Interactions of organic acids with vancomycin-resistant Enterococcus faecium isolated from community wastewater in Texas.

AIMS: Investigate the interactions of organic acids (OAs), acetic, butyric, citric, formic, lactic and propionic acid against 50 Gram-positive vancomycin-resistant Enterococcus faecium (VRE) strains to determine whether pH, undissociated or dissociated acid forms correlate with bacterial inhibition. METHODS AND RESULTS: Concentrations of undissociated and dissociated OAs at the molar minimum inhibitory concentrations (MICM s) of the VRE were calculated using the Henderson-Hasselbalch equation. The pH at the MICM s of all VRE strains against acetic, butyric, formic and propionic acids was similar, 4·66 ± 0·07, but there was a 1·1 pH unit difference for all six OAs. Inhibition of VRE by all six OAs did not appear to be solely dependent on pH or on the undissociated OA species. The inhibition of VRE by all six dissociated acids was within Δ = 3·1 mmol l-1 . CONCLUSIONS: Vancomycin-resistant Enterococcus faecium inhibition correlated with the dissociated OA species. A small decrease in the concentration of the dissociated OAs from optimum may result in allowing VRE strains to escape disinfection. SIGNIFICANCE AND IMPACT OF THE STUDY: When an OA is used to disinfect VRE strains, the concentration of the dissociated OA should be carefully controlled. A concentration of at least 20 mmol l-1 dissociated OA should be maintained when disinfecting VRE.

Inhibition of multidrug-resistant Staphylococci by sodium chlorate and select nitro- and medium chain fatty acid compounds.

AIMS: Determine the antimicrobial effects of 5 µmol ml-1 sodium chlorate, 9 µmol ml-1 nitroethane or 2-nitropropanol as well as lauric acid, myristic acid and the glycerol ester of lauric acid Lauricidin® , each at 5 mg ml-1 , against representative methicillin-resistant staphylococci, important mastitis- and opportunistic dermal-pathogens of humans and livestock. METHODS AND RESULTS: Three methicillin-resistant Staphylococcus aureus and two methicillin-resistant coagulase-negative staphylococci were cultured at 39°C in 5 µmol ml-1 nitrate-supplemented half-strength Brain Heart Infusion broth treated without or with the potential inhibitors. Results revealed that 2-nitropropanol was the most potent and persistent of all compounds tested, achieving 58-99% decreases in mean specific growth rates and maximum optical densities when compared with untreated controls. Growth inhibition did not persist by cultures treated solely with chlorate or nitroethane, with adaptation occurring by different mechanisms after 7 h. Adaptation did not occur in cultures co-treated with nitroethane and chlorate. The medium chain fatty acid compounds had modest effects on all the staphylococci tested except the coagulase-negative Staphylococcus epidermidis strain NKR1. CONCLUSIONS: The antimicrobial activity of nitrocompounds, chlorate and medium chain fatty acid compounds against different methicillin-resistant staphylococci varied in potency. SIGNIFICANCE AND IMPACT OF THE STUDY: Results suggest that differential antimicrobial activities exhibited by mechanistically dissimilar inhibitors against methicillin-resistant staphylococci may yield potential opportunities to combine the treatments to overcome their individual limitations and broaden their activity against other mastitis and dermal pathogens.

Characterization of antibiotic and disinfectant susceptibility profiles among Pseudomonas aeruginosa veterinary isolates recovered during 1994-2003.

AIMS: To evaluate susceptibility of Pseudomonas aeruginosa veterinary isolates to antibiotics and disinfectants. METHODS AND RESULTS: Pseudomonas aeruginosa isolates collected from dogs (n = 155) and other animals (n = 20) from sixteen states during 1994-2003 were tested for susceptibility. Most isolates were resistant to twenty-one antimicrobials tested, and the highest prevalence of resistance was to ß-lactams (93.8%) and sulphonamides (93.5%). Fluoroquinolone resistance did not increase from 1994 to 2003. Ciprofloxacin and enrofloxacin had a 5 and 16% prevalence of resistance, respectively, while sarafloxacin and nalidixic acid had a prevalence of resistance of 97 and 98%, respectively. Strains were pan-resistant to triclosan and chlorhexidine, were highly resistant to benzalkonium chloride and demonstrated high susceptibility to other disinfectants. Didecyldimethylammonium chloride was the most active ammonium chloride. Inducible resistance was observed to cetyl ammonium halides, chlorhexidine and benzyl ammonium chlorides, which formulate disinfectants used in veterinary clinics and dairies. Organic acid inhibition was associated with the dissociated acid species. CONCLUSIONS: Dissociated organic acids appear able to inhibit Ps. aeruginosa, and rates of fluoroquinolone resistance merit sustained companion animal isolate surveillance. SIGNIFICANCE AND IMPACT OF THE STUDY: This is the first report of Ps. aeruginosa susceptibility to 24 disinfectants and illustrates the high resistance of Ps. aeruginosa to both antibiotics and disinfectants.

