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Parathyroid hormone (PTH), which is elevated in patients with chronic renal failure, has been shown to participate in the development of vascular calcification. Previous studies have demonstrated that PTH may promote endothelial expressions of proinflammatory parameters. On the basis of these data, we evaluated whether PTH may have an impact on endothelial osteoprotegerin (OPG), a vascular-protective factor which may control vascular calcification. Endothelial cells were stimulated with 10−12to 10−10mol/l PTH. PKC and PKA are the main cellular pathways of PTH. Inhibitors and activators of PKC or PKA were used to determine whether these signaling pathways are involved in the control of endothelial OPG. PTH induced a decrease in OPG secretion and mRNA expression. Treatment of PTH-stimulated cells by calphostin C (PKC inhibitor) induced a further decrease in OPG secretion, while Rp-cAMP (PKA inhibitor) had no additional effect. In nonstimulated cells, a PKC activator significantly stimulated OPG secretion, while a PKA activator was associated with a decline. These effects were blunted in the presence of calphostin C and Rp-cAMP, respectively. An increase in OPG secretion induced by a PKC activator indicates that the basal OPG secretion is mediated through PKC. The decrease induced by a PKA activator, which is similar to the decrease observed with PTH, suggests that the action of PTH on OPG secretion and mRNA expression may be due to the PKA pathway.

Background Disturbances in vitamin D(3) metabolism are associated with an increased cardiovascular morbidity and mortality. The aim of this study was to assess the effects of calcitriol, the active metabolite of vitamin D3, on pro-atherosclerotic parameters in human umbilical vein cord endothelial cells (HUVEC). Materials and methods Calcitriol at 10(-10) and/or 10(-9) mol L(-1) was given to cultured HUVEC which were either non-stimulated or lipopolysaccharide (LPS) stimulated. Inter cellular adhesion molecule-1 and platelet-endothelial cell adhesion molecule-1, were determined by flow cytometry analysis. The receptor of advanced glycation end product (RAGE) and interleukin-6 (IL-6) mRNA expressions by RT-PCR and IL-6 secretion by enzyme-linked immunosorbent assay (ELISA). Nuclear p65 DNA-binding activity was measured by transcription factor assay kit and the inhibitor-kappaBalpha (IkappaBalpha), phosphorylated-IkappaBalpha (P-IkappaBalpha) and phosphorylated-p38 mitogen-activated protein kinase (MAPK) protein levels were determined by Western blot. Results Calcitriol decreased the adhesion molecules expression, as well as the LPS-induced mRNA expressions of RAGE and IL-6 and LPS induced IL-6 secretion. Furthermore, the LPS induced nuclear factor kappaB (NFkappaB)-p65 DNA-binding activity was also decreased by calcitriol. IkappaBalpha levels were increased and p-IkappaBalpha levels decreased after calcitriol treatment. The increased levels of activated p38 MAPK after LPS treatment were also decreased due to pre-incubation with calcitriol. Conclusions The decreased NFkappaB and p38 activities followed by calcitriol treatment may explain the anti-inflammatory/atherosclerotic properties of calcitriol that were observed previously and were emphasized in this study, demonstrating the inhibitory effect of calcitriol on the pro-inflammatory parameters: adhesion molecules, RAGE and IL-6.

The life expectancy of dialysis patients depends, to a large extent, on blood access which provides uninterrupted and efficient treatment. Dialysis access created by a direct anastomosis between artery and vein usually allows normal dialysis for many years. Blood access by a bridge graft between artery and vein functions for a much shorter time and occludes chiefly because of endothelial hyperplasia at the graft vein anastomosis. This type of fistula is created when the veins of the patient are small. During the last few years the dialysis population is increasingly composed of adult and elderly patients suffering from diabetes mellitus, hypertension, dyslipidemias and atheromatous vascular disease so that a relatively large proportion of dialysis accesses are created using a bridge graft. Since we currently do not have the knowledge of how to arrest or delay the processes which lead to access occlusion, attempts are made to implement prophylactic strategies, find stenoses and dilate them before the access fails. Up to date, controlled trials have not succeeded in proving that this method prolongs access use. These trials did not describe the use of stents following dilatation.Between July 2002 and May 2005, 238 angiographies were performed on blood accesses including 179 angioplasties of stenoses. In sixteen patients a stent was deployed during the angioplasty.In ten patients dialysis was performed using the same access up to the end of the study period, an average of 43 months from the creation of the access. Three patients died with a functioning access and in three the access occluded during the period of followup.This study shows that the use of stents following angioplasty of dialysis access stenoses can improve the duration of use of accesses created through grafts.

