The uptake and incorporation of purines by wild-type Saccharomyces cerevisiae and a mutant resistant to 4-aminopyrazolo (3,4-d) pyrimidine.
Explore the source record for details and available documents.
Adenine↗
SEARCH · Search PubMed
Results for “Aza Compounds”
Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.
Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.
Interaction of AZA analogs of chlorpromazine with the dopamine D2 receptor.
1. Permanently charged AZA analogs of chlorpromazine inhibited the binding of [3H]spiperone and antagonized the apomorphine-induced inhibition of the potassium evoked release of [3H]acetylcholine. 2. The AZA analogs were more potent in binding affinity and antagonist activity than the trimethylammonium analog of chlorpromazine but less potent than chlorpromazine. 3. These results suggest that it is possible to enhance the binding of the permanently charged trimethylammonium analog of chlorpromazine by the addition of a functional group near the quaternary nitrogen which is capable of forming a hydrogen bond with the D2 dopamine receptor. 4. However, it appears that for optimal binding, as achieved with chlorpromazine, the hydrogen-bonding proton should be on the charged nitrogen.
Acetylcholine↗
The action of seven convulsants as antagonists of the GABA response of Limulus neurons.
Explore the source record for details and available documents.
Animals↗
Gaschromatographic determination of polycyclic aromatic hydrocarbons, aza-arenes, aromatic amines in the particle and vapor phase of mainstream and sidestream smoke of cigarettes.
The present arrangement collects particles and semivolatiles of main- and sidestream smoke and allows a recovery of the trapped substances nearly quantitatively and without impurities. The fractionation procedure allows to separate various groups of carcinogens such as PAH, aza-arenes and aromatic amines for analytical and biological studies. Sidestream smoke contains ten times more polycyclic aromatic hydrocarbons (PAH) compared with mainstream smoke. This holds also true for aza-arenes and amines. PAH of the gaseous phases include only 1% of the particle-bound PAH.
Aerosols↗
Rapid purification of immunoglobulin G using aza-arenophilic chromatography: novel mode of protein-solid phase interactions.
A derivative of aza-arenophilic gel having a dichlorosubstituent and an hydroxy ion as a capping nucleophile has been prepared. The properties of this gel in relation to IgG purification have been investigated in details. In the presence of high salt (1.5 M), albumin and some other serum proteins did not bind to the gel. IgG and some other minor proteins, however, were bound to the gel. The bound proteins can be eluted with an acidic buffer. SDS-PAGE showed that the fraction eluted with 0.1 M sodium acetate pH 4.2 consisted mainly of IgGs.
Animals↗
Quantitative analysis of bencynonate in human plasma using a deuterated internal standard by gas chromatography-mass spectrometry with selected-ion monitoring.
A gas chromatographic-mass spectrometric method is described for the quantitative analysis of bencynonate in human plasma. Deuterated bencynonate served as the internal standard and selected-ion monitoring of the fragments of bencynonate and internal standard permitted the quantitation of bencynonate down to 25 pg/ml of plasma. The assay is linear for plasma bencynonate concentrations in the range 25 pg/ml-3 ng/ml. At 0.25 ng/ml the recovery and coefficient of variation are 54.3% and 19.1%, respectively. Application of the method to clinical studies gave data for the pharmacokinetics and relative bioavailability of bencynonate in man.
Animals↗
A bifunctional ligand for Pd(II).
A bifunctional ligand, 6-(5-carboxyl pentyl)-5,7 dioxo-1,4,8, 11-tetraazaundecane, has been shown to produce a neutral, inert complex with Pd(II). The complex is formed in high yield and is stable over a wide pH range. It can be conjugated to proteins through the carboxylic acid side arm using a carbodiimide coupling reagent and may be useful for labeling antibodies or other large molecules.
Aza Compounds↗
The clinical development of a 5 alpha-reductase inhibitor, finasteride.
Finasteride, a 4-aza steroid compound, is an orally active inhibitor of the 5 alpha-reductase enzyme. 5 alpha-Reductase is necessary for the metabolism of testosterone (T) to dihydrotestosterone (DHT) and is found in high levels only in certain tissues such as the prostate. Finasteride has been shown to markedly suppress serum DHT levels in man without lowering testosterone levels. In patients with benign prostate hyperplasia (BPH), finasteride was found to decrease prostate volume by a mean of 28% over a period of 6 months, without causing clinically significant adverse effects. DHT appears to be the primary androgen for prostatic growth. Selective inhibition of 5 alpha-reductase by finasteride may provide a novel approach to BPH therapy by reducing prostate size without affecting T-dependent processes such as fertility, muscle strength, and libido. The clinical development of finasteride for the treatment of benign prostate hyperplasia is reviewed.
