Quinolones: A group of derivatives of naphthyridine carboxylic acid, quinoline carboxylic acid, or NALIDIXIC ACID.4-Quinolones: QUINOLONES containing a 4-oxo (a carbonyl in the para position to the nitrogen). They inhibit the A subunit of DNA GYRASE and are used as antimicrobials. Second generation 4-quinolones are also substituted with a 1-piperazinyl group at the 7-position and a fluorine at the 6-position.Anti-Infective Agents: Substances that prevent infectious agents or organisms from spreading or kill infectious agents in order to prevent the spread of infection.Fluoroquinolones: A group of QUINOLONES with at least one fluorine atom and a piperazinyl group.Ciprofloxacin: A broad-spectrum antimicrobial carboxyfluoroquinoline.NaphthyridinesOfloxacin: A synthetic fluoroquinolone antibacterial agent that inhibits the supercoiling activity of bacterial DNA GYRASE, halting DNA REPLICATION.Microbial Sensitivity Tests: Any tests that demonstrate the relative efficacy of different chemotherapeutic agents against specific microorganisms (i.e., bacteria, fungi, viruses).Norfloxacin: A synthetic fluoroquinolone (FLUOROQUINOLONES) with broad-spectrum antibacterial activity against most gram-negative and gram-positive bacteria. Norfloxacin inhibits bacterial DNA GYRASE.Topoisomerase II Inhibitors: Compounds that inhibit the activity of DNA TOPOISOMERASE II. Included in this category are a variety of ANTINEOPLASTIC AGENTS which target the eukaryotic form of topoisomerase II and ANTIBACTERIAL AGENTS which target the prokaryotic form of topoisomerase II.DNA Gyrase: A bacterial DNA topoisomerase II that catalyzes ATP-dependent breakage of both strands of DNA, passage of the unbroken strands through the breaks, and rejoining of the broken strands. Gyrase binds to DNA as a heterotetramer consisting of two A and two B subunits. In the presence of ATP, gyrase is able to convert the relaxed circular DNA duplex into a superhelix. In the absence of ATP, supercoiled DNA is relaxed by DNA gyrase.DNA Topoisomerase IV: A bacterial DNA topoisomerase II that catalyzes ATP-dependent breakage of both strands of DNA, passage of the unbroken strands through the breaks, and rejoining of the broken strands. Topoisomerase IV binds to DNA as a heterotetramer consisting 2 parC and 2 parE subunits. Topoisomerase IV is a decatenating enzyme that resolves interlinked daughter chromosomes following DNA replication.Enoxacin: A broad-spectrum 6-fluoronaphthyridinone antibacterial agent that is structurally related to NALIDIXIC ACID.QuinolinesAnti-Bacterial Agents: Substances that reduce the growth or reproduction of BACTERIA.Nalidixic Acid: A synthetic 1,8-naphthyridine antimicrobial agent with a limited bacteriocidal spectrum. It is an inhibitor of the A subunit of bacterial DNA GYRASE.Levofloxacin: The L-isomer of Ofloxacin.Drug Resistance, Microbial: The ability of microorganisms, especially bacteria, to resist or to become tolerant to chemotherapeutic agents, antimicrobial agents, or antibiotics. This resistance may be acquired through gene mutation or foreign DNA in transmissible plasmids (R FACTORS).DNA Topoisomerases, Type II: DNA TOPOISOMERASES that catalyze ATP-dependent breakage of both strands of DNA, passage of the unbroken strands through the breaks, and rejoining of the broken strands. These enzymes bring about relaxation of the supercoiled DNA and resolution of a knotted circular DNA duplex.Pefloxacin: A synthetic broad-spectrum fluoroquinolone antibacterial agent active against most gram-negative and gram-positive bacteria.Aza CompoundsDrug Resistance, Bacterial: The ability of bacteria to resist or to become tolerant to chemotherapeutic agents, antimicrobial agents, or antibiotics. This resistance may be acquired through gene mutation or foreign DNA in transmissible plasmids (R FACTORS).Fleroxacin: A broad-spectrum antimicrobial fluoroquinolone. The drug strongly inhibits the DNA-supercoiling activity of DNA GYRASE.DNA, Superhelical: Circular duplex DNA isolated from viruses, bacteria and mitochondria in supercoiled or supertwisted form. This superhelical DNA is endowed with free energy. During transcription, the magnitude of RNA initiation is proportional to the DNA superhelicity.Oxolinic Acid: Synthetic antimicrobial related to NALIDIXIC ACID and used in URINARY TRACT INFECTIONS.Escherichia coli: A species of gram-negative, facultatively anaerobic, rod-shaped bacteria (GRAM-NEGATIVE FACULTATIVELY ANAEROBIC RODS) commonly found in the lower part of the intestine of warm-blooded animals. It is usually nonpathogenic, but some strains are known to produce DIARRHEA and pyogenic infections. Pathogenic strains (virotypes) are classified by their specific pathogenic mechanisms such as toxins (ENTEROTOXIGENIC ESCHERICHIA COLI), etc.Staphylococcus aureus: Potentially pathogenic bacteria found in nasal membranes, skin, hair follicles, and perineum of warm-blooded animals. They may cause a wide range of infections and intoxications.Dermatitis, Phototoxic: A nonimmunologic, chemically induced type of photosensitivity producing a sometimes vesiculating dermatitis. It results in hyperpigmentation and desquamation of the light-exposed areas of the skin.Streptococcus pneumoniae: A gram-positive organism found in the upper respiratory tract, inflammatory exudates, and various body fluids of normal and/or diseased humans and, rarely, domestic animals.Gram-Positive Bacteria: Bacteria which retain the crystal violet stain when treated by Gram's method.Drug Resistance, Multiple, Bacterial: The ability of bacteria to resist or to become tolerant to several structurally and functionally distinct drugs simultaneously. This resistance may be acquired through gene mutation or foreign DNA in transmissible plasmids (R FACTORS).Macrolides: A group of often glycosylated macrocyclic compounds formed by chain extension of multiple PROPIONATES cyclized into a large (typically 12, 14, or 16)-membered lactone. Macrolides belong to the POLYKETIDES class of natural products, and many members exhibit ANTIBIOTIC properties.Gram-Negative Bacteria: Bacteria which lose crystal violet stain but are stained pink when treated by Gram's method.Bacteria, AnaerobicOxazines: Six-membered heterocycles containing an oxygen and a nitrogen.Bacteria: One of the three domains of life (the others being Eukarya and ARCHAEA), also called Eubacteria. They