Rosiglitazone protects human neuroblastoma SH-SY5Y cells against MPP+ induced cytotoxicity via inhibition of mitochondrial dysfunction and ROS production

1-Methyl-4-phenylpyridinium ion (MPP(+)), an inhibitor of mitochondrial complex I, has been widely used as a neurotoxin because it elicits a severe Parkinson's disease-like syndrome with elevation of intracellular reactive oxygen species (ROS) level and apoptotic death. Rosiglitazone, a peroxisome proliferator-activated receptor (PPAR)-gamma agonist, has been known to show various non-hypoglycemic effects, including anti-inflammatory, anti-atherogenic, and anti-apoptotic. In the present study, we investigated the protective effects of rosiglitazone on MPP(+) induced cytotoxicity in human neuroblastoma SH-SY5Y cells, as well as underlying mechanism. Our results suggested that the protective effects of rosiglitazone on MPP(+) induced apoptosis may be ascribed to its anti-oxidative properties, anti-apoptotic activity via inducing expression of SOD and catalase and regulating the expression of Bcl-2 and Bax. These data indicated that rosiglitazone might provide a valuable therapeutic strategy for the treatment of progressive neurodegenerative disease such as Parkinson's disease.     

Operative treatment of congenital torticollis

There were 47 patients with congenital muscular torticollis who underwent operative release. After a mean follow-up of 74 months (60 to 90), they were divided into two groups, one aged one to four years (group 1) and the other aged five to 16 years (group 2). The outcomes were assessed by evaluating the following parameters: deficits of lateral flexion and rotation, craniofacial asymmetry, surgical scarring, residual contracture, subjective evaluation and degree of head tilt. The craniofacial asymmetry, residual contracture, subjective evaluation and overall scores were similar in both groups. However, group 2 showed superior results to group 1 in terms of the deficits of movement, surgical scarring and degree of head tilt. It is recommended that operative treatment for congenital muscular torticollis is postponed until the patient can comply successfully with post-operative bracing and an exercise programme.     

Modified release of coated sugar spheres using drug-containing polymeric dispersions

A drug-containing polymeric dispersion was applied onto nonpareil sugar spheres (18/20 mesh) using a fluid-bed spray coater. Eudragit RS30D was selected as the polymeric coating material. Melatonin secreted by the pineal gland in a circadian rhythm was used as a model drug. The release behaviors of the coated sugar spheres were investigated in gastric fluid (pH 1.4) for 2 h, and then continuously in intestinal fluid (pH 7.4) for 14 h. The release rate of the coated sugar spheres decreased with increasing coating levels. The solvent (ethanol) in the coating dispersions significantly decreased the release of the drug due to the good dispersion of the low solubility melatonin in the polymeric films. The polymer (polyvinylpyrrolidone, PVP) and drug contents in the coating dispersions did not affect the release rate. Most of all, the release profiles were drastically changed according to the type and concentration of plasticizers used. The current coating methods that use drug-containing polymeric dispersions could be useful for simultaneous drug loadings and their modified release. The solubilization and controlled release of poorly water-soluble drugs can be achieved as both the solubilizers and drugs are present in the drug-containing polymeric dispersions.     

Norditerpenoid and dianthramide glucoside alkaloids from cultivated<Emphasis Type="Italic">aconitum</Emphasis> species from Korea

A new norditerpene alkaloid named 8-O-methylhypaconine (1) was isolated along with twelve known alkaloids from the underground parts of an unknown species of Aconitum plant culti vated in Korea. Among the known alkaloids, two dianthramide glucosides, N-(2'-beta-glucopyra nosyl-5'-hydroxysalicyl)-5-hydroxyanthranilic acid methyl ester (2) and N-(2'-beta-glucopyranosyl-5'-hydroxysalicyl)-5-hydroxy-6-methoxyanthranilic acid methyl ester (3), were isolated from Aconitum plants for the first time. The structures were established on the basis of chemical and spectroscopic methods.     

