bluuebunny/crossref_metadata_2025_split huggingface dataset:
Defects in Semiconductors: Some Fatal, Some Vital
Authors: Queisser Hans J. , Haller Eugene E. 
Published: July 2002

REVIEWThe role of defects as essential entities in semiconductor materials is reviewed. Early experiments with semiconductors were hampered by the extreme sensitivity of the electronic properties to minute concentrations of impurities. Semiconductors were viewed as a family of solids with irreproducible properties. Scientific efforts overcame this idiosyncrasy and turned the art of impurity doping into today's exceedingly useful and reproducible technology that is used to control precisely electrical conductivity, composition, and minority-carrier lifetimes over wide ranges. Native defects such as vacancies and self-interstitials control basic processes, foremost self- and dopant diffusion. The structural properties of dislocations and higher dimensional defects have been studied with atomic resolution, but a thorough theoretical understanding of their electronic properties is incomplete. Reactions between defects within the host lattices are increasingly better understood and are used for gettering and electrical passivation of unwanted impurities. Metastable defects such as DX centers and the EL2-related arsenic antisite are briefly discussed. The recent development of isotopically controlled semiconductors has created new research opportunities in this field.
Potent Enhancement of the Sensitivity of
Plasmodium falciparum
to Chloroquine by the Bisbenzylisoquinoline Alkaloid Cepharanthin
Authors: Haruki Kosuke , Bray Patrick G. , Ono Minoru , Ward Stephen A. 
Published: July 2002

ABSTRACT

Cepharanthin is a proprietary extract of
Stephania cepharantha
, widely used in Japan for the treatment of inflammatory diseases. Cephranthin, its component alkaloids, and the standard resistance modulator verapamil were tested against
Plasmodium falciparum
for capacity to modulate sensitivity to chloroquine. Cepharanthin enhanced the activity of chloroquine against resistant clones by a factor of 15 at a concentration of only 200 nM (1.2 ng/ml). It is 50 times more potent than verapamil and 3 times more potent than the sum of its individual alkaloids. Combinations of component alkaloids acted synergistically to sensitize the parasite to chloroquine, possibly explaining the enhanced potency of Cepharanthin. Cepharanthin differed from verapamil in that it further sensitized clones that are considered to be fully susceptible, improving the baseline activity of chloroquine. Potent sensitization of parasites to chloroquine in vitro coupled with low toxicity suggests that coadministration of Cepharanthin might extend the clinical utility of chloroquine.
Valganciclovir Results in Improved Oral Absorption of Ganciclovir in Liver Transplant Recipients
Authors: Pescovitz Mark D. , Rabkin John , Merion Robert M. , Paya Carlos V. , Pirsch John , Freeman R. B. , O'Grady John , Robinson Charles , To Zung , Wren Kristina , Banken Ludger , Buhles William , Brown Frances 
Published: July 2002

ABSTRACTThe pharmacokinetics of an orally administered valine ester of ganciclovir (GCV), valganciclovir (VGC), were studied. These were compared to the pharmacokinetics of oral and intravenous GCV. Twenty-eight liver transplant recipients received, in an open-label random order with a 3- to 7-day washout, each of the following: 1 g of oral GCV three times a day; 450 mg of VGC per os (p.o.) once a day (q.d.); 900 mg of VGC p.o. q.d.; and 5 mg of intravenous (i.v.) GCV per kg of body weight q.d., given over 1 h. GCV and VGC concentrations were measured in blood over 24 h. One-sided equivalence testing was performed to test for noninferiority of 450 mg of VGC relative to oral GCV (two-sided 90% confidence interval [CI] > 80%) and nonsuperiority of 900 mg of VGC relative to i.v. GCV (two-sided 90% CI < 125%). The exposure of 450 mg of VGC (20.56 μg · h/ml) was found to be noninferior to that of oral GCV (20.15 μg · h/ml; 90% CI for relative bioavailability of 95 to 109%), and the exposure of 900 mg of VGC (42.69 μg · h/ml) was found to be nonsuperior to that of i.v. GCV (47.61 μg · h/ml; 90% CI = 83 to 97%). Oral VGC delivers systemic GCV exposure equivalent to that of standard oral GCV (at 450 mg) or i.v. GCV (at 900 mg of VGC). VGC has promise for effective CMV prophylaxis or treatment with once-daily oral dosing in transplant recipients.
[1N,12N]Bis(Ethyl)-cis-6,7-Dehydrospermine: a New Drug for Treatment and Prevention ofCryptosporidium parvumInfection of Mice Deficient in T-Cell Receptor Alpha
Authors: Waters W. R. , Frydman B. , Marton L. J. , Valasinas A. , Reddy V. K. , Harp J. A. , Wannemuehler M. J. , Yarlett N. 
Published: July 2002