are unicellular prokaryotic microorganisms which generally possess rigid cell walls, multiply by cell division, and exhibit three principal forms: round or coccal, rodlike or bacillary, and spiral or spirochetal. Bacteria can be classified by their response to OXYGEN: aerobic, anaerobic, or facultatively anaerobic; by the mode by which they obtain their energy: chemotrophy (via chemical reaction) or PHOTOTROPHY (via light reaction); for chemotrophs by their source of chemical energy: CHEMOLITHOTROPHY (from inorganic compounds) or chemoorganotrophy (from organic compounds); and by their source for CARBON; NITROGEN; etc.; HETEROTROPHY (from organic sources) or AUTOTROPHY (from CARBON DIOXIDE). They can also be classified by whether or not they stain (based on the structure of their CELL WALLS) with CRYSTAL VIOLET dye: gram-negative or gram-positive.Clopidol: A very effective anticoccidial agent used in poultry.DNA, Bacterial: Deoxyribonucleic acid that makes up the genetic material of bacteria.Bacterial Infections: Infections by bacteria, general or unspecified.Novobiocin: An antibiotic compound derived from Streptomyces niveus. It has a chemical structure similar to coumarin. Novobiocin binds to DNA gyrase, and blocks adenosine triphosphatase (ATPase) activity. (From Reynolds, Martindale The Extra Pharmacopoeia, 30th ed, p189)Pseudomonas aeruginosa: A species of gram-negative, aerobic, rod-shaped bacteria commonly isolated from clinical specimens (wound, burn, and urinary tract infections). It is also found widely distributed in soil and water. P. aeruginosa is a major agent of nosocomial infection.Mutation: Any detectable and heritable change in the genetic material that causes a change in the GENOTYPE and which is transmitted to daughter cells and to succeeding generations.Bartonella bacilliformis: The type species of the genus BARTONELLA, a gram-negative bacteria found in humans. It is found in the mountain valleys of Peru, Ecuador, and Southwest Columbia where the sandfly (see PHLEBOTOMUS) vector is present. It causes OROYA FEVER and VERRUGA PERUANA.Evodia: A plant genus of the family RUTACEAE which is used in Chinese medicine (DRUGS, CHINESE HERBAL). Evodiamine and other quinazoline alkaloids (QUINAZOLINES) are obtained from the fruit of E. ruticarpa.Mycobacterium fortuitum: A rapid-growing, nonphotochromogenic species that is potentially pathogenic, producing lesions of lung, bone, or soft tissue following trauma. It has been found in soil and in injection sites of humans, cattle, and cold-blooded animals. (Dorland, 28th ed)Structure-Activity Relationship: The relationship between the chemical structure of a compound and its biological or pharmacological activity. Compounds are often classed together because they have structural characteristics in common including shape, size, stereochemical arrangement, and distribution of functional groups.Drug Resistance, Multiple: Simultaneous resistance to several structurally and functionally distinct drugs.Tetracyclines: Closely congeneric derivatives of the polycyclic naphthacenecarboxamide. (Gilman et al., Goodman and Gilman's The Pharmacological Basis of Therapeutics, 8th ed, p1117)Genes, Bacterial: The functional hereditary units of BACTERIA.Ornidazole: A nitroimidazole antiprotozoal agent used in ameba and trichomonas infections. It is partially plasma-bound and also has radiation-sensitizing action.Aminoglycosides: Glycosylated compounds in which there is an amino substituent on the glycoside. Some of them are clinically important ANTIBIOTICS.Cephalosporins: A group of broad-spectrum antibiotics first isolated from the Mediterranean fungus ACREMONIUM. They contain the beta-lactam moiety thia-azabicyclo-octenecarboxylic acid also called 7-aminocephalosporanic acid.Neisseria gonorrhoeae: A species of gram-negative, aerobic bacteria primarily found in purulent venereal discharges. It is the causative agent of GONORRHEA.Topoisomerase Inhibitors: Compounds that inhibit the activity of DNA TOPOISOMERASES.Bacterial Proteins: Proteins found in any species of bacterium.Gram-Negative Bacterial Infections: Infections caused by bacteria that show up as pink (negative) when treated by the gram-staining method.beta-Lactams: Four-membered cyclic AMIDES, best known for the PENICILLINS based on a bicyclo-thiazolidine, as well as the CEPHALOSPORINS based on a bicyclo-thiazine, and including monocyclic MONOBACTAMS. The BETA-LACTAMASES hydrolyze the beta lactam ring, accounting for BETA-LACTAM RESISTANCE of infective bacteria.Bacteria, AerobicTrimethoprim-Sulfamethoxazole Combination: This drug combination has proved to be an effective therapeutic agent with broad-spectrum antibacterial activity against both gram-positive and gram-negative organisms. It is effective in the treatment of many infections, including PNEUMOCYSTIS PNEUMONIA in AIDS.Quinazolinones: Chemicals with two conjoined aromatic rings incorporating two nitrogen atoms and one of the carbons oxidized with a keto oxygen.Plasmids: Extrachromosomal, usually CIRCULAR DNA molecules that are self-replicating and transferable from one organism to another. They are found in a variety of bacterial, archaeal, fungal, algal, and plant species. They are used in GENETIC ENGINEERING as CLONING VECTORS.Chloramphenicol: An antibiotic first isolated from cultures of Streptomyces venequelae in 1947 but now produced synthetically. It has a relatively simple structure and was the first broad-spectrum antibiotic to be discovered. It acts by interfering with bacterial protein synthesis and is mainly bacteriostatic. (From Martindale, The Extra Pharmacopoeia, 29th ed, p106)QuinolizinesBronchitis, Chronic: A subcategory of CHRONIC OBSTRUCTIVE PULMONARY DISEASE. The disease is characterized by hypersecretion of mucus accompanied by a chronic (more than 3 months in 2 consecutive years) productive cough. Infectious agents are a major cause of chronic bronchitis.Lactams: Cyclic AMIDES formed from aminocarboxylic acids by the elimination of water. Lactims are the enol forms of lactams.Bacteroides fragilis: Gram-negative bacteria occurring in the lower intestinal tracts of man and other animals. It is the most common species of anaerobic bacteria isolated from human soft tissue infections.Enterobacteriaceae: A family of gram-negative, facultatively anaerobic, rod-shaped bacteria that do not form