5-alpha Reductase Inhibitors↗
Topical prophylaxis with moxifloxacin prevents endophthalmitis in a rabbit model.
PURPOSE: The prophylaxis potential of the topical antibiotic, 0.5% moxifloxacin (Vigamox), was evaluated to prevent endophthalmitis after bacterial anterior chamber challenge in a rabbit model. DESIGN: An in vivo laboratory investigation. METHODS: Three regimens of topical 0.5% moxifloxacin were tested for prophylaxis to prevent endophthalmitis: (1) (full prophylaxis) moxifloxacin drops every 15 minutes for 1 hour (five drops), anterior chamber challenge with 5 x 10(4) colony-forming units of Staphylococcus aureus, one drop of moxifloxacin, and four more drops applied over the next 24 hours; (2) (preprophylaxis) prechallenge prophylaxis, S. aureus challenge, and no postchallenge prophylaxis; and (3) (postprophylaxis) no prechallenge prophylaxis, S. aureus challenge, and postchallenge prophylaxis. A saline control was tested concurrently in all three experiments. At 24 hours after injection, the eyes were evaluated by slit lamp in a masked fashion for clinical signs of endophthalmitis, and the anterior and posterior chambers were cultured for bacteria. RESULTS: The median clinical scores for the moxifloxacin group were significantly lower than the saline group for all three treatment regimens. The median clinical score for the full prophylaxis regimen was significantly lower than the preprophylaxis and postprophylaxis regimens alone. The anterior and posterior chambers were negative for S. aureus in all three moxifloxacin treatment regimens. CONCLUSIONS: In a rabbit model, a "proof of principle" was demonstrated that topical antibiotic therapy pre- and postintraocular bacterial challenge could prevent bacterial endophthalmitis. Surgical prophylaxis with topical 0.5% moxifloxacin (Vigamox) may prove to be a valuable adjunct for the prevention of endophthalmitis.
Administration, Topical↗
The effect of cataract surgery on ocular levels of topical moxifloxacin.
PURPOSE: To investigate the effect of cataract surgery on the concentration of moxifloxacin in aqueous and vitreous humor after topical application. DESIGN: Prospective laboratory intervention using a rabbit model. METHODS: Following topical administration of 0.5% moxifloxacin, 60 minutes before surgery and immediately post cataract surgery, aqueous and vitreous humor were sampled at 30, 60, and 120 minutes postsurgery. Moxifloxacin concentrations were determined by high-pressure liquid chromatography (HPLC). Mean tissue concentrations obtained in surgical eyes were compared with concentrations obtained in nonsurgical eyes. The potential effectiveness of moxifloxacin in providing prophylaxis against intracameral bacterial inoculation was investigated by comparing antibiotic concentrations to minimum inhibitory concentration (median MIC90) values for Staphylococcus aureus and Staphylococcus epidermidis. RESULTS: In surgical eyes, mean moxifloxacin concentrations in aqueous were 13.9, 16.2, and 12.2 microg/ml versus 25.3, 32.6, and 15.7 microg/ml in nonoperated eyes at 30, 60, and 120 minutes, respectively. No statistically significant differences were found between surgical and nonsurgical eyes. In surgical eyes, mean moxifloxacin concentrations in vitreous were 66.8, 66.6, and 400.2 ng/ml versus 43.1, 199.8, and 54.4 ng/ml in nonoperated eyes at 30, 60, and 120 minutes, respectively. These differences were not statistically significant. CONCLUSIONS: There were no statistically significant differences in the penetration of topical moxifloxacin in eyes undergoing cataract surgery compared with unoperated eyes. A multiple-drop schedule of moxifloxacin produced aqueous concentrations that were well above the MICs of even resistant strains of the most common organisms implicated in postcataract surgery endophthalmitis.
Administration, Topical↗
The effect of fourth-generation fluoroquinolones gatifloxacin and moxifloxacin on epithelial healing following photorefractive keratectomy.
