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1. Premalignant rat liver nodules produced in the resistant hepatocyte model, by exposure to carcinogenic chemicals (diethyl nitrosamine and 2-acetamidofluorene), and partial hepatectomy, exhibit decreased xenobiotic hydroxylase activities and increased conjugase activities, which are considered responsible for increased resistance to xenobiotic toxicity. 2. However, premalignant rat liver nodules generated by feeding the hypolipidaemic, peroxisomal proliferating drug, ciprofibrate, in a hypolipidaemic model, exhibit decreased hydroxylase activities but decreased conjugase activities also. 3. It is considered that reactive oxygen species (ROS) are generated in both the resistant hepatocyte model and in the hypolipidaemic model, resulting in lipid peroxidation, loss of haem, cytochromes and hydroxylase activities. 4. However, whereas there is a rebounding compensation of conjugase enzymes in the resistant hepatocyte model, this does not occur with the hypolipidaemic model, as peroxidation is probably persistent and the conjugases are continuously destroyed. 相似文献
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Systemic corticosteroid therapy is an established adjunct to beta-adrenergic medications in acute exacerbations of asthma. To date, no study has defined the role of long-acting intramuscular preparations of corticosteroids in pediatric patients with asthma. A pilot study was conducted to prospectively compare symptomatic improvement following a single injection of intramuscular dexamethasone (IMD) to a 3-day regimen of oral prednisone (OP) for children with mild to moderate wheezing episodes that are responsive to nebulized medications in the Pediatric Emergency Department (PED). The following children presenting with acute exacerbations of asthma to the PED were eligible for enrollment: age 3-16 years; more than two prior wheezing episodes; mild to moderate wheezing; and oxygen saturation 95% or more in room air. The study patients were randomly assigned to receive either IMD (n = 21) or OP (n = 21) in addition to a standardized treatment regimen of nebulized albuterol. All of the children were clinically rated for wheezing severity by the Pulmonary Index (PI) score at regular intervals during the study. Discharge home was based on clinical improvement during treatment in the PED; patients who were admitted to the hospital were removed from the study. Follow-up was conducted the fifth day after discharge from the ED either by clinic visit or by telephone. Patients were assessed for symptomatic improvement and relapse or clinical deterioration during the study period by a clinician blinded to group assignment. Forty-two children participated in this pilot study. There were no significant differences between the IMD and OP groups for gender or age. Mean ages were: 82 months (SD 46 months), IMD group; 63 months (SD 36 months), OP group. Clinical progress (based on PI) with treatment in the PED was the same in both groups: pretreatment median, PI = 6; PED discharge median, PI = 2. None of the study patients were hospitalized during the follow-up period, and all reported symptomatic improvement since initial treatment. The data of this pilot study suggest that IMD may be a feasible alternative to OP for treatment of acute wheezing episodes in children with asthma. IMD provides sufficient treatment to prevent clinical deterioration within 5 days after initial therapy for mild to moderate pediatric exacerbations of asthma that are responsive to nebulized medications. 相似文献
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MW Beukers CH Klaassen WJ De Grip D Verzijl H Timmerman R Leurs 《Canadian Metallurgical Quarterly》1997,122(5):867-874
1. Rat histamine H2 receptors were epitope-tagged with six histidine residues at the C-terminus to allow immunological detection of the receptor. Recombinant baculoviruses containing the epitope-tagged H2 receptor were prepared and were used to infect insect Sf9 cells. 2. The His-tagged H2 receptors expressed in insect Sf9 cells showed typical H2 receptor characteristics as determined with [125I]-aminopotentidine (APT) binding studies. 3. In Sf9 cells expressing the His-tagged H2 receptor histamine was able to stimulate cyclic AMP production 9 fold (EC50=2.1+/-0.1 microM) by use of the endogenous signalling pathway. The classical antagonists cimetidine, ranitidine and tiotidine inhibited histamine induced cyclic AMP production with Ki values of 0.60+/-0.43 microM, 0.25+/-0.15 microM and 28+/-7 nM, respectively (mean+/-s.e.mean, n=3). 4. The expression of the His-tagged H2 receptors in infected Sf9 cells reached functional levels of 6.6+/-0.6 pmol mg(-1) protein (mean+/-s.e.mean, n=3) after 3 days of infection. This represents about 2 x 10(6) copies of receptor/cell. Preincubation of the cells with 0.03 mM cholesterol-beta-cyclodextrin complex resulted in an increase of [125I]-APT binding up to 169+/-5% (mean+/-s.e.mean, n=3). 