endospores. Its organisms are distributed worldwide with some being saprophytes and others being plant and animal parasites. Many species are of considerable economic importance due to their pathogenic effects on agriculture and livestock.SOS Response (Genetics): An error-prone mechanism or set of functions for repairing damaged microbial DNA. SOS functions (a concept reputedly derived from the SOS of the international distress signal) are involved in DNA repair and mutagenesis, in cell division inhibition, in recovery of normal physiological conditions after DNA repair, and possibly in cell death when DNA damage is extensive.Mycobacterium avium Complex: A complex that includes several strains of M. avium. M. intracellulare is not easily distinguished from M. avium and therefore is included in the complex. These organisms are most frequently found in pulmonary secretions from persons with a tuberculous-like mycobacteriosis. Strains of this complex have also been associated with childhood lymphadenitis and AIDS; M. avium alone causes tuberculosis in a variety of birds and other animals, including pigs.Escherichia coli Infections: Infections with bacteria of the species ESCHERICHIA COLI.Ureaplasma: A genus of gram-negative, nonmotile bacteria which are common parasitic inhabitants of the urogenital tracts of humans, cattle, dogs, and monkeys.Imipenem: Semisynthetic thienamycin that has a wide spectrum of antibacterial activity against gram-negative and gram-positive aerobic and anaerobic bacteria, including many multiresistant strains. It is stable to beta-lactamases. Clinical studies have demonstrated high efficacy in the treatment of infections of various body systems. Its effectiveness is enhanced when it is administered in combination with CILASTATIN, a renal dipeptidase inhibitor.Stenotrophomonas maltophilia: A species of STENOTROPHOMONAS, formerly called Xanthomonas maltophilia, which reduces nitrate. It is a cause of hospital-acquired ocular and lung infections, especially in those patients with cystic fibrosis and those who are immunosuppressed.Colony Count, Microbial: Enumeration by direct count of viable, isolated bacterial, archaeal, or fungal CELLS or SPORES capable of growth on solid CULTURE MEDIA. The method is used routinely by environmental microbiologists for quantifying organisms in AIR; FOOD; and WATER; by clinicians for measuring patients' microbial load; and in antimicrobial drug testing.Penicillin Resistance: Nonsusceptibility of an organism to the action of penicillins.Klebsiella pneumoniae: Gram-negative, non-motile, capsulated, gas-producing rods found widely in nature and associated with urinary and respiratory infections in humans.Drug Utilization: The utilization of drugs as reported in individual hospital studies, FDA studies, marketing, or consumption, etc. This includes drug stockpiling, and patient drug profiles.Bacterial Outer Membrane Proteins: Proteins isolated from the outer membrane of Gram-negative bacteria.Mycobacterium: A genus of gram-positive, aerobic bacteria. Most species are free-living in soil and water, but the major habitat for some is the diseased tissue of warm-blooded hosts.Spiro Compounds: A group of compounds consisting in part of two rings sharing one atom (usually a carbon) in common.Viridans Streptococci: A large heterogeneous group of mostly alpha-hemolytic streptococci. They colonize the respiratory tract at birth and generally have a low degree of pathogenicity. This group of species includes STREPTOCOCCUS MITIS; STREPTOCOCCUS MUTANS; STREPTOCOCCUS ORALIS; STREPTOCOCCUS SANGUIS; STREPTOCOCCUS SOBRINUS; and the STREPTOCOCCUS MILLERI GROUP. The latter are often beta-hemolytic and commonly produce invasive pyogenic infections including brain and abdominal abscesses.Enterobacter cloacae: A species of gram-negative, facultatively anaerobic, rod-shaped bacteria that occurs in water, sewage, soil, meat, hospital environments, and on the skin and in the intestinal tract of man and animals as a commensal.Erythromycin: A bacteriostatic antibiotic macrolide produced by Streptomyces erythreus. Erythromycin A is considered its major active component. In sensitive organisms, it inhibits protein synthesis by binding to 50S ribosomal subunits. This binding process inhibits peptidyl transferase activity and interferes with translocation of amino acids during translation and assembly of proteins.Urinary Tract Infections: Inflammatory responses of the epithelium of the URINARY TRACT to microbial invasions. They are often bacterial infections with associated BACTERIURIA and PYURIA.Rifampin: A semisynthetic antibiotic produced from Streptomyces mediterranei. It has a broad antibacterial spectrum, including activity against several forms of Mycobacterium. In susceptible organisms it inhibits DNA-dependent RNA polymerase activity by forming a stable complex with the enzyme. It thus suppresses the initiation of RNA synthesis. Rifampin is bactericidal, and acts on both intracellular and extracellular organisms. (From Gilman et al., Goodman and Gilman's The Pharmacological Basis of Therapeutics, 9th ed, p1160)Clindamycin: An antibacterial agent that is a semisynthetic analog of LINCOMYCIN.beta-Lactamases: Enzymes found in many bacteria which catalyze the hydrolysis of the amide bond in the beta-lactam ring. Well known antibiotics destroyed by these enzymes are penicillins and cephalosporins.Salmonella paratyphi A: A serotype of SALMONELLA ENTERICA that causes mild PARATYPHOID FEVER in humans.Citrobacter: A genus of gram-negative, rod-shaped enterobacteria that can use citrate as the sole source of carbon.Enterobacteriaceae Infections: Infections with bacteria of the family ENTEROBACTERIACEAE.Skin Diseases, Infectious: Skin diseases caused by bacteria, fungi, parasites, or viruses.Cilastatin: A renal dehydropeptidase-I and leukotriene D4 dipeptidase inhibitor. Since the antibiotic, IMIPENEM, is hydrolyzed by dehydropeptidase-I, which resides in the brush border of the renal tubule, cilastatin is administered with imipenem to increase its effectiveness. The drug also inhibits the metabolism of leukotriene D4 to leukotriene E4.Mycoplasma pneumoniae: Short filamentous organism of the genus Mycoplasma, which binds firmly to the cells of the respiratory epithelium. It is one of the etiologic agents of non-viral primary atypical pneumonia in man.

