Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.24.3 (collagenase)
 18,340 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Orthotopic liver transplantation as treatment for hereditary enzyme deficiencies in the absence of cirrhosis suffers from significant operative risks, complications, and donor shortages. Transplantation of isolated hepatocytes (HTX) may offer opportunities for the treatment of these diseases and retain the recipient liver. Hepatocytes transplanted into the portal vein, spleen, or omentum lack an ideal growing environment for cell proliferation and maintenance. Therefore, we investigated a method combining 75% recipient hepatectomy with direct injection of hepatocytes into the remaining 25% of liver parenchyma to provide proliferative stimuli and a stable environment during and following liver regeneration. Recipient Gunn rats (glucuronyltransferase deficiency and hyperbilirubinemia) underwent hepatectomy before HTX by direct injection of 10(7) isolated hepatocytes into the remaining parenchyma. Inbred male Wistar and Gunn rats were used as normal and control hepatocyte donors and saline injection served as a sham transplant control. Isolation of donor hepatocytes was performed with a two-step collagenase digestive method (Seglen) with cell viability of 85% to 95%. Liver regeneration was complete by 2 weeks posttransplant. Four weeks following HTX, total serum bilirubin and qualitative bile analysis were performed. A significant decrease in total serum bilirubin levels was observed in Gunn rats receiving Wistar hepatocytes compared with those receiving Gunn hepatocytes and saline control. Bile analysis from HTX rats demonstrated a normal pattern containing bilirubin monoglucuronides and diglucuronides (conjugated bilirubin) in the rats receiving Wistar hepatocytes, whereas the control group receiving Gunn hepatocytes or saline injection demonstrated only unconjugated bilirubin. No differences in histological appearance were noted between groups.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Intrahepatic hepatocyte transplantation following subtotal hepatectomy in the recipient: a possible model in the treatment of hepatic enzyme deficiency. 150 Oct 3

Liver regeneration following partial hepatectomy is significantly impaired in rats with hereditary vasopressin (AVP) deficiency. This suggested that AVP might have a direct effect on cultured rat hepatocytes. Hepatocytes from male Sprague-Dawley rats were isolated using a two-step collagenase perfusion technique and plated at a density of 10(5)/16-mm Primaria plate. After a suitable attachment period, hepatocytes were incubated with minimal essential media, AVP, AVP plus a specific AVP antagonist, or oxytocin. Hepatocyte proliferation was measured by [3H]thymidine incorporation ([3H]Thy) into hepatocyte DNA. AVP (10 nM) increased [3H]Thy significantly (and this effect was blocked by an AVP-specific antagonist (50 nM). Oxytocin had no effect on hepatocyte DNA synthesis. To further investigate the influence of AVP on hepatocyte proliferation, the effect of AVP on transforming growth factor-alpha (TGF-alpha)-stimulated hepatocyte proliferation was also studied. This combination was chosen based on the ability of AVP to inhibit the biologic effects of EGF (a TGF-alpha analog). There was significant attenuation of TGF-alpha (50 nM)-stimulated [3H]Thy in the presence of AVP (10 nM). In summary: (1) AVP stimulates proliferation of cultured rat hepatocytes. (2) The effect of AVP can be significantly abolished by a specific AVP antagonist. (3) The proliferative response of AVP is specific. (4) AVP significantly attenuates TGF-alpha-stimulated hepatocyte hepatic DNA synthesis. Further studies should elucidate the mechanisms for the effects of AVP on hepatic proliferation alone or in combination with other factors.
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PMID:Vasopressin stimulates DNA synthesis in cultured rat hepatocytes. 799 50