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This paper discusses the use of nitrofurazone in the treatment, or prophylaxis, of wound infection, various pyodermas and second and third degree burns, as well as its prophylactic use in skin grafting and donor sites. The literature is reviewed over three decades.
ipa-43d is a hypothetical gene identified by the Bacillus subtilis genome project (Mol. Microbiol. 10, 371-384 1993; Nature 390, 249-256 1997). The ipa-43d protein overexpressed in E. coli was purified to homogeneity and its properties were analyzed biochemically. The ipa-43d protein was found to be tightly associated with FMN and to be capable of reducing both nitrofurazone and FMN effectively. Although the ipa-43d protein catalysis obeys the ping-pong Bi-Bi mechanism, catalysis mode was changed to the sequential mechanism upon coupling with the bioluminescent reaction. Database search showed that B. subtilis possessed four genes (ipa-44d, ytmO, yddN, and yvbT), encoding proteins similar in amino acid sequence to LuxA and LuxB of Photobacterium fischeri, and, in particular, ipa-44d is immediately adjacent to the ipa-43d gene on the chromosome.
Pre-mRNA maturation in trypanosomatids occurs through a process called trans-splicing which involves excision of introns and union of exons in two independent transcripts. For the first time, we present the standardization of Trypanosoma cruzi permeable cells (Y strain) as a model for trans-splicing study of mRNAs in trypanosomes, following by RNase protection reaction, which localizes the SL exon and intron. This trans-splicing reaction in vitro was also used to analyze the influence of NFOH-121, a nitrofurazone-derivative, on this mechanism. The results suggested that the prodrug affects the RNA processing in these parasites, but the trans-splicing reaction still occurred.
No fully effective treatment has been developed since the discovery of Chagas' disease by Carlos Chagas in 1909. Since drug-resistant Trypanosoma cruzi strains are occurring and the current therapy is effectiveness in the acute phase but with various adverse side effects, more studies are needed to characterize the susceptibility of T. cruzi to new drugs. Many natural and/or synthetic substances showing trypanocidal activity have been used, even though they are not likely to be turned into clinically approved drugs. Originally, drug screening was performed using natural products, with only limited knowledge of the molecular mechanism involved in the development of diseases. Trans-splicing, which is unusual RNA processing reaction and occurs in nematodes and trypanosomes, implies the processing of polycistronic transcription units into individual mRNAs; a short transcript spliced leader (SL RNA) is trans-spliced to the acceptor pre-mRNA, giving origin to the mature mRNA. In the present study, permeable cells of T. cruzi epimastigote forms (Y, BOL and NCS strains) were treated to evaluate the interference of two drugs (hydroxymethylnitrofurazone - NFOH-121 and nitrofurazone) in the trans-splicing reaction using silver-stained PAGE analysis. Both drugs induced a significant reduction in RNA processing at concentrations from 5 to 12.5 microM. These data agreed with the biological findings, since the number of parasites decreased, especially with NFOH-121. This proposed methodology allows a rapid and cost-effective screening strategy for detecting drug interference in the trans-splicing mechanism of T. cruzi.
The electrochemical behaviour of three nitrofuran compounds, nitrofurazone, nitrofurantoin and furazolidone, has been studied in three solvent types; aprotic, aqueous and mixed, and at four working electrodes. Particular attention has focused on the 1-electron RNO2/RNO2.- couple as measured by the cyclic voltammetric mode. Using Hg in aqueous buffer, reduction of the NO2 group proceeds directly to the hydroxylamine with no intermediate stages being identified. Addition of an aprotic solvent gave a 2-stage reduction, initially forming the RNO2.- species. At all solid electrodes, however, the RNO2/RNO2.- couple was identified under simple aqueous conditions. The switch to a mixed aqueous/aprotic solvent medium produced only minor changes in the response compared with the situation on Hg. This presents the opportunity of using nitrofuran complexes as model systems for the redox behaviour of nitro aromatic compounds in general at solid electrode surfaces where the latters' more negative reduction potentials makes direct study difficult. The conditions have been defined whereby we can examine pH effects and RNO2.- biological target interactions in simple aqueous media to allow the further refinement of the electrolytic model system for studying bio-reducible drug action.
