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排序方式: 共有367条查询结果,搜索用时 31 毫秒
31.
José Tinoco González Jose María Álamo Martínez Carmen Bernal Bellido Gonzalo Suárez Artacho Luis Miguel Marín Gómez Lydia Barrera-Pulido Javier Padillo Ruíz Miguel Ángel Gómez Bravo 《Cirugía espa?ola》2018,96(5):268-275
Between 1991 and 2013, 1,000 liver transplantations were performed at Virgen del Rocio Hospital (Seville, Spain). A retrospective study was conducted, analyzing the characteristics of recipients and donors, indications, surgical technique, complications and survival in 2 different stages (1991-2002 vs. 2003-2013) coinciding with the implementation of the MELD scale as a prioritization model. The most frequent indication were of hepatopathy of hepatocellular origin in 48.8%. There was a significant increase in the indications for hepatocarcinoma (8.6% and 24.1% P = 0.03), and the rate of retransplantation (5.9% vs 9.6%, P = 0.04). There was a change in the age of donation, going from 27.7 years in 1990 to 62.9 years in 2012 (P = 0.001). The percentage of patients who did not require blood transfusion doubled (6.16 vs. 14.31%, P = .001). Survival of all patients after one, 5 and 10 years was 77, 63.5 and 51.3%, respectively. 相似文献
32.
Prevention of osteocyte and osteoblast apoptosis by bisphosphonates and calcitonin 总被引:53,自引:0,他引:53
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Plotkin LI Weinstein RS Parfitt AM Roberson PK Manolagas SC Bellido T 《The Journal of clinical investigation》1999,104(10):1363-1374
Glucocorticoid-induced osteoporosis may be due, in part, to increased apoptosis of osteocytes and osteoblasts, and bisphosphonates (BPs) are effective in the management of this condition. We have tested the hypothesis that BPs suppress apoptosis in these cell types. Etidronate, alendronate, pamidronate, olpadronate, or amino-olpadronate (IG9402, a bisphosphonate that lacks antiresorptive activity) at 10(-9) to 10(-6) M prevented apoptosis of murine osteocytic MLO-Y4 cells, whether it was induced by etoposide, TNF-alpha, or the synthetic glucocorticoid dexamethasone. BPs also inhibited apoptosis of primary murine osteoblastic cells isolated from calvaria. Similar antiapoptotic effects on MLO-Y4 and osteoblastic cells were seen with nanomolar concentrations of the peptide hormone calcitonin. The antiapoptotic effect of BPs and calcitonin was associated with a rapid increase in the phosphorylated fraction of extracellular signal regulated kinases (ERKs) and was blocked by specific inhibitors of ERK activation. Consistent with these in vitro results, alendronate abolished the increased prevalence of apoptosis in vertebral cancellous bone osteocytes and osteoblasts that follows prednisolone administration to mice. These results suggest that the therapeutic efficacy of BPs or calcitonin in diseases such as glucocorticoid-induced osteoporosis may be due, in part, to their ability to prevent osteocyte and osteoblast apoptosis. 相似文献
33.
We have previously shown that administration of antiprogestin (AP) type II RU486 to ovariectomized (OVX) rats on the morning of pro-oestrus decreases the magnitude of preovulatory gonadotrophin surge. This suggests that the effect of RU486 on LHRH-dependent gonadotrophin release may be independent of its ability to block progesterone actions. The aim of the present research was to study the possible site of RU486 action and to determine whether the gonadotrophin suppressive effect of APs RU486 and ZK299 is dependent on the oestrogen background. Intact or OVX rats in the morning of pro-oestrus were injected s.c. with 4 mg of RU486 or ZK299 (AP type I) at 0900 h on pro-oestrus. At 1830 h, serum concentration of FSH and LH and median eminence (ME) content of LHRH were determined. In the second experiment, the effect of RU486 and ZK299 on pituitary responsiveness to LHRH (100 ng, i.p.) and ME content of LHRH at 1830 h pentobarbital-blocked intact or OVX rats was evaluated. In the last study, the anterior pituitary release of FSH and LH from pro-oestrus or metoestrus donors incubated with or without LHRH (1, 10 or 100 nM) in the presence or absence of APs (20 nM) was evaluated. Both APs reduced serum FSH and LH levels at 1830 h on pro-oestrus in intact and OVX rats. The suppressive effect on gonadotrophin release brought about by AP treatment was also evidenced in PB-blocked intact and OVX rats. This suggested that the inhibitory effect of APs occurred, at least in part, at pituitary level. Furthermore, in the absence of the natural ligand, APs significantly reduced basal and LHRH-stimulated FSH and LH release from pro-oestrous but not from metoestrus pituitaries. In conclusion, these experiments have shown, both 'in vivo' and 'in vitro', that APs RU486 and ZK299 have suppressive effects at pituitary level on basal and LHRH-stimulated FSH and LH secretion, regardless of their antiprogestagenic activity, in pro-oestrus but not in metoestrus. 相似文献
34.