PURPOSE: To compare the rate of epithelial healing following photorefractive keratectomy (PRK) with two commercially available fourth-generation fluoroquinolones, gatifloxacin (Zymar, Allergan, Irvine, California) and moxifloxacin (Vigamox, Alcon Laboratories, Fort Worth, Texas). DESIGN: Double-masked, randomized, prospective trial. METHODS: Thirty-five subjects received gatifloxacin in one eye and moxifloxacin in the fellow eye following PRK with a 9.0-mm epithelial defect. Patients were examined daily after surgery until the epithelium had healed completely in both eyes. Beginning on post-operative day 3, photos were taken and used to confirm epithelial healing or measure the area of residual epithelial defects. Healing times and defect sizes were compared using the Wilcoxon signed-ranks test. RESULTS: Both eyes healed on the same day in 18 of the 35 subjects (51.4%). In 13 of 35 (37.1%) subjects, the moxifloxacin-treated eye healed first, compared with only four of 35 (11.4%) subjects whose gatifloxacin-treated eye healed first. All six of the eyes that took 2 days longer than their fellow eye to heal were gatifloxacin-treated. Median healing time for both groups was 4 days (moxifloxacin range: 3 to 7 days; gatifloxacin range: 3 to 9 days; P = .01), but only 69% of gatifloxacin-treated eyes had healed by day 4 compared with 80% of the moxifloxacin-treated eyes. Overall, on each post-operative day, defect sizes were greater for the gatifloxacin-treated eyes. This difference was statistically significant on day 4 (P = .027). CONCLUSIONS: Eyes treated with moxifloxacin healed faster and had smaller defects compared with those treated with gatifloxacin. This provides another factor to consider in selecting antibiotic prophylaxis for corneal refractive surgery.
Adult↗
Intracameral Vigamox (moxifloxacin 0.5%) is non-toxic and effective in preventing endophthalmitis in a rabbit model.
PURPOSE: To determine whether Vigamox (moxifloxacin 0.5% ophthalmic solution) can be safely injected intracamerally to prevent Staphylococcus aureus endophthalmitis in a rabbit model. DESIGN: Animal study. METHODS: The safety and bactericidal-effectiveness of Vigamox were evaluated in three stages using 189 New Zealand White rabbits. (Stage 1) The toxicity of two intravitreal doses of Vigamox (moxifloxacin 500, 250 microg) was compared with vancomycin (1 mg) and saline. (Stage 2) A reproducible rabbit model of Staphylococcus aureus endophthalmitis was established. (Stage 3) The bactericidal effect of intracameral Vigamox (moxifloxacin 500, 250, 125, 50 microg) was compared with vancomycin (1 mg) and saline. Intracameral antibiotic therapy commenced immediately after Staphylococcus aureus intravitreal challenge (5000 cfu). Toxicity was evaluated by masked clinical examination using a slit-lamp, an indirect ophthalmoscope, and corneal-ultrasound pachymetry. The clinical examination included the exterior eye, cornea, anterior chamber, vitreous, and retina. The presentations were graded on a severity scale of 0, 0.5, 1, 2, and 3. The bactericidal efficacy was determined using intracameral colony counts. RESULTS: In the toxicity studies without bacterial challenge, the clinical scores of rabbits injected intracamerally with Vigamox were statistically equivalent to rabbits given intracameral vancomycin or saline. In the efficacy studies, eyes treated intravitreally with Vigamox, at all doses, or vancomycin were negative for Staphylococcus aureus and nontreated controls remained culture-positive. CONCLUSIONS: Vigamox appears to be nontoxic for intracameral injection and effective in preventing experimental endophthalmitis in the rabbit model. Further studies will determine the clinical role of intracameral Vigamox for surgical prophylaxis and postoperative therapy.
Animals↗
Intracameral Vigamox (moxifloxacin 0.5%) is not effective in preventing endophthalmitis in a rabbit model.
Explore the source record for details and available documents.
Animals↗
Acute endophthalmitis in eyes treated prophylactically with gatifloxacin and moxifloxacin.