Mutation of a conserved serine residue in a quinolone-resistant type II topoisomerase alters the enzyme-DNA and drug interactions. (1/2071)

A Ser740 --> Trp mutation in yeast topoisomerase II (top2) and of the equivalent Ser83 in gyrase results in resistance to quinolones and confers hypersensitivity to etoposide (VP-16). We characterized the cleavage complexes induced by the top2(S740W) in the human c-myc gene. In addition to resistance to the fluoroquinolone CP-115,953, top2(S740W) induced novel DNA cleavage sites in the presence of VP-16, azatoxin, amsacrine, and mitoxantrone. Analysis of the VP-16 sites indicated that the changes in the cleavage pattern were reflected by alterations in base preference. C at position -2 and G at position +6 were observed for the top2(S740W) in addition to the previously reported C-1 and G+5 for the wild-type top2. The VP-16-induced top2(S740W) cleavage complexes were also more stable. The most stable sites had strong preference for C-1, whereas the most reversible sites showed no base preference at positions -1 or -2. Different patterns of DNA cleavage were also observed in the absence of drug and in the presence of calcium. These results indicate that the Ser740 --> Trp mutation alters the DNA recognition of top2, enhances its DNA binding, and markedly affects its interactions with inhibitors. Thus, residue 740 of top2 appears critical for both DNA and drug interactions.  (+info)

