digoxin and Necrosis

Antibodies, long used as discriminating tools in immunoassay, are now being used in vivo, both in diagnosis and therapy. In cardiovascular medicine, applications that have reached the stage of clinical trial include the reversal of digitalis intoxication by digoxin-specific antibodies and the imaging of cardiac necrosis with monoclonal myosin-specific antibodies. An exciting future prospect, still in an early experimental stage, is the application of fibrin-specific monoclonal antibodies to both the visualization of thrombi and emboli and the targeting of fibrinolytic agents.

Topics: Adolescent; Adult; Animals; Antibodies, Monoclonal; Cells, Cultured; Child; Child, Preschool; Clinical Trials as Topic; Digoxin; Dogs; Fibrinolytic Agents; Heart Diseases; Humans; Immunoglobulin Fab Fragments; Infant; Male; Myocardial Infarction; Myocardium; Myosins; Necrosis; Rabbits; Thrombosis

Antibodies, long used as discriminating tools in immunoassay, are now being used in vivo, both in diagnosis and therapy. In cardiovascular medicine, applications that have reached the stage of clinical trial include the reversal of digitalis intoxication by digoxin-specific antibodies and the imaging of cardiac necrosis with monoclonal myosin-specific antibodies. An exciting future prospect, still in an early experimental stage, is the application of fibrin-specific monoclonal antibodies to both the visualization of thrombi and emboli and the targeting of fibrinolytic agents.

Topics: Adolescent; Adult; Animals; Antibodies, Monoclonal; Cells, Cultured; Child; Child, Preschool; Clinical Trials as Topic; Digoxin; Dogs; Fibrinolytic Agents; Heart Diseases; Humans; Immunoglobulin Fab Fragments; Infant; Male; Myocardial Infarction; Myocardium; Myosins; Necrosis; Rabbits; Thrombosis

In order to compare the effectiveness of different therapeutic regimens in reducing infarct size serial determinations of CPK activity (at 4 hourly intervals in the first 48 hours from the admission to CCU, at the 72th and at 120th hours) were performed in 100 patients with transmural AMI (53 anterior and 47 inferior) with no obvious evidence of LV failure and basal CPK levels lower than 50 U/L. 20 patients (control group) have been treated with glucose-insulin-potassium (GIK). 20 patients have been treated with GIK plus Verapamil (GIK + V). Verapamil was administered at the dose of 50 mg in continuous drip. 20 patients received GIK plus digoxin at the dose of 0.25 mg b.i.d. (GIK + D). 40 patients received GIK, Verapamil and digoxin at the above doses (GIK + V + D). Different values of CKr and infarct size (IS.) show a statistically significant difference between the various regimens, which is more evident if we consider the whole series. Infarct size was greater in patients treated with digoxin with respect to controls, while it was smaller in patients treated with Verapamil. Combined Verapamil-digoxin therapy is associated to an enzymatic behaviour not different from controls. Authors emphasize that in uncomplicated AMI digoxin causes an increase in infarct size while Verapamil reduces significantly it. Association of Verapamil allows the use of digoxin, if clinically justified, without increase in infarct size.

Topics: Adult; Aged; Clinical Enzyme Tests; Creatine Kinase; Digoxin; Female; Glucose; Humans; Insulin; Male; Middle Aged; Myocardial Infarction; Myocardium; Necrosis; Potassium; Verapamil

Topics: Animals; Antioxidants; Cardenolides; Cardiotoxicity; Digoxin; Dose-Response Relationship, Drug; Heart; Heart Diseases; Heart Rate; Male; Myocytes, Cardiac; Necrosis; Ouabain; Oxidative Stress; Rats, Wistar; Reactive Oxygen Species; Ventricular Remodeling

Glioblastoma (GBM) is the most common brain tumor in adults and the mesenchymal GBM subtype was reported to be the most malignant, presenting severe hypoxia and necrosis. Here, we investigated the possible role of a hypoxic microenvironment for inducing a mesenchymal and invasive phenotype. The exposure of non-mesenchymal SNB75 and U87 cells to hypoxia induced a strong change in cell morphology that was accompanied by enhanced invasive capacity and the acquisition of mesenchymal marker expression. Further analyses showed the induction of HIF1α and HIF2α by hypoxia and exposure to digoxin, a cardiac glycoside known to inhibit HIF1/2 expression, was able to prevent hypoxia-induced mesenchymal transition. ShRNA-mediated knockdown of HIF1α, and not HIF2α, prevented this transition, as well as the knockdown of the EMT transcription factor ZEB1. We provide further evidence for a hypoxia-induced mesenchymal shift in GBM primary material by showing co-localization of GLUT1, ZEB1 and the mesenchymal marker YKL40 in hypoxic regions of the tumor. Collectively, our results identify a HIF1α-ZEB1 signaling axis that promotes hypoxia induced mesenchymal shift and invasion in GBM in a cell line dependent fashion.

