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Experimental And Clinical Study On Removal Of TNF-α In Plasma By Specific Immunoadsorption Column And CRRT

Posted on:2003-08-01Degree:DoctorType:Dissertation
Country:ChinaCandidate:Q WangFull Text:PDF
GTID:1104360092475326Subject:Surgery
Abstract/Summary:PDF Full Text Request
It has been an important task that effective treatment to multiple organ dysfunction syndrome (MODS) for clinical medicine, because of the MODS has extremely high mortality. Many researches have approved that the systemic inflammatory response syndrome (SIRS) was the foundation of the dynamic process of the MODS. Tumor necrosis factor-alpha (TNF- a )is a key pro-inflammatory cytokine which play a very important role in SIRS pathogenesis. Timely and effectively removal tumor necrosis factor-alpha when it was excessive product the changes of cytokine net in the early stage of the systemic inflammatory response syndrome could be suppressed and which is beneficial for improving the prognosis of the multiple organ dysfunction syndrome. Continuous renal replacement therapy (CRRT) had been extensively used for the rescue for the MODS in the world for many years. However, it only partly not totally eliminate the TNF- a and could not depress the mortality of the MODS. Adsorption therapy has obvious function for removal the tumor necrosis factor-alpha, but it was restricted in the clinical application .Fof this reason, we performed the reseach from the two undermentioned aspects.Firstly, we prepared for the monoclonal antibodies against recombinant human tumor necrosis factor alpha by hybridoma techniques. It was wraped on the polystyrene microsphere carrier connecting poly-L-lysine. After that, we made successfully up the specific immunoadsorption column for the first time,and took some tests about adsorption. Secondly, we treated to 14 patients with MODS after the big apparatus transplantations by the continous renal replacement therapy techniques. They were detected by ELISA that the concentration of the TNF- a , IL-1 P, IL-6, IL-8 in plasmam before and during the CRRT 1,2,3,6,12 hours respectively.The main results and conclusions were as follows:1. Nine groups of hybridoma cell line which can secrete anti-recombinant human tumor necrosis facter alpha were established, and we got some purificative monoclonal antibodies against recombinant human tumor necrosis facter alpha. It grounded for us in whole research.2. The specific across reaction test and the Western blotting showed that these monoclonal antibodies only reacted specificly to the recombinant human tumor necrosis facter alpha that has 17KDa molecular weight. These McAb possess the neutralization ability for the rHTNF- a cytotoxicity and relative affinity in some degree.3. The filtration column has favourable capability and practicality, the most penetrating volume was about 2500 milliliters per hour. It provided a new model for some correlative researches.4.The polystyrene microsphere was chosen for the carrier and coated by poly-L-lysine and anti-recombinant human tumor necrosis facter alpha in turn. Though examining, the two times coating was firm and satisfying. It offered a novel method for this field.5.We produced triumphantly the specific immunoadsoiption column which the most adsorptive rate was more than 90 percent. This column has good stability and repetition. It created a new pattern of specific eliminate the TNF- a in the adsorption therapy and had biggish application value.6.There was remarkable running up of the concentration of the TNF- a , IL-1 P , IL-6, IL-8 in plasmm of those patients with MODS after the bigapparatus transplantations.lt was proved that the TNF- a is the key pro-inflammatory cytokine in the pathogenesis of the MODS after translantation.Observing the variety of TNF- a with dynamic mehtod, will help to guidance the clinical work.7. Partly the TNF- a in these patients could be removaled by CRRT.The main mechanism was the adsorption potentially. It was found that the maximal clearance was gotten for the removal TNF- a by CRRT at 6 hour, and at the same time , the maximal adsorption efficiency was 44%.Although maintaining the circumstance stabilization of the patients temporarily, CRRT could not increase the survival and decrease the mortality in our observation.8. We substan...
Keywords/Search Tags:TNF-α, immunoadsorption, multiple organ dysfunction syndrome, systemic inflammatory response syndrome, continuous renal replacement therapy, pro-inflammatory cytokine
PDF Full Text Request
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