Evaluation of the Aspergillus Western blot IgG kit for diagnosis of chronic aspergillosis.

Immunoprecipitin detection (IPD) is the current reference confirmatory technique for anti-Aspergillus antibody detection; however, the lack of standardization is a critical drawback of this assay. In this study, we evaluated the performance of the Aspergillus Western blot (Asp-WB) IgG kit (LDBio Diagnostics, Lyon, France), a recently commercialized immunoblot assay for the diagnosis of various clinical presentations of chronic aspergillosis. Three hundred eight serum samples from 158 patients with aspergillosis sensu lato (s.l.) were analyzed. More specifically, 267 serum samples were derived from patients with Aspergillus disease, including 89 cases of chronic pulmonary aspergillosis, 10 of aspergilloma, and 32 of allergic bronchopulmonary aspergillosis, while 41 samples were from patients with Aspergillus colonization, including 15 cystic fibrosis (CF) and 12 non-CF patients. For blood donor controls, the Asp-WB specificity was 94%, while the kit displayed a sensitivity for the aspergillosis s.l. diagnosis of 88.6%, with a diagnostic odds ratio (DOR) of 119 (95% confidence interval [CI], 57 to 251). The DOR values were 185.22 (95% CI,78.79 to 435.45) and 43.74 (95% CI, 15.65 to 122.20) for the diagnosis of Aspergillus disease and Aspergillus colonization, respectively. Among the patients, the sensitivities of the Asp-WB in the diagnosis of Aspergillus colonization were 100% and 41.7% in CF and non-CF patients, respectively. The Asp-WB yielded fewer false-negative results than did IPD. In conclusion, the Asp-WB kit performed well for the diagnosis of various clinical presentations of aspergillosis in nonimmunocompromised patients, with an enhanced standardization and a higher sensitivity than with IPD, which is the current reference method.

Anticounterfeiting and Fraud Mitigation Solutions for High-value Food Products.

Globalization and the increasing complexity of supply chains have allowed food fraud to expand to a great extent. Some of the most serious effects of these deceitful activities are damage to a brand's reputation and trust, economic losses, and public health risks. The usual victims of food fraud are dairy, meat, fish, and seafood products, as well as fats/oils and alcoholic drinks. The purpose of this review paper is to present an updated analysis of the currently available anticounterfeit technologies and their application to the four most fraud-affected food supply chains. An assessment that was conducted to determine when the adoption of a combination of technologies could enhance food safety and brand protection is also provided. The obtained results indicate that electronic and data-driven technologies (RFID devices and digital traceability systems) are still in their infancy in the food sectors that are subjected the most to fraudulent activities. Research is necessary to develop innovative digital and physical technologies to "outsmart" such fraudsters and to prevent their illicit actions in the food sector.

Meta-analysis of the association between obstructive sleep apnoea and postoperative outcome.

BACKGROUND: Obstructive sleep apnoea (OSA) is often undiagnosed before elective surgery and may predispose patients to perioperative complications. METHODS: A literature search of PubMed-Medline, Web of Science, Scopus, EMBASE, Cochrane Database of Systematic Reviews, and Cochrane Central Register of Controlled Trials up to November 2010 was conducted. Our search was restricted to cohort or case-control studies in adults diagnosed with OSA by screening questionnaire, oximetry, or polysomnography. Studies without controls, involving upper airway surgery, and with OSA diagnosed by ICD-9 codes alone were excluded. The primary postoperative outcomes were desaturation, acute respiratory failure (ARF), reintubation, myocardial infarction/ischaemia, arrhythmias, cardiac arrest, intensive care unit (ICU) transfer, and length of stay. RESULTS: Thirteen studies were included in the final analysis (n=3942). OSA was associated with significantly higher odds of any postoperative cardiac events [45/1195 (3.76%) vs 24/1420 (1.69%); odds ratio (OR) 2.07; 95% confidence interval (CI) 1.23-3.50, P=0.007] and ARF [33/1680 (1.96%) vs 24/3421 (0.70%); OR 2.43, 95% CI 1.34-4.39, P=0.003]. Effects were not heterogeneous for these outcomes (I(2)=0-15%, P>0.3). OSA was also significantly associated with higher odds of desaturation [189/1764 (10.71%) vs 105/1881 (5.58%); OR 2.27, 95% CI 1.20-4.26, P=0.01] and ICU transfer [105/2062 (5.09%) vs 58/3681 (1.57%), respectively; OR 2.81, 95% CI 1.46-5.43, P=0.002]. Both outcomes showed a significant degree of heterogeneity of the effect among studies (I(2)=57-68%, P<0.02). Subgroup analyses had similar conclusions as main analyses. CONCLUSIONS: The incidence of postoperative desaturation, respiratory failure, postoperative cardiac events, and ICU transfers was higher in patients with OSA.

