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Covalent Binding of Inhaled Formaldehyde to DNA in the NasalMucosa of Fischer 344 Rats: Analysis of Formaldehyde and DNAby High-Performance Liquid Chromatography and Provisional PharmacokineticInterpretation. CASANOVA, M., DEYO, D. F., AND HECK, H. D'A.(1989). Fundam Appl. Toxicol. 12, 397417. Inhalationof 3HCHO and H14CHO(6 ppm, 6 hr) resulted in the formation ofDNA-protein crosslinks in the rat nasal respiratory mucosa.The DNA was extracted and was fractionated into aqueous (AQ)and interfacial (IF) portions. AQ DNA and IF DNA were enzymaticallyhydrolyzed to deoxyribonucleosides in Tris buffer and analyzedby HPLC with liquid scintillation counting (LSC). HCHO was boundexclusively to the IF DNA, indicating that the HCHO was boundas DNA-protein crosslinks. Hydrolysis of the DNA quantitativelyreleased the HCHO; no evidence was obtained for the formationof hydroxymethyl adducts. An adduct detected previously followingincubation of mammalian cells with HCHO, N6-hydroxymethyldeoxyadenosine(hm6dA)[Beland F. A., Fullerton, N. F., and Heflich, R. H. (1984) J.Chromartogr. 308 121131], was shown to be produced byreaction of HCHO with deoxyadenosine (dA) in bis-Tris bufferunder conditions similar to those used for hydrolysis of theDNA. This reaction does not occur in Tris buffer. Evidence wasobtained that most or all of the hm6dA observed can be explainedby this reaction. Based on these results, an improved methodto determine the amount of H14CHO bound to DNA was developed:the DNA is hydrolyzed in Tris buffer and analyzed by HPLC, andthe released H14CHO is derivatized with dimedone and quantitatedby LSC. Rats were exposed to a wide range of H14CHO concentrations(0.3, 0.7, 2, 6, or 10 ppm; 6 hr). DNA-protein crosslinkingoccurred at all concentrations. The formation of crosslinkswas interpreted in terms of a nonlinear pharmacokinetic modelincorporating oxidation of inhaled HCHO as a defense mechanism.The slope of the fitted concentration-response curve at 10 ppmis 7.3-fold greater than at 0.3 ppm, and the fitted detoxicationpathway is half-saturated at an airborne concentration of 2.6ppm. 相似文献
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GORDAN TERRY; STROTHER DALE E.; CRAMER DONALD V.; GOODE JOHN W. 《Toxicological sciences》1987,9(2):287-296
A 90-Day Inhalation Toxicity Study of Raw Shale Oil in Fischer344 Rats. GORDON T., STROTHER, D. E., CRAMER, D. V., AND GOODE,J. W. (1987). Fundam. Appl. Pharmacol. 9, 287296. Thepotential health effects of a raw shale oil were evaluated ina 90-day inhalation study in Fischer 344 rats. Groups of 15male and 15 female rats were exposed 6 hr/day, 5 days/week for13 weeks to aerosol concentrations of 0, 56, 120, or 492 mg/m3.In the high-dose group, 10 males and 7 females died prior tothe termination of the study, most within the first 5 weeksof the experiment. A dose-dependent suppression in weight gainwas seen in all of the shale oil-exposed groups. The failureto gain weight was associated with a variety of clinicopathologicabnormalities, including a dose-related decrease in red andwhite blood cells, with lowered plasma protein levels and increasedserum alkaline phosphatase, and with total bilirubin levelsin males. The exposure of the test animals to aerosolized rawshale oil was also associated with inflammatory and hyperplasticlesions in the lungs and upper respiratory tract, atrophy ofthe thyrnus and thymic-dependent portions of the peripherallymphoid system, and bone marrow. These changes demonstratethat inhalation of raw shale oil aerosol can produce major organtoxicity similar to that found after exposure to other unrefinedoil products. 相似文献
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CANDYCE M. ROBERTS MS KATHRYN SUCHER ScD RD DONALD G. PERRIN PhD STEPHEN RODRIGUEZ PhD 《Journal of the American Dietetic Association》1995,95(8)
