Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0012739 (disseminated intravascular coagulation)
 8,673 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Endotoxic lipopolysaccharide (LPS) is a proinflammatory agonist produced by gram-negative bacteria and a contributor to the majority of the 400,000 septic shock cases recorded annually in US hospitals. The primary target cells for LPS are monocytes and macrophages. Their response consists of massive production of proinflammatory cytokines, reactive oxygen- and nitrogen-intermediates, procoagulants, and cell adhesion molecules. In turn, expression of these LPS-responsive factors contributes to collapse of the circulatory system, to disseminated intravascular coagulation, and to a 30% mortality rate. A common intracellular mechanism responsible for the expression of septic shock genes in monocytes and macrophages involves the activation of NF-kappaB. This transcription factor is regulated by a family of structurally related inhibitors including IkappaBalpha, IkappaBbeta, and IkappaBepsilon, which trap NF-kappaB in the cytoplasm. In this report, the investigators show that LPS derived from different gram-negative bacteria activates cytokine-responsive IkappaB kinases containing catalytic subunits termed IKKalpha (IKK1) and IKKbeta (IKK2). The kinetics of IKKalpha and IKKbeta activation in LPS-stimulated human monocytic cells differ from that recorded on their stimulation with tumor necrosis factor-alpha, thereby implying a distinct activation mechanism. LPS-activated IKK complexes phosphorylate all 3 inhibitors of NF-kappaB: IkappaBalpha, IkappaBbeta, and IkappaBepsilon. Moreover, LPS activates IKKbeta preferentially, relative to IKKalpha. Thus, IKK complex constitutes the main intracellular target for LPS-induced NF-kappaB signaling to the nucleus in human monocytic cells to activate genes responsible for septic shock.
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PMID:IkappaB kinase complex is an intracellular target for endotoxic lipopolysaccharide in human monocytic cells. 1047 96

An increased incidence of TTP has been noted among patients receiving intravascular stents to improve patency in diseased coronary, renal, and peripheral arteries. Placement of transjugular intrahepatic porto-systemic shunt stents is often associated with subsequent development of severe hemolysis. We have prospectively studied the development of microangiopathic hemolysis or TTP in patients undergoing intravascular stent placement for peripheral vascular or renal artery disease. Hemolysis was evaluated both before and after stent placement by measuring complete blood count, total bilirubin, lactate dehydrogenase (LDH), haptoglobin and reticulocyte count, and examining peripheral blood films of all patients. Coagulation parameters, blood urea nitrogen and creatinine were measured to exclude disseminated intravascular coagulation or thrombotic thrombocytopenic purpura as a potential cause of hemolysis. Seventeen patients (median age 69 years) were evaluated. One patient was on ticlopidine. Mean hematocrit fell from 41.8% pre-stenting to 35.5% post-stenting (P = 0.003) but without significant change in reticulocyte count (1.7 vs. 1.6%, P = 0.605), LDH (546 vs. 560 IU/l; P = 0.836), bilirubin (0.62 vs. 0.63 mg/dl; P = 1.0), or haptoglobin (183 vs. 158 mg/dl; P = 0.083). Thus, this drop in hematocrit could not be attributed to hemolysis. Peripheral blood films revealed fewer than 1% schistocytes before and after stent placement in all cases. Absence of significant changes in mean platelet count (240 vs. 210 x 10(9)/L; P = 0.088), fibrinogen (385 vs. 378 mg/dl; P = 0.789), BUN (24.5 vs. 16.8; P = 0.079), and creatinine (1.38 vs. 1.24; P = 0.757) argue against development of TTP or DIC resulting from stent placement. No patient developed new renal impairment, a neurological syndrome, or unexplained fever after stent placement. At a mean of 6 weeks follow-up after stent placement, patients have not developed signs of hemolytic anemia or worsening renal function. Our findings argue against a primary risk of microangiopathic hemolytic anemia or TTP due to intravascular stents in patients not receiving ticlopidine.
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PMID:Intravascular stents do not cause microangiopathic hemolysis or thrombotic microangiopathy. 1054 Mar 68

