Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.21.7 (plasmin)
 9,023 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Carboxypeptidase R (EC 3.4.17.20) (CPR) and carboxypeptidase N (EC 3.4.17.3) (CPN) cleave carboxy-terminal arginine or lysine residues from biologically active peptides such as kinins or anaphylatoxins in the circulation thereby regulating their activities. Although CPN is present in a stable active form in plasma, CPR is generated from proCPR, a plasma zymogen, by proteolytic enzymes such as thrombin, thrombin-thrombomodulin complex and plasmin. We have isolated rat proCPR and CPN cDNA clones which can induce enzymatic activities in culture supernatants of the transfected cells. mRNA of proCPR was detected only in rat liver by Northern hybridization and showed hepatocyte-specific expression. Expression of proCPR mRNA was enhanced following LPS injection, indicating that proCPR production is increased under inflammatory conditions.
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PMID:Molecular cloning and partial characterization of rat procarboxypeptidase R and carboxypeptidase N. 1102 4

Thrombin activatable fibrinolysis inhibitor (TAFI) also named procarboxypeptidase U (CPU), procarboxypeptidase R (CPR) and plasma procarboxypeptidase B (CPB) provides an important link between fibrinolysis and coagulation cascade. Activated TAFI (TAFIa) reduces a generation of plasmin because it cleaves off the carboxy-terminal lysine residues from partially degraded fibrin and thereby abrogates the fibrin cofactor function in the tPA-mediated catalysis of plasminogen to plasmin. TAFI is activated by thrombin-thrombomodulin complex. TAFI transformation to the activated TAFI (TAFIa) induced by thrombin supports the important role of coagulation cascade in regulation of fibrinolysis. This can be proved by a fact that the patients with a factor XI (FXI) deficiency are prone to bleeding from tissues with a high local fibrinolytic activity (urinary tract, nose, oral cavity, tonsils) that can be explained by a decreased thrombin-mediated TAFI activation. On the other hand the prothrombotic mutation of factor V (FV Leiden) associated with a resistance to activated protein C (APC-resistance) possess both mechanisms-an increased thrombin generation in coagulation cascade and a down regulation of fibrinolysis by a way of the thrombin-induced TAFI activation. For the future an inhibition of TAFI (e.g. by FXI inhibitors) offers the therapeutic possibilities to improve the decreased fibrinolysis and increase the efficiency of fibrinolytic therapy in thrombotic disorders. In bleeding disorders (hemophilia A, B) the drugs with a higher efficiency of TAFI for down regulation of an increased fibrinolysis could be used.
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PMID:[Thrombin activatable fibrinolysis inhibitor (TAFI) and its importance in the regulation of fibrinolysis]. 1501 28

Amniotic Fluid Embolism (AFE) is a rare obstetric catastrophe that occurs in approximately 1/50,000 pregnancies and has a mortality rate in excess of 80%. AFE is a condition that is poorly understood and often difficult to diagnose. We report a case of a healthy 27-yr-old gravid two, 35 wk gestation parturient with a previous Cesarean section two years previously, and presently admitted for emergent Cesarean section due to premature uterine contractions. Induction of general anesthesias was performed with no problem and a male preterm infant with Apgar 8 at 1 min was delivered. Amniotic fluid was bloody and 40% placental abruption existed. Following delivery of the placenta, patient suddenly became plethoric and O2 saturation began to decrease and no pulse could be palpated! Immediate CPR was successful but she was hemodynamically unstable and signs of right heart strain was obvious. Right jugular venous catheterization was performed, vasopressors were administered. After a two hours period of relatively stable vital signs, patient's reflexes returned to normal, however, profound coagulopathy on lab data was reported and she was treated with 10 unit Packed Red Blood Cells (PRBCs), 10 unit FFP and 8 unit platelets, Sodium bicarbonate, oxytocin and Methergine. The patient remained hemodynamically unstable while laparotomy-hysterectomy was performed to stop the bleeding. Unfortunately attempts were unsuccessful and patient died four hours later in ICU. Post-mortem findings showed signs of Disseminated Intravascular Coagulation (DIC), no fetal squamous cells in pulmonary vasculature were found and special staining of Cytokeratin marker shows no positive cells in lumen of vessels. The post-mortem diagnosis of AFE is challenging to forensic investigators and pathologists and can be confirmed by histological confirmation of amniotic fluid contents in the pulmonary vasculature, although they may be difficult to identify. In recent years it has been suggested that AFE is an anaphylactoid reaction to fetal antigens and an elevated serum tryptase level is increasingly being used to support the diagnosis. Sudden onset of cardiovascular collapse and early signs of right heart strain and fulminant DIC supports the diagnosis of AFE in this case, although no fetal debri could be find in pathologic staining.
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PMID:Sudden cardiac arrest during cesarean section -- a possible case of amniotic fluid embolism. 1958 89