Raspberry ketones have important therapeutic properties such as anti-influenza and prevention of diabetes. In order to obtain raspberry ketone from Chlamydomonas reinhardtii, two enzymes catalyzing the last two steps of raspberry ketone synthesis, i.e. 4-coumaryl-CoA ligase (4CL) and polyketide synthase (PKS1), were fused using a glycine-serine-glycine (GSG) tripeptide linker to construct an expression vector pChla-4CL-PKS1. The fusion gene 4CL-PKS1 driven by a PSAD promoter was transformed into a wild-type (CC125) and a cell wall-deficient C. reinhardtii (CC425) by electroporation. The results showed the recombinant C. reinhardtii strain CC125 and CC425 with 4CL-PKS1 produced raspberry ketone at a level of 6.7 μg/g (fresh weight) and 5.9 μg/g (fresh weight), respectively, both were higher than that of the native raspberry ketone producing plants (2-4 μg/g).
Acyl Coenzyme A ; Butanones ; Chlamydomonas reinhardtii/genetics* ; Ligases ; Polyketide Synthases

The chalcone synthase (CHS) superfamily of the type III polyketide synthases (PKSs) generates backbones of a variety of plant secondary metabolites. Benzalacetone synthase (BAS) catalyzes a condensation reaction of decarboxylation between the substrates of 4-coumaric coenzyme A and malonyl coenzyme A to generate benzylidene acetone, whose derivatives are series of compounds with various biological activities. A BAS gene Pcpks2 and a bifunctional CHS/BAS PcPKSI were isolated from medicinal plant P. cuspidatum. Crystallographic and structure-based mutagenesis studies indicate that the functional diversity of the CHS-superfamily enzymes is principally derived from small modifications of the active site architecture. In order to obtain an understanding of the biosynthesis of polyketides in P. cuspidatum, which has been poorly described, as well as of its activation mechanism, PcPKS2 was overexpressed in Escherichia coli as a C-terminally poly-His-tagged fusion protein, purified to homogeneity and crystallized, which is helpful for the clarification of the catalytic mechanism of the enzyme and lays the foundation for its genetic engineering manipulation.
Butanones ; Catalytic Domain ; Crystallization ; Fallopia japonica ; enzymology ; Polyketide Synthases ; genetics ; metabolism

A 33-year-old male presented with an acute onset of back pain and abdominal pain. He was 189.9 cm tall and had an arm span of 194 cm, and had mild pectus carinatum as well as arachnodactyly. Plain radiographs showed kyphoscoliosis of the lumbar spine, bamboo spine of the thoracic spine, and sacroiliitis of the pelvis. Abdominal computed tomography revealed debakey type 3 aortic dissection. We prescribed beta blockers to control his blood pressure. According to the modified New York criteria, we diagnosed him with HLA negative ankylosing spondylitis and initiated therapy with nabumetone and sulfasalazine. We later diagnosed Marfan syndrome based on the Ghent criteria and mutation screening at the fibrillin-1. After treatment, he has been followed up without symptoms or complications.
Abdominal Pain ; Arachnodactyly ; Arm ; Back Pain ; Blood Pressure ; Butanones ; Humans ; Male ; Marfan Syndrome ; Mass Screening ; Microfilament Proteins ; New York ; Pelvis ; Sacroiliitis ; Spine ; Spondylitis, Ankylosing ; Sulfasalazine

