An efficient synthesis of 3-(E)-hydroxypropenyl cephem derivatives, key intermediates for 3-(E)-ammoniopropenylcephalosporin antibiotics

An efficient synthesis of 3-(E)-hydroxy- and 3-(E)-acetoxypropenylcephem derivatives, key intermediates for the synthesis of 3-(E)-propenylcephalosporins was achievedvia Stille coupling reaction of 3-trifloxycephem with 3-(E)-tributylstannylallylic alcohol.     

New flavonoids from the aerial parts of Aconitum chiisanense

The studies were carried out to evaluate the constituents in the aerial part of Aconitum chiisanense (Ranunculaceae). From the butanol fraction of the methanol extract, kaempferol 3- O-beta-glucopyranoside-7- O-(6-trans-caffeoyl)-beta-glucopyranosyl-(1-->2)-alpha-rhamnopyranoside (I), quercetin 3- O-beta-glucopyranoside-7- O-(6-trans-caffeoyl)-beta-glucopyranosyl-(1-->2)-alpha-rhamnopyranoside (II), kaempferol 3- O-beta-glucopyranoside-7- O-(6-trans-feruloyl)-beta-glucopyranosyl-(1-->2)-alpha-rhamnopyranoside (III), kaempferol 3- O-beta-glucopyranoside-7- O-(6-benzoyl)-beta-glucopyranosyl-(1-->2)-alpha-rhamnopyranoside (IV), kaempferol 7- O-(6-trans)-caffeoyl)-beta-glucopyranosyl-(1-->2)-alpha-rhamnopyranoside (V), and kaempferol 7- O-beta-glucopyranosyl-(1-->2)-alpha-rhamnopyranoside (VI) were isolated and identified on the basis of their physicochemical and spectroscopic evidence (UV, IR, FAB(-)MS, (1)H-NMR, (13)C-NMR, (1)H- (1)H COSY, HMQC and HMBC). New compounds I-VI were named chiisanin (I), chiiribanin (II), chiiribaconin (III), chiirin (IV), chiiricanin (V), and chiirirhamnin (VI), respectively.     

Clonazepam release from core-shell type nanoparticlesin vitro

AB-type amphiphilic copolymers (abbreviated as LE) composed of poly (L-leucine) (PLL) as the A component and poly (ethylene oxide) (PEO) as the B component were synthesized by the ring-opening polymerization of L-leucine N-carboxy-anhydride initiated by methoxy polyoxyethylene amine (Me-PEO-NH₂) and characterized. Core-shell type nanoparticles were prepared by the diafiltration method. Particle size distribution obtained by dynamic light scattering was dependent on PLL composition and the size for LE-1, LE-2 and LE-3 was 369.6±267, 523.4±410 and 561.2±364 nm, respectively. Shapes of the nanoparticles observed by transmission electron microscope (TEM) were almostly spherical. The critical micelle concentration (CMC) of the nanoparticles determined by a fluorescence probe technique was dependent on the composition of hydrophobic PLL, and the CMC for LE-1, LE-2 and LE-3 was 2. 0×10⁻⁶, 1.7×10⁻⁶ and 1.5×10⁻⁶ (mol/l), respectively. Clonazepam release from core-shell type nanoparticles in vitro was dependent on PLL composition and drug loading content.     

Pretreatment of low dose radiation reduces radiation-induced apoptosis in mouse lymphoma (EL4) cells

Induction of an adaptive response to ionizing radiation in mouse lymphoma (EL4) cells was studied by using cell survival fraction and apoptotic nucleosomal DNA fragmentation as biological end points. Cells in early log phase were pre-exposed to low dose of γ-rays (0.01 Gy) 4 or 20 hrs prior to high dose γ-ray (4, 8 and 12 Gy for cell survival fraction analysis; 8 Gy for DNA fragmentation analysis) irradiation. Then cell survival fractions and the extent of DNA fragmentation were measured. Significant adaptive response, increase in cell survival fraction and decrease in the extent of DNA fragmentation were induced when low and high dose γ-ray irradiation time interval was 4 hr. Addition of protein or RNA synthesis inhibitor, cycloheximide or 5,6-dichloro-1-β-d-ribofuranosylbenzimidazole (DRFB), respectively during adaptation period, the period from low dose γ-ray irradiation to high dose γ-ray irradiation, was able to inhibit the induction of adaptive response, which is the reduction of the extent DNA fragmentation in irradiated EL4 cells. These data suggest that the induction of adaptive response to ionizing radiation in EL4 cells required both protein and RNA synthesis.     