Consensus of German transplant centers on hematopoietic stem cell transplantation in Fanconi anemia.

Allogeneic hematopoietic stem cell transplantation (HSCT) is currently the only curative therapy for the severe hematopoietic complications associated with Fanconi anemia (FA). In Germany, it is estimated that 10-15 transplants are performed annually for FA. However, because FA is a DNA repair disorder, standard conditioning regimens confer a high risk of excessive regimen-related toxicities and mortality, and reduced intensity regimens are linked with graft failure in some FA patients. Moreover, development of graft-versus-host disease is a major contributing factor for secondary solid tumors. The relative rarity of the disorder limits HSCT experience at any single center. Consensus meetings were convened to develop a national approach for HSCT in FA. This manuscript outlines current experience and knowledge about HSCT in FA and, based on this analysis, general recommendations reached at these meetings.

Isolation of more potent oncolytic paramyxovirus by bioselection.

Newcastle disease virus (NDV) is an oncolytic paramyxovirus with a nonsegmented single-stranded RNA genome. In this report, a recombinant oncolytic NDV was passaged in human tumor xenografts and reisolated and characterized after two rounds of bioselection. Several isolates could be recovered that differed from the parental virus with respect to virus spread in tumor cells and the ability to form syncytia in human tumor cells. Three isolates were identified that demonstrated superior oncolytic potency compared with the parental virus as measured by increased oncolytic potency in confluent tumor cell monolayers, in tumor cell spheroids and in a mouse xenograft tumor model. The surface proteins F and HN were sequence analyzed and characterized for fusogenicity. The present study demonstrates that in vivo NDV bioselection can enable the isolation of novel, oncolytic NDV and thus represents a powerful methodology for the development of highly potent oncolytic viruses.

Prediction of outcome by early response in childhood acute lymphoblastic leukemia.

BACKGROUND: In the ALL-BFM studies for treatment of acute lymphoblastic leukemia, reduction of leukemic blasts in peripheral blood after a one-week prednisone pre-phase - the so-called prednisone response - has been used for risk stratification since the 1980s and has been one of the most relevant factors for identification of high-risk patients. In the trial ALL-BFM 95, early cytomorphological marrow response on day 15 of induction therapy was prospectively evaluated and its prognostic value was analyzed in comparison to the prednisone response and other established prognostic factors. RESULTS: Compared to prednisone response, day 15 marrow response was superior in outcome prediction - yet with differential effect depending on blast lineage. Outcome was poor in T cell leukemia patients with prednisone poor-response independent of day 15 marrow response, whereas among patients with prednisone good-response different risk groups could be identified by day 15 marrow response. In contrast, prednisone response lost prognostic significance in precursor B cell leukemia when stratified by day 15 marrow response. CONCLUSIONS: Selective addition of day 15 marrow response to conventional stratification criteria applied on ALL-BFM 95 may significantly improve risk-adapted treatment delivery. Even though cutting-edge trial risk stratification is meanwhile dominated by minimal residual disease evaluation, an improved conventional risk assessment, as presented here, could be of great importance to countries lacking the technical and/or financial resources associated with the application of minimal residual disease analysis.

Key treatment questions in childhood acute lymphoblastic leukemia: results in 5 consecutive trials performed by the ALL-BFM study group from 1981 to 2000.

