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At least 1,135 records · Page 63Linked to original sources
PubMed1993

NPC 15669 reduces mortality associated with sepsis in rats.

N-[9H-(2,7-dimethylfluoren-9-ylmethoxy)carbonyl]-L-leucine (NPC 15669), a leukocyte recruitment inhibitor, was investigated for its ability to enhance survival in a rat model of sepsis, fecal peritonitis. Infusion of NPC 15669 (3 mg kg-1 hr-1 i.v.) for 19, 24 or 48 hr or three to four bolus injections (10 mg/kg) at 2- or 6-hr intervals along with gentamicin effectively cured all animals (> 2-week survival) relative to gentamicin-treated controls (28 +/- 1 hr survival), whereas infusion at a 10-fold lower dose was ineffective. Unlike aspirin and dexamethasone, which were inactive (< 36-hr survival), ibuprofen significantly increased the survival time (66 +/- 1 hr) but did not cure septic rats. The efficacy of NPC 15669 on survival was associated with the reversal of leukopenia and a marked inhibition of neutrophil infiltration into the small intestine. By contrast, i.v. bolus injection or infusion of a related analog, N-[9H-fluoren-9-ylmethoxy)carbonyl]glycine, which does not inhibit leukocyte recruitment, failed to reduce the mortality rate associated with fecal peritonitis-induced sepsis. In addition, NPC 15669 was efficacious therapeutically, even when administered as late as 6 hr after the induction of sepsis (14 of 16 animals survived > 5 days). Together, these data suggest that NPC 15669 may be useful in the treatment of septic shock.

Animals↗
PubMed1996

Bacterial Degradation of Low Concentrations of Phenanthrene and Inhibition by Naphthalene

Phenanthrene-degrading bacteria were isolated from enrichment cultures of soils contaminated with creosote and jet fuel. The isolates from the creosote enrichments were classified by fatty acid methyl ester profiles as Acidovorax delafieldii and Sphingomonas paucimobilis; the bacterium from the jet fuel-contaminated soil was not identified and was designated strain JFD11. All three isolates used phenanthrene as a sole carbon and energy source, and two of the isolates used fluoranthene as a sole carbon and energy source. Anthracene and fluorene were cometabolized by all three strains, but pyrene was not transformed. Naphthalene inhibited all of the strains, and 28-h cultures of A. delafieldii were inhibited by naphthalene concentrations as low as 5 ppm. Short-term degradation experiments were undertaken with center-well flasks and concentrations of phenanthrene ranging from 1.2 to 12.0 &mgr;M. Since initial degradation rates were not a function of phenanthrene concentration, it was inferred that the half-saturation constants were less than the lowest phenanthrene concentration tested.

Journal Article↗
PubMedDate not supplied

[Production of type I interferons in the body exposed to yeast RNA-tiloron molecular complexes].

Molecular complexes forming as a result of interaction between yeast RNA preparations with 2,7-bis[-(diethylaminoethoxy)-fluorene]-9-on dihydrochloride (tilorone) administered parenterally to mice cause the appearance of interferon in high titers compatible to those induced by standard inductors of polyribonucleotide origin, poly(I)-poly(C) and larifan. Some physiologic conditions of interferonogenesis have been studied. The above molecular complexes in the dose range used experimentally were completely nontoxic. Hence, these complexes are promising agents for interferon induction.

Animals↗
PubMed1996

[Determination of polycyclic aromatic hydrocarbons in the working environment during aluminum production].

Polycyclic aromatic hydrocarbons (PAHs) belong to a group od chemicals responsible, to a great extent, for the contamination of the industrial and ambient air. A number of industrial processes such as coke production, coal tar processing, production of electric energy and certain rubber goods as well as metallurgy, especially aluminium metallurgy with its anodes made of coal tar pitch are the major sources of PAH emission. An attempt was made to determine PAH concentrations at selected workposts at an aluminium production plant. Breathing zone air samples were collected by individual dosimetry. Coal tar pitch volatiles were determined by a gravimetric method and individual PAHs by HPLC. The presence of naphtalene, fluorene, phenanthrene, anthracene, fluoranthene, pyrene, triphenylene, benzo/a/anthracene, chrysene, benzo/a/pyrene, benzo/b/fluorenthene, benzo/k/fluoranthene, benzo/a/pyrene, dibenzo/a,h/anthracene, benzo/g,h,i/perylene and indeno/1,2,3-c,d/pyrene was identified at all investigated workposts. The highest concentrations of benzo/a/pyrene and coal tar pitch volatiles were found at workposts of crane operators which is due to the character of the work performed. The replacement of "wet" anode material by the "dry" one should contribute to improving of the working conditions.

