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S J Stohs M A Shara N Z Alsharif Z Z Wahba Z A al-Bayati 《Toxicology and applied pharmacology》1990,106(1):126-135
Oxidative stress may play a role in the toxic manifestations of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). Therefore, the time-dependent effects of 100 micrograms TCDD/kg on various indices of oxidative stress including lipid peroxidation. DNA damage, membrane fluidity, calcium homeostasis, nonprotein sulfhydryl content, and NADPH content of hepatic subcellular fractions of female rats were followed for 12 days. Increases in lipid peroxidation of 400-500% occurred in mitochondrial and microsomal membranes and nuclei, with maximum increases occurring 5-6 days post-treatment. Decreases in the nonprotein sulfhydryl content of mitochondrial and microsomal fractions of approximately 80% were observed by Day 12 posttreatment. Membrane fluidity gradually decreased following administration of TCDD, with decreases of 30-40% being observed in mitochondria, microsomes, and plasma membranes. A sharp increase in the incidence of hepatic nuclear DNA single strand breaks was observed 3 days after treatment with an increase of approximately 600% by Day 9. Following the administration of TCDD, increases of 70-80% occurred in the calcium content of mitochondria and microsomes. An 18% increase in cytosolic calcium was present 12 days after the administration of TCDD. Cytosol and mitochondria both exhibited an initial increase in NADPH content following administration of TCDD, but by Day 12 both had decreased to approximately two-thirds of control values. The results clearly demonstrate that TCDD administration induces an oxidative stress in rat liver. The most pronounced effects were observed in membrane lipid peroxidation and DNA damage with gradual changes being observed in calcium and nonprotein sulfhydryl contents and membrane fluidity. 相似文献
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Lillian L. L. Leong Marian J. Sturm Yahya Ismail Charlene J. Stephens Roger R. Taylor 《Clinical and experimental pharmacology & physiology》1992,19(2):113-118
1. Phospholipase A2 (PLA2) cleaves phospholipids to produce a lyso-phospholipid and free fatty acid and, in view of the biological activity of the products, PLA2 may play a role in many disease states. Lyso-phospholipids and free arachidonic acid increase in ischaemic myocardium, indicating that ischaemia activates the enzyme. 2. Plasma PLA2 activity was measured in patients with acute myocardial infarction, based on the release of labelled arachidonic acid from Escherichia coli cell membrane. Fourteen males (peak serum creatine phosphokinase (CK) above twice upper normal) were studied on day 1 (within 6 h of chest pain onset), days 2-4, and days 6-9. Normal age matched males (n = 13) were also studied. 3. Plasma PLA2 in patients with uncomplicated myocardial infarction (n = 12) was, initially, 1.14 +/- 0.10 (s.e.m.) nmol/min per mL plasma, similar to that in the normal group (1.52 +/- 0.14). On days 2-4, PLA2 activity increased to 1.94 +/- 0.18 (P less than 0.001) and this activity was correlated with the earlier peak CK level (P less than 0.02). On days 6-9, PLA2 activity was 1.49 +/- 0.13 while in two patients who developed complications and underwent open-heart surgery between the last two measurements, there were further increases to 4.22 and 4.04 nmol/min per mL. 4. The increase in plasma PLA2 in uncomplicated myocardial infarction is likely to be due to release from the damaged myocardium; whether it contributes to pathophysiology is uncertain. 相似文献
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Ping L. Zhang Sayeed K. Malek Jeffery W. Prichard Fan Lin Taher M. Yahya Michael S. Schwartzman Ruth P. Latsha Evan R. Norfolk Thomas M. Blasick Mingyue Lun Robert E. Brown James E. Hartle Santosh Potdar 《American journal of transplantation》2005,5(3):604-607
Campath-1H has been used successfully for induction and has resulted in a low rate of acute cellular rejection (ACR) in renal transplantation in combination with various postoperative immunosuppression regimens. This study was undertaken to investigate the extent of monocyte involvement in ACR, with or without Campath-1H induction. We found that monocytes represented the majority of inflammatory cells in grades Ib or higher ACR, but not with Ia type of ACR, regardless of the status of Campath-1H induction. Cases of ACR, following Campath-1H induction, appear to demonstrate a 'pure form' of monocytic ACR, whereas monocytes were mixed with many other types of inflammatory cells in the cases of ACR in the absence of Campath-1H induction. In addition with Campath-1H induction, the cases of monocyte-predominant ACR were found to uniformly exhibit a good response to corticosteroid treatment. We conclude that monocyte-predominate ACR may represent a severe form of rejection, with or without Campath-1H treatment. 相似文献