Between 1981 and 2000, 6 609 children (<18 years of age) were treated in 5 consecutive trials of the Berlin-Frankfurt-Münster (BFM) study group for childhood acute lymphoblastic leukemia (ALL). Patients were treated in up to 82 centers in Germany, Austria, and Switzerland. Probability of 10-year event-free survival (survival) improved from 65% (77%) in study ALL-BFM 81-78% (85%) in ALL-BFM 95. In parallel to relapse reduction, major efforts focused on reducing acute and late toxicity through advanced risk adaptation of treatment. The major findings derived from these ALL-BFM trials were as follows: 1) preventive cranial radiotherapy could be safely reduced to 12 Gy in T-ALL and high-risk ALL patients and eliminated in non-high-risk non-T-ALL patients, if it was replaced by high-dose and intrathecal methotrexate; 2) omission of delayed reintensification severely impaired outcome of low-risk patients; 3) 6 months less maintenance therapy caused an increase in systemic relapses; 4) slow response to an initial 7-day prednisone window was identified as adverse prognostic factor; 5) condensed induction therapy resulted in a significant improvement of outcome; 6) the daunorubicin dose in induction could be safely reduced in low-risk patients; 7) intensification of consolidation/reintensification treatment led to considerable improvement of outcome in high-risk patients.

Transient gut retention and persistence of Salmonella through metamorphosis in the lesser mealworm, Alphitobius diaperinus (Coleoptera: Tenebrionidae).

AIMS: This study was undertaken to determine the retention of Salmonella through Alphitobius diaperinus metamorphosis and its contribution, through defecation, to external contamination. METHODS AND RESULTS: Insects were exposed to a tagged Salmonella enterica and evaluated for external elimination. (i) Each day for 3 weeks, a filter collected frass from a restrained insect for analysis. (ii) Exposed larvae in a closed container were followed through pupation, and newly emerged adults were examined for their retention of marker bacteria. CONCLUSIONS: Exposed adults and larvae produced Salmonella-positive frass for an average of 8 days, ranging from 6 to 11 days and 6 to 12 days, respectively. Nineteen per cent of the larvae carried Salmonella through metamorphosis and eclosion, with 5% of the pupal exuviae being positive as well. SIGNIFICANCE AND IMPACT OF THE STUDY: Many sources of foodborne pathogens within the poultry production facilities, including reservoir populations, currently go unrecognized. This diminishes the ability of producers to mitigate the transfer of pathogens between animals, humans and the environment. Poultry management standards accept the reutilization of litter. Alphitobius diaperinus survive between flock rotations on the reutilized litter, and it was demonstrated in this study that the Salmonella they carry can survive with them.

Metabolic detoxification: mechanism of insect resistance to plant psoralens.

Larvae of the black swallowtail butterfly, Papilio polyxenes Stoll, forage successfully on plants that contain high levels of photosensitizing psoralens. These insects rapidly detoxify psoralens, particularly in the midgut tissue prior to absorption, with the result that appreciable levels of unmetabolized phototoxin do not enter the body circulation where deleterious light-induced interactions with dermal or subdermal tissues would occur.

Generation of a recombinant oncolytic Newcastle disease virus and expression of a full IgG antibody from two transgenes.

The most advanced oncolytic Newcastle disease virus (NDV) strains that are used in clinical trials for the treatment of cancer are wild-type mesogenic strains. These virus strains have an inherent, nongenetically engineered, oncolytic activity and selectively replicate in tumor cells but not in normal human cells. To date no investigations have been performed with genetically engineered mesogenic NDV regarding the oncolytic activity. We describe here the generation of recombinant viruses of the mesogenic naturally oncolytic NDV strain MTH68. We show that not only one, but also two additional transgenes coding for amino-acid chains with a molecular weight of 25 and 50 kDa can be inserted into the viral genome without affecting viral growth, oncolytic potency or tumor-selective replication of the virus. Transgenic expression of the heavy and light chains of a monoclonal antibody, as separate additional transcriptional cassettes, leads to the expression of full immunoglobulin G (IgG) monoclonal antibody by recombinant NDV. Infection of tumor cells with antibody-transgenic viruses results in the efficient production and secretion of a functional full size IgG antibody by the tumor cells, that specifically binds to its target-antigen in tumor tissue. This approach will allow to combine the advantages of oncolytic RNA viruses and monoclonal antibodies in a single powerful anticancer agent with improved or even new therapeutic properties.

The horizontal transfer of Salmonella between the lesser mealworm (Alphitobius diaperinus) and poultry manure.

