BACKGROUND AND PURPOSE: Frovatriptan is a selective 5-HT1B/1D agonist with a long duration of action and a low incidence of side effects. Although several placebo-controlled trials have documented the clinical efficacy and safety of frovatriptan in adults with migraine, this drug has not previously been studied in Asian including Korean patients. METHODS: In this double-blind multicenter trial, 229 patients with migraine were randomized to receive frovatriptan 2.5 mg or placebo upon the occurrence of a moderate-to-severe migraine. The primary outcome was the 2-hour headache response rate. RESULTS: Frovatriptan significantly increased the 2-hour headache response rate compared with placebo (52.9% vs. 34.0%, p=0.004). The headache response rates at 4, 6, and 12 hours were significantly higher in the frovatriptan group than in the placebo group, as was the pain-free rate at 2 hours (19.0% vs. 5.7%, p=0.004), 4 hours (40.7% vs. 23.0%, p=0.006), and 6 hours (56.1% vs. 34.0%, p=0.002). The median time to a headache response was significantly shorter in the frovatriptan group than in the placebo group (2.00 hours vs. 3.50 hours, p<0.001). The use of rescue medications was more common in the placebo group (p=0.005). Chest tightness associated with triptan was infrequent (2.5%), mild, and transient. CONCLUSIONS: These results demonstrate that 2.5-mg frovatriptan is effective and well tolerated in Korean migraineurs for acute treatment of migraine attacks.
Adult ; Asian Continental Ancestry Group ; Carbazoles ; Headache ; Humans ; Incidence ; Migraine Disorders ; Oxalates ; Thorax ; Tryptamines

OBJECTIVETo study the stereoselective glucuronidation of carvedilol (CARV) by three Chinese liver microsomes.

METHODSThe metabolites of CARV were identified by a hydrolysis reaction with beta-glucuronidase and HPLC-MS/MS. The enzyme kinetics for CARV enantiomers glucuronidation was determined by a reversed phase-high pressure liquid chromatography (RP-HPLC) assay using (S)-propafenone as internal standard after precolumn derivatization with 2,3,4,6-tetra-O-acetyl-beta-D-glucopyranosylisothiocyanate.

RESULTSTwo CARV glucuronides were found in three Chinese liver microsomes incubated with CARV. The non-linear regression analysis showed that the values of K(m) and V(max) for (S)-CARV and (R)-CARV enantiomers were (118+/-44) micromol/L, (2 500+/-833) pmol/(min.mg protein) and (24+/-7) micromol/L, (953+/-399) pmol/(min.mg protein), respectively.

CONCLUSIONThese results suggested that there was a significant (P<0.05) stereoselective glucuronidation of CARV enantiomers in three Chinese liver microsomes, which might partly explain the enantioselective pharmacokinetics of CARV.

Carbazoles ; metabolism ; China ; Glucuronic Acid ; metabolism ; Glucuronides ; metabolism ; Microsomes, Liver ; metabolism ; Propanolamines ; metabolism ; Stereoisomerism

Biodenitrogenation of petroleum oil was investigated by a previously isolated carbazole-degrader Pseudomonas sp. XLDN4-9. In a tetradecane-aqueous phase system, biodegradation of carbazole was enhanced by the presence of n-tetradecane. And strain XLDN4-9 was capable of absorbing 95.2% of 2 g/L carbazole dissolved in diesel within 15 hours. Significant denitrogentation of crude oil, diesel and lubricanting oil was detected by strain XLDN4-9. Removal of carbazole, methylcarbazole, and dimethylcarbazole in diesel was confirmed by using GC-MS. After 3 days, 99% of carbazole and 15% of dimethyl carbazole was degraded. And the removal rate of 1-, 2-, 3-, and 4-methyl carbazole was determined to be 63.4%, 87.6%, 78.4%, and 66.5% respectively.
Biodegradation, Environmental ; Carbazoles ; chemistry ; metabolism ; Gas Chromatography-Mass Spectrometry ; Petroleum ; metabolism ; Pseudomonas ; classification ; metabolism

OBJECTIVETo study the chemical constituents from the seed of Trigonella foenum-graecum.

METHODThe compounds were isolated with silica gel chromatography and their structures were identified by physical, chemical properties and spectral analysis.

RESULTSeven compounds were isolated and identified as N,N'-dicarbazyl, glycerol monopalmitate, stearic acid, beta-sitosteryl glucopyranoside, ethyl-alpha-D-glucopyranoside, D-3-O-methyl-chiroinsitol and sucrose.