In this study, I am planning to analyze the contents of Simple formula in Treasured Mirror of Eastern Medicine (TM), and then find out the historical implication of medical science. Simple formula is a prescription that is consisted of a single or three to four kinds of medicines, and this does not follow typical control principles such as 'sovereign, minister, assistant and courier'. While simple formulas are often built after major formulas, TM placed simple formulas to an end of each classified item. It is difficult to find a similar compilation style as that of Simple formula among similar volumes of medical books during the same period of TM. Thus, it can be assumed that TM included simple formulas for special purposes or reasons which are deemed as an important factor in stipulating the features of TM. The tradition of Simple formula, using medicinal herbs which can be easily acquired and trying to make an effect with a small number of herbs, had existed before Goryeo Dynasty. Introduced by Emergency Prescriptions from the Countryside and Samhwaja's Formulary from the Countryside, the tradition of Simple formula is succeeded by Compendium of Prescriptions from the Countryside, and after a while, it is synthetically arranged and recognized through Simple formula of TM. By analyzing simple formulas of TM, I could find out the followings. First, in simple formulas of TM, in which the components are the number of medicinal herbs, the name of prescription, and their application, should be understood as a simply consisted prescription rather than single medicine formulas. Second, simple formulas of TM are 2,001 in total, and are organized in most items. Third, although simple formulas cite a number of formulary, it shows a high degree of dependence to Classified Emergency Materia Medica. This shows that simple formulas that are structured to use medicine according to symptoms based on the effect of each medicinal herb, without understanding or dialectic process of syndrome differentiation. Fourth, while the part of medicinal herbs, Decoction section, focuses on listing the information of each medicinal herb, simple formulas introduce effect, dose, volume and even a mix with other medicinal herbs and an application of them. Therefore, a simple formula evaluates single medicinal herb as a sort of prescription. Fifth, more than half of 33 kinds of medicinal herbs, which are used more than 11 times in simple formulas of TM, are easy to get around the village, and their Korean names of Materia Medica from the Countryside are possible to be seen in Decoction section. However, the fact that Materia Medica from China such as Coptics chinensis and Realgar is included in simple formulas means that they are not limited to Materia Medica from the Countryside, and some of Materia Medica from China were not difficult to be procured in the time of publication of TM. Specific purpose of publishing simple formulas is not written separately. However, through the king's command of King Seonjo (1552-1608) in introduction, the active containing of folk prescriptions, and the emphasis of medicinal herb's volume using simple formulas, it is assumed that the Chosun government at that time tried to provide friendly and practical medical information with simple formulas, to collect and formulate private medical experiences in order to expand their extension of medical information, and to maximize the effect of treatment. The compilation system like TM was highly regarded but was also the target of criticism. In particular, King Jeongjo (1752-1800) criticized the complicatedness of TM and deleted information related to simple formulas through government compilation medical texts such as Explanation of Subtleties for the People's Longevity, New Edition on Universal Relife. However, simple formulas which were not composed of many medicinal herbs could be useful way for treating people who did not have professional medical knowledge and did not have a large range of herbs. In actuality, Secret Works of Universal Benefit, the representative compilation of civil medicinal text which was published after TM included information related to simple formulas, and in Records for rural life of Chosun gentlemen, the framework of simple formulas of TM was maintained and is filled with a vast amount of information. Furthermore, cases of utilizing simple formulas are included in the U-Jam's miscellaneous writings which is a clinical record. In Simple formulas of TM, private medical experiences at the time of Chosun are written first, then recognized by the experts, and finally returned to the public. Although the purpose and the target of these simple formulas publication are not clearly known, it is easy found, does not require any advanced medical knowledge, and above all, the people must have welcomed to the supply of economic simple formulas. Therefore, simple formulas show an aspect of TM, as a medical book for public.
Arsenicals ; Butanones ; China ; Collodion ; Cyclooxygenase 2 Inhibitors ; Dental Cavity Lining ; Emergencies ; Hypogonadism ; Longevity ; Materia Medica ; Mitochondrial Diseases ; Ophthalmoplegia ; Plants, Medicinal ; Prescriptions ; Publications ; Sulfides

