The taxonomic foundation, species circumscription and continental endemisms of Singerocybe: evidence from morphological and molecular data.

The genus Singerocybe (Tricholomataceae, Agaricales, Basidiomycota) has been the subject of controversy since its proposal in 1988. Its taxonomic foundation, species circumscription and geographical distribution have not yet been examined with molecular sequence data. In this study phylogenetic analyses on this group of fungi were conducted based on collections from Europe, eastern Asia, southern Asia, North America and Australia, with four nuclear markers, ITS, nrLSU, tef1-α and rpb2. Molecular phylogenetic analyses, together with morphological observations, strongly support Singerocybe as a monophyletic group and identify the vesicles in the pileal and stipe cuticle as a synapomorphy of this genus. Seven species are recognized in the genus, including one new species and four new combinations. Clitocybe trogioides and Clitocybe trogioides var. odorifera are synonyms of Singerocybe humilis and Singerocybe alboinfundibuliformis respectively. Most of these species are geographically restricted in their distributions. Furthermore our study expands the distribution range of Singerocybe from the North Temperate Zone to Australia (Tasmania) and tropical southern Asia.

Development of high-energy amorphous solid dispersion of nanosized nobiletin, a citrus polymethoxylated flavone, with improved oral bioavailability.

Nobiletin (NOB), a citrus polymethoxylated flavone, attracts attention because of a wide range of pharmacological activities such as anti-inflammation, anticancer, and most notably ameliorative actions on memory impairment and ß-amyloid pathology. However, clinical use of NOB could be partly limited due to its poor solubility and bioavailability, which might necessitate high doses in order to reach therapeutic plasma concentrations in the central nervous system (CNS) after oral administration. In the present study, amorphous solid dispersion (SD) of nanosized NOB (NOB/SD) was prepared by wet-milling technique with the aim of improving dissolution behavior and pharmacokinetic properties of NOB. Physicochemical properties of the NOB/SD were characterized with focus on surface morphology, particle size distribution, dissolution, and crystallinity assessment. Wet-milled NOB particles in NOB/SD appeared to be amorphous with a diameter of approximately 270 nm, and there was marked improvement in the dissolution behavior compared with that of crystalline NOB. After oral administration of NOB/SD, higher exposure of NOB was observed with increases of bioavailability and CNS distribution by 13- and sevenfold, respectively, compared with those of crystalline NOB. These findings suggest that an amorphous, nanosized SD could be a viable option for enhancing the bioavailability and CNS delivery of NOB.

Formulation design and photochemical studies on nanocrystal solid dispersion of curcumin with improved oral bioavailability.

Considerable interest has been focused on curcumin due to its use to treat a wide variety of disorders, however, the therapeutic potential of curcumin could often be limited by its poor solubility, bioavailability, and photostability. To overcome these drawbacks, efficacious formulations of curcumin, including nanocrystal solid dispersion (CSD-Cur), amorphous solid dispersion (ASD-Cur), and nanoemulsion (NE-Cur), were designed with the aim of improving physicochemical and pharmacokinetic properties. Physicochemical properties of the prepared formulations were characterized by scanning/transmission electron microscope for morphological analysis, laser diffraction, and dynamic light scattering for particle size analysis, and polarized light microscope, powder X-ray diffraction and differential scanning calorimetry for crystallinity assessment. In dissolution tests, all curcumin formulations exhibited marked improvement in the dissolution behavior when compared with crystalline curcumin. Significant improvement in pharmacokinetic behavior was observed in the newly developed formulations, as evidenced by 12- (ASD-Cur), 16- (CSD-Cur), and 9-fold (NE-Cur) increase of oral bioavailability. Upon photochemical characterization, curcumin was found to be photoreactive and photodegradable in the solution state, possibly via type 2 photochemical reaction, whereas high photochemical stability was seen in the solid formulations, especially CSD-Cur. On the basis of these observations, taken together with dissolution and pharmacokinetic behaviors, CSD strategy would be efficacious to enhance bioavailability of curcumin with high photochemical stability.

Over 10 years clinical outcomes in patients with mitral stenosis with unilateral commissural calcification treated with catheter balloon commissurotomy: single-center experience.

