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Antimicrobial Agents and Chemotherapy Dec 1984For clarification of the nature of the side effects of macrolide antibiotics on the gastrointestinal tract, the motor-stimulating activity of these agents was studied in...
For clarification of the nature of the side effects of macrolide antibiotics on the gastrointestinal tract, the motor-stimulating activity of these agents was studied in unanesthetized dogs. The results showed that erythromycin and oleandomycin, the 14-membered macrolides with two side chain sugars combined at C3 and C5 in a glycosidic linkage in parallel, strongly stimulate gastrointestinal motor activity, an action accompanied by vomiting at large doses. On the other hand, leucomycin, acetylspiramycin, and tylosin, belonging to a 16-membered macrolide with two side chain sugars in series combined at C5 of the lactone ring, did not induce contractions of the gastrointestinal tract. Motor-stimulating activity by erythromycin and oleandomycin was greatly inhibited by atropine sulfate. These results point to structure-physiological activity relationships.
Topics: Aminoglycosides; Animals; Anti-Bacterial Agents; Atropine; Binding, Competitive; Dogs; Dose-Response Relationship, Drug; Erythromycin; Female; Gastrointestinal Motility; Leucomycins; Male; Micrococcus; Muscle Contraction; Oleandomycin
PubMed: 6524902
DOI: 10.1128/AAC.26.6.863 -
The Journal of Antibiotics Mar 1977Antibiotics, the activity of which enhanced against Pseudomonas aeruginosa by SP127, were restricted to the basic macrolide antibiotics such as erythromycin, maridomycin...
Antibiotics, the activity of which enhanced against Pseudomonas aeruginosa by SP127, were restricted to the basic macrolide antibiotics such as erythromycin, maridomycin and oleandomycin, the neutral macrolide antibiotics such as lankamycin and lankacidin C, vancomycin and enramycin. Synergistic activity of SP127 with the above antibiotics was found against Pseudomonas aeruginosa and several strains of Escherichia coli, but not against Proteus vulgaris and macrolide-resistant Staphylococcus aureus. SP127 had extremely weak proteolytic but no lytic activity. From the isotopic experiments, the action of SP127 was partially attributed to the promotion of antibiotic penetration to cells of Pseudomonas aeruginosa.
Topics: Anti-Bacterial Agents; Bacillus; Bacterial Proteins; Bacteriolysis; Calcium; Caseins; Drug Resistance, Microbial; Drug Synergism; Erythromycin; Leucomycins; Magnesium; Microbial Sensitivity Tests; Pseudomonas aeruginosa; Staphylococcus aureus; Vancomycin
PubMed: 405356
DOI: 10.7164/antibiotics.30.215 -
Antimicrobial Agents and Chemotherapy Apr 1993We examined the effects of sub-MICs of erythromycin (EM) and other macrolide antibiotics on the serum sensitivity of Pseudomonas aeruginosa. P. aeruginosa S-6 grown for...
We examined the effects of sub-MICs of erythromycin (EM) and other macrolide antibiotics on the serum sensitivity of Pseudomonas aeruginosa. P. aeruginosa S-6 grown for 36 and 48 h on agar with 10 micrograms of EM per ml (1/10th the MIC) showed significantly increased sensitivity to human serum bactericidal activity compared with those of bacteria grown on agar without EM (P < 0.05). No changes in serum sensitivity were observed in bacteria grown for less than 24 h. This increased sensitivity was apparent even at a concentration of 1.5 micrograms of EM per ml (1/67th the MIC) in bacteria grown for 48 h (P < 0.01). Among the other macrolide antibiotics tested, clarithromycin also enhanced sensitivity to serum, but there were no changes in the sensitivities of bacteria grown on agar with kitasamycin, josamycin, rokitamycin, or oleandomycin even at a concentration of 12 micrograms/ml (1/16th, 1/16th, 1/8th, and 1/33rd the MICs, respectively). P. aeruginosa S-6 grown on agar with subinhibitory concentrations of EM showed decreased cell surface hydrophobicity in a dose-dependent manner, whereas oleandomycin and rokitamycin, even at a concentration of 12 micrograms/ml, induced a slight decrease in hydrophobicity which was approximately equivalent to that of 1.5 micrograms of EM per ml. Among six other strains of the nonmucoid phenotype, three strains became more sensitive to serum by exposure to 10 micrograms of EM per ml for 48 h. In contrast, no evident correlation between EM treatment and a change in serum sensitivity was observed in six strains of the mucoid phenotype, as judged by the results of experiments with both 2 and 0.4% serum. These results show that EM at subinhibitory concentrations enhances the serum sensitivity of some P. aeruginosa strains. Since induced serum sensitivity was accompanied by a decrease in bacterial cell surface hydrophobicity, EM may render P. aeruginosa more serum sensitive by changing the cell surface structure(s) of this organism.
