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51.
Labombarda F Gonzalez SL Gonzalez DM Guennoun R Schumacher M de Nicola AF 《Journal of neurotrauma》2002,19(3):343-355
Progesterone (PROG) exerts beneficial and neuroprotective effects in the injured central and peripheral nervous system. In the present work, we examine PROG effects on three measures of neuronal function under negative regulation (choline acetyltransferase [ChAT] and Na,K-ATPase) or stimulated (growth-associated protein [GAP-43]) after acute spinal cord transection injury in rats. As expected, spinal cord injury reduced ChAT immunostaining intensity of ventral horn neurons. A 3-day course of intensive PROG treatment of transected rats restored ChAT immunoreactivity, as assessed by frequency histograms that recorded shifts from predominantly light neuronal staining to medium, dark or intense staining typical of control rats. Transection also reduced the expression of the mRNA for the alpha3 catalytic and beta1 regulatory subunits of neuronal Na,K-ATPase, whereas PROG treatment restored both subunit mRNA to normal levels. Additionally, the upregulation observed for GAP-43 mRNA in ventral horn neurons in spinal cord-transected rats, was further enhanced by PROG administration. In no case did PROG modify ChAT immunoreactivity, Na,K-ATPase subunit mRNA or GAP-43 mRNA in control, sham-operated rats. Further, the PROG-mediated effects on these three markers were observed in large, presumably Lamina IX motoneurons, as well as in smaller neurons measuring approximately <500 micro2. Overall, the stimulatory effects of PROG on ChAT appears to replenish acetylcholine, with its stimulatory effects on Na,K-ATPase seems capable of restoring membrane potential, ion transport and nutrient uptake. PROG effects on GAP-43 also appear to accelerate reparative responses to injury. As the cellular basis for PROG neuroprotection becomes better understood it may prove of therapeutic benefit to spinal cord injury patients. 相似文献
52.
María de Oña Navarro Santiago Melón Susana Méndez Beatriz Iglesias Ana Palacio María J. Bernardo José L. Rodriguez-Lambert Ernesto Gómez 《Transplant international》2002,15(11):570-573
Ganciclovir (GCV) prophylaxis or pre-emptive therapy significantly reduce the rate of cytomegalovirus (CMV) disease and viremia, but increase the potential for emergence of ganciclovir-resistant CMV strains. The inhibitor concentration at 50% (IC(50)) of GCV from 156 CMV isolates from 59 renal or heart transplant recipients was calculated by means of a rapid phenotypic susceptibility assay. Twenty-seven strains were from 14 patients undergoing GCV therapy. The IC(50) was higher in patients under the prophylaxis regimen. One CMV strain, from a heart transplant recipient, became GCV-resistant after 1 month of therapy (IC(50)=13.7 micromol/l). These data, together with clinical and virological markers, suggested that a switch to foscarnet was necessary, and good evolution was observed. Thus, assay of CMV susceptibility to GCV could be helpful in clinical management. 相似文献
53.
Mechanism of vascular smooth muscle cells activation by hydrogen peroxide: role of phospholipase C gamma. 总被引:2,自引:0,他引:2
Francisco R González-Pacheco Carlos Caramelo Maria Angeles Castilla Juan J P Deudero Javier Arias Susana Yagüe Sonsoles Jiménez Rafael Bragado Maria Victoria Alvarez-Arroyo 《Nephrology, dialysis, transplantation》2002,17(3):392-398
BACKGROUND: Hydrogen peroxide (H2O2) formation is a critical factor in processes involving ischaemia/ reperfusion. However, the precise mechanism by which reactive oxygen species (ROS) induce vascular damage are insufficiently known. Specifically, activation of phospholipase C gamma (PLCgamma) is a probable candidate pathway involved in vascular smooth muscle cells (VSMC) activation by H2O2. METHODS: The activation of human venous VSMC was measured as cytosolic free calcium mobilization, shape change and protein phosphorylation, focusing on the role of tyrosine phosphorylation-activated PLCgamma. RESULTS: The exposure of VSMC to exogenous H2O2 caused a rapid increase in cytosolic free calcium concentration ([Ca2+]i), and induced a significant VSMC shape change. Both effects were dependent on a tyrosine kinase-mediated mechanism, as determined by the blockade of short-term treatment of VSMC with the protein tyrosine kinase inhibitor, genistein. Giving further support to the putative role of phospholipase C (PLC)-dependent pathways, the [Ca2+]i and VSMC shape change response were equally inhibited by the specific PLC blocker, 1-(6-((17-beta-methoxyestra-1,3,5(10)trien-17-yl)amino)hexyl)-1H-pyrrole-2,5-dione (U73122). In addition, U73122 had a protective effect against the deleterious action (24 h) of H2O2 on non-confluent VSMC. As a further clarification of the specific pathway involved, the exposure to H2O2 significantly stimulated the tyrosine phosphorylation of PLCgamma with a concentration- and time-profile similar to that of [Ca(2+)](i) mobilization. CONCLUSIONS: The present study reveals that H(2)O(2) activates PLCgamma on VSMC through tyrosine phosphorylation and that this activation has a major role in rapid [Ca(2+)](i) mobilization, shape-changing actions and damage by H(2)O(2) in this type of cells. These findings have direct implications for understanding the mechanisms of the vascular actions of H(2)O(2) and may help to design pharmacologically protective strategies. 相似文献
54.