Protein C is the zymogen of an anticoagulant serine protease and is converted to its active form (activated protein C: APC) by thrombin in the presence of thrombomodulin. APC plays an important role in regulating coagulation and fibrinolysis by inactivating not only blood coagulation factors Va and VIIIa but also type-1 plasminogen activator inhibitor (PAI-1). The aim of the present study was to examine the effect of a human APC product (designated as CTC-111), compared with that of heparin, on the disseminated intravascular coagulation (DIC) induced by lipopolysaccharide (LPS) in rats. LPS (1 mg/kg/h) infusion was performed through a femoral vein for 4 h. One-fifth amount of the total dosage of CTC-111 or heparin was injected into the other femoral vein, followed by a 4-h infusion of the remainder. Both CTC-111 (10,000-100,000 U/kg) and heparin (400-800 IU/kg) inhibited the decrease in platelet count and fibrinogen level equally. The prolonged activated partial thromboplastin time and prothrombin time observed in DIC rats were further elongated in both CTC-111- and heparin-treated rats. But, this prolongation was less in CTC-111-treated rats than in the heparin-treated ones. Heparin inhibited the increase in fibrin and fibrinogen degradation products more prominently than CTC-111. On the other hand, CTC-111 strongly inhibited the increase in PAI-1 activity but heparin did not. These results suggest that CTC-111 may enhance fibrinolysis through its direct inhibitory effect on PAI-1. The parameters for liver or renal damage, i.e., plasma glutamic-oxaloacetic transaminase (GOT), glutamic-pyruvic transaminase (GPT), creatinine (Cre) and blood urea nitrogen (BUN), were significantly increased by LPS infusion. Both CTC-111 (100,000 U/kg) and heparin (800 IU/kg) decreased the increase in GOT and GPT levels significantly, whereas neither affected the increase in Cre or BUN. From these results, the activation of the blood coagulation system might partially contribute to the progression of liver damage caused by LPS, and might be less involved in the progression of renal damage in this model. In conclusion, CTC-111 showed both anticoagulant and profibrinolytic activity in the LPS-induced DIC model without excessive prolongation of coagulation time. From these results, CTC-111 is expected to be a useful remedy for DIC without the risk of bleeding.
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PMID:Effect of activated human protein C on disseminated intravascular coagulation induced by lipopolysaccharide in rats. 1105 Jun 97

The effect of higenamine, a benzyl-tetrahydroisoquinoline alkaloid of the roots of Aconitum spp. (Ranunculaceae), on disseminated intravascular coagulation (DIC), was investigated using an experimental DIC rat model. The oral administration of higenamine (10 mg/kg or 50 mg/kg), significantly ameliorated the decrease of fibrinogen level in plasma, the increase of fibrinogen/fibrin degradation product (FDP) level, and the prolongation of prothrombin time (PT) induced by the i. v. infusion of lipopolysaccharide (LPS). The prolongation of activated partial thrombin time (aPTT) and the decrease of platelet count were suppressed. The increase in serum aspartate aminotransferase (AST) and blood urea nitrogen (BUN) were also significantly prevented with higenamine. The above results are suggestive that higenamine has therapeutic potential for DIC and/or accompanying multiple organ failure (MOF).
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PMID:The effects of higenamine on LPS-induced experimental disseminated intravascular coagulation (DIC) in rats. 1198 56

