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51.
Two-year-old mice of the long-living transgenic mice of the alphaMUPA strain were previously found to show higher tumor resistance than the their initial wild-type (WT) strain (Tirosh, 2003). To better understand the mechanism underlying the differences in tumorigenesis rates between the two mouse lines, the rate of tumorigenesis and survival effects were studied in alphaMUPA mice and parental WT mice exposed to dimethylbenz(a)anthracene (DMBA). Each animal received three intragastric feedings of DMBA, each one week apart, at doses of 2, 1, and 1 mg dissolved in 0.2 ml corn oil; thus, the total amount of the carcinogen was 4 mg/mouse. Control mice received corn oil. The alphaMUPA mice exhibited distinctly higher survival rates in experimental chemically-induced tumorigenesis compared to their WT counterparts: 93% vs. 67%, p =2.7. The rate of tumorigenesis differed between the mouse lines (yield was 1.5 and 2.1), owing to a distinct tendency toward decreased tumor frequency in the skin and forestomach in the alphaMUPA mice. The experimental duration was also significantly higher for transgenic mice: 35.9 +/- 1.2 weeks compared to 30.5 +/- 1.3 weeks in WT mice, p <0.01. The lungs, forestomach and skin were target organs for the carcinogenic effect of DMBA. Our observations suggest that aging promotes the rate of spontaneous and induced tumorigenesis. 相似文献
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3-Aminobenzamide, a specific inhibitor of poly(adenosine diphosphoribose) synthesis, has been shown to enhance the response of mammalian cells to ionizing radiation and alkylating agents. Observations such as these usually have been taken to be an indication of the involvement of poly(adenosine diphosphoribose) in the repair of DNA damage. It has been reported that some inhibitors of adenosine diphosphoribosyl transferase (ADPRT) affect cell viability, glucose metabolism, and DNA synthesis when present at low concentrations in the growth medium for extended periods (e.g., lymphoid cells exposed to a few millimolar for 24 h [Milam, K. M., and Cleaver, J. E. Science (Wash. DC), 223: 589, 1984]). The latter report questioned previous interpretations of radiation results based on the use of ADPRT inhibitors which enhance cell killing. We have studied the enhanced radiation lethality of Chinese hamster cells using higher concentrations of these inhibitors, but for shorter periods, in an effort to determine if metabolic perturbations are produced and if they are relatable to enhanced cell killing. The compounds used were 2-aminobenzamide, 3-aminobenzamide, 4-aminobenzamide, benzamide, and nicotinamide, compounds which show a large variation in their potency as inhibitors of ADPRT. It was found that none of the compounds was toxic at the highest doses used (20 mM for 2 h) and that, during a 2-h period, the potent inhibitor 3-aminobenzamide had little or no effect on DNA synthesis. Two h is long enough to yield a near-maximum radiosensitization with 3-aminobenzamide. Although glucose metabolism was affected to varying degrees (up to a 50% inhibition by 4-aminobenzamide in 2 h), there was no correlation between effectiveness in inhibiting ADPRT and effectiveness in inhibiting glucose metabolism. A correlation was observed, however, between the inhibitory potential of ADPRT and the enhancement of radiation response. When used for sufficiently short times, we conclude that the effects at even high concentrations of a potent inhibitor of ADPRT (e.g., 3-aminobenzamide) are consistent with an involvement of poly(adenosine diphosphoribose) synthesis in the expression of a radiation-induced end point like cell killing. 相似文献
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Golomb E Matza D Cummings CA Schwalb H Kodavanti UP Schneider A Houminer E Korach A Nyska A Shapira OM 《Toxicologic pathology》2012,40(5):779-788