Topics: Anti-Bacterial Agents; Chemical Phenomena; Chemistry, Physical; Erythromycin; Hot Temperature; Humans; Microbial Sensitivity Tests; Pseudomonas aeruginosa; Serum Bactericidal Test
PubMed: 8494362
DOI: 10.1128/AAC.37.4.675 -
Journal of Food Protection Feb 2004The distribution of Campylobacter spp. on 13 poultry farms (broiler chicken, quail, pheasant, peacock, and turkey) from eight regions (Vladimir, Vologda, Voronezh,...
The distribution of Campylobacter spp. on 13 poultry farms (broiler chicken, quail, pheasant, peacock, and turkey) from eight regions (Vladimir, Vologda, Voronezh, Kaluga, Liptsk, Moscow, Orenburg, and Orel) in Russia was surveyed. Intestinal materials were plated onto Campylobacter-selective medium and plates were incubated microaerobically at 42 degrees C for 24 or 48 h. Identification was based on colonial morphology, microscopic examination, and biochemical tests; latex agglutination assays were used for confirmation. In total, 116 isolates were derived from 370 samples. Isolation rates were similar, regardless of whether the birds were from small or large broiler production farms. Susceptibility of 48 representative (from these production sources) strains of Campylobacter spp. to 38 antimicrobial compounds was determined by disk diffusion assays. All strains tested were sensitive to amikacin, gentamycin, sisomycin, chloramphenicol, imipenem, oleandomycin, erythromycin, azitromycin, and ampicillin. The strains were also sensitive to 100 microg/disk of carbenicillin, fluoroquinolones, and to nitrofurans. Fluoroquinolone sensitivity was most notable and may be related to its limited application in poultry production within Russia. Hippurate and ribosomal RNA gene primers were developed and used to distinguish Campylobacter jejuni and Campylobacter coli and to provide a measure of strain discrimination. The combination of PCR analysis and randomly amplified polymorphic DNA (RAPD) typing were conducted for selected isolates. The various poultry species and the different locations yielded Campylobacter isolates with discrete randomly amplified polymorphic DNA patterns. The distribution and substantial diversity of Campylobacter spp. isolates appears similar to that previously reported in other countries.
Topics: Animals; Anti-Bacterial Agents; Campylobacter; Chickens; Colony Count, Microbial; DNA, Bacterial; Drug Resistance, Bacterial; Food Contamination; Food Microbiology; Genetic Variation; Microbial Sensitivity Tests; Polymorphism, Restriction Fragment Length; Poultry; Prevalence; Quail; Russia; Species Specificity; Turkeys
PubMed: 14968953
DOI: 10.4315/0362-028x-67.2.239 -
British Journal of Clinical Pharmacology Dec 2002To evaluate the antimalarial agent quinine as a potential in vivo probe for hepatic cytochrome P450 (CYP) 3A4 activity. (Clinical Trial)
Clinical Trial Randomized Controlled Trial
AIMS
To evaluate the antimalarial agent quinine as a potential in vivo probe for hepatic cytochrome P450 (CYP) 3A4 activity.
METHODS
Ten healthy adult volunteers received, by randomized crossover design, either a single oral dose of quinine sulphate (600 mg) alone, or quinine sulphate (600 mg) plus the CYP3A4 inhibitor troleandomycin (TAO; 500 mg every 8 h). Plasma and urine samples were collected before quinine administration, and up to 48 h thereafter, then analysed by h.p.l.c. for both quinine and its CYP3A4-generated metabolite, 3-hydroxyquinine. During both phases, the erythromycin breath test (ERMBT) was administered at specific times to assess hepatic CYP3A4 activity.