ABSTRACTCryptosporidium parvuminfection of T-cell receptor alpha (TCR-α)-deficient mice results in a persistent infection. In this study, treatment with a polyamine analogue (SL-11047) preventedC. parvuminfection in suckling TCR-α-deficient mice and cleared an existing infection in older mice. Treatment with putrescine, while capable of preventing infection, did not clearC. parvumfrom previously infected mice. These findings provide further evidence that polyamine metabolic pathways are targets for new anticryptosporidial chemotherapeutic agents.
Differential Effects of Antiretroviral Nucleoside Analogs on Mitochondrial Function in HepG2 Cells
Authors: Pan-Zhou Xin-Ru , Cui Lixin , Zhou Xiao-Jian , Sommadossi Jean-Pierre , Darley-Usmar Victor M. 
Published: July 2002

ABSTRACT

Numerous studies have reported effects of antiviral nucleoside analogs on mitochondrial function, but they have not correlated well with the observed toxic side effects. By comparing the effects of the five Food and Drug Administration-approved anti-human immunodeficiency virus nucleoside analogs, zidovudine (3′-azido-3′-deoxythymidine) (AZT), 2′,3′-dideoxycytidine (ddC), 2′,3′-dideoxyinosine (ddI), 2′,3′-didehydro-2′,3′-deoxythymidine (d4T), and β-L-2′,3′-dideoxy-3′-thiacytidine (3TC), as well as the metabolite of AZT, 3′-amino-3′-deoxythymidine (AMT), on mitochondrial function in a human hepatoma cell line, this issue has been reexamined. Evidence for a number of mitochondrial defects with AZT, ddC, and ddI was found, but only AZT induced a marked rise in lactic acid levels. Only in mitochondria isolated from AZT (50 μM)-treated cells was significant inhibition of cytochrome
c
oxidase and citrate synthase found. Our investigations also demonstrated that AZT, d4T, and 3TC did not affect the synthesis of the 11 polypeptides encoded by mitochondrial DNA, while ddC caused 70% reduction of total polypeptide content and ddI reduced by 43% the total content of 8 polypeptides (including NADH dehydrogenase subunits 1, 2, 4, and 5, cytochrome
c
oxidase subunits I to III, and cytochrome
b
). We hypothesize that in hepatocytes the reserve capacity for mitochondrial respiration is such that inhibition of respiratory enzymes is unlikely to become critical. In contrast, the combined inhibition of the citric acid cycle and electron transport greatly enhances the dependence of the cell on glycolysis and may explain why apparent mitochondrial dysfunction is more prevalent with AZT treatment.
Comparative Activities of Ciprofloxacin and Levofloxacin against
Streptococcus pneumoniae
in an In Vitro Dynamic Model
Authors: Zinner Stephen H. , Simmons Kelly , Gilbert Deborah 
Published: July 2002

ABSTRACT
The activities of levofloxacin (500 mg every 24 h) and ciprofloxacin (750 mg every 12 h) against six pneumococcal isolates in an in vitro dynamic model were compared. For one strain, levofloxacin reduced the inoculum by over 4 log CFU/ml and ciprofloxacin reduced the inoculum by over 2 log CFU/ml. For four isolates, both drugs reduced inocula by 4 log CFU/ml within 6 h, suggesting that this dose of ciprofloxacin should be as effective as levofloxacin against these pneumococci.
Multicenter Surveillance of Antimicrobial Resistance of
Streptococcus pneumoniae
,
Haemophilus influenzae
, and
Moraxella catarrhalis
in Taiwan during the 1998–1999 Respiratory Season
Authors: Hsueh Po-Ren , Liu Yung-Ching , Shyr Jainn-Ming , Wu Tsu-Lan , Yan Jing-Jou , Wu Jiunn-Jong , Leu Hsieh-Shong , Chuang Yin-Ching , Yeu-Jen Lau  , Luh Kwen-Tay 
Published: July 2002