Vasopressin V2 receptor enhances gain of baroreflex in conscious spontaneously hypertensive rats. (2/2071)

The aim of the present study was to determine the receptor subtype involved in arginine vasopressin (AVP)-induced modulation of baroreflex function in spontaneously hypertensive rats (SHR) and Wistar-Kyoto (WKY) rats using novel nonpeptide AVP V1- and V2-receptor antagonists. Baroreceptor heart rate (HR) reflex was investigated in both SHR and WKY rats which were intravenously administered the selective V1- and V2-receptor antagonists OPC-21268 and OPC-31260, respectively. Baroreflex function was assessed by obtaining alternate pressor and depressor responses to phenylephrine and sodium nitroprusside, respectively, to construct baroreflex curves. In both SHR and WKY rats baroreflex activity was tested before and after intravenous administration of vehicle (20% DMSO), OPC-21268 (10 mg/kg), and OPC-31260 (1 and 10 mg/kg). Vehicle did not significantly alter basal mean arterial pressure (MAP) and HR values or baroreflex function in SHR or WKY rats. The V1-receptor antagonist had no significant effect on resting MAP or HR values or on baroreflex parameters in both groups of rats, although this dose was shown to significantly inhibit the pressor response to AVP (5 ng iv; ANOVA, P < 0.05). In SHR but not WKY rats the V2-receptor antagonist significantly attenuated the gain (or slope) of the baroreflex curve (to 73 +/- 3 and 79 +/- 7% of control for 1 and 10 mg/kg, respectively), although AVP-induced pressor responses were also attenuated with the higher dose of the V2-receptor antagonist. These findings suggest that AVP tonically enhances baroreflex function through a V2 receptor in the SHR.  (+info)

Carrier-mediated lung distribution of HSR-903, a new quinolone antibacterial agent. (3/2071)

