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排序方式: 共有294条查询结果,搜索用时 31 毫秒
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2.
R Maffei Facino M Carini C Genchi O Tofanetti I Casciarri 《Pharmacological research》1989,21(5):549-560
Fascioliasis causes a dramatic decrease in drug-metabolizing ability of the hepatic monooxygenase (MFO) and glucuronosyltransferase (GT) enzyme systems in the rat. The present study was undertaken to determine whether lipid peroxidation is involved in the enzymatic loss. Peroxidative damage of membrane lipids (as assessed by the tissue content of malonic dialdehyde, MDA, and the diene conjugation absorption in microsomal membranes) was found to occur over the entire course of the liver infection (concomitant to a decrease in glutathione levels), and to different degrees in relation to the various steps of the parasite cycle. The onset (MDA six times the controls; delta E 1% = 1.55 at the 20th day) coincides with the beginning of the loss of MFO (-30%) and GT (-20% at the 20th day), and peaks between the 30th and 40th day (MDA eight times the controls; delta E 1% = 1.96), when the loss in the enzyme activities is maximal (MFO - 60/70%; GT - 65/95%). There was a strict correlation at all the observation times between the extent of lipid peroxidation and the decrease in drug metabolizing ability: this supports the view that lipid peroxidation is the major agent in the impairment of MFO and GT enzyme activities, and very likely in the initiation of the pathological degeneration of the liver tissue. As evidenced by histological examination, the phagocytic response of the liver tissue to the parasite invasion and growth leads to oxidative stress, which is the causative agent in the initiation and development of lipid peroxidation. 相似文献
3.
R Gandini E Cunietti R Assereto D Castoldi O Tofanetti E Baggio 《Arzneimittel-Forschung》1987,37(7):836-839
40 mg of isosorbide mononitrate (isosorbide-5-mononitrate, IS5MN) in conventional (Ismo 20) and sustained release formulations (Ismo Diffutab) were administered to 5 male healthy volunteers. The administration of the sustained release formulation was repeated for seven days in order to evaluate the possible occurrence of accumulation. Pharmacokinetic data showed that the sustained release formulation reached significantly lower and delayed mean peak plasma levels compared with the conventional formulation, respectively 452.8 +/- 67.8 ng/ml and 706.7 +/- 57.3 (mean +/- SE) (p less than 0.05). Peak times were 4.6 +/- 0.2 and 2.4 +/- 0.2 (p less than 0.005) h, respectively. A longer plasma half-life together with larger AUC for the sustained release formulation was also observed. The pharmacokinetic parameters of the sustained release formulation are consistent with a therapeutic usefulness and suggest further clinical evaluation. 相似文献
4.
Chronic exposure of rats to the hypolipidemic agent tiadenol causes a dramatic dose-dependent increase of peroxisomal beta-oxidation activity. To elucidate which metabolite of the drug is the "proximate" inducer (tiadenol is eliminated completely in metabolized form after acute administration) we investigated the qualitative and quantitative metabolic profile of the drug at different doses (50, 150, 300 mg/Kg in two-weeks chronically treated rats, in parallel to that of a model compound, tiadenol-disulfoxide, a weak inducer of palmitoyl-CoA oxidation activity. No changes in the biodisposition of tiadenol (and tiadenol-disulfoxide) were found following chronic treatment for all the doses tested. For both the compounds a strict correlation was evidenced between the extent of formation of carboxylic metabolites and their inductive potencies on peroxisomal beta-oxidation activity. This indicates that tiadenol carboxylic metabolites act as the enzymatic effectors. 相似文献
5.
6.