Concept mapping is an instructional strategy that requires learners to identify, graphically display, and link key concepts in instructional reading material. Although proven effective in numerous disciplines as a means to promote critical thinking and self-directed learning, concept mapping has not been tested in diet therapy. The objective of this study was to implement concept mapping as a small-group, cooperative learning strategy in an upper-division diet therapy course and to evaluate student attitudes about the effect of concept mapping on knowledge, self-directed learning, problem-solving, and collaborative skills. Students in the first semester (n=27) initially learned course material by lecture (4 weeks) followed by an integrated mapping/lecture format (12 weeks); the second semester (n=25) used an integrated mapping lecture format for the full 16 weeks. At the end of both semesters, students completed a 10-item original survey questionnaire. Responses for first (n=25) and second (n=21) semesters were analyzed independently. Results indicated that a majority of students thought participation in concept mapping enhanced knowledge of diet therapy principles (n=19 of 25; 18 of 21), self-directed learning (n=14 of 25; 18 of 21), critical thinking (n=21 of 25; 14 of 21), problem-solving (n=22 of 25; 16 of 21), and collaboration (n=24 of 25; 20 of 21) skills. When noncooperation of teammates was a factor, concept mapping was viewed as more frustrating and time consuming than lecture. This study demonstrated concept mapping as an effective learning strategy for diet therapy; it improves students’ ability to engage in self-directed learning, critical thinking, collaboration, and creative problem solving. Results suggest that concept mapping is most effective when accompanied with comprehensive training, coordinated lectures, instructor guidance, and long-term practice. J Am Diet Assoc. 1995; 95:908–911. 相似文献
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JORGE M. DAVIDENKO M.D. MARIO DELMAR M.D. Ph .D. JACQUES BEAUMONT Ph .D. DONALD C. MICHAELS Ph .D. PACO LORENTE Ph .D. JOSÉ JALIFE M.D. 《Journal of cardiovascular electrophysiology》1994,5(11):945-960
Inhibition and Facilitation in Cardiac Muscle. Introduction: The effects of subthreshold electrical pulses on the response to subsequent stimulation have been described previously in experimental animal studies as well as in the human heart. In addition, previous studies in cardiac Purkinje fibers have shown that diastolic excitability may decrease after activity (active inhibition) and, to a lesser extent, following subthreshold responses (electrotonic inhibition). However, such dynamic changes in excitability have not been explored in isolated ventricular muscle, and it is uncertain whether similar phenomena may play any role in the activation pal-terns associated with propagation abnormalities in the myocardium. Methods and Results: Experiments were performed in isolated sheep Purkinje fibers and papillary muscles, and in enzymatically dissociated guinea pig ventricular myocytes. In all types of preparations introduction of a conditioning subthreshold pulse between two subthreshold pulses was followed by a transient decay in excitability (electrotonic inhibition). The degree of inhibition was directly related to the amplitude and duration of the conditioning pulse and inversely related to the postconditioning interval. Yet, inhibition could be demonstrated long after (> 1 sec) the end of the conditioning pulse. Electrotonic inhibition was found at all diastolic intervals and did not depend on the presence of a previous action potential. In Purkinje fibers, conditioning action potentials led to active inhibition of subsequent responses. In contrast, in muscle cells, such action potentials had a facilitating effect (active facilitation). Electrotonic inhibition and active facilitation were observed in both sheep ventricular muscle and guinea pig ventricular myocytes. Accordingly, during repetitive stimulation with pulses of barely threshold intensity, we observed: (1) bistability (i.e., with the same stimulating parameters, stimulus: response patterns were either 1:1 or 1:0, depending on previous history), and (2) abrupt transitions between 1:1 and 1:0 (absence of intermediate wenckebach-like patterns). Simulations utilizing an ionic model of cardiac myocytes support the hypothesis that electrotonic inhibition in well-polarized