Anti-allergy activities of Kuji amber extract and kujigamberol.

Amber is fossilized tree resin and several biologically active compounds were isolated from ambers using the growth-restoring activity of the mutant yeast [Saccharomyces cerevisiae (zds1∆ erg3∆ pdr1∆ pdr3∆)] involving Ca2+-signal transduction. The aim of this study is to investigate the anti-allergic effect of both the methanol extract of Kuji amber (MEKA) and its main biologically active constituent, kujigamberol (15,20-dinor-5,7,9-labdatrien-18-ol) having activity against the mutant yeast. Both MEKA and kujigamberol inhibited the degranulation of RBL-2H3 cells by stimulation of thapsigargin (Tg) (IC50 = 15.0 µg/ml and 29.1 µM) and A23187 (IC50 = 19.6 µg/ml and 24.9 µM) without cytotoxicity, but not by stimulation of IgE + DNP-BSA (Ag) (IC50 > 50.0 µg/ml and 50.0 µM). However, both inhibited Ca2+-influx in RBL-2H3 cells by all three stimulations in a dose dependent manner. Leukotriene C4 production in RBL-2H3 cells stimulated by A23187 was also inhibited by both through the inhibition of ERK1/2 phosphorylation. In an ovalbumin-induced rhinitis model of guinea pigs, nasal administration of MEKA and kujigamberol inhibited nasal blockade in a dose-dependent manner and the effect was about 5 times potent than that of a steroid clinical drug, mometasone furoate. The growth-restoring activity of MEKA and kujigamberol against the mutant yeast is involved in the anti-allergic activities against cells and animals, and both are expected to be candidates for the development of new anti-allergy agents.

Efficacy of neuromuscular electrical stimulation for preventing quadriceps muscle wasting in patients with moderate or severe acute stroke: A pilot study.

BACKGROUND: Stroke-related muscle wasting is one of the factors leading to long-term disability and functional dependency. No study has reported an effective therapeutic intervention for such muscle wasting. OBJECTIVE: The purpose of this study was to investigate the effects of neuromuscular electrical stimulation (NMES) on quadriceps muscle mass preservation in patients with acute moderate or severe stroke by using ultrasonography (US). METHODS: Twenty patients with acute, moderate, or severe stroke (age: 68±11 years) were divided into usual care group (control group) and intervention groups (NMES group), respectively. Patients in the NMES group underwent NMES treatment for bilateral quadriceps muscles for 2 weeks in addition to the usual care. Quadriceps muscle thickness was measured on admission and 2 weeks after the first measurement. RESULTS: The quadriceps muscle thickness on the paretic and non-paretic sides in the NMES group (-12.4% ±12.7%, -5.5% ±15.3%, respectively) significantly decreased to a lesser degree than that in the control group (-29.5% ±12.1%, P = 0.004; and -22.0% ±16.8%, P = 0.04, respectively). CONCLUSIONS: NEMS seemed to have preserved the quadriceps muscle mass in patients with moderate or severe acute stroke.

Yeast Ca(2+)-signal transduction inhibitors isolated from Dominican amber prevent the degranulation of RBL-2H3 cells through the inhibition of Ca(2+)-influx.

A new norlabdane compound, named kujigamberol has previously been isolated from Kuji amber (but not from Baltic amber) by activity guided fractionation. However, there has been no study of biological compounds in Dominican amber. Biological activities were examined using the hypersensitive mutant yeast (zds1Δ erg3Δ pdr1Δ pdr3Δ) with respect to Ca(2+)-signal transduction, enzymes and rat basophilic leukemia (RBL)-2H3 cells. The structures were elucidated on the basis of spectral analysis including high resolution (HR)-EI-MS, 1D NMR and 2D NMR. Three diterpenoid compounds, 5(10)-halimen-15-oic acid (1), 3-cleroden-15-oic acid (2) and 8-labden-15-oic acid (3), which are different from the bioactive compounds in Kuji and Baltic ambers, were isolated from Dominican amber. They inhibited both calcineurin (CN) (IC50=40.0, 21.2 and 34.2µM) and glycogen synthase kinase-3ß (GSK-3ß) (IC50=48.9, 43.8 and 41.1µM) which are involved in the growth restored activity against the mutant yeast. The most abundant compound 2 showed inhibitory activity against both degranulation and Ca(2+)-influx in RBL-2H3 cells. The compounds having the growth restoring activity against the mutant yeast have potential as anti-allergic compounds.

