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Frequency of patch-test positivity in patients with psoriasis: a prospective controlled study.

Current information on the incidence of patch-test positivity and the spectrum of allergens in psoriatics is conflicting. We compared the rates of patch-test positivity to common allergens and topical medicaments in 200 patients suffering from chronic plaque psoriasis (group I) with 51 patients with other non-allergic skin complaints (group II) and 54 patients suspected of having allergic contact dermatitis (group III). Positive patch-test results to one or more allergens were detected in 21.6% of patients in group I, 23.5% in group II and 50.0% in group III. Psoriatics with > or = 5 years old disease had a higher rate of patch-test positivity than those with shorter disease duration (p<0.01). The site of lesions showed no correlation with patch-test positivity. The commonest allergens showing positivity in group I were dithranol (6.5%), nickel (6%), fragrance mix (5%), neomycin (2%) and nitrofurazone (2%). In spite of the comparable rates of patch-test positivity in psoriatics and general dermatology outpatients, the predominance of sensitivity to topical medicaments and fragrance in the former group was striking. A separate psoriasis series focusing on topical agents may give more accurate information on this subject.

Adult↗

Analysis of veterinary drug residues in fish and shrimp composites collected during the Canadian Total Diet Study, 1993-2004.

Thirty shrimp, marine fish, freshwater fish, and canned fish composite samples collected and prepared as part of the Canadian Total Diet Study were analysed for 39 different veterinary drug residues. The analyses were undertaken to obtain baseline data that could be used to estimate the dietary exposure of Canadians to these residues. The most frequently observed residue was AOZ (four out of 30 samples), the metabolite of furazolidone, at a range of 0.50 to 2.0 ng g(-1) wet weight. Other residues detected included enrofloxacin (three samples; 0.3-0.73 ng g(-1)), leucomalachite green (three samples; 0.73-1.2 ng g(-1)), oxolinic acid (two samples; 0.3-4.3 ng g(-1)), AMOZ (the metabolite of furaltadone; one sample; 0.40 ng g(-1)), chloramphenicol (one sample; 0.40 ng g(-1)), and SEM (the metabolite of nitrofurazone; one sample; 0.8 ng g(-1)). The results of this survey indicate that Canadians are exposed to low ng g-1 concentrations of some banned and unapproved veterinary drug residues via the consumption of certain fish and shrimp.

Animals↗

Evaluation of the antimicrobial efficacy of urinary catheters impregnated with antiseptics in an in vitro urinary tract model.

OBJECTIVES: To evaluate the long-term efficacy of urinary Foley catheters (latex and silicone) impregnated with (1) chlorhexidine and silver sulfadiazine (CXS) and (2) chlorhexidine, silver sulfadiazine, and triclosan (CXST) in inhibiting extra-luminal bacterial adherence and to compare their efficacy with that of silver hydrogel latex (SH) and nitrofurazone-treated silicone (NF) catheters. DESIGN: The antimicrobial spectrum of these catheters was evaluated using a zone of inhibition assay. A novel in vitro urinary tract model was developed to study the potential in vivo efficacy of antimicrobial catheters in preventing extraluminal bacterial colonization. The "meatus" was inoculated daily with Staphylococcus aureus, Staphylococcus epidermidis, Escherichia coli, Enterococcus faecalis, Pseudomonas aerginosa, and Candida albicans. The "bladder" portion of the model was cultured daily to determine bacterial growth. RESULTS: Both CXS and CXST catheters had a broader antimicrobial spectrum than SH and NF catheters. In the in vitro model, CXST latex and silicone catheters exhibited significantly better efficacy (3 to 25days) against uropathogens, compared with CXS (1 to 14 days) and control (0 to 5 days) catheters (P = .01). CXST latex catheters exhibited significantly longer protection against Staphylococcus aureus, Staphylococcus epidermidis, Escherichia coli, and Pseudomonas aeruginosa, compared with SH catheters (P = .01). CXST silicone catheters resisted colonization with Staphylococcus aureus and Staphylococcus epidermidis for a significantly longer period (23 to 24 days) than did NF catheters (9 to 11 days) (P = .01). CONCLUSION: Catheters impregnated with synergistic combinations of chlorhexidine, silver sulfadiazine, and triclosan exhibited broad-spectrum, long-term resistance against microbial colonization on their outer surfaces.

