OBJECTIVETo investigate the preliminary efficacy and safety of ambrisentan, a selective endothelin receptor antagonist, in patients with pulmonary arterial hypertension (PAH).

METHODSA total of 15 patients with PAH, including 10 patients with idiopathic PAH and 5 patients with associated connective-tissue disease, received 2.5 mg or 5 mg of ambrisentan once daily for 12 weeks. Before and after 12 weeks treatment, 6-minute walk test (6-MWD), WHO functional classification (WHO FC) and N-terminal pro-brain natriuretic peptide (NT-proBNP) were measured.

RESULTSAfter 12 weeks treatment, the 6-MWD was significantly increased [(376.5 ± 108.2) m vs.(460.3 ± 95.7) m, P = 0.021] and the systolic pulmonary artery was significantly decreased [(85.0 ± 33.3) mm Hg (1 mm Hg = 0.133 kPa)vs. (70.5 ± 30.5) mm Hg,P = 0.015] and NT-proBNP was significantly reduced [892.0 (99.0-2245.0) ng/L vs. 205.0 (56.0-534.0) ng/L, P = 0.026] than before treatment. WHO FC was improved in 4 patients after 12 weeks treatment. No patient was withdrawn from this study for safety reasons.

CONCLUSIONSAmbrisentan treatment can effectively improve the exercise capacity, and reduce systolic pulmonary artery pressure and NT-proBNP in PAH patients. Ambrisentan use is safe and could be well tolerated in Chinese PAH patients.

Adult ; Antihypertensive Agents ; therapeutic use ; Familial Primary Pulmonary Hypertension ; Female ; Humans ; Hypertension, Pulmonary ; drug therapy ; Male ; Middle Aged ; Phenylpropionates ; therapeutic use ; Prospective Studies ; Pyridazines ; therapeutic use ; Treatment Outcome

Radiotherapy, frequently used for treatment of solid tumors, carries two main obstacles including acquired radioresistance in cancer cells during radiotherapy and normal tissue injury. Phenylpropanoids, which are naturally occurring phytochemicals found in plants, have been identified as potential radiotherapeutic agents due to their anti-cancer activity and relatively safe levels of cytotoxicity. Various studies have proposed that these compounds could not only sensitize cancer cells to radiation resulting in inhibition of growth and cell death but also protect normal cells against radiation-induced damage. This review is intended to provide an overview of recent investigations on the usage of phenylpropanoids in combination with radiotherapy in cancer treatment.
Antineoplastic Agents/*therapeutic use ; Apoptosis/drug effects/radiation effects ; Chromones/therapeutic use ; Combined Modality Therapy ; Cytoprotection/drug effects/radiation effects ; Humans ; Neoplasms/pathology/*radiotherapy ; Phenylpropionates/therapeutic use ; Plants ; Radiation Tolerance/drug effects ; Radiation-Sensitizing Agents/*therapeutic use ; *Radiotherapy

Several new drug targets of anti-atherosclerosis, emerging in the recent years, such as PPAR agonists, cholesteryl ester transfer protein (CETP) inhibitors, infusion of apolipoprotein A-I (apoA-I), liver X receptor (LXR) activators and phospholipid transfer protein (PLTP) inhibitors etc were reviewed.
Apolipoprotein A-I ; therapeutic use ; Atherosclerosis ; drug therapy ; metabolism ; Benzoates ; chemistry ; therapeutic use ; Benzylamines ; chemistry ; therapeutic use ; Cholesterol Ester Transfer Proteins ; antagonists & inhibitors ; metabolism ; DNA-Binding Proteins ; agonists ; metabolism ; Humans ; Liver X Receptors ; Molecular Structure ; Orphan Nuclear Receptors ; Oxazines ; chemistry ; therapeutic use ; Peroxisome Proliferator-Activated Receptors ; agonists ; metabolism ; Phenylpropionates ; chemistry ; therapeutic use ; Quinolines ; chemistry ; therapeutic use ; Receptors, Cytoplasmic and Nuclear ; agonists ; metabolism

OBJECTIVETo investigate long-term efficacy and safety of ambrisentan monotherapy in patients with pulmonary arterial hypertension (PAH).

