ABSTRACT
Angioplasty and stenting of short segment obstructions is highly effective in the treatment of aorto-iliac occlusive disease. However, long-segment, diffuse and calcific aorto-iliac atherosclerosis is most effectively treated with surgical bypass. While aorto-femoral bypass procedures are durable and effective, too often patients are elderly, high risk and poor candidates for open surgery. Endografting of the abdominal aorta and iliac arteries is aimed at improving the short and long-term results of endovascular treatment of extensive, end-stage aorto-iliac disease. Aorto-iliac endografts are widely used in the treatment of aneurysmal disease. Early experiences with endografts in the treatment of occlusive disease are promising. However, evidence that long-term patency of endografts will be substantially better than angioplasty and stenting is not yet available. Prospective clinical trials are needed to determine the role of endografts in the treatment strategy of aorto-iliac occlusive disease.
Subject(s)
Angioscopy , Aorta, Abdominal/surgery , Arterial Occlusive Diseases/surgery , Blood Vessel Prosthesis Implantation/methods , Iliac Artery/surgery , Blood Vessel Prosthesis , HumansABSTRACT
Spectra of hydrogenlike atoms embedded in a Debye plasma are investigated. The state energies and the transition rates are studied using a fully relativistic formalism based on the Dirac equation. The effect of the plasma is described by introducing an exponential screening to the nuclear Coulomb potential (the Debye screening). Systematic trends with respect to both the nuclear charge and the screening parameter are observed for all calculated quantities. The pattern of splittings of ns(1/2), np(1/2) and np(3/2) is modified in a specific way due to the combined relativity and plasma effect. The transition rates decrease with an increase of the Debye parameter as well as with an increase of Z.
ABSTRACT
BACKGROUND: Arterial diameter changes in response to flow. Chronic flow-mediated arterial enlargement may be mediated through metalloproteinase activity in the extracellular matrix of the arterial wall. We examined flow-mediated enlargement in the setting of increasing competitive matrix metalloproteinase (MMP) inhibition and with respect to gelatinase A and B expression and activity. METHODS: Left common femoral arteriovenous fistulas (AVFs) were created in dose-response (52) and time course (34) cohorts of rats. Dose-response rats received either vehicle alone or 12.5, 25, or 37. 5 mg/kg b.i.d. RS 113,456, a competitive MMP inhibitor. Heart rate, blood pressure, and weight were measured at intervals following AVF construction. Aortic and common iliac diameters were measured on postoperative day (POD) 21. Untreated time course rats were sacrificed on PODs 0 (no AVF), 3, 7, 14, and 21. Aortic diameter was measured and the vessels were harvested for tissue analysis. Equal amounts of aortic RNA underwent reverse transcription and polymerase chain reaction with primers for MMP-2, MMP-9, and GAPDH. Zymography was performed on iliac artery tissue to measure gelatinolytic activity. RESULTS: A significant, stepwise reduction in flow-mediated aortic and left common iliac enlargement following left femoral AVF creation was noted with progressively higher doses of RS 113,456 without apparent hemodynamic or toxic effects. Right common iliac diameter was unchanged. Over 21 days following AVF creation, there was an upward trend in expression and activity for MMP-2 not evident for MMP-9. CONCLUSION: Flow-mediated arterial enlargement is limited by competitive MMP inhibition in a dose-dependent fashion. MMP-dependent flow-mediated enlargement may involve differential expression and activity of MMP-2 and MMP-9.
Subject(s)
Arteries/drug effects , Enzyme Inhibitors/pharmacology , Matrix Metalloproteinase Inhibitors , Pyrans/pharmacology , Animals , Arteries/physiology , Arteriovenous Shunt, Surgical , Dose-Response Relationship, Drug , Male , Matrix Metalloproteinase 2/metabolism , Matrix Metalloproteinase 9/metabolism , Rats , Rats, Sprague-Dawley , VasodilationSubject(s)
Antifungal Agents/chemistry , Antifungal Agents/pharmacology , Ascomycota/metabolism , Antifungal Agents/metabolism , Ascomycota/chemistry , Ascomycota/classification , Candida albicans/drug effects , Fermentation , Glycolipids/chemistry , Glycolipids/metabolism , Glycolipids/pharmacology , Microbial Sensitivity Tests , Molecular StructureABSTRACT
Two novel triterpene sulfates have been isolated from Fusarium compactum by bioactivity-directed fractionation using an assay which measures the inhibition of proteolytic activity of rhinovirus 3C protease on a fluorogenic peptide substrate. The compounds were purified by countercurrent and reverse phase chromatographies. NMR, MS, UV and IR studies revealed two triterpene sulfates, uncommon metabolites of terrestrial fungi.