Anti-Infective Agents, Urinary↗

The effectiveness of processed grapefruit-seed extract as an antibacterial agent: I. An in vitro agar assay.

OBJECTIVES: Grapefruit-seed extract (GSE) Citricidal has, in recent reports, been reported to be successful in combating a variety of common infectious agents. In our study, drops of concentrated grapefruit-seed extract were tested for antibacterial properties against a number of gram-positive and gram-negative organisms. DESIGN: Sixty-seven (67) distinct biotypes were tested for their susceptibilities to the GSE as well as to 5 other topical antibacterials (Silvadene, Sulfamylon, Bactroban, Nitrofurazone, and Silvadene, Nystatin). Wells were punched into Mueller-Hinton agar plates, which were then inoculated with the organism to be tested; each well was then inoculated with one of the antibacterial agents. After an overnight incubation period, the plates were checked for zones of bacterial susceptibility around the individual wells, with a measured susceptibility zone diameter of 10 mm or more considered a positive result. RESULTS: The GSE was consistently antibacterial against all of the biotypes tested, with susceptibility zone diameters equal to or greater than 15 mm in each case. CONCLUSIONS: Our preliminary data thus suggest an antibacterial characteristic to GSE that is comparable to that of proven topical antibacterials. Although the GSE appeared to have a somewhat greater inhibitory effect on gram-positive organisms than on gram-negative organisms, its comparative effectiveness against a wide range of bacterial biotypes is significant.

Anti-Bacterial Agents↗

The evaluation of wound-healing potential of Hypericum hookerianum leaf and stem extracts.

OBJECTIVES: Hypericum hookerianum Wight and Arnott of the family Hypericaceae is a well-known plant among the 20 different species of Hypericum found in India. Because of its use as a wound-healing agent in traditional practices and literature references, the present study was undertaken to evaluate the wound-healing potential of this plant. DESIGN: Methanol extracts of the leaves (HHLM) and stems (HHSM) of H. hookerianum were studied for their wound-healing properties in the form of ointment, using two types of wound models in 36 rats. Ointments of the dried extract of the leaves and stems of this plant were applied in two different concentrations (5% w/w and 10% w/w ointment of extracts in simple ointment base) in both the wound models used in the present study. The effects were studied on incision (skin-breaking strength) and excision (percent wound contraction and epithelialization time) wound models. SUBJECT: The methanol extract of both leaves and stem of H. hookerianum; 72 white albino rats of either gender containing six groups for each experimental model with six animals in each group. RESULTS AND CONCLUSION: The extract ointments at both concentrations performed significant in both the wound models. The leaf extract in both concentrations showed greater activity than the stem. Ointments of both extracts of H. hookerianum showed significant effects on wound contraction, wound closure time, tensile strength, regeneration of tissues at the wound site, among other effects. All these effects were comparable to those of a standard drug, nitrofurazone ointment (0.2% w/w). This investigation confirms the use of aerial parts of H. hookerianum as a potential wound-healing agent, a property known from folklore medicine.

Animals↗

Transferable nitrofuran resistance conferred by R-plasmids in clinical isolates of Escherichia coli.

A high proportion of nitrofuran-resistant strains has been found in a collection of antibiotic-resistant Gram-negative bacteria isolated from patients with urinary tract infections. Some of the Escherichia coli carried R-plasmids that conferred resistance to nitrofurantoin and nitrofurazone. The mechanism of resistance is not clear; only in lactose non-fermenting recipients was there a decrease in the nitrofuran-reducing ability of whole-cell suspensions. One of the plasmids conferred enhanced resistance to UV light on DNA repair defective mutants but not on repair efficient strains. In some resistant strains, the total resistance was apparently the result of a combination of chromosomal and plasmid-borne genes. The presence of the plasmid may allow the development of higher resistance levels by mutation of chromosomal genes.

Drug Resistance, Microbial↗

Bactericidal activity of nitrofurans against growing and dormant Mycobacterium bovis BCG.