METHODSPatients with PAH who received 2.5 mg or 5 mg of ambrisentan once daily between July 10, 2011 and August 30, 2012 for at least 6 months were enrolled. The efficacy endpoints were change in exercise capacity, World Health Organization (WHO) functional class and N-terminal pro-brain natriuretic peptide (NT-proBNP) level, echocardiographic parameters. The safety endpoint was the safety of long-term ambrisentan administration, as defined by the incidence and severity of adverse events.

RESULTSA total of 18 patients with PAH were enrolled. Mean age was (39 ± 17) years, 8 (55.6%) were female, and 11 (61.1%) patients were in WHO functional class III. The median duration of treatment was 17 months (range: 6-26 months). After treatment, the 6MWD was significantly increased[ (495 ± 97) m vs. (400 ± 91) m, P < 0.001], NT-proBNP was significantly reduced [308 (53-1 645) ng/L vs. 80(22-454) ng/L, P = 0.005], the systolic pulmonary artery was significantly decreased [(62 ± 30) mmHg vs. (82 ± 41) mmHg, P = 0.001] and left ventricular end diastolic diameter was significantly increased [(44 ± 6) mm vs. (40 ± 6) mm, P < 0.004] compared to pre-treatment. WHO functional class was improved compared with baseline in 11(61.1%) patients, stable in 7(38.9%) patients. No patient died during the treatment period. No patient was withdrawn from this study for safety reasons.

CONCLUSIONSLong-term treatment of ambrisentan can effectively improve the exercise capacity, reduce systolic pulmonary artery pressure and NT-proBNP in PAH patients. Ambrisentan is safe and well tolerated in Chinese PAH patients.

Adult ; Blood Pressure ; Female ; Humans ; Hypertension, Pulmonary ; drug therapy ; Male ; Middle Aged ; Natriuretic Peptide, Brain ; metabolism ; Peptide Fragments ; metabolism ; Phenylpropionates ; therapeutic use ; Pyridazines ; therapeutic use ; Treatment Outcome ; Young Adult

AIMTo search for new compounds with strong anti-inflammatory activity and low gastrointestinal (GI) side effects.

METHODSA series of alpha-substituted p-(methanesulfonyl) phenyl-propenamides were synthesized. Their anti-inflammatory activities against xylene-induced mice ear swelling and carrageenan-induced rat paw edema were evaluated, and their GI side effects in rats were examined.

RESULTSTwenty-five target compounds (II1-25) were obtained, and their structures were determined by IR, 1H NMR, MS and elemental analysis. Thirteen compounds (II1,3,5,8-13,15,18,19,23) exhibited marked anti-inflammatory activity comparable to diclofenac sodium (DC) and rofecoxib (RC) in xylene-induced mice ear swelling model, and twelve compounds (II1,3,5,7,8,10-12,17,18,20,23) showed remarkable anti-inflammatory activity comparable to DC and RC in carrageenan-induced rat paw edema. Compounds II3,8,10,11,18,20 showed GI side effects less than DC (P < 0.01), and no significant difference compared with RC and CMC-Na (P > 0.05).

CONCLUSIONalpha-Substituted p-(methanesulfonyl)phenylpropenamides showed strong anti-inflammatory activity but few GI side effects and deserve to be further investigated.

Animals ; Anti-Inflammatory Agents, Non-Steroidal ; adverse effects ; chemical synthesis ; pharmacology ; therapeutic use ; Carrageenan ; Edema ; chemically induced ; drug therapy ; Mice ; Peptic Ulcer ; chemically induced ; Phenylpropionates ; adverse effects ; chemical synthesis ; pharmacology ; Rats ; Structure-Activity Relationship ; Sulfones ; adverse effects ; chemical synthesis ; pharmacology ; Xylenes