PURPOSE: To study the use of prophylactic fourth-generation fluoroquinolone antibiotics, gatifloxacin and moxifloxacin, and bacterial sensitivity in cases of acute postoperative endophthalmitis following cataract surgery. DESIGN: Retrospective, consecutive, observational case series. METHODS: Forty-two eyes of 42 patients with acute endophthalmitis occurring within six weeks after cataract surgery were identified. All patients were seen in a referral vitreoretinal practice over a two-year time interval. The number of patients using prophylactic gatifloxacin or moxifloxacin and results of bacterial culture and sensitivity to all fluoroquinolone antibiotics were recorded. RESULTS: Thirty-one of 42 eyes (74%) were treated with perioperative gatifloxacin or moxifloxacin and 24 eyes (57%) were continuously taking one of these antibiotics at the time of diagnosis. Nineteen eyes (45%) had a positive bacterial culture. The most frequent organism isolated was coagulase-negative Staphylococcus. Sensitivities were performed for 14 gram-positive organisms, and sensitivities to ciprofloxacin (50%), ofloxacin (44%), levofloxacin (46%), gatifloxacin (38%), and moxifloxacin (38%) were noted. Five organisms were resistant to gatifloxacin and moxifloxacin with a minimum inhibitory concentration of 8 microg/ml. All gram-positive organisms were sensitive to vancomycin. Median visual acuity improved from hand motions to 20/40 at last follow-up. CONCLUSION: Acute endophthalmitis can develop after cataract surgery despite the prophylactic use of fourth-generation fluoroquinolone antibiotics. Gram-positive organisms causing acute endophthalmitis are frequently resistant to all fluoroquinolones, including a significant number of cases resistant to gatifloxacin and moxifloxacin.
Acute Disease↗
The in vitro impact of moxifloxacin and gatifloxacin concentration (0.5% vs 0.3%) and the addition of benzalkonium chloride on antibacterial efficacy.
PURPOSE: Varied concentrations of moxifloxacin (MOX) and gatifloxacin (GAT) and the addition of 0.005% benzalkonium chloride (BAK) were evaluated for eliminating Staphylococcus aureus (SA), Pseudomonas aeruginosa (PA), and coagulase-negative Staphylococcus (CNS). DESIGN: In vitro laboratory investigation. METHODS: The time-kill survival of SA, PA, and CNS were tested at one, two, three, six, eight, and 24 hours to: (1) Mueller-Hinton broth, (2) BAK, (3) 0.5% MOX, (4) 0.5% GAT, (5) 0.3% MOX, (6) 0.3% GAT, (7) 0.3% GAT plus BAK, (8) 0.5% MOX plus BAK, (9) 8 microg/ml GAT, and (10) 8 mug/ml MOX. Antibiotic interactions (GAT and BAK) were determined by checkerboard testing. The outcome measures were (1) time-to-kill, (2) killing-rates, and (3) fractional inhibitory concentration (FIC) indices. RESULTS: MOX and GAT at either 0.5% or 0.3% had equivalent antibacterial effects. BAK alone or the addition of BAK to either antibiotic eliminated SA and CNS within one hour, whereas 0.3% GAT plus BAK eliminated bacteria faster than 0.5% MOX (P = .016). For PA, BAK alone had no antibacterial effect. The kill rates of MOX and GAT were equivalent. FIC indices indicated that GAT and BAK were indifferent against SA and CNS, but antagonistic to PA. CONCLUSION: As a preservative, MOX and GAT have equivalent antibacterial activity with similar killing rates. BAK appears to independently complement GAT for eliminating SA and CNS, but has no effect on PA. The in vitro predictive clinical effect due to varied antibiotic concentration and the addition of BAK requires confirmatory clinical studies for validation.
Anti-Infective Agents↗
Evaluation of vardenafil and sildenafil on cardiac repolarization.
This novel study evaluated the effects of vardenafil and sildenafil on QT and corrected QT (QTc) duration using a model that minimizes experimental error to obtain the most accurate assessment of observed QTc effects. A placebo-controlled and positive-controlled, period-balanced, double-blinded, 6-way crossover study evaluated therapeutic and supratherapeutic oral doses of vardenafil (10 and 80 mg, respectively) and sildenafil (50 and 400 mg, respectively), therapeutic doses of moxifloxacin (400 mg), and a placebo in 58 healthy men (mean age 53 years), with dosing every 3 days. Six replicate, 12-lead, digital electrocardiograms (ECGs) were recorded at 3 time points before and 5 time points after dosing to cover the time course of maximum exposure to study drugs and their metabolites. An independent laboratory blindly analyzed approximately 17,000 ECGs. For the placebo, mean change in QTcF (Fridericia) duration 1 hour after dose (approximate Tmax of vardenafil and sildenafil) was 0 ms (+/-0.7 SD). QT/QTc variability was small across regimens, indicating statistically powerful results. Moxifloxacin demonstrated an expected 8-ms mean change and was the only drug to prolong absolute QT. Placebo-corrected mean changes in QTcF duration (90% confidence interval) at 1 hour after dose were 8 ms (range 6 to 9) for vardenafil 10 mg and 6 ms (range 5 to 8) for sildenafil 50 mg. QTci (linear and nonlinear per patient) yielded similar trends: 4 ms (range 3 to 6) for vardenafil 10 mg and 4 ms (range 2 to 5) for sildenafil 50 mg. Dose response demonstrated very shallow QTc relations for study drugs. Therapeutic and supratherapeutic doses produced only small increases in the QTcF interval, which were considered to be clinically irrelevant. This well-controlled, statistically powerful study in middle-aged men demonstrated that vardenafil and sildenafil produced no increase of absolute QT and only similar, small increases of the QTc interval, with a shallow dose-response curve. The study design and conduct may serve as a guide for future QT assessment of new drugs.