UAV-spray application in vineyards: Flight modes and spray system adjustment effects on canopy deposit, coverage, and off-target losses.

Improvements in the spray application of plant protection products enhance agricultural sustainability by reducing environmental contamination, but by increasing food quality and human safety. Currently, Unmanned Aerial Vehicles (UAVs) are raising interest in spray applications in 3D crops. However, operational configurations of UAV-spray systems need further investigation to maximise the deposition in the canopy and minimise the off-target losses. Our experimental research focused on investigating the effects on the canopy spray deposition and coverage due to different UAV-spray system configurations. Twelve configurations were tested under field conditions in an experimental vineyard (cv. Barbera), derived from the combination of different UAV flight modes (band and broadcast spray applications), nozzle types (conventional and air inclusion), and UAV cruise speeds (1 and 3 m s-1). Also, the best treatment, among those tested, by using the UAV-spray system and a traditional airblast sprayer were compared. The data was analysed by testing the effects of the three operational parameters and their two- and three-way interactions by means of linear mixed models. The results indicated that the flight mode deeply affects spray application efficiency. Compared to the broadcast spray modes, the band spray mode was able to increase the average canopy deposition from 0.052 to 0.161 µL cm-2 (+ 309 %) and reduce the average ground losses from 0.544 to 0.246 µL cm-2 (- 54 %). The conventional airblast sprayer, operated at a low spray application rate, showed higher canopy coverage and lower ground losses in comparison to the best UAV-spray system configuration.

[Silica causes difficulties]. / La silice cause des difficultés.

Silicosis and sarcoidosis are two very distinct entities in the literature. All the additional non-invasive examinations, including the chest CT scan, often do not differentiate them. The history, including occupational exposure to identified silica particles, is a discriminating factor. However, due to the pathogenic power of silica, it would be possible to have the simultaneous development of these two pathologies in the same patient. To illustrate this situation, here is the case of a 62-year-old patient, who presented initially with a picture of dyspnea and productive cough. The chest CT showed micronodular peribronchovascular infiltrates and mediastinal lymphadenopathy. The other additional examinations did not find anything specific. In the diagnostic process, the patient had multiple endoscopic samples which did not make it possible to be conclusive on one or the other of these pathologies. He therefore underwent a surgical lung biopsy which revealed histological lesions compatible with the two pathologies. Recent studies suggest that inhaled particles, especially silica, could be responsible for the pattern of sarcoidosis. However, it is difficult to say whether, in this case, silica was responsible for the development of sarcoidosis.

Diffraction and mossbauer studies of minerals from lunar soils and rocks.

Constituents of lunar soils and rocks were studied by powder and singlecrystal x-ray diffraction. In addition to identification of minerals, including rare amphibole, mica, and aragonite, a detailed study of the important rock-forming minerals of the plagioclase, pyroxene, and olivine groups has begun. Mössbauer spectra were recorded from lunar soils, ground rock samples, and separates of iron-bearing minerals. The proportions of iron-bearing minerals were estimated from computer-fitted areas for the bulk samples. The Fe(2+) in the lower-density fraction of pyroxene was ordered, whereas that of the higher-density fraction was disordered.

Most probable number methodology for quantifying dilute concentrations and fluxes of Escherichia coli O157:H7 in surface waters.

AIMS: To better understand the transport and enumeration of dilute densities of Escherichia coli O157:H7 in agricultural watersheds, we developed a culture-based, five tube-multiple dilution most probable number (MPN) method. METHODS AND RESULTS: The MPN method combined a filtration technique for large volumes of surface water with standard selective media, biochemical and immunological tests, and a TaqMan confirmation step. This method determined E. coli O157:H7 concentrations as low as 0.1 MPN per litre, with a 95% confidence level of 0.01-0.7 MPN per litre. Escherichia coli O157:H7 densities ranged from not detectable to 9 MPN per litre for pond inflow, from not detectable to 0.9 MPN per litre for pond outflow and from not detectable to 8.3 MPN per litre for within pond. The MPN methodology was extended to mass flux determinations. Fluxes of E. coli O157:H7 ranged from <27 to >10(4) MPN per hour. CONCLUSION: This culture-based method can detect small numbers of viable/culturable E. coli O157:H7 in surface waters of watersheds containing animal agriculture and wildlife. SIGNIFICANCE AND IMPACT OF THE STUDY: This MPN method will improve our understanding of the transport and fate of E. coli O157:H7 in agricultural watersheds, and can be the basis of collections of environmental E. coli O157:H7.

