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Sri Jayewardenepura Kotte, Sri Lanka

Vila-Rico M.,Ramon Llull University | Colome-Calls N.,Vall dHebron Institute dOncologia | Martin-Castel L.,Vall dHebron Institute dOncologia | Gay M.,Barcelona Institute for Research in Biomedicine | And 4 more authors.
Journal of Proteomics | Year: 2015

Transthyretin (TTR) is an amyloidogenic tetrameric protein, present in human plasma, associated with several familial amyloidoses. Variability of TTR is not only due to point mutations in the encoding gene but also to post-translational modifications (PTMs) at Cys10, being the most common PTMs the S-sulfonation, S-glycinylcysteinylation, S-cysteinylation and S-glutathionylation. It is thought that PTMs at Cys10 may play an important biological role in the onset and pathological process of the amyloidosis. We report here the development of a methodology for quantification of PTMs in serum samples, as well as for the determination of serum TTR levels, from healthy (wt) and TTR-amyloidotic (V30M mutation) individuals. It involves an enrichment step by immunoprecipitation followed by mass spectrometry analysis of (i) the intact TTR protein and (ii) targeted LC-MS analysis of peptides carrying the PTMs of interest. Analysis of serum samples by the combination of the two methods affords complementary information on the relative and absolute amounts of the selected TTR PTM forms. It is shown that methods based on intact protein are biased for specific PTMs since they assume constant response factors, whereas the novel targeted LC-MS method provides absolute quantification of PTMs and total TTR variants. Biological significance: The study of TTR has a high clinical relevance since it is responsible for diverse familial polyneuropathies. In particular, more than 80 point mutations have been described through genetic studies. However, genetic heterogeneity alone fails to explain the diverse onset and pathological process of the TTR related amyloidosis. The use of proteomic characterization is required to gather information about the PTMs variants present in serum, which have been suggested to be relevant for the amyloidotic pathology. This article is part of a Special Issue entitled: HUPO 2014. © 2015 Elsevier B.V. Source

Nazar A.L.,Nephrology and Transplant Unit
Saudi journal of kidney diseases and transplantation : an official publication of the Saudi Center for Organ Transplantation, Saudi Arabia | Year: 2014

We report the case of a 45-year-old chronic smoker who presented with acute paraplegia occurring during coitus and subsequently developed acute renal failure (ARF) requiring dialysis. He had absent peripheral pulses in the lower limbs with evidence of acute ischemia. Doppler study showed dissecting aneurysm of thoracic aorta, thrombotic occlusion of the distal aorta from L1 level up to bifurcation and occlusion of the right renal artery by a thrombus that was confirmed by magnetic resonance imaging of the spine. He was not subjected to any vascular intervention as his lower limbs were not salvageable due to delay in the diagnosis. Post-coital aortic dissection and aortic dissection presenting with acute paraplegia and ARF are very rare. This is probably the first case report with post-coital acute aortic dissection presenting with paraplegia and ARF. This case emphasizes the importance of a careful examination of peripheral pulses in patients presenting with ARF and paraplegia. Source

Nazar A.L.,Nephrology and Transplant Unit | Ariyaratne P.,Nephrology and Transplant Unit
Saudi journal of kidney diseases and transplantation : an official publication of the Saudi Center for Organ Transplantation, Saudi Arabia | Year: 2014

Chronic kidney disease is one of the main public health concerns in Sri Lanka. In comparison with dialysis, successful kidney transplantation improves both patient survival and quality of life, relieves the burden of dialysis in patients suffering from end-stage renal disease and decreases the cost of healthcare to the society and government. The objective of this retrospective cohort study was to evaluate graft and patient survival rates in patients who were transplanted from living donors at the Nephrology Unit of the National Hospital of Sri Lanka from January 2005 to January 2011. Data were collected using an interviewer-administered questionnaire and through a review of past medical records. The Kaplan-Meier method was used to determine the survival rate, the log rank test was used to compare survival curves and the Cox proportional hazard model was used for multivariate analysis. Mean follow-up was 26.44±16.6 months. The five-year death-censored graft survival of kidney transplant recipients from living donors in our center was 93.5% and the five-year patient survival was 82.2%, which is comparable with other transplant programs around the world. The number of acute rejection episodes was an independent risk factor for graft survival. Delayed graft function, younger recipient age and unknown cause of end-stage renal disease were found to be risk factors for graft failure but after adjusting for confounding factors, and the difference was not apparent. Source

Wijetunge S.,University of Peradeniya | Ratnatunga N.V.I.,University of Peradeniya | Abeysekera T.D.J.,Nephrology and Transplant Unit | Wazil A.W.M.,Nephrology and Transplant Unit | Selvarajah M.,Nephrology Unit
Indian Journal of Nephrology | Year: 2015

Chronic kidney disease of unknown etiology (CKDU) is endemic among the rural farming communities in several localities in and around the North Central region of Sri Lanka. This is an interstitial type renal disease and typically has an insidious onset and slow progression. This study was conducted to identify the pathological features in the different clinical stages of CKDU. This is a retrospective study of 251 renal biopsies identified to have a primary interstitial disease from regions endemic for CKDU. Pathological features were assessed and graded in relation to the clinical stage. The mean age of those affected by endemic CKDU was 37.3 ± 12.5 years and the male to female ratio was 3.3:1. The predominant feature of stage I disease was mild and moderate interstitial fibrosis; most did not have interstitial inflammation. The typical stage II disease had moderate interstitial fibrosis with or without mild interstitial inflammation. Stage III disease had moderate and severe interstitial fibrosis, moderate interstitial inflammation, tubular atrophy and some glomerulosclerosis. Stage IV disease typically had severe interstitial fibrosis and inflammation, tubular atrophy and glomerulosclerosis. The mean age of patients with stage I disease (27 ± 10.8 years) was significantly lower than those of the other stages. About 79.2%, 55%, 49.1% and 50% in stage I, II, III and IV disease respectively were asymptomatic at the time of biopsy. Source

Del Carmen Rial M.,Institute of Nephrology | Abbud-Filho M.,Sao Jose do Rio Preto Medical School | Torres Goncalves R.,Federal University of Rio de Janeiro | Martinez-Mier G.,Mexican Institute of Social Security | And 4 more authors.
Transplantation Proceedings | Year: 2010

One of the main goals in the current care of kidney transplant recipients is to extend long-term graft survival. Efficacious immunosuppressive agents devoid of nephrotoxicity are needed. In human clinical transplantation, sirolimus combined with other immunosuppressive drugs has proven to be a powerful immunosuppressant capable of preventing acute graft rejection, as well as of improving renal function, renal histology, and graft survival when compared with immunosuppressive regimens that include calcineurin inhibitors. The valuable experience gained through many clinical studies allows clinicians to plan sirolimus use. We present a review of the clinical experience and literature review on the use of sirolimus in the first 12 months posttransplantation. © 2010 Elsevier Inc. All rights reserved. Source

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