ABSTRACT

A susceptibility surveillance study of 276 isolates of
Streptococcus pneumoniae
, 301 of
Haemophilus influenzae
, and 110 of
Moraxella catarrhalis
was carried out from November 1998 to May 1999 in Taiwan. High rates of nonsusceptibility to penicillin (76%), extended-spectrum cephalosporins (56%), azithromycin (94%), clarithromycin (95%), and trimethoprim-sulfamethoxazole (TMP-SMX) (65%) for
S. pneumoniae
isolates and high rates of nonsusceptibility to amoxicillin (58%) and TMP-SMX (52%) for
H. influenzae
isolates were found. Higher percentages of
S. pneumoniae
isolates nonsusceptible to aminopenicillins, extended-spectrum cephalosporins, macrolides, and TMP-SMX were observed among penicillin-intermediate and -resistant isolates. All quinolones tested were active in vitro against these three organisms.
A Novel Complex Mutant β-Lactamase, TEM-68, Identified in a
Klebsiella pneumoniae
Isolate from an Outbreak of Extended-Spectrum β-Lactamase-Producing Klebsiellae
Authors: Fiett Janusz , Pałucha Andrzej , Mia˛czyńska Beata , Stankiewicz Maria , Przondo-Mordarska Hanna , Hryniewicz Waleria , Gniadkowski Marek 
Published: July 2002

ABSTRACT

Twenty-two
Klebsiella pneumoniae
and two
K. oxytoca
extended-spectrum β-lactamase (ESBL)-producing isolates were collected in 1996 from patients in two pediatric wards of the University Hospital in Wrocław, Poland. Molecular typing has revealed that the
K. pneumoniae
isolates represented four different epidemic strains. Three kinds of enzymes with ESBL activity (pI values of 5.7, 6.0, and 8.2) were identified. The pI 6.0 β-lactamases belonged to the TEM family, and sequencing of the
bla
TEM
genes amplified from representative isolates revealed that these enzymes were TEM-47, previously identified in
K. pneumoniae
isolates from pediatric hospitals in Łódź and Warsaw. One of the TEM-47-producing strains from Wrocław was very closely related to the isolates from the other cities, and this indicated countrywide spread of the epidemic strain. The pI 5.7 β-lactamase was produced by a single
K. pneumoniae
isolate for which, apart from oxyimino-β-lactams, the MICs of β-lactam–inhibitor combinations were also remarkably high. Sequencing revealed that this was a novel TEM β-lactamase variant, TEM-68, specified by the following combination of mutations: Gly238Ser, Glu240Lys, Thr265Met, and Arg275Leu. The new enzyme has most probably evolved from TEM-47 by acquiring the single substitution of Arg275, which before was identified only twice in enzymes with inhibitor resistance (IR) activity. TEM-68 was shown to be a novel complex mutant TEM β-lactamase (CMT-2) which combines strong ESBL activity with relatively weak IR activity and, when expressed in
K. pneumoniae
, is able to confer high-level resistance to a wide variety of β-lactams, including inhibitor combinations. This data confirms the role of the Arg275Leu mutation in determining IR activity and documents the first isolation of
K. pneumoniae
producing the complex mutant enzyme.
Comparison of Fluconazole and Itraconazole in a Rabbit Model of Coccidioidal Meningitis
Authors: Sorensen Kevin N. , Sobel Raymond A. , Clemons Karl V. , Pappagianis Demosthenes , Stevens David A. , Williams Paul L. 
Published: July 2002