Control of sigma virus multiplication by the ref(2)P gene of Drosophila melanogaster: an in vivo study of the PB1 domain of Ref(2)P.

Ref(2)P has been described as one of the Drosophila proteins that interacts with the sigma virus cycle. We generated alleles to identify critical residues involved in the restrictive (inhibiting viral multiplication) or permissive (allowing viral multiplication) character of Ref(2)P. We demonstrate that permissive alleles increase the ability of the sigma virus to infect Drosophila when compared to null alleles and we confirm that restrictive alleles decrease this capacity. Moreover, we have created alleles unfunctional in viral cycling while functional for Ref(2)P fly functions. This type of allele had never been observed before and shows that fly- and virus-related activities of Ref(2)P are separable. The viral status of Ref(2)P variants is determined by the amino-terminal PB1 domain polymorphism. In addition, an isolated PB1 domain mimics virus-related functions even if it is similar to a loss of function toward fly-related activities. The evolutionary tree of the Ref(2)P PB1 domain that we could build on the basis of the natural allele sequences is in agreement with an evolution of PB1 domain due to successive transient selection waves.

First Report of Leaf Smut on Fescue (Festuca rubra) Caused by Urocystis agropyri in Interior Alaska.

In June and early July of 2003 and July of 2007, a smut disease was found on fescue (Festuca rubra L.) at the Fairbanks Golf and Country Club and vicinities, Interior Alaska. Diseased plants were pale green-to-slightly yellow and stunted. The lesions were long, narrow, yellowish green streaks parallel to the veins of leaves and sheaths. At a later stage, sori developed under the epidermis and the leaves and sheaths turned silvery gray. Rupture of the epidermis resulted in the release of masses of black spores that covered the leaves, especially along and within infected sheaths. Microscopic observation showed spore balls consisting of one-to-four, dark reddish brown teliospores surrounded by small, hyaline-to-light brown sterile cells. The spore balls were globose to elongate and 16 to 32 × 18 to 38 µm. The teliospores were globose, dark reddish brown, and 7.5 to 20 µm in diameter. Urocystis agropyri is recognized by R. W. Smiley et al. (2) and J. D. Smith et al. (3) as occurring on turf grasses; K. Vánky (4) restricts this species to Elymus spp. and recognizes U. ulei as the valid species infecting Festuca spp, including F. rubra. On the basis of host symptoms and morphology of spores, the smut found on F. rubra in Alaska fits better with published descriptions of U. agropyri (Preuss) Schrot (2,3), however, it likely is not conspecific with flag smut of wheat. For molecular verification of this identification, DNA was isolated from teliospores with a DNeasy Plant Mini Kit (Qiagen, Valencia, CA). Primers were designed for amplification of the large subunit ribosomal gene based on the only two published sequences of U. ranunculi (Lib.) Moesz (GenBank Accession No. AF009879) and U. colchici (Schltdl.) Rabenh (GenBank Accession No. AF009878) (1). A 400-bp PCR product was amplified by the forward primer 3'-GCATTGTAAACTCAGAAGTGTTATCCG-5' and reverse primer 5'-TTCCCTAAACCTATATCCGGCG-3'. Nucleotide sequence of the PCR product (GenBank Accession No. AY547283) shared 97.7% homology with U. ranunculi and 98.2% with U. colchici. Comparison of nucleotide sequences will be more meaningful in the identification of species of Urocystis when additional sequences are published. To our knowledge, this is the first report of U. agropyri from turfgrass in Alaska. References: (1) D. Begerow et al. Can. J. Bot. 75:2045, 1997. (2) R. W. Smiley et al. Compendium of Turfgrass Diseases. 3rd ed. The American Phytopathological Society, St Paul, MN, 2005. (3) J. D. Smith et al. Page 189 in: Fungal Diseases of Amenity Turf Grassess. E. & F. N. Spon, London, 1989. (4) K. Vánky. Page 308 in: European Smut Fungi. Gustav Fischer Verlag, NY. 1994.

An algorithm for the reconstruction of high-energy neutrino-induced particle showers and its application to the ANTARES neutrino telescope.