HSR-903 [(S)-(-)-5-amino-7-(7-amino-5-azaspiro[2. 4]hept-5-yl)-1-cyclopropyl-6-fluoro-1, 4-dihydro-8-methyl-4-oxoquinoline-3-carboxylic acid methanesulfonate] is a newly synthesized quinolone with a potent antibacterial activity and a low toxicity. The lung concentration of unchanged HSR-903 was about nine times higher than that in plasma after oral administration (5 mg/kg) in rats. In comparative studies, HSR-903 was accumulated more efficiently than levofloxacin, ciprofloxacin, and lomefloxacin in rat lung. To clarify the mechanism of the specific distribution of HSR-903 into the lung, the uptake of [14C]HSR-903 was studied using isolated rat lung cells and an isolated rat lung perfusion technique. Initial uptake of HSR-903 by isolated lung cells was temperature dependent, saturable, stereospecific, and Na+ and Cl- dependent. The Hill coefficients (1. 90 for Na+ and 1.13 for Cl-) suggest that two Na+ and one Cl- are associated with the transport of one HSR-903 molecule. The uptake of HSR-903 was inhibited by other quinolone antibacterial agents, grepafloxacin, and sparfloxacin. The extraction ratio of HSR-903 in isolated lung perfusion was temperature dependent and saturable. These findings suggest that HSR-903 is taken up by the lung cells via a carrier-mediated transport mechanism, resulting in a concentrative distribution into the lung.  (+info)

Activation of a cGMP-stimulated cAMP phosphodiesterase by protein kinase C in a liver Golgi-endosomal fraction. (4/2071)

The ability of Ca2+/phospholipid-dependent protein kinase (protein kinase C, PKC) to stimulate cAMP phosphodiesterase (PDE) activity in a liver Golgi-endosomal (GE) fraction was examined in vivo and in a cell-free system. Injection into rats of 4 beta-phorbol 12-myristate 13-acetate, a known activator of PKC, caused a rapid and marked increase in PKC activity (+325% at 10 min) in the GE fraction, along with an increase in the abundance of the PKC alpha-isoform as seen on Western immunoblots. Concurrently, 4 beta-phorbol 12-myristate 13-acetate treatment caused a time-dependent increase in cAMP PDE activity in the GE fraction (96% at 30 min). Addition of the catalytic subunit of protein kinase A (PKA) to GE fractions from control and 4 beta-phorbol 12-myristate 13-acetate-treated rats led to a comparable increase (130-150%) in PDE activity, suggesting that PKA is probably not involved in the in-vivo effect of 4 beta-phorbol 12-myristate 13-acetate. In contrast, addition of purified PKC increased (twofold) PDE activity in GE fractions from control rats but affected only slightly the activity in GE fractions from 4 beta-phorbol 12-myristate 13-acetate-treated rats. About 50% of the Triton-X-100-solubilized cAMP PDE activity in the GE fraction was immunoprecipitated with an anti-PDE3 antibody. On DEAE-Sephacel chromatography, three peaks of PDE were sequentially eluted: one early peak, which was stimulated by cGMP and inhibited by erythro-9 (2-hydroxy-3-nonyl) adenine (EHNA); a selective inhibitor of type 2 PDEs; and two retarded peaks of activity, which were potently inhibited by cGMP and cilostamide, an inhibitor of type 3 PDEs. Further characterization of peak I by HPLC resolved a major peak which was activated (threefold) by 5 microM cGMP and inhibited (87%) by 25 microM EHNA, and a minor peak which was insensitive to EHNA and cilostamide. 4 beta-Phorbol 12-myristate 13-acetate treatment caused a selective increase (2.5-fold) in the activity associated with DEAE-Sephacel peak I, without changing the K(m) value. These results suggest that PKC selectively activates a PDE2, cGMP-stimulated isoform in the GE fraction.  (+info)

A mutation in QRDR in the ParC subunit of topoisomerase IV was responsible for fluoroquinolone resistance in clinical isolates of Streptococcus pneumoniae. (5/2071)

Forty-one strains of Streptococcus pneumoniae were isolated at Seoul National University Children's Hospital from 1991 to 1997. Isolates were divided into six groups based on MICs of three quinolones, ciprofloxacin, ofloxacin and norfloxacin. Sequencing showed that the isolates which were intermediately resistant to three quinolones or resistant to at least one kind of quinolone had one missense mutation, Lys137-->Asn(AAG-->AAT) substitution in the ParC subunit of topoisomerase IV without additional mutation in QRDR of the GyrA subunit of DNA gyrase. In conclusion, the ParC subunit of DNA topoisomerase IV is the primary target site for fluoroquinolone in S. pneumoniae and Lys137-->Asn substitution renders the quinolone resistance in S. pneumoniae.  (+info)

Inflammatory pseudotumor in a cat with cutaneous mycobacteriosis. (6/2071)