Twenty five new beta-aminoalcohols containing nabumetone moiety were prepared via the reduction of potassium borohydride with a convenient and efficient procedure, starting from beta-aminoketones that have been synthesized by our group. Their chemical structures were determined by IR, MS, 1H NMR, 13C NMR, HR-MS and antidiabetic activities were screened in vitro. Preliminary results revealed that the antidiabetic activity of most beta-aminoalcohols were better than that of the corresponding beta-aminoketones. Although most compounds showed weak antidiabetic activity, the alpha-glucosidase inhibitory activity of compounds 5hd(1) and 5id(2) reached 74.37% and 90.15%, respectively, which were superior to the positive control. The relative peroxisome proliferator-activated receptor response element (PPRE) activity of five compounds were more than 60%, among them compound 5ca possessed the highest activity (112.59%). As lead molecules of antidiabetic agents, compounds 5hd(1), 5id(2) and 5ca deserve further study.
Amino Alcohols ; chemical synthesis ; chemistry ; pharmacology ; Butanones ; chemical synthesis ; chemistry ; pharmacology ; Cyclooxygenase 2 Inhibitors ; chemical synthesis ; chemistry ; pharmacology ; Glycoside Hydrolase Inhibitors ; Hypoglycemic Agents ; chemical synthesis ; chemistry ; pharmacology ; Peroxisome Proliferator-Activated Receptors ; agonists ; metabolism ; Response Elements ; alpha-Glucosidases ; metabolism

OBJECTIVETo investigate the pathological changes of major organs in rats that have inhaled methyl ethyl ketone peroxide (MEKP) aerosol and to provide clues to the oxidative damage mechanism of MEKP.

METHODSA total of 100 Sprague-Dawley rats (male-to-female ratio = 1:1) were randomly and equally divided into blank control group, solvent control group, and 50, 500, and 1000 mg/m(3) MEKP exposure groups to inhale clean air, solvent aerosol, or MEKP for 6 h per day, 5 d per week, for 13 weeks. A rat model of subchronic MEKP exposure was established. The clinical manifestations during exposure were recorded. The organ coefficients of the kidney, thymus, and testis were calculated. The histopathological changes of the lung, liver, and testis were observed by HE staining.

RESULTSThe male rats in 1000 mg/m(3) MEKP exposure group had significantly lower organ coefficients of the kidney and testis than those in blank control group, solvent control group, and 50 and 500 mg/m(3) MEKP exposure groups (P < 0.05). The rats in 1000 mg/m(3) MEKP exposure group had a significantly lower organ coefficient of the thymus than those in blank control group and solvent control group (P < 0.05). Some rats in 500 and 1000 mg/m3 MEKP exposure groups had significant damage to the lung, liver, and testis, which demonstrated a worsening trend as the dose increased. Pulmonary hyperinflation, hyperemia, bleeding, interstitial pneumonia, and even lung abscess were seen in the damaged lung. Nuclear enrichment, hepatocyte steatosis, and mild cellular edema in the portal area were seen in the damaged liver. Variable degeneration, necrosis, and dysplasia of spermatogenic cells and significant decrease in sperms in spermatogenic cells were seen in the damaged testis. The female rats in blank control group, solvent control group, and 50, 500, and 1000 mg/m(3) MEKP exposure groups showed no pathological changes in the ovary.

CONCLUSIONInhalation of MEKP aerosol can cause oxidative damage to the liver, lung, kidney, thymus, and testis in rats, particularly to the testis in male rats.

Animals ; Butanones ; administration & dosage ; toxicity ; Female ; Inhalation Exposure ; Kidney ; drug effects ; pathology ; Liver ; drug effects ; pathology ; Lung ; drug effects ; pathology ; Male ; Rats ; Rats, Sprague-Dawley ; Testis ; drug effects ; pathology ; Thymus Gland ; drug effects ; pathology