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Mammalian cell cytotoxicity and genotoxicity analysis of drinking water disinfection by-products 总被引:19,自引:0,他引:19
Plewa MJ Kargalioglu Y Vankerk D Minear RA Wagner ED 《Environmental and molecular mutagenesis》2002,40(2):134-142
Cytotoxicity and genotoxicity assays were used to analyze drinking water disinfection by-products (DBPs) in Chinese hamster ovary (CHO) AS52 cells. The DBPs were chosen because they are common in drinking water, resulting from conventional disinfection using chlorination and chloramination. Data were also available to compare these results with cytotoxicity and mutagenicity studies in Salmonella typhimurium. The rank order in decreasing chronic cytotoxicity measured in a microplate-based assay was bromoacetic acid (BA) > 3-chloro-4-(dichloromethyl)-5-hydroxy-2[5H]-furanone (MX) > dibromoacetic acid (DBA) > chloroacetic acid (CA) > KBrO(3) > tribromoacetic acid (TBA) > EMS (ethylmethanesulfonate, positive control) > dichloroacetic acid (DCA) > trichloroacetic acid (TCA). The induction of DNA strand breaks by these agents was measured by alkaline single-cell gel electrophoresis (SCGE, comet assay) and the rank order in decreasing genotoxicity was BA > MX > CA > DBA > TBA > EMS > KBrO(3), while DCA and TCA were refractory. BA was more cytotoxic (31x) and genotoxic (14x) than MX in CHO cells. BA was over 400x more genotoxic than potassium bromate. The brominated haloacetic acids (HAAs) were more cytotoxic and genotoxic than their chlorinated analogs. The HAAs expressed a statistically significant inverse relationship in CHO cell cytotoxicity and genotoxicity as a function of increased numbers of halogen atoms per molecule. A quantitative comparison was conducted with results from a previous study with cytotoxicity and mutagenicity in S. typhimurium. There was no correlation between chronic CHO cell and bacterial cell cytotoxicity. DBP-induced CHO cell cytotoxicity was not related to mutagenic potency in S. typhimurium. Cytotoxicity in CHO cells was statistically significant and highly correlated to CHO cell genotoxicity. Finally, we determined that the DBP genotoxic potency in CHO cells and the mutagenic potency in S. typhimurium were not related. This suggests that toxicity data in S. typhimurium did not quantitatively predict the toxic effects of DBPs in mammalian cell systems. The microplate CHO cell cytotoxicity and genotoxicity assays were well suited for the analysis of DBPs, especially when the quantity of test material is limited. 相似文献
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The purpose of this clinical study was to determine: (1) the increase in minute ventilation required to maintain preinsufflation arterial carbon dioxide tension (PaCO2) during laparoscopic cholecystectomy, and (2) whether end-tidal PCO2 (PetCO 2) can be used as an index of PaCO2 and, therefore, of the adequacy of minute ventilation during the pneumoperitoneum. We measured PaCO2,PetCO 2, expired minute volume (Vexp) standardized for body surface area (SA), airway and intra-abdominal pressure (Paw, Pabd) during general anaesthesia for laparoscopic cholecystectomy just before and 30 min after the creation of a CO2 pneumoperitoneum in 28 healthy (ASA class 1 and 2) consenting adults. They were in the reverse Trendlenburg position (20°) with a 5° lateral tilt. Expired minute volume was increased from 3.75 (SEM ± 0.12) to 4.19 (0.15) L·min?1·m?2 to maintain PaCO2 close to control levels: 38.9 (0.8) vs 40.1 (0.6) mmHg 5.19 (0.1) vs 5.35 (0.08) kPa). In most of the patients (23/28),PetCO 2 was less than 41 mmHg with a correlation between PaCO2 andPetCO 2. In ten of these patients, (Pa-Pet)CO2 was greater than the normal range. In 5/28, (Pa-Pet)CO2 was negative. The “driving pressure” (Paw-Pabd) increased from 8.7 (1.0) to 10.4 (1.1) cm H2O, without any correlation between the increase in Paw-Pabd and that in \(\dot Vexp\) . The results indicate the need for extra ventilatory requirement during laparoscopy and thatPetCO 2 is an imperfect index of PaCO2 under these circumstances. 相似文献
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