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1.
Sbrana Isabella; Puliti Aldamaria; Seidel Albrecht; Glatt Hansruedi; Turchi Gino 《Mutagenesis》1995,10(6):505-512
Regioisomers of pyrene and benzo[a]pyrene quinones were testedfor their ability to induce structural and numerical aberrationsand spindle disturbance in Chinese hamster epithelial liver(CHEL) cells in culture. All quinones tested were clastogenicPyrene-1,8-quinone (P-1,8-Q) and benzo[a]pyrene3,6quinone(BP-3,6-Q) induced strikingly high levels of triradials. Inaddition, dicentrics and ring chromosomes were very common inBP-3,6-Q-treated cultures. Isomers of these compounds, pyrene-1,6-quinone(P-1,6-Q) and benzo[a]pyrene-1,6-quinone (BP-1,6-Q), inducedunobtrusive patterns of chromosomal aberrations. We suspectthat the P-1,8-Q and BP-3,6-Q moieties bound to the DNA werestill reactive, and formed crosslinks and/or underwent redoxcycling leading to high local concentrations of reactive oxygenspecies. In addition, P-1,8-Q and BP-3,6-Q induced c-mitoses,hyperdiploidies and polyploidies, in particular endoreduplications.These effects were not seen with the other two test compounds,or they were only detected at the highest concentrations used,which were strongly cytotoxic (c-mitoses with P-1,6-Q, polyploidieswith BP-1,6-Q).
6To whom correspondence should be addressed at: European Centre for the Validation of Alternative Methods (ECVAM), Joint Research Centre (JRC), TP58O, 121020 Ispra, Italy 相似文献
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Ansgar Michael Chromik Annette M Müller Martin Albrecht Sabrina Rottmann Jan-Michel Otte Thomas Herdegen Waldemar Uhl Ulrich Mittelk?tter 《Journal of investigative surgery》2007,20(5):273-282
Taurolidine (TRD) has antimicrobial and anti-inflammatory properties. However, the anti-inflammatory effects of TRD in inflammatory bowel diseases (IBD) have not been investigated. Here, we have analyzed the toxicity of TRD after oral long-term application in mice and examined the impact of oral TRD in a dextran sulfate sodium (DSS) model of experimental colitis. Female C57/BL6 mice received TRD in various concentrations (0.1% to 0.4%) for 60 days. Toxicity was evaluated by use of a disease activity index (DAI) and histological examination of major metabolic organs. Furthermore, the impact of 0.2% TRD on a chronic DSS colitis was examined by daily DAI, histological crypt damage score (CDS), bacterial translocation into mesenteric lymph nodes (MLN), and colonic expression of tumor necrosis factor (TNF) alpha, transforming growth factor (TGF) beta, interleukin (IL)-1beta, IL-6, cytochrome oxidase (COX)-2, and monocyte chemotactic protein (MCP)-1 by real-time polymerase chain reaction (PCR). Oral TRD administration for 60 days was well tolerated by the animals and did not show any toxic effects in terms of DAI and histological changes. TRD treatment of DSS colitis led to increased survival of 100%, compared to 33% in the untreated colitis group (p < or = .005). Clinical amelioration was mirrored by significantly reduced DAI and CDS in the TRD treated colitis. Colonic cytokine expression and bacterial translocation into MLN showed no differences between both groups. We thus report for the first time that oral application of TRD results in amelioration of an experimental IBD model. We hypothesize direct intraluminal antimicrobial effects of TRD as well as anti-inflammatory effects during the acute phase of DSS colitis. 相似文献
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The metabolism of [1-14C] glutamate to 14CO2 and the glutamate dehydrogenase (GLDH) activity towards alpha-ketoglutarate (alpha-KG) formation were measured in bulk isolated astrocytes derived from control rats and rats with acute hepatic encephalopathy (HE) induced with thioacetamide. In addition, the effects of in vitro treatment of control and HE astrocytes and non-synaptic mitochondria with toxic (3mM) NH4Cl concentration were followed. [1-14C] glutamate oxidation measured as a whole was identical in control and HE astrocytes and was inhibited by ammonia to the same degree in either fraction. In the presence of a glutamate transamination inhibitor--3mM aminooxyacetic acid (AOA), when only the GLDH-mediated part (25% of total) of the glutamate oxidation remained active, the inhibitory effect of ammonia treatment was