Sinomenine and magnoflorine, major constituents of Sinomeni caulis et rhizoma, show potent protective effects against membrane damage induced by lysophosphatidylcholine in rat erythrocytes.

The effects of the water extract of Sinomeni Caulis et Rhizoma (SCR-WE) and its major constituents, sinomenine (SIN) and magnoflorine (MAG), on moderate hemolysis induced by lysophosphatidylcholine (LPC) were investigated in rat erythrocytes and compared with the anti-hemolytic effects of lidocaine (LID) and propranolol (PRO) as reference drugs. LPC caused hemolysis at concentrations above the critical micelle concentration (CMC), and the concentration of LPC producing moderate hemolysis (60 %) was approximately 10 µM. SCR-WE at 1 ng/mL-100 µg/mL significantly inhibited the hemolysis induced by LPC. SIN and MAG attenuated LPC-induced hemolysis in a concentration-dependent manner from very low to high concentrations (1 nM-100 µM and 10 nM-100 µM, respectively). In contrast, the inhibiting effects of LID and PRO on LPC-induced hemolysis were observed at higher concentrations (1-100 µM) but not at lower concentrations (1-100 nM). Neither SIN nor MAG affected micelle formation of LPC, nor, at concentrations of 1 nM-1 µM, did they attenuate the hemolysis induced by osmotic imbalance (hypotonic hemolysis). Similarly, SCR-WE also did not modify micelle formation or hypotonic hemolysis, except at the highest concentration. These results suggest that SIN and MAG potently protect the erythrocyte membrane from LPC-induced damage and contribute to the beneficial action of SCR-WE. The protective effects of SIN and MAG are mediated by some mechanism other than prevention of micelle formation or protection of the erythrocyte membrane against osmotic imbalance.

Pisiferdiol restores the growth of a mutant yeast suffering from hyperactivated Ca2+ signalling through calcineurin inhibition.

In the course of our screening program for a new inhibitor of the Ca(2+) signalling pathway using mutant yeast [Saccharomyces cerevisiae (zds1Δ erg3Δ pdr1Δ pdr3Δ)], a mouse PP2Cα activator, pisiferdiol, isolated from Chamaecyparis pisifera, was found to alleviate the Ca(2+) signal-mediated growth inhibition. Pisiferdiol showed growth inhibition activity against the mpk1Δ strain compared with the cnb1Δ strain and induced Li(+) sensitivity to the wild-type strain, indicating that it suppresses the calcineurin pathway in the yeast. However, the Li(+) sensitivity to ptc1Δ strain by pisiferdiol was diminished. Pisiferdiol showed growth restored activity in the zds1Δ strain without immunophilins Fkb1p or Cph1p, and in the pmc1Δ strain. It inhibited calcineurin-induced expression in the reporter gene assay and decreased the protein expression (Western blots) of calcineurin (Cnb1p) in addition to a decrease of Swe1p and phosphorylation of Cdc28p in the mutant yeast. These results showed that pisiferdiol could suppress indirectly the action of calcineurin and restored the growth inhibition of the mutant yeast through Ptc1p activation.

Combined use of an occlusion balloon catheter and a microcatheter for embolization of the unselectable right inferior phrenic artery supplying hepatocellular carcinoma.

We report the combined use of an occlusion balloon catheter and a microcatheter for transcatheter arterial embolization (TAE) of hepatocellular carcinoma (HCC) fed by the unselectable right inferior phrenic artery (IPA). In one case, HCC was fed by the reconstructed right IPA via a small branch arising from the proximate portion of the celiac artery. In another, the tumor was fed by the right IPA that had been previously embolized with coils. TAE was successfully performed through a microcatheter placed in the celiac artery immediately proximal to the occluding balloon catheter of the celiac trunk and coil embolization of the left gastric artery.