameters and determined that cefotaxime (
k
cat

/K
m

, 1.47 × 10
6
s
−1
M
−1
), cefoxitin (
k
cat

/K
m

, 62.2 s
−1
M
−1
), and aztreonam (
k
cat

/K
m

, 1.34 × 10
3
s
−1
M
−1
) are good substrates and that imipenem (
k
+2
/K
, 1.20 × 10
2
s
−1
M
−1
) is a poor substrate. However, CTX-M-18 and CTX-M-19 exhibited too high a

K
m

value (2.7 to 5.6 mM) against ceftazidime to obtain their catalytic activity (
k
cat
). Comparison of the MICs with the catalytic efficiency (
k
cat

/K
m

) of these enzymes showed that some β-lactams, including cefotaxime, ceftazidime, and aztreonam showed a similar correlation. Using the previously reported crystal structure of the Toho-1 β-lactamase, which belongs to the CTX-M-type β-lactamase group, we have suggested characteristic interactions between the enzymes and the β-lactams ceftazidime, cefotaxime, and aztreonam by molecular modeling. Aminothiazole-bearing β-lactams require a displacement of the aminothiazole moiety due to a severe steric interaction with the hydroxyl group of Ser167 in CTX-M-19, and the displacement affects the interaction between Ser130 and the acidic group such as carboxylate and sulfonate of β-lactams.
Analysis of the Effects of Chlorhexidine on Oral Biofilm Vitality and Structure Based on Viability Profiling and an Indicator of Membrane Integrity
Authors: Hope C. K. , Wilson M. 
Published: April 2004

ABSTRACT

Multispecies biofilms modeling interproximal plaque were grown on a hydroxyapatite substratum in a constant-depth film fermentor and then immersed in a viewing solution containing fluorescent indicators of membrane integrity. Confocal laser scanning microscopy (CLSM) revealed the structure and spatial distribution of cell vitality within the biofilms. Chlorhexidine gluconate (CHX) was added to the viewing solution to achieve concentrations of 0.05 and 0.2% (wt/vol) before further CLSM time-lapse series were captured. Image analysis showed that exposure to 0.2% CHX caused the biofilm to contract at a rate of 1.176 μm min
−1
along the
z
axis and also effected changes in total fluorescence measurements and viability profiles through the biofilms after a delay of 3 to 5 min. At a concentration of 0.05% CHX, total fluorescence measurements for the biofilm exhibited barely detectable changes after 5 min. Fluorescence profiles (fluorescence versus time versus depth), however, clearly showed that a time-dependent effect was present, but the clearest indicator of the effect of dilute CHX over time was viability profiling. These findings suggest the possibility of using fluorescent indicators of membrane integrity in conjunction with viability profiling to evaluate the penetration of the bactericidal effects of membrane-active antimicrobial compounds into biofilm.
Antibiotic Susceptibility in Relation to Penicillin-Binding Protein Genes and Serotype Distribution of
Streptococcus pneumoniae
Strains Responsible for Meningitis in Japan, 1999 to 2002
Authors: Ubukata Kimiko , Chiba Naoko , Hasegawa Keiko , Kobayashi Reiko , Iwata Satoshi , Sunakawa Keisuke 
Published: April 2004