Exposure to air pollution has been associated with acute myocardial ischemia, impaired myocardrial function, and ST-segment depression. Particulate matter (PM)-associated metals, especially vanadium and nickel, have been implicated in observed cardiovascular impairments. We aimed to assess the effect of single intratracheal pulmonary exposure to vanadium-rich respirable oil combustion PM (HP-10) on the intrinsic myocardial ischemic tolerance and mitochondrial integrity in rats. The authors subjected isolated heart tissue slices derived from saline or PM-exposed rats to low glucose low oxygen induced ischemia followed by oxygenated condition with glucose supplementation. Mitochondrial structural integrity was determined by TEM (transmission electron microscopy) and functionality by the 3-(4, 5 dimethylthiazol-2yl)-2, 5 diphenyltetrazolium bromide (MTT) assay. Rats exposed to PM exhibited no apparent inhibition of mitochondrial dehydrogenase activity in oxygenated conditions at 24 or 48 hr post-PM exposure. However, in conditions of simulated ischemia/reoxygenation, these heart slices showed a delayed but consistent and significant decrease in dehydrogenase activity compared to controls at 48 hr after exposure to PM. Electron microscopy revealed significant myocardial mitochondrial injury upon exposure to PM characterized by mitochondrial swelling and fusion. The authors conclude that exposure to soluble vanadium-rich PM induces mitochondrial functional impairment and structural abnormality, which compromises mitochondrial respiration and results in decreased tolerance to ischemia/reoxygenation in rats. 相似文献
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Herzl Chai James J.-W. Lee Brian R. Lawn 《Journal of the Mechanical Behavior of Biomedical Materials》2010,3(1):116-120
We present definitive evidence for crack growth from internal defects called ‘tufts’ in human enamel. Transverse slices (normal to the tooth axis) sawn from extracted human teeth are embedded in a polycarbonate sandwich configuration and tested in simple flexural loading. The evolution of ensuing cracks across the enamel sections is viewed in situ by a video camera. The observations unequivocally identify tufts as sources of internal tooth fracture. In sufficiently thin slices the enamel becomes translucent, allowing for through-thickness observations of the crack topography. Crack segments that appear to be disjointed on a section surface link up into a contiguous primary crack below the surface, suggesting some crack resistance by ‘bridging’ behind the advancing crack tip. The role of these and other microstructural factors in determining the resilience of tooth structures is considered. 相似文献
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Objective
Millimeter-scale (“miniature”) specimens enable in-situ evaluation of mechanical properties of engineering materials at reduced cost. Here three such specimens for measuring fracture toughness (KC) are developed and implemented to new dental materials. The latter include concurrent methacrylate-based and new ether-based resin composites designed to reduce polymerization stress and enhance service life in restored teeth.Methods
Fracture toughness of four experimental and one commercial dental resin composites are evaluated using three-point bending (3PB), wedge double-cantilever-beam (WDCD) and edge chipping miniature test specimens. The values of KC were compared with those obtained following ISO standard method ISO6872: 2014. The stress intensity factor (K) for the 3PB and WDCB specimens was determined using linear fracture mechanics analyses made in conjunction with the Finite Element technique, with due consideration given to the finite width of pre-crack.Results
Analytic expressions for predicting KC were developed for all three miniature specimens. The width of pre-crack, generally neglected for conventional specimens, significantly affect K. Measured KC conclusively agree with those of commercial or well-studied materials as obtained using conventional specimens, with error bounded by 5–10 percent.Significance
The edge chipping test was successfully applied for the first time to non-brittle materials like dental resin composites. The miniature specimens developed will expedite the evaluation of fracture toughness of dental resin composites by saving materials and provide needed in-situ assessment capability. The chipping test which requires no introduction of initial crack and involves no use of elastic constants is especially suitable to functionally graded materials and in-situ study of restored teeth. The WDCB specimen enables stable crack growth, a useful trait in fatigue studies. 相似文献60.
Guilherme F. Perini Fabio P.S. Santos Vaneuza Funke Jefferson Ruiz Ben-Hur Ferraz Neto Nelson Hamerschlak 《Leukemia research》2009,33(12):e234-e235
This is the case report of a 47-year-old woman referred to our institution due to acute liver failure related to imatinib, who was submitted to a successful liver transplantation. Nilotinib was safely used post-transplant. 相似文献