dicumarol and Necrosis

The effectiveness of anticoagulant therapy for venous thromboembolism, with regards to both acute phase and long term prophylaxis, in patients with recurrent deep venous thrombosis (DVT) and persistence of risk factors, has been confirmed by many studies. However, it is not free of complications such as hemorrhage or, more rarely, skin necrosis. The patient, observed by us since 1994, was treated with oral vitamin K antagonists: he was affected by post-thrombotic syndrome and deficiency of congenital procoagulant factors (factor II heterozygote and MTHFR positive heterozygote) and secondary deficiency of procoagulant factors due to the consumption of protein C, with appearance of skin necrosis that occurred after many years of oral anticoagulant treatment. The change of therapy from oral anticoagulant to low molecular weight heparin and the use of local dressing, led to the resolution of the clinical symptoms and on to healing.

Topics: Administration, Oral; Adult; Anticoagulants; Dicumarol; Drug Eruptions; Humans; Male; Necrosis; Skin; Time Factors

Cell swelling is associated with the activation of an increase in the osmosensitive taurine release (OTR) rate, which serves to decrease cell volume as part of a process known as regulatory volume decrease. OTR, which is sensitive to many pharmacological agents including anion channel blockers and signalling pathway modulators, has also been suggested to play a role in cell cycle progression. At non-cytotoxic concentrations, the anion channel blocker NPPB (25 microM), the extra-cellular signal-regulated kinase inhibitor PD98059 (50 microM), and the c-Jun NH2-terminal kinase inhibitor SP 600125 (5 microM) each decreased the OTR rate by > or =50%, decreased cell proliferation, and increased G0/G1 cell cycle arrest.

Topics: 4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid; Animals; Anthracenes; Apoptosis; Astrocytoma; Cell Cycle; Cell Line, Tumor; Cell Proliferation; Dicumarol; Extracellular Signal-Regulated MAP Kinases; Flavonoids; Imidazoles; Ion Channels; JNK Mitogen-Activated Protein Kinases; Necrosis; Niflumic Acid; Nitrobenzoates; Osmolar Concentration; Pyridines; Rats; Taurine

Topics: Adult; Anticoagulants; Carcinoma, Squamous Cell; Catheters, Indwelling; Dicumarol; Esophageal Neoplasms; Female; Humans; Necrosis; Skin; Skin Diseases

The enzyme DT-diaphorase mediates the two-electron reduction of quinones to hydroquinones. It has previously been shown that the toxicity of 2-methyl-1,4-naphthoquinone to rats is decreased by pre-treatment of the animals with compounds that increase tissue levels of this enzyme. In contrast, the severity of the haemolytic anaemia induced in rats by 2-hydroxy-1,4-naphthoquinone was increased in animals with high levels of DT-diaphorase. In the present experiments, the effect of alterations in tissue diaphorase activities on the toxicity of a third naphthoquinone derivative, 2,3-dimethyl-1,4-naphthoquinone, has been investigated. This compound induced severe haemolysis and slight renal tubular necrosis in control rats. Pre-treatment of the animals with BHA, a potent inducer of DT-diaphorase, diminished the severity of the haemolysis induced by this compound and abolished its nephrotoxicity. Pre-treatment with dicoumarol, an inhibitor of this enzyme, caused only a slight increase in the haemolysis induced by 2,3-dimethyl-1,4-naphthoquinone, but provoked a massive increase in its nephrotoxicity. Modulation of DT-diaphorase activity in animals may therefore not only alter the severity of naphthoquinone toxicity, but also cause pronounced changes in the site of toxic action of these substances. The factors that may control whether induction of DT-diaphorase in animals will decrease or increase naphthoquinone toxicity are discussed.

Topics: Administration, Oral; Animals; Butylated Hydroxyanisole; Dicumarol; Female; Hemolysis; Kidney Tubules; NAD(P)H Dehydrogenase (Quinone); Naphthoquinones; Necrosis; Oxidation-Reduction; Rats; Rats, Sprague-Dawley

Coumarins have been associated with non-predictable hepatic injury. In the case of dicoumarol, there is no hard evidence in the literature of a causal connection with liver damage. We report the case of a 73-year-old woman who developed a fatal liver disease of a mixed hepatocellular-cholestatic type after 3 months of treatment with dicoumarol. A thorough diagnostic work-up did not reveal any other possible cause of the liver disease.

