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)

We present a case of unknown fever and abnormal liver functions which developed during the course of pain management for herpes zoster with repeated epidural blocks with 0.5% lidocaine 10 ml. The patient was a 67 year old woman. At her first admission to dermatology, there were no abnormal findings in her blood examinations. She complained of severe pain from herpes zoster. She was admitted to the pain clinic. She received thoracic epidural blocks with 0.5% lidocaine 10 ml repeatedly three or four times a week. Two weeks later, she developed general fatigue, appetite loss, nausea and a high fever. Blood examinations revealed the elevation of glutamic oxalacetic transaminase (GOT), glutamic pyruvic transaminase (GPT), alkaline phosphatase (ALP), and gamma glutamyltrans peptidase (gamma-GTP), C reactive protein (CRP), and blood sedimentation rate (BSR). Many examinations including abdominal and thoracic computer tomography and abdominal echograph could not reveal the cause of high fever and abnormal blood examinations. We continued the thoracic epidural block for her herpes zoster pain. GOT, GPT, ALP, and gamma-GTP gradually went down to normal values in next two weeks, though fever still persisted. At this time, lymphocyte cell simulation test with 0.5 % lidocaine was positive and eosinophylic cell had increased to 5%. After ceasing the epidural block, fever resolved and blood examinations returned to normal values. These findings suggest strongly that 0.5% lidocaine induced fever and hepatitis.
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PMID:[Unknown fever and abnormal liver functions after repeated epidural blocks with lidocaine for management of herpes zoster pain]. 818 88

PT-100 upregulates cytokine expression competitively inhibiting the dipeptidyl peptidase activity of fibroblast activation protein (FAP) and dipeptidyl peptidase IV (DPP-IV). This dose-escalation study was conducted to evaluate the safety of PT-100 in patients receiving myelosuppressive chemotherapy and to assess its effects on neutrophil recovery.PT-100 was administered orally for 7 days as a 200 microg, 400 microg, 800 microg, or 1,200 microg total daily dose (divided twice daily) to 6, 6, 17, and 5 patients, respectively. Patients received 2 cycles of chemotherapy: The first cycle served as each individual patient's control. Patients had to develop Grade 3+ neutropenia in Cycle 1 in order to receive PT-100 in Cycle 2. Most patients received PT-100 on Days 2-8 of chemotherapy in Cycle 2, except at 800 microg where an additional cohort (n = 8) was treated on a Days 5-11 schedule. Five of 7 patients receiving 800 microg on Days 2-8 experienced a >/=1-day improvement in Grade 3+ neutropenia in Cycle 2 versus Cycle 1. Overall, PT-100 was well tolerated. A reduction in chemotherapy-related nausea, vomiting, fatigue, alopecia, and diarrhea was noted in patients receiving PT-100. Edema/peripheral swelling, hypotension, hypovolemia, and dizziness were the most common nonhematologic adverse events considered related to PT-100. Two Grade 3 adverse events were considered related to PT-100: syncope (1,200 microg) and orthostatic hypotension (800 microg). A maximum tolerated dose was not reached. Given the accelerated neutrophil recovery, preclinical evidence of antitumor activity, and tolerable toxicities of PT-100, additional studies to optimize the PT-100 dosing schedule in patients receiving myelosuppressive chemotherapy are needed.
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PMID:Phase I trial of PT-100 (PT-100), a cytokine-inducing small molecule, following chemotherapy for solid tumor malignancy. 1698 58