ABSTRACT

The antibiotic susceptibilities, genotypes of penicillin (PEN)-binding protein genes (
pbp
), and serotype distributions of
Streptococcus pneumoniae
isolates from meningitis patients were investigated by a nationwide surveillance group in Japan between 1999 and 2002. We analyzed 146 isolates from children (≤17 years old) and 73 from adults (≥18 years old). Isolates with or without abnormal
pbp1a
,
pbp2x
, or
pbp2b
genes identified by PCR were classified into six genotype patterns and 90% MIC (MIC
90
) values for PEN: (i) strains with three normal genes (17.2% of isolates; MIC
90
, 0.031 μg/ml); (ii) strains with abnormal
pbp2x
(22.1%, 0.063 μg/ml); (iii) strains with abnormal
pbp2b
(1.0%, 0.125 μg/ml); (iv) strains with abnormal
pbp2x
and
pbp2b
(7.4%, 0.25 μg/ml); (v) strains with abnormal
pbp1a
and
pbp2x
(12.7%, 0.25 μg/ml); and (vi) strains with three abnormal PBP genes (39.7%, 4 μg/ml), which are termed genotypic PEN-resistant
S. pneumoniae
(gPRSP). Panipenem, a carbapenem, showed an excellent MIC
90
(0.125 μg/ml) against gPRSP, followed by meropenem and vancomycin (0.5 μg/ml), cefotaxime and ceftriaxone (1 μg/ml), and ampicillin (4 μg/ml). Strains of gPRSP were significantly more prevalent in children (45.2%) than in adults (27.4%). The most frequent serotypes were 6B, 19F, 23F, 6A, and 14 in children and 23F, 22, 3, 10, 6B, and 19F in adults. Serotypes 6B, 6A, 19F, 23F, and 14 predominated among gPRSP. In children, 7- and 11-valent pneumococcal conjugate vaccines would cover 76.2 and 81.3% of isolates, respectively, although coverage would be lower in adults (43.9 and 56.0%, respectively). These findings suggest the need for early introduction of pneumococcal conjugate vaccines and continuous bacteriological surveillance for meningitis.
Rapidly Increasing Prevalence of β-Lactamase-Nonproducing, Ampicillin-Resistant
Haemophilus influenzae
Type b in Patients with Meningitis
Authors: Hasegawa Keiko , Chiba Naoko , Kobayashi Reiko , Murayama Somay Y. , Iwata Satoshi , Sunakawa Keisuke , Ubukata Kimiko 
Published: April 2004

ABSTRACT

A total of 395
Haemophilus influenzae
strains from 226 Japanese institutions participating in the Nationwide Surveillance Study Group for Bacterial Meningitis were received from 1999 to 2002. All strains were analyzed by PCR to identify the resistance genes, and their susceptibilities to β-lactam agents were determined. Of these strains, 29.1% were β-lactamase nonproducing and ampicillin (AMP) susceptible (BLNAS) and lacked all resistance genes; 15.4% were β-lactamase producing and AMP resistant and had the
bla
TEM-1
gene; 30.6% were β-lactamase nonproducing and AMP resistant (low-BLNAR) and had a Lys-526 or His-517 amino acid substitution in
ftsI
encoding PBP 3; 13.9% were β-lactamase nonproducing and AMP resistant (BLNAR) and had an additional substitution of Thr-385 in
ftsI
; 9.1% were amoxicillin-clavulanic acid resistant (BLPACR I) and had the
bla
TEM-1
gene and a Lys-526 or His-517 amino acid substitution in
ftsI
; and 1.8% showed resistance similar to that of the BLPACR I group (BLPACR II) but had
bla
TEM-1
gene and
ftsI
substitutions, as was the case for the BLNAR strains. All but three strains were serotype b. The prevalence of BLNAR strains has increased rapidly: 0% in 1999, 5.8% in 2000, 14.1% in 2001, and 21.3% in 2002. The MICs at which 90% of BLNAR isolates were inhibited were as follows: AMP, 16 μg/ml; cefotaxime, 1 μg/ml; ceftriaxone, 0.25 μg/ml; and meropenem, 0.5 μg/ml. All of these values were higher than those for the BLNAS counterpart strains. The relatively wide distributions of the β-lactam MICs for BLNAR strains presumably reflect variations in
ftsI
gene mutations. Pulsed-field gel electrophoresis suggested the rapid spread of specific
H. influenzae
type b strains throughout Japan. Expedited vaccination, rapid identification, and judicious antibiotic use could slow their spread.
Antibacterial Activities of Rhodamine B-Conjugated Gelsolin-Derived Peptides Compared to Those of the Antimicrobial Peptides Cathelicidin LL37, Magainin II, and Melittin
Authors: Bucki Robert , Pastore Jennifer J. , Randhawa Paramjeet , Vegners Rolands , Weiner Daniel J. , Janmey Paul A. 
Published: April 2004