Topics: Adult; Anticoagulants; Dicumarol; Fatal Outcome; Female; Hepatic Encephalopathy; Humans; Liver Function Tests; Necrosis

Inducibility of oxidative stress in rat liver in vivo by menadione-associated redox cycling activation under redox enzyme modulating conditions was examined by monitoring hepatocyte injury and 8-hydroxydeoxyguanosine (8-OHdG) levels of liver DNA. In addition, the treatment-associated liver tumor initiating activity was assessed in terms of development of gamma-glutamyl-transpeptidase (GGT)- and glutathione S-transferase placental form (GST-P)-positive foci and hyperplastic nodules. With or without following menadione treatment (50 mg/kg, i.g.), redox enzyme modulations of increased cytochrome P450 reductase activity induced by phenobarbital (PB)-Na (100 mg/kg, i.p. for 5 days), inhibition of DT-diaphorase by dicumarol (25 mg/kg, i.p.) and depletion of glutathione by phorone (200 mg/kg, i.p.), with or without further supplement of iron EDTA-Na-Fe(III) (70 mg/kg, i.p.), caused both substantial hepatocyte necrosis and 8-OHdG production in Fischer 344 male rats. Subsequent feeding with a 0.05% PB diet for 64 weeks resulted in slightly increased development of GGT-positive foci but not GST-P positive lesions or hyperplastic nodules, suggesting a lack of tumor-initiating activity of the oxidative DNA damage associated with redox enzyme modulations with or without menadione.

Topics: 8-Hydroxy-2'-Deoxyguanosine; Animals; Body Weight; Cytochrome Reductases; Deoxyguanosine; Dicumarol; DNA; DNA Damage; gamma-Glutamyltransferase; Glutathione; Iron; Ketones; Liver; Liver Neoplasms, Experimental; Male; NAD(P)H Dehydrogenase (Quinone); Necrosis; Neoplasms, Experimental; Organ Size; Oxidation-Reduction; Phenobarbital; Quinone Reductases; Rats; Rats, Inbred F344; Time Factors; Vitamin K

Topics: Aged; Breast Diseases; Dicumarol; Edema; Female; Gangrene; Humans; Middle Aged; Necrosis; Thrombophlebitis

Topics: Aged; Breast Diseases; Breast Neoplasms; Dicumarol; Female; Gangrene; Hemorrhage; Humans; Middle Aged; Necrosis; Pulmonary Embolism; Thrombophlebitis

Topics: Analgesics; Animals; Blood Circulation; Dicumarol; Necrosis; Rats; Skin Transplantation

Topics: Acenocoumarol; Anticoagulants; Coumarins; Dicumarol; Drug Therapy; Ecchymosis; Ethyl Biscoumacetate; Gangrene; Necrosis; Phenindione; Pulmonary Embolism; Purpura; Skin Diseases; Thrombophlebitis; Toxicology; Warfarin

Topics: Acenocoumarol; Anticoagulants; Coumarins; Dermatology; Dicumarol; Estrogens; Ethyl Biscoumacetate; Heparin; Iatrogenic Disease; Necrosis; Toxicology

Topics: Dicumarol; Female; Hemorrhage; Humans; Necrosis; Puerperal Disorders; Skin Diseases; Thrombophlebitis; Toxicology

Topics: Animal Experimentation; Animals; Blood Circulation; Dicumarol; Humans; Necrosis; Niacin; Nicotinic Acids; Pharmacology; Postoperative Care; Rats; Research; Skin Transplantation; Surgical Flaps; Theophylline; Thromboembolism; Xanthinol Niacinate

Topics: Dicumarol; Disease; Gastrointestinal Hemorrhage; Hemorrhage; Intestinal Diseases; Intestine, Small; Necrosis

Topics: Dicumarol; Gangrene; Humans; Necrosis; Skin

Topics: Administration, Cutaneous; Coumarins; Dicumarol; Gangrene; Hemorrhage; Necrosis; Skin

Topics: Coumarins; Dicumarol; Humans; Necrosis; Skin Diseases

Topics: Coagulants; Coumarins; Dicumarol; Gangrene; Hemorrhage; Humans; Necrosis; Skin

Topics: Coumarins; Dicumarol; Necrosis