RESULTS
Compared with control, TAO treatment significantly decreased the mean time-averaged ERMBT result by 77% (95% CI, 68, 85%), the mean apparent oral clearance of quinine (CL/F ) by 45% (95% CI, 39, 52%), and the mean apparent formation clearance of 3-hydroxyquinine (CL3-OH) by 81% (95% CI, 76, 87%). There was no correlation between the TAO-mediated percent decrease in the time-averaged ERMBT result and the percent decrease in CL/F or in CL3-OH. When TAO and control treatments were analysed separately, there were no significant correlations between the time-averaged ERMBT result and CL/F, CL3-OH, or single plasma quinine concentration at 12, 24, and 48 h.
CONCLUSIONS
Quinine may be a useful probe to detect inhibition of liver CYP3A4 activity within an individual. Further studies are needed to determine whether it can provide a quantitative measure of CYP3A4 activity suitable for intersubject comparison.
Topics: Administration, Oral; Adult; Aged; Antimalarials; Area Under Curve; Breath Tests; Cross-Over Studies; Cytochrome P-450 Enzyme System; Dose-Response Relationship, Drug; Erythromycin; Female; Humans; Liver; Male; Metabolic Clearance Rate; Middle Aged; Molecular Probes; Ovarian Neoplasms; Quinidine; Quinine; Troleandomycin
PubMed: 12492613
DOI: 10.1046/j.1365-2125.2002.01687.x -
The Journal of Biological Chemistry Sep 2001The accumulation of various 25-hydroxylated C(27)-bile alcohols in blood and their excretion in urine are characteristic features of cerebrotendinous xanthomatosis (CTX)...
The accumulation of various 25-hydroxylated C(27)-bile alcohols in blood and their excretion in urine are characteristic features of cerebrotendinous xanthomatosis (CTX) a recessively inherited inborn error of bile acid synthesis caused by mutations in the mitochondrial sterol 27-hydroxylase (CYP27) gene. These bile alcohols may be intermediates in the alternative cholic acid side chain cleavage pathway. The present study was undertaken to identify enzymes and reactions responsible for the formation of these bile alcohols and to explain why Cyp27(-/-) mice do not show CTX-related abnormalities. Microsomal activities of 5beta-cholestane-3alpha,7alpha,12alpha-triol 25- and 26-hydroxylases, 5beta-cholestane-3alpha,7alpha,12alpha,25-tetrol 23R-, 24S-, and 27-hydroxylases and testosterone 6beta-hydroxylase, a marker enzyme for CYP3A, in Cyp27(-/-) mice livers were markedly up-regulated (5.5-, 3.5-, 6.5-, 7.5-, 2.9-, and 5.4-fold, respectively). In contrast, these enzyme activities were not increased in CTX. The activities of 5beta-cholestane-3alpha,7alpha,12alpha-triol 25- and 26-hydroxylases and 5beta-cholestane-3alpha,7alpha,12alpha,25-tetrol 23R-, 24R-, 24S-, and 27-hydroxylases were strongly correlated with the activities of testosterone 6beta-hydroxylase in control human liver microsomes from eight unrelated donors. Troleandomycin, a specific inhibitor of CYP3A, markedly suppressed these microsomal side chain hydroxylations in both mouse and human livers in a dose-dependent manner. In addition, experiments using recombinant overexpressed human CYP3A4 confirmed that these microsomal side chain hydroxylations were catalyzed by a single enzyme, CYP3A4. The results demonstrate that microsomal 25- and 26-hydroxylations of 5beta-cholestane-3alpha,7alpha,12alpha-triol and microsomal 23R-, 24R-, 24S-, and 27-hydroxylations of 5beta-cholestane-3alpha,7alpha,12alpha,25-tetrol are mainly catalyzed by CYP3A in both mice and humans. Unlike Cyp27(-/-) mice, CYP3A activity was not up-regulated despite marked accumulation of 5beta-cholestane-3alpha,7alpha,12alpha-triol in CTX.