Urea Cycle Disorders (UCD) is an inborn error of urea synthesis in which ammonium and other nitrogenous precursors of urea accumulate leading to episodic coma and a high mortality rate. Therapy with peritoneal dialysis, essential amino acids or their nitrogen-free analogues has increased survival. The authors report 5 cases of urea cycle disorders, all of whom developed and were rescued from hyperammonemic coma. However, the eventual outcome was quite variable. Argininosuccinate lyase deficiency (ALD) Case 1. A 2 month old male infant, a product of a consanguineous marriage (Suphanburi province); developed poor feeding on day 7, lethargy, convulsion, hepatomegaly and respiratory alkalosis leading to respiratory failure and coma. Hyperammonemia, elevation of glutamic acid and argininosuccinic acid and its anhydrides confirmed the diagnosis of ALD. He is now 9 years old and severely retarded. Case 2. A male infant with history of lethargy, poor feeding on day 3, treated as sepsis and required respiratory support for 6 days; subsequently readmitted at age 2 weeks with vomitting, lethargy, seizure activity and hyperammonemia, and was treated by a local pediatrician in Songkhla province. There was a history of parental consanguinity and he was referred to Siriraj Hospital on day 64 with severe essential amino acid deficiency and acrodermatitis enteropathica with markedly elevated plasma citrulline level. In spite of aggressive treatment; the patient developed sepsis and he expired on day 78. Ornithine transcarbamylase deficiency (OTC) Case 3. An eleven-month-old male infant, the product of a non-consanguineous marriage, developed neonatal onset of hyperammonemia on day 5 after poor feeding, lethargy, hypothermia, seizure, apnea and coma. He was rescued from neonatal hyperammonemic coma on day 9 after aggressive treatment, but expired at eleven months of age after overwhelming sepsis. Case 4. A male infant, sibling of case 3 was referred to Siriraj Hospital on day 8 with hyperammonemia and coma. In spite of intensive genetic counseling given after the birth of their first child with OTC, the couple chose to have another baby without informing any physician. The baby developed vomiting and lethargy on day 2; subsequently hyperammonemia was noted. In spite of aggressive treatment given; hepatic dysfunction, renal failure and disseminated intravascular coagulation defects occurred on day 15. He expired on day 18 after parental permission for discontinuation of all treatment. Argininosuccinate synthetase deficiency (ASS) or Citrullinemia. Case 5. A seven week old female infant, the product of a consanguineous marriage and of Pakistani ethnic origin; developed intermittent vomiting from day 6. Initial diagnoses included ruminations, sepsis and pyloric stenosis for which she was operated on (day 30); however, vomiting continued; subsequently seizures, hyperammonemic coma developed and she was rescued from hyperammonemic coma within 30 hours. Significant elevations of citrulline and L-glutamine were demonstrated. She was discharged in excellent condition to her home in Dubai, the United Arab Emirates.
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PMID:Urea cycle disorders in Thai infants: a report of 5 cases. 1240 52

A 66-year-old man with erysipelas was admitted with complaints of oliguria and massive proteinuria/hematuria. He was diagnosed as having acute poststreptococcal glomerulonephritis(APSGN) due to erysipelas infected by group A streptococcus pyogenes. On admission, his white cell count increased to 31,000, and CRP was 27.3 mg/dl. Serum urea nitrogen and creatinine were increased to 90.1 mg/dl and 4.5 mg/dl, respectively. He had diabetes mellitus(HbA1c 7.9%) and liver dysfunction(total bilirubin 3.5 mg/dl, AST 76 IU, ALT 41 IU) caused by alcoholic liver cirrhosis. Hypocomplementemia was found in addition to ASO 216 U/ml and ASK 10,240 x. After antibiotics treatment was initiated, inflammation of the erysipelas began to improve. Disseminated intravascular coagulation syndrome, probably due to sepsis, occurred on the 5th hospital day. He died of gastrointestinal bleeding on the 18th hospital day. Renal autopsy revealed 37% formation of fibrocellular crescents, and marked mesangiolysis was noted by light microscopy. Granular deposition of C3 and IgG was seen along the capillary walls on immunofluorescence study. Intramembranous deposits were scattered on electron microscopy. This case illustrates a fulminant type of APSGN, which was in part attributed to the presence of diabetes and alcoholic liver cirrhosis. Histological findings of crescent formation and marked mesangiolysis may account for the fulminant clinical course.
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PMID:[A case of fulminant acute poststreptococcal glomerulonephritis showing mesangiolysis and crescent formation preceded by erysipelas]. 1247 94

Abuse of 3,4-methylenedioxymethamphetamine (MDMA,Ecstasy) is still growing over the last years and reports of severe or even fatal complications, such as arrhythmias, hyperpyrexia, rhabdomyolysis, disseminated intravascular coagulopathy (DIC), acute renal or liver failure or brain oedema are also increasing. We report the case of a 21-year-old male who took a suicidal overdose of MDMA and subsequently developed severe hyperpyrexia (>43 degrees C/109.4 degrees F), rhabdomyolysis with an initial myoglobin level of 88,000 microg/l, disseminated intravascular coagulation (DIC) and beginning renal and liver failure. Infusing dantrolene 140 mg (2.5 mg/kg body weight) i.v. and using supportive cooling was effective in treating hyperpyrexia. To support renal function and diuresis we increased the intravenous fluid supply up to 5 l per day which led to a raised elimination of myoglobin, urea nitrogen and creatinine within 1 week. Hemodialysis was not necessary. DIC was treated according to laboratory parameters by supply of antithrombin (AT) III, fresh frozen plasma, prothrombin complex concentrates (PPSB) and continuous aprotinin 100,000 IE/h.
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PMID:[Hyperpyrexia and rhabdomyolysis after ecstasy (MDMA) intoxication]. 1283 72