ABSTRACT

Coccidioidal meningitis is a devastating disease that requires long-term therapy with little hope of cure. A rabbit model of coccidioidal meningitis was used to compare the therapeutic efficacies of fluconazole (FCZ) and itraconazole (ITZ). Hydrocortisone-treated male New Zealand white rabbits were infected intracisternally with 5.0 × 10
4
to 5.4 × 10
4
arthroconidia of
Coccidioides immitis
. Oral treatment with polyethylene glycol 200 (PEG) (
n
= 9), FCZ (
n
= 8; 80 mg/kg of body weight/day), or ITZ (
n
= 8; 80 mg/kg/day) began 5 days after infection and continued for 28 consecutive days. Both FCZ and ITZ reduced the number of CFU of
C. immitis
organisms in the spinal cord and brain compared with the number in PEG-treated animals (
P
≤ 0.003), but the results for FCZ and ITZ were not different from each other. Histopathologic severity (semiquantitative scoring system by an observer blinded to treatment) was equally reduced in both FCZ and ITZ treatment groups compared with that in controls (
P
≤ 0.0004). Both treatments resulted in lower cerebrospinal fluid (CSF) protein concentrations and leukocyte counts and faster clearing of
C. immitis
from CSF compared with the results for PEG-treated controls. Neither drug affected CSF glucose levels. Both compounds were effective at reducing neurological and systemic signs and extending survival (
P
≤ 0.014). FCZ was more effective at reducing head and body shakes, posture changes, and incontinence; ITZ was more effective at reducing continuous fever. Mean levels of FCZ and ITZ in the serum and CSF were determined by bioassay; at 17 to 26 h postdosing, levels were 28.1 to 40.0 and 22.4 to 29.9 μg/ml, respectively, for FCZ and 0.77 to 2.51 and 0 μg/ml, respectively, for ITZ. The sera of most animals developed antibody to
C. immitis
, but azole treatment attenuated antibody development in CSF and its titer. In conclusion, both FCZ and ITZ were efficacious, but neither was curative in a rabbit model of coccidioidal meningitis.
Activities of Taurolidine In Vitro and in Experimental Enterococcal Endocarditis
Authors: Torres-Viera C. , Thauvin-Eliopoulos C. , Souli M. , DeGirolami P. , Farris M. G. , Wennersten C. B. , Sofia R. D. , Eliopoulos G. M. 
Published: July 2002

ABSTRACTIn vitro, the antimicrobial agent taurolidine inhibited virtually all of the bacteria tested, including vancomycin-resistant enterococci, oxacillin-resistant staphylococci, andStenotrophomonas maltophilia, at concentrations between 250 and 2,000 μg/ml. Taurolidine was not effective in experimental endocarditis. While it appears unlikely that this antimicrobial would be useful for systemic therapy, its bactericidal activity and the resistance rates found (<10−9) are favorable indicators for its possible development for topical use.
Comparison of the Echinocandin Caspofungin with Amphotericin B for Treatment of Histoplasmosis following Pulmonary Challenge in a Murine Model
Authors: Kohler Steve , Wheat L. Joseph , Connolly Patricia , Schnizlein-Bick Carol , Durkin Michelle , Smedema Melinda , Goldberg Janet , Brizendine Edward 
Published: July 2002

ABSTRACTTwenty clinical isolates ofHistoplasma capsulatumwere tested for their in vitro susceptibilities to caspofungin in comparison to those to amphotericin B by following National Committee for Clinical Laboratory Standards guidelines for yeasts. The mean MICs were 16.6 μg/ml (range, 8 to 32 μg/ml) for caspofungin and 0.56 μg/ml (range, 0.5 to 1.0 μg/ml) for amphotericin B. Survival experiments used a 105dose in a pulmonary challenge model with B6C3F1mice. All mice that received amphotericin B at 2 mg/kg of body weight every other day (q.o.d.), 30% of mice that received caspofungin at 8 mg/kg/day, and 20% of mice that received caspofungin at 4 mg/kg/day survived to day 15, while mice that received caspofungin at 2 mg/kg/day and all control mice that received the vehicle died by day 14. Amphotericin B at 2 mg/kg q.o.d. markedly reduced the fungal burden in the lungs and spleens, as measured byHistoplasmaantigen detection techniques and quantitative cultures, for each comparison. Caspofungin at 10 mg/kg twice a day (b.i.d.) did not reduce the fungal burden, as measured by antigen detection techniques, but slightly reduced the levels of fungi in both the lungs and spleens, as determined by quantitative cultures. Caspofungin at 5 mg/kg b.i.d. did not affect fungal burden. Overall, caspofungin had only a slight effect on survival or fungal burden.
Mycobacterium aviumGrown inAcanthamoeba castellaniiIs Protected from the Effects of Antimicrobials
Authors: Miltner Elizabeth C. , Bermudez Luiz E. 
Published: July 2002