PURPOSE: The aim of this study is to explore non-steroid anti-inflammation drugs (NSAIDs) potency for pelvic floor muscle pain by measuring local concentration in a rat model. MATERIALS AND METHODS: We used nine NSAIDs, including nabumetone, naproxen, ibuprofen, meloxicam, piroxicam, diclofenac potassium, etodolac, indomethacin, and sulindac, and 9 groups of female Wister rats. Each group of rats was fed with one kind of NSAID (2 mg/mL) for three consecutive days. Thereafter, one mL of blood and one gram of pelvic floor muscle were taken to measure drug pharmacokinetics, including partition coefficient, lipophilicity, elimination of half-life (T1/2) and muscle/plasma converting ratio (Css, muscle/Css, plasma). RESULTS: Diclofenac potassium had the lowest T1/2 and the highest mean Css, muscle/Css, plasma (1.9 hours and 0.85+/-0.53, respectively). The mean Css, muscle/Css, plasma of sulindac, naproxen and ibuprofen were lower than other experimental NSAIDs. CONCLUSION: Diclofenac potassium had the highest disposition in pelvic floor muscle in a rat model. The finding implies that diclofenac potassium might be the choice for pain relief in pelvic muscle.
Animals ; Anti-Inflammatory Agents, Non-Steroidal/*therapeutic use ; Butanones/therapeutic use ; Chronic Pain/*drug therapy ; Diclofenac/therapeutic use ; Female ; Muscles/drug effects ; Naproxen/therapeutic use ; Pelvic Floor/*pathology ; Pelvic Pain/*drug therapy ; Piroxicam/therapeutic use ; Rats ; Rats, Wistar ; Thiazines/therapeutic use ; Thiazoles/therapeutic use

OBJECTIVETo observe the rate of efficacy and adverse drug reaction of non-steroidal anti-inflammatory drugs (NSAIDs) in the population with osteoarthritis and rheumatoid arthritis, based on available clinical data.

METHODSUsing Meta analysis to evaluate the data of effect and safety profile of NSAIDs from 19 articles on randomized clinical trials published from 1990 to 2001 in Chinese journals. The total number of patients enrolled for evaluation on rates of effectiveness and adverse drug reaction were 1 732 and 2 925, respectively.

RESULTSData on the effect and safety were comparatively heterogeneous among different kinds of NSAIDs. The effective rates (95% CI) were as follows: nabunetone, 66.7% (61.9% - 71.4%); meloxicam, 68.4% (59.2% - 77.6%); naproxen, 64.5% (59.8% - 69.1%); nimesulide, 79.8% (75.7% - 84.0%); ibuprofen, 77.2% (70.7% - 83.8%); diclofenac, 77.1% (69.2% - 85.0%); oxaprozin, 65.8% (59.5% - 72.0%). Rates of adverse drug reaction (95% CI) were as follows: nabunetone, 16.3% (12.5% - 20.0%); meloxicam, 10.2% (4.2% - 16.2%); naproxen, 29.2% (24.8% - 33.6%); nimesulide, 20.2% (16.0% - 24.3%); ibuprofen, 16.7% (14.7% - 18.8%); diclofenac, 19.3% (11.9% - 26.7%); oxaprozin, 12.7% (8.9% - 16.7%) respectively.

CONCLUSIONThe rates of effect and adverse reaction on patients having osteoarthritis and rheumatoid arthritis with NSAIDs treatment would largely depend on the drugs being used. Within 2 - 8 weeks of treatment, the effective rate and rate of adverse drug reaction with commonly used NSAIDs as nabumeton, meloxicam, etc., were 59.2% - 85.0% and 4.2% - 33.6%, respectively.

Anti-Inflammatory Agents, Non-Steroidal ; adverse effects ; therapeutic use ; Arthritis, Rheumatoid ; drug therapy ; Butanones ; adverse effects ; therapeutic use ; China ; Diclofenac ; adverse effects ; therapeutic use ; Humans ; Ibuprofen ; adverse effects ; therapeutic use ; Naproxen ; adverse effects ; therapeutic use ; Osteoarthritis ; drug therapy ; Propionates ; adverse effects ; therapeutic use ; Randomized Controlled Trials as Topic ; Sulfonamides ; adverse effects ; therapeutic use ; Thiazines ; adverse effects ; therapeutic use ; Thiazoles ; adverse effects ; therapeutic use

