Stratification of atopic dermatitis patients by patterns of response to proactive therapy with topical tacrolimus: low serum IgE levels and inadequately controlled disease activity at the start of treatment predict its failure.

PURPOSE: Topical calcineurin inhibitors (TCIs) are an important anti-inflammatory drug for treating atopic dermatitis (AD). However, those treatment responses are variable. In this study, we stratified AD patients by patterns of response to remission maintenance therapy (proactive therapy) with topical tacrolimus, a typical TCI. Thereafter, we explored patient features that predict the success or failure of proactive therapy using TCI (TCI proactive therapy). METHODS: A single-arm open-label clinical study aimed to evaluate the efficacy of TCI proactive therapy was conducted in 31 patients with AD. Patients were treated with TCS to induce remission (remission-induction period) followed by daily TCI ointment (0.1% tacrolimus) application for 4 weeks (maintenance therapy period), and twice-weekly application for 12 weeks (proactive therapy period). Based on its results, treatment outcomes were correlated with the patients' clinical and laboratory findings. RESULTS: Of the 31 patients enrolled in the study, 21 successfully completed maintenance therapy (TCI responders). Among them, 13 completed (proactive-completed group) and 8 failed proactive therapy (proactive-dropout group). At the beginning of maintenance therapy, the serum IgE level was significantly higher in the TCI responders than in those who failed maintenance therapy (p = 0.049). At the beginning of proactive therapy, the mean-SCORing Atopic Dermatitis (SCORAD) score was significantly different between the proactive-completed (11.7 ± 4.6) and proactive-dropout (16.6 ± 4.2) groups (p = 0.025). In proactive-dropout group patients, worsened disease activity correlated well with the elevation of serum lactate dehydrogenase (LDH) and Thymus and activation-regulated chemokine (TARC) levels and peripheral eosinophil count. CONCLUSION: AD patients were stratified into three different response patterns to TCI proactive therapy. Patients with less involvement of IgE in the pathogenesis and inadequate remission induction by TCS may not be expected to respond well to TCI proactive therapy.Key messagesAD patients can be stratified into three types according to their pattern of responsiveness to TCI proactive therapy.The efficacy of TCI proactive therapy is lower in AD patients with lower serum IgE levels.TCI proactive therapy should be done after the achievement of adequate remission induction by TCS.

Clinical effectiveness of efinaconazole 10% solution for treatment of onychomycosis with longitudinal spikes.

Onychomycosis with longitudinal spikes in the nail plate has been reported to be refractory to oral drugs as with dermatophytoma. We evaluated the efficacy of 10% efinaconazole solution in the treatment of onychomycosis with longitudinal spikes. Of the 223 subjects who were enrolled in a previous study, a post-hoc analysis of 82 subjects with longitudinal spikes was performed in this study. The opacity ratio of longitudinal spikes was decreased over time from 8.1 to 0.9 at the final assessment. In addition, the longitudinal spike disappearance rate increased early after the application to 81.7% at the final assessment. Therefore, 10% efinaconazole solution can be a first-line drug for longitudinal spikes, which have been regarded as refractory to oral drugs.

Efficacy of long-term treatment with efinaconazole 10% solution in patients with onychomycosis, including severe cases: A multicenter, single-arm study.

We evaluated the efficacy of efinaconazole 10% topical solution in long-term use, for up to 72 weeks, for onychomycosis, including severe cases. Among 605 participants, 219 patients diagnosed as having onychomycosis were evaluated for the efficacy of efinaconazole. The treatment success rate (<10% clinical involvement of the target toenail) at the final assessment time point was 56.6%, the complete cure rate was 31.1% and the mycological cure rate was 61.6%, all of which increased over time, demonstrating that continuous application contributed to the improvement of cure rate. Even in severe cases, reduction of the affected nail area was observed, showing the potential efficacy of the treatment. Responses to a quality of life questionnaire among patients with onychomycosis, OnyCOE-t, suggested that efinaconazole treatment improved the patients' quality of life. The incidence of adverse drug reaction in the patients eligible for the assessment was 6.3%, and this developed only in the administration site in all cases. No systemic adverse event was observed. In addition, no increase in the incidence of adverse drug reaction due to long-term use was found. Efinaconazole therapy was proved to exhibit excellent balance between efficacy and safety, and thus may serve as a useful treatment option for onychomycosis.

[Analyses of Volatile Components of Lavender (Lavandula angustifolia HIDCOTE and Lavandula x intermedia GROSSO) as Influenced by Cultivar Type, Part, and Growth Season].