There is need to determine the nature of enduring reservoirs of Salmonella contributing to perpetual contamination within poultry flocks. The dispersal of Salmonella between birds, litter and the lesser mealworm has been established, but the extent that these act as critical components in the epidemiology of Salmonella infection during broiler grow-out and flock rotation has not been delineated; in particular, the level of participation by the lesser mealworm beetles (LMB) as agents of retention and dispersal. This study defines this route of transmission and provides empirical data on bacterial loads that facilitate Salmonella transfer. Results showed differential Salmonella transfer dependent on bacterial concentration. At 103  cfu/ml, only a small, but not significant, amount of Salmonella was transferred, from the LMB to the manure and back to uninfected LMB; while from 105 to 107  cfu/ml, a significant acquisition and transfer occurred both internally and externally to the LMB over 4 and 24 hr exposures. These data will be used in correlation with facility management practices to develop intervention strategies to mitigate the establishment and spreading of reservoir Salmonella populations contributing to pre-harvest contamination of poultry flocks.

Transferability of antimicrobial resistance from multidrug-resistant Escherichia coli isolated from cattle in the USA to E. coli and Salmonella Newport recipients.

OBJECTIVES: This study aimed to evaluate conjugative transfer of cephalosporin resistance among 100 strains of multidrug-resistant Escherichia coli (MDRE) to Salmonella enterica serotype Newport and E. coli DH5α recipients. METHODS: Phenotypic and genotypic profiles were determined for MDRE as well as for Salmonella Newport (trSN) and E. coli DH5α (trDH) transconjugants. RESULTS: Of 95 MDRE donor isolates, 26 (27%) and 27 (28%) transferred resistance to trSN and trDH recipients, respectively. A total of 27 MDRE (27%) were confirmed as extended-spectrum ß-lactamase (ESBL)-producers based on the double-disk synergy assay and whole-genome sequencing (WGS). WGS was performed on 25 of the ESBL-producing isolates, showing that 2 isolates carried blaCTX-M-6, 22 possessed blaCTX-M-32 and 1 was negative for blaCTX-M genes. Fourteen of the ESBLs sequenced were qnrB19. Differential transfer of IncA/C and IncN from MDRE32 was observed between trSN32 and trDH32. IncN-positive trDH32 displayed an ESBL phenotype, whereas IncA/C-positive trSN32 displayed an AmpC phenotype. The rate of ESBL transfer to trSN and trDH recipients was 11% and 96%, respectively. CONCLUSIONS: Twenty-seven MDRE were phenotypically identified as ESBL-producers. WGS of 25 MDRE revealed that 2 and 22 isolates carried blaCTX-M-6 and blaCTX-M-32, respectively. One multidrug-resistant isolate exhibited conversion from an AmpC phenotype to an ESBL phenotype with the transfer of only the IncN plasmid. The rate of resistance transfer to Salmonella or E. coli recipients was nearly identical. However, the ESBL phenotype was transferred with significantly greater prevalence to E. coli compared with Salmonella Newport (96% and 11%, respectively).

In Vitro Effects of Thymol-ß-D-Glucopyranoside on Salmonella enterica Serovar Typhimurium and Escherichia coli K88.

Although thymol is bactericidal against many pathogens in vitro, its in vivo effectiveness against pathogens in the lower gastrointestinal tract is limited because of its rapid absorption in the proximal gut. Thymol-ß-D-glucopyranoside (ß-thymol), a conjugated form of thymol, can deliver thymol to the lower gastrointestinal tract and has shown antibacterial effects. In the present study, we examined the in vitro effects of ß-thymol on Salmonella enterica serovar Typhimurium (ST) and Escherichia coli K88 (K88). We inoculated one-half strength Mueller-Hinton broth with 5.8 ± 0.09 log CFU/ml novobiocin- and naladixic acid-resistant (NN) ST (NVSL 95-1776) and 5.1 ± 0.09 log CFU ml(-1) NN-resistant K88, with or without porcine feces (0.1% [wt/vol]) (fecal incubations). The resultant bacterial suspensions were distributed under N2 to triplicate sets of tubes to achieve initial concentrations of 0, 3, 6, and 12 mM for ST treatments and 0, 3, 12, and 30 mM for K88 treatments. Samples were incubated at 39°C and then plated onto NN-containing brilliant green agar and NN-containing MacConkey agar; ST and K88 CFU concentrations were determined via 10-fold dilutions, and viable cell counts were performed at 0, 6, and 24 h. No differences in ST CFU counts were observed in ß-thymol-treated tubes without the added porcine feces (i.e., pure culture) at 6 or 24 h. However, in tubes that contained fecal incubations, ST CFU counts were reduced (P < 0.05) from controls at 6 h in tubes treated with 6 and 12 mM ß-thymol, whereas in tubes treated with 3, 6, and 12 mM ß-thymol the CFU counts were reduced (P < 0.05) at 24 h. No differences were observed in K88 CFU counts in pure culture or in fecal incubations at 6 h, but K88 CFU counts were reduced (P < 0.05) in both pure and fecal incubations at 24 h. The results from this study demonstrate that ß-thymol, in the presence of fecal suspensions, has anti-Salmonella and anti-E. coli effects, suggesting a role of ß-glycoside-hydrolyzing microbes for the release of bactericidal thymol from ß-thymol.