A novel algorithm to reconstruct neutrino-induced particle showers within the ANTARES neutrino telescope is presented. The method achieves a median angular resolution of [Formula: see text] for shower energies below 100 TeV. Applying this algorithm to 6 years of data taken with the ANTARES detector, 8 events with reconstructed shower energies above 10 TeV are observed. This is consistent with the expectation of about 5 events from atmospheric backgrounds, but also compatible with diffuse astrophysical flux measurements by the IceCube collaboration, from which 2-4 additional events are expected. A [Formula: see text] C.L. upper limit on the diffuse astrophysical neutrino flux with a value per neutrino flavour of [Formula: see text] is set, applicable to the energy range from 23 TeV to 7.8 PeV, assuming an unbroken [Formula: see text] spectrum and neutrino flavour equipartition at Earth.

Incidence of Severe Infections and Infection-Related Mortality During the Course of Giant Cell Arteritis: A Multicenter, Prospective, Double-Cohort Study.

OBJECTIVE: To assess the incidence of infections leading to hospitalization, the mortality rate related to infections, and the determinants of these factors in patients with giant cell arteritis (GCA). METHODS: In total, 486 patients with GCA (75% women) were enrolled at the time of diagnosis. All patients fulfilled the American College of Rheumatology criteria for GCA. As controls, age- and sex-matched subjects were randomly selected from the general population and matched to patients at the time of diagnosis of GCA. Both groups were prospectively followed up over a 5-year period. RESULTS: Severe infections were more frequent among patients with GCA during the first year after diagnosis, compared to general population controls (incidence rate ratio 2.1, 95% confidence interval [95% CI] 1.2-3.4; incidence rate 11.1/100 patient-years [95% CI 8.3-14.6] in patients with GCA versus 5.9/100 patient-years [95% CI 4-8.4] in controls). Specifically, septic shock and infectious colitis were more frequent among the patients with GCA. Mortality caused by infections was higher in patients with GCA compared to controls (P < 0.0001 by log rank test). In analyses adjusted for age, among patients with GCA, a diagnosis of diabetes (hazard ratio [HR] 3.3, 95% CI 1.4-7.7) and a corticosteroid dosage that was >10 mg/day after 12 months of treatment (HR 4.61, 95% CI 1.38-15.36) were associated with death attributed to severe infection. The observed overall incidence of mortality was increased in patients with GCA during the early period of enrollment in the study (before 1997) (P = 0.0001 by log rank test), but thereafter was the same as that in the general population controls. CONCLUSION: Frequencies of severe infections and rates of infection-related mortality are increased during the first year after the diagnosis of GCA. The risk of infection increases in GCA patients with older age or in the presence of diabetes, or is greater when the dosage of corticosteroids has been increased to >10 mg/day after 12 months of treatment.

Cooperative Clinical Conferences: Nursing Student Pediatric Clinical Innovation.

BACKGROUND: A gap exists between nursing student classrooms (i.e., clinical training) and newly graduated RNs' real-world nursing experiences. The Cooperative Clinical Conference (CCC) was piloted for prelicensure nursing clinical groups as a vehicle to allow students to reflect on their learning and physiology and disease, as it relates to the pediatric patient in the context of the entire plan of care for pediatric patients. METHOD: Participating nursing student clinical groups were allotted 15 to 20 minutes to give group case presentations of de-identified patient scenarios, representative of the patient population on the assigned clinical unit. RESULTS: The CCC as a learning opportunity in the clinical area was rated highly on evaluations by faculty and student participants in terms of their achievement of both learning objectives and satisfaction. CONCLUSION: The CCC represented a feasible and acceptable method of enhanced learning and professional development with and for undergraduate nursing students in the pediatric clinical environment. [J Nurs Educ. 2016; 55(7):416-419.].

Unusual variability of the Drosophila melanogaster ref(2)P protein which controls the multiplication of sigma rhabdovirus.