A. Valdivieso J. Bustamante J.G. Uriarte P. Ruiz I. Pijoan M.J. Suarez J. Ortiz de Urbina 《Transplantation proceedings》2010,42(2):660-662
Management of patients with hepatocellular carcinoma (HCC) recurrence after liver transplantation (OLT) is not well established. We conducted a retrospective analysis of our results in the treatment of HCC recurrence after OLT Patients. The 23 HCC recurrences developed after 182 OLT performed for HCC within Milan criteria, had an average follow-up of 60 months.
Results
The median time to recurrence was 23.4 months. Surgical resection of the recurrence was possible in 11 patients, but an R-0 resection was obtained in 8 patients. Four of these 8 patients developed another recurrence, with 3 succumbing due to tumor recurrence and 1 alive at 12 months with recurrence. The other 4 patients without recurrences, include 3 who are alive at 19, 31, and 86 months and 1 who died at 32.6 months due to hepatitis C recurrence. The 3 patients with palliative resections developed recurrences. Twelve patients were rejected for surgery: 8 were treated symptomatically, 2 with systemic chemotherapy, and 2 with everolimus and sorafenib. This last treatment was also prescribed for 2 patients after R-0 surgery who are alive at 19 and 31 months and for 1 patient after R-1 surgery who is alive at 19 months. Of 15 patients who died, 13 succumbed to HCC recurrence. The average survival from transplantation was 61.7 ± 37.5 and 48 ± 34.3 months for patients without and with recurrence, respectively (P < .001). The survival from the recurrence was significantly higher among patients with R-0 surgery: 32.3 ± 21.5 versus 11.9 ± 6.9 months (P = .006).Conclusions
HCC recurrence after OLT of patients within Milan criteria was low but had a great impact on survival. Few cases are amenable to R-0 resection, but when possible it was associated with a significantly increased survival, although with an high incidence of a new recurrence. There is a rationale for the use of sorafenib and mammalian target of rapamycin based immunosuppression, which warrants randomized studies. 相似文献55.
Penna G Mondaini N Amuchastegui S Degli Innocenti S Carini M Giubilei G Fibbi B Colli E Maggi M Adorini L 《European urology》2007,51(2):524-33; discussion 533
OBJECTIVE: This prospective study quantified cytokine and chemokine levels in seminal plasma of patients with chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) and benign prostatic hyperplasia (BPH), to evaluate inflammatory mediators as possible surrogate markers for diagnosis and treatment efficacy. METHODS: Seminal plasma levels of eight cytokines and nine chemokines were evaluated by multiplex arrays in 83 men: 20 healthy controls and 9 men with CP/CPPS IIIA, 31 with CP/CPPS IIIB, and 23 with BPH. Prostate samples obtained by transurethral resection of the prostate from 13 patients with BPH were analysed by immunohistochemistry to detect interleukin 8 (IL-8)-producing cells and characterise inflammatory infiltrates. RESULTS: Significantly increased levels of cytokines (IL-1alpha, IL-1beta, IL-6, IL-10, IL12p70) and chemokines (CCL1, CCL3, CCL4, CCL17, CCL22, CXCL8/IL-8) were observed in seminal plasmas from patients with CP/CPPS or BPH. However, only IL-8 was significantly elevated compared to controls (median [quartiles] 1984 [1164-2444] pg/ml), in patients with CP/CPPS IIIA (15,240 [10,630-19,501] pg/ml; p<0.0001), CP/CPPS IIIB (2983 [2033-5287] pg/ml; p=0.008), and BPH (5044 [3063-11,795] pg/ml, p<0.0001), discriminating CP/CPPS IIIA versus IIIB (accuracy=0.882+/-0.078; p=0.001). Inflammatory infiltrates were detected in prostate samples from 13 of 13 BPH patients, and IL-8-producing prostate cells in 11 of 13 samples. IL-8 concentration in seminal plasma was positively correlated with symptom score and prostate-specific antigen levels both in CP/CPPS and BPH patients. CONCLUSIONS: IL-8 is expressed in situ by epithelial and stromal prostate cells and is functional, as shown by recruitment of cells expressing cognate receptors in BPH prostate tissue, indicating its involvement in disease pathogenesis. Among all the cytokines and chemokines analysed, IL-8 appears to be the most reliable and predictive surrogate marker to diagnose prostate inflammatory conditions, such as CP/CPPS and BPH. 相似文献
56.