Structure-activity relationships for inhibitory insect myosuppressins: contrast with the stimulatory sulfakinins.

Unusual among insect neuropeptides, the decapeptide myosuppressins are capable of inhibiting contractions of visceral muscle, including the isolated cockroach hindgut. The C-terminal pentapeptide Val-Phe-Leu-Arg-Phe-NH2 has been identified as the myosuppressin active core, the minimum number of residues required to elicit hindgut myoinhibitory activity. Activity of the same magnitude as the parent neuropeptide requires the C-terminal heptapeptide fragment Asp-His-Val-Phe-Leu-Arg-Phe-NH2. Evaluation of a series of substitution analogs delineates structural features critical for myoinhibitory activity within this important fragment. The branched, hydrophobic residues in myosuppressin position 6 (Val) and particularly position 8 (Leu), their absence in the myostimulatory sulfakinins, and the different roles played by the shared Asp residue (myosuppressin position 4; leucosulfakinin position 5) in peptide-receptor interaction, account in large degree for the contrasting biological activities elicited by these otherwise structurally similar peptide families. The results may have broad significance for other invertebrate myotropic systems, such as the locust heart and the pharyngeal retractor muscle of the mollusc Helix aspersa.

Diuretic activity of C-terminal group analogues of the insect kinins in Acheta domesticus.

A series of insect kinin analogues, AFFPWG-X, modified at the C-terminal group, were evaluated in a cricket Malpighian tubule secretion bioassay. The results were compared with activity profiles observed in a cockroach hindgut myotropic bioassay for these analogues. Although the replacement of the C-terminal amide group with a negatively charged acid leads to a precipitious drop in diuretic activity, it can be partially restored with the introduction of ester groups such as methyl or benzyl. The presence of branched chain character in the C-terminal group or a C-terminal alpha-carbon-amide distance spanning five methylene group spacers is incompatible with the receptor interaction required for biological activity. Significant diuretic activity is retained with four or fewer methylene groups in this region. C-terminal group analogues containing -SCH3, -NHCH2CH2OCH3, or -OCH2(C6H5) offered the greatest retention of diuretic activity while providing increased hydrophobicity and/or steric bulk. The data are of potential value in the development of mimetic analogues of this insect neuropeptide family. Mimetic analogues are potentially valuable tools to insect neuroendocrinologists studying diuresis and/or engaged in the development of future pest management strategies.

Pseudodipeptide analogs of the pyrokinin/PBAN (FXPRLa) insect neuropeptide family containing carbocyclic Pro-mimetic conformational components.

Three N-terminal amino acid residues of the C-terminal core pentapeptide Phe-X-Pro-Arg-Leu-NH2 (X = Gly, Ser, Thr, Val) of the pryokinin/PBAN insect neuropeptide family were replaced by nonpeptide moieties. To reestablish some of the conformational properties lost upon removal of the peptide bonds and Pro of the three amino acid residue block, carbocyclic Pro-mimetic components were incorporated into pseudodipeptide analogs. The most active analog contained a trans-DL-1,2-cyclopentanedicarboxyl carbocyclic component and proved to be over 3 orders of magnitude more potent than a simple, straight chain pseudodipeptide analog and approached the potency of the pentapeptide core in a cockroach hindgut myotropic bioassay. The pseudodipeptide analog retains a critical carbonyl residue which can participate in a hydrogen bond that stabilizes a beta-turn conformation in the active core region of the pyrokinin/PBAN peptides. This study demonstrates that knowledge of active conformation can be used to enhance the biological potency of pseudopeptide mimetic analogs of insect neuropeptides. The analogs represent a milestone in the development of pseudopeptide and nonpeptide mimetic analogs of this peptide family, which has been associated with such critical physiological processes as hindgut and oviduct contraction, pheromone biosynthesis, diapause induction, and induction of melanization and reddish coloration in a variety of insects. Mimetic analogs are potentially valuable tools to insect neuroendocrinologists studying these physiological processes and/or engaged in the development of future pest management strategies.