ventricular muscle is the result of partial activation of Ik following subthreshold pulses. On the other hand, active facilitation may be the result of an activity-induced decrease in the conductance of IK1. Conclusion: Diastolic excitability of well-polarized ventricular myocardium may be transiently depressed following local responses and transiently enhanced following action potentials. On the other hand, diastolic excitability decreases during quiescence. Active facilitation and electrotonic inhibition may have an important role in determining the dynamics of excitation of the myocardium in the presence of propagation abnormalities. 相似文献
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Immunomodulation by Metals 总被引:1,自引:0,他引:1
ZELIKOFF JUDITH T.; SMIALOWICZ RALPH; BIGAZZI PIERLUIGI E.; GOYER ROBERT A.; LAWRENCE DAVID A.; MAIBACH HOWARD I.; GARDNER DONALD 《Toxicological sciences》1994,22(1):1-7
A symposium entitled Immunomodulation by Metals was held atthe 32nd Annual Meeting of the Society of Toxicology (SOT) inNew Orleans, Louisiana. The symposium was cosponsored by theImmunotoxicology and Metals Specialty Sections of SOT and wasdesigned to describe the types of adverse immunological reactionswhich occur in response to environmental and/or occupationalexposure to metals. Epidemiological evidence and underlyingmechanisms responsible for the observed alterations were alsodiscussed. The following is a summary of each of the individualpresentations. 相似文献
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JONES DEAN P.; KAGAN VALERIAN E.; AUST STEVEN D.; REED DONALD J.; OMAYE STANLEY T. 《Toxicological sciences》1995,26(1):1-7
A symposium entitled Impact of Nutrients on Cellular Lipid Peroxidationand Antioxidant Defense System was held at the 33rd Annual Meetingof the Society of Toxicology (SOT) at the Loews Anatole Hotelin Dallas, Texas. The symposium was sponsored by the Food SafetySpecialty Section and focused on the role of particular nutrientsin cellular lipid peroxidation and antioxidant defense system.Emphasis was placed on defining underlying mechanisms for damageand protection, as well as potential ramification in human healthissues. The following are extractions of some of the highlightsfrom each presentation. 相似文献
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FORSTER DONALD P.; FROST BRIAN; KAMBERSKA ZUZANA; HOLUB JIRI 《European journal of public health》1999,9(2):103-108
Background: There were a number of similarities, except fortheir effectiveness, in the health care systems of Czechoslovakiaand England and Wales between the Second World War and the late1980s. In a comparison of Czechoslovakia with England and Wales,the objectives of this study were to examine data sources andto report time trends and regional distributions in hospitalbed supply, hospital doctor supply and hospital utilisation.Methods: For the specialties of general medicine and generalsurgery in both countries from 1960 to 1986, data were collatedon bed supply, hospital doctor supply, discharge rates and lengthof stay. Issues concerning the comparability of the data wereaddressed, for example those of the definitions of specialty,length of stay and casemix. Results: In the period 1960 to 1986,in the specialties of general medicine and general surgery,there was a relative excess in the supply of hospital doctorsand beds in Czechoslovakia compared with England and Wales.Hospital performance in terms of discharge rates, dischargesper bed and length of stay remained relatively static in Czechoslovakiaduring this period compared to marked increases in dischargerates and reduced length of stay in England and Wales. Bothcountries recorded reductions in the regional variation of bedand doctor supply and hospital utilisation. Conclusions: Internationalstudies of hospital utilisation need to be interpreted carefullyin the light of definitions of hospital stay, casemix, the useof day cases and the availability of other services. Subjectto these caveats, discharge rates were high and duration ofstay long In Czechoslovakia compared with England and Wales;however, both countries achieved important improvements in regionalequity. 相似文献