Pulse radiolysis was used to establish one-electron transfer equilibria between radical cations of methyl or benzyl viologens (V2+) and nitroaryl compounds (ArNO2): a nitroimidazole (misonidazole or metronidazole), 4-nitrobenzoate or nitrofurazone. The equilibrium constants in water at pH 8 were estimated over the temperature range approximately 5 to 75 degrees C. The difference delta E in mid-point one-electron reduction potentials between the nitro compounds and the viologens varied with temperature T; increasing temperature made the nitro compounds apparently less electron-affinic compared to the effects of temperature on the viologen potential. Values of delta(delta E)/delta T were in the range -0.7 to -1.1 mV K-1 at 25 degrees C. If delta[E(V2+/V.+)]/delta T = -0.9 mV K-1 for methyl viologen then delta[E(ArNO2/ArNO2.-)]/delta T is about -2 mV K-1 for these compounds.
Topical antibiotics offer a useful alternative to oral and parenteral agents in certain conditions and have some advantages such as easy to use, lower side effects, higher drug concentrations in the infected area, lower risk of developing bacterial resistance and being economical. The goals of topical antimicrobial therapy are to control microbial colonization, thus preventing development of invasive infections, prophylaxis and treatment of wound infections, pyodermas, burn infections and acne vulgaris, and eradication of Staphylococcus aureus nasal carriage. Topical antibiotics of choice include bacitracin, neomycin, polymyxin B, mupirocin, nitrofurazone and fusidic acid. In this review article, the characteristics and clinical uses of topical antimicrobials have been summarized.
A zebrafish larval rearing system experienced a surge in mortality rates soon after the introduction of new stocks. A comprehensive water analysis of pH, nitrites, nitrates, ammonia, chlorine, carbonate hardness, general hardness, and conductivity identified no anomalies. Observations via light microscopy of affected fry revealed consistent signs of impaired mobility, blood clotting, and eventual heart hemorrhage resulting in the death of 90 to 100% of the fry by the age of 2 weeks. Collection of sufficient tissue samples for a histological investigation proved problematic due to the fry's diminutive size. Because a causal agent could not be isolated satisfactorily, the use of a broad-spectrum antibiotic was deemed necessary. After considering many broad-spectrum antibiotics for treatment, we implemented a two-tiered approach for treatment. The rearing system was treated with a nitrofurazone derivative, whereas the adult populations were treated using multi-antibiotic food pellets. The rearing system was treated for 3 weeks, and the adult population was treated for 2 weeks. After the completion of the antibiotic treatments, the biological filters of all of the medicated systems were seeded with nitrifying bacterial cultures. Upon the maturation of the rearing systems' biological filters, mortality rates returned to pre-outbreak levels. There have been no re-occurrences of the fish mortality since the completion of treatment. This epidemic provided some valuable lessons, lessons that if followed, will ensure faster response to unknown pathogens in the future.
Comparative study of the microbicidal activity of some traditional (hydrogen peroxide, boric acid, nitrofurazone) and currently available (Baliz-2, dioxidine, chlorhexidine bigluconate, pervomur) antiseptics against the most commonly encountered causative agents of purulent surgical infection showed 0.8%, 1.2%, and 2.4% pervomur solutions to possess the highest bactericidal and sporicidal activity. This circumstance allowed weak (0.8 and 1.2%) solutions of pervomur to be used in the clinic in 68 patients for the management of purulent postoperative complications and localized purulent infection, which improved the results of treatment significantly.
The authors presented the results of treatment of 115 patients with infection-dependent bronchial asthma. The most noticeable effect was observed in the patients on combined therapy including impulse irrigation of the bronchi (during sparing fibrobronchoscopy) with intal and heparin solutions as compared to the controls receiving this procedure with heparin solution (without intal) and a group of patients who had received intal inhalation by a routine method. A positive therapeutic effect was observed earlier in the patients receiving therapeutic bronchofibroscopy with heparin solution than in patients whose combined therapy included bronchoscopic sanation with nitrofurazone solution. The efficacy of the use of impulse irrigation of the bronchi (in sparing fibrobronchoscopy) with intal and heparin solutions in infection-dependent bronchial asthma was emphasized by the authors.
Eight horses ranging in age from 4 days to 9 years were treated for peritonitis. Escherichia coli was isolated in four cases and Nocardia sp in one case. In each case, a catheter placed in the peritoneal cavity allowed drainage of a large amount of purulent fluid. Retrograde peritoneal lavage was performed through a Foley catheter or medical tubing, using Ringer's lactate solution containing kanamycin, povidone iodine, or nitrofurazone. All except two horses responded well to repeated lavage.