Advanced glycation end products (AGEs), which are elevated in diabetic and uremic patients, may induce vascular dysfunctions, and calcitriol may improve the cardiovascular complications. Therefore, we examined whether calcitriol may modify the endothelial response to AGEs stimulation. Knowing the importance of nuclear factor-kappaB in endothelial inflammatory responses, the effect of AGEs and calcitriol on this pathway was also studied. Calcitriol was added to endothelial cells previously incubated with AGE-human serum albumin (HSA). AGE-HSA induced a decrease in endothelial nitric oxide synthase (eNOS) mRNA expression and enzyme activity. Addition of calcitriol to AGE-HSA-treated endothelial cells improved the decreased action of AGEs on the eNOS system. AGE-HSA increased the AGEs receptor mRNA and protein, which were both blunted by calcitriol. The parallel elevation of interleukin-6 mRNA in the presence of AGE-HSA was also blunted by calcitriol. The NF-kappaB-p65 DNA binding activity was enhanced and associated with a decrease in inhibitor kappaBalpha (IkappaBalpha) and an increase in phosphorylated (p)-IkappaBalpha levels. Addition of calcitriol blunted the AGEs-induced elevation of NF-kappaB-p65 DNA binding activity, a phenomenon related to an increased expression of IkappaBalpha. This increase was correlated to declined p-IkappaBalpha levels. The present results support the concept that calcitriol may act as a vascular protective agent counteracting the probable deleterious actions of AGEs on endothelial cell activities.

Psychiatric patients' coping capacity with various life situations is limited due to their mental illness. This difficulty is even more pronounced when dealing with severe physical conditions such as kidney failure, the need for dialysis and kidney transplant. In the past, similar to patients who suffered from additional physical conditions, patients with major psychiatric disorders, long-term psychotic illness such as schizophrenia, were not considered candidates for dialysis treatment. Although these attitudes have changed, there is still concern that psychiatric patients would find it difficult to cooperate with the long-term treatment required following kidney transplant, and that lack of careful adherence to medication regimens could lead to rejection of the implant. This article describes five mentally ill individuals who suffer from terminal kidney failure, and illustrates the dilemma associated with dialysis and kidney transplant in psychiatric patients. Close cooperation between the psychiatric staff and the nephrology team can lead to the hoped for outcomes.

Complete remission can be achieved in 60-80% of adults with diffuse aggressive non-Hodgkin's lymphoma. However, 20-40% of them will subsequently relapse. Nevertheless, formal follow-up guidelines for recurrence detection have never been advocated. We analyzed the pattern of relapse in 30 patients with intermediate- and high-grade non-Hodgkin's lymphoma and the value of intensive protocol for relapse detection. This protocol includes frequent follow-up visits, complete blood count, and serum LDH tests along with annual chest, abdominal, and pelvic CT scans. The median duration of complete remission was 12 months. Twenty-five relapses (83%) were suspected after an interim history and/or physical examination, whereas only 5 relapses (17%) were detected by routine radiographic or laboratory follow-up studies. The majority of relapses (19/30) were detected in sites that included the sites of prior disease. For the first 12 months of complete remission, the estimated cumulative save in charge for a follow-up strategy, based on regular visits in the hematology clinic and performing laboratory and radiologic studies as clinically indicated, is 44% of the cost of a routine intensive evaluation. A reliable and cost-effective follow-up method for non-Hodgkin's lymphoma patients in complete remission should include frequent history and physical examination. Complementary studies should be performed according to clinical indications.