OBJECTIVES: Treatment of mitral valve stenosis with catheter balloon commissurotomy (CBC) yields acceptable immediate results even when one commissure shows calcification. However, the long-term outcomes in such cases remain unclear. METHODS: We examined the immediate and long-term (mean: 11+/-5 years) outcomes of 57 patients who underwent 58 CBC procedures. Patients were classified into group A (no commissural calcification, n=44) or group B (unilateral commissural calcification, n=13). From the appearance of the mitral valve just after CBC, commissurotomy was judged to be bilateral, incomplete, or excessive. End points were death, recurrence of congestive heart failure necessitating hospitalization, embolism, repeat CBC, or mitral valve replacement. RESULTS: There were significant numbers of unfavorable mitral valve morphologies evaluated according to Sellors classification, estimated by echocardiograms; Sellors class I: 20 patients in group A vs. none in group B (p<0.05). Class II: 24 in group A vs. 10 in group B. and class III: none in group A vs. 3 in group B (p<0.05). CBC increased the mitral valve area (Gorin formula) from 1.3+/-0.3 to 2.1+/-0.5 cm2 in patients in group A and from 1.1+/-0.2 to 1.8+/-0.4 cm2 in those in group B (p=n.s.). Among the latter, there were significantly more excessive commissurotomies than in group A and no bilateral commissurotomy. The overall or event-free survival rate during the follow-up of group B showed a lower tendency than in group A (overall: group A: 86.2% vs. group B: 84.6%, p, n.s. event-free: 56.8% vs. 46.2%, respectively, p=n.s.). Univariate predictors of all events in group B included post-CBC pulmonary arterial pressure, and the pattern of commissurotomy after CBC (p<0.05). Excessive commissurotomy increased clinical events some years later, after the procedure. CONCLUSIONS: In this study, involving a small number of subjects, long-term outcomes of patients with unilateral commissural calcification receiving CBC showed no significant difference as compared to those with commissural calcification absence. However, it is necessary to perform careful follow-up of CBC patients with unilateral commissural calcium.

Prospective randomized trial comparing a nitinol self-expanding coronary stent with low-pressure dilatation and a high-pressure balloon expandable bare metal stent.

The recent SCORES trial demonstrated that lower dilatation pressures seen with self-expanding (SE) stents may be associated with lower rates of target lesion revascularization (TLR). To determine whether SE stents with low-pressure dilatation are as safe and effective as balloon expandable (BE) stents. We randomly assigned 254 patients with 279 coronary lesions to groups receiving either SE with low-pressure dilatation <12 atm (n = 143) or conventional BE stents (n = 136). Thereafter, acute results and long-term outcomes were compared. Baseline patient and angiographic characteristics were similar in two groups. The incidence of procedural complications, such as slow flow, side branch occlusion, and edge dissection were significantly lower in the SE group than in the BE group (overall: SE, 17; BE, 35; P < 0.01), and the occurrence of myocardial infarction tended to be lower in SE than in BE (SE, 1; BE, 4; not significant). Although acute gain was significantly smaller with SE than BE (SE, 2.21 +/- 0.65 mm; BE, 2.42 +/- 0.62; P < 0.01), probably due to gradual expansion of the SE stent, nearly identical minimum luminal diameters on follow-up angiography (SE, 2.14 +/- 0.92 mm vs. BE, 2.22 +/- 0.93; not significant) and similar angiographic restenosis (SE, 18.1% vs. BE, 20.5%). and TLR rates (SE, 16.1% vs. BE, 14.0%) were apparent. This prospective randomized trial demonstrates that SE stents with low-pressure dilatation is safe and effective strategy for treating coronary arterial stenosis.

Prevention of no-reflow/slow-flow phenomenon during rotational atherectomy--a prospective randomized study comparing intracoronary continuous infusion of verapamil and nicorandil.