Nyqvist D Speier S Rodriguez-Diaz R Molano RD Lipovsek S Rupnik M Dicker A Ilegems E Zahr-Akrawi E Molina J Lopez-Cabeza M Villate S Abdulreda MH Ricordi C Caicedo A Pileggi A Berggren PO 《Diabetes》2011,60(10):2571-2577
OBJECTIVE
Freshly isolated pancreatic islets contain, in contrast to cultured islets, intraislet endothelial cells (ECs), which can contribute to the formation of functional blood vessels after transplantation. We have characterized how donor islet endothelial cells (DIECs) may contribute to the revascularization rate, vascular density, and endocrine graft function after transplantation of freshly isolated and cultured islets.RESEARCH DESIGN AND METHODS
Freshly isolated and cultured islets were transplanted under the kidney capsule and into the anterior chamber of the eye. Intravital laser scanning microscopy was used to monitor the revascularization process and DIECs in intact grafts. The grafts’ metabolic function was examined by reversal of diabetes, and the ultrastructural morphology by transmission electron microscopy.RESULTS
DIECs significantly contributed to the vasculature of fresh islet grafts, assessed up to 5 months after transplantation, but were hardly detected in cultured islet grafts. Early participation of DIECs in the revascularization process correlated with a higher revascularization rate of freshly isolated islets compared with cultured islets. However, after complete revascularization, the vascular density was similar in the two groups, and host ECs gained morphological features resembling the endogenous islet vasculature. Surprisingly, grafts originating from cultured islets reversed diabetes more rapidly than those originating from fresh islets.CONCLUSIONS
In summary, DIECs contributed to the revascularization of fresh, but not cultured, islets by participating in early processes of vessel formation and persisting in the vasculature over long periods of time. However, the DIECs did not increase the vascular density or improve the endocrine function of the grafts.Clinical islet transplantation can restore endogenous insulin production and glycemic control in patients with type 1 diabetes, yet increased knowledge, and hence refinement, would allow for a wider application of this therapy (1). Pancreatic islets are interspersed by a dense and tortuous capillary network that facilitates an efficient exchange of oxygen, nutrients, and hormones between the endocrine cells and the bloodstream. Transplanted islets are revascularized by blood vessels that grow into the islets from the host organ via angiogenesis (2), although the acquired vasculature has a significantly lower vessel density compared with the endogenous islets (3). Furthermore, during the initial avascular engraftment period, a dramatic reduction in insulin content and high rate of cell death occur within the islets (4). Therapies that enhance the angiogenic capacity of islets by overexpression of vascular endothelial growth factor-A (VEGF-A) can increase the vascular density of islet grafts and improve metabolic function (5,6).Recently, we and others showed that donor islet endothelial cells (DIECs) can form functional vessels within transplanted islets (7,8). Immediately after isolation (i.e., in freshly isolated islets), a large number of intraislet endothelial cells (ECs) are present (7–9). However, if the islets are cultured, the intraislet ECs rapidly disappear, and by 4 days, only ∼5% of the initial content is detected (7). Therefore, freshly isolated islets, in contrast to cultured islets, contain an extra pool of ECs that potentially could promote islet revascularization and function after transplantation. Here, we have performed a detailed characterization of the role of DIECs in the revascularization of transplanted islets. 相似文献57.
We report the endovascular treatment of two patients presenting with aortoduodenal fistulae. The first patient was a 66-year-old man admitted with hematemesis. He was on clopidogrel and had received a cryopreserved aortic graft for a mycotic abdominal aortic aneurysm five years earlier. Computed tomography (CT) showed aortic pseudoaneurysms in close contact with the duodenum. Endovascular repair was carried out. Twenty-seven months after the procedure the patient remains asymptomatic. The second patient was a 78-year-old man admitted with abdominal pain and nausea. CT revealed an abdominal aortic pseudoaneurysm and aortoduodenal fistula. He suffered from severe chronic obstructive pulmonary disease that greatly increased his surgical morbidity and mortality. An endovascular repair was performed under epidural anesthesia. The patient died of a postoperative pneumonia 38 days after surgery. These two cases illustrate the importance of endovascular aortic repair especially when an open surgical procedure is either difficult or impossible. 相似文献
58.