ABSTRACTThe growing number of antibiotic-resistant bacteria necessitates the search for new antimicrobial agents and the principles by which they work. We report that cell membrane-permeant rhodamine B (RhB)-conjugated peptides based on the phosphatidylinositol-4,5-bisphosphate binding site of gelsolin can kill the gram-negative organismsEscherichia coliandPseudomonas aeruginosaand the gram-positive organismStreptococcus pneumoniae. RhB linkage to the QRLFQVKGRR sequence in gelsolin was essential for the antibacterial function, since the unconjugated peptide had no effect on the bacteria tested. Because RhB-QRLFQVKGRR (also termed PBP10), its scrambled sequence (RhB-FRVKLKQGQR), and PBP10 synthesized fromd-isomer amino acids show similar antibacterial properties, the physical and chemical properties of these derivatives appear to be more important than specific peptide folding for their antibacterial functions. The similar activities of PBP10 and all-d-amino-acid PBP10 also indicate that a specific interaction between RhB derivatives and bacterial proteins is unlikely to be involved in the bacterial killing function of PBP10. By using a phospholipid monolayer system, we found a positive correlation between the antibacterial function of PBP10, as well as some naturally occurring antibacterial peptides, and the intrinsic surface pressure activity at the hydrophobic-hydrophilic interface. Surprisingly, we observed little or no dependence of the insertion of these peptides into lipid monolayers on the phospholipid composition. These studies show that an effective antimicrobial agent can be produced from a peptide sequence with specificity to a phospholipid not found in bacteria, and comparisons with other antimicrobial agents suggest that the surface activities of these peptides are more important than specific binding to bacterial proteins or lipids for their antimicrobial functions.
Effects of Drug Resistance Mutations L100I and V106A on the Binding of Pyrrolobenzoxazepinone Nonnucleoside Inhibitors to the Human Immunodeficiency Virus Type 1 Reverse Transcriptase Catalytic Complex
Authors: Locatelli Giada A. , Campiani Giuseppe , Cancio Reynel , Morelli Elena , Ramunno Anna , Gemma Sandra , Hübscher Ulrich , Spadari Silvio , Maga Giovanni 
Published: April 2004

ABSTRACT

We have previously described a novel class of nonnucleoside reverse transcriptase (RT) inhibitors, the pyrrolobenzoxazepinone (PBO) and the pyridopyrrolooxazepinone (PPO) derivatives, which were effective inhibitors of human immunodeficiency virus type 1 (HIV-1) RT, either wild type or carrying known drug resistance mutations (G. Campiani et al., J. Med. Chem. 42:4462-4470, 1999). The lead compound of the PPO class, (
R
)-(−)-PPO464, was shown to selectively target the ternary complex formed by the viral RT with its substrates nucleic acid and nucleotide (G. Maga et al., J. Biol. Chem. 276:44653-44662, 2001). In order to better understand the structural basis for this selectivity, we exploited some PBO analogs characterized by various substituents at C-3 and by different inhibition potencies and drug resistance profiles, and we studied their interaction with HIV-1 RT wild type or carrying the drug resistance mutations L100I and V106A. Our kinetic and thermodynamic analyses showed that the formation of the complex between the enzyme and the nucleotide increased the inhibition potency of the compound PBO354 and shifted the free energy (energy of activation, ΔG
#
) for inhibitor binding toward more negative values. The V106A mutation conferred resistance to PBO 354 by increasing its dissociation rate from the enzyme, whereas the L100I mutation mainly decreased the association rate. This latter mutation also caused a severe reduction in the catalytic efficiency of the RT. These results provide a correlation between the efficiency of nucleotide utilization by RT and its resistance to PBO inhibition.
Novel 4′-Substituted Stavudine Analog with Improved Anti-Human Immunodeficiency Virus Activity and Decreased Cytotoxicity
Authors: Dutschman Ginger E. , Grill Susan P. , Gullen Elizabeth A. , Haraguchi Kazuhiro , Takeda Shingo , Tanaka Hiromichi , Baba Masanori , Cheng Yung-Chi 
Published: April 2004