A 5-year-old, castrated male, domestic Shorthair Cat had an ulcerated mass with fistulous tracts on the left hind paw. Homogeneous tan tissue diffusely infiltrated the dermis and subcutis of the paw and extended proximally so that, short of amputation, complete excision was not feasible. Biopsy specimens consisted of granulation tissue with marked proliferation of spindle cells. Neutrophils and histiocytic cells were scattered among the spindle cells. The histiocytic cells had abundant foamy or vacuolated cytoplasm, but features of granulomatous inflammation, such as epithelioid macrophages or granuloma formation, were not observed. The initial impression was inflammatory granulation tissue, but the degree of fibroplasia prompted inclusion of fibrosarcoma in the differential diagnosis. Cutaneous mycobacteriosis was diagnosed when numerous acid-fast bacteria were identified with Kinyoun's stain; Mycobacterium avium was subsequently cultured. The cat was euthanatized because of lack of response to enrofloxacin therapy. At necropsy, lesions were localized to the hind limb. Not only is mycobacteriosis an uncommon cause of cutaneous masses in cats, but this case was unusual because of the lack of granuloma formation and the similarity of the mass to a spindle cell tumor.  (+info)

Indomethacin-induced gastric antral damage in hamsters: are neutrophils involved? (7/2071)

BACKGROUND: A direct role for neutrophils in the pathophysiology of indomethacin-induced gastric damage is controversial. Therefore, such damage was evaluated in hamsters. METHODS: Gastric antral damage was evaluated 4 h after the oro-gastric administration of indomethacin (30 mg/kg). Prior to indomethacin, hamsters were treated with various pharmacological agents: rebamipide, methotrexate or anti-neutrophil serum (ANS). The number of circulating neutrophils was determined from Wright-Giemsa stained blood smears. Myeloperoxidase (MPO) activity was measured as a marker of gastric antral neutrophil infiltration. RESULTS: Indomethacin caused primarily gastric antral damage. By histology, this damage did not penetrate the muscularis mucosa. A significant increase in gastric antral MPO activity was also found in indomethacin-treated hamsters. Rebamipide decreased macroscopic gastric antral damage in a dose-related fashion. Methotrexate treatment reduced the circulating blood neutrophil number by 38-44%, but did not affect gastric damage. ANS treatment resulted in near complete neutropenia, and also in a substantial reduction (84%) in gastric antral MPO activity. However, gastric antral damage was not significantly altered by ANS. CONCLUSIONS: Neutrophils are not directly involved in the pathophysiology of indomethacin-induced damage to the hamster gastric antrum.  (+info)

Pharmacodynamic effects of subinhibitory concentrations of rufloxacin on bacterial virulence factors. (8/2071)

It has been reported that subinhibitory concentrations (sub-MICs) of some fluoroquinolones are still capable of affecting the topological characteristics of DNA (inhibition DNA-gyrase) and that this leads to a reduction in some of the factors responsible for bacterial virulence (by means of the disruption of protein synthesis and alterations in phenotype expression), even though the microorganisms themselves are not killed. The present study investigated the ability of sub-MICs of rufloxacin, an orally absorbed monofluorinated quinolone with a long half-life (28 to 30 h), to interfere with the bacterial virulence parameters of adhesiveness, hemagglutination, hydrophobicity, motility, and filamentation, as well as their interactions with host neutrophilic defenses such as phagocytosis, killing, and oxidative bursts. It was observed that Escherichia coli adhesiveness was significantly reduced at rufloxacin concentrations of 1/32 MIC, hemagglutination and hydrophobicity were significantly reduced at concentrations of, respectively, 1/4 MIC and 1/8 MIC, and motility was significantly reduced at concentrations of 1/16 MIC; filamentation was still present at concentrations of 1/4 MIC. Phagocytosis was not affected, but killing significantly increased from 1/2 MIC to 1/8 MIC; oxidative bursts measured by means of chemiluminescence were not affected. The fact that sub-MICs are still effective in interfering with the parameters of bacterial virulence is useful information that needs to be correlated with pharmacokinetic data in order to extend our knowledge of the most effective concentrations that can be used to optimize treatment schedules, for example, single administrations, particularly in noncomplicated lower urinary tract infections.  (+info)