The ref(2)P gene of Drosophila melanogaster was identified by the discovery of two alleles, Po and Pp, respectively, permissive and restrictive for sigma rhabdovirus multiplication. A surprising variability of this gene was first noticed by the observation of size differences between the transcripts of permissive and restrictive alleles. In this paper, another restrictive allele, Pn, clearly distinct from Pp, is described: it exhibits a weaker antiviral effect than Pp and differs from Pp by its molecular structure. Five types of alleles were distinguished on the basis of their molecular structure, as revealed by S1 nuclease analysis of 17 D. melanogaster strains; three alleles were permissive and two restrictive. Comparison of the sequences of four haplotypes revealed numerous point mutations, two deletions (21 and 24 bp) and a complex event involving a 3-bp deletion, all affected the coding region. The unusual variability of the ref(2)P locus was confirmed by the high ratio of amino acid replacements to synonymous mutations (7:1), as compared to that of other genes, such as the Adh (2:42). Nevertheless, nucleotide sequence comparison with the Drosophila erecta ref(2)P gene shows that selective pressures are exerted to maintain the existence of a functional protein. The effects of this high variability on the ref(2)P protein are discussed in relation to its specific antiviral properties and to its function in D. melanogaster, where it is required for male fertility.

Block of human cardiac Kv1.5 channels by loratadine: voltage-, time- and use-dependent block at concentrations above therapeutic levels.

OBJECTIVE: The aim of this study was to analyze the effects of loratadine on a human cardiac K+ channel (hKv1.5) cloned from human ventricle and stably expressed in a mouse cell line. METHODS: Currents were studied using the whole-cell configuration of the patch-clamp technique in Ltk- cells transfected with the gene encoding hKv1.5 channels. RESULTS: Loratadine inhibited in a concentration-dependent manner the hKv1.5 current, the apparent affinity being 1.2 +/- 0.2 microM. The blockade increased steeply between -30 and 0 mV which corresponded with the voltage range for channel opening, thus suggesting that the drug binds preferentially to the open state of the channel. The apparent association and dissociation rate constants were (3.6 +/- 0.5) x 10(6).M-1.s-1 and 3.7 +/- 1.6.s-1, respectively. Loratadine, 1 microM, increased the time constant of deactivation of tail currents elicited on return to -40 mV after 500 ms depolarizing pulses to +60 mV from 36.2 +/- 3.4 to 64.9 +/- 3.6 ms (n = 6, P < 0.01), thus inducing a 'crossover' phenomenon. Application of trains of pulses at 1 Hz lead to a progressive increase in the blockade reaching a final value of 48.6 +/- 4.3%. Recovery from loratadine-induced block at -80 mV exhibited a time constant of 743.0 +/- 78.0 ms. Finally, the results of a mathematical stimulation of the effects of loratadine, based on an open-channel block model, reproduced fairly well the main effects of the drug. CONCLUSIONS: The present results demonstrated that loratadine blocked hKv1.5 channels in a concentration-, voltage-, time- and use-dependent manner but only at concentrations much higher than therapeutic plasma levels in man.

Behavioral correlates of social dominance.

The behavioral correlates of dominance in the squirrel monkey were explored using a variety of operant tasks. Compared to more submissive animals, more dominant ones showed higher operant rates, more consistent work output, and a higher degree of "frustration tolerance." These data suggest that dominance in the squirrel monkey is not related solely to physical size, but to a variety of behavioral traits which lead to more adjustive problem-solving behavior.

Interaction between phenobarbital and thioridazine.

The effects of thioridazine (TDZ) on serum phenobarbital (PB) and phenytoin (PHT) were studied in mentally retarded persons. Persons taking these drug combinations were identified and matched on the basis of age, sex, body weight, and antiepileptic drug (AED) dosage with persons from the same population who were taking only the AEDs. Trough, steady state serum levels were obtained as part of regular AED monitoring schedules. Serum level of PB per unit dose was significantly less with concomitant administration of TDZ (100 to 200 mg/day) than when PB was given alone. This effect seemed to be TDZ dose-responsive. TDZ had no consistent effects on serum PHT.

Pilot study of fluzinamide (N-methyl-3-[3-(trifluoromethyl)phenoxy]-1-azetidinecarboxamide) in refractory partial seizures.

We conducted a pilot study of fluzinamide in 15 adults with refractory partial seizures. After a baseline period, fluzinamide was added to the existing regimen of phenytoin and carbamazepine and increased to maximum tolerated dose. Common side effects included dizziness, diplopia, ataxia, headache, nausea, and rash, resulting in patient withdrawal in six cases. Seizures became less frequent in four of the nine patients who completed the 8-week trial.

Effects of the two enantiomers, S-16257-2 and S-16260-2, of a new bradycardic agent on guinea-pig isolated cardiac preparations.