Administration of the antiprogesterone RU486 to 4-day cyclic rats from metoestrus to pro-oestrus increases serum levels of LH while decreasing levels of FSH. If it is assumed that there is only one gonadotrophin-releasing hormone, there is no direct explanation for the decrease in FSH concentrations. The purpose of these experiments was to investigate the effect of RU486 on gonadotrophin secretion in cyclic rats during periods when the secretion of LH and FSH diverges. RU486 blunted the transient increase in FSH concentration on the afternoon of metoestrus and the compensatory ovarian hypertrophy on the next day of oestrus in unilaterally ovariectomized 4-day cyclic rats. In addition, bilateral ovariectomy reversed the effect of RU486 on the basal secretion of FSH. RU486 induced an increase in basal LH concentrations. Since ovarian inhibin decreases the basal release of FSH, and decreases in peripheral inhibin seem to be responsible for the transient rise in FSH during the oestrus cycle, the effect of RU486 on serum levels of LH and FSH during dioestrus in rats injected with a sheep anti-inhibin serum (AIS) were further evaluated. Treatment with AIS increased FSH levels in oil-treated rats without altering the levels of LH. In contrast, the effects of AIS on FSH secretion were blunted in RU486-treated rats. The results suggest that inhibin might be involved in the RU486-induced decrease of FSH secretion in cyclic rats. 相似文献
35.
L.M. Marin-Gomez M.A. Gomez-Bravo J.A. Alamo-Martinez L. Barrera-Pulido C. Bernal Bellido G. Surez Artacho J.M. Pascasio 《Transplantation proceedings》2009,41(6):2184-2186
Objective
To present the correlation between dosage and plasma concentration of tacrolimus and the consequences for short-term hepatorenal function of conversion to Advagraf (tacrolimus extended-release capsules) in liver transplant recipients.Patients and Methods
This observational study on adult liver transplant recipients examined tacrolimus levels after conversion to Advagraf therapy. Mean (SD) patient age was 51 (44-59) years. Conversion occurred at 43 (19-85) months posttransplantation, and follow-up was 193 (106.5-243.25) days. Dosage was adjusted milligram for milligram. Levels of tacrolimus, total bilirubin, aspartate aminotransferase, alanine aminotransferase, γ-glutamyl transferase, alkaline phosphatase, and creatinine were recorded on the day before conversion to Advagraf and 1, 3, 6, and months afterward.Results
Of the 79 patients in whom therapy was converted to Advagraf, 31 (39.2%) had alcoholic cirrhosis, 19 (24.1%) had viral disease, 10 (12.7) had mixed disease, 8 (10.1%) had cholestatic disease, 4 (5.1%) had metabolic disease, and 7 (8.8%) had other diseases. Despite no modification of Advagraf dosage during follow-up in most patients, mean tacrolimus levels decreased from the first month after conversion; however, at 6 months after conversion, they tended to equal the initial value. Renal function and liver biochemistry values demonstrated no significant change during follow-up.Conclusion
Although tacrolimus levels decreased initially after conversion to Advagraf therapy, 1:1 conversion is safe for hepatorenal function in liver transplant recipients. 相似文献36.
Bellido D Craig PO Mozgovoj MV Gonzalez DD Wigdorovitz A Goldbaum FA Dus Santos MJ 《Vaccine》2009,27(1):136-145
Brucella spp. lumazine synthase (BLS) is a highly immunogenic decameric protein. It has been previously evaluated as a carrier to increase the immunogenicity of peptides fused to its N-termini. VP8 is a sialic acid binding domain of rotavirus external capsid protein VP4, which is involved in virus adhesion to host cells. In this work, the C486 bovine rotavirus (BRV) VP8 core protein (VP8d) was fused to the structure of BLS with the aim to produce an enhancement of the immune response against BRV VP8 and to evaluate the possible use of this antigen for vaccine development. The feasibility of using BLS as an antigen delivery system of polypeptides larger in size than those previously tested was also evaluated. Groups of female mice were immunized with BLS-VP8d fusion protein, VP8d or an equimolar mixture of purified VP8d and BLS (BLS+VP8d). Dams immunized with BLS-VP8 induced 97.5-100% protection against homologous challenge with C486 BRV; while pups born to dams immunized either with VP8d or BLS+VP8d presented a significant lower level of protection. The neutralizing antibody pattern was also significantly different among these experimental groups, and in concordance with challenge experiment. Overall, these results demonstrate that the BLS-VP8d chimeric protein is properly folded and stable, and that the BLS scaffold is a potent antigen delivery system that enhances the antibody response against BRV and elicits complete homotypic passive protection in a suckling mouse model. 相似文献
37.