CONCLUSIONAll the compounds were obtained from this plant for the first time and N,N'-dicarbazyl is a new natural product.

Carbazoles ; chemistry ; isolation & purification ; Plants, Medicinal ; chemistry ; Seeds ; chemistry ; Stearic Acids ; chemistry ; isolation & purification ; Trigonella ; chemistry

A 48-year-old woman was incidentally found to have bilateral adrenal masses, 2.8 cm in diameter on the right, and 2.3 cm and 1.7 cm in diameter on the left, by abdominal computed tomography. The patient had a medical history of hypertension, which was not being controlled by carvedilol, at a dose of 25 mg daily. She presented with signs and symptoms that suggested Cushing Syndrome. We diagnosed adrenocorticotropic hormone (ACTH)-independent Cushing Syndrome based on the results of basal and dynamic hormone tests. Adrenal vein sampling (AVS) was performed to localize a functioning adrenal cortical mass. AVS results were consistent with hypersecretion of cortisol from both adrenal glands, with a cortisol lateralization ratio of 1.1. Upon bilateral laparoscopic adrenalectomy, bilateral ACTH-independent adrenal adenomas were found. The patient's signs and symptoms of Cushing Syndrome improved after surgery just as the blood pressure was normalized. After surgery, the patient was started on glucocorticoid and mineralocorticoid replacement therapy.
Adenoma ; Adrenal Glands ; Adrenalectomy ; Adrenocorticotropic Hormone ; Blood Pressure ; Carbazoles ; Cushing Syndrome ; Female ; Humans ; Hydrocortisone ; Hypertension ; Propanolamines ; Veins

Pressure overload diseases such as valvular stenosis and systemic hypertension morphologically manifest in patients as cardiac concentric hypertrophy. Preventing cardiac remodeling due to increased pressure overload is important to reduce the morbidity and mortality. A recent clinical study has shown that carvedilol has beneficial effects on the survival rate of patients with heart failure. This may be due to the actions of carvedilol such as beta-adrenoceptor blockade and the alpha1-adrenergic receptor blockade effects. Therefore, we investigated whether carvedilol can reverse preexisting cardiac hypertrophy and we compared the effects of racemic carvedilol and the carvedilol enantiomers. Cardiac hypertrophy was induced in rats by suprarenal transverse abdominal aortic constriction (AC). Fifteen weeks after AC surgery, concentric hypertrophy was identified in the AC group by performing echocardiography. Low dose S- and SR-carvedilol (2 mg/kg/day), which were orally administered for three weeks, caused significant regression of the cardiac hypertrophy, and this most significantly occurred in the rats that received S-carvedilol. However, R-carvedilol did not reduce cardiac hypertrophy. Regression of cardiac hypertrophy by carvedilol was confirmed on the echocardiograms and electrocardiograms. These results suggest that carvedilol could reverse the development of leftventricular concentric hypertrophy that is induced by pressure overload. S-carvedilol is proposed to be superior to SR-and R-carvedilol as a beneficial treatment for cardiac hypertrophy.
Animals ; Carbazoles ; Cardiomegaly ; Constriction ; Constriction, Pathologic ; Echocardiography ; Electrocardiography ; Heart Failure ; Humans ; Hypertension ; Hypertrophy ; Propanolamines ; Rats ; Survival Rate

A 42-year-old male patient presented with refractory hypertension and congestive heart failure. He had taken hydrochlorthiazide 50 mg, carvedilol 25 mg, diltiazem 180 mg, and losartan 100 mg per day. Aortogram revealed a severe luminal narrowing in the distal thoracic aorta with a peak systolic pressure gradient of 60 mmHg across the lesion. Endovascular management was performed with 22 x 80 mm self-expandable Nitinol-S stent after predilation with 10 x 40 mm balloon. After endovascular management, the patient's blood pressure, left ventricular ejection fraction (LVEF) and dilated LV dimension were remarkably improved.
Adult ; Aorta ; Aorta, Thoracic ; Blood Pressure ; Carbazoles ; Diltiazem ; Heart ; Heart Failure ; Humans ; Hypertension ; Losartan ; Male ; Phenobarbital ; Propanolamines ; Stents ; Stroke Volume

AIMTo design and synthesize new methoxyl carbazole analogues as antitumor compounds.

METHODSMethoxyl-nitrobiphenyls (3a-3c) were prepared through the Ullmann reaction of 4,5-dimethoxyl-2-bromonitrobenzene and methoxyl-iodobenzene compounds with the catalysis of copper powder, and then reduced by P(EtO)3 to obtain methoxyl carbazoles 4a-4c. The modification at 9-position of the methoxyl carbazoles (4a-4c) gives 16 carbazole derivatives (5a-5p). These compounds were confirmed by 1HNMR, MS, IR and elemental analysis.

