Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027960 (mole)
 21,279 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Both heterologous IgG and Fab fragments of appropriate affinity and specificity have been shown capable of reversing advanced cardiac glycoside toxicity. Fab fragments are more rapidly excreted and theoretically have a smaller risk of unwanted immunologic effects, but relative rates of toxicity reversal have not been established. Rates of reversal of advanced digoxin toxicity by digoxin-specific IgG and Fab fragments were therefore compared in a dog model of advanced digoxin intoxication. Initial studies confirmed more rapid distribution of sheep Fab fragments (M.W. 50,000) than of the parent IgG molecule (M.W. 150,000) after intravenous injection. Twenty-five pentobarbital-anesthetized dogs were given 0.3 mg/kg digoxin intravenously, resulting in rapid onset of ventricular tachycardia in all animals. Eight dogs subsequently given nonspecific IgG or Fab died in asystole or ventricular fibrillation an average of 55 minutes after digoxin administration. Ten of 11 dogs given 1.33 moles of binding sites per mole of digoxin as intact IgG returned to sinus rhythm at a mean time of 85 minutes after antibody infusion. In contrast, six of six dogs given an equivalent dose of specific Fab fragments returned to sinus rhythm in a significantly shorter mean time of 36 minutes (P less than 0.01). Variability of time to arrhythmia reversion was less in Fab-treated dogs. These data demonstrate a decisive advantage of specific Fab fragments over intact IgG for potential clinical use in advanced, life-threatening digoxin intoxication.
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PMID:Contrasting rates of reversal of digoxin toxicity by digoxin-specific IgG and Fab fragments. 66 76

The ability to induce alcoholic cardiomyopathy has been tested in a variety of animal species. Myocardial alterations consistent with subclinical heart disease have been produced in many of these studies through a direct effect of ethanol or its metabolites upon the heart or a neurohumoral mechanism. In the rat most studies have, however, failed to finding diminished contractility in the basal state. In long-term animals the acute left ventricular responses to isoproterenol and calcium as well as pacing were reduced. Long-term studies in mongrel dogs fed 36 per cent of calories as ethanol produced an early decrease in left ventricular diastolic compliance related to interstitial collagen accumulation. Diminished contractility developed by four years. In addition to the morphologic evidence of distorted sarcoplasmic reticulum, in vitro experiments suggest important acute effects. Each mole of ethanol is bound tightly to each mole of protein comprising the Ca-ATPase pump, which is inhibited. Impaired uptake and binding of calcium by the sarcoplasmic reticulum has been observed in chronic alcohol models at one to two day intervals following the last exposure to ethanol. In addition, the flux of calcium ion does not appear normal in terms of access to contractile protein, where the calcium regulated inhibition of the troponin interaction with myosin is impaired. Experimental studies in a canine model of alcoholism revealed that the ventricular fibrillation threshold was moderately reduced in the basal state after 18 months and was diminished further after acute exposure.
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PMID:Experimental models for studying the effects of ethanol on the myocardium. 331 64