A series of benzimidazole derivatives with the side chain on the nitrogen atom oriented to the prime site of factor Xa (FXa) were designed and synthesized. Compounds with substituted aminocarbonylmethyl groups as the side chain showed potent FXa inhibitory activity. Compounds 1 and 2 exhibited most potent inhibitory activity and were effective as anticoagulants in a DIC model.
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PMID:Structure-activity relationships of potent and selective factor Xa inhibitors: benzimidazole derivatives with the side chain oriented to the prime site of factor Xa. 1526 Dec 87

During the systemic inflammatory state induced by sepsis, the potential for coagulopathy exists because of up-regulation of natural procoagulants and anti-fibrinolytics, and down-regulation of natural anti-coagulants, with protein C (PC) being a critical example of the latter case. PC functions as an anti-coagulant, profibrinolytic, and anti-inflammatory agent, and, thus, its administration or deficiency may affect the course and outcome of sepsis in patients. In this study, a cecal ligation and puncture model of septic peritonitis was applied to wild-type mice and littermates with a targeted heterozygous deficiency of PC (PC(+/-)) to characterize the importance of a PC-deficiency on polymicrobial sepsis. An enhanced mortality rate was found to accompany a PC deficiency. Plasma cytokines, as well as organ-specific expression of cytokine transcripts, were elevated in PC(+/-) mice. No signs of severe disseminated intravascular coagulation (DIC) were observed in wild-type or PC(+/-) mice, as indicated by an increase in fibrinogen levels and the invariability of platelet counts after cecal ligation and puncture. Consumption of coagulation factors was similar in both genotypes and a decrease in the PC mRNA and protein levels was more prominent in PC(+/-) mice. Renal and organ muscle damage was enhanced in PC(+/-) mice, as shown by increases in plasma blood urea nitrogen, creatinine, and creatinine kinase. Hypotension and bradycardia were more enhanced in PC(+/-) mice than in wild-type mice, thus provoking a more severe septic shock response. Thus, the hemodynamic role of PC during sepsis is of critical importance to the outcome of the disease.
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PMID:A protein C deficiency exacerbates inflammatory and hypotensive responses in mice during polymicrobial sepsis in a cecal ligation and puncture model. 1546 7

Disseminated intravascular coagulation (DIC) is a pathological syndrome, which occurs following the uncontrolled widespread activation of blood coagulation, resulting in the intravascular formation of fibrin, which may lead to thrombotic occlusion of small and midsize vessels. The effects of 1-(alpha-naphthylmethyl)-6,7-dihydroxy-1,2,3,4-tetrahydroisoquinoline (YS-49, CAS 132836-42-1) and 1-(beta-naphthylmethyl)-6,7-dihydroxy-1,2,3,4-tetra-hydroisoquinoline (YS-51, CAS 213179-96-5) on the experimental DIC induced by lipopolysaccharide (LPS) in rats, were investigated. The oral administration of YS-49 and YS-51 (10 or 50 mg/kg) attenuated the dramatic increase of serum fibrinogen/fibrin degradation product (FDP) level, the decrease of plasma fibrinogen concentration and the number of platelets in blood and the prolongation of prothrombin time (PT) and activated partial thromboplastin time (aPTT) induced by LPS. The liver and kidney function parameters, aspartate amino-transferase (AST) and blood urea nitrogen (BUN), were also improved with YS-49 and YS-51. The above results suggest that YS-49 and YS-51 have therapeutic potential for DIC and/or accompanying multiple organ failure.
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PMID:Effects of two tetrahydroisoquinolines (YS-49 and YS-51) on experimental disseminated intravascular coagulation induced by lipopolysaccharide in rats. 1561 11


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