Tumor necrosis factor-like weak inducer of apoptosis (TWEAK) is a cytokine of the TNF superfamily that activates the Fn14 receptor. TWEAK may regulate cell proliferation, cell death, cell differentiation, and inflammation. TWEAK and Fn14 are constitutively present in the kidney. Sources of TWEAK and Fn14 include intrinsic renal cells and infiltrating leukocytes. Basal Fn14 expression is low, but Fn14 is greatly upregulated during kidney injury. TWEAK contributes to kidney inflammation promoting chemokine secretion by renal cells through canonical and non-canonical NFκB activation. TWEAK also promotes tubular cell proliferation. However, TWEAK induces mesangial and tubular cell apoptosis under proinflammatory conditions. These data indicate that TWEAK is a multifunctional cytokine in the kidney, the actions of which are modulated by the cell microenvironment. Confirmation of the role of TWEAK in kidney injury came from functional studies in experimental animal models. The TWEAK/Fn14 pathway contributed to cell death and interstitial inflammation during acute kidney injury, to glomerular injury in lupus nephritis, to hyperlipidemia-associated kidney injury, and to tubular cell hyperplasia following unilateral nephrectomy. Circulating soluble TWEAK (sTWEAK) levels are a potential biomarker of adverse outcomes in chronic kidney disease and urinary sTWEAK is a potential biomarker of lupus nephritis activity. The available evidence suggests that TWEAK may provide diagnostic information and be a therapeutic target in renal injury. Its role in human kidney disease should be further explored. 相似文献
59.
Gastaca M Valdivieso A Ruiz P Gonzalez J Ventoso A de Urbina JO 《Clinical transplantation》2011,25(3):E320-E326
Hepatic venous outflow obstruction (HVOO) is a rare complication after orthotopic liver transplantation (OLT) usually related to technical issues or to malposition or kinking of the hepatic graft. When HVOO is diagnosed during the early post-transplant period, surgical options are technically very demanding and outcomes discouraging. Therefore, angioplasty and stent placement have been indicated to avoid a chronic lesion of the graft. Three cases of HVOO after OLT are reported. HVOO was diagnosed during the early post-transplant period and was due to graft malposition in two patients and kinking of the vena cava anastomosis in one. All patients were successfully treated with a 300-cc gel-filled breast implant surgically placed in the right hepatic fossa with the liver graft resting on it. Massive ascites in all three patients disappeared and renal impairment resolved within two wk post-implant placement. No prosthesis-related complications have been observed after a follow-up ranging from 30 to 58 months. We describe a simple and effective method of maintaining the liver graft in an adequate position to achieve prolonged relief of the outflow obstruction for the whole graft and discuss the advantages of a breast implant over stent placement or the use of different balloon catheters. 相似文献
60.
OBJECTIVES: To assess the effect of four anesthetic techniques on recovery after a single dose of 0.2 mg/kg of cisatracurium. PATIENTS AND METHOD: After giving informed consent, 96 patients of both sexes, ASA I-III, were enrolled. Anesthesia was induced with fentanyl, propofol O2-N2O (FiO2 40%) after which the patients were randomly assigned to four groups according to maintenance technique: propofol by infusion, sevoflurane, desflurane or isoflurane at 1.3 MAC. Neuromuscular block was monitored (electromyographic recording of the pollicis adductor). Variables recorded were time of maximum block, duration of action of 1% and 25%, and recovery indices at T0-TR75 andT25%-T75%. ANOVA was performed ( = 0.05 and beta = 0.1). RESULTS: The groups were homogeneous. Time until recovery of 25% of baseline amplitude of the first response to a train of four (TOF) (T1) was longer in the desflurane group (68.4 +/- 11.1 min) than in the propofol group (60.2 +/- 9.4 min; p < 0.05). Time until recovery of 75% of the TOF-ratio was longer in the sevoflurane (96.8 +/- 13.1 min), desflurane (101.5 +/- 14.4 min) and isoflurane (94.1 +/- 13.9 min) groups than in the propofol group (83.7 +/- 1.3 min) (p < 0.0001).Times until recovery of T1 up to 1% were not statistically different: 45.8 +/- 10.7 (propofol), 50.6 +/- 11.0 (sevoflurane), 51.3 +/- 11.5 (desflurane) and 46.5 +/- 11.2 min (isoflurane). The 25% - 75% recovery index was also similar at 19.0 +/- 9.3 (propofol), 20.0 +/- 5.1 (sevoflurane), 25.7 +/- 12.4 (desflurane) and 20.9 +/- 7.9 (isoflurane). CONCLUSIONS: The inhaled anesthetics studied prolong the duration of clinical effect of cisatracurium more than does propofol. 相似文献