Deeg HJ; Storb R; Thomas ED; Flournoy N; Kennedy MS; Banaji M; Appelbaum FR; Bensinger WI; Buckner CD; Clift RA 《Blood》1985,65(6):1325-1334
Seventy-five patients, 13 to 49 years of age, with acute nonlymphoblastic leukemia in first remission were treated with cyclophosphamide, fractionated total body irradiation, and marrow transplantation from an HLA-identical sibling and randomized to receive either cyclosporine (CSP) (n = 36) or methotrexate (MTX) (n = 39) as prophylaxis for graft-v-host disease (GVHD). All patients engrafted, and 22 who were given CSP and 21 who were given MTX, are alive at 20 to 47 (median, 35) months (P = .5). Engraftment as assessed by granulocyte recovery (P less than .0005) and platelet transfusion requirement (P = .01) was faster in patients on CSP. Twelve patients (33%) on CSP and 22 (56%) on MTX developed acute GVHD of grades II through IV (P = .07) and 15 of 30 on CSP and 14 of 32 on MTX that were at risk developed chronic GVHD. The most frequent causes of death were interstitial pneumonitis and marrow relapse of leukemia, which occurred with similar frequency in both groups. Beneficial effects observed in patients on CSP included less severe mucositis and shorter duration of hospitalization; adverse effects included renal function impairment and hypertension. These data confirm that CSP is a useful immunosuppressant in patients undergoing marrow transplantation but fail to show a significant improvement in survival as compared with the standard regimen of MTX. 相似文献
7.
Phase I trial of interleukin-2 after unmodified HLA-matched sibling bone marrow transplantation for children with acute leukemia 总被引:1,自引:1,他引:1
Robinson N; Sanders JE; Benyunes MC; Beach K; Lindgren C; Thompson JA; Appelbaum FR; Fefer A 《Blood》1996,87(4):1249-1254
Allogeneic bone marrow transplantation (BMT) for advanced acute leukemia is associated with a high risk of relapse. It is postulated that interleukin-2 (IL-2) administered after BMT might induce or amplify a graft-versus-leukemia effect and thereby reduce the relapse rate. To identify an IL-2 regimen for testing this hypothesis, a phase I trial of IL-2 (Roche) was performed in children in complete remission (CR) without active graft-versus-host disease (GVHD) off immunosuppressive agents after unmodified allogeneic matched-sibling BMT for acute leukemia beyond first remission. Beginning a median of 68 days after BMT, 17 patients received escalating doses of induction IL-2 (0.9, 3.0, or 6.0 x 10(6) IU/m2/d representing levels I, II, and III) for 5 days by continuous intravenous infusion (CIV). After 6 days of rest, they received maintenance IL-2 (0.9 x 10(6) IU/m2/d) for 10 days by CIV infusion. Levels I and II were well-tolerated, but, of 6 patients at level III, 1 developed pulmonary infiltrates, 1 developed hypotension (both resolved), and 1 died of bacterial sepsis and acute respiratory distress syndrome. Grade II acute GVHD developed in 1 patient at level I and 1 at level III. The maximum tolerated dose of induction IL-2 was level II. IL-2 induced lymphocytosis, with an increase in CD56+ and CD8+ cells. Ten patients remain in CR at 5+ to 67+ months. Thus, a regimen of IL-2 has been identified that did not induce a high incidence of acute GVHD when administered to children after unmodified allogeneic BMT. Its clinical activity will be assessed in a phase II trial. 相似文献
8.
