Abstract:
:Polyamine levels are greatly increased in alveolar macrophages (AMs) during Pneumocystis pneumonia (PCP), leading to increased production of H(2)O(2), which causes AMs to undergo apoptosis. One of the mechanisms by which polyamine levels in AMs are elevated is enhanced uptake of exogenous polyamines. In this study, the possibility of targeting polyamine uptake as a treatment for PCP was examined. Four anthracene- and one benzene-polyamine conjugates that are potential polyamine transport inhibitors, including N1-anthracen-9-ylmethyl-butane-1,4-diamine; N-(4-aminobutyl)-N-anthracen-9-ylmethylbutane-1,4-diamine; N-[4-(4-aminobutylamino)butyl]-N-anthracen-9-ylmethylbutane-1,4-diamine; N-(4-amino-butyl)-N'-(10-[[4-(4-amino-butylamino)butylamino]-methyl]anthracen-9-ylmethyl)butane-1,4-diamine (44-Ant-44); and benzene-polyamine conjugate N-(4-amino-butyl)-N'-(4-[[4-(4-amino-butylamino)butylamino]-methyl]benzyl)butane-1,4-diamine (44-Bn-44), were tested. Compounds 44-Ant-44 and 44-Bn-44 were found to have a very low toxicity to AMs in vitro and were evaluated for their therapeutic effect on PCP in vivo. Sprague-Dawley rats infected with P. carinii for 28 days were intranasally instilled with 50 microl of a 1 mM solution of 44-Bn-44 or 44-Ant-44 every 2 days. Twenty-one days after initiation of the treatment, three to five rats from each group were sacrificed and examined for lung pathology, organism burden, and apoptosis of AMs. Both 44-Bn-44 and 44-Ant-44 reduced organism burdens; however, only 44-Ant-44 decreased the severity of the infection with reduced lung inflammation, increased clearance of exudates, increased air space, and decreased apoptosis of AMs. 44-Ant-44 also significantly prolonged the survival of treated animals. These results suggest that polyamine uptake is a potential target for treatment of PCP.
journal_name
Antimicrob Agents Chemotherjournal_title
Antimicrobial agents and chemotherapyauthors
Liao CP,Phanstiel O 4th,Lasbury ME,Zhang C,Shao S,Durant PJ,Cheng BH,Lee CHdoi
10.1128/AAC.00662-09subject
Has Abstractpub_date
2009-12-01 00:00:00pages
5259-64issue
12eissn
0066-4804issn
1098-6596pii
AAC.00662-09journal_volume
53pub_type
杂志文章abstract::The novel triazole D0870 was tested for in vitro activity, as well as in vivo in a murine model of pulmonary blastomycosis. In vitro, D0870 had inhibitory and fungicidal activity against Blastomyces dermatitidis (MIC = 0.048 microgram/ml; minimal fungicidal concentration = 0.097 microgram/ml). In vivo, D0870 was appro...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.37.5.1177
更新日期:1993-05-01 00:00:00
abstract::Hemolytic-uremic syndrome (HUS) is a serious complication of infection by Shiga toxin-producing Escherichia coli. Shiga toxin type 2 (Stx2) is responsible for the renal toxicity that can follow intestinal infection and hemorrhagic colitis due to E. coli. A chimeric mouse-human antibody, designated c alpha Stx2, that h...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 临床试验,杂志文章
doi:10.1128/AAC.49.5.1808-1812.2005
更新日期:2005-05-01 00:00:00
abstract::An in vitro model of monocyte-derived dendritic cells (MO-DC) and CD4(+) T cells, representing the primary targets of sexual human immunodeficiency virus (HIV) transmission, was used to evaluate the antiviral and immune suppressive activity of new classes of nonnucleoside reverse transcriptase inhibitors, diaryltriazi...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.48.10.3684-3689.2004
更新日期:2004-10-01 00:00:00
abstract::Ribavirin (RBV) is a broad-spectrum antiviral agent that inhibits the production of infectious Hantaan virus (HTNV). Although the mechanism of action of RBV against HTNV is not understood, RBV is metabolized in human cells to both RBV-5'-monophosphate, which inhibits IMP dehydrogenase, resulting in a decrease in intra...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.00790-06
更新日期:2007-01-01 00:00:00
abstract::Lamivudine is a major drug approved for treatment of chronic hepatitis B virus (HBV) infection. Emergence of drug-resistant mutants with amino acid substitutions in the YMDD motif is a well-documented problem during long-term lamivudine therapy. Here we report a novel lamivudine-resistant strain of HBV with an intact ...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.00239-06
更新日期:2006-11-01 00:00:00
abstract::Fenpropimorph was shown to inhibit the accumulation of the pyrimidine bases uracil and cytosine from the growth media in Saccharomyces cerevisiae. Uracil prototrophs of S. cerevisiae were more resistant to the growth-inhibitory effects of fenpropimorph than were uracil auxotrophs. High concentrations of uracil rescued...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.38.5.1004
更新日期:1994-05-01 00:00:00
abstract::Antibiotic dynamics in the fluid obtained from subcutaneously implanted chambers in rats were similar to those observed in serum following single intramuscular injections of carbenicillin. ...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.4.2.196
更新日期:1973-08-01 00:00:00
abstract::Amphotericin B and N-D-ornithyl amphotericin B methyl ester were compared for therapeutic efficacies against experimentally induced cryptococcal meningitis and Candida albicans endocarditis with pyelonephritis in rabbits. Antifungal activity of the two polyenes in vitro was similar for the yeasts used in these experim...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.28.6.751
更新日期:1985-12-01 00:00:00
abstract::Three sizes of inserted regions of DNA (800, 1,000, and 1,500 bp) were shown to be common among class I integrons in unrelated clinical isolates of Enterobacteriaceae from different European hospitals. Sequencing showed that 800-bp inserted regions comprised identical sequences including aacA4, that 1,000-bp inserted ...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.43.3.686
更新日期:1999-03-01 00:00:00