ABSTRACTMycobacterium aviumis a common cause of systemic bacterial infection in patients with AIDS. Infection withM. aviumhas been linked to bacterial colonization of domestic water supplies and commonly occurs through the gastrointestinal tract.Acanthamoeba castellanii, a waterborne protozoan, may serve as an environmental host forM. avium. It has been shown that growth ofM. aviumin amoebae enhances invasion and intracellular replication of the bacteria in human macrophages and intestinal epithelial cell line HT-29 as well as in mice. We determined that growth ofM. aviumwithinA. castellaniiinfluenced susceptibility to rifabutin, azithromycin, and clarithromycin. No significant activity againstM. aviumwas seen with rifabutin, azithromycin, and clarithromycin when used to treat monolayers on both day 1 and day 4 after infection. When tested in a macrophage-like cell line (U937), all compounds showed significant anti-M. aviumactivity. Growth ofM. aviumin amoebae appears to reduce the effectiveness of the antimicrobials. These findings may have significant implications for prophylaxis ofM. aviuminfection in AIDS.
In Vitro Activities of Gemifloxacin versus Five Quinolones and Two Macrolides against 271 Spanish Isolates of
Legionella pneumophila
: Influence of Charcoal on Susceptibility Test Results
Authors: García M. T. , Pelaz C. , Giménez M. J. , Aguilar L. 
Published: July 2002

ABSTRACT

The MICs at which 90% of isolates are inhibited for gemifloxacin, trovafloxacin, and grepafloxacin were low (≤0.01 μg/ml) for 271
Legionella
isolates when they were determined by the broth microdilution method but increased (≥6 dilutions) when they were determined by the agar dilution method. This was due to the charcoal in the agar dilution medium, as shown by the progressive decrease in the MICs when the charcoal concentrations decreased. As free drug is the active fraction, charcoal binding should be considered.
Impact of n-6 Polyunsaturated Fatty Acids on Growth of Multidrug-Resistant
Pseudomonas aeruginosa
: Interactions with Amikacin and Ceftazidime
Authors: Giamarellos-Bourboulis E. J. , Grecka P. , Dionyssiou-Asteriou A. , Giamarellou H. 
Published: July 2002

ABSTRACT

Twenty-six multidrug-resistant
Pseudomonas aeruginosa
isolates were exposed over time to 300 μg of gamma-linolenic acid or arachidonic acid per ml or to the combination of both acids at 150 μg/ml each with ceftazidime and amikacin with or without albumin to observe the in vitro interactions of the antibiotics. Antibiotics and albumin were applied at their levels found in serum. Synergy between acids and antibiotics was found against 13 isolates, and it was expressed after 5 h of growth in the presence of albumin. The results indicate that further application in experimental infection models is merited.
Nonylphenolethoxylates as Malarial Chloroquine Resistance Reversal Agents
Authors: Crandall Ian , Charuk Jeffrey , Kain Kevin C. 
Published: July 2002