Air Pollutants, Occupational↗
PubMedDate not supplied

Conformational studies on beta-amyloid protein carboxy-terminal region (residues 34-42): strategic use of amide backbone protection as a structural probe.

Analogues of beta-amyloid (32-42) peptide, containing N-(2-hydroxy-4-methoxybenzyl) (Hmb) amide backbone substitutions at various positions have been prepared using fluoren-9-ylmethoxycarbonyl (Fmoc)-polyamide based solid phase peptide synthesis. On-line N alpha-Fmoc deprotection monitoring during assembly exhibited hindered release in the native and beta A(34-42, (Hmb)Gly38) analogue syntheses. No such hindrance was observed during the synthesis of beta A(34-42, (Hmb)Gly37) nor beta A(34-42, (Hmb)Val36). However, the latter contained an exceptionally slow coupling reaction. Cleaved peptides were analysed for solubility in a variety of solvents and insoluble pellets tested for congophilic staining. X-ray analysis of Fmoc (and H-) beta A(34-42) and the corresponding (Hmb)Gly38 analogues as dimethylformamide swollen gels gave very similar structures. Secondary structure prediction and model-building of ordered arrays, compatible with our results, suggest that beta A(34-42) forms a beta-hairpin structure, with the reverse turn at Val36-Gly37-Gly38-Val39 both in solution and on the resin during synthesis.

Amides↗
PubMed2002

Artemether-lumefantrine for treating uncomplicated falciparum malaria.

BACKGROUND: Artemether-lumefantrine is being promoted by the World Health Organization for treating uncomplicated malaria. It is expensive. We sought evidence of its superiority over existing treatment regimens. OBJECTIVES: To compare artemether-lumefantrine with other antimalarial drugs for treating uncomplicated falciparum malaria. SEARCH STRATEGY: We searched the Cochrane Infectious Diseases Group specialized trials register (April 2002), the Cochrane Controlled Trials Register (Issue 2, 2002), MEDLINE (1966 to April 2002), EMBASE (1988 to April 2002), conference proceedings, and reference lists of articles. We contacted experts in malaria research and the pharmaceutical company that manufactures artemether-lumefantrine. SELECTION CRITERIA: Randomized and quasi-randomized trials comparing artemether-lumefantrine administered orally with standard treatment regimens (single drug or combination). DATA COLLECTION AND ANALYSIS: Two reviewers independently applied inclusion criteria to potentially relevant trials, assessed trial quality, and extracted data. Parasitaemia on day 28 (day 42 for sulfadoxine-pyrimethamine and day 63 for mefloquine) was the primary outcome. Adverse event information was collected from the studies. MAIN RESULTS: Eight trials (2117 participants) met the inclusion criteria. In the four studies against single agents, failure rates for artemether-lumefantrine tended to be higher in comparisons against sulfadoxine-pyrimethamine, halofantrine, and mefloquine. This difference was statistically significant for mefloquine. When compared with chloroquine, artemether-lumefantrine was better in two studies, but the failure rate for chloroquine at these sites was over 50%. All single agent studies used four doses of artemether-lumefantrine. In comparisons against combination treatment, three trials tested artemether-lumefantrine against mefloquine-artesunate and showed that artemether-lumefantrine was inferior for day 28 cure (Relative Risk 6.33, 95% confidence interval 3.08 to 13.01). If this comparison is confined to the two trials where participants received six doses, artemether-lumefantrine was associated with higher cure rates, but this was not statistically significant (Relative Risk 4.20, 95% confidence interval 0.55 to 31.93). REVIEWER'S CONCLUSIONS: Artemether-lumefantrine is more effective than chloroquine in chloroquine resistant areas. Artemether-lumefantrine is less effective than mefloquine or mefloquine combined with artesunate. We found no evidence to confirm or refute whether artemether-lumefantrine was better than sulfadoxine-pyrimethamine.

Antimalarials↗