Lipoamide dehydrogenase from Mycobacterium smegmatis was purified to homogeneity over 60-fold. Of 20 amino acid residues identified at the amino terminus of the enzyme, 18 and 17 were identical to the sequences of Mycobacterium leprae and Pseudomonas fluorescens lipoamide dehydrogenases, respectively. The visible spectrum of the isolated enzyme was characteristic of a flavin in apolar environment. Reduction of the enzyme with dithionite results in the appearance of an absorbance shoulder at 530-550 nm, suggesting that reducing equivalents of the two-electron reduced enzyme reside predominantly on the redox-active disulfidedithiol. The kinetic mechanism of the forward (NAD+ reducing) and reverse (NADH oxidizing) reactions proved difficult to study due to severe substrate inhibition by NAD+ and NADH. The rate of lipoamide reduction was found to depend upon the NAD+/NADH ratio, with the reaction being activated at low ratios and inhibited at high ratios. The use of 3-acetylpyridine adenine dinucleotide allowed initial velocity kinetics to be performed and revealed that the kinetic mechanism is ping pong. In addition to catalyzing the reversible oxidation of dihydrolipoamide, the enzyme displayed high oxidase activity (30% of the lipoamide reduction rate), hydrogen and t-butyl peroxide reductase activity (10% of the lipoamide reduction rate), and both naphthoquinone and benzoquinone reduction (approximately 200% of the lipoamide reduction rate). The enzyme failed to catalyze the redox cycling of nitrocompounds, but could anaerobically reduce nitrofurazone. The lipoamide-reducing reaction was reversibly inactivated by sodium arsenite, but no decrease in diaphorase activity was observed under these conditions.
Previous work has demonstrated that hydrazine after formylation to its corresponding hydrazone may be activated both in vivo and in vitro to a methylating intermediate resulting in the formation of O6-methyl- and N7-methylguanines in DNA. Incubation of calf thymus DNA with the hydrazine derivative, hydralazine, and formaldehyde resulted in the production of N7-methylguanine and two aberrant bases in DNA. These bases were separated by strong cation-exchange high-performance liquid chromatographic fractionation of neutral thermal hydrolysates. Administration of hydralazine to rats resulted in the formation of N7-methylguanine in liver DNA, but the two unknown bases observed in the in vitro experiment could not be demonstrated in vivo. In contrast to hydrazine, administration of hydralazine resulted in the methylation of DNA only at doses approaching the LD50, suggesting that formylation does not represent a significant mechanism for hydralazine toxicity in the system described. Hydralazine in combination with formaldehyde resulted in the formation of triazolophthalazine, a metabolite which has been characterized in man. The ability of 17 other hydrazine derivatives to alkylate liver DNA was determined after single administration to young adult male Sprague-Dawley rats or C57BL6 mice. Quantifiable amounts of N7-methylguanine were measured in liver DNA from animals treated with 10 of the 17 compounds. In 3 of the 10 cases quantifiable amounts of O6-methylguanine were also measured. Methylation of liver DNA guanine was obtained with hydrazine, hydralazine, procarbazine, isoniazid, phenylhydrazine, nialamide, nitrofurazone, maleic hydrazide, sulfomethoxypyridazine, and sulfamethiazole and two hydrazine-formaldehyde polymerization products, formalazine and tetraformyltrisazine.
Using ABP as an index of Sertoli cell secretory function, several important features of the Sertoli cell have emerged: 1. The stimulation of ABP production by FSH clearly points to the Sertoli cell as a target cell for FSH (3,4,9-16,21,24). 2. The dramatic effects of androgens on ABP production both in immature and mature rats also suggest that the Sertoli cell is a target cell for androgen (3,12,14,16,25). 3. The striking reduction in ABP production in the cryptorchid testis raises the question whether impairment of Sertoli cell function is the primary reason for the loss of germ cells that occurs in this condition (20). 4. Drugs like nitrofurazone or ethionine, or X-irradiation only slightly affect the secretory function of the Sertoli cells (ABP production), indicating that these treatments most probably have direct effects on the germ cells as well. Thus, measurement of ABP production rate is a very important tool in order to evaluate how hormones, drugs and physical injuries might affect the secretory function of the Sertoli cell. This test system might be of great use in order to study the physiology and hormonal regulation of the Sertoli cells. It might also be valuable in pharmacological and toxicological studies.
