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排序方式: 共有73条查询结果,搜索用时 15 毫秒
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Vigilio Ballabeni Massimiliano Tognolini Simona Bertoni Renato Bruni Alessandra Guerrini Gabriela Moreno Rueda Elisabetta Barocelli 《Pharmacological research》2007,55(1):23-30
Ocotea quixos essential oil was shown to possess significant inhibitory activity of platelet aggregation and clot retraction in rodent plasma. This study is aimed at fully characterizing the antiplatelet activity of the whole essential oil and its main components trans-cinnamaldehyde and methyl cinnamate also in human plasma, at investigating the mechanism underlying such activity and at evaluating the potential antithrombotic activity of subacute treatment of mice with Ocotea essential oil. In vitro Ocotea essential oil and trans-cinnamaldehyde inhibited arachidonic acid-, U46619-, ADP-, phorbol12-myristate13-alcetate-, collagen-induced platelet aggregation and thrombin-induced clot retraction in human and rodent plasma; Ocotea oil and trans-cinnamaldehyde competitively antagonized contractions induced by thromboxane A2 receptor agonist U46619 in rat isolated aortic ring (K(B) = 18 and 3.2 microg ml(-1), respectively). In vivo Ocotea oil, orally administered in a subacute treatment (30-100 mg kg(-1) day(-1) for 5 days) to mice, prevented acute thrombosis induced by collagen-epinephrine intravenous injection. This antithrombotic activity was not accompanied by pro-haemorragic side effect, as detected by the inactivity in bleeding test, thus showing a favourable safety profile compared to the conventional antiplatelet agent, acetylsalicylic acid. Present findings indicate that Ocotea essential oil possesses potent and safe antithrombotic activity attributable to its antiplatelet and vasorelaxant effects. The main constituent trans-cinnamaldehyde seems to be the primary responsible for this activity through a putative mechanism involving the inhibition of thromboxane A2 receptors. 相似文献
3.
E Barocelli M Chiavarini G Morini V Ballabeni T Vitali C Silva M Impicciatore 《Agents and actions》1991,33(1-2):173-176
The incomplete tachyphylaxis of the contractile response to the H1-stimulants observed on guinea-pig oesophageal muscularis mucosae seems to be H2- and H3-antagonist as well as atropine- and tetrodotoxin-resistant. Lidocaine and eserine partially prevented this process probably by a mechanism independent of their main activity. The dualistic antagonism exerted by mepyramine and methysergide on reproducible histamine responses could be explained by a kinetic condition of "hemi-equilibrium state" together with changes of drug-receptor interaction and by non-specific properties of methysergide. On the whole, the present data indicate that the role of histamine in this tissue has still to be defined. 相似文献
4.
D Hess B Thürlimann O Pagani S Aebi D Rauch P Ballabeni B Rufener M Castiglione-Gertsch A Goldhirsch 《Annals of oncology》2004,15(12):1760-1765
BACKGROUND: Few chemotherapy regimens are suitable for the treatment of elderly patients with advanced breast cancer. With the aim of finding a regimen with a low burden of subjective non-overlapping toxic effects, vinorelbine and capecitabine were chosen to be investigated in a phase I dose-finding study. PATIENTS AND METHODS: Thirty-six patients with advanced breast cancer were stratified for the presence of bone and non-bone involvement and treated at four dose levels from capecitabine 800 mg/m2 orally days 1-14 and vinorelbine 20 mg/m2 intravenously days 1 and 8, to capecitabine 1250 mg/m2 orally days 1-14 and vinorelbine 25 mg/m2 intravenously days 1 and 8, for a maximum of six cycles. None of the patients had received prior chemotherapy for metastatic/advanced disease. Fifty-three per cent of patients with bone metastases and 67% of patients without bone metastases had visceral disease. The median age was 70 years for the 15 with bone involvement patients and 73 years for the 21 without bone involvement patients. RESULTS: Twenty-eight patients were fully evaluable for hematological dose-limiting toxicity (DLT), and all patients for other DLTs and for antitumor activity. One DLT with grade 3 venous thrombosis at dose level 2 and two dose-limiting neutropenia events at level 3 occurred in patients without bone involvement. Two dose-limiting neutropenia events were observed at dose level 2 for patients with bone involvement. Thus, the recommended dose was defined at level 1 (capecitabine 1000 mg/m2 days 1-14 and vinorelbine 20 mg/m2 days 1 and 8) for patients with bone involvement. For patients without bone involvement, the recommended dose was at level 2 (capecitabine 1250 mg/m2 days 1-14 and vinorelbine 20 mg/m2 days 1 and 8). For patients without bone involvement the overall response rate was 48% and the time to progression (TTP) was 4.5 months [95% confidence interval (CI) 3.3-6.9]. For patients with bone involvement the overall response rate was 53% and TTP was 5.3 months (95% CI 2.7-7.8). CONCLUSIONS: This regimen of capecitabine and vinorelbine is well tolerated and effective in elderly patients with metastatic breast cancer. Toxicity was mainly hematological and was observed at a lower dose in patients with bone involvement. A phase II study with the two different dose levels for elderly patients with and without bone involvement is currently being conducted. 相似文献
5.