1. The electromechanical effects of two enantiomers, S-16257-2 (S57) and S-16260-2 (R60), were studied and compared in guinea-pig isolated atria and ventricular papillary muscles. The possible stereoselectivity of the interaction on the cardiac Na+ channel was analysed by comparing the effects of the two enantiomers on the onset and recovery kinetics of the frequency-dependent Vmax block. 2. In spontaneously beating right atria, S57 and R60 (10(-8)M-10(-4M) exerted a negative chronotropic effect (pIC50 = 5.07 +/- 0.19 and 4.76 +/- 0.18, respectively) and prolonged the sinus node recovery time, this effect being more marked with S57. In electrically driven left atria, S57 decreased (P < 0.05) contractile force only at 10(-4M) and R60 at concentrations > or = 5 x 10(-5M), whereas in papillary muscles the negative inotropic effect appeared at concentrations > 10(-5M). 3. In papillary muscles driven at 1 Hz, S57 and R60 at concentrations higher than 5 x 10(-6M) produced a concentration-dependent decrease in the maximum upstroke velocity (Vmax) and amplitude of the cardiac action potential without altering the resting membrane potential or the action potential duration. S57 and R60 had no effect on the characteristics of the slow action potentials elicited by isoprenaline in ventricular muscle fibres depolarized in high K+ (27 mM) solution. 4. At 5 x 10(-5M), S57 and R60 produced a small tonic Vmax block. However, in muscles driven at rates between 0.5 and 3 Hz both enantiomers produced an exponential decline in Vmax (frequency-dependent Vmax block) which augmented at higher rates of stimulation. The onset and offset rates of the frequency-dependent Vmax block were similar for both drugs. Both S57 and R60 prolonged the recovery time constant from the frequency-dependent block from 20.1 +/- 2.9 ms to 2-3 s.5. At 5 x 10-5 M, S57 and R60 shifted the membrane responsiveness curve in a hyperpolarizing direction.6. It can be concluded that S57 and R60, the two enantiomers of the new bradycardic agent, produced a similar frequency-dependent Vmax block which indicated that the interaction with the Na+ channel was not stereospecific. The analysis of the onset and offset kinetics of the frequency-dependent Vmax block suggested that both enantiomers can be considered as Na+ channel blockers with intermediate kinetics,e.g., class IA antiarrhythmic drugs.

Mechanisms of block of a human cloned potassium channel by the enantiomers of a new bradycardic agent: S-16257-2 and S-16260-2.

1. The effects of S-16257-2 (S57) and S-16260-2 (R60), the two enantiomers of a new bradycardic agent, were studied on human cloned K+ channels (hKv1.5) stably expressed in a mouse L cell line using the whole-cell configuration of the patch-clamp technique. 2. S57 and R60 did not modify the sigmoidal activation time course of the current but reduced the amplitude and increased the rate of the decay of the current during the application of depolarizing pulses. Both, S57 and R60 produced a concentration-dependent block of hKv1.5 channels with apparent KD values of 29.0 +/- 1.9 microM and 40.9 +/- 4.0 microM, respectively. Thus, S57 was 1.4 fold more potent than R60 in blocking hKv1.5 channels. 3. The blockade produced by S57 and R60 was voltage-dependent and increased steeply between -30 and 0 mV, which corresponded with the voltage range for channel opening. This result indicated that both enantiomers block the hKv1.5 channels, preferentially, when they are in the open state. Between 0 and +60 mV the blockade exhibited a shallow voltage-dependence which was described by an electrical distance of 0.18 +/- 0.002 and 0.19 +/- 0.004 for S57 and R60, respectively. 4. S57 and R60 also increased the rate of decline of the current during the application of depolarizing pulses. The time constant of such decline (tau Block) was faster in the presence of R60 than in the presence of S57 (16.2 +/- 1.5 ms vs. 24.0 +/- 2.6 ms; P < 0.01). The apparent association rate constants (k) were similar for S57 and R60 ((0.52 +/- 0.13) x 10(6) M-1 s-1 and (0.66 +/- 0.13) x 10(6) M-1 s-1, respectively), whereas the dissociation rate constant (l) was faster for R60 than for S57 (25.8 +/- 1.8 s-1 and 13.0 +/- 2.4 s-1, respectively). 5. Both enantiomers slowed the deactivation of the tail currents elicited upon repolarization to -40 mV, thus inducing a 'crossover' phenomenon. These results suggested that drug unbinding is required before hKv1.5 channels can close. 6. It is concluded that R60 and S57 produced a similar time- voltage- and state-dependent block of hKv1.5 channels that can be interpreted as open channel block by the charged form of each enantiomer. The main difference between R60 and S57 were linked to the apparent dissociation rate constants.