Subject(s)
Cholestenes/isolation & purification , Protease Inhibitors/isolation & purification , Triterpenes/isolation & purification , Cholestenes/chemistry , Cholestenes/pharmacology , Fermentation , Fusarium , Humans , Magnetic Resonance Spectroscopy , Microbial Sensitivity Tests , Protease Inhibitors/chemistry , Protease Inhibitors/pharmacology , Stereoisomerism , Triterpenes/chemistry , Triterpenes/pharmacologySubject(s)
Antifungal Agents/chemistry , Antifungal Agents/isolation & purification , Fatty Acids, Unsaturated/isolation & purification , Oligosaccharides/isolation & purification , Antifungal Agents/pharmacology , Fatty Acids, Unsaturated/chemistry , Fatty Acids, Unsaturated/pharmacology , Fusarium , Glycosides/chemistry , Glycosides/isolation & purification , Glycosides/pharmacology , Microbial Sensitivity Tests , Molecular Structure , Oligosaccharides/chemistry , Oligosaccharides/pharmacologyABSTRACT
A new method is described for the selective isolation of species of Myxococcus directly from soil by dilution plating. The method involves suppression of competing microorganisms with antibiotics combined with air drying and wet heat treatment of soils. Fungi were eliminated by supplementing the plating medium with cycloheximide and nystatin. Non-sporulating bacteria were controlled by air drying soils and then heating aqueous soil dilutions for 10 min at 56 degrees C. The predominant sporulating bacteria in soil, Streptomyces and Bacillus, were suppressed by adding either tiacumicin B, ristocetin or vancomycin to the medium. Swarming of Myxococcus colonies was controlled with a casein digest-yeast extract plating medium (CY-C10 agar). Ultrasound treatment of soil suspensions gave the highest number of Myxococcus colonies in the soils studied, but these cultures could be recovered without ultrasound. Strains of Myxococcus fulvus, M. xanthus, M. coralloides, M. stipitatus and M. virescens were isolated from soil using this technique. Soils examined yielded one or two Myxococcus species per sample.
Subject(s)
Aminoglycosides , Bacteriological Techniques , Myxococcus/isolation & purification , Soil Microbiology , Anti-Bacterial Agents , Culture Media/chemistry , Fidaxomicin , Hot Temperature , Microbial Sensitivity Tests , UltrasonographyABSTRACT
The novel calcineurin inhibitor, dibefurin, has been isolated from the fungal culture AB 1650I-759. The isolation was bioactivity-directed fractionation using an assay which measures the phosphatase activity of calcineurin. The compound was purified by countercurrent, reverse phase and gel filtration chromatographies. Several studies, including crystallographic, NMR and MS, revealed that dibefurin is a novel dimeric compound of a unique structural type.
Subject(s)
Benzofurans/pharmacology , Calmodulin-Binding Proteins/antagonists & inhibitors , Enzyme Inhibitors/pharmacology , Fungi/metabolism , Phosphoprotein Phosphatases/antagonists & inhibitors , Benzofurans/chemistry , Calcineurin , Chromatography, Gel , Crystallography, X-Ray , Enzyme Inhibitors/chemistry , Fermentation , Magnetic Resonance Spectroscopy , Molecular Structure , Spectroscopy, Fourier Transform InfraredABSTRACT
The fuscandins, antifungal agents of the papulacandin class, are produced by a strain of Fusarium sambucinum. Fermentation yielded 60 mg/liter of fusacandin A and minor amounts of fusacandin B. As expected, the fusacandins inhibit (1,3)-beta-glucan synthesis. Fusacandin A is slightly less active than papulacandin B against Candida albicans and, like papulacandin, loses activity in the presence of serum.
Subject(s)
Aminoglycosides , Antifungal Agents/pharmacology , Anti-Bacterial Agents/pharmacology , Antifungal Agents/isolation & purification , Candida albicans/drug effects , Fatty Acids, Unsaturated/isolation & purification , Fatty Acids, Unsaturated/pharmacology , Fermentation , Fusarium , Microbial Sensitivity Tests , Oligosaccharides/isolation & purification , Oligosaccharides/pharmacologyABSTRACT
A novel series of microbial metabolites were discovered in fermentation broths of two soil isolates. Both cultures were identified as strains of Micromonospora chalcea. Production of the metabolites, named macquarimicins, was monitored by an HPLC assay. A seven-day fermentation yielded 27 mg/liter of macquarimicin A. With MICs of 50 to 100 micrograms/ml, macquarimicin A has only very low activity against strains of Bacteroides and other anaerobes. Macquarimicin B has inhibitory activity against the leukemia cell line P-388.