ABSTRACT

The antiviral drug 2′,3′-didehydro-3′-deoxythymidine (D4T; also know as stavudine and Zerit), which is used against human immunodeficiency virus (HIV), causes delayed toxicity (peripheral neuropathy) in long-term use. After examining a series of 2′,3′-didehydro-3′-deoxy-4′-substituted thymidine (4′-substituted D4T) analogs, 4′-ethynyl D4T was found to have a fivefold-better antiviral effect and to cause less cellular and mitochondrial toxicity than D4T. The antiviral activity of this compound can be reversed by dThd but not by dCyd. The compound acted synergistically with β-
l
-2′,3′-deoxy-3′-thiacytidine (also known as lamivudine) and β-
l
-2′,3′-dideoxy-2′,3′-didehydro-5-fluorocytidine (also known as elvucitabine) and additively with 2′,3′-dideoxyinosine (also known as didanosine and Videx) and 3′-azido-3′-deoxythymidine (also known as Retovir and zidovudine) against HIV. 4′-Ethynyl D4T is phosphorylated by purified human thymidine kinase 1 (TK-1) from CEM cells with a faster relative
V
max
and a lower

K
m

value than D4T. The efficiency of TK-1 in the phosphorylation of 4′-ethynyl D4T is fourfold better than that of D4T. While D4T is broken down by the catabolic enzyme thymidine phosphorylase, the level of breakdown of 4′-ethynyl D4T was below detection. Since 4′-ethynyl D4T has increased anti-HIV activity and decreased toxicity and interacts favorably with other currently used anti-HIV drugs, it should be considered for further development as an anti-HIV drug.
In Vitro Interactions between Antifungals and Immunosuppressants against
Aspergillus fumigatus
Authors: Steinbach William J. , Schell Wiley A. , Blankenship Jill R. , Onyewu Chiatogu , Heitman Joseph , Perfect John R. 
Published: April 2004

ABSTRACT

The optimal treatment for invasive aspergillosis remains elusive, despite the increased efficacy of newer agents. The immunosuppressants cyclosporine (CY), tacrolimus (FK506), and sirolimus (formerly called rapamycin) exhibit in vitro and in vivo activity against
Candida albicans
,
Cryptococcus neoformans
, and
Saccharomyces cerevisiae
, including fungicidal synergy with azole antifungals. We report here that both FK506 and CY exhibit a clear in vitro positive interaction with caspofungin against
Aspergillus fumigatus
by disk diffusion, microdilution checkerboard, and gross and microscopic morphological analyses. Microscopic morphological analyses indicate that the calcineurin inhibitors delay filamentation, and in combination with caspofungin there is a positive interaction. Our findings suggest a potential role for combination therapy with calcineurin pathway inhibitors and existing antifungal agents to augment activity against
A. fumigatus
.
Peritoneal Fluid Titer Test for Peritoneal Dialysis-Related Peritonitis
Authors: Strijack Christine , Harding Godfrey K. M. , Ariano Robert E. , Zelenitsky Sheryl A. 
Published: April 2004

