Tricyclic antidepressant fatality: postmortem tissue concentrations.
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Adult↗
Biomedical subjects
F Apple
Publications and source records attributed to F Apple.
Brain energy stores in C57BL/6 mice after C. parvum injection.
Activation of the immune system has been associated with the development of fatigue of unknown cause. We were interested in brain energy stores (e.g., phosphocreatine (PCr) and creatine kinase) after immune activation to investigate whether this system was altered. In this model, fatigue (defined as > 50% reduction in spontaneous running) was induced in C57BL/6 mice after a single injection of Corynebacterium parvum antigen. Maximal fatigue (about 86% reduction on day 10 post injection) was associated with reduced (about 29%) brain PCr/gamma-ATP and increased creatine kinase levels (approximately 31%), suggesting an active process of brain ATP depletion and replenishment. These findings need to be further delineated to establish the relationship between immune activation, reduced brain energy pools and fatigue.
Animals↗
Ferritin: a cytoprotective antioxidant strategem of endothelium.
Phagocyte-mediated oxidant damage to vascular endothelium is likely involved in various vasculopathies including atherosclerosis and pulmonary leak syndromes such as adult respiratory distress syndrome. We have shown that heme, a hydrophobic iron chelate, is rapidly incorporated into endothelial cells where, after as little as 1 h, it markedly aggravates cytotoxicity engendered by polymorphonuclear leukocyte oxidants or hydrogen peroxide (H2O2). In contrast, however, if cultured endothelial cells are briefly pulsed with heme and then allowed to incubate for a prolonged period (16 h), the cells become highly resistant to oxidant-mediated injury and to the accumulation of endothelial lipid peroxidation products. This protection is associated with the induction within 4 h of mRNAs for both heme oxygenase and ferritin. After 16 h heme oxygenase and ferritin have increased approximately 50-fold and 10-fold, respectively. Differential induction of these proteins determined that ferritin is probably the ultimate cytoprotectant. Ferritin inhibits oxidant-mediated cytolysis in direct relation to its intracellular concentration. Apoferritin, when added to cultured endothelial cells, is taken up in a dose-responsive manner and appears as cytoplasmic granules by immunofluorescence; in a similar dose-responsive manner, added apoferritin protects endothelial cells from oxidant-mediated cytolysis. Conversely, a site-directed mutant of ferritin (heavy chain Glu62----Lys; His65----Gly) which lacks ferroxidase activity and is deficient in iron sequestering capacity, is completely ineffectual as a cytoprotectant. We conclude that endothelium and perhaps other cell types may be protected from oxidant damage through the iron sequestrant, ferritin.
Animals↗
Lipase and pancreatic amylase activities in tissues and in patients with hyperamylasemia.
Lipase, pancreatic amylase, and total amylase activities were measured in nondiseased and diseased human pancreatic tissues and in six different locations of the human digestive system. In addition, it was determined whether serum lipase and pancreatic amylase tests could replace the total amylase test to improved diagnostic efficiency in the evaluation of acute pancreatitis in hyperamylasemia patients. Nondiseased pancreatic tissue contained 4.5 times more lipase activity than total amylase activity. Diseased pancreatic tissue contained less activity for both lipase and total amylase compared to normal tissue. The total amylase activity of the pancreas was comprised solely of pancreatic amylase. Tissue obtained from six different anatomic locations in the digestive system contained 35 to 45 times less lipase and total amylase activity compared to the pancreas. Total amylase activity of the digestive system tissues were comprised of 25% pancreatic and 75% salivary isoamylases. Lipase, pancreatic amylase, and total amylase levels also were determined in serial serum samples from 17 consecutive hyperamylasemia patients admitted with possible acute pancreatitis. The serum lipase level remained higher than normal longer than either the total amylase and pancreatic amylase levels. In patients with hyperamylasemia of pancreatic origin, a poor correlation was observed at admission between serum pancreatic amylase and serum lipase. Not all patients with elevated lipase had an elevated pancreatic amylase level and vice versa. However, in every patient pancreatic disease would have been detected by the elevation of either lipase or pancreatic amylase levels. Diagnostic efficiency for pancreatic disease using serum pancreatic amylase, lipase, and total amylase tests was 94.1%, 76.5%, and 64.7%, respectively. These data suggest that lipase and pancreatic amylase tests are specific for the pancreas and might be considered replacements for total amylase as the stat or routine laboratory test for the diagnosis of pancreatic tissue injury.
Acute Disease↗
Falsely increased CK-MB results obtained with the new reformulated CK-MB wash IV solution in the Stratus analyzer.
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Autoanalysis↗
Clinical and analytical evaluation of two immunoassays for direct measurement of creatine kinase MB with monoclonal anti-CK-MB antibodies.