Ginsenoside Rs3, a genuine dammarane-glycoside from Korean red ginseng

A genuine dammarane-glycoside, named as ginsenoside Rs₃, was isolated from the MeOH extracts of Korean red ginseng (Panax ginseng C.A. Meyer) through repeated silica gel column chromatographies and its chemical structure was determined as (20S)-protopanaxadiol 3-O-[6″-O-acetyl-β-D-glucopyranosyl (1→2)-β-D-glucopyranoside on the basis of several spectral and physical evidences including HMBC and FAB-MS.     

A case of prominent epicardial fat mimicking a tumor on echocardiography

Epicardial fat may anteriorly produce an echo-free space that can be mistaken for pericardial fluid. We recently experienced a 67-year-old woman with prominent epicardial fat which was presented as an echogenic tumor-like mass. She underwent open pericardiostomy to relieve large amount of pericardial effusion. Operative findings revealed only prominent epicardial fat. Biopsy of the pericardial and fat tissues revealed an inflammation and normal fat cells without any malignant cell infiltration.     

Bone marrow edema and associated pain in early stage osteonecrosis of the femoral head: prospective study with serial MR images

PURPOSE: To determine the accuracy of magnetic resonance (MR) cholangiography for demonstration of the biliary tract and detection of biliary complications in patients who have undergone orthotopic liver transplantation. MATERIALS AND METHODS: Breath-hold half-Fourier rapid acquisition with relaxation enhancement MR cholangiography was performed in 25 patients who had undergone orthotopic liver transplantation. MR cholangiograms were prospectively and independently interpreted by two radiologists for depiction of the biliary tract and ductal anastomosis and for complications (eg, biliary dilatation, stricture, stones). MR cholangiographic findings were correlated with findings from direct cholangiography (n = 24) and surgery (n = 1). RESULTS: MR cholangiography completely demonstrated first-order intrahepatic bile ducts in 23 (92%) patients, the donor extrahepatic bile duct in 25 (100%), the recipient extrahepatic bile duct in 17 of 18 (94%), and the anastomosis in 24 (96%). The sensitivity, specificity, accuracy, positive predictive value, and negative predictive value of MR cholangiography for detection of biliary dilatation and stricture were each 100%. Complete interobserver agreement occurred in the detection of biliary dilatation and stricture. The sensitivity, specificity, accuracy, positive predictive value, and negative predictive value of MR cholangiography for detection of stones were 100% for one radiologist and 86%, 100%, 96%, 100%, and 95%, respectively, for the other. Both radiologists agreed on the diagnosis of bile duct stones in six of seven cases (kappa = 0.90). CONCLUSION: MR cholangiography enables accurate depiction of the biliary tract and detection of biliary complications in patients with an orthotopic liver transplant.     

Stereoselective synthesis of (±)-epibatidine analog: (±)-2β-(2-chloro-5-pyridinyl)-8-azabicyclo[3.2.1]octane

Stereoselective synthesis of (+/-)-epibatidine analog 2, which contains the 8-azabicyclo[3.2.1]octane ring system, was achieved by using palladium-catalyzed Heck-type coupling reaction from 3.     

Prognostic significance of c-kit mutation in localized gastrointestinal stromal tumors.

PURPOSE: Constitutive mutational activation of c-kit has been found to be associated with the pathogenesis of gastrointestinal stromal tumors (GISTs). The prognostic significance of c-kit mutations, however, is still controversial. EXPERIMENTAL DESIGN: We examined 86 patients curatively resected for localized GIST. Genomic DNA was extracted from paraffin-embedded tumor tissues. Exons 9, 11, 13, and 17 of the c-kit gene were amplified by PCR and sequenced. RESULTS: Mutations in exon 11 were detected in 61 tumors, and mutations in exon 9 were observed in three tumors, whereas no mutations were detected in exons 13 or 17. The overall c-kit mutation frequency was 74%. Amino acid alterations in the 61 tumors with exon 11 mutations were deletion in 33 tumors, substitution in 20, both deletion and substitution in 4, insertion in 1, and duplication in 3. Histologically, tumors with c-kit mutations showed higher mitotic counts and higher cellularity. The 5-year relapse-free survival (RFS) in patients having GISTs with c-kit mutations was 21%, compared with 60% in those without c-kit mutations. Significantly higher RFS rates were observed in patients with tumors having mitotic counts < 5 mitoses/50 high power field, spindle-cell histology, tumor size < 5 cm, or gastric GISTs. Multivariate analyses indicated association of poorer RFS with a higher mitotic count > or = 5 of 50 high power fields; odds ratio (OR) = 3.0], presence of c-kit mutations (OR = 5.6), and a larger tumor size (> or = 5 cm; OR = 4.2). CONCLUSIONS: The presence of c-kit mutation, along with high mitotic count and larger tumor size, was an independent factor for poor prognosis in patients with localized GISTs.