ABSTRACT

Standard microbiological tests (i.e., MIC) do not account for the unique factors of peritoneal dialysis (PD)-related peritonitis which can significantly influence treatment response. Our goals were to develop a peritoneal fluid titer (PFT) test and to conduct a pilot study of its association with clinical outcome. The methodology was developed by using spent dialysate collected from patients with bacterial PD-related peritonitis prior to the initiation of antibiotics. Dialysate was processed and spiked with antibiotic to simulate two standard intraperitoneal regimens: cefazolin plus tobramycin and cefazolin alone. Thirty-six clinical isolates, including
Staphylococcus epidermidis
,
Staphylococcus aureus
,
Escherichia coli
,
Klebsiella pneumoniae
,
Enterobacter cloacae
, and
Pseudomonas aeruginosa
, were tested. In the pilot study, dialysate was collected from 14 patients with bacterial PD-related peritonitis. Titers were determined by using each patient's dialysate and infecting pathogen. Titers were highly reproducible, with discrepancies in only 1% of cases. Overall, PFTs were notably higher against gram-positive bacteria (
P
< 0.0001). The addition of tobramycin increased titers significantly from zero to values of 1/16 to 1/64 against
E. cloacae
and
P. aeruginosa
(
P
< 0.0001). In the pilot study, peritoneal fluid inhibitory titers were significantly associated with clinical outcome, with a median value of 1/96 for patients who were cured compared to 1/32 for those who failed treatment (
P
= 0.036). In conclusion, this study provides preliminary support for the PFT as a pharmacodynamic index specific to the treatment of PD-related peritonitis. With further characterization and validation in patients, the PFT test may advance the study of antibiotic therapies for PD-related peritonitis.
Screening for Microtubule-Disrupting Antifungal Agents by Using a Mitotic-Arrest Mutant of
Aspergillus nidulans
and Novel Action of Phenylalanine Derivatives Accompanying Tubulin Loss
Authors: Kiso Tetsuo , Fujita Ken-Ichi , Ping Xu , Tanaka Toshio , Taniguchi Makoto 
Published: April 2004

ABSTRACT

The microtubule, which is one of the major targets of anthelmintics, anticancer drugs, and fungicides, is composed mainly of α- and β-tubulins. We focused on a unique characteristic of an
Aspergillus nidulans benA33
mutant to screen for microtubule-disrupting antifungal agents. This mutant, which has a β-tubulin with a mutation of a single amino acid, undergoes mitotic arrest due to the formation of hyperstable microtubules at 37°C. The heat sensitivity of the mutant is remedied by some antimicrotubule agents. We found that an agar plate assay with the mutant was able to distinguish three types of microtubule inhibitors. The growth recovery zones of the mutant were formed around paper disks containing microtubule inhibitors, including four benzimidazoles, ansamitocin P-3, griseofulvin, and rhizoxin, on the agar plate at 37°C. Nocodazole, thiabendazole, and griseofulvin reversed the mitotic arrest of the mutant and promoted its hyphal growth. Ansamitocin P-3 and rhizoxin showed growth recovery zones around the growth-inhibitory zones. Benomyl and carbendazim also reversed mitotic arrest but produced weaker growth recovery than the aforementioned drugs. Other microtubule inhibitors, such as colchicine, Colcemid, paclitaxel, podophyllotoxin, TN-16, vinblastine, and vincristine, as well as some cytoskeletal inhibitors tested, did not show such activity. In our screening, we newly identified two mycotoxins, citrinin and patulin, two sesquiterpene dialdehydes, polygodial and warburganal, and four phenylalanine derivatives, arphamenine A,
l
-2,5-dihydrophenylalanine (DHPA),
N
-tosyl-
l
-phenylalanine chloromethylketone, and
N
-carbobenzoxy-
l
-phenylalanine chloromethyl ketone. In a wild-type strain of
A. nidulans
, DHPA caused selective losses of microtubules, as determined by fluorescence microscopy, and of both α- and β-tubulins, as determined by Western blot analysis. This screening method involving the
benA33
mutant of
A. nidulans
is useful, convenient, and highly selective. The phenylalanine derivatives tested are of a novel type of microtubule-disrupting antifungal agents, producing an accompanying loss of tubulins, and are different from well-known tubulin inhibitors affecting the assembly of tubulin dimers into microtubules.