abstract::For 177 gram-negative isolates, the MICs for ciprofloxacin ranged from 0.02 microgram/ml (Escherichia coli) to 0.31 microgram/ml (Pseudomonas aeruginosa). In time-kill curves, ciprofloxacin at 8 X the MIC almost completely killed 10(6) CFU of P. aeruginosa by 24 h. Ciprofloxacin at 4 X the MIC allowed bacterial regrow...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.26.4.597
更新日期:1984-10-01 00:00:00
abstract::A spontaneous Escherichia coli mutant, named Q3, resistant to nalidixic acid was obtained from a previously described clinical isolate of E. coli, Q2, resistant to fluoroquinolones but susceptible to nalidixic acid (E. Cambau, F. Bordon, E. Collatz, and L. Gutmann, Antimicrob. Agents Chemother. 37:1247-1252, 1993). Q3...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.41.1.85
更新日期:1997-01-01 00:00:00
abstract::The mepRAB gene cluster of Staphylococcus aureus encodes a MarR family repressor (MepR; known to repress mepA expression), a MATE family multidrug efflux pump (MepA), and a protein of unknown function (MepB). In this report, we show that MepR also is autoregulatory, repressing the expression of its own gene. Exposure ...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.50.4.1276-1281.2006
更新日期:2006-04-01 00:00:00
abstract::We analyzed the relationship between rifampin MICs and rpoB mutations of 40 clinical isolates of Mycobacterium tuberculosis. A point mutation in either codon 516, 526, or 531 was found in 13 strains requiring MICs of > or = 64 micrograms/ml, while 21 strains requiring MICs of < or = 1 microgram/ml showed no alteration...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.40.4.1053
更新日期:1996-04-01 00:00:00
abstract::Posaconazole and itraconazole were more potent inhibitors of ergosterol synthesis, in both intact cells and cell extracts from Absidia corymbifera and Rhizopus oryzae, than voriconazole and fluconazole. Similarly, expression of CYP51 from R. oryzae in Saccharomyces cerevisiae significantly increased resistance to fluc...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.00747-06
更新日期:2006-11-01 00:00:00
abstract::An antibiotic-producing pseudomonad was isolated from a seawater sample from a La Jolla, Calif., tidepool. The pseudomonad produces two novel antibacterial compounds, 2-n-pentyl-4-quinolinol and 2-n-heptyl-4-quinolinol. It also synthesizes indole-3-carboxaldehyde, 6-bromoindole-3-carboxaldehyde, and the known antibiot...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.11.3.411
更新日期:1977-03-01 00:00:00
abstract::Violacein is a violet pigment extracted from the gram-negative bacterium Chromobacterium violaceum. It presents bactericidal, tumoricidal, trypanocidal, and antileishmanial activities. We show that micromolar concentrations efficiently killed chloroquine-sensitive and -resistant Plasmodium falciparum strains in vitro;...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.00693-08
更新日期:2009-05-01 00:00:00
abstract::As an obligate aerobe, Mycobacterium tuberculosis uses its electron transport chain (ETC) to produce energy via oxidative phosphorylation. This pathway has recently garnered a lot of attention and is a target for several new antimycobacterials. We tested the respiratory adaptation of M. tuberculosis to phenoxyalkylben...
journal_title:Antimicrobial agents and chemotherapy
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abstract::The type II fatty acid synthesis (FASII) pathway is essential for bacterial lipid biosynthesis and continues to be a promising target for novel antibacterial compounds. Recently, it has been demonstrated that Chlamydia is capable of FASII and this pathway is indispensable for Chlamydia growth. Previously, a high-conte...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/AAC.00716-17
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journal_title:Antimicrobial agents and chemotherapy
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journal_title:Antimicrobial agents and chemotherapy
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更新日期:1974-05-01 00:00:00
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journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
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journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
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abstract::Forty years after the last endemic smallpox case, variola virus (VARV) is still considered a major threat to humans due to its possible use as a bioterrorism agent. For many years, the risk of disease reemergence was thought to solely be through deliberate misuse of VARV strains kept in clandestine laboratories. Howev...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章,评审
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更新日期:2020-03-24 00:00:00
abstract::A method utilizing immobilized major group rhinoviruses and biotinylated soluble intercellular adhesion molecule 1 has been developed for the detection of capsid binders. Binding measurements indicate a loss in relative affinity of biotinylated soluble intercellular adhesion molecule 1 for rhinoviruses by capsid binde...
journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
doi:10.1128/aac.37.8.1693
更新日期:1993-08-01 00:00:00
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journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
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更新日期:1980-03-01 00:00:00
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journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
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更新日期:1998-04-01 00:00:00
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journal_title:Antimicrobial agents and chemotherapy
pub_type: 杂志文章
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journal_title:Antimicrobial agents and chemotherapy
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journal_title:Antimicrobial agents and chemotherapy
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更新日期:2017-08-24 00:00:00