Negredo E Garrabou G Puig J Lòpez S Morén C Bellido R Ayen R Cardellach F Miró O Clotet B 《Antiviral therapy》2008,13(2):231-240
BACKGROUND: Tenofovir disoproxil fumarate (TDF) has a safe toxicity profile; however, administration together with didanosine (ddl) increases ddl levels causing mitochondrial damage and CD4+ T-cell decline. We assessed whether a simple reduction of the ddl dose in patients receiving ddl (400 mg/day) and TDF could revert this side effect. METHODS: Immunological and mitochondrial changes were analysed in 20 patients at baseline, after 14 months of receiving ddl (400 mg/day), TDF (300 mg/day) and nevirapine (NVP; 400 mg/day) and 14 months after a ddl dose reduction to 250 mg/day. Immunological analyses measured CD4+ and CD8+ T-cell counts and mitochondrial studies in peripheral blood mononuclear cells assessed mitochondrial DNA content by quantitative real-time PCR, cytochrome c oxidase (COX) activity by spectrophotometry and mitochondrial protein synthesis (COX-II versus beta-actin or COX-IV expression) by western blot. RESULTS: Treatment with TDF, ddl (400 mg/day) and NVP for 14 months produced significant decreases in mitochondrial parameters and CD4+ T-cell counts. The reduction in ddl dose resulted in mitochondrial DNA recovery; however, the remaining mitochondrial parameters remained significantly decreased. Levels of CD4+ T-cells were partially restored in 35% of patients. Subjects presenting a significant reduction in CD4+ T-cells during the high ddl dose period showed greater mitochondrial impairment in this stage and better mitochondrial and immunological recovery after drug reduction. CONCLUSIONS: Administration of high ddl doses together with TDF was associated with mitochondrial damage, which may explain the observed CD4+ T-cell decay. A reduction of the ddl dose led to mitochondrial DNA recovery, but was not sufficient to recover baseline CD4+ T-cell counts. Other mitochondrial toxicity in addition to DNA gamma-polymerase inhibition could be responsible for CD4+ T-cell toxicity. 相似文献
38.
I Mathov L I Plotkin C L Sgarlata J Leoni T Bellido 《Journal of bone and mineral research》2001,16(11):2050-2056
Bisphosphonates (BPs) are analogues of pyrophosphate, which are widely used for the treatment of different pathologies associated with imbalances in bone turnover. Recent evidence suggested that cells of the osteoblastic lineage might be targets of the action of BPs. The objective of this work was to determine whether BPs induce proliferation of osteoblasts and whether this action involves activation of the extracellular signal-regulated kinases (ERKs). We have shown that three different BPs (olpadronate, pamidronate, and etidronate) induce proliferation in calvaria-derived osteoblasts and ROS 17/2.8 as measured by cell count and by [3H]thymidine uptake. Osteoblast proliferation induced by all BPs diminished to control levels in the presence of U0126, a specific inhibitor of the upstream kinase MEK 1 responsible for ERK phosphorylation. Consistent with this, BPs induced ERK activation as assessed by in-gel kinase assays. Phosphorylation of ERK1/2 was induced by the BPs olpadronate and pamidronate within 30 s, followed by rapid dephosphorylation, whereas etidronate induced phosphorylation of ERKs only after 90 s of incubation and returned to basal levels within 15-30 minutes. In addition, both BP-induced cell proliferation and ERK phosphorylation were reduced to basal levels in the presence of nifedipine, an L-type voltage-sensitive calcium channel (VSCC) inhibitor. These results show that BP-induced proliferation of osteoblastic cells is mediated by activation of ERKs and suggest that this effect requires influx of Ca2+ from the extracellular space through calcium channels. 相似文献
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