Docstoc

Preliminary Studies on Proteomics and Peritoneal Dialysis

Document Sample
Preliminary Studies on Proteomics and Peritoneal Dialysis Powered By Docstoc
					Preliminary Studies on Proteomics
      and Peritoneal Dialysis
      Reference: Brewis IA, Topley N.
    Proteomics and peritoneal dialysis:
  Early days but clear potential. Nephrol
   Dial Transplant. 2010;25:1749–1753.
     Global Analysis of Proteomics
• Proteomics and its application have lead the post-genomic
  technologies, as it has helped in the understanding the central role
  of proteins and protein–protein interactions in the entire aspects of
  cellular function.
• Quantification and global identifications of proteins, not only help
  in understanding a diseased or healthy individual but also lead to
  the discovery of biomarkers.
• Biomarker discovery has profuse scientific evidence from
  proteomics and suggests that most of the diseases are caused due
  to changes in certain proteins in the plasma.
• The clinical specimen or biological fluids probably contain a protein
  profile, which indicates diseases in that organ system like studies on
  urine can be related to kidney and bladder diseases, cerebrospinal
  fluid for neurological conditions.
  Proteomics to Study Peritoneal Dialysis

• Paucity of data is the main reason for few studies on
  peritoneal effusions.
• Peritoneal dialysis is considered as an effective mode of renal
  replacement therapy.
• This offers analysis of peritoneal dialysis effluents (PDE) from
  all types of patients and can also provide critical information
  about PD exclusively, along with general information about
  the peritoneal environment. A study from this paper was the
  first to show the differences between diabetic PDE and
  normal peritoneal fluid.
• The methods involved two dimensional electrophoresis (2DE);
  a gel-based approach for the analysis of proteins and was
  later confirmed by western blotting.
• Inclusions like vitamin D-binding protein, haptoglobin and α2-
  macroglobulin at raised levels, and complement component
  C4A and immunoglobulin κ at lower levels were considered
  and confirmed through western blotting.
• Change in the permeability of the peritoneal membrane,
  caused by the loss of vitamin binding protein, haptoglobin and
  α2-macroglobulin leads to loss and leakage of medium-sized
  protein.
• This paper also proposes that peritoneal membrane scleroses
  are caused due to certain mechanisms.
• Differentiation and identification of proteins in diabetic PDE
  and normal fluid will surely help in further studies.
• Another sophisticated methodology, gel electrophoresis then
  liquid chromatography-mass spectrometry (GeLC-MS) was
  considered with nine pediatric PD patients for the
  identification of 189 PDE proteins.
• Different levels of C4A and immunoglobulin κ were shown in
  20 chronic PD patients with altering transport rates.
• Identification of 5 proteins was done at different levels among
  the transport groups after 2DE. Increased levels of C4A and
  immunoglobulin κ in higher transport vs. lower transport
  patients were confirmed, in particular by further validation
  set of 24 patients by ELISA.
• This further emphasizes that proteomics can be used in
  comparing differences in different subgroups.
• Analysis revealed that these proteins were derived from the
  extracellur matrix, suggesting retention of PD fluid within the
  extracellular matrix.
• Thus, information about the localization and changes in
  proteins in the peritoneal membrane is provided by
  proteomics.
• Proteomics technology has lead to the discovery of unknown
  proteins like gelsolin and intelectin. Gelsolin plays a role in
  protecting mesothelial cell damage against infection and is
  used as a marker in sepsis.
• Intelectin has a defensive role against permeable intestinal
  bacteria and parasites in the peritoneal cavity.
Time Now for more Extended Studies
• Till date only initial studies have been carried out, and prospective studies
  involving greater number of patients is required for more information
  about the changes in the peritoneal dialysate proteins that are associated
  with particular phenotypes like nutritional status, risk of peritoneal
  infection, membrane function, residual renal function and fibrosis.
• This information can be used for further advanced analysis.
• Less number of proteins is identified till date with majority of the proteins
  yet to be discovered.
• With the present expensive and technically challenging ways, efforts are
  emphasized on identification of novel proteins to enable new hypothesis
  to be formed or identification of novel prospective biomarkers, through a
  range of workflow choices.
• In addition, proteomics technology has adapted 2DE-based difference gel
  electrophoresis (DIGE) or Lcbased MS labeling workflows, such as isobaric
  tags for relative and absolute quantification (iTRAQ) as gold standards for
  relative protein quantification.
  The Achilles’ Heel of Proteomics
• Analysis of biological fluids is not an easy process and the potential
  of biological marker discovery is limited, as it is a challenging
  process and this has lead to the lowest discovery.
• A difference of 10 orders of magnitude is observed among largely
  and the least abundant proteins in the biological fluids.
• The available analytical technologies have 2–4 orders of magnitude
  dynamic range for protein detection.
• This suggests that there is a deficit and hence not all proteins can
  be discovered using these methods.
• Still these methods have importance as they can be used in the
  identification of proteins, which had not been previously identified.
• Although certain sample fractionation approaches can be used to
  improve specificity, hypothetical changes are essential in
  proteomics technology in the discovery of all proteins.
           Looking into the Future
• Preliminary studies on PDE proteomics promotes understanding PD.
• Function of the kidney, pathological damage of the peritoneum can
  be identified without invasive techniques.
• Discovery of biomarkers helps in measuring peritoneal damage and
  changes in transport through noninvasive methods.
• In addition to this, the effect of different dialysis fluids and
  prolonged PD period on protein profiles might also be investigated
  to offer better understanding of the pathological processes.
• Advanced studies are guaranteed in this field for better diagnosis,
  prognosis and therapeutic monitoring of pathological processes.
• Proteomics is a podium in providing assistance in both
  understanding and utilization of PD.
 Comprehensive Basket
in Anemia Management

				
DOCUMENT INFO
Shared By:
Categories:
Tags:
Stats:
views:5
posted:10/20/2011
language:English
pages:10