Long-Term Survival (>25 Years) of Deceased Donor Kidney Transplant Recipients: a Single-Center Experience

INTRODUCTION: The aim of this preliminary work is to analyze the clinical features of 52 patients with a functional transplanted kidney for >25 years (all first transplant and all deceased donor recipients) and to compare with a similar though more complete study from Hôpital Necker-Paris 2012. METHODS: The mean graft survival at 25 years is 12.7% and at 30 years is 10%. The actual mean serum creatinine concentration is 1.3 mg/L. We analyzed recipient age (mean, 35.9 years) and gender (29 men and 23 women). Donor age was 26.7 ± 10.3 years. Seven patients (13.4%) were transplanted with 1 HLA mismatch, 42.3% with 2 mismatches, and 44.2% with 3 mismatches. Mean cold ischemia time was 15.45 ± 7.7 hours. Of the recipients, 76% had immediate graft function; 38% experienced 1 acute rejection episode and 4 patients had 2 rejection crises. The initial immunosuppressive regimen was azathioprine (AZA) + prednisolone (Pred) in 14 patients, cyclosporin (CSA) + Pred in 13 patients, and CSA + AZA + Pred in 25 patients. Of these patients, 19% maintained their initial regimen, and 54% (28 patients) were very stable on a mixed CSA regimen for >25 years. RESULTS: We present the major complications (diabetes, neoplasia, and hepatitis C virus positivity). CONCLUSION: Our results in deceased donor kidney recipients for >25 years are similar to the mixed population (deceased donors and living donors) presented by the Necker group, although 54% of our patients remain on CSA immunosuppression, contradicting the idea that its use is not compatible with good long-term kidney function in transplant recipients

Science, society, politics, and the media: joining efforts to manage the risk of termite infestation in the Azores

SRA 2008 Annual Meeting. Sunday, 7 December 2008 to Wednesday, 10 December 2008.Termites are well-established and serious pests of structural wood infestation in different parts of the world. Presently, in the Azores archipelago (Portugal), the drywood termite Cryptotermes brevis (Insecta, Isoptera) has been referred to four of the nine islands, and the damages to the buildings and other artefacts are severe and constitute a serious threat, especially in its main towns. In order to control the situation there has been a considerable scientific and political investment to survey and classify the infestation, and to develop mitigation strategies, over the last five years. Nevertheless, the infestation is far from being controlled and, also, most of the Azorean citizens are still unaware of the dangers and risks associated to this urban pest. If, however, effective educational and management practices are initiated soon, the losses from C. brevis can be greatly reduced. Therefore, the major aims of this research project are: (i) to understand people’s perspectives about the consequences of the termite infestation and their appraisal about the effectiveness of the proposed and existing management strategies; (ii) to understand the functions of the media in the making of public opinion; (iii) to develop simple ways of communicating complex technical information according to people’s perception of who is accountable and trustworthy, in order to avoid misunderstandings between science, politics, managers and society; (iv) to develop and implement devices focused on the communication between the population and the main stakeholders, to promote the involvement of citizens and their commitment as essential partners of the termite control. This paper aims to integrate data from the abovementioned stakeholders in order to identify communication problems, to create adequate strategies to solve conflicts, to facilitate dialogue and partnerships among stakeholders and to promote termite risk literacy. Data was gathered using several techniques, including interviews, descriptive-interpretative analysis of media, scientific discourses and existing operational programs. Data shows that the lack of integration among stakeholders is the most obvious barrier to be overcome by the communication devices to implement

Acetic Acid Induces Sch9p-dependent Translocation of Isc1p from the Endoplasmic Reticulum into Mitochondria

Changes in sphingolipid metabolism have been linked to modulation of cell fate in both yeast and mammalian cells. We previously assessed the role of sphingolipids in cell death regulation using a well characterized yeast model of acetic acid-induced regulated cell death, finding that Isc1p, inositol phosphosphingolipid phospholipase C, plays a pro-death role in this process. Indeed, isc1∆ mutants exhibited a higher resistance to acetic acid associated with reduced mitochondrial alterations. Here, we show that Isc1p is regulated by Sch9p under acetic acid stress, since both single and double mutants lacking Isc1p or/and Sch9p have the same resistant phenotype, and SCH9 deletion leads to a higher retention of Isc1p in the endoplasmic reticulum upon acetic acid exposure. We also found that the higher resistance of all mutants correlates with higher levels of endogenous mitochondrial phosphorylated long chain bases (LCBPs), suggesting that changing the sphingolipid balance in favour of LCBPs in mitochondria results in increased survival to acetic acid. In conclusion, our results suggest that Sch9p pathways modulate acetic acid-induced cell death, through the regulation of Isc1p cellular distribution, thus affecting the sphingolipid balance that regulates cell fate

Mitochondrial- and Endoplasmic Reticulum-Associated Oxidative Stress in Alzheimer's Disease: From Pathogenesis to Biomarkers

Alzheimer's disease (AD) is the most common cause of dementia in the elderly, affecting several million of people worldwide. Pathological changes in the AD brain include the presence of amyloid plaques, neurofibrillary tangles, loss of neurons and synapses, and oxidative damage. These changes strongly associate with mitochondrial dysfunction and stress of the endoplasmic reticulum (ER). Mitochondrial dysfunction is intimately linked to the production of reactive oxygen species (ROS) and mitochondrial-driven apoptosis, which appear to be aggravated in the brain of AD patients. Concomitantly, mitochondria are closely associated with ER, and the deleterious crosstalk between both organelles has been shown to be involved in neuronal degeneration in AD. Stimuli that enhance expression of normal and/or folding-defective proteins activate an adaptive unfolded protein response (UPR) that, if unresolved, can cause apoptotic cell death. ER stress also induces the generation of ROS that, together with mitochondrial ROS and decreased activity of several antioxidant defenses, promotes chronic oxidative stress. In this paper we discuss the critical role of mitochondrial and ER dysfunction in oxidative injury in AD cellular and animal models, as well as in biological fluids from AD patients. Progress in developing peripheral and cerebrospinal fluid biomarkers related to oxidative stress will also be summarized