ABSTRACT

Malaria-associated morbidity and mortality are increasing because of widespread resistance to one of the safest and least expensive antimalarials, chloroquine. The availability of an inexpensive agent that is capable of reversing chloroquine resistance would have a major impact on malaria treatment worldwide. The interaction of nonylphenolethoxylates (NPEs, commercially available synthetic surfactants) with drug-resistant
Plasmodium falciparum
was examined to determine if NPEs inhibited the growth of the parasites and if NPEs could sensitize resistant parasites to chloroquine. NPEs inhibited the development of the parasite when present in the low- to mid-micromolar range (5 to 90 μM), indicating that they possess antimalarial activity. Further, the presence of <10 μM concentrations of NPEs caused the 50% inhibitory concentrations for chloroquine-resistant lines to drop to levels (≤12 nM) observed for sensitive lines and generally considered to be achievable with treatment courses of chloroquine. Long-chain (>30 ethoxylate units) NPEs were found to be most active in
P. falciparum
, which contrasts with previously observed maximal activity of short-chain (∼9 ethoxylate units) NPEs in multidrug-resistant mammalian cell lines. NPEs may be attractive chloroquine resistance reversal agents since they are inexpensive and may be selectively directed against
P. falciparum
without inhibiting mammalian tissue P glycoproteins. Antimalarial preparations that include these agents may prolong the effective life span of chloroquine and other antimalarials.
Rifampin Reduces Concentrations of Trimethoprim and Sulfamethoxazole in Serum in Human Immunodeficiency Virus-Infected Patients
Authors: Ribera Esteban , Pou Leonor , Fernandez-Sola Antoni , Campos Francisco , Lopez Rosa M. , Ocaña Imma , Ruiz Isabel , Pahissa Albert 
Published: July 2002

ABSTRACT

To determine whether rifampin reduces concentrations of trimethoprim (TMP) and sulfamethoxazole (SMX) in serum of human immunodeficiency virus (HIV)-infected persons, levels of these agents were determined by high-performance liquid chromatography before and after more than 12 days of standard antituberculosis treatment for 10 patients who had been taking one double-strength tablet of co-trimoxazole once daily for more than 1 month. Statistically significant, 47 and 23% decreases in TMP and SMX mean areas under the concentration-time curve from 0 to 24 h (AUC
0–24
), respectively, were observed after administration of rifampin.
N
-Acetyl-SMX profiles without and with rifampin were similar. The steady-state AUC
0–24
metabolite/parent drug ratio increased by 32% with rifampin administration. Our study shows that rifampin reduces profiles of TMP and SMX in serum of HIV-infected patients.
Synergy, Pharmacodynamics, and Time-Sequenced Ultrastructural Changes of the Interaction between Nikkomycin Z and the Echinocandin FK463 against
Aspergillus fumigatus
Authors: Chiou Christine C. , Mavrogiorgos Nikolaos , Tillem Elizabeth , Hector Richard , Walsh Thomas J. 
Published: July 2002

ABSTRACT

We investigated the potential synergy between two cell wall-active agents, the echinocandin FK463 (FK) and the chitin synthase inhibitor nikkomycin Z (NZ), against 16 isolates of filamentous fungi. Susceptibility testing was performed with a broth macrodilution procedure by NCCLS methods. The median minimal effective concentration (MEC) of FK against all
Aspergillus
species was 0.25 μg/ml (range, 0.05 to 0.5 μg/ml). For
Fusarium solani
and
Rhizopus oryzae
, MECs of FK were >512 μg/ml. The median MEC of NZ against
Aspergillus fumigatus
was 32 μg/ml (range, 8 to 64 μg/ml), and that against
R. oryzae
was 0.5 μg/ml (range, 0.06 to 2 μg/ml); however, for the other
Aspergillus
species, as well as
F. solani
, MECs were >512 μg/ml. A checkerboard inhibitory assay demonstrated synergy against
A. fumigatus
(median fractional inhibitory concentration index = 0.312 [range, 0.15 to 0.475]). The effect was additive to indifferent against
R. oryzae
and indifferent against other
Aspergillus
spp. and
F. solani
. We further investigated the pharmacodynamics of hyphal damage by MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] assay and examined the time-sequenced changes in hyphal ultrastructure. Significant synergistic hyphal damage was demonstrated with the combination of NZ (2 to 32 μg/ml) and FK (0.03 to 0.5 μg/ml) over a wide range of concentrations (
P
< 0.001). The synergistic effect was most pronounced after 12 h of incubation and was sustained through 24 h. Time-sequenced light and electron microscopic studies demonstrated that structural alterations of hyphae were profound, with marked transformation of hyphae to blastospore-like structures, in the presence of FK plus NZ, while fungi treated with a single drug showed partial recovery at 24 h. The methods used in this study may be applicable to elucidating the activity and interaction of other cell wall-active agents. In summary, these two cell wall-targeted antifungal agents, FK and NZ, showed marked time-dependent in vitro synergistic activity against
A. fumigatus
.