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991.
Panzella L Manini P Crescenzi O Napolitano A d'Ischia M 《Chemical research in toxicology》2003,16(4):502-511
All trans retinoic acid (1), a cancer chemopreventive agent and a pluripotent morphogen, was found to react efficiently with nitrite ions in a biphasic system consisting of CH(2)Cl(2)/0.1 M phosphate buffer (pH 3) 1:1 v/v to give a complex mixture of nitration products. Repeated TLC fractionation of the reaction mixtures after methylation allowed isolation of the main products, which could be identified as the 12-nitro derivatives 3a,b and the decarboxylated 12,14-dinitro and 5,6-epoxy-14-nitro derivatives 4 and 5a by spectral analysis. Use of (15)NO(2)(-) followed by extensive 2D NMR analysis, including (1)H,(15)N heteronuclear multiple bond correlation experiments, allowed identification of nitronitrate derivatives as additional constituents of the mixture. Under similar conditions, 1 methyl ester gave mainly 3a,b. 5,6-Epoxyretinoic acid (2) reacted smoothly with acidic nitrite to give mainly 5a and its isomer 5b whereas its methyl ester afforded 14-nitro derivatives 9a,b as chief products. The observed patterns of reactivity along with mechanistic experiments would suggest that nitrite-induced nitration of 1 proceeds through complex reaction pathways set in motion by attack of NO(2) to the 12- and 14-positions. Separate experiments showed that 1 can inhibit nitrite-induced N-nitrosation of 2,3-diaminonaphthalene at pH values of 4 and 5.5, as well as decomposition of caffeic acid under similar conditions. Overall, these results provide the first detailed insight into the reaction behavior of a retinoid toward reactive nitrogen species and shed light on previously overlooked nitrite scavenging properties of 1 of potential relevance to the mechanism of its antiinflammatory, antimutagenic, and cancer chemopreventive action. 相似文献
992.
BACKGROUND: Although the core feature of dementia is progressive cognitive disruption, non-cognitive behavioural problems are expressed in most patients with dementia during the course of their illness. While psychotropic drugs are frequently used to control behavioural symptoms, comorbidities, which are very common in the geriatric population, could often limit their use. Gabapentin may be a potential treatment in such situations. METHODS: In this open, baseline comparison study 20 patients with probable Alzheimer's disease with behavioural alterations and serious comorbidities (paralytic ileus, open-angle glaucoma, ischaemic cardiopathy, hepatic failure or severe prostatic hyperplasia) received gabapentin for 15 months. Patients were allowed to continue any previous therapy for concurrent diseases. However, concomitant antipsychotic or benzodiazepine intake was not permitted. RESULTS: Gabapentin appeared to be efficacious and well tolerated in this patient population, and did not appear to interact with other drugs. General benefit is reflected by a reduction of caregiver stress. No patients withdrew before the end of the study and no serious adverse events were reported. CONCLUSION: The results of this study in patients with probable Alzheimer's disease with behavioural alterations and serious comorbidities indicate that gabapentin provides significant and sustained efficacy in terms of behaviour, with associated reductions in caregiver burden. The results of an ongoing larger, randomised, double-blind study of gabapentin are keenly awaited and may help to provide a safer and more efficacious treatment option for this group of patients. 相似文献
993.
PURPOSE: To assess the relationship among weight concerns, smoking, and perceived difficulty in quitting among Argentinean adolescents. METHODS: Logistic regression and profile analyses, stratified by sex, were used to estimate the associations among 8th and 11th grade students (n=2524). RESULTS: Weight concerns were associated with current smoking status and also with perceived quitting difficulty among female, but not male, Argentinean high school students. Profile analyses determined parallel profiles of weight concerns between female smokers and nonsmokers and between male smokers and nonsmokers. CONCLUSIONS: The presence of weight concerns among adolescent females may require special consideration in smoking prevention and cessation programs. 相似文献
994.
Neon colour spreading occurs when sections of a lattice are replaced by segments of a different colour. This colour appears to diffuse out of the segments, and produce a slightly tinted transparent surface floating above the lattice. In two of the four experiments reported here, observers varied the colour of an area in a test display, until it matched the neon colour perceived in a corresponding (illusory) area in a comparison display. We found that the neon colour is an additive mixture of the colour of the segments and the colour complementary to the lattice, as suggested by Bressan (Vision Research 35 (1995) 375). In the other two experiments, we separately manipulated the presence and alignment of lattice and segments, to test whether the neon effect is fully predicted by a combination of colour diffusion and simultaneous colour contrast. We found that the colour induced in a neon figure is more saturated than the colour induced in a comparable non-neon figure. We discuss the implications of these results on our current understanding of the mechanisms of neon colour spreading. 相似文献
995.