much more pronounced in HE astrocytes than in control astrocytes. The ability of non-synaptic mitochondria to utilize glutamate to CO2 was not changed in presence of 3mM NH4Cl, whereas a substantial decrease of CO2 production (about 80%) in both the control and HE preparations was observed in the presence of 3mM AOA. GLDH activity was not at all affected by either of the experimental conditions, both in astrocytes and purified non-synaptic mitochondria. Thus, the inhibition of glutamate oxidation in astrocytes by ammonia and the compounded inhibitory effect of HE, ammonia and AOA appeared to be located beyond the glutamate dehydrogenation step within the tricarboxylic acid cycle. 相似文献
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Chronic hyperglycemic diabetes in the rat is associated with a selective impairment of cerebral vasodilatory responses 总被引:3,自引:0,他引:3
Diabetes has been reported to impair vasodilatory responses in the peripheral vascular tissue. However, little is known about vasodilatory function in the diabetic brain. We therefore studied, in the N2O-sedated, paralyzed, and artificially ventilated rat, the effects of chronic hyperglycemic diabetes on the cerebral blood flow (CBF) responses to 3 acutely imposed vasodilatory stimuli: hypoglycemia (HG) (plasma glucose = 1.6-1.9 mumol ml-1), hypoxia (HX) (PaO2 = 35-38 mm Hg), or hypercarbia HC) (PaCO2 = 75-78 mm Hg). In addition, we evaluated the somatosensory evoked potential (SSEP) and plasma catecholamine changes in rats exposed to acute glycemic reductions. Diabetes was induced via streptozotocin (STZ, 60 mg kg-1 i.p.). All results in diabetic rats were compared to those obtained in age-matched nondiabetic controls. The animals were studied at 6-8 weeks (HG experiments) or 4-6 months (HG, HX, and HC experiments) post-STZ. Values for CBF were obtained for the cortex (CX), subcortex (SC), brainstem (BS), and cerebellum (CE) employing radiolabeled microspheres. Up to three CBF determinations were made in each animal. In 6-8 week diabetics vs. controls, CBF increased to a lesser value in the CX, SC, and BS (p less than 0.05). Thus, in the diabetics, going from chronic hyperglycemia to acute hypoglycemia, CBF values (in ml 100 g-1 min-1 +/- SD) increased (p less than 0.05) from 89 +/- 22 to 221 +/- 57 in the CX, from 82 +/- 21 to 160 +/- 52 in the SC, and from 79 +/- 34 to 237 +/- 125 in the BS. In controls, going from normoglycemia to acute hypoglycemia, the CBF changes (p less than 0.05) were 128 +/- 27 to 350 +/- 219 (CX), 117 +/- 11 to 358 +/- 206 (SC), and 130 +/- 29 to 452 +/- 254 (BS). CBF changes and absolute values in the CE were similar in the two groups. At 4-6 months post-STZ, a complete loss of the hypoglycemic CBF response was found in the CX, SC, and CE. In the BS, a CBF response to hypoglycemia was seen in the diabetic rats, with the CBF increasing from 114 +/- 28 (hyperglycemia) to 270 +/- 204 ml 100 g-1 min-1 (p less than 0.05), compared to a change from 147 +/- 36 (normoglycemia) to 455 +/- 299 ml 100 g-1 min-1 (p less than 0.05) in the control group.(ABSTRACT TRUNCATED AT 250 WORDS) 相似文献
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C. Craig Blackmore MD MPH Eric K. Hoffer MD Emily Albrecht PA-C Frederick A. Mann MD 《Journal of the American College of Radiology》2004,1(6):410-414
We describe a model of how physician assistants can be used in an academic medical center to expand radiologist productivity, and to enhance the departmental academic and educational missions. At Harborview Medical Center, following a training program and graduated responsibility under supervision, physician assistants provide initial interpretation of radiology studies, consultation to referring physicians, and perform less complicated interventional procedures. Acceptance of physician assistants by the radiologists, radiology residents, and referring physicians has been high. Although the impact of physician assistants on departmental clinical productivity is difficult to measure, our data suggest that radiologists are more efficient when physician assistants are assigned to service, both in terms of numbers of studies interpreted, and timeliness of reporting and billing. As a result of the success of our program, we believe that physician assistants can have an important role in radiology practice. 相似文献