3',5'-Cyclic-GMP Phosphodiesterases↗
Chemotaxis-mediated biodegradation of cyclic nitramine explosives RDX, HMX, and CL-20 by Clostridium sp. EDB2.
Cyclic nitramine explosives, RDX, HMX, and CL-20 are hydrophobic pollutants with very little aqueous solubility. In sediment and soil environments, they are often attached to solid surfaces and/or trapped in pores and distribute heterogeneously in aqueous environments. For efficient bioremediation of these explosives, the microorganism(s) must access them by chemotaxis ability. In the present study, we isolated an obligate anaerobic bacterium Clostridium sp. strain EDB2 from a marine sediment. Strain EDB2, motile with numerous peritrichous flagella, demonstrated chemotactic response towards RDX, HMX, CL-20, and NO(2)(-). The three explosives were biotransformed by strain EDB2 via N-denitration with concomitant release of NO(2)(-). Biotransformation rates of RDX, HMX, and CL-20 by the resting cells of strain EDB2 were 1.8+/-0.2, 1.1+/-0.1, and 2.6+/-0.2nmol h(-1)mgwet biomass(-1) (mean+/-SD; n=3), respectively. We found that commonly seen RDX metabolites such as TNX, methylenedinitramine, and 4-nitro-2,4-diazabutanal neither produced NO(2)(-) during reaction with strain EDB2 nor they elicited chemotaxis response in strain EDB2. The above data suggested that NO(2)(-) released from explosives during their biotransformation might have elicited chemotaxis response in the bacterium. Biodegradation and chemotactic ability of strain EDB2 renders it useful in accelerating the bioremediation of explosives under in situ conditions.
Aza Compounds↗
Nitroreductase catalyzed biotransformation of CL-20.
Previously, we reported that a salicylate 1-monooxygenase from Pseudomonas sp. ATCC 29352 biotransformed CL-20 (2,4,6,8,10,12-hexanitro-2,4,6,8,10,12-hexaaza-isowurtzitane) (C(6)H(6)N(12)O(12)) and produced a key metabolite with mol. wt. 346 Da corresponding to an empirical formula of C(6)H(6)N(10)O(8) which spontaneously decomposed in aqueous medium to produce N(2)O, NH(4)(+), and HCOOH [Appl. Environ. Microbiol. (2004)]. In the present study, we found that nitroreductase from Escherichia coli catalyzed a one-electron transfer to CL-20 to form a radical anion (CL-20(-)) which upon initial N-denitration also produced metabolite C(6)H(6)N(10)O(8). The latter was tentatively identified as 1,4,5,8-tetranitro-1,3a,4,4a,5,7a,8,8a-octahydro-diimidazo[4,5-b:4',5'-e]pyrazine [IUPAC] which decomposed spontaneously in water to produce glyoxal (OHCCHO) and formic acid (HCOOH). The rates of CL-20 biotransformation under anaerobic and aerobic conditions were 3.4+/-0.2 and 0.25+/-0.01 nmol min(-1)mg of protein(-1), respectively. The product stoichiometry showed that each reacted CL-20 molecule produced about 1.8 nitrite ions, 3.3 molecules of nitrous oxide, 1.6 molecules of formic acid, 1.0 molecule of glyoxal, and 1.3 ammonium ions. Carbon and nitrogen products gave mass-balances of 60% and 81%, respectively. A comparative study between native-, deflavo-, and reconstituted-nitroreductase showed that FMN-site was possibly involved in the biotransformation of CL-20.
Aza Compounds↗