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151.
A new series of thirteen 2-[3-(substituted amino)-6-chloro-1,1-dioxo-1,4,2-benzodithiazin-7-yl]-3-phenyl-4(3H)-quinazolinones 4-16 were prepared in order to evaluate their cytotoxic activity against 12 human cancer cell lines. The bioassay indicated that the quinazolinone derivatives 5, 8-12, 15, and 16 possess cancer-cell growth-inhibitory properties. Compounds 5 and 12 showed a high level of selectivity for certain cell lines. The most active compounds 9, 10, 15, and 16 showed moderate antiproliferative activity and were approximately 4-fold less potent than cisplatin. 相似文献
152.
153.
Direct evidence for accumulation of 1,2,3,4-tetrahydroisoquinoline (TIQ), an endo- and exogenous substance suspected of producing Parkinsonism in humans, has not yet been shown. This study aimed to examine TIQ disposition in the whole rat brain and in the striatum and substantia nigra (SN). TIQ was administered to male Wistar and Dark Agouti rats (20, 40 and 100 mg/kg i.p.) alone or jointly with specific CYP2D inhibitor quinine (20, 40, 80 mg/kg i.p.), acutely or chronically. TIQ concentration in brain of both strains was several-fold higher than in plasma. The level of its metabolite, 4-OH-TIQ, was very low in the brain and plasma of TIQ-treated Wistar while in those receiving additionally quinine or in Dark Agouti rats, 4-OH-TIQ was absent or negligible. Inhibition of CYP2D catalyzing TIQ 4-hydroxylation in the liver had no influence on TIQ accumulation in the brain. Exogenous TIQ was actively transported from periphery into the brain by the organic cation transporter system, mainly OCT3, and quickly eliminated from it by P-glycoprotein. TIQ accumulation after chronic injection to Wistar rats was short-lasting and limited to SN. High concentration of TIQ in SN induces while in the liver inhibits the nigral and hepatic activity CYP2D, respectively. 相似文献
154.
Preventive action of green tea from changes in the liver antioxidant abilities of different aged rats intoxicated with ethanol 总被引:3,自引:0,他引:3
Augustyniak A Waszkiewicz E Skrzydlewska E 《Nutrition (Burbank, Los Angeles County, Calif.)》2005,21(9):925-932
OBJECTIVE: The present study investigated the influence of green tea as a source of water-soluble antioxidants on the liver antioxidant potential of different aged rats chronically intoxicated with ethanol. METHODS: Rats (2, 12, and 24 mo old) were fed for 5 wk on a control or an ethanol Lieber-DeCarli diet with and without green tea (7 g/L). The activity and level of enzymatic and non-enzymatic antioxidants and the level of markers of protein and lipid oxidation in the liver of rats were examined. RESULTS: The activities of superoxide dismutase and catalase and levels of vitamins C, E, A, and beta-carotene were significantly decreased, whereas activities of glutathione peroxidase and glutathione reductase and the level of reduced glutathione significantly increased during aging. The ethanol diet caused a significant decrease in activity of antioxidant enzymes and in the level of non-enzymatic antioxidants tested. Administration of green tea to ethanol-treated rats of different ages partly normalized the activity of enzymes and the level of non-enzymatic antioxidants. Changes in antioxidant ability observed during aging were accompanied by increased levels of markers of lipid and protein modifications that also were intensified by ethanol. Green tea caused a decrease in lipid and protein oxidation in aged and ethanol-treated rats. The protective effect of green tea was confirmed by the significantly lower activity of biomarkers of liver damage (alanine and aspartate aminotransferases) in the serum of rats that received green tea with ethanol compared with rats from the control ethanol group. CONCLUSIONS: The use of green tea appears to be beneficial to rat liver by decreasing oxidative stress caused by ethanol and/or aging. 相似文献
155.
Wieslaw A. Jedrychowski Frederica P. Perera Umberto Maugeri Elzbieta Mroz Maria Klimaszewska‐Rembiasz Elzbieta Flak Susan Edwards John D. Spengler 《Paediatric and perinatal epidemiology》2010,24(5):492-501
Jedrychowski WA, Perera FP, Maugeri U, Mroz E, Klimaszewska‐Rembiasz M, Flak E, Edwards S, Spengler JD. Effect of prenatal exposure to fine particulate matter on ventilatory lung function of preschool children of non‐smoking mothers. Paediatric and Perinatal Epidemiology 2010. Impaired fetal development is associated with a number of adult chronic diseases and it is believed that these associations arise as a result of the phenomenon of prenatal programming, which involves persisting changes in structure and function of various body organs caused by ambient factors during critical and vulnerable periods of early development. The main goal of the study was to assess the association between lung function in early childhood and prenatal exposure to fine particulate matter (PM2.5), which represents a wide range of chemical compounds potentially hazardous for fetal development. Among pregnant women recruited prenatally to the study, personal measurements of PM2.5 were performed over 48 h in the second trimester of pregnancy. After delivery, infants were followed for 5 years; the interviewers visited participants in their homes to record children's respiratory symptoms every 3 months in the child's first 2 years of life and every 6 months thereafter. In the fifth year of the follow‐up, children were invited for standard lung function testing of levels of forced vital capacity (FVC), forced expiratory volume in 1 s (FEV1) and forced expiratory volume in 0.5 s (FEV0.5). There were 176 children of non‐smoking mothers, who performed at least two acceptable spirometry measurements. Multivariable linear regression showed a significant deficit of FVC at the highest quartile of PM2.5 exposure (beta coefficient = ?91.9, P = 0.008), after adjustment for covariates (age, gender, birthweight, height and wheezing). Also FEV1 level in children was inversely correlated with prenatal exposure to PM2.5, and the average FEV1 deficit amounted to 87.7 mL (P = 0.008) at the higher level of exposure. Although the effect of PM2.5 exposure on FEV0.5 was proportionally weaker (?72.7, P = 0.026), it was also statistically significant. The lung function level was inversely and significantly associated with the wheezing recorded over the follow‐up. The findings showed that significant lung function deficits in early childhood are associated with prenatal exposure to fine particulate matter, which may affect fetal lung growth. 相似文献
156.