Depletion of oxygen triggers the shift-down of Mycobacterium bovis BCG to a state of dormancy. Bacilli in their dormant state are resistant to standard anti-mycobacterials. The nitroimidazole metronidazole was the first compound identified to show bactericidal activity against dormant tubercle bacilli. In contrast to metronidazole's selective toxicity for dormant bacilli, we report here that the nitrofurans nitrofurantoin, furaltadone and nitrofurazone showed bactericidal activity against dormant and growing bacteria. Importantly, the bactericidal effect of nitrofurans on dormant bacilli was 35- to 250-fold higher compared with metronidazole.

Anti-Bacterial Agents↗

Comparative genotoxic evaluation of 2-furylethylenes and 5-nitrofurans by using the comet assay in TK6 cells.

The genotoxicity of three 2-furylethylene derivatives and four 5-nitrofurans was evaluated by using the comet assay in human lymphoblastoid cultured TK6 cells. The 2-furylethylene derivatives were 2-furyl-1-nitroethene, 1-(5-bromofur-2-yl)-2-nitroethene and 1-(5-bromofur-2-yl)-2-bromo-2-nitroethene, while the 5-nitrofurans were nitrofurantoin, nitrofurazone, furazolidone and 5-nitro-2-furanacrolein. The treatments lasted for 3 h in the absence of metabolic activation. No genotoxic effects were observed for two of the 2-furylethylene compounds, while the derivative 1-(5-bromofur-2-yl)-2-nitroethene showed a statistically significant response mainly at the highest concentration tested; this effect was considered biologically relevant and the compound was classified as slightly genotoxic. On the other hand, for the classical 5-nitrofurans tested there is a tendency towards a dose-related increase of the DNA damage in the comet assay and the observed increases for the parameters analysed (Olive tail moment, tail % DNA and tail length) were significant for all compounds. Then, the four 5-nitrofurans tested were considered genotoxic. These results show that the position of the nitro group influences the genotoxicity of the assayed compounds. Thus, in this comet assay, the 2-furylethylene derivatives having the nitro group attached outside the furan ring appear to be much less genotoxic than the 5-nitrofurans.

Cell Line, Tumor↗

Nitrocompound activation by cell-free extracts of nitroreductase-proficient Salmonella typhimurium strains.

A characterization of nitrocompounds activation by cell-free extracts (CFE) of wild-type (AB(+)), SnrA deficient (B(+)), Cnr deficient (A(+)) and SnrA/Cnr deficient (AB(-)) Salmonella typhimurium strains has been done. The Ames mutagenicity test (S. typhimurium his(+) reversion assay) was used, as well as nitroreductase (NR) activity determinations where the decrease in absorbance generated by nitrofurantoin (NFN) reduction and NADP(H) oxidation in the presence of NFN, nitrofurazone (NFZ), metronidazole (MTZ) and 4-nitroquinoline-1-oxide (4NQO) were followed. Different aromatic and heterocyclic compounds were tested for mutagenic activation: 2-nitrofluorene (2-NF); 2,7-dinitrofluorene (2,7-DNF); 1-nitropyrene (1-NP), 1,3-dinitropyrene (1,3-DNP); 1,6-dinitropyrene (1,6-DNP); and 1,8-dinitropyrene (1,8-DNP). Differential mutagenicity was found with individual cell free extracts, being higher when the wild type or Cnr containing extract was used; nevertheless, depending on the nitrocompound, activation was found when either NR, SnrA or Cnr, were present. In addition, all nitrocompounds were more mutagenic after metabolic activation by CFE of NR proficient strains, although AB(-) extract still showed activation capacity. On the other hand, NR activity was predominantly catalyzed by wild type CFE followed by A(+), B(+) and AB(-) extracts in that order. We can conclude that results from the Ames test indicate that Cnr is the major NR, while NFN and NFZ reductions were predominantly catalyzed by SnrA. The characterization of the residual NR activity detected by the mutagenicity assay and the biochemical determinations in the AB(-) CFE needs further investigation.

Biotransformation↗

Studies on oxygen-insensitive nitrofuran reductase in Escherichia coli B/r.

