Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.4.21.69 (APC)
 16,337 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

1. The initial site of damage in analgesic abuse is the renal medulla and the characteristic lesion is renal papillary necrosis. The papillary necrosis appears to be an ischaemic infarct. The cortical lesion of chronic interstial nephritis is a non-specific change and secondary to obstruction to tubules in the necrotic medulla. 2. Medullary perfusion and the concentration mechanism appear to be important factors in the genesis of renal papillary necrosis. 3. Experimental and clinical studies suggest that abuse of compound analgesics containing aspirin, phenacetin and caffeine result in renal papillary necrosis and the clinical syndrome of analgesic nephropathy. In the APC mixture aspirin appears to be the major nephrotoxic agent while phenacetin plays a synergistic but secondary role in the renal nephrotoxicity.
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PMID:Pathology, aetiology and pathogenesis of analgesic nephropathy. 107 Sep 95

The influence of coffee and caffeine consumption on hemostatic factors was studied in 2 randomized trials. Both studies were conducted in young, healthy adults. In the first study, 107 participants were randomly allocated to one or 3 intervention groups, drinking filtered coffee, boiled coffee or no coffee at all, respectively, for a period of 9 weeks. In the second study, 69 subjects received either 4-6 tablets containing 75 mg caffeine or the same amount of placebo tablets, while using decaffeinated coffee. In this double-blind study caffeine intake from any other source was not allowed. Blood samples for hemostatic factors were obtained at baseline and after 9 weeks of intervention. The findings indicate no effect of coffee consumption on fibrinogen, clotting factor VII activity, factor VIII antigen, protein C and protein S and also no effect of caffeine consumption on fibrinogen and factor VII activity.
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PMID:Coffee, caffeine and hemostasis: results from two randomized studies. 214 67

A survey of 763 patients with rheumatoid arthritis and 145 with osteoarthritis in six clinics in New Zealand showed no association between aspirin intake and a score designed to detect analgesic nephropathy. Analgesic nephropathy was diagnosed clinically in three patients taking APC (aspirin, phenacetin, and caffeine or codeine or both) and in one who took aspirin and phenylbutazone and was suspected in one who took aspirin and paracetamol. Isolated aspirin was not implicated. The study showed that most people can take large quantities of salicylates without renal injury.The findings are, however, consistent with the view that there is a risk from APC compounds taken in large quantity, but the numbers at risk in this study were small. Aspirin may have an additive effect with other analgesics in causing renal damage. An increased frequency of urinary tract symptoms in those taking analgesics requires further investigation.
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PMID:Aspirin and the kidney. New Zealand Rheumatism Association Study. 482 Oct 7

In this multicenter study a nonnarcotic analgesic available for moderate pain, naproxen sodium, 550 mg, was compared to a combination that is used extensively for moderate to severe pain, aspirin, phenacetin, caffeine and codeine phosphate (APC/C) (60 mg of codeine phosphate). Women with pain after major gynecologic surgery reported a similar pattern in pain reduction with the two medications except for a relatively sharper increase in pain intensity between four and six hours after administration of APC/C. A smaller number of patient complaints suggested that naproxen sodium was better tolerated than APC/C.
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PMID:Naproxen sodium vs. a combination of aspirin, phenacetin, caffeine and codeine phosphate for pain after major gynecologic surgery. A multicenter comparison. 637 36

The analgesic efficacy of a hydrocodone-acetaminophen combination, a codeine-acetaminophen combination, a codeine-APC (aspirin, phenacetin, and caffeine) combination, and a placebo was evaluated in outpatients who had moderate or severe pain after the surgical removal of impacted third molars. Each of the active medications had a significant effect on essentially all measures of total and peak analgesia; they did not differ significantly on any measure of analgesia. Adverse effects were transitory and, in general, appear to have been related to the centrally acting component of each combination analgesic.
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PMID:An evaluation of the analgesic efficacy of three opioid-analgesic combinations in postoperative oral surgery pain. 693 24

Groups of 40 male and 40 female C57BL/6 mice were maintained for 75-80 weeks on meal form diets containing aspirin, phenacetin and caffeine either singly or in combination. The maximum daily doses of phenacetin alone and the APC combination were approximately one-half of their previously determined respective oral LD50's. Mild, nonprogressive histopathologic changes of the urinary tract were noted with these changes first evident in animals given the highest dose of phenacetin. Sulfhemoglobinemia was also induced in all groups of animals given phenacetin alone or in combination indicating that toxic doses were administered oral LD50's. Mild, nonprogressive histopathologic changes of the urinary tract were noted with these changes first evident in animals given the highest dose of phenacetin. Sulfhemoglobinemia was also induced in all groups of animals given phenacetin alone or in combination indicating that toxic doses were administered oral LD50's. Mild, nonprogressive histopathologic changes of the urinary tract were noted with these changes first evident in animals given the highest dose of phenacetin. Sulfhemoglobinemia was also induced in all groups of animals given phenacetin alone or in combination indicating that toxic doses were administered. Under the conditions of this study, evidence of carcinogens was not demonstrated for any of the drugs given alone or in combination.
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PMID:Eighteen month oral study of aspirin, phenacetin and caffeine, in C57Bl/6 mice. 722 15