157.
G Lutze H Buhl R H?cker C Socha U Socha H Urbahn 《Zeitschrift für die gesamte innere Medizin und ihre Grenzgebiete》1986,41(18):502-505
The influence of physical stress (bicycle ergometer and track) on 13 parameters of the plasmatic coagulation system was investigated in trained and untrained test persons. Shortenings of the coagulation times as well as distinct increases of the activity or concentration were observed in the partial thromboplastin time (PTT), the factor VIII activity (VIII:C) and the factor VIII-associated antigen (VIIIR:Ag). The results are discussed with regard to their causes and their clinical importance. 相似文献
158.
Christiane Damgé Marie Socha Nathalie Ubrich Philippe Maincent 《Journal of pharmaceutical sciences》2010,99(2):879-889
Nanoparticles prepared with a blend of a biodegradable polyester (poly(ε-caprolactone)) and a polycationic nonbiodegradable acrylic polymer (Eudragit® RS) have been used as a drug carrier for oral administration of a short-acting insulin analogue, aspart-insulin. Insulin-loaded nanoparticles, about 700 nm in diameter, encapsulated 97.5% of insulin and were able to release about 70% of their content in vitro in a neutral medium over 24 h. When administered orally to diabetic rats, insulin-loaded nanoparticles (50 IU/kg) decreased fasted glycemia for a prolonged period of time and improved the glycemic response to glucose in a time-dependent manner, with a maximal effect between 12 and 24 h after their administration. In parallel, plasma insulin levels increased. However, higher (100 IU/kg) and lower (25 IU/kg) doses of insulin did not exert any biological effect. It is concluded that polymeric nanoparticles composed of poly(ε-caprolactone)/Eudragit® RS are able to preserve the biological activity of the insulin analogue aspart-insulin; however, the postprandial peak suppression was prolonged more than 24 h by comparison with regular insulin working only 6–8 h. This effect may be explained by the monomeric configuration of aspart-insulin, which is probably better taken up by the intestinal mucosa than regular insulin. © 2009 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 99:879–889, 2010 相似文献
159.
The interaction of mianserin with ethanol in central nervous system (CNS) was investigated. Mianserin was administered at a single dose of 5 or 20 mgkg(-1) i.p. or as daily injections in a dose of 2.5 mgkg(-1) given for 14 days. The influence of mianserin on acute ethanol toxicity (LD(50)), on ED(50) of ethanol in rota-rod test, on the duration of ethanol sleeping time as well as on spontaneous locomotor activity and ethanol-induced hypothermia was investigated. Moreover, the influence of mianserin administered in a dose of 10 mgkg(-1) i.p. on post-ethanol changes in the bioelectric brain activity (EEG) recordings in rabbits was also investigated. The electrodes were implanted into midbrain reticular formation (MRF), dorsal hippocampus (Hp) and frontal cortex (C).Mianserin administered as a single dose of 5 mgkg(-1) was found to decrease LD(50) of ethanol and its ED(50) in rota-rod test. Mianserin administered as a single dose of 5 or 20 mgkg(-1) prolongs ethanol sleeping time in mice but given daily for 14 days has no influence on this time. Mianserin-induced hypothermia was observed after administration of single dose as well as increase of ethanol-induced hypothermia after administration of higher dose (20 mgkg(-1)). Mianserin administered daily for 14 days had no influence on post-ethanol changes in body temperature. Single dose of mianserin 20 mgkg(-1) decreases locomotor activity in mice while repeated administration has no influence on locomotor activity. In contrast, both single dose and repeated administration of mianserin prevents increased locomotor activity of animals observed after ethanol (2.5 mgkg(-1)).Mianserin administered to rabbits (10 mgkg(-1)) induces increase of share of low frequency 0.5-4 cps and decrease of share of frequencies 4-7 and 7-10 cps in EEG recordings from MRF and Hp. The recordings from frontal cortex show increase of share of frequencies 10-13 cps. Ethanol increases the share of low frequencies in EEG recordings and decreases the share of fast frequencies. Mianserin increases its influence on fast frequencies. 相似文献
160.
The perioperative course of 41 patients undergoing 85 endoscopic laser resections of central airway lesions under general anaesthesia was reviewed. The CO2 laser was used in 60 procedures and the Nd:YAG in 25. Intravenous anaesthesia and Venturi ventilation were utilized for 65 resections; 20 procedures involved predominantly inhalation anaesthesia via the ventilating bronchoscope. Significant intraoperative complications included arterial desaturation (SaO2 less than 90 per cent) in 26 per cent of procedures, and refractory hypertension requiring vasodilator therapy in 19 per cent. Intravenous anaesthesia was associated with a longer duration of recovery room care and a higher incidence of postoperative respiratory complications (delayed extubation, recovery room re-intubation and ventilation, and post-extubation stridor). Inhalation anaesthesia appeared to simplify the intraoperative management and decrease the incidence, duration and severity of immediate postoperative respiratory complications. 相似文献