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Merbromin (mercurochrome)--a photosensitizer for singlet oxygen reactions.

Merbromin, produced in many countries and used world wide as an antiseptic under the trademark "mercurochrome", is shown to be an efficient sensitizer for type II (singlet oxygen) photo-oxygenations by using 2-methyl-2-butene, (+)-limonene, (+)-alpha-pinene, alpha,alpha'-dimethylstilbenes and (--)-L-methionine as oxygen acceptors. Type I photo-oxygenations are negligible. An estimate of the quantum yield of singlet oxygen formation by merbromin in methanol gives a value of about 0.1.

Cyclohexenes↗

Spectrophotometric determination of some fluoroquinolone antibacterials by binary complex formation with xanthene dyes.

Two simple, rapid and sensitive spectrophotometric methods for the determination of levofloxacin, norfloxacin and ciprofloxacin have been performed in pure form, pharmaceutical tablets and spiked human urine. Both methods are based on the formation of a binary complex between the drugs and one of the two xanthene dyes, eosin Y or merbromin in aqueous buffered medium. Under the optimum conditions, the binary complexes showed absorption maxima at 547 nm for eosin Y and 545 nm for merbromin. Using eosin Y, the calibration graph was linear over the range 2-8 microg ml(-1) for the three drugs with mean percentage recoveries 99.935 +/- 0.648, 99.973 +/- 0.678 and 100.011 +/- 0.606 for levofloxacin, norfloxacin and ciprofloxacin, respectively. While in case of merbromin, the concentration range was 2-15 microg ml(-1) with mean percentage recoveries 99.960 +/- 0.491, 100.017 +/- 0.510 and 99.980 +/- 0.506 for the three drugs, respectively. The proposed methods were successfully applied to determine these drugs in their tablet formulations and spiked human urine and the results compared favorably to that of reference methods. The suggested methods have the advantage of being applicable for the determination of the three drugs without prior extraction. They are recommended for quality control and routine analysis where time, cost effectiveness and high specificity of analytical techniques are of great importance.

Anti-Infective Agents↗

Mercury and organomercurial resistances determined by plasmids in Pseudomonas.

Mercury and organomercurial resistance determined by genes on ten Pseudomonas aeruginosa plasmids and one Pseudomonas putida plasmid have been studied with regard to the range of substrates and the range of inducers. The plasmidless strains were sensitive to growth inhibition by Hg(2+) and did not volatilize Hg(0) from Hg(2+). A strain with plasmid RP1 (which does not confer resistance to Hg(2+)) similarly did not volatilize mercury. All 10 plasmids determine mercury resistance by way of an inducible enzyme system. Hg(2+) was reduced to Hg(0), which is insoluble in water and rapidly volatilizes from the growth medium. Plasmids pMG1, pMG2, R26, R933, R93-1, and pVS1 in P. aeruginosa and MER in P. putida conferred resistance to and the ability to volatilize mercury from Hg(2+), but strains with these plasmids were sensitive to and could not volatilize mercury from the organomercurials methylmercury, ethylmercury, phenylmercury, and thimerosal. These plasmids, in addition, conferred resistance to the organomercurials merbromin, p-hydroxymercuribenzoate, and fluorescein mercuric acetate. The other plasmids, FP2, R38, R3108, and pVS2, determined resistance to and decomposition of a range of organomercurials, including methylmercury, ethylmercury, phenylmercury, and thimerosal. These plasmids also conferred resistance to the organomercurials merbromin, p-hydroxymercuribenzoate, and fluorescein mercuric acetate by a mechanism not involving degradation. In all cases, organomercurial decomposition and mercury volatilization were induced by exposure to Hg(2+) or organomercurials. The plasmids differed in the relative efficacy of inducers. Hg(2+) resistance with strains that are organomercurial sensitive appeared to be induced preferentially by Hg(2+) and only poorly by organomercurials to which the cells are sensitive. However, the organomercurials p-hydroxymercuribenzoate, merbromin, and fluorescein mercuric acetate were strong gratuitous inducers but not substrates for the Hg(2+) volatilization system. With strains resistant to phenylmercury and thimerosal, these organomercurials were both inducers and substrates.

Chemical Phenomena↗

Elimination of mercury, cadmium and antibiotic resistance from Acinetobacter lwoffi and Micrococcus sp. at high temperature.

Resistance determinants for HgCl2 and CdCl2 were eliminated along with a number of antibiotic resistance factors from Acinetobacter lwoffi and Micrococcus sp. at 44 degrees C. These organisms were orginally resistant to HgCl2, merbromin, CdCl2, Pb(NO3)2, benzylpenicillin, erythromycin, carbenicillin, tetracycline and sulfadiazine. Four different types of mutants from A. lwoffi (type I to IV) and one type of mutant from Micrococcus sp. (type V) were obtained, depending on the loss of particular resistance factors for HgCl2, merbromin, CdCl2 and antibiotics. In general, frequency of elimination of all the missing markers was very low (in the range of 10(-3) per bacterium). However, the missing determinants did not revert spontaneously.

Acinetobacter↗

Allergic contact dermatitis from mercury antiseptics and derivatives: study protocol of tolerance to intramuscular injections of thimerosal.