Different ability of clenbuterol and salbutamol to block sodium channels predicts their therapeutic use in muscle excitability disorders 总被引:1,自引:0,他引:1
Activation of muscle beta(2)-adrenergic receptors successfully counteracted sarcolemma inexcitability in patients suffering from hyperkalemic periodic paralysis (HPP), a hereditary disease caused by mutations in the gene encoding the skeletal muscle sodium channel. Looking for potential modulation of these channels by beta(2)-adrenergic pathway using patch-clamp technique, we found that clenbuterol blocked sodium currents (I(Na)) in rat skeletal muscle fibers and in tsA201 cells transfected with the human channel isoform, whereas salbutamol did not. The effects of clenbuterol were independent of beta-adrenoceptor stimulation. Instead, clenbuterol structure and physicochemical characteristics as well as I(Na) blocking properties resembled those of local anesthetics, suggesting direct binding to the channels. Similar experiments with the chemically similar beta-antagonists propranolol and nadolol, suggested the presence of two hydroxyl groups on the aromatic moiety of the drugs as a molecular requisite for impeding sodium channel block. Importantly, clenbuterol use-dependently inhibited action potential firing in rat skeletal muscle fibers, owing to beta-adrenoceptor-independent I(Na) block. From a clinical point of view, our study defines the rationale for the safe use of salbutamol in HPP patients, whereas clenbuterol may be more indicated in patients suffering from myotonic syndromes, a condition characterized by sarcolemmal overexcitability, because use-dependent I(Na) block can inhibit abnormal runs of action potentials. 相似文献
996.
997.
Esposito S Marchisio P Cavagna R Gironi S Bosis S Lambertini L Droghetti R Principi N 《Vaccine》2003,21(23):3162-3168
To evaluate the effectiveness of influenza vaccination in reducing respiratory-related morbidity among children with recurrent respiratory tract infections (RRTIs) and their household contacts, 127 children aged 6 months-9 years (78 males; median age, 3.7 years) with a history of RRTIs (>/=6 episodes per year if aged >/=3 years; >/=8 episodes per year if aged <3 years) were randomized to receive the intranasal virosomal influenza vaccine (n=64 with 176 household contacts) or a control placebo (n=63 with 173 household contacts). During influenza season, the vaccinated children had fewer respiratory infections, febrile respiratory illnesses, prescribed antibiotics and antipyretics, and missed school days than the controls, and similar benefits and a reduction in the loss of parental work were observed among their household contacts. This study shows that the benefits of influenza vaccination extend to children with RRTIs and their family members and encourages to recommend its use in such children. 相似文献
998.
Brominated flame retardants belong to a new class of environmental contaminants. To obtain new information regarding the effects of 2,2',4,4',5-brominated diphenyl ether (BDE-99), one of the most frequently reported congeners in freshwater biota, the inhibition of algal growth of Raphidocelis subcapitara (also known as Selenastrum capricornutum) and acute toxicity to Daphnia magna were examined. The experimental design also involved a comparison with the polychlorinated biphenyl (PCB) Aroclor 1254. The uptake of BDE-99 by R. subcapitata and the transfer to D. magna (i.e., a higher level of aquatic biota in the food chain) was also assessed to verify the bioaccumulation phenomenon. After 24 h, BDE-99 appeared to be less toxic than Aroclor 1254 to D. magna, but the two compounds showed a similar toxicity at 48 h. In contrast to Aroclor 1254, BDE-99 was nontoxic to R. subcapitata at up to 100 microM, the highest tested concentration. However, the dose-dependent decrease in survival and impairment of reproduction of D. magna fed with BDE-99-treated algal culture demonstrate uptake by R. subcapitata. Because of the high persistence and bioconcentration, polybrominated diphenyl ethers as well as PCBs might be of environmental concern for years. 相似文献
999.
Eriksson L Jaworska J Worth AP Cronin MT McDowell RM Gramatica P 《Environmental health perspectives》2003,111(10):1361-1375
This article provides an overview of methods for reliability assessment of quantitative structure-activity relationship (QSAR) models in the context of regulatory acceptance of human health and environmental QSARs. Useful diagnostic tools and data analytical approaches are highlighted and exemplified. Particular emphasis is given to the question of how to define the applicability borders of a QSAR and how to estimate parameter and prediction uncertainty. The article ends with a discussion regarding QSAR acceptability criteria. This discussion contains a list of recommended acceptability criteria, and we give reference values for important QSAR performance statistics. Finally, we emphasize that rigorous and independent validation of QSARs is an essential step toward their regulatory acceptance and implementation. 相似文献
1000.