Sitagliptin is a dipeptidyl peptidase-4 (DPP IV, CD26) inhibitor indicated for treatment of Type II diabetes as a second line therapy after metformin. We report fifteen sitagliptin intolerant patients who developed anterior and posterior rhinorrhea, cough, dyspnea, and fatigue. Symptoms typically developed within 1 to 8 weeks of starting, and resolved within 1 week of stopping the drug. Peak expiratory flow rates increased 34% in 8 patients who stopped sitagliptin. Similar changes were found in 4 out of 5 persons who had confirmatory readministration. Chart review identified 17 patients who tolerated sitagliptin and had no symptomatic changes. The sitagliptin intolerant group had higher rates of clinically diagnosed allergic rhinitis (15/15 vs. 6/18; p = 0.00005), Fisher's Exact test) and angiotensin converting enzyme inhibitor - induced cough (6/13 vs. 1/18; p = 0.012). Nasal and inhaled glucocorticoids may control the underlying allergic inflammation and abrogate this new sitagliptin - induced pharmacological syndrome. Potential mucosal and central nervous system mechanisms include disruption of neuropeptides and/or cytokines that rely on DPP IV for activation or inactivation, and T cell dysfunction.
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PMID:Rhinorrhea, cough and fatigue in patients taking sitagliptin. 2046 26

Sitagliptin and vildagliptin are dipeptidyl peptidase 4 (DPP-4) inhibitors, also known as "gliptins". They are approved for use as oral glucose-lowering agents, although they have no proven impact on morbidity or mortality. Their glucose-lowering effect is limited and their long-term risks are poorly documented. A third gliptin, saxagliptin, is now authorised in the European Union for second-line treatment of type 2 diabetes, in combination with metformin, a glucose-lowering sulphonylurea, or a glitazone. Clinical evaluation of saxagliptin is mainly based on 8 double-blind randomised trials in about 5000 patients, including 4 trials of second-line combination therapy (1 non-inferiority trial versus sitagliptin, and 3 placebo-controlled trials). The reduction in the mean HbAlc levels with saxagliptin was about 0.3% to 0.8% (in absolute values) versus placebo, which is similar to that reported with other gliptins. The adverse effect profile of saxagliptin is similar to that of the other gliptins, and includes infections (especially urinary tract and sinus infections), gastrointestinal disorders, musculoskeletal disorders, fatigue, and depression. There also appears to be an increased risk of bone fractures. Potential long-term adverse effects include infectious, cardiac, hepatic, pancreatic and cutaneous disorders. Unlike the other gliptins, saxagliptin is metabolised by the cytochrome P450 isoenzyme CYP 3A4, hence a high potential for pharmacokinetic interactions. The risk-benefit balance of saxagliptin is no better than that of other gliptins, and saxagliptin carries a higher risk of drug interactions. In practice, when metformin or glibenclamide monotherapy fails, it is better to continue with a standard treatment strategy, such as resorting to insulin or abandoning strict glycaemic control.
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PMID:Saxagliptin. No more effective than other gliptins, but a high potential for drug interactions. 2148 86

Mitochondria are dynamic subcellular organelles that convert nutrient intermediates into readily available energy equivalents. Optimal mitochondrial function is ensured by a highly evolved quality control system, coordinated by protein machinery that regulates a process of continual fusion and fission. In this work, we provide in vivo evidence that the ATP-independent metalloprotease OMA1 plays an essential role in the proteolytic inactivation of the dynamin-related GTPase OPA1 (optic atrophy 1). We also show that OMA1 deficiency causes a profound perturbation of the mitochondrial fusion-fission equilibrium that has important implications for metabolic homeostasis. Thus, ablation of OMA1 in mice results in marked transcriptional changes in genes of lipid and glucose metabolic pathways and substantial alterations in circulating blood parameters. Additionally, Oma1-mutant mice exhibit an increase in body weight due to increased adipose mass, hepatic steatosis, decreased energy expenditure and impaired thermogenenesis. These alterations are especially significant under metabolic stress conditions, indicating that an intact OMA1-OPA1 system is essential for developing the appropriate adaptive response to different metabolic stressors such as a high-fat diet or cold-shock. This study provides the first description of an unexpected role in energy metabolism for the metalloprotease OMA1 and reinforces the importance of mitochondrial quality control for normal metabolic function.
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PMID:Loss of mitochondrial protease OMA1 alters processing of the GTPase OPA1 and causes obesity and defective thermogenesis in mice. 2243 42