BACKGROUND/AIMS: The use of proton pump inhibitors or misoprostol is known to prevent the gastrointestinal complications of nonsteroidal anti-inflammatory drugs (NSAIDs). Rebamipide is known to increase the mucosal generation of prostaglandins and to eliminate free oxygen radicals, thus enhancing the protective function of the gastric mucosa. However, it is unknown whether rebamipide plays a role in preventing NSAID-induced gastropathy. The aim of this study was to determine the effectiveness of rebamipide compared to misoprostol in preventing NSAID-induced gastrointestinal complications in patients requiring continuous NSAID treatment. METHODS: We studied 479 patients who required continuous NSAID treatment. The patients were randomly assigned to groups that received 100 mg of rebamipide three times per day or 200 microg of misoprostol three times per day for 12 weeks. The primary endpoint of the analysis was the occurrence rate of gastric ulcers, as determined by endoscopy after 12 weeks of therapy. RESULTS: Of the 479 patients in the study, 242 received rebamipide, and 237 received misoprostol. Ultimately, 44 patients (18.6%) withdrew from the misoprostol group and 25 patients (10.3%) withdrew from the rebamipide group. There was a significant difference in withdrawal rate between the two groups (p=0.0103). The per protocol analysis set was not valid because of the dropout rate of the misoprostol group; thus, the intention to treat (ITT) analysis set is the main set for the efficacy analysis in this study. After 12 weeks, the occurrence rate of gastric ulcers was similar in the rebamipide and misoprostol groups (20.3% vs 21.9%, p=0.6497) according to ITT analysis. In addition, the therapeutic failure rate was similar in the rebamipide and misoprostol groups (13.6% vs 13.1%, p=0.8580). The total severity score of the gastrointestinal symptoms was significantly lower in the rebamipide group than in the misoprostol group (p=0.0002). The amount of antacid used was significantly lower in the rebamipide group than in the misoprostol group (p=0.0258). CONCLUSIONS: Rebamipide can prevent gastric ulcers when used with NSAIDs and can decrease the gastrointestinal symptoms associated with NSAID administration. When the possibility of poor compliance and the potential adverse effects of misoprostol are considered, rebamipide appears to be a clinically effective and safe alternative.
Adult ; Aged ; Alanine/administration & dosage/adverse effects/*analogs & derivatives ; Anti-Inflammatory Agents, Non-Steroidal/*adverse effects ; Anti-Ulcer Agents/*administration & dosage/adverse effects ; Arthritis/drug therapy ; Butanones/adverse effects ; Diclofenac/adverse effects/analogs & derivatives ; Double-Blind Method ; Drug Administration Schedule ; Gastric Mucosa ; Humans ; Middle Aged ; Misoprostol/*administration & dosage/adverse effects ; Quinolones/*administration & dosage/adverse effects ; Stomach Ulcer/chemically induced/*prevention & control ; Thiazines/adverse effects ; Thiazoles/adverse effects ; Treatment Outcome

BACKGROUND: Whether or not the excitation-contraction (EC) uncoupler, diacetyl monoxime (DAM) and cytochalacin D (Cyto D) alter the ventricular fibrillation activation patterns is unclear. METHODS: We recorded single cell action potentials and performed optical mapping in isolated perfused swine right ventricles at different concentrations of DAM and cyto D during ventricular fibrillation and dynamic pacing. RESULTS: Increasing concentration of DAM results in progressively shortened action potential duration measured to 90% repolarization (APD90), reduced slope of the action potential duration restitution(APDR) curve, decreased Kolmogorov-Sinai entropy, and reduced number of ventricular fibrillation wavefronts. In all right ventricles, 15 to 20 mmol/l DAM converted ventricular fibrillation to ventricular tachycardia. The ventricular fibrillation could be reinduced after the DAM was washed out. In comparison, cyto D (10 to 40 mol/l) has no effects on APDR curve or the dynamics of ventricular fibrillation. The effects of DAM on ventricular fibrillation are associated with reduced number of wavefronts and dynamic complexities in ventricular fibrillation. CONCLUSION: These results are compatible with Restitution Hypothesis of ventricular fibrillation and suggest that DAM may be unsuitable as an EC uncoupler for optical mapping studies of ventricular fibrillation in the swine right ventricles.
Action Potentials ; Diacetyl ; Entropy ; Heart Ventricles* ; Swine* ; Tachycardia, Ventricular ; Ventricular Fibrillation*