Volatile components originating from Lavandula angustifolia Hidcote and Lavandula x intermedia Grosso plants cultivated in a medicinal plant garden of Hoshi University located in southern Tokyo were investigated using thermal desorption-GC-MS. Sampling of the flowers and herbs of the lavender was performed at different developmental stages, i.e., summer, autumn, and winter (herbs only) using solid phase micro extraction fibers. Linalool, linalyl acetate, ß-caryophyllene, ß-myrcene, α-ocimene, ß-ocimene, and terpinen-4-ol were the predominant constituents originating from the flowers of both plants. Additional volatile compounds such as borneol, eucalyptol, and camphor were found in the Lavandula x intermedia flowers. The number of volatile compounds originating from the Lavandula angustifolia flowers in summer was greater than that in autumn. 3-Hexen-1-ol, 3-carene, and p-cymen-8-ol were volatile compounds characteristic of the herbs, and α-ocimene, allo-ocimene, and terpinen-4-ol were detected only from flowers. In comparing volatile compounds obtained from fresh herbs with those from dried herbs, camphor, ß-caryophyllene, and borneol were absent in dried herbs. For people who visit the plant garden, smelling the fragrances of plants directly is believed to deliver not only pleasure but also beneficial therapeutic properties.

Ante-mortem diagnosis of pulmonary tumour thrombotic microangiopathy in a patient with unrecognised extramammary Paget's disease.

Pulmonary tumour thrombotic microangiopathy (PTTM) resulting in fatal pulmonary hypertension is a rare complication of malignancy. Patients with PTTM generally suffer rapid deterioration of hypoxaemia, and a diagnosis is often only made at autopsy. We report a case of extramammary Paget's disease associated with PTTM. An ante-mortem diagnosis was made based on cytology of blood aspirated from a pulmonary artery catheter in a wedged position. Together with a review of the literature, this case highlights the potential diagnostic value of blood cytology in patients with cancer with rapidly progressing pulmonary hypertension.

Investigation of 5-(3-Trifluoromethylbenzylidene)thiazolidine-2,4-dione as a Matrix for Analyses of Biogenic Monoamine Transmitters Using MALDI-MS.

In order to discover new matrices suitable for the analyses of low molecular-weight compounds using positive-ion mode matrix-assisted laser desorption/ionization (MALDI) time-of-flight mass spectrometry (MS), 5-(3-trifluoromethylbenzylidene)thiazolidine-2,4-dione (3-CF3-BTD) was synthesized, and its effectiveness was compared with that when commercially available α-cyano-4-hydroxycinnamic acid was used. 3-CF3-BTD was sufficiently sensitive to analyze neurotransmitters, i.e., dopamine, serotonin, histamine, and epinephrine, in amounts of several picomoles. Similar to vacuum MALDI experiments, atmospheric-pressure MALDI-MS measurements using 3-CF3-BTD as a matrix also detected dopamine.

Anti-type VII collagen autoantibodies, detected by enzyme-linked immunosorbent assay, fluctuate in parallel with clinical severity in patients with epidermolysis bullosa acquisita.

Epidermolysis bullosa acquisita (EBA) is an autoimmune subepidermal blistering disease caused by autoantibodies against type VII collagen. An enzyme-linked immunosorbent assay (ELISA) is currently available to detect autoantibodies in EBA. There have been reports suggesting generically that ELISA indices reflect EBA disease severity; however, there is, as yet, no conclusion as to whether ELISA indices fluctuate with disease activity over time in each EBA patient. This study aimed to investigate whether ELISA titers fluctuate with EBA disease activity and to validate the clinical significance of checking ELISA values in EBA by monitoring type VII collagen ELISA titers and disease severity, evaluated in terms of numbers of blisters and erosions as a clinical score, over time in three Japanese patients with EBA. All three cases in this study, which were treated successfully, showed titers of anti-type VII collagen autoantibodies detected by ELISA that fluctuated in parallel with disease activity. Especially in case 1, we could determine that the expanding erosions were not due to flare-ups of EBA because the ELISA indices stayed low, although new lesions continued to appear. In fact, control of infection and nutrition helped the lesions to become epithelialized. In conclusion, we found that repeated ELISA measurements are useful in monitoring disease activity and making decisions in EBA treatment plans.

[Fiberoptic tracheal intubation through the supraglottic airway device air-Q in a patient with Shprintzen-Goldberg syndrome].

We report a case of successful fiberoptic tracheal intubation through the supraglottic airway device air-Q in a 14-year-old boy in whom intubation was difficult because of Shprintzen-Goldberg syndrome. Shprintzen-Goldberg syndrome is a rare congenital disorder of connective tissue. The patient showed dysmorphic facies and weakness of connective tissue, and was scheduled to undergo abdominal surgery. After induction of general anesthesia, both attempts of laryngoscope-guided and AirwayScope -guided tracheal intubation failed, but a size-2 air-Q could be easily inserted. Fiberoptic tracheal intubation through the air-Q was successfully performed without any difficulty and was safe for his weak airway connective tissue. Supraglottic airway air-Q is a useful conduit for fiberoptic tracheal intubation under general anesthesia, especially in the case of a patient with weak connective tissue in whom intubation is difficult.

Proteomics of the rodent malaria parasite using matrix-assisted laser desorption/ionization quadrupole ion trap time-of-flight tandem mass spectrometry.

Plasmodium berghei strain NK65 is a rodent malaria parasite species widely used as a model of the human-infectious malaria parasite. Because a rodent malaria parasite model allows issues to be addressed which would not be possible with human-infectious species, e.g., mode of action and in vivo screening, a convenient method to analyze the malaria parasite proteome is required. The proteins of P. berghei separated using two-dimensional polyacrylamide gel electrophoresis were analyzed using matrix-assisted laser desorption/ionization quadrupole ion trap time-of-flight tandem mass spectrometry.