Evidence for the involvement of 5-HT2A receptors in mild mesenteric ischemia/reperfusion dysfunctions in mice 总被引:1,自引:0,他引:1
Simona Bertoni Paola Ghizzardi Fiore Cattaruzza Vigilio Ballabeni Mariannina Impicciatore Massimiliano Tognolini Costanza A.M. Lagrasta Elisabetta Barocelli 《Pharmacological research》2007,56(6):550-555
In this study, the involvement of 5-HT2A receptors on mesenteric ischemia-reperfusion injury was examined in mice. Intestinal ischemia produced by 45 min occlusion of superior mesenteric artery was followed by 24h reperfusion (I/R). The 5-HT2A selective antagonist, ketanserin (0.5 mgkg(-1)) or the 5-HT2A agonist DOI (0.25 mgkg(-1)) was intravenously administered before ischemia and 8h after the beginning of reperfusion. The effects were compared with those obtained in sham operated animals (S). Ketanserin prevented the upper gastrointestinal transit delay induced by I/R (P<0.01), protected intestine from leukocyte recruitment as indicated by jejunal myeloperoxidase activity (P<0.05) and reverted Evans Blue extravasation elicited by I/R in lung, colon and jejunum (P<0.05). On the other hand, 5-HT2A activation by DOI mimicked the effects of I/R in S mice prolonging small intestine transit (P<0.05) and enhancing neutrophil accumulation in jejunal tissues (P<0.05). Furthermore, the reduction of ADP-induced platelet aggregation in plasma of I/R mice was prevented by ketanserin treatment. All together, these findings support the critical involvement of 5-HT2A receptor subtype in mediating the damage induced by mesenteric I/R in mice. 相似文献
6.
Bruno O Schenone S Ranise A Barocelli E Chiavarini M Ballabeni V Bertoni S 《Arzneimittel-Forschung》2000,50(2):140-147
The preparation and screening of antipyretic, anti-inflammatory, analgesic, gastroprotective and antiplatelet activities of original non-acidic aminobenzo-pyranopyrimidine derivatives are described. Major and dose-dependent analgesic and antipyretic properties were detected in all the compounds after oral administration (6.25-100 mg kg-1) in the mouse writhing test and in the E. coli lipopolysaccharide-induced fever in the rat, respectively. Unlike the reference drug indometacin (ED50 ulcer = 9.1 mg kg-1), no gastrolesivity was displayed by all the new compounds up to 150 mg kg-1 so that therapeutical indices equal or higher than that of indometacin were calculated. Furthermore, at 100 mg kg-1 they were able to prevent ethanol-induced gastric mucosal injury in rats. At a 1 mmol/l concentration the compounds under study were as effective as acetylsalicylic acid in inhibiting in vitro platelet aggregation induced by adenosine diphosphate. 相似文献
7.
Prognostic and predictive relevance of microsatellite instability in colorectal cancer 总被引:2,自引:0,他引:2
Storojeva I Boulay JL Heinimann K Ballabeni P Terracciano L Laffer U Mild G Herrmann R Rochlitz C 《Oncology reports》2005,14(1):241-249
Microsatellite instability (MSI) is the phenotypic hallmark of a deficient DNA mismatch-repair system, observed in 10-20% of sporadic colorectal cancers (CRC). Since the prognostic and predictive value of this genetic alteration has been assessed mainly in non-randomised, uncontrolled studies, we investigated the potential of MSI to predict patient survival and response to adjuvant chemotherapy in tumour specimens from a randomised trial of the Swiss Group for Clinical Cancer Research (SAKK) that tested the value of 5-fluorouracil/mitomycin adjuvant chemotherapy. MSI status was determined in matched normal and tumour tissue samples from 160 patients using a panel of 9 microsatellite markers. There was no correlation between high frequency MSI (MSI-H) and overall (OS) or disease-free survival (DFS) in the untreated control group of patients (HR=1.13, p=0.80; and HR=0.89, p=0.81, respectively). Furthermore, MSI-H phenotype did not predict for a larger benefit of adjuvant chemotherapy on OS or DFS (HR=0.49, p=0.41; HR=0.49, p=0.41, respectively), making a potential value of this molecular marker as a predictive factor in CRC unlikely. Our data do not confirm the prognostic relevance of MSI-H status in colorectal cancer patients found in some other studies. In addition, microsatellite instability did not correlate with the extent of chemotherapy benefit, although we observed a statistically non-significant favourable impact of 5-FU-based treatment in the MSI-H group compared to MSI-L/MSS patients. Larger prospective randomised trials are required to conclusively establish a potential clinical significance of MSI in colorectal cancer. 相似文献
8.