  • PMQR determinants represent an unrecognized threat, capable to compromise the in vitro activity of quinolones if expressed in a favourable genetic environment and to favour selection of resistant mutants by widening the mutant selection window of these agents. (microbiologyresearch.org)
  • The study proved that second generation quinolones, such as enrofloxacin, significantly change the phase of depolarization and repolarization of the ventricles, at the same time increasing the risk of ventricular arrythmia. (edu.pl)
  • Arayne MS, Sultana N, Ali SN (2013) Spectrophotometric Determination of Quinolones by Charge Transfer Complexation with Chloranilic Acid: Synthesis and Characterization. (omicsonline.org)
  • Tendon damage occur within 48 hours of starting treatment with a quinolone but onset of signs and symptoms of adverse effects may be delayed several months after stopping treatment. (mims.co.uk)
  • Tendon damage (especially to the Achilles tendon but also other tendons) can occur within 48 hours of starting quinolone treatment. (mims.co.uk)
  • The results suggest that a prolonged administration of quinolones can increase the risk of arrhythmias. (edu.pl)
  • A simple and sensitive spectrophotometric method has been described for the assay of quinolones in bulk drug and in pharmaceutical formulations . (omicsonline.org)
  • Quinolones should also be prescribed with special caution in patients at increased risk of tendon injury, including those over 60 years of age and those with renal impairment or solid organ transplants. (mims.co.uk)
  • There was an increase in the QTc and the TpTe interval in the group treated with quinolones. (edu.pl)
  • We show that the endochin-like quinolone (ELQ) class of compounds contains extremely potent inhibitors of T. gondii growth in vitro and is effective against acute and latent toxoplasmosis in mice. (pnas.org)
  • Following on from the finding that the complex of quinolone and gyrase on DNA results in truncated mRNAs in vitro, the results presented in this thesis show that in vivo, the addition of quinolone drugs results in the production of truncated mRNAs which are presumably translated into truncated proteins. (bl.uk)
  • Evaluates the in vitro activity of seven quinolones against non-glucose fermenting Gram-negative bacilli isolated from clinical specimens of cancer patients. (ebscohost.com)
  • The in vitro activity of eight antimicrobial agents, including four quinolones, against 108 strains of enteropathogens was determined. (eurekamag.com)
  • Recent publications report in vitro activity of quinolone 3-esters against the bc1 protein complex of Plasmodium falciparum and the parasite. (unl.pt)
  • In the next section, Pharmacology, the intricate field of quinolone pharmacokinetics (PK) and pharmacodynamics (PD) is evaluated. (cdc.gov)
  • Aortic ruptures or aneurysms in patients taking quinolones was increased by 66% over those taking amoxicillin within that most at-risk 60-day time period mentioned above. (regenexx.com)
  • Structural development, haematological immunological and pharmacological effects of quinolones. (nih.gov)
  • The thrust of this review is on the structural development, pharmacological, haematological and immunological effects of quinolones. (nih.gov)
  • Effects of Quinolones on the Immune System, p 467-473. (asmscience.org)
  • étudier la sensibilité des souches d' E. coli aux β-lactamines et quinolones. (ajol.info)
  • Multiclass method for the determination of quinolones and β-lactams, in raw cow milk using dispersive liquid-liquid microextraction and ultra high performance liquid chromatography-tandem mass spectrometry. (sigmaaldrich.com)
  • Simultaneously, systemic quinolone therapy rose from 28 percent in 1998 to over 56 percent in 2002. (managedcaremag.com)
  • The MHRA advises prescribers that systemic quinolones can very rarely cause long-lasting (up to months or years), disabling, and potentially irreversible adverse reactions, sometimes affecting multiple systems, organ classes and senses. (mims.co.uk)
  • Garenoxacin is a novel quinolone that does not have a fluorine substituent at the C-6 position in the quinoline ring. (aspetjournals.org)
  • Reporting susceptibilities to various quinolones provides the information necessary to choose an appropriate therapy that will minimize the selection of mutations leading to resistance. (cdc.gov)
  • Liquid formulations of various quinolones for PO or parenteral administration usually contain freely soluble salts in stable aqueous solutions. (merckvetmanual.com)
  • The present invention is directed to a lyophilized preparation which contains a synthetic quinolone antibacterial compound and, as a solo additive, a pH-adjusting agent, and which exhibits an excellent reconstituting property. (patents.com)
  • The invention provides a method for producing a lyophilized preparation containing a synthetic quinolone antibacterial compound as an active ingredient, characterized by including, sequentially, cooling an aqueous solution containing a synthetic quinolone antibacterial compound and a pH-adjusting agent to yield a frozen product, elevating the temperature of the frozen product, and re-cooling the resultant to prepare the lyophilized preparation. (patents.com)