Optimized conditions for the extraction of secondary volatile metabolites in Angelica roots by accelerated solvent extraction

Accelerated solvent extraction (ASE) of three common Angelica species found in Asia: Angelica sinensis (Oliv.) Diels from China, Angelica acutiloba (Sieb. et Zucc.) Kitagawa from Japan, and Angelica gigas Nakai from Korea was investigated. Preliminary experiments, including the selection of the solvent, extraction time, pressure, static cycle and time were investigated to optimize experimental parameters. Kováts indices and mass spectra were used to identify the components in the various fractions. These were then confirmed using gas chromatography–mass spectrometry (GC–MS). A total of 18 compounds were identified, with qualitative differences and similarities observed among the cultivars. From the 18 compounds found in the ASE extract of danggui cultivars, the major components were decursin, decursinol angelate (A. gigas); butylidene dihydrophthalide, 4-hydroxy-4-methyl-2-pentanone (A. sinensis); and 9,12-octadecanoic acid in Angelica acutiloba. The optimum ASE operating conditions were n-hexane as extraction solvent, extraction temperature and pressure of 80 °C and 1500 atm, respectively, static cycle of 2 min, and static time of 10 min. Under these conditions, the percentages of main analytes were increased.     

Biochemical and molecular modeling studies of the O-methylation of various endogenous and exogenous catechol substrates catalyzed by recombinant human soluble and membrane-bound catechol-O-methyltransferases

Catechol-O-methyltransferase (COMT, EC 2.1.1.6) catalyzes the O-methylation of a wide array of catechol-containing substrates using s-adenosyl-L-methionine as the methyl donor. In the present study, we have cloned and expressed the human soluble and membrane-bound COMTs (S-COMT and MB-COMT, respectively) in Escherichia coli and have studied their biochemical characteristics for the O-methylation of representative classes of endogenous catechol substrates (catecholamines and catechol estrogens) as well as exogenous catechol substrates (bioflavonoids and tea catechins). Enzyme kinetic analyses showed that these two recombinant human COMTs are functionally active, with catalytic and kinetic properties nearly identical to those of crude or purified enzymes prepared from human tissues or cells. Kinetic parameters for the O-methylation of various substrates were characterized. In addition, computational modeling studies were conducted to better understand the molecular mechanisms for the different catalytic behaviors of human S- and MB-COMTs with respect to s-adenosyl-L-methionine, various substrates, and also the regioselectivity for the formation of mono-methyl ether products. Our modeling data showed that the binding energy values (Delta G) calculated for most substrates agreed well with the measured kinetic parameters. Also, our modeling data precisely predicted the regioselectivity for the O-methylation of these substrates at different hydroxyl groups, the predicted values matched nearly perfectly with the experimental data.     

Modified Ravitch procedure: using a pectus bar for posttraumatic pectus excavatum

Guidelines for surgical management of posttraumatic pectus excavatum have not been established due to the variable clinical manifestations and limited number of cases. A 34-year-old man who was involved in a truck-mixer vehicle crash 6 months previously complained of a depressed anterior chest wall deformity. The patient had successfully undergone subperichondral resection, sternal osteotomy, and pectus bar insertion placed under the depressed sternum, followed by bar rotation for elevation of the chest wall. This case illustrates that a modified Ravitch procedure, using a pectus bar, may be an alternative for posttraumatic pectus excavatum.     

Botulinum toxin A for the management of vulvodynia

Clinically, botulinum toxin A blocks the cholinergic innervation of the target tissue. Recently, it has been proved effective not only at a neuromuscular junction but also within parasympathetic or sympathetic neural synapses. Seven women with pain on genitalia that could not be controlled with conventional pain managements were enrolled in this study. Twenty to 40 U of botulinum toxin A were used in each injection. Injection sites were the vestibule, levator ani muscle or the perineal body. Repeat injections were administered every 2 weeks if the patient's symptoms had not fully subsided. In all patients, pain had disappeared with botulinum toxin A injections. Five patients needed to be injected twice; the other two patients needed only one injection. We did not observe complications related to botulinum toxin A injections, such as pain, hemorrhage, infection, muscle paralysis or other complications. The subjective pain score improved from 8.3 to 1.4, and no one has experienced a recurrence (the follow-up period was four to 24 months, with a mean follow-up of 11.6 months). Botulinum toxin A is effective in blocking nociception. Even though further investigation and well-controlled study will be necessary, we suggest that the botulinum toxin therapy would be useful and safe in managing vulvodynia of muscular or neuroinflammatory origins.