We examined the clinical and analytical performance of two immunoassays (Becton Dickinson CK-MB; Ciba-Corning Magic Lite CK-MB) in which monoclonal anti-CK-MB antibodies are used for directly measuring creatine kinase (EC 2.7.3.2) isoenzyme MB (CK-MB) in serum, and also one electrophoretic method (Ciba-Corning). Within- and between-assay precision for both immunoassays was good at the upper reference limits (less than 10% CV). Analytical recoveries ranged from 102 to 114%. Both immunoassays were free from interference by CK-BB, mitochondrial-CK, macro-CK, adenylate kinase, and CK-MM. Retrospectively, we evaluated four categories of patients, using both immunoassays and electrophoresis: normal controls, acute myocardial infarction (AMI) patients, severe skeletal muscle trauma patients, and acutely ill patients known not to have AMI. In general, there were excellent correlations among all three methods. CK-MB activity (U/L) measured by the Becton Dickinson immunoassay was approximately 50% of the mass concentration (microgram/L) of the Magic Lite immunoassay and 50% of the activity concentration (U/L) determined by electrophoresis. Both immunoassays were easy to perform and sensitive to the low CK-MB concentrations often found with low total-CK activities.
Adult↗
Creatinine clearance: enzymatic vs Jaffé determinations of creatinine in plasma and urine.
We measured creatinine in plasma and urine samples from 17 normal subjects and 10 renally impaired subjects by four different methods: two enzymatic--Ektachem iminohydrolase and Boehringer Mannheim amidohydrolase--and two Jaffé reaction based--Beckman Astra 8 and Technicon AutoAnalyzer I. Creatinine clearances, standardized for body surface area, were also calculated. In both groups of subjects plasma creatinine values were significantly (p less than 0.05) lower, by 3 to 4 mg/L, when measured enzymatically than when measured by the Jaffé reaction. Additionally, creatinine clearances were significantly (p less than 0.05) greater by at least 30 mL/min when calculated from enzymatically measured creatinine values vs Jaffé method values for creatinine. The benefits of lack of interference with enzymatically measured creatinine concentrations and clearances should be assessed in relation to the lack of agreement with long-established (Jaffé) methods for determining creatinine (and inulin) clearances.
Amidohydrolases↗
Cocaine, cocaine metabolite, and ethanol concentrations in postmortem blood and vitreous humor.
The use of postmortem cocaine and metabolite concentrations is a complex subject. This study was undertaken to determine (1) the usefulness of vitreous humor as a specimen, compared with blood, to quantitate cocaine and cocaine metabolites; (2) whether there is a preferential site of disposition for cocaethylene between vitreous humor and blood; and (3) if the presence of cocaethylene influences the concentration of benzoylecgonine in postmortem specimens. Cocaine, benzoylecgonine, and cocaethylene were quantitated in blood and vitreous humor by gas chromatography-mass spectrometry, and ethanol was quantitated by gas chromatography in 62 medical examiner cases. No differences were found between mean concentrations of vitreous cocaine 0.613 mg/L (standard deviation [SD] 0.994 mg/L), cocaethylene 0.027 mg/L (SD 0.59 mg/L), and ethanol 0.092 g/dL (SD 0.13 g/dL) compared to blood cocaine 0.489 mg/L (SD 1.204 mg/L), cocaethylene 0.022 mg/L (SD 0.055 mg/L), and ethanol 0.058 g/dL (SD 0.91 g/dL), respectively. However, a statistical difference was found between mean benzoylecgonine concentrations in vitreous 0.989 mg/L (SD 1.597 mg/L) and blood 1.941 mg/L (SD 2.912 mg/L) (p = 0.0004). Regression analysis demonstrated that linear relationships were present between concentrations of vitreous and blood cocaine (r = 0.854) and benzoylecgonine (r = 0.763). However, the correlation coefficients were lower for cocaethylene (r = 0.433) and ethanol (r = 0.343). There were variations between the concentrations of cocaine and metabolites both in terms of magnitude and also direction of change. Mean concentrations of benzoylecgonine in blood and vitreous were higher in cases where ethanol was absent, 2.593 mg/L (SD 3.195 mg/L) and 1.431 mg/L (SD 2.021 mg/L), compared to when ethanol was present, 1.199 mg/L (SD 2.396 mg/L) and 0.469 mg/L (SD 0.553 mg/L). This study demonstrates that vitreous humor may be used to quantitate cocaine and cocaine metabolites; however, because the concentrations of cocaethylene in vitreous humor and blood were not well correlated, vitreous humor may not be a reliable specimen for measuring cocaine and cocaine metabolite concentrations.
Autopsy↗