Subject(s)
Anti-Bacterial Agents/isolation & purification , Antibiotics, Antineoplastic/isolation & purification , Macrolides , Animals , Anti-Bacterial Agents/chemistry , Anti-Bacterial Agents/therapeutic use , Antibiotics, Antineoplastic/therapeutic use , Chromatography, High Pressure Liquid , Fermentation , Leukemia P388/drug therapy , Microbial Sensitivity Tests , Micromonospora , Tumor Cells, Cultured/drug effectsABSTRACT
Determination of the mechanism of action of FK506 and cyclosporin A has yielded new molecular targets involved in signal transduction during T cell activation. A common target of FK506 and cyclosporin A is inhibition of activation of the NFAT transcription factor, for which a specific binding region is present in the promoter of the IL-2 gene. A reporter gene assay has been used to screen for agents that interfere with this early step in T cell activation. Simple aromatic compounds that block NFAT-dependent transcription and show in vitro immunosuppressive activity were isolated from the broth and mycelia of two Streptomyces sp. fermentations. The compounds were active at concentrations that were not directly cytotoxic.
Subject(s)
Hydroquinones/isolation & purification , Pentanols/isolation & purification , Pentanones/isolation & purification , Transcription Factors/isolation & purification , Transcription, Genetic/drug effects , Animals , Cattle , Fermentation , Gene Expression Regulation, Enzymologic , Hydroquinones/chemistry , Hydroquinones/pharmacology , Immunosuppression Therapy , Lac Operon/drug effects , Lymphocyte Activation/drug effects , Mice , Mice, Inbred BALB C , Mice, Inbred C57BL , Pentanols/chemistry , Pentanols/pharmacology , Pentanones/chemistry , Pentanones/pharmacology , Streptomyces , T-Lymphocytes/drug effects , Transcription Factors/chemistry , Transcription Factors/pharmacology , beta-Galactosidase/geneticsABSTRACT
The dorrigocins are new secondary metabolites produced by submerged fermentation of a streptomycete which was isolated from a soil sample collected in Australia. The dorrigocins show moderate antifungal activity and reverse the morphology of ras-transformed NIH/3T3 cells from a transformed phenotype to a normal one. The producing culture was identified as Streptomyces platensis subsp. rosaceus strain AB1981F-75.
Subject(s)
3T3 Cells/cytology , 3T3 Cells/drug effects , Antibiotics, Antineoplastic/biosynthesis , Antibiotics, Antineoplastic/pharmacology , Antifungal Agents/biosynthesis , Antifungal Agents/pharmacology , Cell Transformation, Neoplastic/drug effects , Cell Transformation, Neoplastic/genetics , Genes, ras , Streptomyces/classification , Streptomyces/metabolism , Animals , Antibiotics, Antineoplastic/isolation & purification , Antifungal Agents/isolation & purification , Fermentation , Humans , Mice , Neoplasms, Experimental/drug therapy , Piperidones/chemical synthesis , Piperidones/isolation & purification , Piperidones/pharmacologySubject(s)
Antiviral Agents/pharmacology , Citrinin/analogs & derivatives , Cysteine Endopeptidases/drug effects , Cysteine Proteinase Inhibitors/pharmacology , Mycotoxins/pharmacology , Pyrones/pharmacology , Rhinovirus/enzymology , Viral Proteins , 3C Viral Proteases , Antiviral Agents/chemistry , Chemical Phenomena , Chemistry, Physical , Citrinin/chemistry , Citrinin/pharmacology , Cysteine Proteinase Inhibitors/chemistry , Humans , Magnetic Resonance Spectroscopy , Microbial Sensitivity Tests , Mycotoxins/chemistry , Pyrones/chemistryABSTRACT
A radioligand test to detect inhibitors of endothelin-1 binding to its receptors in bovine atrial and porcine cerebral membranes was used to screen fungal metabolites from stationary fermentations. Inhibitory activity, observed in culture extracts of two Acremonium species, led to the discovery of aselacins A, B and C. Aselacin A inhibits binding to both membrane fractions with IC50s of approximately 20 micrograms/ml.