Topics: Adipokines; Basic Helix-Loop-Helix Transcription Factors; Brain Neoplasms; Cell Hypoxia; Cell Line, Tumor; Cell Movement; Cell Shape; Chitinase-3-Like Protein 1; Digoxin; Epithelial-Mesenchymal Transition; Glioblastoma; Glucose Transporter Type 1; Homeodomain Proteins; Humans; Hypoxia-Inducible Factor 1, alpha Subunit; Lectins; Necrosis; Neoplasm Invasiveness; Phenotype; RNA Interference; Signal Transduction; Transcription Factors; Transfection; Zinc Finger E-box-Binding Homeobox 1

Topics: Acute Disease; Cardiotonic Agents; Digitalis Glycosides; Digoxin; Fatal Outcome; Female; Gastrointestinal Hemorrhage; Humans; Infant; Intestine, Small; Necrosis

We report a case of myocardial necrosis in a newborn after treatment of the mother with long-term subcutaneous terbutaline. No such serious side effects in the fetus have previously been reported. We speculate that this myocardial damage was due to beta-sympathomimetic therapy.

Topics: Captopril; Cardiomyopathies; Digoxin; Echocardiography; Electrocardiography; Female; Furosemide; Humans; Infant, Newborn; Injections, Subcutaneous; Male; Necrosis; Obstetric Labor, Premature; Pregnancy; Terbutaline

Topics: Aged; Angiography; Arterial Occlusive Diseases; Digoxin; Female; Fibromuscular Dysplasia; Humans; Intestine, Small; Mesenteric Arteries; Mesenteric Vascular Occlusion; Necrosis

The role of calcium was investigated in myocardial cell necrosis induced by cardiac glycoside. Experimental poisoning caused an increase of Ca45. Excessive intracellular calcium uptake must be the determining factor in the aetiology of myocardial cell damage. The possible involvement of calcium increase in the genesis of cardiac glycoside induced myocardial cell necrosis is discussed.

Topics: Adenosine Triphosphatases; Animals; Autoradiography; Biological Transport, Active; Calcium; Cardiomyopathies; Digoxin; Female; Male; Microscopy, Electron; Necrosis; Rabbits

Topics: Acute Disease; Body Surface Area; Digoxin; Electrocardiography; Humans; Myocardial Infarction; Necrosis; Propranolol

Serum creatine phosphokinase (CPK) activity has been determined before and after intramuscular injection of lidocaine, diazepam or saline in humans and lidocaine, diazepam, digoxin and saline in pigs and rabbits. Two ml volum of each of the drugs was given to humans as well as to the experimental animals. No changes in CPK activity were found after saline in humans or rabbits but a minor increase was demonstrated in pigs. A marked increase of CPK activity was demonstrated after lidocaine or diazepam in humans and after lidocaine, diazepam or digoxin in pigs and rabbits. Post mortem examination of the injection sites in the animals revealed extensive muscle tissue necrosis after lidocaine, diazepam and digoxin. No damage of the tissue was found after saline. CPK activity was also determined in rabbits receiving 2 ml of dilutions of diazepam in saline. The injection sites were examined post mortem. The CPK activity was increased in animals receiving 1:2 and 1:8 dilutions while a 1:20 dilution did not give rise to changes in the enzyme activity. The necrotic area diminished when diazepam was diluted and no pathological changes were found at the injection sites after the 1:20 dilution. Measuring the CPK activity in rabbits after an intramuscular injection seems to be a sensitive method for the determination of local toxicity.

Topics: Animals; Creatine Kinase; Diazepam; Digoxin; Female; Humans; Injections, Intramuscular; Lidocaine; Male; Muscles; Necrosis; Rabbits; Sodium Chloride; Swine

Topics: Animals; Digoxin; Heart Failure; Humans; Infusions, Parenteral; Injections, Intramuscular; Injections, Intravenous; Necrosis; Osmolar Concentration; Pharmaceutical Vehicles; Staining and Labeling; Swine; Time Factors

Topics: Animals; Digoxin; Heart Failure; Humans; Injections, Intramuscular; Injections, Intravenous; Muscular Diseases; Necrosis; Rectum; Suppositories; Swine; Time Factors