Oxygen-insensitive nitrofuran reductase in Escherichia coli B/r was clearly resolved by DEAE-cellulose column chromatography into two components, one NADPH-linked, and the other both NADPH- and NADH-linked. It is known that the strain requires resistance to nitrofurazone in two mutational steps. It is known that the the first step mutants had no NADPH-linked component and the second step ones had neither this component nor the NAD(P)-H-linked one. The NADPH- and NADH-linked activities of the latter component were similarly inactivated by heat or urea treatment. In addition, it was found that these activities were significantly inhibited by dicoumarol, an NAD(P)H dehydrogenase inhibitor, to similar extents. These results suggest that the activities of the NAD(P)H-linked component originate from a single enzyme. On the other hand, the NADPH-linked component was less sensitive to heat, urea and dicoumarol.

Cell-Free System↗

Susceptibility testing of topical antibacterials against methicillin-resistant Staphylococcus aureus.

Methicillin-resistant Staphylococcus aureus (MRSA) isolates that were collected from 44 consecutive patients during 1 year in a community hospital were tested for susceptibility to five commonly used topical antibacterial agents. Agar-well susceptibility testing, which was based on zones of inhibition, was used to compare the effectiveness of the antibacterials against MRSA. Nitrofurazone was effective in inhibition of bacterial growth and was relatively inexpensive. Mupirocin was found to be effective but more costly for treatment of MRSA. Varying degrees of susceptibility to silver sulfadiazine, mafenide acetate, and bacitracin were noted in the cultures that were obtained at this medical center. On the basis of our findings from susceptibility tests compared with those of another center, we recommend that all hospitals undertake topical sensitivity testing of their MRSA isolates. Appropriate and effective topical antibacterial therapy can then be planned within each center.

Anti-Infective Agents, Local↗

A clinical study of antimicrobial agents delivered to burn wounds from a drug-loaded synthetic dressing.

This report is of an investigation of the release of antimicrobial agents from a solid barrier dressing when applied to second- and third-degree burn wounds. The synthetic dressings were formed by a mixture of polyethylene glycol-400 (PEG), poly-2-hydroxethyl methacrylate (PHEMA) and one of the test drugs: silver sulfadiazine (AgSD), gentamicin, silver nitrate, or nitrofurazone. The dressings were formed directly on the burn wounds of 33 patients from a paste prepared from a mixture of PEG-PHEMA and drug. These dressings remained in place for 3 days, covering 12 to 64 square inches of the wound. In six patients, the entire burn wounds were covered with the dressings in which the treated areas were each about 200 square inches. The use of drug-loaded synthetic dressings extended to cover major portions of the burn wounds reduced the work required for nursing care and lessened patient discomfort.

Adolescent↗

An alternative dressing material for the split-thickness skin graft donor site: oxidized regenerated cellulose.

The split-thickness skin graft (STSG) donor sites have been treated with various and plenty of dressing techniques and materials. An ideal STSG donor site dressing should have antibacterial, hemostatic, and promoting epidermal healing properties. We have performed a prospective study to evaluate the effect of the oxidized regenerated cellulose on STSG donor site healing. Between January 2002 and January 2005, 40 patients who were operated in any kind of reconstructive operations with STSG donor sites were included in the study. One half of the wound was covered with oxidized regenerated cellulose and the other half of the same wound of the same patient was covered with fine mesh gauze treated with Furacin (nitrofurazone). The patients were grouped into 2 depending on the dressing technique: group I, semiclosed and group II, closed. The wounds were evaluated for healing time, infection, pain perception of the patient, and final esthetic results. The oxidized regenerated cellulose side of the group I was healed in a mean of 6.5 +/- 0.51 days; in group II, 5.4 +/- 0.50 days (range, 5-6 days). The fine mesh gauze treated with Furacin in group I was healed in a mean of 9.9 +/- 0.97 days (range, 8-11 days); in group II, 8.4 +/- 0.99 days (range, 7-10 days). There was a statistical significance between the oxidized regenerated cellulose side and the fine mesh gauze side (P < 0.001) in group I and group II separately. The difference between group I and group II was statistically significant in the oxidized regenerated cellulose side (P < 0.001), and the difference between group I and group II was statistically significant in the fine mesh gauze side (P < 0.005). The antibacterial, hemostatic, and absorbable property of the oxidized regenerated cellulose could ensure the utilization as an alternative STSG donor site dressing, especially because the positive influence over the wound healing was proven.

