Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.6.1.2 (alanine aminotransferase)
 26,722 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A 71-year-old man with chronic atrial fibrillation was treated with aspirin because of a right cerebral infarction. Oral anticoagulation was not initiated because of a secondary hemorrhagic transformation. Six years later after a left cerebral transient ischemic attack aspirin was replaced by ticlopidine. Two weeks after starting ticlopidine he experienced abdominal cramps and diarrhea. Also dark urine and gray-colored stools were noticed, so that the patient stopped taking ticlopidine. 40 days after starting ticlopidine he was admitted to our hospital because of cholestatic jaundice. Serum alkaline phosphatase (305 U/l) and gamma GT (143 U/l) were elevated, the total bilirubin was 18.6 mg/dl at peak. GOT and GPT were 2.7 fold increased. After exclusion of a viral infection and autoimmune disease liver biopsy was performed, which showed a centroacinar cholestasis compatible with a drug-induced liver damage. 79 days after discontinuation of the drug laboratory signs of cholestasis had disappeared. In patients in whom long-term therapy with ticlopidine is indicated regularly laboratory tests and clinical examinations should be done to recognize infrequent side effects such as the cholestatic hepatitis in time.
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PMID:[Cholestatic hepatitis as a rare side effect of therapy with ticlopidine]. 1096 56

Action potential duration (APD) alternans (APD-ALT), defined as beat-to-beat oscillations in APD, has been proposed as an important clinical marker for chronic atrial fibrillation (cAF) risk when it occurs at pacing rates of 120-200 beats/min. Although the ionic mechanisms for occurrence of APD-ALT in human cAF at these clinically relevant rates have been investigated, little is known about the effects of myofilament protein kinetics on APD-ALT. Therefore, we used computer simulations of single cell function to explore whether remodeling in myofilament protein kinetics in human cAF alters the occurrence of APD-ALT and to uncover how these mechanisms are affected by sarcomere length and the degree of cAF-induced myofilament remodeling. Mechanistically based, bidirectionally coupled electromechanical models of human right and left atrial myocytes were constructed, incorporating both ionic and myofilament remodeling associated with cAF. By comparing results from our electromechanical model with those from the uncoupled ionic model, we found that intracellular Ca2+ concentration buffering of troponin C has a dampening effect on the magnitude of APD-ALT (APD-ANM) at slower rates (150 beats/min) due to the cooperativity between strongly bound cross-bridges and Ca2+-troponin C binding affinity. We also discovered that cAF-induced enhanced thin filament activation enhanced APD-ANM at these clinically relevant heart rates (150 beats/min). In addition, longer sarcomere lengths increased APD-ANM, suggesting that atrial stretch is an important modulator of APD-ALT. Together, these findings demonstrate that myofilament kinetics mechanisms play an important role in altering APD-ALT in human cAF. NEW & NOTEWORTHY Using a single cell simulation approach, we explored how myofilament protein kinetics alter the formation of alternans in action potential duration (APD) in human myocytes with chronic atrial fibrillation remodeling. We discovered that enhanced thin filament activation and longer sarcomere lengths increased the magnitude of APD alternans at clinically important pacing rates of 120-200 beats/min. Furthermore, we found that altered intracellular Ca2+ concentration buffering of troponin C has a dampening effect on the magnitude of APD alternans.
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PMID:Increased thin filament activation enhances alternans in human chronic atrial fibrillation. 3014 84