BACKGROUND: The potential exists for microcirculatory impairment during rotational coronary atherectomy (RA) due to embolization of plaque debris, platelet aggregation, or vasospasm. This prospective randomized pilot study aimed to confirm favorable effects of nicorandil during RA compared with verapamil. METHODS: We randomly assigned 200 patients with 219 coronary lesions planned to undergo RA with intracoronary infusion of nicorandil cocktail (100 patients, 109 lesions), which contained nicorandil 24 mg, nitroglycerin 5 mg, and heparin 10,000 U in 1000 mL saline, or verapamil cocktail (100 patients, 110 lesions), which contained verapamil 10 mg instead of nicorandil. Drug cocktails were infused through a 4F Teflon sheath of the rotablator system during RA. The primary end point was incidence of no-reflow/slow-flow phenomenon; secondary end points were those of continuous ST elevation, Q-wave myocardial infarction (MI), and non-Q-wave MI. RESULTS: Group baseline and coronary angiographic characteristics were similar. Rotational atherectomy was performed successfully, and no patients died or required emergency coronary artery bypass grafting. Incidence of no-reflow/slow-flow phenomenon was significantly lower in the nicorandil group (nicorandil 5/109 lesions, verapamil 13/110 lesions, P < .005). Incidences of persistent ST-segment elevation and non-Q-wave MI were significantly lower in the nicorandil group (ST-segment elevation: nicorandil 3/100 patients, verapamil 10/100 patients, P < .05; non-Q-wave MI: nicorandil 2/100, verapamil 9/100 patients, P < .05). One patient each in the 2 groups experienced Q-wave MI. CONCLUSION: Our findings suggest that continuous intracoronary infusion of nicorandil during RA prevents acute periprocedural complications. Nicorandil should be used as adjunctive treatment during RA.

Endoscopic hemostasis using fibrin adhesive to treat hemorrhage in the upper digestive system.

PURPOSE: There are several methods of achieving endoscopic hemostasis of hemorrhage in the upper digestive system. We compared the therapeutic results and advantages of using a local injection of fibrin adhesive for endoscopic hemostasis, which we have found more effective than other hemostatic methods. METHODS: Between October 2000 and April 2002, 16 patients with hemorrhage in the upper digestive system underwent endoscopic hemostasis using fibrin adhesive. The hemorrhage was caused by a hemorrhagic tendency from liver disease, anticoagulant therapy, or failed hemostasis with clipping or local ethanol injection. The fibrin adhesive was injected through a standard 21-gauge endoscopic needle using the so-called sandwich method. RESULTS: Hemostasis was successfully achieved by a single local injection of fibrin adhesive, in all except one patient who had been on anticoagulant therapy for a long time and needed an additional local injection of fibrin adhesive. CONCLUSION: Fibrin adhesive does not cause any tissue injury, and a sufficient amount can be injected endoscopically even in patients with liver dysfunction and those on anticoagulant therapy. Thus, we think that endoscopic hemostasis with fibrin adhesive is safe and effective.

Myocardial perfusion during transient slow-flow in the patient with old vein graft intervention: assessment by serial measurement of pressure-derived fractional flow reserve and thermodilution-derived coronary flow reserve.

A patient with distal slow-flow after stenting in the old vein graft intervention was reported. This case is a first in whom guidewire-based serial measurement of pressure-derived fractional flow reserve (FFR(myo)) and thermodilution-based coronary flow reserve (CFR(thermo)) clearly demonstrated the serial change of microvascular circulation. During slow-flow, CFR(thermo) remained in low value despite significant improvement of FFR(myo) from 0.61 to 0.90. After thrombus aspiration and nicorandil injection, coronary flow reestablished immediately. CFR(thermo) improved significantly from 1.3 during slow-flow to 3.6 after restoration of flow.

Low dose of wortmannin reduces radiosensitivity of human glioblastoma cells through the p53 pathway.

Wortmannin is an inhibitor of PI3-kinase and acts on cultured cells at dosages below 1 microM. Wortmannin also inhibits the gene products of the PI3-kinase family such as ATM or DNA-PK at dosages above 10 microM in cultured cells. There are many reports on the enhancement of radiosensitivity by a high dose of wortmannin inhibiting the proteins of the PI3-kinase family. However, there have been no reports on the effect on radiosensitivity of low doses of wortmannin inhibiting PI3-kinase. We found that low doses of wortmannin reduced the radiosensitivity of human A172 glioblastoma cells. This effect was shown only in wild-type p53 cells, but was not shown in mutant p53 cells such as T98G or A172/248W carrying a dominant point-mutated p53 gene. This result indicates that the PI3-kinase, or another wortmannin-sensitive enzyme, may affect the signal transduction of p53. We examined the response of the p53 pathway by X-ray irradiation. A low dose of wortmannin did not affect the accumulation of p53 and the phosphorylation of p53 at ser-15, but reduced the induction of WAF1 and enhanced the induction of GADD45.