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991.
Bartolini M Giamberardino MA Lisotto C Martelletti P Moscato D Panascia B Savi L Pini LA Sances G Santoro P Zanchin G Omboni S Ferrari MD Brighina F Fierro B 《The journal of headache and pain》2011,12(3):361-368
The objective of this study was to evaluate patients’ satisfaction with acute treatment of migraine with frovatriptan or almotriptan by preference questionnaire. One hundred and thirty three subjects with a history of migraine with or without aura (IHS 2004 criteria), with at least one migraine attack in the preceding 6 months, were enrolled and randomized to frovatriptan 2.5 mg or almotriptan 12.5 mg, treating 1–3 attacks. The study had a multicenter, randomized, double blind, cross-over design, with treatment periods lasting <3 months. At study end patients assigned preference to one of the treatments using a questionnaire with a score from 0 to 5 (primary endpoint). Secondary endpoints were pain free and pain relief episodes at 2 and 4 h, and recurrent and sustained pain free episodes within 48 h. Of the 133 patients (86%, intention-to-treat population) 114 of them expressed a preference for a triptan. The average preference score was not significantly different between frovatriptan (3.1 ± 1.3) and almotriptan (3.4 ± 1.3). The rates of pain free (30% frovatriptan vs. 32% almotriptan) and pain relief (54% vs. 56%) episodes at 2 h did not significantly differ between treatments. This was the case also at 4 h (pain free: 56% vs. 59%; pain relief: 75% vs. 72%). Recurrent episodes were significantly (P < 0.05) less frequent under frovatriptan (30% vs. 44%), also for the attacks treated within 30 min. No significant differences were observed in sustained pain free episodes (21% vs. 18%). The tolerability profile was similar between the two drugs. In conclusion, our study suggests that frovatriptan has a similar efficacy of almotriptan in the short-term, while some advantages are observed during long-term treatment. 相似文献
992.
Noto D Cefalù AB Barraco G Fayer F Minà M Yue P Tarugi P Schonfeld G Averna MR 《Atherosclerosis》2011,216(2):409-413
Primary hypobetalipoproteinemia (pHBL) is characterized by plasma cholesterol levels <5th percentile of a population distribution. Plasma non-cholesterol sterols (NCS) are markers of cholesterol liver synthesis and intestinal absorption. Plasma NCS were measured in 111 pHBL subjects, 108 low cholesterol (LC) and 253 normal cholesterol (NC) controls to gain information on cholesterol metabolism in pHBL, and to assess whether NCS measurements may aid in distinguishing pHBL from LC controls. pHBL subjects compared with LC controls were characterized by increased cholesterol absorption (campesterol/TC) while the synthesis (lathosterol/TC) was not increased. The analysis of pHBL subjects divided by gene defect showed a high campesterol/TC ratio in familial HBL (FHBL) carriers of apolipoproteinB (ApoB) truncations longer than ApoB48 and in FHBL without known gene defect ("not linked"). One not linked kindred was characterized by an increase of the 7-dehydrocholesterol/latho ratio. In a discriminant analysis plasma NCS did not improve the power of TC levels to distinguish FHBL from LC controls. In conclusion, increased cholesterol absorption was found in FHBL subjects harbouring truncations of ApoB>ApoB48, and FHBL harbouring as yet unknown molecular defects. Not linked FHBL kindred are not homogeneous in terms of plasma NCS levels. NCS cannot replace genetic HBL analysis. 相似文献
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To investigate the effect of different antihypertensive agents on blood pressure (BP) variability (BPV) and the underlying mechanism, we analyzed the ambulatory BP monitoring data of 577 patients before and after 3-month antihypertensive treatment, in the Natrilix SR Versus Candesartan and Amlodipine in the Reduction of Systolic Blood Pressure in Hypertensive Patients (X-CELLENT) Study, a multicenter, multinational, randomized, double-blind, placebo-controlled study with 4 parallel treatment arms (placebo, candesartan, indapamide sustained release, and amlodipine). Within-subject mean and SD of 24-hour BP, weighted by time interval between consecutive readings, were calculated in 3 time frames (daytime, nighttime, and 24 hours) to evaluate BP and BPV. The mean 24-hour heart rate (HR) and HR variability were calculated with the same algorithms. We found that the 3 antihypertensive drugs had a similar BP-lowering effect (P<0.001 for all), but amlodipine (P<0.007) and indapamide sustained release (P<0.04) were the only agents associated with a significantly decreased BPV after 3-month treatment. On the other hand, the major determinants of BPV at baseline were age, mean BP, and the corresponding HR variability. However, the reduction in BPV by amlodipine was significantly associated with the reduction in BP (P<0.006) and the reduction in HR variability (P<0.02), whereas the corresponding reduction by indapamide sustained release was only associated with the reduction in HR variability at night (P=0.004). In summary, 3-month amlodipine or indapamide sustained release treatment was associated with a significant reduction in BPV, and the mechanism of those reductions was possibly attributable to lowering BP or ameliorating the autonomic nervous system regulation or both. The combination of the 2 agents might help to optimize such properties. 相似文献
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Cardinale D Guaitoli G Tondi D Luciani R Henrich S Salo-Ahen OM Ferrari S Marverti G Guerrieri D Ligabue A Frassineti C Pozzi C Mangani S Fessas D Guerrini R Ponterini G Wade RC Costi MP 《Proceedings of the National Academy of Sciences of the United States of America》2011,108(34):E542-E549
Human thymidylate synthase is a homodimeric enzyme that plays a key role in DNA synthesis and is a target for several clinically important anticancer drugs that bind to its active site. We have designed peptides to specifically target its dimer interface. Here we show through X-ray diffraction, spectroscopic, kinetic, and calorimetric evidence that the peptides do indeed bind at the interface of the dimeric protein and stabilize its di-inactive form. The "LR" peptide binds at a previously unknown binding site and shows a previously undescribed mechanism for the allosteric inhibition of a homodimeric enzyme. It inhibits the intracellular enzyme in ovarian cancer cells and reduces cellular growth at low micromolar concentrations in both cisplatin-sensitive and -resistant cells without causing protein overexpression. This peptide demonstrates the potential of allosteric inhibition of hTS for overcoming platinum drug resistance in ovarian cancer. 相似文献