Bensinger WI; Weaver CH; Appelbaum FR; Rowley S; Demirer T; Sanders J; Storb R; Buckner CD 《Blood》1995,85(6):1655-1658
Peripheral blood stem cells (PBSCs) are widely used in autologous transplantation because of ease of collection and rapid hematopoietic reconstitution. However, PBSCs have rarely been used for allogeneic transplantation because of concerns about donor toxicities from cytokine administration and the theoretical increased risk of graft- versus-host-disease (GVHD) from the large number of T cells infused. Eight patients with advanced malignancies received allogeneic PBSC transplants from genotypically HLA-identical sibling donors. All donors received 5 days of recombinant human granulocyte colony-stimulating factor (rhG-CSF; 16 micrograms/kg/day) subcutaneously and were leukapheresed for 2 days. After treatment of the patient with total body irradiation and cyclophosphamide (n = 7) or etoposide, thiotepa, and cyclophosphamide (n = 1), PBSCs were infused immediately after collection and without modification. All patients received cyclosporine and either methotrexate (n = 6) or prednisone (n = 2) for GVHD prophylaxis, rhG-CSF was well tolerated with mild bone pain requiring acetaminophen occurring in two donors. All patients engrafted and in seven hematopoietic recovery was rapid, with 500 neutrophils/microL achieved by day 18 and 20,000 platelets/microL by day 12. Complete donor engraftment was documented by Y chromosome analysis in all four sex-mismatched donor-recipient pairs tested and by DNA analysis in two sex-matched pairs. One patient died on day 18 of veno-occlusive disease of the liver with engraftment but before chromosome analysis could be performed (results are pending in 1 patient). A second patient died of fungal infection 78 days after transplant. Grade 2 acute GVHD occurred in two patients and grade 3 GVHD occurred in one patient. One patient is 301 days from transplant in remission with chronic GVHD; the remaining five patients are alive and disease free 67 to 112 days after transplantation. Preliminary results indicate that allogeneic PBSCs mobilized by rhG-CSF can provide rapid hematologic recovery without an appreciably greater incidence of acute GVHD than would be expected with marrow. Further follow-up is required to determine the incidence of chronic GVHD and any potential beneficial effects on relapse after transplant. 相似文献
9.
Allogeneic peripheral blood stem cell transplantation in patients with advanced hematologic malignancies: a retrospective comparison with marrow transplantation 总被引:16,自引:10,他引:16
Bensinger WI; Clift R; Martin P; Appelbaum FR; Demirer T; Gooley T; Lilleby K; Rowley S; Sanders J; Storb R; Buckner CD 《Blood》1996,88(7):2794-2800
Allogeneic peripheral blood stem cell (PBSC) transplants from HLA- identical siblings were performed in 37 patients with advanced hematologic malignancies. Outcomes were compared to a historical group of 37 similar patients with advanced hematologic malignancies receiving bone marrow (BM) transplants from HLA-identical donors. The PBSC group and historical BM group were well matched for diagnosis, disease stage, age, and graft-versus-host disease (GVHD) prophylaxis. Patients received PBSC transplants between 1993 to 1995 while BM patients were treated between 1989 to 1994. Engraftment, measured by the time to reach a peripheral neutrophil count > 500/L and platelet count > 20,000/microL without transfusions, occurred on days 14 and 11 in the patients transplanted with PBSC compared to days 16 and 15 in the patients receiving BM (P = .00063, .00014). The PBSC group required a median of 8 U of red blood cells and 24 U of platelets compared to 17 U of red blood cells and 118 U of platelets for BM transplant recipients (P = .0005, .0001). The estimated risks of developing grades 2 to 4 acute GVHD were 37% for the PBSC group and 56% for the BM group (P = .18), while the estimated risks of grades 3 to 4 acute GVHD were 14% for the PBSC group and 33% for the BM group, P = .05). Chronic GVHD occurred in 7 of 18 evaluable patients receiving PBSC and 6 of 23 evaluable patients receiving BM, P = .5. The estimated risks of transplant-related mortality at 200 days were 27% versus 45% (P = .33) relapse were 70% versus 53% (P = .27) and of overall survival were 50% and 41% (P = .39) for patients transplanted with PBSC or BM, respectively. This retrospective comparison suggests that compared to marrow transplantation from HLA-identical donors, allogeneic PBSC transplantation from HLA-identical donors is associated with faster engraftment, fewer transfusions, and no greater incidence of acute or chronic GVHD. 相似文献
10.
Two patients with aplastic anemia were treated with high-dose cyclophosphamide and marrow transplantation from their normal, genetically identical twin. Both patients rapidly recovered normal marrow function, but marrow failure recurred 13 and 18 months later. Because donor and host pairs were identical twins, these cases of graft failure could not have resulted from the usual cause of graft failure, ie, immunological reactivity of host cells against unshared minor histocompatibility antigens of the donor. These results imply that there are at least two mechanisms responsible for graft failure after marrow transplantation for severe aplastic anemia. 相似文献