BACKGROUND: Mercury derivatives are frequent contact allergens and their cross-reactivity is not constant. Thimerosal is an organic mercurial used as an antiseptic and as a preservative in most vaccines. OBJECTIVE: To evaluate cross-reactivity, exposure factors, and tolerance to vaccines containing thimerosal in patients sensitized to mercury derivatives. METHODS DESIGN: Observational study (cross-sectional); PATIENTS: 125 patients were recruited for the study, 72 women and girls and 53 boys and men, average age 18.7 years old, range 3 to 65, with positive patch tests to mercury derivatives and/or thimerosal; INTERVENTIONS: All patients were studied by means of enquiry, patch tests, intradermal tests, and intramuscular challenge with thimerosal. RESULTS: A sensitization to thimerosal was observed in 57 patients. Twenty-four of these 125 patients presented a positive intradermal reaction. Ammoniated mercury seems to be a good marker of mercury sensitization eliciting positive reaction in 78% of all patients and merbromin in 66%. In most cases, (100/125) cross-reactivity was found among mercury derivatives. The intramuscular injection of thimerosal induced a mild local reaction in only 5 patients (4% of the total, 9% of thimerosal positive reactions). Childhood vaccinations, merbromin used as an antiseptic, broken thermometers, and the use of drops were the main sources of exposure. CONCLUSIONS: The majority of the patients showed positive tests to both organic and inorganic mercury derivatives. Vaccination with thimerosal is relatively safe, even for individuals with delayed type hypersensitivity to this chemical, since more than 90% of allergic patients tolerated intramuscular challenge tests with thimerosal. A simplified protocol of patch tests to study mercury derivatives is proposed. It would be advisable to restrict the use of mercurial antiseptics and mercury thermometers.

Adolescent↗

Hypersensitivity to Hg2+ and hyperbinding activity associated with cloned fragments of the mercurial resistance operon of plasmid NR1.

The region of plasmid NR1 concerned with resistance to Hg2+ and organomercurials consists of sequences found on restriction endonuclease fragments EcoRI-H and EcoRI-I. When both fragments were cloned together into a derivative of plasmid ColE1, the hybrid plasmid conferred properties indistinguishable from those of the parental plasmid, NR1: resistance to Hg2+ and to the organomercurials merbromin and fluoresceinmercuric acetate and the inducible synthesis of the enzyme mercuric reductase. When fragment EcoRI-I was cloned into plasmid ColE1, cells containing the plasmid was as sensitive to Hg2+ and organomercurials as plasmidless strains. When fragment EcoRI-H was cloned into ColE1, cells with the hybrid plasmid were hypersensitive to Hg2+ and organomercurials. This hypersensitivity was inducible by prior exposure to low, subtoxic Hg2+ or merbromin levels. It was associated with an inducible hyperbinding activity attributed to a gene governing Hg2+ uptake and found on fragment EcoRI-H (which contains the proximal portion of a mercuric resistance [mer] operon).

Cloning, Molecular↗

Inhibition profiling of human carbonic anhydrase II by high-throughput screening of structurally diverse, biologically active compounds.

Human carbonic anhydrase II (CA II), a zinc metalloenzyme, was screened against 960 structurally diverse, biologically active small molecules. The assay monitored CA II esterase activity against the substrate 4-nitrophenyl acetate in a format allowing high-throughput screening. The assay proved to be robust and reproducible with a hit rate of approximately 2%. Potential hits were further characterized by determining their IC(50) and K(d) values and tested for nonspecific, promiscuous inhibition. Three known sulfonamide CA inhibitors were identified: acetazolamide, methazolamide, and celecoxib. Other hits were also found, including diuretics and antibiotics not previously identified as CA inhibitors, for example, furosemide and halazone. These results confirm that many sulfonamide drugs have CA inhibitory properties but also that not all sulfonamides are CA inhibitors. Thus many, but not all, sulfonamide drugs appear to interact with CA II and may target other CA isozymes. The screen also yielded several novel classes of nonsulfonamide inhibitors, including merbromin, thioxolone, and tannic acid. Although these compounds may function by some nonspecific mechanism (merbromin and tannic acid), at least 1 (thioxolone) appears to represent a genuine CA inhibitor. Thus, this study yielded a number of potentially new classes of CA inhibitors and preliminary experiments to characterize their mechanism of action.

Carbonic Anhydrase II↗

Susceptibility to mercurials of clinical Pseudomonas aeruginosa isolated in México.

Susceptibility to inorganic mercuric ions and to organomercurials of 237 Pseudomonas aeruginosa clinical strains isolated in Mexico was determined by agar dilution tests. Resistant strains fell into two classes: i) narrow-spectrum resistant strains (27% of total isolates) resistant only to mercuric ions and to merbromin, and most grouped in pyocin type 1; and ii) broad-spectrum resistant strains (5%) with additional resistances to thimerosal, phenylmercury, methylmercury and p-hydroxymercuribenzoate, that belonged mostly to pyocin type 10. Mercurial resistant isolates showed a higher proportion of resistance to antibiotics and metals than did mercurial sensitive isolates, and broad-spectrum resistant strains had the highest frequency of resistance to antibiotics and to tellurite and arsenate.

Humans↗

Allergic contact dermatitis and mercury exanthem due to mercury chloride in plastic boots.

We report a 5-year-old child with previous skin intolerance from Mercurochrome (merbromin), who developed a severe allergic contact dermatitis of both feet when wearing new polyvinyl chloride (PVC) boots. Within a few days, he developed a mercury exanthem involving both legs, groins and lateral parts of the trunk. Patch tests showed strong reactions to organic and inorganic mercury compounds, in particular to mercury chloride (mercury chloride; HgCl2), 0.01% pet., which was identified by atomic absorption spectrometry and polarography in the boots worn. New hidden sources of mercury in consumer goods may represent a potential source of danger for the future, if its use is not more strictly regulated.

Anti-Infective Agents, Local↗

Mycobacterium chelonei iatrogenic infections.

We report on two outbreaks of Mycobacterium chelonei subsp. abscessus cutaneous infections, which occurred between June 1974 and April 1975 in a series of 24 patients (15 studied bacteriologically) subjected to venous stripping for varicose veins. The source of infection was the aqueous solution of merbromin used in presurgical care.

Drug Contamination↗