RESULTIn vitro antitumor activities evaluation in vitro demonstrated that IC50 value of the target compounds 4c, 5a, 5b, 5g, 5h, 5i, 5l, 5n and 5p against HT-29 cells were 12.1, 10.6, 8.1, 3.1, 4.4, 10.1 and 9.2 micromol x L(-1) respectively, and IC50 value of the target compound 4a against KB was 17.7 micromol x L(-1).

CONCLUSIONSome of the target compounds have better inhibitory effects against H-29 and KB cells.

Antineoplastic Agents ; chemical synthesis ; chemistry ; pharmacology ; Carbazoles ; chemical synthesis ; chemistry ; pharmacology ; HT29 Cells ; drug effects ; Humans ; KB Cells ; drug effects ; Molecular Structure

PURPOSE: This study was designed to pursue the basic relationship between MMP-2 and ligament injury via ex vivo stretching of the anterior cruciate ligament (ACL) and its changes by signal transduction pathway. MATERIALS AND METHODS: After femur-ACL-tibia complex was harvested from rats, release of MMP-2 in stretch group and non-stretch group was checked using gelatin zymography. Firstly, authors investigated whether MMP-2 was released from the ligament or not and if so, how long it was released. In addition, the complexes were divided into two groups. In group I, 5 and 12N weights were used to stretch the complex for 10, 30, and 60-minute. In group II, after the ligament complexes were stretched by 15N for 30 minutes, various signal pathway inhibitors such as pertusis toxin, SP600125, PD98059, KT5720, curcumin, and Bay11-7082 were added to their supernatants. MMP-2 activity was evaluated. RESULTS: MMP-2 was immediately released after ligament injury and its activity was increased in proportion to stretching duration and magnitude. As for the signal pathways, inhibition of JNK, ERK, AP-1, and NF-k beta pathways caused MMP-2 expression to be decreased. CONCLUSION: It is considered that the release of MMP-2 plays an important role in remodeling process after ACL injury.
Animals ; Anterior Cruciate Ligament ; Anthracenes ; Carbazoles ; Curcumin ; Flavonoids ; Gelatin ; Knee ; Ligaments ; Matrix Metalloproteinase 2 ; Nitriles ; Pyrroles ; Rats ; Signal Transduction ; Sulfones ; Transcription Factor AP-1 ; Weights and Measures

BACKGROUND AND OBJECTIVES: In Duchenne and Becker muscular dystrophies, cardiac function deteriorates with time resulting in heart failure which is often fatal. We prospectively evaluated the effect of enalapril and carvedilol on left ventricular (LV) dysfunction in middle childhood and adolescent patients with muscular dystrophy. SUBJECTS AND METHODS: Twenty-three patients with LV dysfunction (22 with Duchenne muscular dystrophy, 1 with Becker muscular dystrophy) were enrolled. We prescribed enalapril (13 patients) or carvedilol (10 patients) randomly from July 2008 to August 2010 and followed up the patients until September 2011. The changes in LV function parameters before and after the treatment were evaluated by echocardiography. RESULTS: The mean age at the start of treatment with enalapril or carvedilol was 12.6+/-3.7 years (median 13 years), and mean follow-up duration was 20.1+/-8.9 months. In the enalapril group, LV fractional shortening (FS) increased from 25.8+/-2.1 to 26.6+/-3.0 (p=0.241). In the carvedilol group, LV FS increased from 26.4+/-1.1 to 28.6+/-4.2 (p=0.110). In all 23 patients, LV FS significantly increased from 26.1+/-1.7 (before) to 27.6+/-3.7 (after treatment) (p<0.046). Indexed LV dimension at end diastole and LV end-diastolic volume decreased slightly, but without statistical significance by tri-plane volumetry. LV diastolic functional parameters were maintained during follow-up period. CONCLUSION: Enalapril or carvedilol could improve LV systolic function in middle childhood and adolescent patients with muscular dystrophy without significant adverse effects.
Adolescent ; Carbazoles ; Cardiomyopathies ; Diastole ; Echocardiography ; Enalapril ; Follow-Up Studies ; Heart Failure ; Humans ; Muscular Dystrophies ; Muscular Dystrophy, Duchenne ; Propanolamines ; Prospective Studies ; Ventricular Dysfunction, Left