Mor M Bordi F Silva C Rivara S Zuliani V Vacondio F Morini G Barocelli E Ballabeni V Impicciatore M Plazzi PV 《Il Farmaco; edizione pratica》2000,55(1):27-34
New histamine H3-receptor antagonists were synthesised and tested on rat brain membranes and on electrically stimulated guinea-pig ileum. The new compounds have a central polar group represented by a 2-alkylimidazole or a 2-thioimidazoline nucleus. The effect of the polar group basicity on the optimal length of the alkyl chain, connecting this group to a 4(5)-imidazolyl ring, was investigated. The best affinity values, obtained by displacement of [3H]-RAMHA from rat brain, were obtained for the 2-alkylimidazole derivatives (2a-f) with tetramethylene chain (pKi 8.03-8.97), having an intermediate basicity between that of the previously reported 2-thioimidazoles (1a-i) and that of 2-alkylthioimidazolines (3a-h). In contrast, a general lowering of affinity (pKi 5.90-7.63) was observed for compounds of the last series (3a-h), with a complex dependence on the terminal lipophilic group and chain length. 相似文献
9.
Laurencet F Ballabeni P Rufener B Hess U Cerny T Fey M Luthi JM Plancherel C Zulian GB;Swiss Group for Clinical Research 《Acta haematologica》2007,117(1):40-47
A multicenter trial was performed to confirm the therapeutic efficacy and the toxicity profile of the combination of cladribine, cyclophosphamide and prednisone in low-grade non-Hodgkin's lymphoma (NHL) and chronic lymphocytic leukemia (CLL). Twenty-three adults with previously treated (61%) or untreated (39%) NHL International Working Formulation A or Binet B and C CLL were administered cladribine 0.1 mg/kg/day as a subcutaneous bolus for 5 days, intravenous cyclophosphamide 500 mg/m2 on day 1, and oral prednisone 40 mg/m2 on days 1-5, every 4 weeks. Unexpected early hematological toxicities led to dose modifications for pretreated patients who received cladribine for 3 days only up to a maximum of five courses. Responses were observed in 75%, with 7 patients obtaining a complete clinical and hematological response. Median duration of complete response was 9 months. Median time to progression or relapse was 31 months. Myelosuppression and infections were dose limiting whereas posttreatment complications, including fatalities, resulted from infections. Median overall survival time from trial entry was 60 months. Activity of the combination of cladribine, cyclophosphamide and prednisone was confirmed. However, in the specific setting of a multicenter trial, unexpected fatal infectious episodes occurred in pretreated patients. Great caution is thus required in these susceptible patients and the routine use of corticosteroids should probably be abandoned. 相似文献
10.
Bruno O Brullo C Bondavalli F Ranise A Schenone S Tognolini M Ballabeni V Barocelli E 《Medicinal chemistry (Shāriqah (United Arab Emirates))》2007,3(2):127-134
New series of 5-alkoxy-benzopyranopyrimidine derivatives were developed from the chemical modulation of the substituent in position 2 of the scaffold, with the aim to produce analgesic/antiphlogistic agents more potent than analogues previously reported. The 2-hydrazino derivatives exhibited a good analgesic activity in writhing test; the analgesic doses of the compounds did not affect mice spontaneous locomotor activity thus any confounding sedative effect could be excluded. These derivatives revealed an aspirin-like profile with a strong inhibition of AA-induced platelet aggregation, probably due to a strong, non selective, inhibition of cyclooxygenases. In spite of the inhibition of COX activity displayed in vitro, the compounds did not cause gastric damage in rats after acute oral administration. A different pharmacological profile was observed for the 2-azido derivatives, particularly in vivo. 相似文献