Covalent anthocyanin-flavonol complexes from the violet-blue flowers of Allium 'Blue Perfume'.

Three covalent anthocyanin-flavonol complexes (pigments 1-3) were extracted from the violet-blue flower of Allium 'Blue Perfume' with 5% acetic acid-MeOH solution, in which pigment 1 was the dominant pigment. These three pigments are based on delphinidin 3-glucoside as their deacylanthocyanin and were acylated with malonyl kaempferol 3-sophoroside-7-glucosiduronic acid or malonyl-kaempferol 3-p-coumaroyl-tetraglycoside-7-glucosiduronic acid in addition to acylation with acetic acid. By spectroscopic and chemical methods, the structures of these three pigments 1-3 were determined to be: pigment 1, (6(I)-O-(delphinidin 3-O-(3(I)-O-(acetyl)-ß-glucopyranoside(I))))(2(VI)-O-(kaempferol 3-O-(2(II)-O-(3(III)-O-(ß-glucopyranosyl(V))-ß-glucopyranosyl(III))-4(II)-O-(trans-p-coumaroyl)-6(II)-O-(ß-glucopyranosyl(IV))-ß-glucopyranoside(II))-7-O-(ß-glucosiduronic acid(VI)))) malonate; pigment 2, (6(I)-O-(delphinidin 3-O-(3(I)-O-(acetyl)-ß-glucopyranoside(I))))(2(VI)-O-(kaempferol 3-O-(2(II)-O-ß-glucopyranosyl(III))-ß-glucopyranoside(II))-7-O-(ß-glucosiduronic acid(VI)))); and pigment 3, (6(I)-O-(delphinidin 3-O-(3(I)-O-(acetyl)-ß-glucopyranoside(I))))(2(VI)-O-(kaempferol 3-O-(2(II)-O-(3(III)-O-(ß-glucopyranosyl(V))-ß-glucopyranosyl(III))-4(II)-O-(cis-p-coumaroyl)-6(II)-O-(ß-glucopyranosyl(IV))-ß-glucopyranoside(II))-7-O-(ß-glucosiduronic acid(VI)))) malonate. The structure of pigment 2 was analogous to that of a covalent anthocyanin-flavonol complex isolated from Allium schoenoprasum where delphinidin was observed in place of cyanidin. The three covalent anthocyanin-flavonol complexes (pigment 1-3) had a stable violet-blue color with three characteristic absorption maxima at 540, 547 and 618nm in pH 5-6 buffer solution. From circular dichroism measurement of pigment 1 in the pH 6.0 buffer solution, cotton effects were observed at 533 (+), 604 (-) and 638 (-) nm. Based on these results, these covalent anthocyanin-flavonol complexes were presumed to maintain a stable intramolecular association between delphinidin and kaempferol units closely related to that observed between anthocyanin and hydroxycinnamic acid residues in polyacylated anthocyanins. Additionally, an acylated kaempferol glycoside (pigment 4) was isolated from the same flower extract, and its structure was determined to be kaempferol 3-O-sophoroside-7-O-(3-O-(malonyl)-ß-glucopyranosiduronic acid).

Structural features of polyacylated anthocyanins using matrix-assisted laser desorption/ionization and electrospray ionization time-of-flight mass spectrometry.

In our continuing studies to isolate water-soluble vacuolar pigments, we expect to elucidate more structural details using mass spectrometry (MS). Because of its sensitivity, only a small amount of pigment extracted from natural plants is required for MS measurement. Nuclear magnetic resonance is also a useful spectroscopic method for structural determination. In this study, two soft ionization techniques, electrospray ionization (ESI) and matrix-assisted laser desorption/ionization (MALDI), on time-of-flight (TOF) mass spectrometers, were used to analyze five polyacylated anthocyanins with more than two aromatic acid molecules in the side chains. ESI is advantageous for the detection of individual molecular ions, while MALDI is essential for the detection of characteristic fragment ions originating from the anthocyanidin. Although 2,5-dihydroxybenzoic acid (DHBA) is an effective matrix in MALDI-TOFMS to obtain informative fragment ions of polyacylated anthocyanins, α-cyano-4-hydroxycinnamic acid (CHCA) is the preferred matrix for the identification of aglycones. In particular, in measurements of polyacylated anthocyanins with two acylated glycoside chains, fragment ions originating from anthocyanidin can only be observed in MALDI-TOFMS using CHCA as the matrix.

[A case of post-spinal tinnitus which improved after undergoing epidural anesthesia].

A 34-year-old woman suffering from post-spinal tinnitus for 8 years was scheduled for a cesarean section under epidural anesthesia selected to prevent a deterioration of this condition due to a possible decrease in the cerebrospinal fluid level. Unexpectedly, the tinnitus disappeared completely after the epidural injection of 2% lidocaine 27 ml and following continuous epidural infusion. It is conceivable that moderate quantities of local anesthetics into the epidural space might have acted as an effective method similar to that of epidural physiologic saline injection in order to improve the cerebrospinal pressure.