Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0015672 (fatigue)
 51,768 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

An extended period of recovery of vascular resistance, far outlasting the recovery period of oxygen consumption, follows exercise of dog skeletal muscle when flow is restricted relative to the intensity of the exercise pattern. The duration of this postexercise prolonged vasodilation is graded and is related to the blood flow, duration of muscle stimulation, fatigue of the muscles, and total muscle tension development. To test whether prolonged vasodilation is mediated by prostaglandins or histamine, the prostaglandin synthetase inhibitors indomethacin or meclofenamate and the antihistamine tripelennamine were administered intravenously to anesthetized dogs between two 20-min exercise bouts of the anterior calf muscles at 4 twitches/s. Blood flow was held constant at approximately 20 ml 100 g-1 min-1, typically resulting in a venous O2 content below 2.0 ml/100 ml during exercise. The duration of vascular resistance recovery was evaluated by measuring the time at which vascular resistance returned to 90% (t90) of the recovery level (mean +/- SE). All the drugs caused a significant decline in the t90, but none reduced the recovery time to that following free-flow exercise, where the t90 is less than 1 min and the return of vascular resistance parallels the return of oxygen consumption to control. Thus, prostaglandin and/or histamine release may be at least partially responsible for prolonged vasodilation.
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PMID:Prostaglandin and histaminergic mediation of prolonged vasodilation after exercise. 40 1

We report a rare case of Bartter's syndrome in a 35-year-old woman with type 2 diabetes mellitus. The patient presented with leg weakness, fatigue, polyuria and polydipsia. Hypokalemia, metabolic alkalosis, and high renin and aldosterone concentrations were present, but the patient was normotensive. Gitelman's syndrome was excluded because of the presence of hypercalciuria, secondary hyperparathyroidism and bilateral nephrocalcinosis. The patients condition improved upon administration of a prostaglandin synthetase inhibitor (acemetacin), oral potassium chloride and potassium-sparing diuretics. Five months later, the patient discontinued acemetacin because of epigastric discomfort; at the same time, severe hypokalemia and hyperglycemia developed. Glucagon stimulation and water deprivation tests were performed. Type 2 diabetes mellitus with nephrogenic diabetes insipidus was diagnosed. To avoid further gastrointestinal complications, the patient was treated with celecoxib, a selective cyclooxygenase 2 inhibitor. This case serves as a reminder that Bartter's syndrome is associated with various metabolic derangements including nephrogenic diabetes insipidus, nephrocalcinosis and diabetes mellitus. When treating Bartter's syndrome, it is also prudent to remember that the long-term use of nonsteroidal anti-inflammatory drugs and potassium-sparing diuretics may result in serious adverse reactions.
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PMID:Bartter's syndrome with type 2 diabetes mellitus. 1925 37

This is a case report series of four patients who exhibited signs and symptoms of acute liver dysfunction during participation in a Phase I trial of a novel non-steroidal anti-inflammatory drug (NSAID) designed to inhibit microsomal prostaglandin synthase 1 (MPGES1). Within one month of trial initiation, all four patients presented with epigastric pain, fatigue, nausea, and increasing liver function tests (LFTs). Two out of four patients required hospitalization, underwent liver biopsies, and were treated with N-acetylcysteine. The remaining two patients were managed as outpatients. Liver biopsies were consistent with drug induced liver injury (DILI). Within three months of stopping the investigational drug, symptoms subsided and LFTs normalized in all patients. This case report series signifies the importance of NSAIDs and novel drug agents in general as potentially hepatotoxic substances, the need for a high level of suspicion of DILI when considering possible etiologies of acute liver failure, and the need for prompt withdrawal of the causative agent in management of patients presenting with DILI.
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PMID:Trial and error: investigational drug induced liver injury, a case series report. 2405 16