The principle of derivative spectrum is described, which is based on the simultaneous use of the first derivative of ratio spectra and measurements of zero-crossing wavelengths. The method can be used to analyze one of three components in ternary mixture and eliminate the interference of others. This method is used to determine the ternary mixture of aspirin, phenacetin and caffeine in APC simultaneous with satisfactory results. The regression coefficient is higher than 0.9992, the relative standard derivatives (RSD) is less than 3.2%, the recovery is between 93.3%-106.3%.
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PMID:[Simultaneous determination of aspirin, phenacetin and caffeine in compound APC by derivative ratio UV adsorption spectrum method]. 1294 85

Quantitative infrared (IR) and Raman spectroscopic approach for determination of phenacetin (Phen) and salophen (Salo) in binary solid mixtures with caffeine: phenacetin/caffeine (System 1) and salophen/caffeine (System 2) is presented. Absorbance ratios of 746 cm(-1) or 721 cm(-1) peaks (characteristic for each of determined compounds in the Systems 1 and 2) to 1509 cm(-1) and 1616 cm(-1) (attributed to Phen and Salo, respectively) were used. The IR spectroscopy gives confidence of 98.9% (System 1) and 98.3% (System 2), while the Raman spectroscopic data are with slightly higher confidence of 99.1% for both systems. The limits of detection for the compounds studied were 0.013 and 0.012 mole fraction for IR and Raman methods, respectively. Solid-state linear dichroic infrared (IR-LD) spectral analysis of solid mixtures was carried out with a view to obtaining experimental IR spectroscopic assignment of the characteristic IR bands of both determined compounds. The orientation technique as a nematic liquid crystal suspension was used, combined with the so-called reducing-difference procedure for polarized spectra interpretation. The possibility for obtaining supramolecular stereo structural information for Phen and Salo by comparing spectroscopic and crystallographic data has also been shown. An independent high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) analysis was performed for comparison and validation of vibrational spectroscopy data. Applications to 10 tablets of commercial products APC and Sedalgin are given.
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PMID:Determination of phenacetin and salophen analgetics in solid binary mixtures with caffeine by infrared linear dichroic and Raman spectroscopy. 1797 43

Topoisomerase II (topo II) is required for chromosome segregation and for reprogramming replicons. Here, we show that topo II couples DNA replication termination with the clearing of replication complexes for resetting replicons at mitosis. Topo II inhibition impairs completion of DNA replication, accounting for replication protein A (RPA) stabilization onto ssDNA. Topo II inhibition does not affect the caffeine-sensitive ORC1 degradation found upon origin firing, but it impairs the cdk-dependent degradation/chromatin dissociation of an ORC1/2 reservoir at mitosis. Our results show that ORC1 degradation is rescued by Pin1 depletion and that this topo II-dependent clearing of ORC1/2 from chromatin involves the APC.
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PMID:A topoisomerase II-dependent mechanism for resetting replicons at the S-M-phase transition. 1838 89

Cdh1 activates the Anaphase Promoting Complex/Cyclosome (APC/C(Cdh1)) throughout G(1) to degrade key cell cycle proteins. Cdh1 is not essential for cell proliferation, in spite of the fact that overexpression of some its degradation substrates is highly toxic. We report here that cdh1Delta cells are sensitive to stresses that activate the CWI (Cell Wall Integrity) and Hog1 MAP kinase pathways. Stresses did not activate APC/C(Cdh1) and cellular sensitivity was thus clearly due to constitutively elevated substrate levels. To explore the contribution of stabilization of individual APC/C(Cdh1) substrates to stress sensitivity, we generated cell lines expressing stabilized substrate mutants under their endogenous promoters. Cells expressing stabilized Hsl1 were sensitive to caffeine and failed to activate the Slt2 pathway. Cells expressing partially stable Clb2 were particularly sensitive to different stresses, possibly due to reduced Sic1 levels. Cells expressing stabilized Cdc5 were much less stress sensitive. Interestingly sensitivity of cdh1Delta cells does not seem to be restricted to G(1) but is manifested also during S and G(2) when the APC/C(Cdh1) is inactive anyway. We thus hypothesize that a role of G(1) specific APC/C(Cdh1) activity is to reset substrate levels to enables appropriate regulation of substrate accumulation in the subsequent phases of the cell cycle.
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PMID:APC/CCdh1 specific degradation of Hsl1 and Clb2 is required for proper stress responses of S. cerevisiae. 1971 62


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