Drug monitoring of PEG-asparaginase treatment in childhood acute lymphoblastic leukemia and non-Hodgkin's lymphoma.

This is an updated review of the pharmacokinetic profile of PEG-asparaginase (PEG-ASNase) in childhood acute lymphoblastic leukemia (ALL) or non-Hodgkin's lymphoma (NHL). In a total of 271 children undergoing ALL/NHL or relapsed ALL treatment according to the Berlin-Frankfurt-Münster (BFM) protocols, drug monitoring of ASNase serum activity was performed after PEG-ASNase infusions. From December 1996 to July 2000, 1667 samples after 362 intravenous administrations of either 500, 750, 1000 or 2500 IU/m2 PEG-ASNase were analyzed. Three weeks after infusion when relating the ASNase activity to the four-dose levels significant differences were not observed. Large interpatient variability was seen at each dose level resulting in a relevant number of patients not achieving adequate treatment intensity. Neither the extent of ASNase pre-treatment nor a prior event of a hypersensitivity reaction against unmodified ASNase had any impact on PEG-ASNase pharmacokinetics. It is concluded that escalation of the dose of PEG-ASNase did not result in a significant prolongation of time with activity values considered therapeutic. Depending on the desired endpoint, a second administration of PEG-ASNase seems to be more favorable than increasing the dose. For a safer recommendation, further investigations assessing the pharmacodynamic profile are required. Drug monitoring is advisable for early detection of patients with rapid elimination in order to ensure maximum treatment intensity.

Phytophotodermatitis from celery among grocery store workers.

We detected 19 cases of phytophotodermatitis during a cross-sectional epidemiological investigation of two Oregon grocery stores that were part of the same supermarket chain. Outdoor sunlight exposure during the workshift and tanning salon use were identified as risk factors; the most severe cutaneous reactions tended to occur among tanning salon users. Although both stores carried the same brands and varieties of produce, all 19 cases occurred among employees of one store, which had held a celery sale coincident with the outbreak, resulting in a quadrupling of the usual volume of celery sold. We found elevated psoralen levels in two of three celery samples obtained from the affected store; cutaneous provocation tests with trimmed surfaces of these celery samples produced phototoxic reactions. Preliminary experiments with one brand of celery have demonstrated psoralen levels as high as 25 micrograms/cm2 of trimmed surface. These observations suggest that clinical phytophotodermatitis among grocery store workers may be caused by healthy celery and results from a complex interaction of exposure variables, including ultraviolet radiation from tanning salon use, frequency of handling celery, celery brand, and sporadic elevation of psoralen content from environmental stresses.

Occurrence of the toxin dehydroabietic acid in Salmonella typhimurium.

Many strains of Salmonella typhimurium studied in our lab demonstrated marked differences in the pathogenicity for guinea pig, chicken and Hela cells. As a result, a pathogenic strain of S. typhimurium, strain 9SR2, was evaluated for lipophilic components that may be associated with virulence using gas chromatography/mass spectrometry. The hydroxylated fatty acids 2-hydroxytetradecanoic acid (2-OH-14:0) and 3-hydroxytetradecanoic acid (3-OH-14:0) often present in lipid A, a potent endotoxin, were observed as their methyl esters. The cyclic fatty acids methylene-hexadecanoic acid (C17delta) and methyleneoctadecanoic acid (C19delta) also were detected. The nephrotoxic and neurotoxic diterpenoid resin acid, dehydroabietic acid, was observed for the first time from S. typhimurium in both the total lipid and diglyceride fractions and determined as its methyl ester at m/z 314.2246. Due to its previously established toxicity, dehydroabietic acid may be a factor associated with virulence of S. typhimurium.

Isopimpinellin is not phototoxic in a chick skin assay.

Synthetic isopimpinellin (5,8-dimethoxypsoralen), confirmed to contain as impurities only trace quantities at most of psoralen, bergapten (5-methoxypsoralen) and xanthotoxin (8-methoxypsoralen), is not phototoxic when tested in a chick skin bioassay system. These findings are at variance with earlier studies showing isopimpinellin to be phototoxic against chick skin and support the conclusion that isopimpinellin is photobiologically inactive. As recently proposed by others, the several reports of isopimpinellin photoactivity are most likely attributable to contamination by small amounts of highly active psoralens such as bergapten or xanthotoxin.