Topics: Animals; Bile Acids and Salts; Catalysis; Cholestanetriol 26-Monooxygenase; Cytochrome P-450 CYP3A; Cytochrome P-450 Enzyme System; Ethanolamines; Humans; Hydroxylation; Male; Mice; Mice, Knockout; Microsomes, Liver; Middle Aged; Mixed Function Oxygenases; Mutation; Nitrates; Steroid Hydroxylases; Troleandomycin; Up-Regulation; Xanthomatosis, Cerebrotendinous
PubMed: 11454857
DOI: 10.1074/jbc.M103025200 -
Molecular Microbiology Oct 2004Expression of specific short peptides can render cells resistant to macrolide antibiotics. Peptides conferring resistance to structurally different macrolides including...
Expression of specific short peptides can render cells resistant to macrolide antibiotics. Peptides conferring resistance to structurally different macrolides including oleandomycin, azithromycin, azaerythromycin, josamycin and a ketolide cethromycin were selected from a random pentapeptide expression library. Analysis of the entire collection of the resistance peptides allowed their classification into five distinct groups according to their sequence similarity and the type of resistance they confer. A strong correlation was observed between the structures of macrolide antibiotics and sequences of the peptides conferring resistance. Such a correlation indicates that sequence-specific interactions between the nascent peptide and the macrolide antibiotic and/or the ribosome can occur in the ribosomal exit tunnel.
Topics: Amino Acid Sequence; Base Sequence; Drug Resistance; Escherichia coli; Macrolides; Molecular Structure; Peptides
PubMed: 15469510
DOI: 10.1111/j.1365-2958.2004.04290.x -
Foods (Basel, Switzerland) Mar 2024The amount of macrolide (MAL) residues in aquatic products, including oleandomycin (OLD), erythromycin (ERM), clarithromycin (CLA), azithromycin (AZI), kitasamycin...
Dispersive Solid-Phase Extraction and Ultra-Performance Liquid Chromatography-Tandem Mass Spectrometry-A Rapid and Accurate Method for Detecting 10 Macrolide Residues in Aquatic Products.
The amount of macrolide (MAL) residues in aquatic products, including oleandomycin (OLD), erythromycin (ERM), clarithromycin (CLA), azithromycin (AZI), kitasamycin (KIT), josamycin (JOS), spiramycin (SPI), tilmicosin (TIL), tylosin (TYL), and roxithromycin (ROX), was determined using solid-phase extraction and ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). The residues were extracted with 1% ammonia acetonitrile solution and purified by neutral alumina adsorption. Chromatographic separation was completed on an ACQUITY UPLC BEH C column with acetonitrile-0.1% formic acid aqueous solution as the mobile phase, and mass spectrometry detection was performed by multiple reaction monitoring scanning with the positive mode in an electrospray ion source (ESI). Five isotopically labeled compounds were used as internal standards for quality control purposes. The findings indicated that across the mass concentration span of 1.0-100 μg/L, there was a strong linear correlation ( > 0.99) between the concentration and instrumental response for the 10 MALs. The limit of detection of UPLC-MS/MS was 0.25-0.50 μg/kg, and the limit of quantitation was 0.5-1.0 μg/kg. The added recovery of blank matrix samples at standard gradient levels (1.0, 5.0, and 50.0 μg/kg) was 83.1-116.6%, and the intra-day precision and inter-day precisions were 3.7 and 13.8%, respectively. The method is simple and fast, with high accuracy and good repeatability, in line with the requirements for accurate qualitative and quantitative analysis of the residues for 10 MALs in aquatic products.
PubMed: 38540855
DOI: 10.3390/foods13060866 -
British Journal of Anaesthesia Apr 2001We determined the contribution of cytochrome P450 (CYP) isoforms to the metabolism of midazolam by kinetic analysis of human liver microsomes and CYP isoforms and by...
