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.     

Effect of protease inhibitors on degradation of recombinant human epidermal growth factor in skin tissue

Recombinant human epidermal growth factor (rhEGF), a polypeptide of 53 amino acid residues, is subject to degradation by numerous enzymes, especially proteases, when it is applied on the skin for the treatment of open wound. Amastatin, aprotinin, bestatin, EDTA, EGTA, gabexate, gentamicin, leupeptin, and TPCK were investigated for the possible protease inhibitors, which may use to protect rhEGF from degradation by the enzymes in the skin. Skin homogenates containing protease inhibitors and rhEGF were incubated at 37°C for 30 minutes. After the reaction was stopped with trifluoroacetic acid, the amount of rhEGF remaining in the sample was determined with an HPLC method. The percentages of rhEGF degraded, at the skin/PBS ratio of 0.25, in the mouse, rat, and human skin homogenate were 85%, 70%, and 46%, respectively. The degree of degradation of rhEGF in the cytosolic fraction was higher than that in the membrane fraction and these enzyme reactions were completed in 30 minutes. Bestatin, EGTA, and TPCK showed significant inhibitory effects on the degradation of rhEGF in the two fractions (p<0.05), while the other protease inhibitors had no significant inhibitory effects or, even resulted in deleterious effects. Therefore, the formulation containing one or several inhibitors among these effective inhibitors would be a promising topical preparation of rhEGF for the treatment of open wound.     

Metabolism of saikosaponin c and naringin by human intestinal bacteria

By human intestinal bacteria, saikosaponin c was transformed to four metabolites, prosaikogenin E1 (E1) prosaikogenin E2 (E2), prosaikogenin E3 (E3) and saikogenin E. Metabolic time course of saikosaponin c was as follows; in early time, saikosaponin c was converted to E1 and E2, and then these were transformed to saikogenin E via E3. Also, this metabolic pathway was similar to the metabolism of saikosaponin c by rat intestinal bacteria.Bacteroides JY-6 andBacteroides YK-4, the bacteria isolated from human intestinal bacteria, could transform saiko-saponin c to E via E1 (or E2) and E3. However, these bacteria were not able to directly transform E1 and E2 to saikogenin E. Naringin was mainly transformed to naringenin by human intestinal bacteria. The minor metabolic pathway transformed naringin to naringenin via prunin. By JY-6 or YK-4, naringin was metabolized to naringenin only via prunin.     

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.     

Hydrolysis kinetics of metampicillin by high performance liquid chromatography

The hydrolysis of metampicillin to ampicillin was investigated using high performance liquid chromatography. We developed the simultaneous determination of metampicillin and ampicillin using a Zorbax CN column and 5% acetonitrile and 8% methanol in 0.02 M phosphate buffer (pH 7.0) as mobile phase. Metampicillin was hydrolyzed to ampicillin with half life of 41.5 min at physiological pH and temperature. In acidic pH, metampicillin was rapidly hydrolyzed to ampicillin within a chromatographic separation.     

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.     

Hypothermia does not result in more complications after colon surgery

Our objective was to determine the incidence of complications in postoperative patients who were either normothermic or hypothermic. A recent, widely publicized paper concluded that the maintenance of normothermia could reduce the incidence of infectious complications and shorten hospitalization in patients undergoing colorectal surgery. However, some controversy arose regarding the methods of this paper. Patients were deliberately rendered hypothermic, were given more than 3.5 days of prophylactic antibiotics and were transfused significantly more units of blood. We reviewed the charts of 150 consecutive patients who underwent elective partial or subtotal colectomy with primary anastomosis. Among the key items analyzed were intraoperative and postoperative temperature, use of warming devices, duration of surgery, transfusions, interval to oral intake and bowel function, length of stay, complications, infections, and laboratory values. Hypothermia was defined as intraoperative temperature <95.5 degrees F. There were 101 normothermic patients and 49 hypothermic patients. Hypothermic patients had a mean age of 68.7 years versus 66.8 for the normothermic patients (P = 0.472). Comorbidities were similar in both groups. Warming devices were used in >90 per cent of the patients in both groups. The rates of postoperative infections and complications were similar in both groups. Postoperative lengths of stay were also not different. Despite finding that one-third of our patients were hypothermic during elective colon resection, hypothermia had no effect on outcome variables. In contrast to the previous study, the incidence of infectious complications was identical in our patients. Before ascribing postoperative complications and increased resource utilization as adverse effects of hypothermia, further studies are indicated.