Subject(s)
Acremonium/metabolism , Endothelin Receptor Antagonists , Endothelins/metabolism , Indoles/pharmacology , Peptides, Cyclic/pharmacology , Animals , Binding, Competitive , Cattle , Fermentation , In Vitro Techniques , Peptides, Cyclic/biosynthesis , SwineABSTRACT
In the course of screening with the mixed lymphocyte reaction, a new inhibitor of protein kinase C with immunosuppressive activity was isolated from the fermentation broth and mycelia of Streptomyces sp. AB 1869R-359. Although certain similarities exist, this strain is morphologically and physiologically distinct from other reported producers of staurosporine-related compounds. We have found that this strain produces relatively high levels of staurosporine and the new minor compound MLR-52, which possesses the indolo[2,3-a]carbazole chromophore of staurosporine, but differs in the substitution pattern of the sugar moiety. Their structures have been elucidated by mass and NMR spectra. MLR-52 has been shown to inhibit the enzymatic activity of protein kinase C and the murine mixed lymphocyte reaction.
Subject(s)
Alkaloids , Immunosuppressive Agents , Protein Kinase C/antagonists & inhibitors , Alkaloids/chemistry , Alkaloids/isolation & purification , Alkaloids/metabolism , Alkaloids/pharmacology , Animals , Culture Media , Female , Fermentation , Immunosuppressive Agents/chemistry , Immunosuppressive Agents/isolation & purification , In Vitro Techniques , Lymphocyte Culture Test, Mixed , Mice , Mice, Inbred BALB C , Mice, Inbred C57BL , Staurosporine/analogs & derivatives , Streptomyces/metabolismABSTRACT
The ardeemins are a new family of secondary metabolites produced by submerged fermentation of a fungus which was isolated from a soil sample collected in Brazil. Based on taxonomic studies, the producing culture was identified as Aspergillus fischeri var. brasiliensis strain AB 1826M-35. 5-N-Acetylardeemin potentiated the cytotoxicity of the anticancer agent vinblastine in multidrug resistant human tumor cells.
Subject(s)
Antibiotics, Antineoplastic/isolation & purification , Aspergillus/chemistry , Heterocyclic Compounds/isolation & purification , Antibiotics, Antineoplastic/pharmacology , Chromatography, High Pressure Liquid , Drug Interactions , Drug Resistance, Microbial , Fermentation , Heterocyclic Compounds/pharmacology , Humans , Pyrimidinones/isolation & purification , Pyrimidinones/pharmacology , Tumor Cells, Cultured/drug effects , Vinblastine/therapeutic useABSTRACT
A novel antibiotic complex, named the calbistrins, has been discovered in the culture broth of a soil fungus. The producing organism, designated AB 1875C-28, was identified as a strain of Penicillium restrictum. Calbistrin A, the most potent of the 4-membered complex, has MICs of 0.78 micrograms/ml against Candida albicans. Only poor activity is observed against non-candida yeasts, filamentous fungi and bacteria.
Subject(s)
Antifungal Agents/biosynthesis , Antifungal Agents/pharmacology , Penicillium/chemistry , Polyenes/chemical synthesis , Polyenes/pharmacology , Animals , Aspergillus/drug effects , Candida/drug effects , Fermentation , Lethal Dose 50 , Mice , Microbial Sensitivity Tests , Microbiological Techniques , Penicillium/classification , Saccharomyces cerevisiae/drug effectsABSTRACT
Tirandalydigin is a new tetramic acid antibiotic which was discovered in a screen designed to find compounds with activity against pathogenic anaerobic bacteria. It was named tirandalydigin because it possesses structural features that are common to both tirandamycin and streptolydigin. The producing culture, strain AB 1006A-9, is a Streptomyces and was compared to the streptomycetes that synthesize tirandamycin and streptolydigin. It is closely related to the former culture and was named Streptomyces tirandis subsp. umidus. Tirandalydigin has MICs in the range of 0.5 to 32 micrograms/ml against many pathogenic anaerobes, streptococci, enterococci and legionellae.
Subject(s)
Aminoglycosides , Anti-Bacterial Agents/isolation & purification , Streptomyces/classification , Anti-Bacterial Agents/pharmacology , Bacteria/drug effects , Chromatography, High Pressure Liquid , Fermentation , In Vitro Techniques , Microbial Sensitivity Tests , Microscopy, Electron, ScanningABSTRACT
The dunaimycins are a new complex of spiroketal 24-membered macrolides discovered in the fermentation broth of two actinomycetes. Based on taxonomic studies these two cultures, which were isolated from soil, were identified as Streptomyces diastatochromogenes strains AB 1691Q-321 and AB 1711J-452. The dunaimycins possess both immunosuppressive and antimicrobial activity.