Procedures have been developed which enable the study of antimutagenic specificity of certain antimutagenic chemicals against chemical mutagens/carcinogens. Modifications of the Ames Salmonella assay, the Bacillis subtilis rec assay of Kada and co-workers, and the Luria-Delbrück fluctuation test, along with procedures we have developed utilizing E. coli K12 strain ND160 developed by Dworkin, all are employed in these studies. Using these procedures, a number of naturally-occurring compounds and/or their derivatives have been shown to produce antimutagenic specificity either against changes at different specific genetic loci or against activity of specific chemical mutagens such as nitrofurazone, ethyl methanesulfonate, or caffeine. Compounds that demonstrate this activity include cinnamaldehyde, chlorophyllin, an extract of Glycyrrhiza glabra, spermine, and mixtures of guanosine and cytidine. The data demonstrate that some antimutagens act specifically against spontaneous mutations, while others inhibit the development of chemically-induced mutations at specific loci. These results have potential application to the prevention of chemical toxicological damage.
Recent carcinogenicity studies conducted and evaluated by the National Toxicology Program/National Institute of Environmental Health Sciences were examined to determine the frequency of chemically increased incidences of neoplasia. Many of the chemicals originally selected for study were chosen because of an a priori suggestion that they might be carcinogens. Of the 143 chemical studies evaluated, usually involving male and female rats and mice, 42 (29%) did not induce any neoplasms, 20 (14%) gave marginal or equivocal neoplastic responses, and 81 (57%) showed positive neoplastic responses in one or more of the 524 species-gender experiments. Of these 81 positive studies, 60 (74%) were considered positive based on malignant neoplasia, 16 (20%) were positive due primarily to benign neoplasia, but had supporting evidence of malignant neoplasia in the same organ/tissue, and 5 (6%) were positive based only on benign neoplasia. These five chemicals are a) allyl isothiocyanate (transitional cell papillomas of the urinary bladder in male rats), b) 2-amino-4-nitrophenol (tubular cell adenomas of the kidney in male rats), c) asbestos intermediate range chrysotile (adenomatous polyps of the large intestine in male rats), d) decabromodiphenyl oxide (neoplastic nodules of the liver in male and female rats), and e) nitrofurazone (fibroadenomas of the mammary gland in female rats and benign mixed tumors and granulosa cell tumors of the ovary in female mice). For all but one of these lesions (mammary gland), the occurrence in historic controls is low. Thus, only 5 of the 143 chemicals studied (3.5%) induced benign neoplasia alone, and those observed benign neoplasms are known to progress to malignancy. Accordingly, we consider chemically induced benign neoplasia to be an important indicator of a chemical's carcinogenic potential in rodents, and believe it should continue to be made an integral part of the overall weight-of-the-evidence evaluation process for identifying potential human health hazards.
Nitrofurans and dinitrocarbanilide are extracted from food according to the multiresidue method and detected by Reversed-phase-HPLC with UV-detection at 360 nm. Records of the UV-spectra confirm the results qualitatively. Possibilities for further confirmation are discussed. Substances in amounts below 0.01 mg/kg can only be determined with particular care. Statistical confirmation of this method and possible problems are mentioned. An interlaboratory collaborative study confirmed the method: furazolidone, furaltadone, nitrofurazone, nitrofurantoin, and nicarbazin (the dinitrocarbanilide containing component) were added to homogenized eggs in amounts of 0.005-0.150 mg/kg. The procedure can be standardized as an official analytical method at a detection limit of 0.005 mg/kg for nitrofurans and 0.01 mg/kg for nicarbazin.
Enzymically activated nitrofurazone reacts with co-valently closed circular DNA (derived from Escherichia coli minicells carrying lambdadv) to give at least two kinds of damage: breaks which are detected on neutral sucrose gradients and alkali-labile lesions in DNA which are converted to breaks when the DNA is subsequently Treated with alkali. DNA, isolated from nimicells exposed to the drug, also contains lesions which are converted to breaks upon treatment with endonuclease preparations obtained from Micrococcus luteus. Minicells repaired both breaks and nuclease-susceptible lesions within 2 h but did not repair alkali labile lesions within that time. Experiments with three other nitrofurans show that there are considerable differences in the degree to which DNA is damaged by activated metabolites of various derivatives and that the potency of the compounds as mutagens and carcinogens is correlated with the amount of damage caused to minicell DNA.