Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0039730 (thalassemia)
 10,305 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Since a few thousand years ago, the earthworm has been used as a drug for various diseases in China and the Far East. However, modern scientific pharmacological studies have not so far been performed. We extracted a very strong fibrinolytic enzyme from the earthworm, Lumbricus rubellus. This enzyme was heat-stable and displayed a very broad optimal pH range. Purification of the enzyme was performed and three partially purified fractions were obtained. These three fractions were further subdivided, and six purified fractions (F-I-0, 1, 2, F-II, and F-III-1,2) were finally obtained. Based on results of their enzymatic activities against various substrates, the fraction I enzymes are thought to represent chymotrypsin-like enzymes and the fraction III enzymes to represent trypsin-like enzymes. The fraction II enzyme appears to be neither a trypsin-nor chymotrypsin-like enzyme nor an elastase. We therefore designed trials for in vivo experiments on human volunteers. 120 mg of lyophilized earthworm powder was administered orally to 7 healthy volunteers (aged 28-52 years old) three times after meals every day for 17 days. Blood was withdrawn once a day before and at 1, 2, 3, 8, 11 and 17 days after commencing the administration. The fibrin degradation products (FDP) value, tissue plasminogen activator (t-PA) antigen level and t-PA activities were measured in the blood. Before the administration, the t-PA antigen level was 5.6 +/- 0.38 ng/ml, and it gradually increased until the 17th day. The FDP level was increased on the 1st and 2nd day after the administration, but had decreased and normalized by the 17th day. The fibrinolytic activities also tended to show an increase during the experiment. These results suggest that earthworm powder represents a possible oral thrombolytic agent. The earthworm enzyme may thus be applicable for treating patients with thalassemia.
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PMID:Novel thrombolytic therapy discovered from traditional oriental medicine using the earthworm. 129 86

Hepatic veno-occlusive disease (VOD) is the most common life threatening complication of preparative-regimen-related toxicity for bone marrow transplantation (BMT). The frequency of VOD varies greatly, from 1-2% in centers performing pediatric BMT for thalassemia to over 50% in some centers doing BMT for hematologic malignancy. The term liver toxicity syndrome is a clinicopathologic definition which encompasses the range of histopathology within the hepatic venules and surrounding sinusoids and hepatocytes. These histologic abnormalities are statistically associated with a clinical syndrome of jaundice, ascites, and painful hepatomegaly developing early post-transplant. Newer modalities which may aid accuracy are transvenous liver biopsy along with determination of the gradient between the wedged and free hepatic venous pressures, and measurement of blood coagulatory components, particularly protein C levels. Analyses of clinical risk factors for VOD are confounded by lack of a clear hierarchy of risk when comparing heterogeneous patient populations, the methods of patient selection and choice of controls, and whether analysis is univariate or multivariate. Prospective multivariate analyses indicate that the risk of developing liver toxicity is independently correlated with intensity of conditioning therapy, pre-transplant viral hepatitis, use of antimicrobial therapy with acyclovir, amphotericin, or vancomycin (reflecting fever), and mismatched or unrelated allogeneic marrow grafts. These analyses plus morphologic and biochemical data support the hypothesis that VOD is caused by cytoreductive injury to hepatocytes and endothelium in zone three of the liver acinus, and in turn strongly influenced by factors which induce the release of tumor necrosis factor-alpha (TNF-alpha) leading to enhancement or activation of coagulation with obstruction of hepatic sinusoids and venules. Pharmacokinetic measurements of busulfan as a conditioning agent demonstrate a correlation between high steady-state busulfan levels and liver toxicity and suggest that safer and/or more efficacious plasma busulfan concentrations can be obtained by making individual dose adjustments and by changing the schedule of administration. Conservative therapy of severe VOD, including the use of peritoneal-pleural shunts for relief of ascites, is unsatisfactory. Results from prophylactic studies aimed at preventing VOD by heparin or prostaglandin E1 indicate considerable differences with toxicity and efficacy. Use of the TNF-alpha blocker, pentoxifylline, has also shown promise in lessening VOD. A statistical model which predicts patients likely to have an unfavorable outcome from VOD has been used to select premorbid patients for promising new therapeutic modalities, such as recombinant tissue plasminogen activator.
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PMID:Hepatic veno-occlusive disease--liver toxicity syndrome after bone marrow transplantation. 142 75

Hepatic veno-occlusive disease (HVOD) following bone marrow transplantation is potentially fatal. Criteria for diagnosis and starting treatment are mainly based on adult studies. Recombinant tissue plasminogen activator (rtPA) has been used with variable success. rtPA and heparin were given to 12 children (nine with immunodeficiency, two malignancy, one thalassaemia) with moderate to severe HVOD. Of the 12, 10 responded with a fall in bilirubin concentration; eight survived with complete resolution of HVOD. Four of the five patients with associated multiorgan failure (MOF) died despite rtPA treatment. One child suffered significant, and one minor, bleeding during rtPA treatment. A scoring system for quantifying the severity of HVOD in children is proposed, incorporating the criteria used to diagnose HVOD, risk factors for its development and also parameters reflective of the patient's general condition. This will facilitate early diagnosis and management of those cases which, if not treated promptly, are likely to deteriorate with an adverse outcome. Our experience suggests rtPA and heparin are an effective treatment for HVOD in children, with relatively little toxicity provided therapy is started before MOF develops.
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PMID:Recombinant tissue plasminogen activator for treatment of hepatic veno-occlusive disease following bone marrow transplantation in children: effectiveness and a scoring system for initiating treatment. 1269 27

Increased frequency of thrombosis has been observed in patients with hemoglobin E/beta-thalassemia (Hb E/beta-thal) disease, particularly those who have previously been splenectomized. We compared various hemostatic and thrombotic markers in blood from 15 Hb E/beta-thal patients who were not splenectomized (NS), 15 who had been splenectomized (S), and 15 normal controls (NC). Levels of plasma thrombin-antithrombin, beta2 thromboglobulin, C-reactive protein, tissue plasminogen activator antigen were significantly higher in the S group than in either the NS or the NC groups, and levels of prothrombin fragment 1.2 were significantly higher in the S than in the NC group. Levels of plasminogen activator inhibitor-1 antigen were significantly higher in the S than in the NS group. Levels of protein C, protein S, antithrombin, and fibrinogen were significantly lower in the S and NS groups than in the NC group. Plasma lipoprotein(a) levels in the S and NS groups were not statistically different from NC. Our findings indicated that there is evidence of chronic low-grade coagulation and platelet activation, chronic low-grade inflammation, endothelial cell injury, impaired fibrinolysis, and decreased naturally occurring anticoagulants in splenectomized Hb E/beta-thal patients. These changes may account for the increased risk of thrombosis in these patients.
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PMID:Hemostatic and thrombotic markers in patients with hemoglobin E/beta-thalassemia disease. 1765 9