Absorption↗

Characterization of a dam mutant of Haemophilus influenzae Rd.

The gene encoding Dam methyltransferase of Haemophilus influenzae was mutagenized by the insertion of a chloramphenicol-resistance cassette into the middle of the Dam coding sequence. This mutant construct was introduced into the H. influenzae chromosome by transformation and selection for Cam(R) transformants. The authors have shown that several phenotypic properties, resistance to antibiotics, dyes and detergent as well as efficiency of transformation, depend on the Dam methylation state of the DNA. Although the major role of the methyl-directed mismatch repair (MMR) system is to repair postreplicative errors, it seems that in H. influenzae its effect is more apparent in repairing DNA damage caused by oxidative compounds. In the dam mutant treated with hydrogen peroxide, MMR is not targeted to newly replicated DNA strands and therefore mismatches are converted into single- and double-strand DNA breaks. This is shown by the increased peroxide sensitivity of the dam mutant and the finding that the sensitivity can be suppressed by a mutH mutation inactivating MMR. In the dam mutant treated with nitrofurazone the resulting damage is not converted into DNA breaks but the high sensitivity is also suppressed by a mutH mutation.

Anti-Bacterial Agents↗

Role of contact allergens in pompholyx.

Fifty patients of both sexes with clinically suspected pompholyx were patch tested with the Indian Standard Patch Test Battery approved by the Contact & Occupational Dermatosis Forum of India (CODFI). Most of these patients were young adults between 20-39 years of age with a mean age of 30 years. The mean duration of symptoms was 4 years. The occupational profile of the patients included students (20%), housewives (16%), housewives engaged in farming (12%), labourers (12%), farmers (12%) and paramedical workers (6%). The miscellaneous group, including salesmen, teachers and photographers, accounted for the remaining 22%. The clinical patterns of presentation of pompholyx included cheiropompholyx (60%), cheiropompholyx and podopompholyx (36%) and podopompholyx alone (4%). Patch test analysis of these patients revealed that, out of the 50 subjects tested, 20 (40%) reacted to one or more allergens. Nickel sulphate was the commonest offending allergen (14%) followed by potassium dichromate and phenylene diamine and nitrofurazone (8% each), fragrance mix (6%) and cobalt chloride (4%), in descending order of frequency. Hence, patch testing may be considered for all patients with recurrent episodes of pompholyx as allergic contact dermatitis may be relatively common in such patients and the avoidance of offending allergens may be of substantial benefit to these patients.

Adolescent↗

Phenotype of recombinant Leishmania donovani and Trypanosoma cruzi which over-express trypanothione reductase. Sensitivity towards agents that are thought to induce oxidative stress.

Trypanothione reductase is thought to be important in maintaining an intracellular reducing environment in trypanosomatids. To investigate the role of trypanothione reductase we transfected Leishmania donovani and Trypanosoma cruzi with an expression vector containing the L. donovani trypanothione reductase gene and achieved over-expression of enzyme activity (10-14-fold) in transformed cells. Following treatment of L. donovani cells with the thiol-oxidizing agent diamide, the ability to regenerate dihydrotrypanothione from trypanothione disulphide was considerably enhanced in cells which over-expressed trypanothione reductase. However, the growth of transformed and control cells was equally sensitive to inhibition by nifurtimox, nitrofurazone and gentian violet, drugs that are thought to act by inducing oxidative damage. Likewise, growth of transformed and control cells were equally susceptible to inhibition by hydrogen peroxide, and control and transformed L. donovani promastigotes metabolized hydrogen peroxide at comparable rates. Thus, these experiments suggest that the ability to regenerate dihydrotrypanothione from trypanothione disulphide is not a rate-limiting step in the metabolism of hydrogen peroxide.

Animals↗

Contact allergy to furazolidone.

A case of occupational contact allergy to furazolidone, used as an animal feed additive and as an antimicrobial drug in veterinary medicine, is described. The patient did not react to furazolidone 2% pet. Using PEG-400 and alcohol as patch test vehicles resulted in positive patch test reactions. No cross-reactions were observed to other nitrofuran derivatives (nitrofurazone, nitrofurantoin) or to furfural. The literature on contact allergy to nitrofurans is reviewed.

Adult↗