5. The addition of 0.03 mM cholesterol-beta-cyclodextrin complex did not affect histamine-induced cyclic AMP production. The EC50 value of histamine was 3.1+/-1.7 microM in the absence of cholesterol-beta-cyclodextrin complex and 11.1+/-5.5 microM in the presence of cholesterol-beta-cyclodextrin complex (mean+/-s.e.mean, n=3). Also, the amount of cyclic AMP produced in the presence of 100 microM histamine was identical, 85+/-18 pmol/10(6) cells in the absence and 81+/-11 pmol/10(6) cells in the presence of 0.03 mM cholesterol-beta-cyclodextrin complex (mean+/-s.e.mean, n=3). 6. Immunofluorescence studies with an antibody against the His-tag revealed that the majority of the His-tagged H2 receptors was localized inside the insect Sf9 cells, although plasma membrane labelling could be identified as well. 7. These experiments demonstrate the successful expression of His-tagged histamine H2 receptors in insect Sf9 cells. The H2 receptors couple functionally to the insect cell adenylate cyclase. However, our studies with cholesterol complementation and with immunofluorescent detection of the His-tag reveal that only a limited amount of H2 receptor protein is functional. These functional receptors are targeted to the plasma membrane. 相似文献
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A Kr?mer-Guth T Quaschning H Pavenst?dt J Galle M Nauck MW Baumstark P Schollmeyer W M?rz C Wanner 《Canadian Metallurgical Quarterly》1997,12(7):1336-1343
BACKGROUND: Recent studies suggest that dyslipidaemia accelerates the progression of diabetic nephropathy, but the various pathomechanisms underlying such abnormalities are not completely delineated. METHODS: We isolated, radiolabelled, and characterized very-low-density lipoproteins (VLDL) and low-density lipoproteins (LDL) from eight diabetic patients with moderate impairment of renal function and dyslipidaemia and studied their interaction with LDL receptors in human glomerular epithelial cells. RESULTS: While diabetic VLDL showed no compositional changes, LDL particles contained a higher proportion of triglycerides at the expense of cholesterol in comparison with healthy controls. Despite differences in composition, both VLDL and LDL from patients exhibited reduced receptor affinity and cellular uptake capacity by glomerular epithelial cells. Since LDL composition was altered intracellular cholesterol homeostasis was investigated. Due to reduced cholesterol content and lower uptake capacity, diabetic LDL were less effective in suppressing intracellular sterol synthesis and in activating acylcholesterol acyltransferase than LDL from controls. Electrophoretic mobility of apoB from diabetic patients was enhanced as compared to controls, most probably due to the higher degree of glycation (17 + 1.7 versus 11 + 1%, P < 0.05) but not to oxidation (TBARS 0.5 + 0.2 versus 0.2 + 0.1 mumol/1). Oxidized LDL was not taken up in significant amounts, indicating no scavenger receptor activity in glomerular epithelial cells. CONCLUSION: The receptor-specific uptake of diabetic VLDL and LDL by glomerular epithelial cells is impaired. Compositional changes of the LDL particle and glycation of the protein moiety may contribute to altered glomerular uptake. However, glycation of the protein moiety may be superior to compositional changes. Because glomerular structures like mesangial matrix and endothelial cells are known for preferential binding of modified lipoproteins, further studies are required to elucidate their potential role in the progression of diabetic glomerulosclerosis. 相似文献
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CF Hildebolt TK Pilgram M Dotson N Yokoyama-Crothers J Muckerman J Hauser S Cohen E Kardaris MW Vannier P Hanes MK Shrout R Civitelli 《Canadian Metallurgical Quarterly》1997,32(7):619-625
To determine whether postmenopausal bone loss and factors associated with osteoporosis affect tooth retention, we examined vertebral and proximal femoral (postcranial) bone mineral density in relation to tooth loss and attachment loss in a cross-sectional study of 135 postmenopausal women (age range 41-70 yr). Women had at least 10 teeth and no evidence of moderate or severe periodontal disease. Full-mouth attachment loss measurements were made using a pressure-sensitive probe, and bone density was determined by dual-energy X-ray absorptiometry. Attachment loss was correlated with tooth loss (number of remaining teeth, radiologically determined), but not with vertebral or proximal femur bone density. Multivariate analysis showed current smoking (p = 0.01), years since menopause (p = 0.02) and the interaction of age and current smoking (p < 0.01), to be statistically significant predictors of attachment loss in our study population. 相似文献
130.