We determined the contribution of cytochrome P450 (CYP) isoforms to the metabolism of midazolam by kinetic analysis of human liver microsomes and CYP isoforms and by examining the effect of chemical inhibitors and monoclonal antibodies against CYP isoforms in vitro. Midazolam was metabolized to 1'-hydroxymidazolam (1'-OH MDZ) by human liver microsomes with a Michaelis-Menten constant (Km) of 4.1 (1.0) (mean (SD)) micromol litre(-1) and a maximum rate of metabolism (Vmax) of 5.5 (1.1) nmol min(-1) mg protein(-1) (n = 6). Of the nine representative human liver CYP isoforms, CYP1A2, 2A6, 2B6, 2C9, 2C19, 2D6, 2E1, 3A4 and 3A5, three (CYP2B6, 3A4 and 3A5) showed midazolam 1'-hydroxylation activity, with Kms of 40.7, 1.7 and 3.0 micromol litre(-1), respectively, and Vmax values of 12.0, 3.3 and 13.2 nmol min(-1) nmol P450(-1), respectively (n = 4). Midazolam 1'-hydroxylation activity of human liver microsomes correlated significantly with testosterone 6beta-hydroxylation activity, a marker of CYP3A activity (r2 = 0.77, P = 0.0001), but not with S-mephenytoin N-demethylation activity, a marker of CYP2B6 activity (r2 < 0.01, P = 0.84) (n = 11). Troleandomycin and orphenadrine, chemical inhibitors of CYP isoforms, inhibited the formation of 1'-OH MDZ by human liver microsomes. Monoclonal antibody against CYP3A4 inhibited the formation of 1'-OH MDZ by 79%, whereas monoclonal antibody against CYP2B6 had no effect on midazolam 1'-hydroxylation by human liver microsomes (n = 5). These results indicate that only CYP3A4, but not CYP2B6 or CYP2C, is involved in the metabolism of midazolam in vitro.
Topics: Anesthetics, Intravenous; Anti-Anxiety Agents; Antibodies, Monoclonal; Aryl Hydrocarbon Hydroxylases; Cytochrome P-450 CYP1A2; Cytochrome P-450 CYP2B6; Cytochrome P-450 Enzyme Inhibitors; Cytochrome P-450 Enzyme System; Enzyme Inhibitors; Humans; Hydroxylation; Microsomes, Liver; Midazolam; Orphenadrine; Oxidoreductases, N-Demethylating; Steroid 16-alpha-Hydroxylase; Steroid Hydroxylases; Troleandomycin
PubMed: 11573629
DOI: 10.1093/bja/86.4.540 -
European Journal of Biochemistry May 1994Cell-free extracts from the oleandomycin producer, Streptomyces antibioticus, possess an intracellular glycosyltransferase capable of inactivating oleandomycin by...
Cell-free extracts from the oleandomycin producer, Streptomyces antibioticus, possess an intracellular glycosyltransferase capable of inactivating oleandomycin by glycosylation of the 2'-hydroxyl group in the desosamine moiety of the molecule [Vilches, C., Hernández, C., Méndez, C. & Salas, J. A. (1992) J. Bacteriol. 174, 161-165]. Using a four-step purification procedure, we have purified an enzyme activity from the culture supernatants from this organism which is able to release glucose from the inactive glycosylated molecule thus reactivating the antibiotic activity. This enzyme activity appeared in the culture supernatants immediately before oleandomycin is detected. The enzyme (molecular mass 87 kDa) showed a high degree of substrate specificity, not acting on other glycosylated macrolides such as methymycin, lankamycin and rosaramicin which are substrates for the glycosyltransferase. A second activity was detected corresponding to a 34-kDa polypeptide which probably originates from proteolytic cleavage of the larger polypeptide. The 87-kDa polypeptide possibly catalyses the last biosynthetic step in oleandomycin biosynthesis by S. antibioticus.
Topics: Biotransformation; Chromatography, Ion Exchange; Electrophoresis, Paper; Electrophoresis, Polyacrylamide Gel; Enzyme Activation; Enzymes; Glycosylation; Kinetics; Oleandomycin; Streptomyces antibioticus; Substrate Specificity
PubMed: 8200337
DOI: 10.1111/j.1432-1033.1994.tb18850.x